Innovative Management of Rhythm Disorders in Adults with Congenital Heart Disease

Atrial Arrhythmias

Atrial arrhythmias are the most prevalent rhythm disorders in ACHD, with IART being the predominant arrhythmia followed by AF.²⁰ Both contribute to heart failure, thromboembolism, and impaired quality of life.^21,22 The underlying substrate is heterogeneous, comprising atriotomy scars, suture lines from baffles or conduits, atrial dilation, and areas of low-voltage myocardium that anchor reentry circuits.²³ Electrophysiologists specialized in CHD generally favor the label IART over atrial flutter. Unlike “typical” or “atypical” flutter, IART avoids presupposing the existence of a standard cavotricuspid isthmus. In the ACHD population, the anatomy is often unconventional: the tricuspid valve may be rudimentary, absent, displaced into the pulmonary venous atrium, or even split between atria. In AV septal defects, the right-sided valve itself is not truly tricuspid, rendering “cavotricuspid” a misnomer. On top of this structural variability, electrocardiographic signatures are often less clear-cut, and reentry frequently involves complex double-loop or figure-of-eight circuits traversing the AV valve to vena cava region. High-density mapping catheters now permit rapid identification of low-voltage corridors and fractionated potentials, enabling tailored ablation of non-cavotricuspid–dependent circuits with improved acute success.²⁴

Fontan patients represent a particularly vulnerable group. Surgical modifications of the atria, incisions, baffles, elevated venous pressures, and progressive atrial fibrosis create an arrhythmogenic milieu that evolves over decades.25 In these patients, arrhythmias are not only symptomatic but may be poorly hemodynamically tolerated and precipitate thromboembolism and Fontan circulatory failure. Mapping challenges include catheter stability in markedly dilated right atria among patients with classic modified Fontan procedures and access to the pulmonary venous atrium in those with total cavopulmonary connections.⁹ Integration of imaging modalities, such as intracardiac echocardiography (ICE) and preprocedural computed tomography (CT) or cardiac magnetic resonance (CMR) imaging, with electroanatomic mapping, facilitates access via transcaval, transbaffle, or robotic magnetic-guided retrograde aortic approaches.^26,27

Ventricular Arrhythmias

Patients with CHD who face an elevated risk of ventricular arrhythmias and SCD can be broadly categorized into two conceptual groups: those in whom reentrant monomorphic VT arises from well-defined anatomic circuits, as in rTOF, and those with more diffuse arrhythmogenic substrates, exemplified by patients with systemic right ventricles.²⁸ Reentrant monomorphic VT was first recognized decades ago in patients with rTOF, with inducible VT identified as an important marker of risk.²⁹ More recently, the critical anatomic isthmuses underlying these reentrant circuits have been more precisely delineated.³⁰ The pathophysiologic substrate is defined by so-called slow-conducting anatomical isthmuses (SCAIs) that are bordered by patches, valve annuli, or surgical scars. Among the four principal isthmuses that have been characterized, the isthmus between the ventricular septal defect patch and pulmonary anulus is most commonly implicated in reentrant VT (Figure 1).¹⁰

Figure 1

Traditional risk factors such as QRS duration, nonsustained VT, and extensive ventricular fibrosis provide modest predictive power for VT and SCD in rTOF. By contrast, inclusion of electrophysiological studies with inducibility of VT and identification of SCAIs appears to provide additional prognostic value.^10,31 Three-dimensional late gadolinium enhancement CMR imaging (3D-LGE-CMR) has emerged as a potential tool to noninvasively identify high-risk substrates.^32,33 Electrocardiographic markers also provide valuable insights. Fragmented low-amplitude R′ wave in lead V1 and terminal S waves in inferior leads have been attributed to conduction abnormalities across the septal isthmus, establishing a mechanistic link between right ventricular activation and these common electrocardiographic patterns.³⁴ Preventive strategies are under active investigation. The “Catheter Ablation of Ventricular Tachycardia Before Transcatheter Pulmonary Valve Replacement in Repaired Tetralogy of Fallot” (CATAPULT-TOF) study is testing whether ablation of critical isthmuses involved in inducible VT together with prophylactic ablation of SCAIs prior to transcatheter pulmonary valve replacement reduces the risk of subsequent clinical VT and SCD.³⁵ This approach embodies a shift toward mechanism-based prevention, integrating hemodynamic and arrhythmic interventions.

