Atrial Fibrillation Ablation in Congenital Heart Disease: Therapeutic Challenges and Future Perspectives

Abstract

The increasing prevalence of atrial fibrillation (AF) in adults with congenital heart disease raises significant questions regarding its management. The unique underlying anatomic and physiological background further adds to the difficulty in eliminating the AF burden in these patients. Herein, we provide an overview of the current knowledge on the pathophysiology and risk factors for AF in adult congenital heart disease, with a special focus on the existing challenges in AF ablation. Emerging imaging modalities and ablation techniques might have a role to play. Evidence regarding the safety and efficacy of AF ablation in adult congenital heart disease is summarized, especially for patients with an atrial septal defect, Ebstein anomaly of the tricuspid valve, tetralogy of Fallot, and Fontan circulation. Finally, any remaining gaps in knowledge and potential areas of future research are highlighted.

Nonstandard Abbreviations and Acronyms

ACHD

adult congenital heart disease

RA

right atrium

ToF

tetralogy of Fallot

The annual incidence of atrial fibrillation (AF) in adult congenital heart disease (ACHD) is estimated at ≈7.62 in 1000 per year. ¹ This is considerably higher compared with the reported annual incidence of 1.41 in 1000 in the general population. ¹ The AF burden also varies with age, with patients with ACHD aged <50 years and 50 to 59 years having 20‐fold and 10‐fold higher AF incidence, compared with the general population, respectively. ¹ Moreover, contrary to the general population, where male sex is associated with a 1.5‐fold AF risk, being a man may not be a risk factor for AF in all ACHD types. ¹

Although intra‐atrial reentrant tachycardia is the prevailing type of atrial arrhythmia, the number of patients with ACHD presenting with AF has steadily increased along with the improved survival and aging of this population over the past decades. ² , ³ Specific lesions within the ACHD spectrum have been associated with increased risk for AF. These include atrial pathology or right‐sided lesions, such as secundum atrial septal defect (ASD), atrioventricular septal defect, Ebstein anomaly of the tricuspid valve, tetralogy of Fallot (ToF), tricuspid atresia, and other complex ACHD. ¹ Of interest, progression of AF from paroxysmal to persistent or permanent seems to be more frequent among patients with ACHD, occurring only within 3 years after the first episode. ⁴ Hence, AF constitutes a significant clinical burden in the ACHD population and is associated with substantial morbidity and death. ⁵

Despite the progress made within the ACHD therapeutic arena, managing AF is still a challenging issue in ACHD. Therapeutic decision‐making is based on the underlying cardiac lesion, the subsequent hemodynamics, and the patient's quality of life. ⁶ Rhythm control is generally preferred as the initial strategy to prevent major hemodynamic consequences. ⁵ Αntiarrhythmic drugs have poor efficacy and are frequently associated with negative inotropic and dromotropic effects. This renders catheter ablation the first‐line rhythm control therapy in a significant number of patients with ACHD. ⁵ , ⁷ However, evidence on AF catheter ablation in ACHD has only recently begun to aggregate.

The current review outlines the arrhythmogenic mechanisms behind AF in the most common and challenging forms of ACHD. It also discusses specialized strategies, as well as the safety and efficacy of AF ablation in this challenging population.

Pathophysiology and Risk Factors for AF in ACHD

The electrophysiologic mechanisms of AF development and maintenance in ACHD are multiple and complex. As in patients without ACHD, AF is engendered by triggers and is thereafter perpetuated due to an underlying arrhythmogenic substrate. Focal electrical activity provoked by micro‐reentries or triggered activity is the basis for AF genesis. ⁸ Ιntraoperative epicardial mapping studies have demonstrated that activation patterns might differ between paroxysmal and persistent AF. ⁹

Although pulmonary veins are considered the primary source of AF in structurally normal hearts, AF in ACHD may arise from other non–pulmonary vein ectopic foci (“extrapulmonary triggers”), such as the right atrium (RA) and crista terminalis, the left atrial roof/posterior wall, the left atrial appendage, the superior vena cava (right or left persistent), the coronary sinus ostium, the interatrial septum, and the ligament or vein of Marshall. ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ All these sites have been known to contain atrial myocytes with potential arrhythmogenic electrical activity. ¹⁴ According to a large observational study, patients with AF initiating from non–pulmonary vein ectopy are younger and more frequently have nonparoxysmal AF, right atrial enlargement, and biatrial remodeling compared with patients with AF initiating from pulmonary vein triggers only. ¹¹ However, the non–pulmonary vein triggers (focal or reentrant) have not been fully elucidated yet; more research is required to identify those substrates, localize the trigger sources and, therefore, guide future AF ablation in patients with ACHD.

