Despite improvements in surgical and anesthesiological techniques, the incidence of AF after thoracic surgery has remained substantially unchanged over the past two decades [1–7]. Although several studies have analysed the risk factors for this arrhythmia and possible preventive strategies, its exact pathophysiology has not been elucidated yet. Few data are available regarding the impact of AF on survival after thoracic surgery [4–7]. Our study confirms the negative impact of AF on hospital mortality after lobectomy for lung cancer; in addition, it provides the first evidence that patients with postoperative AF who survive 5 years have a significantly reduced long-term survival.
Our data also identified preoperative paroxysmal AF, postoperative FBS and blood transfusions as independent predictors of postoperative AF. While paroxysmal AF and transfusion requirement are well-known AF risk factors, because of the electrical and histological abnormalities of patient atrial tissue and because of the amplified inflammatory response associated with transfusion of blood components [2, 12–14], the correlation between postoperative FBS and AF has not been reported previously. A possible explanation of such correlation is the peri-operative stress of the FBS procedure, resulting in a hyperadrenergic state with increased levels of catecholamines. The latter enhance triggered activity and automaticity, which are key factors in the development of atrial arrhythmia [15, 16].
An intriguing observation of the present study was an increased AF occurrence in patients undergoing left lobectomy compared with those subjected to right one (62% vs. 38%). A plausible reason could be related to the increased manipulation and increased trauma of the left cardiac structures (left atrial auricular and left pulmonary vein) . However, this statistical relationship was not confirmed at multivariable level.
Our data confirm that AF following lobectomy for lung cancer increases early postoperative mortality and causes significant adverse effects, prolonging the length of ICU and hospital stay [2–4]. Postoperative AF was here associated with three- to six-fold increased risk of both hospital mortality and ICU admission, and with two- to three-day increase in total hospital length.
A relevant finding of our study was the negative impact of postoperative AF on long-term survival. Previous investigations on the subject focused on the peri-operative period and failed to include the analysis of long-term survival, because postoperative follow-up was interrupted after about 3 years [4, 5]. The association between postoperative AF and postoperative survival is controversial [4–6]. Amar and co-workers  first demonstrated that early supraventricular tachydysrhythmias (SVT) were associated with reduced postoperative survival, in a population of 78 patients with non-small cell lung carcinoma. At the conclusion of that study (median follow-up: 17 months), only 1 of 10 patients with SVT was alive, whereas 39 of 68 (57%) who did not develop SVT were alive (p = 0.01) . Murthy and colleagues  reported the association of postoperative AF with increased risk of late adverse outcomes in 198 patients after esophagectomy. In that case series, drawn from 921 patients, median survival was shorter for those affected by AF compared with controls (11.5 vs. 14.5 months); however, when hospital mortality was excluded from analysis, survival was not different (14.5 vs. 16.9 months) . Cardinale and colleagues , after 233 lung cancer operations with a mean follow-up of 18 ± 8 months, recorded no difference of 3-year mortality between patients with and without AF.
All the above mentioned studies analysing a possible direct association between postoperative AF and mortality after thoracic surgery, however, have limitations due to heterogeneous cancer populations, small sample sizes, incomplete matching or exclusion of many patients from analysis, and follow-up not extended beyond three years [4–6]. Our study had much longer follow-up (median 36; maximum 179 months). Among 5-year survivors we found that postoperative AF was an independent predictor of poor long-term survival.
The mechanisms by which postoperative AF may cause mortality in later years are difficult to analyze. Despite attempts to account for confounding mechanisms, it is possible that AF is associated with mortality because it usually occurs in patients with a more severe comorbidity profile [1–3]. Plausible mechanisms supporting a direct effect of postoperative AF include heart failure and the potential AF recurrence with attendant thromboembolic sequelae [18, 19].
Our findings are consistent with the data presented by Groth and co-workers . The risk of dying for lung cancer exceeds the risk of dying of cardiovascular disease immediately after lung surgery, but this relation diminished with time. Being postoperative AF a mirror of cardiac status, an important implications for NSCLC survivors is the need for a long-term surveillance and prophylaxis of arrhythmias along with the planned lung follow-up.
There are limitations to the present study. Firstly, this is a single center study and its design is retrospective, although the data were prospectively collected. Secondly, the statistical analysis is limited by the large difference between the number of patients with AF and of those without it. Thirdly, the association we observed between AF and late mortality does not necessarily indicate causation, although studies on the general population affected by chronic AF and studies reporting the outcome of cardiac surgery patients with postoperative AF, revealed a direct AF effect in causing late mortality [18, 21]. In our study subgroup analysis of AF patients by tumor stage, and by cause of death was not feasible, due to the small number of subjects in each subgroup. Similarly, we cannot evaluate the possible role of systematic mediastinal lymph node dissection, because we routinely performed mediastinal sampling lymphadenectomy. Finally, we did not collect information about post-discharge AF recurrence, nor did we control for the effect of drug administration after patient discharge, due to unreliable information on anti-arrhythmic medications and long-term use of anticoagulation therapy. Because of these limitations, the proposed mechanisms explaining the statistically significant association that we found between postoperative AF and poorer 5-year survival remain speculative. Despite these limitations, to date our study is the largest capturing the late deleterious effects of AF and examining the clinically relevant question of whether AF after pulmonary lobectomy for cancer is associated with increased long-term mortality.