Intraoperative Conduction Mapping

Conduction disturbances, including postoperative AV block and sinus node dysfunction, remain major challenges in ACHD. Anatomical variability of the conduction system, such as inferior displacement of the AV node in AV septal defect or anterior positioning in congenitally corrected transposition of the great arteries, increases susceptibility to spontaneous AV block and iatrogenic injury during catheter-based and surgical procedures.³

High-density intraoperative conduction mapping allows real-time localization of the His-Purkinje system on the beating heart. By applying multielectrode grids intraoperatively, the conduction system can be localized and assist with planning incision sites and patch placements. Early studies have shown that this strategy significantly reduces postoperative pacemaker implantation rates in complex repairs, including AV septal defects and heterotaxy syndromes.³⁶ In a prospective cohort, integration of intraoperative mapping into surgical planning halved the incidence of postoperative complete AV block, underscoring its preventive potential.¹⁵ Intraoperative mapping also provides unique insights into the developmental variability of conduction pathways, generating datasets that may refine preoperative imaging predictions and computational models. As these approaches mature, they may become integral to multidisciplinary surgical-electrophysiological collaborations in CHD surgery.

High-density Mapping and Imaging Integration

Conventional point-by-point mapping is often long and cumbersome in ACHD, where circuits traverse nontraditional isthmuses and scar corridors. High-density mapping catheters, with closely spaced multipolar electrodes, generate rapid, high-resolution activation and voltage maps, unveiling slow-conduction channels and functional lines of block that were previously difficult to delineate. For atrial arrhythmias, high-density mapping has improved recognition of non-cavotricuspid isthmus-dependent IART circuits in atrial switch or Fontan patients, thereby increasing acute ablation success (Figure 2).¹² Integration of imaging modalities has further enhanced substrate definition. Fusion of CMR or CT data into electroanatomic maps facilitates catheter navigation around complex postsurgical geometries. ICE has become an essential adjunct, guiding transbaffle punctures, confirming tissue contact, and detecting complications in real time.³⁸

Figure 2

Robotic Magnetic Navigation

Robotic magnetic navigation represents a major advance in catheter stability and maneuverability, particularly in scenarios where manual techniques are limited, such as vascular constraints that preclude reaching the arrhythmia, high-risk or non-feasible trans-septal, transbaffle, or transconduit access to the pulmonary venous atrium, challenges in manipulating a manual catheter within the target chamber, or failure to maintain stable tissue contact needed to deliver effective and durable ablation lesions.¹³ By remotely controlling a magnetically responsive catheter with externally applied magnetic fields, operators can achieve consistent tissue contact and access to regions that are otherwise difficult to reach. Multicenter experiences, albeit limited, have demonstrated the safety and efficacy of robotic magnetic-guided ablation in ACHD in complex anatomies, including in patients with atrial switch baffles, systemic venous anomalies, and total cavopulmonary connection Fontan surgeries.³⁹ Beyond improving acute success, robotic magnetic navigation minimizes radiation exposure for patients and operators while alleviating operator fatigue during prolonged interventions (Figure 3).

Figure 3

Pulsed Field Ablation

While radiofrequency ablation remains the predominant energy source for catheter ablation in ACHD, cryoablation has primarily been used in selected patients with perinodal arrhythmias⁴⁰ and atrial fibrillation.^41,42 The introduction of PFA is a paradigm shift in energy delivery in that it employs nonthermal electrical fields to induce irreversible electroporation of cardiomyocytes, sparing adjacent structures such as the esophagus and phrenic nerve.⁴³ Large randomized and registry-based studies in paroxysmal and persistent AF have shown PFA to be noninferior in efficacy and superior in safety compared with conventional thermal energy sources.⁴⁴ The MANIFEST-17K (Multi-National Survey on the Safety of the Post-Approval Clinical Use of Pulsed Field Ablation in 17,000+ Patients) registry extended these findings to more than 17,000 patients and confirmed low complication rates, including an absence of atrioesophageal fistula.⁴⁵

