CTEPH Underdiagnosed After Pulmonary Embolism: Study
75% of patients developed CTEPH-like symptoms 3 months after PE
The incidence of chronic thromboembolic pulmonary hypertension (CTEPH) after an episode of acute pulmonary embolism (PE) is likely underestimated, a study suggests.
This occurs despite the high frequency of symptoms consistent with CTEPH, underscoring that an appropriate diagnostic work-up of CTEPH is rarely undertaken.
The study, “CTEPH: a Kaiser Permanente Northern California experience,” was published in Thrombosis Research.
CTEPH is a rare form of pulmonary hypertension (PH) caused when blood clots form. Unlike other types of PH, CTEPH is potentially curable through a surgery.
CTEPH is a known complication of PE, a blockage of an artery caused by blood clots that become stuck in the lungs. Although patients have a wide range of persistent symptoms after an acute PE, CTEPH is rarely taken into account. A validated and reliable cost-effective diagnostic method is also lacking.
How common is CTEPH after pulmonary embolism?
Researchers led a real-world study to evaluate the incidence of CTEPH after an acute PE and the use of several common diagnostic tests as quick and cost-effective ways to screen for CTEPH.
The study was made up of 1,973 patients (mean age, 62.4) from the MAPLE study cohort, which includes people with an acute PE from a center in the Kaiser Permanente Northern California (KPNC) system from January 2013 to April 2015. KPNC is a healthcare delivery system that serves more than 4 million people in northern California.
Patients were included in the study if they were 18 or older and had not been diagnosed with CTEPH before the PE episode. Patients who had had a PE within 30 days were excluded.
Symptoms were collected and cross-referenced with imaging data to determine practice patterns. The researchers also assessed several risk factors for CTEPH in order to obtain a prediction score to help identify patients at high risk.
Risk factors included recurrent PE and a pulmonary artery systolic pressure (PASP) higher than 50 mmHg, among others. Systolic blood pressure measures the pressure in the arteries when the heart beats.
The presence of right ventricular hypertrophy (enlargement) on an electrocardiogram (ECG) and increased levels of B-type natriuretic peptide (BNP) were also assessed as they “could possibly be used as a rapid, cost-effective CTEPH screening method,” the scientists wrote. “A reliable diagnostic algorithm utilizing these inexpensive and easily accessible tests may both amplify and expedite the detection of previously unrecognized CTEPH cases.”
CTEPH diagnostic tests included right heart catheterization — the “gold standard” in diagnosing PH — and methods of pulmonary blood vessel imaging, such as ventilation/perfusion (V/Q) scanning.
Incidence of CTEPH ‘underestimated’ after acute PE
Results showed that 75% of patients developed symptoms consistent with CTEPH over three months after acute PE. But the incidence of CTEPH was very low overall at 2.3%, being significantly higher among those with symptoms compared to those without symptoms.
According to the researchers, “the proper work-up for CTEPH following acute PE is rarely completed for patients with persistent symptoms.” In fact, only 5.6 % of these patients underwent a V/Q scan. As such, “the true CTEPH incidence is likely underestimated with this current pattern of practice and could explain in part the wide range of CTEPH incidence rates quoted, including the low incidence rate in this study.”
The most reported symptom was dyspnea, or difficulty breathing (63.7%), followed by malaise and fatigue (44.4%).
“Persistent symptoms such as dyspnea, the most reported symptom in our study … are commonly endorsed by patients with previous acute PE and could help identify those at risk of developing CTEPH,” the researchers wrote.
Recurrent PE and a PASP higher than 50 mmHg were the statistically significant risk factors for CTEPH found in the study. Participants with recurrent PE had a risk 19.3 times higher, while those with a PASP higher than 50 mmHg were 10.4 times more likely to develop the condition.
The researchers emphasized that a “diagnosis of CTEPH should ideally be achieved before the development of PH to this degree.”
Compared with increased levels of BNP alone, right ventricular hypertrophy criteria showed a lower sensitivity (2.6 % vs. 76.3%) but a higher specificity (98.8% vs. 44.4%) in diagnosing CTEPH. Sensitivity is the ability to correctly identify people with a certain condition, whereas specificity is the ability to correctly identify people without it.
Despite the higher sensitivity of BNP levels, these were “not sensitive enough for extensive widespread use in screening,” the researchers wrote, adding that “ECG criteria for [right ventricular hypertrophy] and BNP levels should not be utilized as standalone or even combined screening tools for CTEPH in the absence of more sensitive and specific diagnostic tests.”
The study showcases that there is a lack of guidelines to determine which diagnostic tools should be used and when they should be used after an acute PE in this patient population. It suggests more research is needed to clarify the true CTEPH numbers, what the best diagnostic tests are, and when is the right time to use them.
“These discoveries may help guide future development of diagnostic algorithms that can effectively rule out and accurately identify this potentially curable disease in a timely manner,” the researchers said.