Histological and morphological myocardial changes, as well as subsequent structural remodeling, are involved in AF initiation. ¹⁵ In ACHD, long‐lasting atrial enlargement (and remodeling) caused by residual septal defects, valvular disease (eg, Ebstein anomaly and tricuspid atresia), partial anomalous pulmonary venous return, Fontan circulation, or acquired conditions and comorbidities may favor AF development. ¹⁵ , ¹⁶ Duration of atrial volume overload has been identified as a key factor linked with atrial fibrosis and AF genesis per se. ¹⁵ Moreover, AF can be triggered by left atrial dilation and myopathy, induced by left ventricular diastolic dysfunction in patients with left heart obstructive disease (including those with multiple obstructive left heart lesions, eg, Shone complex). ¹⁷

Furthermore, myocardial scars and fibrosis due to prior cardiac surgeries, patches, or atrial baffles (after atrial switch procedure in patients with transposition of the great arteries) stimulate ion channel changes and, therefore, reentry mechanisms constituting a substrate vulnerable to AF. ¹² , ¹⁶ Detailed intracardiac electroanatomic mapping studies have demonstrated stable single‐ or multiple‐loop circuits in the context of extensive atrial scarring linked with electrical dissociation of the dilated atrial chambers. ¹⁸ AF could also result from sinus node dysfunction in the context of the underlying ACHD or as a postoperative complication. ¹⁶ In addition, patients with ACHD who had undergone ablation for intra‐atrial reentrant tachycardia may be prone to develop AF later in life. ⁵

Apart from the conventional risk factors associated with AF (ie, age, sex, obesity, arterial hypertension, diabetes, dyslipidemia, heart failure, and coronary artery disease), ¹⁹ , ²⁰ patients with ACHD are also subject to specific risk factors due to the underlying congenital heart defect. The anatomic complexity, number of previous corrective or palliative surgeries, arterial hypoxemia in patients with cyanosis, hemodynamic stress, and conduction system abnormalities may further predispose to AF in ACHD. ⁵ , ¹⁶ Of interest, rare congenital diseases have been also associated with AF development, including endocardial fibroelastosis and left ventricular noncompaction. Endocardial fibroelastosis often coexists with other congenital defects, such as hypoplastic left heart syndrome, and is characterized by ventricular stiffness, atrial dilation, and subsequent arrhythmias. ²¹ Regarding the left ventricular noncompaction, AF could be attributed to endogenous disease‐associated myopathy or atrial enlargement due to cardiac dysfunction. ²²

Novel Technologies for AF Detection in ACHD

Novel technologies and approaches have been developed for remote monitoring of heart activity. Recently, wearable devices, using either photoplethysmography or ECG, have emerged for detecting paroxysmal or asymptomatic AF and facilitating timely management. ²³ These advancing devices can be useful in individuals with ACHD to quantify the arrhythmia burden, evaluate the response to medications or ablation, and identify the best time for intervention. ²⁴ Nevertheless, most wearable devices have not been validated in ACHD, due to the wide anatomic and physiological heterogeneity. Therefore, caution is warranted in the implementation of these revolutionary technologies in clinical practice in these patients. ²⁴

Machine learning and artificial intelligence algorithms could improve the accuracy and efficiency of AF detection. They hold promises for AF identification based on normal‐sinus‐rhythm ECG and for future development of AF risk‐stratification schemes. ²⁵ A recent study reported high performance in predicting AF among individuals with ACHD with the use of neural network models. ²⁶ Notably, the complexity as well as the increasing survival of ACHD complicate the development of machine learning–based risk stratification models in this population. ²⁶

AF Ablation Challenges in ACHD and Emerging Techniques

Although AF ablation has emerged as a standardized therapeutic option for AF in patients with normally structured hearts, ¹⁹ it remains a challenging treatment strategy in patients with ACHD due to the complex anatomy and the subsequent procedural difficulties. To date, relevant experience is scanty, and most ablation strategies, such as pulmonary vein isolation, connecting linear lesion sets to the left‐sided mitral isthmus, and cavotricuspid isthmus ablation, are extrapolated from the patients without ACHD. ²⁷ , ²⁸ As AF ablation is intricate in ACHD, it should be performed by a multidisciplinary team of ACHD experts in tertiary centers. ²⁷ , ²⁹

In patients with ACHD, it is of importance to additionally consider that new‐onset AF may reflect a worsening hemodynamic profile, such as the emergence of new/worsening valve disease, shunts, ventricular dysfunction, or surgical pathway obstruction. ³⁰ Managing these conditions could possibly reduce the arrhythmia burden. Subsequently, before addressing AF, patients with ACHD should be evaluated for possible underlying structural causes that may have triggered AF. ³⁰ Whether preoperative AF ablation or intraoperative cryoablation is preferred, in case a concurrent operation is required, depends on the congenital defect, the hemodynamics, and the required surgery; careful individual decisions should be made in expert centers.