In adults with CHD, PFA may offer an advantage in anatomically constrained regions because its nonthermal, electroporative mechanism can generate lesions without bulk heating, potentially reducing thermal injury to adjacent viable myocardium or delicate structures.^14,46 However, its performance in regions adjacent to surgical patches or dense scar tissue remains uncertain and requires careful study, especially given risks such as coronary spasm and variable lesion formation in heterogeneous substrates. Early feasibility studies suggest that PFA may be effective in ablating outflow tract ectopy and even scar-related VT.⁴⁷ However, long-term durability in heavily scarred ventricular substrates remains uncertain, complications are not negligible, and ACHD-specific PFA studies are lacking.

Implantable Cardioverter-Defibrillators

Implantable cardioverter-defibrillators remain the cornerstone of SCD prevention in ACHD, but their application is challenged by the heterogeneous population with diverse mechanisms leading to SCD, limitations of existing risk models, and uncertainties inherent to SCD prediction.⁴⁸ Vascular access limitations and complex anatomy may preclude transvenous leads, resulting in an important role for the subcutaneous ICD.⁴⁸ First implanted in 2008, the subcutaneous ICD has since evolved into a system with improved testing, sensing algorithms, programming, and MRI compatibility. Although initial studies included only a small number of patients with CHD, later series have confirmed feasibility, provided careful screening is undertaken to limit inappropriate shocks, particularly in those with wide QRS complexes such as in rTOF.^49,50 Limitations include the inability to provide antitachycardia pacing (ATP) or chronic bradycardia support, making patient selection crucial. Modern algorithms (eg, Smart Pass) and dual-zone programming have reduced inappropriate shock rates from 14% to 3.5%.⁵¹ With the exception of unipolar leads, compatibility with most pacemakers is achievable, which is relevant to the ACHD cohort given the high prevalence of coexisting bradyarrhythmias (Figure 4).⁵²

Figure 4

Next-generation systems aiming to transcend the limitations of conventional subcutaneous ICDs have entered clinical practice. The MODULAR ATP concept, which combines a leadless pacemaker wirelessly communicating with a subcutaneous ICD, has met key safety and efficacy end points, enabling ATP without transvenous leads.⁵³ In early human experience, the intercommunicating system successfully delivered ATP to terminate arrhythmias while maintaining low complication rates.⁵³ In parallel, extravascular ICDs (EV-ICDs) using a substernal lead have demonstrated the ability to deliver both defibrillation and limited pacing.⁵⁴ Their applicability in ACHD is uncertain since many adults with repaired CHD have undergone prior sternotomy or mediastinal surgery, conditions for which EV-ICD implantation is generally considered contraindicated or high-risk; however, the feasibility of concomitant EV-ICD implantation during cardiac surgery has been reported.⁵⁵ Thus, for now, modular subcutaneous ICD/leadless pacing systems hold clear promise for adults with CHD, while EV-ICDs may emerge as an attractive option in highly selected patients, particularly when implantation can be performed concomitantly with cardiac surgery as further data and technological refinements become available.

Leadless Pacing

Lead-related complications are particularly problematic in ACHD due to distorted anatomy, prior surgeries, and elevated infection risk. Leadless pacemakers, delivered percutaneously to the subpulmonary ventricle, eliminate the need for transvenous leads and pockets, thereby reducing infection risk and preserving venous access. Feasibility studies in ACHD have demonstrated safe implantation even in complex anatomy, although long-term data remain limited (Figure 5).⁵⁶-⁵⁸

Figure 5

Dual-chamber leadless pacing systems that are now entering clinical practice may further broaden therapeutic options for patients with ACHD.^59,60 For example, reports are emerging of leadless dual-chamber pacing in patients with Fontan palliation using a lateral tunnel or extracardiac conduit in the setting of AV block.⁶¹ Although important concerns include right-to-left shunting following large-bore transbaffle access and the risk of thromboembolic events, promising results have been reported using a strategy of shunt closure after implantation and long-term anticoagulation.⁶¹ Nevertheless, additional safety data with long-term follow-up are required before this approach can be expanded beyond carefully selected cases.

