Arrhythmias in Adults with Congenital Heart Disease: What the General Cardiologist Should Know

The population of adults with congenital heart disease (ACHD) is steadily increasing, and it is now likely that more adults than children are living with a history of CHD.^1,2 Due to the unique preoperative (congenital) and postoperative haemodynamic and conduction abnormalities, ACHD face distinct medical challenges compared with the general population. This review aims to provide an updated overview of the epidemiology and characteristics of tachyarrhythmias in ACHD. With the increasing global prevalence of ACHD, and the earlier and higher risk of arrhythmias inherent to congenital heart disease, effective arrhythmia management in this population has become an essential aspect of care for all general cardiologists. Additionally, we will discuss the role of pulmonary valve replacement in the management of repaired tetralogy of Fallot (rTOF).

Prevalence of Adults with Congenital Heart Disease

With advances in medical care, the population of ACHD is steadily increasing, along with the complexity of their medical conditions, including various forms of tachyarrhythmias.^3–7 The prevalence of ACHD depends on the incidence of CHD in live birth, the timing of implementation of the CHD program, and the quality, accessibility and affordability of the CHD program. Open-heart surgery for CHD was first performed in the 1940s in North America. According to an administrative database, the prevalence of ACHD in Quebec was 4.09 per 1,000 adults in 2000 and 6.12 per 1,000 adults in 2011.^1,2 From a Taiwan nationwide database, the CHD prevalence in the population aged 18–59 years was 2.17 per 1,000 adults in 2014, with severe CHD accounting for 11.70% of ACHD.⁶ The five leading ACHD diagnoses were ventricular septal defect, secundum atrial septal defect, patent ductus arteriosus, pulmonary stenosis and TOF.⁶ The distribution of each type of CHD in adult patients from our previous study is also summarised in Figure 1.⁶

Data on ACHD prevalence may also be estimated from CHD incidence at birth and the survival estimate for each type of CHD. By using this approach, the prevalence of ACHD was estimated to be between 1.77 and 4.91 per 1,000 adults in six high-income countries between 2001 and 2011.^8,9 The prevalence of ACHD is generally lower than the incidence of CHD at birth for the following reasons: case mortality, loss of follow-up because of spontaneously resolved CHD or asymptomatic surgically repaired CHD and poor adherence to medical follow-up schedules. The current prevalence of ACHD is estimated to range from two to six per 1,000 adults, with approximately 10% classified as severe cases.

Arrhythmia burden is substantial in patients with CHD and tends to increase with age. It represents a common cause of heart failure-related hospitalisations, and is a significant contributor to overall morbidity and mortality in this population.¹⁰ ACHD are at high risk for arrhythmias due to a combination of factors, including surgical scarring, displacement or malformation of the conduction system, hypoxic tissue injury, myocardial ischaemia, chronic pressure or volume overload and genetic predispositions; all these factors promote arrhythmogenesis.¹¹ Common types of arrhythmias in ACHD include tachyarrhythmias, bradyarrhythmias, ventricular arrhythmias and sudden cardiac death (SCD).¹¹ In the following sections, we will provide a detailed overview of the various types of arrhythmias commonly observed in ACHD.

Tachyarrhythmias in Adults with Congenital Heart Disease

In ACHD, tachyarrhythmias can be attributed to factors inherent to CHD itself, including preoperative and postoperative haemodynamic abnormalities, conduction system anomalies specific to certain defects, and surgical scarring. Additionally, factors common to the general population, such as ageing, conduction system variations (e.g. accessory pathways, dual atrioventricular nodal pathways) and comorbidities, also contribute to arrhythmia risk. Conduction system abnormalities are relatively common and may show specific patterns in certain CHDs.^12–17 Patients with Ebstein’s anomaly and congenitally corrected transposition of great arteries (CC-TGA) are likely to have accessory pathways, while patients with heterotaxy are likely to have twin atrioventricular (AV) nodes (Table 1). These associated conduction system abnormalities may serve as substrates of re-entrant tachyarrhythmias. Acquired risks of arrhythmias are summarised in Table 2.

