Impaired extracellular DNA clearance is associated with postoperative atrial fibrillation and mortality after cardiac...

Postoperative atrial fibrillation (POAF) is considered a convergence of preexisting vulnerability and periprocedural stressors. Although clinical risk scores such as the CHA₂DS₂-VA score capture clinical risk factors, they do not account for biological processes. Neutrophil activation and the release of extracellular DNA, counterbalanced by endogenous deoxyribonuclease (DNase) activity, may represent a mechanistically relevant pathway in POAF development.

We investigated neutrophil markers and DNase activity as indicators of POAF.

503 patients undergoing major cardiovascular surgery were investigated. Double-stranded DNA (dsDNA), citrullinated histone H3, neutrophil elastase, myeloperoxidase, and DNase activity were measured before surgery. Associations with POAF were assessed using logistic regression adjusted for the CHA₂DS₂-VA score. Cardiovascular and all-cause mortality was evaluated using Cox regression. Incremental prognostic information was assessed by comparing nested regression models.

POAF occurred in 42.1% of patients. Although baseline dsDNA levels did not differ between groups, multivariable analysis identified dsDNA as independently associated with POAF. DNase activity was independently associated with lower risk of POAF. The DNase factor, calculated as dsDNA divided by DNase activity, conferred an increased risk of POAF. Inclusion of the DNase factor significantly improved model fit beyond the CHA₂DS₂-VA score. During a median follow-up of 72 months, 109 patients (21.7%) died. dsDNA independently predicted mortality. Higher DNase activity was independently associated with lower mortality.

Preoperative extracellular DNA burden and DNase activity associate with POAF and long-term mortality after major cardiovascular surgery. Impaired regulation of extracellular DNA reflects a vulnerability phenotype not captured by established clinical risk scores and provides incremental prognostic information.