Preprocedural planning, multimodality imaging, and intraprocedural guidance are warranted to assess the anatomy and achieve successful ablation. Noninvasive imaging techniques, including echocardiography, computed tomography, or magnetic resonance imaging, should be used to evaluate the atrial size and anatomy. ⁵ Right and left heart catheterization may be useful in cases in which noninvasive assessment is inadequate to depict specific anatomic areas, such as the systemic venous baffle obstruction in patients with transposition of great arteries and atrial switch procedure. ⁵ Additionally, in patients with ACHD and anatomic variations, 3‐dimensional representation of cardiac structures using advanced electroanatomic mapping systems is essential for guiding AF ablation. ⁵ , ²⁷ It enables the identification of crucial anatomic sites, including the His bundle, valve annuli, and phrenic nerve, which may be dislocated in ACHD patients, as well as fibrotic regions and prosthetic materials, including atrial baffles and ASD devices. ⁵ , ²⁷ Moreover, 3‐dimensional reconstruction allows the illustration of the catheters in the cardiac chambers; electrical recordings of these catheters provide essential electrophysiological data, such as wall thickness, conduction patterns, and speed. ³¹ In addition, the application of 3‐dimensional printing in ablation procedures in ACHD would be of added value to optimize preprocedural planning. ³² An example of a 3‐dimensional–printed heart model with planned ablation route is provided in the Figure. Fusion of 3‐dimensional electroanatomic mapping with a computed tomography scan or magnetic resonance reconstructions offers identification of the catheter position in relation to the endocardium and discrimination between scar tissue and poor contact, enabling atrial ablation in patients with complex anatomy. ³³ , ³⁴ Further advanced modalities and techniques should be used to identify AF drivers and facilitate AF ablation in ACHD. Voltage maps are valuable for detecting precisely the fibrotic areas and scars that may be responsible for AF generation. ³¹ , ³⁵ Late‐gadolinium enhancement cardiac magnetic resonance can be used to evaluate ablation scar following ablation and assess pulmonary vein isolation, detecting targets for possible repeat ablation procedures. ³¹ Activation maps could also be used to identify the target areas for AF ablation. ³⁵ Magnetic navigation system has emerged as an advanced technique that enables the remote monitoring of catheters through a magnetic field. Contrary to the conventional ablation techniques, magnetic navigation system catheters are more flexible, and they can reach areas that are difficult or even impossible to reach with conventional ablation catheters due to complex cardiac surgery or limited venous access. Adequate catheter–tissue contact is also ensured to achieve the appropriate cardiac lesion. ³⁶ In this way, the accuracy of the ablation technique is augmented, while the fluoroscopy time is significantly reduced. ³⁵ Moreover, the use of irrigated‐tip catheters is recommended in patients with ACHD to create greater lesions in potentially thickened fibrotic regions. ⁵ Contact force technology enhances the quality of the ablation lesions, increasing the safety of the procedure. ³⁷

Figure . Three‐dimensional–printed heart model with planned ablation route to mimic the radiofrequency ablation of atrial fibrillation in a patient with mirror‐image dextrocardia.

IVC indicates inferior vena cava; LIPV, left inferior pulmonary vein; LSPV, left superior pulmonary vein; RIPV, right inferior pulmonary vein; RSPV, right superior pulmonary vein; and SVC, superior vena cava. Reproduced from “https://link.springer.com/article/10.1007/s42242‐021‐00125‐8” as created by Ma et al. (Ma Y, Ding P, Li L, et al. Three‐dimensional printing for heart diseases: clinical application review. Biodes Manuf. 2021;4 (3):675–687. doi: 10.1007/s42242‐021‐00125‐8 ¹⁰¹ ). The figure is licensed under the Creative Commons Attribution 4.0 International License (“http://creativecommons.org/licenses/by/4.0“) and no changes have been made.

The accumulating body of evidence pinpoints radiofrequency catheter ablation of AF as a safe and effective technique in ACHD with comparable success rates to subjects without ACHD. ³⁸ , ³⁹ , ⁴⁰ Especially in complex anatomic cases (eg, patients with atrial patch/baffles or an occlusion device in the atrial septum), radiofrequency‐assisted transseptal perforation has emerged as a valuable option for permitting left atrial access and ablation. ⁴¹ Less evidence is available on the outcomes of AF cryoablation in ACHD, ⁴² , ⁴³ , ⁴⁴ , ⁴⁵ despite the fact that cryoablation has been shown as noninferior to radiofrequency ablation in individuals with normally structured hearts. ⁴⁶ According to the experience by Krause et al, ⁴⁴ cryoablation plus an additional radiofrequency ablation of atrial tachycardia led to promising success rates without major complications (84% success, including 1 redo procedure). Another recent study suggests that intraoperative use of cryoablation in AF or intra‐atrial reentrant tachycardia can also be feasible and safe, having no intraoperative complications and promising midterm results. ⁴⁵

