Today, ladies and gentlemen, the topic of my presentation is atrial arrhythmias in patients with tetralogy of Fallot. This table shows that patients with tetralogy of Fallot have a mild risk of developing sinus node dysfunction atrioventricular conduction block and an intermediate risk for not only developing ventricular arrhythmias, but also atrial arrhythmias, including atrial fibrillation. Various supraventricular tachycardias have been reported in patients with tetralogy of Fallot. And these tachyarrhythmias include atrioventricular node-oriented tachycardias, atrioventricular node-oriented tachycardias, ectopic atrial tachycardias, typical counterclockwise cavotracosmous isthmus-dependent atrial flutter, intraatrial oriented tachycardias, and atrial fibrillation. And particularly, intraatrial oriented tachycardias and atrial fibrillation occur in this population. In nearly 800 patients with tetralogy of Fallot, risk factors for development of atrial flutter and atrial fibrillation have been identified. And in this study, it was shown that older age at time of repair and the presence of tricuspid regurgitation was associated with the development of atrial flutter and atrial fibrillation. The same is we see here in this graph, where we can clearly see that tricuspid regurgitation was the most common lesion associated with development of atrial flutter and atrial fibrillation. Atrial arrhythmias can be treated, of course, with antiarrhythmic drugs. If you want to acutely terminate a supraventricular tachycardia, you can use the electrocardioversion, which is quite effective. If an atrial pacemaker lead is present, you can also choose for overdrive pacing, but bear in mind that if you want to overdrive a regular atrial tachyarrhythmia, it might convert to atrial fibrillation. And then we have the antiarrhythmic drugs. Important to realize is that on pharmacological conversion of intra-atrial and tachycardias and atrial fibrillation in patients with tetralogy of Fallot, there is no data available. The usage of class III antiarrhythmic drugs is associated with the development of doxade and the use of class Ia and Ic with the development of ventricular tachycardia. And on top of that, we have the severe sinus bradycardia, which might occur after the cardioversion. With respect to antiarrhythmic drug use for long-term management, you can choose between either rhythm control or rate control. Patients with tetralogy of Fallot, they follow within the moderate congenital heart disease group, and when they have right ventricular dysfunction, the most effective drug is amiodarone. But when it comes to rate control, you can choose between the beta-blocking drugs and the calcium channel antagonists. In general, it is that antiarrhythmic drugs should be used instead of a rate control strategy. The antiarrhythmic drugs are usually moderately effective. The data we have obtained about the antiarrhythmic drugs are usually derived from patients with acquired cardiovascular diseases. And generally, is the usage of class I drugs discouraged? Amiodarone is an effective drug, but there is a high burden of long-term side effects. And when you select an antiarrhythmic drug for a patient with tetralogy of Fallot, consider the presence of sinus node dysfunction, atriofundicular conduction diseases, heart failure, and other cardiovascular comorbidities. Ablation therapy, on the other hand, has the potential to be a curative treatment modality. An essential for performing a successful ablation procedure is the use of an advanced mapping system. Mapping in general is used to unmask the underlying mechanisms and to identify the substrate. In patients with tetralogy of Fallot, the following electropathological changes have been identified. These patients often have a prolongation of atrial refectorinus, which is facilitated by atrial stretch. There is a chronic bradycardia due to sinuno-atrial dysfunction. There are multiple areas of intra-atrial conduction delay. And there is a presence of long suture lines and patches. And on top of that, there are multiple areas of scar tissue present throughout the atrium. Over the past decades, there have been considerable improvements in both mapping and ablation technologies. Nearly 20 years ago, we only had the fluoroscopic image. We had the multiple polar catheters. And by sweeping the multipolar catheters inside the heart chamber, we were able to record electrograms simultaneously. And then the operator had to reconstruct in his mind the pattern of activation. Well, nowadays, this is very much facilitated by the usage of three-dimensional electroanatomical mapping systems. There is also a growing experience in ablation therapy in patients with tetralogy of Fallot. Because over time, the surgical skills have been improved. The clinical care has been improved. And that means that the patients also become older. And when they become older, they have a higher risk for developing atrial tachyarrhythmias. The catheter ablation itself has often been improved. So we moved from the non-irrigated to the irrigated tip catheters. We nowadays have real-time contact force measurements, which enable us to more accurately differentiate between poor contact and scar tissue, both giving rise to low voltage potentials. The long stirruble sheets aid us in maneuvering the catheter inside the dilated atria and also to gain a more stable catheter position. The three-dimensional electroanatomical mapping systems are used to create activation maps and voltage maps. And particularly, the voltage maps are used to identify the areas of scar tissue. The integration of a real-time intracardiac ultrasound aids visualization, for example, of the intraatrial septum, which facilitates the septal puncture required for pulmonary vein isolation. When you construct MRI or CT images before the procedure, you can upload them in the mapping system. You can put your high-density mapping maps on top of them. And another advanced system is the so-called remote magnetic navigation system, which is particularly valuable for patients with a complex anatomy. And this