Prognostic factors of atrial fibrillation following elective coronary artery bypass grafting: the impact of quantified intraoperative myocardial ischemia

Atrial Fibrillation (AF) remains the most common arrhythmia after cardiac surgery. Its incidence depends on patient's preoperative profile and the type of operation performed. AF occurs in approximately 28-33% of the patients undergoing coronary artery bypass grafting (CABG) [1–3] and in 30-63% of those operated for coexisting ischemic heart and valve disease [3, 4]. The majority of AF arrhythmias appear within the first 4-5 postoperative days and the peak frequency is in the 2^nd or 3^rd postoperative day [5, 6]. It has been reported that patients with postoperative AF have longer Intensive Care Unit (ICU) stay, longer hospitalization, and higher incidence of re-admissions increasing the cost of hospitalization by 30% [3, 7]. This study is focused on the definition or pre- and peri-operative factors associated with the development of AF after CABG. The primary point is to find those patients at increased risk that may benefit of a precautionary preoperative anti-arrhythmic treatment.

AF is the result of the dispersion of atrial refractoriness resulting in multiple reentry wavelets in the atria [8]. In the postsurgical state of the heart several parameters may alter the refractoriness of adjacent atrial areas predisposing to reentry circuits and to the development of atrial fibrillation: inflammation [9], heightened sympathetic and vagal stimulation [10, 11], fluid overload and postoperative ventricular stunning resulting in atrial pressure elevation [12, 13], chronic distention of the left atrium [14, 15], metabolic derangements such as hypoglycemia [16] and altered thyroid function, including both hyper- and hypo-thyroidism [17], alterations of the cardiac structure and electrophysiological profile of the atria due to the surgical atrial trauma itself [5], and ischemic atrial injury [18, 19].

The intraoperative ischemia of the atrial wall has been considered as the most important factor related to the pathophysiological changes resulting in postoperative AF [20]. It has been shown that during a heart operation both the atrial septum and atrial wall remain warmer than the wall of the left ventricle [4, 21, 22]. Therefore, the protection of the atrial wall remains relatively inadequate compared to that of the left ventricular wall. Based on that consumption several trials have been carried out to identify the impact of different techniques of myocardial protection on the incidence of postoperative atrial arrhythmias without any clear benefit for any of the various strategies applied [23]. In our opinion the amount of cardioplegia is the most important factor related to the postoperative occurrence of AF. Jideus et al [24] showed that larger amounts of cardioplegia are related to lower incidence of postoperative AF. In our cohort of patients we observed a statistically significant relation between myocardial injury and postoperative AF. As shown in Figure 1 describing the distribution of the _avMII_ante values in relation to the frequency of postoperative AF, values of _avMII_ante < 0.27 mls.m²/kg.min were related to a higher incidence of AF after CABG surgery (p = 0.011). Furthermore, when performing the same analysis using the lowest values of the MII_ante (_minMII_ante) we observed that the _av.MII_ante was a stronger predictor of postoperative atrial fibrillation than the _minMII_ante indicating that one inadequate cardioplegia delivery is less important than more ones (Figure 1).

The prolonged CPB-time in cardiac surgery may result from any one or more of the following factors: delay in first placing the aortic cross clamp, prolonged cardioplegic deliveries, extended warm shot and prolonged reperfusion period, and not just prolonged ischemic intervals. In our study we found that CPB-time above 120 minutes was statistically related to postoperative AF. However, in contrast to other authors [25, 26] we haven't found any relation between the aortic cross clamp time and the frequency of postoperative AF. Furthermore, the quality of the coronary arteries and the number of bypasses performed, although reported as factors related to the length of ischemic time, showed no statistical influence on the outcome of postoperative AF.

