Novel blood test predicts worse survival in PAH

A novel blood test that measures elevated circulating cell-free DNA may be used to evaluate disease severity and predict worse survival in patients with pulmonary arterial hypertension, according to new data published in Circulation.

The blood test measures DNA fragments shed by damaged cells. Researchers found that the fragments, known as cell-free DNA, were elevated in patients with PAH and rose with disease severity. Cell-free DNA is a newer analytical technique that is growing in its potential use, including for early detection of heart and lung transplant rejection and also early detection of cancer, according to a press release issued by the NHLBI.

“Researchers have been actively searching for novel, less-invasive approaches to evaluate PAH severity, disease progression and response to therapy for more than a decade,” Michael A. Solomon, MD, MBA, co-director of the NIH Clinical Center Pulmonary Arterial Hypertension Section and part of the NHLBI Cardiovascular Branch, said in the release. “These cell-free DNA analyses represent progress toward that goal.”

Researchers measured plasma cell-free DNA in 209 patients with WHO Group 1 PAH from two large U.S. medical centers and 49 controls. Cohort A, which comprised patients identified at Allegheny General Hospital, included 48 patients (median age, 62 years; 75% women) and cohort B, which comprised patients identified at Tufts Medical Center, included 161 patients (median age, 59 years; 69% women). Researchers collected data for REVEAL 2.0 scores and outcome determinations. All patients in cohort A and B were categorized into low- (n = 29 and n = 60), medium- (n = 7 and n = 45) and high- (n = 12 and n = 56) REVEAL risk groups, respectively.

In both PAH cohorts, cell-free DNA concentrations differed in those with PAH of varying REVEAL 2.0 risk score and controls (P < .002). According to the researchers, cell-free DNA concentrations were greater among patients in the high-risk group compared with the low-risk group (P < .002). For cohort B, death or lung transplant occurred in 14 patients in the lowest cell-free DNA tertile, 23 patients in the middle tertile and 35 patients in the highest tertile.

Both cell-free DNA levels stratified as tertiles (P = .0001) and REVEAL 2.0 risk groups (P < .0001) predicted transplant-free survival among patients with PAH, according to the researchers.

Adding cell-free DNA to REVEAL 2.0 improved the discrimination in this patient population (P = .02).

Methylation analysis in patients with PAH increased cell-free DNA that originated from erythrocyte progenitors, neutrophils, monocytes, adipocytes, natural killer cells, vascular endothelium and cardiac myocytes compared with controls (P < .05), according to the results.

Cell-free DNA concentrations obtained from erythrocyte progenitor cells, cardiac myocytes and vascular endothelium were greatest among patients with PAH who were in the high-risk group compared with the low-risk group (P < .02), the researchers wrote.

“Here we’re proposing a one-time test where you collect a vial of blood from a patient and use that to predict survival. We’re very encouraged by the early results,” Sean Agbor-Enoh, MD, PhD, chief of the NHLBI Laboratory of Applied Precision Omics, said in the release.

The researchers concluded that valuation of these results in a larger, prospective cohort with serial samples “will help better define the role of cell-free DNA in clinical PAH risk prediction,” they wrote in the study.

Reference:

• Novel blood test helps evaluate severity in pulmonary arterial hypertension, a rare lung disease. Published Aug. 25, 2022. Accessed Aug. 25, 2022.