Ablation in patients with concomitant AF and heart failure with preserved ejection fraction has been recently correlated with optimal heart failure with preserved ejection fraction outcomes. A recent randomized controlled trial demonstrated that AF ablation improved invasive exercise hemodynamic parameters, exercise capacity, and symptoms in patients with heart failure with preserved ejection fraction with comorbid AF. ⁴⁷ In this background, patients with ACHD with diastolic dysfunction, especially those with unrepaired lesions or those with postcorrection persistent diastolic dysfunction, may also benefit from AF ablation.

Patients with ACHD usually present with systemic venous abnormalities that make the ablation procedures intricate. A persistent left superior vena cava or a dilated coronary sinus are commonly encountered in ACHD. ⁴⁸ Moreover, the inferior vena cava may be interrupted below the hepatic veins, and the supracardinal vein may persist and connect the distal inferior vena cava to the azygos or hemiazygos vein. ⁴⁸ Alternative venous paths may be required for AF ablation in ACHD. Access can be obtained via the azygos or hemiazygos veins; however, these routes are longer and twisted, and therefore long catheters may be needed. Additionally, the jugular vein, subclavian veins, femoral collaterals, or hepatic veins can be accessed. ⁴⁸

ACHD Forms Treated With AF Ablation

Atrial Septal Defect

Patients with hemodynamically significant left‐to‐right atrial shunt are exposed to long‐standing volume overload causing increased myocardial stiffness, injury, fibrosis, and eventually atrial structural and electrophysiological remodeling. ⁴⁹ , ⁵⁰ Subsequently, AF is commonly encountered in adults with ASDs. Of note, left‐to‐right shunts result in increased right atrial and right ventricular volume, implying that the RA may contribute to AF development in patients with ASD. Therefore, AF ablation should presumably target both pulmonary veins and RA in this subpopulation. ⁵¹

The major challenge in performing ablation in patients with repaired ASDs is the technical difficulty of transseptal access to the left atrium. AF ablation before or during ASD closure (eg, Maze surgical procedure) may be safer and technically easier in patients with uncorrected ASDs. ⁵² , ⁵³ , ⁵⁴ However, as early ASD closure may reduce the arrhythmia burden, first removing the hemodynamic burden of the pretricuspid shunt lesion and then addressing AF (if still persistent) may be preferred. ³⁰ Besides, surgical patches for ASD closure and ASD occlude devices are not particularly technically challenging for transseptal access when AF ablation is performed in experienced ACHD centers. In patients with unrepaired ASDs, AF ablation can be performed through the ASD or via a transseptal puncture on the interatrial septum. In general terms, access to the left atrium through the ASD is technically feasible and safe in case the sheath can be sufficiently advanced into the left atrium and placed suitably for AF ablation. In contrast, when catheter–tissue contact is inadequate, and the unsuitable catheter position would increase the risk of adverse events (eg, cardiac tamponade, left atrial rupture), access via a transseptal puncture is preferred. ⁵² Limited data are available regarding the safety and efficacy of AF ablation in patients with unrepaired ASDs. A study of 18 patients reported similar arrhythmia‐free survival and complication rates in patients with ASDs and those with normally structured hearts. ⁵² However, isolated AF ablation without a strategy to close the ASD in patients with unrepaired ASDs and a significant left‐to‐right shunt is not recommended.

After ASD repair, the decrease in right ventricular dimensions results in reverse structural remodeling; however, preexisting AF usually persists, possibly due to poor postrepair electromechanical improvement. ⁵⁵ , ⁵⁶ Additionally, ASD closure devices may trigger postclosure AF due to the induced atrial inflammation and stretching. ⁵⁷ Current data suggest that catheter ablation in patients with ASD closure devices, although complex and challenging, is feasible when performed by ACHD experts in tertiary centers. Previous studies have reported successful AF ablation in patients with closure devices accessing the left atrium via a double transseptal puncture in the native interatrial septum, posteroinferior to the device, guided by intracardiac echocardiography and fluoroscopy. ⁵⁸ , ⁵⁹ Lakkireddy et al ⁵⁹ reported similar postablation AF recurrence and perioperative complication rates between patients with ASD occluders and matched controls. However, transseptal access through portions of the native septum may not be achievable when the occluder is oversized, and there is no residual place for puncture in the interatrial septum. It has been proposed that access through the native septum is feasible when the device diameter is ≤26 mm; in the presence of larger devices, though, direct puncture across the occluder is preferable. ⁶⁰

