Abstract 10765: Plasma Cell-Free DNA Predicts Survival and Maps Tissue-Specific Sources of Injury in Pulmonary Arterial Hypertension
| Autor: | Samuel B Brusca, Jason M Elinoff, Yvette Zou, Moon K Jang, Hyesik Kong, Cumhur Y Demirkale, Junfeng Sun, Fayaz Seifuddin, Mehdi Pirooznia, Hannah A Valantine, Carl Tanba, Abhishek Chaturvedi, Manreet Kanwar, Raymond L Benza, Ioana R Preston, sean agborenoh, Michael A Solomon |
|---|---|
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Circulation. 144 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circ.144.suppl_1.10765 |
| Popis: | Background: Cell-free DNA (cfDNA) is a non-invasive marker of tissue injury. Although being incrementally used as a clinical biomarker, its significance in pulmonary arterial hypertension (PAH) is unknown. Methods: Plasma cfDNA was isolated in two independent PAH cohorts (A, n=48; B, n=161) and healthy controls (n=48). Clinical variables and survival status were collected for Registry to Evaluate Early And Long-term PAH Disease Management (REVEAL 2.0) scores and outcome determinations. Total cfDNA levels were compared amongst controls and PAH patients and also used to predict transplant-free survival. A subset of samples from cohort B (n=96) and controls (n=16) were subjected to bisulfite sequencing and methylation analysis to quantify tissue-specific sources of cfDNA. Results: Median (IQR) cfDNA concentrations were higher in cohort A PAH patients (exploratory cohort) compared to controls and increased according to REVEAL 2.0 risk group: controls 13.7 (10.8-18.8) vs low risk 14.4 (10.0-19.9) vs medium risk 14.6 (11.3-28.2) vs high risk 31.5 (17.2-45.6) ng/ml (P Conclusions: cfDNA is elevated in PAH patients, correlates with disease severity and predicts worse survival. Methylation analysis of cfDNA in PAH patients is consistent with prevailing paradigms of disease pathogenesis. Thus, cfDNA may add prognostic power to PAH risk assessment and provide insight into disease progression. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|