CTEPH: A Kaiser Permanente Northern California Experience

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and life-threatening form of pulmonary hypertension and the only potentially curable form of the World Health Organization Pulmonary Hypertension classes. Thus, the prompt and accurate diagnosis of this condition is imperative. Despite widespread chronic symptoms following acute pulmonary embolism (PE), the condition is rarely considered, and an externally validated inexpensive diagnostic algorithm is lacking.

A long-term, retrospective cohort study was conducted to assess the incidence of CTEPH following acute PE in a real-world study population. Additional data were collected regarding the practice patterns of diagnostic testing and imaging, particularly in patients with persistent or recurrent symptoms. Amongst diagnosed CTEPH patients, previously established risk factors were evaluated for degree of risk and commonly used diagnostic tests (electrocardiogram [ECG] right ventricular hypertrophy [RVH] pattern, B-type natriuretic peptide [BNP] elevations) employed during this period were evaluated and assessed for feasibility as screening tests. The study population was obtained from the MAPLE study cohort, comprised of patients presenting with acute PE in 21 community medical centers across the Kaiser Permanente Northern California system from January 2013 to April 2015. Diagnosis of CTEPH was confirmed via pulmonary vascular imaging (ventilation/perfusion [V/Q] scanning, computed tomography angiography, pulmonary angiography) and diagnostic right heart catheterization (RHC). Probable diagnoses were defined as a combination of suggestive echocardiographic and RHC findings. Additional inclusion criteria included age (≥18 years) with at least 2 years follow up and no previous diagnosis of CTEPH or PE during the prior 30 days.

There were 1973 patients who met inclusion criteria (mean age 62.4 years). Despite 75 % of patients developing symptoms consistent with CTEPH >3 months following acute PE, only 5.6 % of these symptomatic patients underwent V/Q scanning. There was overall a very low cumulative incidence of CTEPH (2.3 %), which was significantly higher amongst patients with symptoms compared to those without symptoms. When controlled for confounding in the multivariate analysis, only recurrent PE (HR 19.3, P < 0.001) and pulmonary artery systolic pressure >50 mmHg (HR 10.4, P < 0.001) were statistically significant predictors of CTEPH. Of the non-invasive diagnostic tests, ECG criteria for RVH were found to be poorly sensitive (2.6 %), but very specific (98.8 %) for CTEPH. Elevated levels of BNP alone were more sensitive than RVH ECG criteria (76.3 %) but poorly specific (44.4 %).

The diagnosis of CTEPH is uncommonly made following acute PE. Despite the frequency of persistent symptoms consistent with CTEPH following acute PE, the appropriate diagnostic work-up is rarely undertaken as evidenced in this cohort. This suggests that CTEPH is underappreciated and rarely considered, likely underestimating the true incidence in this cohort. Future studies are needed to elucidate the true prevalence of CTEPH and further investigate both the optimal diagnostic tools and timing of appropriate screening. 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.