Clinical data support that transseptal access through the device is safe and efficacious, ⁵⁴ , ⁶⁰ , ⁶¹ , ⁶² , ⁶³ , ⁶⁴ with success rates comparable with those described in patients in whom access was gained through the native septum. ⁵⁴ , ⁵⁹ , ⁶⁵ However, to avoid potential septal spit or device dislodgement in the process of penetrating the device, ⁶³ an upsized dilator may be used to dilate the puncture site and enable the sheath to go through the device. ⁵⁴ These additional stages in the AF ablation procedure result in increased fluoroscopy and total procedural times. ⁵⁴ Notably, no significant residual shunt was found in most cases of transseptal access through the device, implying that spontaneous closure usually occurs after ablation. This could be possibly explained by the polymer meshes' elasticity and “shape memory.” Endothelialization may also contribute to filling residual postprocedural gaps. ⁵⁴ , ⁶⁶ , ⁶⁷

Transseptal puncture through a device is widely believed to be a high‐risk procedure. To minimize the risk of potential procedural complications, AF ablation using transseptal approach is recommended in patients with atrial septal rims ≥5 mm and at least 6 months after device placement. ⁵³ Of note, previous studies included only patients with Amplatzer devices, whereas there is no experience in puncturing other device types. ⁵³ Further studies are required to confirm the safety of AF ablation in patients with implemented devices other than Amplatzer.

Regarding patients with surgically corrected ASDs, transseptal access can be facilitated through the surgical patch, potentially using a balloon dilator, similar to the approach followed for patients with closure devices. ⁵⁹ , ⁶⁸ , ⁶⁹ Only previous use of a wide Gore‐Tex patch was found prohibitive for transseptal access, as it is a hard material to be perforated. ⁵⁹

Tetralogy of Fallot

AF has been documented as the prevailing atrial arrhythmia in patients aged >55 years with ToF, with a reported prevalence of 30%. ⁷⁰ The arrhythmogenic potential in adults after surgical correction of ToF could be attributed to the right atrial pressure overload (due to the right ventricular dysfunction); the tricuspid, mitral, or pulmonary regurgitation; and the atrial surgical scars in case of previous ventricular septal defect repair via right atriotomy. ⁷¹ , ⁷² The different types of ToF repair, including ventriculotomy, transannular patch, or palliative shunt, have not been associated with differences in the AF rate. ⁷³ , ⁷⁴

Evidence on AF ablation in patients with ToF remains scarce. Limited data showed that ablation is feasible and effective in such patients. ⁴² , ⁷⁵ However, the effectiveness of AF ablation in these patients merits further study.

The procedural success rates depend on the extent of the anatomic complexity, while the detailed depiction of the anatomy, using 3‐dimensional mapping, combined with computed tomography or magnetic resonance imaging or angiography and intracardial ultrasound, is fundamental. ⁷⁶ The coronary sinus remains a stable reference site for the catheter location in ToF. Due to atrial hypertrophy, irrigated or 8‐mm electrode tip radiofrequency catheters are preferred. The fibrotic regions often constitute the base for multiple reentrant circuits. Therefore, during ablation, as the circuit patterns change, there is often a conversion from 1 atrial tachycardia to another. The sub‐Eustachian isthmus (between the tricuspid valve annulus and inferior vena cava) and the posterolateral RA are the main arrhythmogenic areas in ToF hearts. Moreover, low‐voltage areas that are representative of surgical scars might also be targeted to eliminate the circuit. ⁷⁰

Ebstein Anomaly of the Tricuspid Valve

AF incidence in patients with Ebstein anomaly ranges from 8% to 50%. ⁷⁷ The arrhythmogenic potential in these patients is mainly attributed to the congenital conduction abnormalities, the right atrial dilatation due to the tricuspid valve dysfunction, and the scars following surgical repair. ⁷⁷ A Maze procedure is commonly performed in patients with Ebstein anomaly with AF undergoing surgery (eg, tricuspid repair or replacement). In such cases, a biatrial procedure seems to offer higher freedom rates for recurrent arrhythmia. ⁷⁸ Prophylactic surgical ablation is also proposed in patients without arrhythmia but at high risk (significant dilatation of the atria, mitral valve disease, multiple incisions) to prevent future events. ⁷⁸

Catheter ablation presents difficulties due to the morphology of the RA, the tricuspid valve, and the atrialized ventricle, resulting in longer‐than‐average procedural time. ⁷⁷ , ⁷⁸ A steerable sheath can be used in case of severe RA enlargement to improve tissue contact. ⁷⁷ Moreover, during endocardial mapping, fractionated potentials recorded from the RA and the atrialized right ventricle can lead to interference with the true atrial and ventricular potentials. ⁷⁹ Notably, the presence of concomitant abnormalities, such as ASD or patent foramen ovale may facilitate access to the pulmonary veins in patients with Ebstein anomaly.