Intraoperative infarction was statistically related to postoperative AF. This fact is also suggested by other authors [27, 28]. In our opinion it is possible that posterior infarcts are directly involved inducing ischemia of the atrial wall and septum while the anterior ones are indirectly implicated through the development of acute atrial enlargement. This last hypothesis is supported by the results of Knotzer et al [29] who observed that post-CABG high filling pressure in both atria due to ventricular stunning are statistically related to an increased incidence of postoperative AF. In the same study it has been shown that systemic hypoxia is also related to the development of postoperative AF. Such observation is also supported by our study. The systemic hypoxia may result from preexisting compromise of the patient's respiratory function with decreased pulmonary reserves or may be related to other parameters such as perioperative myocardial infarction causing interstitial pulmonary edema, or positive fluid balance. Positive fluid balance was found relative to the occurrence of postoperative AF in our study. A plausible explanation is that the positive fluid balance influences the development of AF through higher filling pressures of the left atrium and pulmonary congestion resulting in hypoxia. However, its role as a prognosticator is questionable. Both Osranek et al [15] and Place and colleagues [30] failed to identify net fluid balance either intra-operatively or postoperatively as a significant factor related to AF.

Postoperative low cardiac output has been reported as a parameter statistically related to postoperative AF [31]. In our opinion this observation is the result of the high inotropic support used in these patients to attain sufficient cardiac output. In this study indeed we found that high inotropic support (doses of Dopamine or Dobutamine, > 15 μg/kg/min) was statistically related to the incidence of postoperative AF.

A long ICU stay was found to be statistically related to the occurrence of AF after CABG. However this is a false presumption since a protracted ICU recovery may depend on other factors such us hypoxia, perioperative myocardial infarction and sepsis that predispose the patient to the development of postoperative arrhythmias.

We found that age > 65 years was a significant predictor of AF after CABG. Advanced age has been documented as the most consistent predictor of AF after cardiac surgery [1, 2, 15, 27, 28, 31–33]. Older patients present alterations in their atrial electrophysiological profile due to degenerative and inflammatory processes and therefore are more susceptible to the development of atrial fibrillation, especially in port cardiac surgery settings [34]. This could also explain why patients with a history of episodes of AF prior to surgery have a greater risk to develop AF after surgery. In this study indeed all patients with episodes of AF within 3 months prior to surgery and AF after CABG belonged to the advanced age group (> 65 years old); on the contrary most patients with early preoperative onset AF and without post-CABG AF were less than 65 years old.

Both low ejection fraction and congestive heart failure prior to surgery have been recognized as independent predictors of AF [2, 4, 35]. These conditions result in chronic retention of blood in the atria, dilation of the atrial chambers and enlargement of their walls, providing an excellent substrate for the development of reentry circuits in the presence of intraoperative ischemia. This observation was also valid in our study, where an ejection fraction lower than 40% was statistically related to the incidence of AF after surgery.

Furthermore, we observed that patients presenting proximal lesions to the right coronary artery showed an increased incidence of AF which was statistically significant. Similar observations were made by Mendes et al [36] and Kolvekar and colleagues [19], supporting the role of diseased sino-atrial node and atrio-ventricular node arteries originating from the RCA in the development of AF.

Finally, patients suffering from COPD were at higher risk to develop AF. A plausible explanation is that patients suffering from impaired respiratory function are more likely to present hypoxia postoperatively especially if more contributing factors such as positive fluid balance, increased pulmonary artery and atrial pressures, perioperative myocardial infarction, lung atelectasis, infection and lung dysfunction related to the cardiopulmonary bypass, coexist.

Based on our results the incidence of postoperative atrial fibrillation can be predicted by specific preoperative and perioperative parameters. Advanced age represents an optimal substrate for the development of the arrhythmia especially when combined with increased stress of the atrial wall. This stress may result from chronic stress to the atrial wall such as the one observed in patients with low ejection fraction and congestive heart failure, intraoperative ischemic injury and postoperative stress factors like myocardial infarction and positive fluid balance. Intraoperative ischemic injury is sufficiently expressed by the M.I.I which is related to the magnitude of atrial mass (approximated here by the BMI), the amount of cardioplegia delivered and the time between the cardioplegic deliveries. M.I.I represents an excellent predictor of postoperative AF after conventional coronary artery surgery. Patients presenting such predictors of AF may benefit from the precautionary early commencement of anti-arrhythmic treatment.