Conduction System Pacing

Conduction system pacing (CSP), encompassing His bundle pacing and left bundle branch area pacing (LBBAP), has rapidly evolved as a physiologic alternative to conventional ventricular pacing and cardiac resynchronization therapy (CRT). While most evidence arises from acquired heart disease, experience in congenital populations is expanding. Early reports demonstrate that CSP is technically feasible and can achieve narrower QRS durations, improved systemic ventricular synchrony, and stable pacing thresholds in patients with various forms of repaired or unrepaired CHD. Observational series in cohorts with congenitally corrected transposition of the great arteries, AV septal defects, and rTOF have confirmed successful engagement of the conduction system despite marked anatomic variability.^17,62,63 Imaging and mapping techniques such as CT-based conduction modeling, electroanatomic mapping, and ICE are increasingly used to identify displaced AV conduction tissue and guide lesion-specific implantation. Among the CSP modalities, LBBAP has gained favor for its broader target zone, lower capture thresholds, and superior sensing stability compared to His bundle pacing, though distal septal injury and lead extraction remain concerns. Despite encouraging procedural success and early functional benefits, data remain limited by small sample sizes, short follow-up, and the absence of randomized trials in CHD. Continued refinement of imaging-guided implantation, lesion-tailored approaches, and long-term registry data will be essential to define the role of CSP as a standard pacing paradigm in CHD (Figure 6).

Figure 6

Cardiac Resynchronization Therapy

CRT retains an important role for patients with systemic ventricular dysfunction and ventricular dyssynchrony. However, lead placement is often complicated by venous anomalies, surgical baffles, or extensive scar tissue. Procedural adaptations, such as surgical epicardial leads, transbaffle puncture, and endocardial LV pacing, have been employed with variable success.¹⁶ In systemic right ventricle and complex anatomy, hybrid pacing strategies combining CSP with coronary sinus or epicardial leads have shown potential for enhanced resynchronization.⁶⁴ For example, His bundle pacing or LBBAP combined with systemic ventricular epicardial leads has shown promise in achieving effective resynchronization in patients with congenitally corrected transposition of the great arteries and a suboptimal response to CSP.⁶⁴

Cardiac resynchronization of the subpulmonary right ventricle, such as in patients with rTOF or Ebstein anomaly, has generated much interest. In selected patients, acute hemodynamic benefits have been demonstrated with pacing of the right ventricular basal free wall.^65,66 In a small case series of permanent right ventricular basal free wall pacing in patients with rTOF or Ebstein anomaly, right bundle branch block, and moderate-to-severe right ventricular dysfunction, improvements were reported in New York Heart Association functional class, QRS duration, and right ventricular function.⁶⁷ Larger studies are needed to better identify patients most likely to benefit from this strategy and to evaluate potential downstream effects on SCD risk.

The Wireless Stimulation Endocardially for Cardiac Resynchronization Therapy (WISE-CRT) system, which consists of a leadless sensor in the systemic ventricle and a subcutaneous generator, represents a theoretically attractive strategy for CRT in patients with Fontan palliation because the leadless sensor is designed for the systemic ventricle, and the “co-implant” requirement could potentially be fulfilled by an existing epicardial pacing system.⁶⁸ The future may see personalized selection between CRT, CSP, and hybrid strategies based on lesion-specific anatomy and location of the conduction system.