Current literature is limited regarding the outcomes of AF catheter ablation in Ebstein anomaly, and existing evidence comes mostly from case reports. Successful AF ablation has been reported in 2 single cases of patients with Ebstein anomaly. ⁸⁰

Fontan Circulation

The classic Fontan circulation (anastomosis of the RA directly to the right pulmonary artery) has been associated with a high incidence of atrial arrhythmias, including AF, possibly due to the right atrial distention, atrial pressure overload, atrial scars, or obstruction in the Fontan circuit. ⁸¹ The modifications of the Fontan operation (total cavopulmonary connection using a lateral tunnel or extracardiac conduit) have reduced the arrhythmia burden; however, AF still occurs in patients following a modified Fontan procedure. ⁸¹ , ⁸² The fact that even patients with extracardiac conduits develop AF implies that mechanisms such as preprocedural, hypoxemia‐induced, structural, and functional changes, as well as autonomic dysfunction may also play a proarrhythmogenic role. ⁸³

To date, there is scanty information regarding the safety and efficacy of AF ablation in patients following a Fontan procedure and derives only from case reports and small cohorts that grouped patients with Fontan circulation together with other patients with ACHD. ²⁹ , ⁸⁴ , ⁸⁵ Accessing the pulmonary venous atrium in this population is a challenging endeavor. In patients with atriopulmonary connection, right atrial pressure overload leads to extreme wall thickness that entangles the creation of transmural ablation lesions. ⁸⁶ In the setting of total cavopulmonary connections, ablation can be accomplished by penetrating an existing patent fenestration or by performing a transcaval or transconduit puncture. ⁸³ The transcaval access includes perforating a site of overlap between the inferior vena cava and the pulmonary venous atrial wall. This approach has proven feasible in patients with extracardiac conduits and sufficient cavoatrial overlap (>3 mm). ⁸⁷ Moreover, successful ablation of atrial arrhythmia has been described using a transconduit approach. ⁸⁸ In case conduit crossing is impossible because of large‐scale calcifications, ⁸⁷ , ⁸⁸ the pulmonary venous atrium can be reached via a retrograde aortic route with the use of magnetic navigation system. ⁸³ , ⁸⁹ However, this approach seems to be intricate, too. Potential difficulties include transversing the systemic semilunar and atrioventricular valve and catheter handling in the tortuous retrograde aortic course. ⁹⁰

An alternative option for controlling the arrhythmia burden in these patients is the surgical conversion of atriopulmonary to total cavopulmonary connection along with cryoablation. ⁹¹

Safety and Efficacy of AF Catheter Ablation in ACHD

According to current data, the success rate of a single AF catheter ablation (defined as freedom from AF at the follow‐up period) in patients with ACHD varies widely from 26.3% to 92% (Table). ³⁸ , ⁴⁰ , ⁴² , ⁴³ , ⁴⁴ , ⁵¹ , ⁵² , ⁵⁴ , ⁵⁹ , ⁶³ , ⁹² , ⁹³ , ⁹⁴ , ⁹⁵ , ⁹⁶ , ⁹⁷ Notably, the procedure seems to be more effective in patients with ASD. ⁶⁴ However, the AF recurrence rate is high, reaching up to 56.1% in previous studies (Table); therefore, repeated ablation attempts may be needed to manage AF. Anatomic complexity, persistent AF pattern, and left atrial size have been proposed as independent predictors of arrhythmia recurrence after AF catheter ablation. ²⁹

Table .

Studies Evaluating the Safety and Efficacy of AF Catheter Ablation in Patients With ACHD

