Author + information
- Samuel B. Brusca,
- Jason M. Elinoff,
- Moon K. Jang,
- Cumhur Y. Demirkale,
- Hannah A. Valantine,
- Michael A. Solomon and
- Sean Agbor-Enoh
Cell-free DNA (cfDNA) has recently been utilized as a marker of transplant rejection and is also elevated in states associated with vascular endothelial damage, including septic shock and cardiopulmonary bypass. The present study is the first to investigate the potential for cfDNA to predict disease severity in pulmonary arterial hypertension (PAH).
Patients were participants in an IRB-approved PAH natural history study at the NIH Clinical Center. Prior to plasma sample analysis, patients were separated into mild (n = 7) and severe (n = 8) groups. The severe group having both abnormal tricuspid annular systolic plane excursion (TAPSE) by echocardiogram and peak oxygen consumption (VO2) < 75% predicted by cardiopulmonary exercise test and the mild group having both normal TAPSE and peak VO2 ≥ 75% predicted. Controls (n = 7) were healthy adult volunteers. cfDNA was isolated from plasma and quantified using real-time PCR.
The severe PAH group had a lower mean TAPSE (13.6 vs 21.71 mm; P = 0.004), a lower peak VO2 (14.16 vs 23.07 ml/kg/min; P < 0.0001), a shorter 6-minute walk distance (392 vs 510 m; P = 0.012), and a higher mean pulmonary artery pressure (58 vs 40.57 mm Hg; P = 0.01) compared to the mild PAH group. Plasma cfDNA concentrations were significantly different across the three groups (severe PAH, mild PAH, and controls; ANOVA; P = 0.032). Mean plasma cfDNA concentration was significantly higher in the severe PAH group vs controls (36.2 vs 19.39 ng/ml; P = 0.033, Tukey-Kramer adjustment for multiple comparisons), while there was a trend toward a higher cfDNA concentration in patients with severe compared to mild PAH (36.2 vs 21.96 ng/ml; P = 0.13). There was no difference in cfDNA concentration between patients with mild PAH and healthy controls (21.96 vs 19.39 ng/ml; P = 0.78).
Plasma cfDNA levels are higher in patients with severe PAH compared with healthy controls. This may be indicative of ongoing vascular endothelial injury or progressive right ventricular dysfunction and therefore may represent a novel way to monitor disease activity at the cellular level. Further investigation of the characteristics of circulating cfDNA in PAH patients is ongoing.
Sunday, March 17, 2019, 8:12 a.m.-8:22 a.m.
Session Title: Highlighted Original Research: Pulmonary Hypertension and Venous Thrombo-Embolic Disease and the Year in Review
Abstract Category: 35. Pulmonary Hypertension and Venous Thrombo-embolic Disease
Presentation Number: 902-04
- 2019 American College of Cardiology Foundation