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Atrial fibrillation occurs in the first few days after cardiac surgery (postoperative atrial fibrillation, POAF) as a result of acute-phase triggers. Although historically thought of as a transient arrhythmia, accumulating evidence suggests that POAF is an independent predictor of poor survival years after surgery. In addition, there is an association between POAF occurring in the acute postoperative phase and thromboembolic complications such as stroke occurring months to years after discharge. This suggests that POAF may not be confined to the acute postoperative phase but may be a recurrent subclinical arrhythmia.

To determine the incidence of AF episodes after discharge, we used continuous rhythm monitoring devices to follow patients without a history of AF following their open chest cardiac surgical procedure. In Chapter 3 and 4, we describe our results from continuous rhythm monitoring for a month and for 3 years respectively. Firstly, we found that more than 25% of patients developed AF in the month following discharge form hospital, the so-called late POAF (Chapter 3). Predictors of late POAF included comorbidities such as prior myocardial infarction, diabetes mellitus, obesitas and baseline CRP levels. In chapter 4 we further extended the rhythm-monitoring period to 3 years with an implantable loop recorder in patients without a history of AF. We demonstrated that up to 50% of patients developed AF episodes lasting 1,5 hours on average during the months to years following surgery. Patients who developed late POAF were older and had higher CHA2DS2VASc and HATCH scores with right atrial volume as an independent predictor of late POAF. Our findings in these chapters suggest that the risk profile for POAF and notably for late POAF resembles the risk profile of AF in general including a structural substrate for AF.

The complexity of the atrial structural substrate is reflected by the complexity of electrical conduction during induced AF. Patients with several cardiovascular comorbidities (high CHA2DS2VASc scores), show enhanced level of pathological atrial wall changes leading to complex fibrillating patterns during AF. To explore the electrophysiological substrate for POAF, we measured the complexity of fibrillating patterns of electrically induced AF on the right atrial wall (Chapter 4). For this purpose we induced AF during cardiac surgery by burst pacing and mapped the electrical activation of the right atrium using a 256 unipolar electrode plaque. In line with the previous findings, we found more complex activation patterns (i.e. higher number of waves and fractionation index) in patients who subsequently developed POAF and also those with late-POAF. This illustrates the effects of age and several co-morbidities on the atrial wall, which may not have led to (symptomatic) AF prior to surgery but may be prone to development of a stronger substrate with time.

Interestingly, enhanced complexity of the electrophysiological substrate in animal models involves higher number of wavelets and higher number of breakthrough waves, i.e. waves migrating to the opposing layer of the atrial wall due to dyssynchronous activation of the endocardium compared with epicardium. To investigate the mechanism of transmural propagation of the atrial wall described in animal models, we developed a highly detailed 3 dimensional computer model of the human atria. In this computer model, specific atrial anatomical structures were implemented and the mechanism of fibrosis related dissociation between endo-epicardial layers was demonstrated. We found a clear association between endo-epicardial dissociated activity due to increased levels of fibrosis and the number of breakthrough waves. To validate this model, we developed a crocodile shaped clamp electrode containing a double layer of unipolar electrode plaques. The electrode was designed to be inserted into the right atrium with one arm and to be approximated on the atrial wall on both sides. Using this technique, we were able to quantify for the first time in human, the amount of electrical uncoupling between the two layers of the atrial wall. We found that the endo-epicardial dissociation is enhanced with complex substrates for AF. In addition, there is indeed a clear correlation between endo-epicardial dissociation and the number of waves migrating to the opposing layer of the atrial wall, the so-called breakthrough waves. To further elucidate on these findings, we describe in Chapter 6 a method to detect the location of electrodes on the opposing side of the atrial wall by measuring the phase of depolarization during AF. We were able to demonstrate that mean-phase coherence between 2 electrodes, decays with distance between them. This method may be helpful in detecting the 3-D substrate of AF less invasively.

In conclusion, using continuous rhythm monitoring strategies combined with baseline substrate quantification in patients without a history of AF we found up to 50% late POAF recurrences. Patients developing late POAF were older with additional comorbidities and showed a more complex fibrillation pattern during electrically induced AF compared to those who did not develop POAF. In addition, we sought for the effects of atrial structural substrate on endo-epicardial dissociation and found a correlation between enhanced electrical dyssynchrony and breakthrough waves in a computer model of human atria. We also demonstrated the 3D substrate for AF in human by direct contact endo-epicardial mapping. Future research should determine the clinical consequences of late POAF and the range of the underlying structural substrate, which predisposes patients to AF development.