{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:07:55Z","timestamp":1789614475327,"version":"build-2803163510"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic toggle=\"yes\">t<\/jats:italic>\n                      test. Outcomes (hemocompatibility-related adverse event\u2013free survival and infection-free survival) by cfDNA tertiles were compared by log-rank tests.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      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;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001), and mtDNA was 1.5-fold higher (134\u2009707 versus 82\u2009054 copies\/mL;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =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\u2009423 versus 7912 copies\/mL;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.019). After LVAD placement in cohort 2, ncfDNA nearly halved (18\u2009980 versus 10\u2009228 copies\/mL;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;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\u20136.56];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.006) and hemocompatibility-related adverse event\u2013free (hazard ratio, 3.24 [95% CI, 1.03\u201310.3];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.034) survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  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