Limitations of Conventional Risk Stratification

Conventional risk stratification models for SCD in CHD face inherent methodological and conceptual limitations. Lesion-specific scores, such as those developed for rTOF or the systemic right ventricle, capture relevant anatomic substrates but consider a limited number of potential predictors and are often derived from retrospective cohorts that may reflect historical surgical techniques, center-specific practices, or selectively high-risk populations.⁴⁸ Their variables may rely on invasive or center-dependent measurements, and calibration deteriorates when applied to contemporary or external cohorts. In contrast, models encompassing heterogeneous CHD populations improve statistical power but sacrifice lesion-level granularity, implicitly assuming shared mechanisms across fundamentally distinct anatomies and thereby diluting clinically meaningful predictors. Both model types typically depend on static parameters and dichotomous cutoffs, overlook time-dependent risk evolution, and rarely incorporate competing nonarrhythmic causes of death that influence net survival benefit from interventions such as ICD implantation (Table 1). As a result, risk estimates remain imprecise for many patients occupying intermediate-risk zones, reinforcing the need for dynamic, multimodal, and lesion-aware frameworks that integrate imaging, electrophysiologic, and biomarker data to support individualized prediction and decision-making.

Substrate-guided Prevention Framework

A substrate-guided prevention framework emphasizes identifying and modifying the underlying anatomic and electrophysiologic substrates that predispose to ventricular arrhythmias rather than relying solely on probabilistic models of event occurrence. In CHD, advances in CMR and high-density electroanatomic mapping have clarified that regions of fibrosis, surgical scarring, and slow conduction form discrete arrhythmogenic isthmuses that can be targeted for intervention. Late gadolinium enhancement on CMR and 3D reconstruction can delineate these substrates, enabling preemptive or intraoperative ablation strategies in lesions such as rTOF.³² The CATAPULT-TOF study exemplifies this approach by testing whether prophylactic ablation of SCAIs during transcatheter pulmonary valve replacement reduces post-procedural VT.³⁵ This integration of arrhythmia prevention into structural interventions illustrates the paradigm shift toward targeted, mechanism-based SCD prevention.

Genetics

Genetic insights are increasingly relevant to arrhythmic risk in ACHD. While primary arrhythmia syndromes such as Brugada or long QT syndrome are not CHD per se, variants in cardiac transcription factors that cause structural malformations, notably NKX2-5, TBX5, and GATA4, are associated with progressive conduction disease, AV block, and malignant ventricular arrhythmias.^69,70 Recognition of these associations has clinical implications for surveillance, device planning, and family counseling. As genomic sequencing becomes more widely adopted, integration of genetic risk markers into predictive models may refine arrhythmic risk assessment in ACHD.

Artificial Intelligence

Artificial intelligence, particularly deep learning applied to ECGs and imaging, offers powerful tools for individualized prediction of arrhythmic outcomes.⁷¹ In rTOF, convolutional neural networks trained on 12-lead ECGs have demonstrated superior predictive accuracy for VT, ICD shocks, and death compared with conventional risk factors.¹⁸ Beyond ECGs, AI applied to multimodal data, including imaging, hemodynamics, and electronic health records, can generate continuous risk scores and dynamically update predictions over time. These approaches have the potential to shift risk stratification from binary thresholds toward personalized, probabilistic models of arrhythmic risk.

Digital Twins

Digital twin technology—ie, patient-specific computational models calibrated to imaging, electrophysiology, and hemodynamic data—represents a frontier innovation. Personalized digital twin models of rTOF have been shown to identify VT-critical isthmuses with high concordance to invasive mapping.⁷² In silico testing of ablation strategies within the twin environment allows virtual optimization of lesion sets before invasive procedures, potentially reducing procedural time and risk. Similarly, digital twins may help determine whether ICD implantation is necessary by simulating arrhythmic vulnerability under varying physiologic conditions.⁷³ Early feasibility studies support the accuracy of this approach, though large-scale validation is pending.

Integrated Prevention Strategy

Moving forward, prevention of SCD in ACHD will likely rely on a multimodal strategy. Substrate definition via imaging and mapping, genetic risk markers, AI-driven predictive analytics, and digital twin simulations can be combined to generate individualized profiles of arrhythmic vulnerability. Such precision medicine approaches may allow clinicians to better target ICDs, ablation, and pacing therapies to those at highest risk while sparing low-risk patients from unnecessary interventions.⁴ Ultimately, the integration of these technologies into prospective multicenter registries and randomized trials is essential to refine risk stratification, reduce arrhythmic mortality, and guide evidence-based clinical practice.