Due to the limited cardiac reserve in ACHD, particularly in those with severe cases, tachyarrhythmias pose a significant risk, exacerbating heart failure and potentially leading to SCD. From our previous study, compared with the general population, the standardised mortality ratio was higher, particularly in adults with severe CHD, with a higher proportion of deaths attributable to cardiac, labour-related and SCD.⁶

The risk of tachyarrhythmias in adults with severe CHD is generally higher than that in adults with simple CHD.⁶ From our previous nationwide study, among adults with severe CHD, the cumulative risk of tachyarrhythmia by age 30 years was >20% in complex CHD (25.5 ± 5.5%), Ebstein’s anomaly (22.3 ± 2.6%) and tricuspid atresia (21.0 ± 4.7%). The cumulative risk of tachyarrhythmia by age 50 years was >20% in most of the adults with severe CHD. In adults with simple CHD, the risk of tachyarrhythmia by age 50 years was between 10 and 20%.⁶ The cumulative risks of tachyarrhythmia by age 20, 40 and 59 years from our previous study are shown in Figure 2.⁶

Supraventricular Tachyarrhythmias

Intra-atrial Re-entrant Tachycardia

Intra-atrial re-entrant tachycardia (IART) is one of the most common types of arrhythmias observed in ACHD.¹⁸ In many cases, IART is associated with prior surgical procedures involving incisions in the right atrium. Patients with complex CHD, such as those with complete TGA who underwent Senning or Mustard procedures, those with tricuspid atresia who received classical Fontan operation, or those with repaired TOF often develop right atrial enlargement and extensive atrial scarring. These structural changes increase the risk of developing IART.¹⁹ Initial treatment for IART includes cardioversion, medical therapy using Class IC or Class III antiarrhythmic agents and overdrive pacing. Class I agents are not recommended in CHD patients with concurrent coronary artery disease or ventricular dysfunction, and amiodarone may be considered to prevent recurrences of IART at these conditions.²⁰ For patients with complex CHD or those at high risk of thrombus formation, warfarin is commonly recommended to prevent thrombosis.

Currently, radiofrequency ablation has become a preferred first-line therapy for patients with frequent IART episodes, especially when guided by a 3D electroanatomic mapping system. Although the success rate can reach up to 90%, recurrence of IART remains high in certain patient groups; for example, approximately 40% in patients who underwent the Fontan procedure. For patients requiring open-heart surgery, the Maze procedure is considered an appropriate treatment option.

Atrioventricular Re-entrant Tachycardia

Atrioventricular re-entrant tachycardia is caused by the presence of an abnormal accessory pathway. It is commonly observed in patients with Ebstein’s anomaly and CC-TGA. Radiofrequency ablation is considered the first-line treatment for this condition.

Atrial Fibrillation

AF is the most common tachyarrhythmia in the older adult population, resulting from ageing-related electrophysiological changes and structural remodelling in the atria, which increase the predisposition to AF.^21–23 In the general population, the incidence of AF is higher in men than in women, with the risk increasing after the age of 55 years.²² The incidence is 0.1% in adults aged <55 years and 9.0% in adults aged >80 years.²²

ACHD are prone to developing atrial tachyarrhythmias at an early age due to prior surgical incisions, structural conduction barriers (such as varied valve orifices, venous structures, septal defects and the crista terminalis), sinus node dysfunction and the effects of chronic haemodynamic or hypoxic stress, including fibrosis and hypertrophy.^{21,22,24–26} Regular atrial tachycardia, which often precedes AF, progressively shortens atrial refractoriness, leading to an increased incidence of AF.^27,28

Our previous study indicated that ageing was a common risk factor for AF in ACHD and the non-ACHD general populations.²⁹ The incidence of AF in ACHD aged <60 years was 10–20-fold higher than in the comparison cohorts (>20-fold: aged <50 years; >10-fold: aged 50–59 years), and the onset of AF in ACHD was 30 years earlier than in the comparison non-ACHD groups, with incidence plateauing around age 70 years.²⁹ Yet, the incidence in non-ACHD individuals continued to rise. AF in ACHD is a big medical challenge, but its incidence does taper with advanced age, and the AF burden is not expected to expand in a never-ending way.³⁰ The impact of the traditional risk factors of AF in ACHD needs to be clarified by future studies.