system improves your catheter maneuverability and also it enables reproducible catheter moves inside the heart chamber. And here you see the setup of the system. So the patient lies here on the table. There are two large magnets on both sides. And here you see the catheter, which is used in this system. So it's more like a spaghetti catheter, which is steered by the magnets inside the body. And here you see how this catheter can be bent in curves, which are nearly impossible to do manually. So here you can easily maneuver your way throughout the latest or abnormal atrial anatomy. Then we have also development in the various ablation technologies. So we used to have only RF energy, but nowadays we have the cryothermal energy and the pulse field ablation, particularly for the pulmonary vein isolation. So based on the electroanatomical activation maps, different mechanisms can be identified. And in patients with tautology of Fallot, it's mainly the cavotracuspid isthmus-dependent atrial flutter with a zone of slow conduction in the inferior part of the atrium. The second most common arrhythmia is the intra-atriorientic tachycardia. And in the intra-atriorientic tachycardia, the wavelength propagates through multiple areas of scar tissue. And we terminate this tachycardia by creating linear lesions across the zones of slow conduction of the crucial pathways of conduction. And the problem with the intra-atriorientic tachycardia is that when you terminate one corridor, the waveform propagates around the other areas of scar tissue, and in that case, multiple forms of intra-atriorientic tachycardia can develop. And the last type of arrhythmia observed in this patient group is the focal atrial tachycardia, which is less frequently observed, where you have a circumscript region where the activation pattern arises, and from there, it spreads to multiple sides of the atria. The question always arises, what exactly is scar tissue? And it should identify scar tissue as non-excitable tissue, but we often have crucial pathways of conduction inside the re-entries embedded within the low-voltage areas. And already many years ago, we identified the cut-off value for low-voltage tissue by using bipolar voltages by comparing electrograms obtained from patients without congenital heart disease, and for example, focal atrial tachycardia, atrial flutter, and atrial ventricular nodal re-entry tachycardia, and we compared that with the amplitude of bipolar voltages obtained from patients with intra-atriorientic tachycardia, and we observed that the voltages smaller than 0.1 millivolt were mainly present in the patients with intra-atriorientic tachycardia. And this cut-off value is therefore often used to quickly identify your area of interest. Here you see an example where you have clearly a focal pattern of activation originating from the right atrium, from where it spreads to multiple directions. And here you see an example of an activation map of an atrial flutter in a patient with tautology of fallot, where it's clearly a counterclockwise activation. And then here you can see an activation map where you have an intra-atriorientic tachycardia, and where the tachycardia was terminated by creating a linear lesion between a scar tissue from the abscetomy scar and the cava tracuspid isthmus. What about the success rate of ablation therapy in this patient group? What do we know? Many years ago, we performed a multicenter study where we included 38 patients with tautology of fallot, the mean age of 43 years. This group underwent a total correction at the age of 70, and nearly 26 years later, this patient underwent an ablation procedure. And here you see the summary of the outcome of the ablation procedures. So the majority of the patients indeed presented with the cava tracuspid isthmus-dependent atrial flutter and the intra-atriorientic tachycardia. You can also see that some of these patients underwent multiple ablation procedures, and also that if they underwent a second or a third ablation procedure, the mechanism underlying eurythmia could also be different. So initially you had an atrial flutter, but then they developed in the second procedure an intra-atriorientic tachycardia, or it was vice versa. They started with an intra-atriorientic tachycardia, and in the second procedure, they developed an atrial flutter. The patients were followed, and the entire follow-up period was about 45 months. And here we see the outcome in relation to the ablation procedure, and the majority of the patients were in sinus rhythm at the end of the follow-up period, but also six patients had developed atrial fibrillation. So what have we learned so far from ablated therapy in patients with congenital heart disease? Well, the majority of the mechanisms, they're either just focal or reentry, with the majority being reentry and only a minority being focal. And if you have successive atrial tachyarrhythmias developing over time, they may be caused by different mechanisms, and also the successive atrial tachyarrhythmias may also develop from different atrial sites. Ablated therapy in this patient group can be a potential curative treatment modality, and the average success rates of the majority of the papers involving patients with the challenge of follow have a procedure success rate of ranging between 70 and 80%. When you have successive atrial tachyarrhythmias developing from different atrial sites, it indicates that there is a progression of electropathology and that the successive atrial tachycardia, also called the so-called recurrences, are not actually recurrence but novel atrial tachyarrhythmias, and also that they are not caused by arrhythmiogenicity of prior ablation lesions. And despite the fact that they have recurrent arrhythmias over time, the long-term follow-up indicates that the majority of patients with congenital heart disease undergoing ablated therapy remain in sinus rhythm, and that's on average 70%. The next challenge in patients with tautology of follow is the emergence of atrial fibrillation. And we know from a study of nearly 500 patients with congenital