Post-operative atrial fibrillation: a maze of mechanisms

Abstract

Post-operative atrial fibrillation (POAF) is one of the most frequent complications of cardiac surgery and an important predictor of patient morbidity as well as of prolonged hospitalization. It significantly increases costs for hospitalization. Insights into the pathophysiological factors causing POAF have been provided by both experimental and clinical investigations and show that POAF is 'multi-factorial'. Facilitating factors in the mechanism of the arrhythmia can be classified as acute factors caused by the surgical intervention and chronic factors related to structural heart disease and ageing of the heart. Furthermore, some proarrhythmic mechanisms specifically occur in the setting of POAF. For example, inflammation and beta-adrenergic activation have been shown to play a prominent role in POAF, while these mechanisms are less important in non-surgical AF. More recently, it has been shown that atrial fibrosis and the presence of an electrophysiological substrate capable of maintaining AF also promote the arrhythmia, indicating that POAF has some proarrhythmic mechanisms in common with other forms of AF. The clinical setting of POAF offers numerous opportunities to study its mechanisms. During cardiac surgery, biopsies can be taken and detailed electrophysiological measurements can be performed. Furthermore, the specific time course of POAF, with the delayed onset and the transient character of the arrhythmia, also provides important insight into its mechanisms. This review discusses the mechanistic interaction between predisposing factors and the electrophysiological mechanisms resulting in POAF and their therapeutic implications.

Figure 1

Time course of atrial fibrillation incidence after cardiac and non-cardiac surgery and time course of C-reactive protein after cardiac surgery. Atrial fibrillation incidence after non-cardiac surgery peaks at post-operative day 1 and then rapidly declines to 2% at day 6, while atrial fibrillation incidence after cardiac surgery peaks at post-operative day 2 and slowly declines to around 6 % at day 6. This suggests a ‘cardiac factor’, related to the specific setting of cardiac surgery. The time course of C-reactive protein is surprisingly similar to that of atrial fibrillation incidence after cardiac surgery, supporting the role for inflammation in the mechanism of post-operative atrial fibrillation (modified from references ^,,).

Figure 2

Time course of substrate development and surgery-related factors in the occurrence of atrial fibrillation. Time course of pro-arrhythmic mechanisms is depicted in two hypothetical patients undergoing cardiac surgery. Both chronic as well as acute factors related to the operation on day 0 are shown. When the intensity of pro-arrhythmic factors reaches a certain threshold, atrial fibrillation will occur. Patient 1 has no relevant cardiovascular history, only hypertension (green) at the age of 57. Patient 2 already developed hypertension (red) at a younger age, followed by diabetes (red), mitral regurgitation (red), and COPD (red) at an older age, respectively. Both patients have no history of AF and undergo on-pump coronary artery bypass grafting at the same age. However, patient 2 has developed an AF substrate by the time of operation due to above mentioned cardiovascular diseases. Acute, surgery-related factors occur in both patients: cardiopulmonary bypass (CPB, yellow), inflammation (CRP, purple), oxidative stress (yellow), and sympathetic activation (yellow). Patient 2 develops post-operative atrial fibrillation (exceeds the ‘AF threshold’), while patient 1 remains with sinus rhythm. AF, atrial fibrillation; COPD, chronic obstructive pulmonary disease.