Nox2 up-regulation is associated with an enhanced risk of atrial fibrillation in patients with pneumonia

BACKGROUND: Community-acquired pneumonia (CAP) may be complicated by atrial fibrillation (AF) but the underlying mechanism is still unclear. Nox2-derived oxidative stress has been suggested to favour AF. METHODS: We consecutively enrolled 432 patients hospitalised for CAP. Nox2 activity, as assessed by serum levels of soluble Nox2 (sNox2-dp), was evaluated in each CAP patient. A 12-lead electrocardiography was repeated every 24 h. All patients were followed up until discharge. RESULTS: Forty-one patients with CAP (9.5%) experienced a new episode of AF within 24-72 h after hospital admission. Patients who experienced AF showed higher blood levels of sNox2-dp compared to those who did not (35.2±15.1 vs 27.0±12.5 pg/mL; p<0.001). Pneumonia Severity Index score (p=0.014), history of paroxysmal AF (p<0.001) and sNox2-dp (p=0.019) were independently associated with AF. At discharge, serum sNox2-dp levels were significantly decreased in the entire cohort (27.8±13.0 vs 21.9±6.8 pg/mL; p<0.001). Twenty-three out of 41 CAP patients with AF returned to sinus rhythm (56%); patients who remained in AF showed significantly higher baseline and discharge levels of sNox2-dp compared to those without AF (p<0.001) or with the 23 AF patients who returned to sinus rhythm (p<0.05). In vitro study showed that platelets or leucocytes incubated with endotoxin, at concentrations similar to those found in the circulation of CAP patients, elicited Nox2 up-regulation, suggesting endotoxin as a trigger of oxidative stress. CONCLUSIONS: AF may be detected in the early phase of CAP and is associated with Nox2 activation, suggesting a role for oxidative stress in promoting this cardiac arrhythmia. TRIAL REGISTRATION NUMBER: NCT01773863.