heart disease that patients with congenital heart disease originally present with bruxismal atrial fibrillation, as we can see on the left side of the slide, but on the right side of the slide we can see that if the patients age, the prevalence of bruxismal atrial fibrillation decreases, and the patients with more persistent and permanent types of atrial fibrillation increases. The development of atrial fibrillation in patients with tautology of follow is rather a complex system, because you have triggers and you have substrates, and they are both required for the development of atrial fibrillation, but the triggers and the substrate are influenced by various parameters, including the age, the sex, ethnicity, underlying genetics, and numerous non-modifiable and modifiable risk factors, and they all give rise to atrial fibrillation. When atrial fibrillation progresses from the bruxismal form to the more persistent types of atrial fibrillation, there is also a change from a trigger-driven to a more substrate-mediated type of atrial fibrillation. And if you take a look at the literature in all patients with atrial fibrillation, so irrespective of the underlying heart disease, we can see here the mechanisms which have been reported, so the patients can have one foci or can have multiple foci. There can be a mother wave giving rise to multiple daughter waves. There can be a single fixed rotor, or it can be moving across the atria. There are unstable re-entry circuits. There may be just simple multiple wavelets. There may be a combination of foci and multiple wavelets, and on top of that, there may be endoapicardia, asynchrony, underlying atrial fibrillation. So the exact mechanism, particularly the mechanism of atrial fibrillation in patients with tetrazoidal fallot, is so far unknown. And that is a problem, because atrial fibrillation in this group arises at a very young age. And here you see in a cohort of nearly 200 patients with congenital heart disease, which included 21 patients with tetrazoidal fallot, that the average age on which atrial fibrillation for the first time presented was around the age of 50. But as you can see here, there are also multiple patients with younger age and even at the age of 20 who developed atrial fibrillation. But on the other hand, there were also patients at the age of 70 or nearly 80 who developed the first episode of atrial fibrillation. There's also often a coexistence of atrial tachyarrhythmias and atrial fibrillation. So in this study, in the 21 patients included with tetrazoidal fallot, you can see that 11 patients had the coexistence of atrial fibrillation and atrial tachycardia. By that, I mean that they presented with either atrial tachycardia or atrial fibrillation, but there was no intervention in between. So they spontaneously presented with either regular atrial tachyarrhythmia and atrial fibrillation. Another feature is that the progression of atrial fibrillation in patients with congenital heart disease is also quite fast. So in the entire population, it was 26% with progress from the paroxysmal form to the long-standing persistent and permanent form in less than five years. And in the 80 patients who completed a follow-up of the entire follow-up, seven patients progressed to the persistent types of atrial fibrillation in less than five years. So I think this justifies a more aggressive treatment approach. If you take a look at the papers publishing on the pulmonary vein outcomes in isolation outcomes in patients with congenital disease, there are two major studies. And this is the first study, including 250, 40 patients with congenital heart disease. And if we take a look at the patient with tetralofalo, we can see that there are eight patients included. And in the other study, there were four patients with the tetralofalo included. So the evidence of outcomes of pulmonary vein isolation in this patient group is quite limited. But why would a pulmonary vein isolation in patients with tetralofalo be effective? Well, first of all, you may simply isolate the trigger because it's located inside the pulmonary veins. You may interrupt crucial pathways of conduction. You may denervate the atria, or you may just simply modify the arrhythmogenic substrate, whatever that may be. But on the other hand, you could also think, why would pulmonary vein isolation be not effective in this patient group? There could be simple reconduction, and that is solvable. It could also be that there are triggers outside the pulmonary vein, and we know that triggers are facilitated by atrial stretch, so there could also be trigger activity originating from the right side. There can be an extensive arrhythmogenic substrate outside the left atrial-posterior wall, and that may be just because atrial fibrillation in this patient group is more a right atrial disease instead of a left atrial disease. So to summarize our knowledge on atrial fibrillation in patients with tetralofalo, we can say that the pathophysiology of atrial fibrillation is mainly unknown. There is progression to permanent atrial fibrillation with aging. If progression occurs, it occurs rather fast. The role of the pulmonary veins, I think it's still a question and needs to be further investigated. So what would we like to answer? First of all, we'd like to know, are the triggers mainly from the pulmonary veins? Should we actually isolate the pulmonary veins in patients with tetralofalo? What is exactly the definition of the arrhythmogenic substrate? We cannot simply use the parameters of the arrhythmogenic substrate of a patient without congenital heart disease and translate it to the patient with congenital heart disease. And what is then the location of the arrhythmogenic substrate? Could we develop some kind of anatomical approach for that? And only then, if we have the answer to these questions, we can effectively treat atrial fibrillation in patients with tetralofalo. I would like to thank you for your attention.

atrial arrhythmias

tetralogy of Fallot

sinus node dysfunction

ablation therapy

tricuspid regurgitation

advanced mapping systems