{"doi":"10.1161/circheartfailure.124.013302","title":"Cell-Free DNA Profiles End-Organ Injury and Predicts Outcomes in Advanced Heart Failure With Left Ventricular Assist Device Implantation","abstract":"BACKGROUND: Adverse events after durable left ventricular assist devices (LVADs) pose a challenge to survival. However, there are limited risk stratification approaches. Plasma cell-free DNA (cfDNA) offers potential as a biomarker for assessing end-organ injury and risk stratification. METHODS: The study included a multicenter prospective cohort of patients with heart failure with and without LVAD (cohort 1), a separate cohort of patients with heart failure with paired samples before and after LVAD (cohort 2) implantation, and a comparator group of healthy controls. Nuclear cfDNA (ncfDNA) and mitochondrial cfDNA were quantified by digital droplet polymerase chain reaction. Tissue-specific cfDNA was identified using whole-genome bisulfite sequencing. Differences in cfDNA levels by LVAD use were assessed with the Wilcoxon rank-sum test or the paired t test. Outcomes (hemocompatibility-related adverse event–free survival and infection-free survival) by cfDNA tertiles were compared by log-rank tests. RESULTS: Cohort 1 had 76 patients with LVAD and 144 without LVAD. Cohort 2 had 40 patients with LVAD with samples before and after LVAD. ncfDNA levels were 4-fold higher (9794 versus 2386 copies/mL; P <0.001), and mtDNA was 1.5-fold higher (134 707 versus 82 054 copies/mL; P =0.01) in cohort 1 compared with healthy controls (n=48). Patients without LVAD had higher ncfDNA levels compared with those with LVAD in cohort 1 (11 423 versus 7912 copies/mL; P =0.019). After LVAD placement in cohort 2, ncfDNA nearly halved (18 980 versus 10 228 copies/mL; P <0.001), with significant reductions in innate immune, vascular endothelium, gastrointestinal, and liver cfDNA levels. The highest pre-LVAD tertile of ncfDNA was associated with worse infection-free (hazard ratio, 2.94 [95% CI, 1.31–6.56]; P =0.006) and hemocompatibility-related adverse event–free (hazard ratio, 3.24 [95% CI, 1.03–10.3]; P =0.034) survival. CONCLUSIONS: LVAD implantation was associated with reductions in systemic and tissue-specific cfDNA levels. cfDNA levels offer promise for improving risk stratification of LVAD candidates for post-LVAD outcomes.","journal":"Circulation Heart Failure","year":2025,"id":583432,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9404,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":627889,"name":"T. Andargie","orcid":"0000-0003-2888-1316","position":1,"is_corresponding":false},{"id":262681,"name":"Xin Tian","orcid":"0000-0003-1896-2462","position":2,"is_corresponding":false},{"id":657090,"name":"Michael Keller","orcid":"0000-0002-6695-4582","position":3,"is_corresponding":false},{"id":1495592,"name":"Isabella Cavagna","orcid":"0009-0003-4968-647X","position":4,"is_corresponding":false},{"id":1001264,"name":"Neelam Redekar","orcid":"0000-0002-4819-9034","position":5,"is_corresponding":false},{"id":376615,"name":"Tom Hill","orcid":"0000-0002-4661-6391","position":6,"is_corresponding":false},{"id":627891,"name":"Hyesik Kong","orcid":"0000-0001-7540-2045","position":7,"is_corresponding":false},{"id":1083840,"name":"Woojin Park","orcid":"0000-0001-9982-0057","position":8,"is_corresponding":false},{"id":883194,"name":"Xinyue Zhao","orcid":"0000-0003-2684-1345","position":9,"is_corresponding":false},{"id":1495593,"name":"P. Balasubramanian","orcid":"0000-0002-0821-1326","position":10,"is_corresponding":false},{"id":694865,"name":"Daniel Tang","orcid":"0000-0001-7142-1783","position":11,"is_corresponding":false},{"id":355238,"name":"Andrew H. Karaba","orcid":"0000-0003-2785-317X","position":12,"is_corresponding":false},{"id":246494,"name":"Moon Kyoo Jang","orcid":"0000-0002-1657-2877","position":13,"is_corresponding":false},{"id":264823,"name":"Michael A. Solomon","orcid":"0000-0001-7400-6614","position":14,"is_corresponding":false},{"id":96109,"name":"Hannah A. 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