According to a recent study from a national Swedish registry, comparing AF in the general population, AF in ACHD is associated with significantly higher risk of ischaemic stroke (adjusted HR 5.16), especially in those with complex CHD (adjusted HR 8.34).³¹ Therefore, to prevent the possible thromboembolic events, anticoagulation should be considered in ACHD with AF after intracardiac repair, with cyanosis, after Fontan palliation, with a systemic right ventricle or with a CHA₂DS₂-VASc score >1.²⁰

The treatment of AF in ACHD is similar to that in the general population, including the use of anticoagulants, rate control and antiarrhythmic medications to maintain normal sinus rhythm. However, the effectiveness of medical therapy in preventing AF recurrence is often limited. Radiofrequency ablation, guided by a 3D electroanatomic mapping system, is considered a more effective treatment option. In addition, the Maze procedure for intra-atrial ablation also plays a role in AF management, especially when ACHD undergo open-heart surgery for other indications.

Twin Atrioventricular Nodes and Tachyarrhythmia

Twin AV nodes (TWAVNs) had been described early in the cardiac specimens of heterotaxy syndrome, congenitally corrected transposition of great arteries and double inlet ventricle.^{13,17,32–34} The association was particularly high in patients with heterotaxy syndrome, especially the right isomerism. These TWAVNs may manifest two discrete QRS morphologies on the same ECG or separate ECGs, which may be diagnosed by serial ECG examination (Figure 1).^12,30,35 The TWAVNs in patients may constitute substrates of re-entrant tachycardia, even during the foetal stage.^{14,16,30,35,36} In CHD with abnormal AV connections, our previous study suggested a developmental hierarchy in the propensity to show TWAVNs, but not for accessory pathways.¹² TWAVNs were present in 43.4% of heterotaxy, 10.6% of DIV, 10% of CC-TGA and 1.6% of AV canal defect cases.¹² Our observations suggested that the presence of TWAVNs in CHD with abnormal AV connection was associated with a developmental hierarchy of cardiac morphology. The earlier cardiac developmental errors occur, the higher the likelihood of TWAVNs and the greater the chance of supraventricular tachycardia.¹²

Ventricular Arrhythmia and Sudden Cardiac Death

Ventricular Arrhythmia

Ventricular arrhythmias (VAs) in ACHD can generally be categorised into two groups. The first group includes patients with well-defined barriers to ventricular conduction, typically caused by surgical scarring or anatomical structures. These barriers create discrete isthmuses that give rise to macroreentrant ventricular tachycardia (VT), which is commonly monomorphic. CHDs in this category include rTOF and other surgically corrected conotruncal anomalies, such as TOF-like double outlet right ventricle, isolated ventricular septal defect and certain forms of pulmonary stenosis.³⁷

Although SCD is a major concern in patients with VT, risk stratification should be individualised for those with rTOF and other repaired conotruncal defects before considering ICD implantation. Programmed ventricular stimulation plays a critical role in assessing arrhythmic risk. In selected low-risk patients, such as younger individuals with well-functioning ventricles and a single, well-tolerated monomorphic VT, catheter ablation and timely pulmonary valve replacement (PVR) may improve clinical outcomes (for more details, please see the section below: Specific Congenital Heart Diseases in Adults: Tetralogy of Fallot).³⁷

The second group consists of patients with diffuse or patchy myocardial fibrosis, who often present with polymorphic VTs or VF. Ebstein’s anomaly, systemic right ventricle and congenital aortic stenosis fall into this group. In these kinds of patients, the role of programmed ventricular stimulation is less well established, and catheter ablation generally has limited efficacy in the management of these arrhythmias.³⁸ In ACHD with diffuse substrate-related VAs, the risk of SCD increases significantly with the progression of heart failure over time.³⁸