No.	Authors; year	Study type	Study population (N)	ACHD type, N (%)	Age, y	Follow‐up duration, mo	Success rate of a single procedure, %	Recurrence, N (%)	Complications, N (%)	Death, N (%)
1	Hu et al; 2023 92	Multicenter retrospective cohort	145	Secundum ASD: 28 VSD: 12 Bicuspid aortic valve: 69 Subaortic stenosis: 1 AV canal defect: 7 ToF: 4 Sinus venosus ASD with anomalous PV connection: 4 Ebstein anomaly: 3 Shone complex: 3 Coarctation with BAV: 3 Pulmonary stenosis: 1 Cleft mitral valve: 1 Fontan circulation: 3 CC‐TGA: 2 TGA: 1 Pulmonary atresia with 2‐ventricle repair: 2 Double‐outlet RV: 1	57±12	26 (IQR, 14–69)	92	37	12 (8.3) 1 Sinus node dysfunction 2 PV stenosis 1 small pericardial effusion 1 retroperitoneal bleed 2 femoral hematoma 2 infection 1 torsades de pointes	10 (6.9)
2	Griffiths et al; 2022 42	Multicenter retrospective cohort	240	ASD: 78 (32.5) TGA: 14 (5.8) Anomalous PVs: 13 (54.2) ToF: (3.3) Cor triatriatum: 7 (2.9) Single ventricle physiology: 2 (0.8) Other: 118 (49.2)	55.2±13.3	12	45.0	34.5	16 (6.7%) Major complications: 3 (1.3) Minor complications: 13 (5.4)	1/240 (0.4)
3	Krause et al; 2022 44	Prospective cohort	19	ASD: 2 (10.6) AVSD: 3 (15.8) CoA: 2 (10.6) Double‐chambered right ventricle: 2 (10.6) Ebstein anomaly: 1 (5.3) ToF: 2 (10.6) Other: 7 (36.8)	58 (IQR, 47–63)	26 (IQR, 9–49)	84	9/19 (47)	1 (5), right‐sided phrenic nerve palsy	0
4	Moore et al; 2021 85	Retrospective cohort	31	TGA: 4 (12.9) ASD: 4 (12.9) CoA: 3 (9.6) Other: 20 (64.5)	51±17	12	76%	NA	Major complications: 0 Minor complications: 2 (6) 1 Oropharyngeal bleeding 1 Prolonged fluoroscopy	0
5	Kottmaier et al; 2020 93	Retrospective cohort	46	ASD: 27 (59) VSD: 4 (9) Anomalous PV return: 3 (7) Tricuspid atresia: 1 (2) Ebstein anomaly: 3 ToF: 2 (4) Shone complex: 2 (4) TGA: 1 (2) Single ventricle: 3 (7)	52.8±13	18	42	NA	Major complications: 0 Minor complications: 6 (13) groin hematomas	0
6	Ogiso et al; 2020 94	Retrospective cohort	20	Catheter ablation before percutaneous ASD closure	61.4±10.5	50±30	NA	2/20 (10)	1 (2.8) intrapelvic hematoma	NA
7	Garg et al; 2020 62	Meta‐analysis	64	ASD with device occluder	54.22±8.82	6–22	77.7	Septal puncture: 23.07 Device puncture: 16.66 Overall: 22	Inadvertent epicardial puncture: 3 (4.6) Groin hematoma: 1 (1.6)	NA
8	Zhao et al; 2020 95	Retrospective cohort	10	Situs inversus dextrocardia	58.9±10.1	35.27 (IQR, 6–72)	3/10 (30)	NA	NA	NA
9	Sohns et al; 2018 40	Retrospective cohort	57	ASD: 26 (45.6) VSD: 2 (3.5) Ebstein anomaly: 4 (7.0) CoA: 4 (7.0) ToF: 2 (3.5) Other: 19 (33.3)	51.1±14.8	41±36	15/57 (26.3%)	32/57 (56.1%)	Major complications: 1/57 (1.8) Pericardial tamponade Minor complications: 12/57 (21.1)	NA
10	Liang et al; 2019 39	Multicentre retrospective cohort	84	ASD: 27 (32.1) VSD: 9 (10.7) Pulmonic/subpulmonic stenosis: 7 (8.3) Anomalous PV return: 8 (9.5) ToF: 7 (8.3) TGA: 7 (8.3) Other: 19 (22.6)	51.5±12.1	24±27	43/81 (53.1)	21/81 (28.8) At the 3‐mo postablation blanking period	Major complications: 0 Minor complications: 7/84 (8.3)	2/84 (2.3)
11	Guarguagli et al; 2019 29	Retrospective cohort	58	ASD/PFO: 22 (36.2) VSD: 1 (1.7) AVSD: 3 (5.1) CoA: 7 (12) Ebstein anomaly: 3 (5.1) Other: 21 (36.2)	51 (IQR, 44–63)	24 (IQR, 11–69)	32.8 at 1 y	NA	Major complications: 0	1/58
12	Pranata et al; 2019 64	Meta‐analysis	393	CHD	54.23±11.58	NA	58.02 At 1 y	NA	Major complications: 5/393 (1.2) Minor complications: 26/393 (6.6)	NA
13	Turagam et al; 2019 96	Multicenter retrospective cohort	28	Persistent left superior vena cava	61±8	12	21/28 (75) At 1 y	7/28 (25) At 1 y	Major complications: 0 Minor complications: 4/28 (14) Groin hematoma: 3 (11) Small pericardial effusion 1 (3)	NA
14	Nakagawa et al; 2019 97	Retrospective cohort	30	ASD with closure device	63±12	49±23	79 at 5 y	6/30 (20)	0	NA
15	Kamioka et al; 2019 51	Retrospective cohort	11	ASD	54±20	14±9	NA	Before ASD closure: 2/11 (18) At 10±6 mo After ASD closure: 0/11 (0)	Major complications: 0	NA
16	Abadir et al; 2019 43	Retrospective cohort	10	ASD: 6 (60) ASD associated with VSD: 1 (10) Quadricuspid aortic valve with aortic stenosis: 1 (10) Sinus venosus ASD with partial anomalous PV return: 1 (10) CoA with a persistent left superior vena cava: 1 (10)	57.9 (IQR, 48.2–61.7)	34 (IQR, 17–54)	6/10 (60) at 1 y	4/10 (40)	Major complications: 0	NA
17	Sang et al; 2017 63	Prospective cohort	16	ASD with closure device	56±12	16±6	12/16 (75)	6/16 (25)	Major complications: 0 Minor complications: 1/16 (6.3) groin hematoma	NA
18	Nie et al; 2014 52	Retrospective cohort	18	ASD unrepaired	64.06±9.82	20	10/18 (55.5)	44.4	Major: 1 (5.5) acute heart failure	NA
19	Philip et al; 2012 38	Retrospective cohort	36	ASD: 22 (61) VSD: 6 (17) ASD and VSD: 3 (8) ToF: 1 (3%) Double‐outlet left ventricle and TGA: 1 (3) CoA: 1 (3) Ebstein anomaly: 3 (8) Bland–Garland White syndrome with cardiomyopathy: 2 (6)	53.4±2	7	42 at 300 d	NA	6/36 (17) Vascular access site: 3/36 (8.3) Embolic event: 2/36 (5.6) Pulmonary stenosis: 1/36 (2.8)	NA
20	Santangeli et al; 2011 54	Prospective cohort	39	ASD with closure device	54±6	14±4 mo	30/39 (77)	9/39 (23)	Major complications: 0	NA
21	Lakkireddy et al; 2008 59	Prospective cohort	45	ASD repaired: 28 (62) PFO repaired: 17 (38)	52±11	15±4 mo	76	24	2/45 (4): trace pericardial effusion 1/45 (2): TIA 2/45 (4): PV stenosis	NA

