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Original article
Nox2 up-regulation is associated with an enhanced risk of atrial fibrillation in patients with pneumonia
  1. Francesco Violi1,
  2. Roberto Carnevale1,
  3. Camilla Calvieri2,
  4. Cristina Nocella1,
  5. Marco Falcone3,
  6. Alessio Farcomeni3,
  7. Gloria Taliani4,
  8. Roberto Cangemi1,
  9. in collaboration with the SIXTUS study group
    1. 1Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
    2. 2Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Sapienza University of Rome, Rome, Italy
    3. 3Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
    4. 4Infectious and Tropical Diseases Unit, Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
    1. Correspondence to Professor Francesco Violi, I Clinica Medica, Sapienza University of Rome, Viale del Policlinico 155, Roma 00161, Italy; francesco.violi{at}


    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.

    • Pneumonia
    • Oxidative Stress

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