Sudden Cardiac Death

ACHD are at increased risk for SCD, which accounts for approximately 20% of all deaths in this population.^39,40 Proven or presumed arrhythmias are responsible for approximately 80% of these cases.⁴⁰ VA is the most documented rhythm at the time of SCD. Several factors have been associated with an increased risk of sudden arrhythmic death in ACHD, including the type of CHD, ventricular dysfunction, prolonged QRS duration, increased QT dispersion, ischaemic heart disease and a history of supraventricular tachycardias.^40–42

ICD implantation is indicated as a secondary prevention strategy in ACHD who have survived SCD due to VF or haemodynamically unstable VT following a comprehensive evaluation to determine the cause and exclude reversible factors.⁴³ Some antiarrhythmic drugs can be used with ICDs to help reduce the burden of VAs. While the benefit of ICD therapy for both primary and secondary prevention is well established in patients with biventricular circulation or a single left ventricle, its effectiveness in those with single or systemic right ventricles remains less clearly defined.⁴³

Bradyarrhythmias in Adults with Congenital Heart Disease

A common cause of sinus bradycardia in ACHD is surgical trauma to the sinoatrial node or its arterial supply, particularly following operations, such as the Fontan, Glenn, Senning or Mustard procedures. Other aetiologies include congenital sinus node dysfunction (e.g. heterotaxy syndrome, particularly left isomerism), congenital AV block (e.g. endocardial cushion defect, transposition of the great arteries), acquired AV block and conduction disturbances following interventions, such as ventricular septal defect closure, subaortic stenosis relief or AV valve replacement.^13,44

Regular Holter monitoring is recommended for ACHD with sinus node dysfunction or AV block. Chronic sinus node dysfunction and bradycardia with ineffective atrial haemodynamics may lead to atrial remodelling and increase the risk of IART. Given the association between postoperative AV block and SCD, pacemaker implantation is often indicated more broadly in this population than in individuals with structurally normal hearts.⁴³ Patients who undergo surgery involving the left ventricular outflow tract, atrioventricular valve replacement or ventricular L-looping should be considered for early postoperative pacemaker implantation to prevent high mortality associated with permanent postoperative AV block.^45,46

Specific Congenital Heart Diseases in Adults

Tetralogy of Fallot

TOF is the most common cyanotic disease in ACHD, with an incidence of 0.16 per 1,000 adults in Taiwan and 0.23 per 1,000 adults in Canada.^2,6 The survival after total correction reached approximately 97%, and most of those repaired TOF patients survived to adulthood. However, adverse cardiovascular effects, including progressive pulmonary regurgitation, ventricular dysfunction and heart failure, and tachyarrhythmia, may lead to high morbidity in later life and mortality. TOF patients typically have right bundle branch block and pulmonary regurgitation or stenosis. If a transannular patch was used during surgical repair, pulmonary regurgitation may progressively worsen over time. Due to electromechanical interactions from right bundle branch block, right ventricular dysfunction can develop early. Although the precise threshold for irreversible right ventricular dysfunction in rTOF patients remains uncertain, MRI assessment of right ventricular function plays a key role in determining the optimal timing for PVR. Notably, the presence of tachyarrhythmias before PVR is associated with a higher likelihood of post-replacement arrhythmias and adverse outcomes.⁴⁷

The burden of tachyarrhythmia in TOF patients varied with the duration of postoperative follow-up and the study cohort type. According to data from the Alliance for Adult Research in Congenital Cardiology, tachyarrhythmia occurred in 29.9% of adult TOF patients and in a higher percentage of older patients.⁴⁸ In our previous nationwide database study, risk of tachyarrhythmia increased with age, and was 26.6% at age 50 years and 40.1% at age 59 years.⁶ Timely pulmonary valve replacement is likely to be effective to reduce the risk of tachyarrhythmias. From our institutional study, after the initial quiescent 10 years following total repair, the annual risks of tachyarrhythmia/sudden cardiac arrest (SCA) increased to 0.295 and 1.338% in patients aged 10–30 and 30–60 years, respectively. The higher risk of tachyarrhythmia/SCA in PVR patients might be reduced by PVR, but only in those without tachyarrhythmia/SCA before PVR. Among our patients, PVR (85% surgical PVR and 15% percutaneous) had been performed annually in 1.57% between 10 and 30 years after repair.⁴⁷ The predictors for tachyarrhythmia/SCA after PVR were a history of tachyarrhythmia/SCA before PVR, New York Heart Association functional class III or IV before PVR and age >28 years at PVR.⁴⁷