ACHD indicates adult congenital heart disease; AF, atrial fibrillation; ASD, atrial septal defect; AVSD, atrioventricular septal defect; BAV, bicuspid aortic valve; CC‐TGA, congenitally corrected transposition of great arteries; CoA, coarctaction of the aorta; IQR, interquartile range; NA, not applicable; PFO, patent foramen ovale; PV, pulmonary vein; RV, right ventricle; TGA, transposition of great arteries; TIA, transient ischemic attack; ToF, tetralogy of Fallot; and VSD, ventricular septal defect.

The highest rate of arrhythmia recurrence has been observed in patients with Fontan circulation. Previous data revealed that recurrent arrhythmias in this population derived from different atrial sites to the first ablated one. ⁹⁸ , ⁹⁹ This observation implies that arrhythmogenic due to the prior ablated lesions or prior failed ablation attempts may not be primarily involved in the recurrence genesis. ⁹⁸ , ⁹⁹ In contrast, progressive atrial cardiomyopathy has been proposed as a possible responsible mechanism for the new AF episodes in patients with Fontan circulation. ⁸³ , ⁹⁸ , ⁹⁹

Existing evidence supports that the procedural complication rate in ACHD is low and comparable to that reported in patients without ACHD. ⁸⁵ , ¹⁰⁰ Most ACHD studies described no major complications after AF ablation, ³⁹ , ⁴³ , ⁵¹ , ⁵⁴ , ⁶³ , ⁸⁷ , ⁹³ , ⁹⁶ whereas periprocedural adverse events such as access site complications, acute heart failure, pericardial effusion or tamponade, transient ischemic attack, pulmonary vein stenosis, and phrenic nerve palsy are scarcely observed. ³⁸ , ⁴⁰ , ⁴² Moreover, previous studies reported minor complications (including groin hematoma, oropharyngeal bleeding, sedation‐related complications, and infection) in up to 21.1% ³⁹ , ⁴⁰ , ⁴² , ⁶³ , ⁸⁷ , ⁹³ , ⁹⁶ (Table). Consequently, AF catheter ablation seems to be a safe procedure, even for patients with complex CHD.

Conclusions

The recent technological advances in catheter ablation techniques and imaging modalities rendered AF ablation feasible in patients with ACHD. Due to the underlying complex anatomic variants of this heterogenous population, special personalized ablation strategies and multiple procedures may be required. AF ablation can be safe and efficient when performed by ACHD specialists in expert tertiary centers. Further studies are needed to provide insight into the long‐term results of catheter ablation in ACHD and guide the prompt AF management in this patient group.

Sources of Funding

This work was supported by Pfizer through the European Thrombosis Investigator Initiated Research Program (ERISTA, Reference Number: WI246683). The funder had no role in the design or conduct of the study; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclosures

None.