Inflammatory Cytokines During Cardiac Rehabilitation After Heart Surgery and Their Association to Postoperative Atrial Fibrillation

Abstract

Inflammation is associated with atrial fibrillation (AF), but little is known about the association of AF with the inflammatory serum cytokines after the acute postoperative phase. Thus, we aimed to explore how plasma cytokines concentrations modify during a 3-week cardiac rehabilitation after heart surgery, comparing patients who developed postoperative AF (POAF) and those with permanent AF with patients free from AF (NoAF group). We enrolled 100 consecutive patients and 40 healthy volunteers as a control group. At the beginning of cardiac rehabilitation, 11 days after surgery, serum levels of MPO, PTX3, ADAM17, sST2, IL-25, and IL-33 were dramatically higher, whereas TNFα and IL-37 levels were much lower in NoAF, POAF, and permanent AF patients than in the healthy volunteers. After rehabilitation, most of the cytokines changed tending towards normalization. POAF patients (35% of the total) had higher body mass index and abdominal adiposity than NoAF patients, but similar general characteristics and risk factors for POAF. However, ADAM-17 and IL-25 were always lower in POAF than in NoAF patients, suggesting a protective role of IL-25 and ADAM 17 against POAF occurrence. This finding could impact on therapeutic strategies focusing on the postoperative prophylactic antiarrhythmic interventions. Cardiac surgery is frequently complicated by postoperative atrial fibrillation (POAF), which is associated with increased morbidity and costs 1,2. POAF occurs in a third of patients undergoing cardiac bypass surgery 3 and up to 40% of patients undergoing valvular surgery 4 , usually within the first three days after the intervention. Post-operative atrial arrhythmias can also occur after non-cardiac surgery, especially after thoracic and large abdominal surgery, but with lower incidence 5. Previous studies have demonstrated that inflammation is closely related to the pathogenesis of atrial fibrillation (AF) 6 and there is strong evidence supporting an association between inflammation and AF. The inflammatory cardiac diseases, such as myocarditis, are known to be associated with an increased incidence of arrhythmia, including AF 7. Cardiac surgery is an acute stressful event generating a chain of inflammatory reactions, as a consequence of the aortic clamp, the organ reperfusion injury during cardiopulmonary bypass for extracorporeal circulation and the surgical injury itself. The underlying inflammatory pathway involves leukocyte activation 8. The inflammatory cascade after the surgery, represented by many circulating cytokines, may play a prominent role in initiating POAF. In fact, the cytokines, a network of intracellular proteins produced by lymphocytes, monocytes, and macrophages in response to inflammatory stimuli, have been assessed as potential mediators in the occurrence of AF 9. While a few studies evaluated the concentrations of biohumoral markers of inflammation perioperatively, very little is known about the serum levels of cytokines after the acute post-operative phase, i.e. some days after surgery when the pat...

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