A recent study from the International Multicentre TOF Registry, using propensity score-matched individuals receiving PVR, showed that these individuals had a lower risk of a composite endpoint of death or sustained VT, but not the composite secondary outcome of advanced heart failure (New York Heart Association functional class III or IV), nonsustained VT or sustained supraventricular tachycardia (ectopic atrial tachycardia, atrial flutter or AF) requiring treatment.⁴⁹ There was no association between PVR and the primary outcome in patients with right ventricular end-systolic volume index ≤80 ml/m².⁴⁹

As outlined in the 2018 AHA/ACC guideline for the management of ACHD, cardiac MRI is considered the gold standard for assessing right ventricular size and function in patients with rTOF.³ The guideline recommends PVR if two or more of the following criteria are met:

• Mild or moderate right ventricular or left ventricular systolic dysfunction.
• Severe right ventricular dilatation, defined as:

– right ventricular end-diastolic volume index ≥160 ml/m²

– right ventricular end-systolic volume index ≥80 ml/m²

– right ventricular end-diastolic volume ≥2× left ventricular end-diastolic volume

– right ventricular systolic pressure due to right ventricular outflow tract obstruction greater than or equal to two-thirds of systemic pressure.

• Progressive decline in objective exercise tolerance.

Additionally, in patients with sustained tachyarrhythmias, PVR may be considered even in those with borderline right ventricular dysfunction from pulmonary regurgitation.

Ebstein’s Anomaly

Ebstein’s anomaly is a rare type of CHD, characterised by an apical displacement of the tricuspid valve and right ventricle dysfunction, resulting in a spectrum of haemodynamic and electrophysiological abnormalities. From our nationwide database, the prevalence of Ebstein’s anomaly in neonates and adults was 4.7 and 1.9 per 100,000, respectively.^6,50 The clinical presentation of Ebstein’s anomaly varies widely, with a poorer prognosis for individuals who present with symptoms early in life and require surgery during infancy.^15,51

In addition to the common occurrences of accessory pathway in Ebstein’s anomaly patients, which may lead to atrioventricular re-entrant tachycardia or pre-excited AF, late complications include progressive right atrial dilatation and ventricular dysfunction, which also predisposes patients to atrial and ventricular arrhythmias.⁵² Nevertheless, advances in surgical repair and arrhythmia management have improved survival outcomes for adults with Ebstein’s anomaly.⁵³

Our recent study of Ebstein’s anomaly patients who survived to adulthood revealed fair outcomes, with transplant-free survival by age 60 years as 0.885 ± 0.061.⁵⁴ Pre-excitation was present in 30.2% of the patients. Among patients with pre-excitation, the incidence of adult-onset supraventricular tachycardia reached 83.6% by age 50 years.⁵⁴ The occurrences of adult-onset atrial tachyarrhythmias increase with ageing, with incidences of 21.7, 37.5 and 58.9% by ages 50, 60 and 70 years, respectively. The presence of atrial tachyarrhythmias was the most significant predictor for adverse cardiovascular outcomes in adult patients with Ebstein’s anomaly.⁵⁴ Timely interventions to prevent excessive right-sided chamber dilatation may help reduce the risk of atrial tachyarrhythmias.⁵⁵

Conclusion

Adults with congenital heart disease face a significant and evolving arrhythmic burden due to structural, surgical and age-related factors. Early recognition, risk stratification and individualised management – including timely interventions, such as pulmonary valve replacement – are essential to improve outcomes. Ongoing surveillance and multidisciplinary care are key to reducing morbidity and mortality.