Low levels of endothelial nitric oxide synthase (eNOS) might serve as a potential indicator for recurrent atrial fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia and a major cause of thromboembolic stroke in clinical practice. This condition often recurs frequently, emphasizing the urgent need to understand its long-term progression, especially when triggered by acute events. Growing evidence indicates a relationship between AF and oxidative processes. During AF episodes, the atrial myocardium sustains significant oxidative damage, which may contribute to atrial remodeling. Nitric oxide (NO) is produced by enzymes called NO synthases (NOS). The three isoforms of NOS are neuronal NOS (nNOS, NOS1), inducible NOS (iNOS, NOS2), and endothelial NOS (eNOS, NOS3). Similar to acute coronary syndrome, AF has been shown to reduce left atrial endocardial eNOS levels and significantly decrease NO production. However, no research currently exists that examines the relationship between AF recurrence and NOS activity. The aim of this study is to evaluate the potential of eNOS levels as a marker for predicting AF recurrence.

The study population included 320 consecutive patients admitted to our hospital between August 2023 and January 2025 with AF. A total of 44 patients were excluded from the study. Ultimately, the study sample comprised 276 patients. Blood samples were collected into tubes for NT-proBNP, NO, eNOS, and iNOS. The samples were centrifuged (4000g, 4°C) for 10 minutes, and the serum was separated and stored at −25°C until analysis. Patients were divided into two groups based on whether AF recurred during their 6-month follow-up.

The mean age of the sample was 73.1±9.7 years. 138 (50%) patients were male. There was no significant difference between the levels of NT-proBNP, NO and iNOS. Univariate logistic regression analysis revealed significant correlations between eNOS and recurrnes of AF. The eNOS level was lower in patients with recurrent AF patients, and the optimal eNOS cut-off value of ≤ 93.4 pg/mL predicted recurrent AF patients with 68% sensitivity and 93.4% specificity (AUC:0.803 [95% CI: 0.751-0.848, p<0.001]).

This study investigates the role of eNOS activity in AF recurrence for the first time in the literature. It has been shown that lower eNOS levels are linked to a higher risk of AF recurrence.Figure 1:

ROC curve analysis of eNOS