Introduction

Arrhythmias are arguably the most important complication in patients who undergo the Fontan operation. They are an important cause of clinical deterioration and death, whether they occur immediately after surgery or many years later [1]. The relationship between arrhythmias (electrical problems) and hemodynamics (mechanical issues) is complex and can be compared with the chicken versus egg discussion. Mechanical problems like poor ventricular function and valve regurgitation predispose the patient to arrhythmias. In turn, arrhythmias can lead to poor ventricular function, and to the development of problems like protein-losing enteropathy (PLE), and thrombus formation. Once established, the vicious cycle of arrhythmias can be hard to interrupt. Arrhythmia has been described as a strong “predictor of mortality” and “key marker of deterioration” with a 23-fold increased risk of death [1]. However, the Fontan is not one operation. At least two major modifications, namely the intracardiac lateral tunnel (ILT) and the extracardiac conduit (ECC), have been described since the original atriopulmonary connection (APC) type of Fontan, and they have had a significant impact on the incidence and severity of arrhythmias.

Incidence

The incidence of early post-operative arrhythmias after the APC Fontan is estimated to be around 10–30% [2, 3]. This is however now only of historical interest as the APC is now rarely performed. More important is the incidence of late arrhythmias in this population, with estimates of the occurrence of late bradyarrhythmias (predominantly loss of sinus rhythm with a slower junctional escape rhythm) in up to 40% of patients and late tachyarrhythmias in up to 80% [1, 4] (Table 1).

Table 1 Arrhythmia incidence. Incidence of arrhythmia in the Fontan population in the current published literature. Breakdown of incidence per Fontan subtypes included as available. APC, atriopulmonary conduit; TCPC, total cavopulmonary connection; RA, right atrium; RV, right ventricle; ILT, intracardiac lateral tunnel; ECC, extracardiac conduit; JET, junctional ectopic tachycardia; SVT, supraventricular tachycardia; ECLT, extracardiac lateral tunnel; A flutter, atrial flutter; A fib, atrial fibrillation; IART, intra-atrial re-entrant tachycardia; AVRT, atrio-ventricular re-entrant tachycardia; EAT, ectopic atrial tachycardia; VT, ventricular tachycardia
Full size table

de Leval developed the total cavo-pulmonary connection (TCPC) primarily based on his observation that the APC Fontan was an inefficient circulation, with the theory that streamlining the flow of blood from the inferior vena cava (IVC) through the right atrium (RA) to the pulmonary artery (PA) could improve outcomes including reducing the incidence and severity of arrhythmias [25]. The surgical method of TCPC he described now goes by the name intracardiac lateral tunnel (ILT). His hopes of hemodynamic improvement were immediately realized with a lower incidence of arrhythmias, which were better tolerated by the patients [17, 26]. Marcelletti almost immediately went a step beyond de Leval and described the extracardiac conduit (ECC) Fontan, thus seeking to avoid the RA completely to achieve the primary aim of eliminating the potential for arrhythmias [27, 28].

The incidence of arrhythmias has significantly decreased since the adoption of the ILT and the ECC modifications of the Fontan operation. Numerous studies have shown this decreased incidence with ILT and ECC as compared with APC. Quinton et al. [1] describe a reduction in the incidence of late arrhythmia in the ILT and ECC groups down to 23%; however, the cohort data shows a sharp increase in the arrhythmia burden in the APC group at the 20–25-year mark post-Fontan, and Quinton notes that the ILT and ECC will need to be followed further to evaluate for a similar increase in arrhythmia as these cohorts age. Pundi et al. [23••] and Dennis et al. [4] both similarly describe a decrease in the incidence of late arrhythmia by about 70% in the ILT and ECC groups as compared with the APC group; however, they also note that these findings may be an underestimate given the shorter follow-up duration in these cohorts.

Early bradyarrhythmias are estimated to occur in 4–22% of patients after the ILT and in 0–27% after the ECC (Table 1). Studies that directly compare one cohort to the other have described differing results with some showing an increased tendency for early bradyarrhythmias in the ILT group [8, 11, 18], and others showing a higher tendency in the ECC group [7, 17]. Late occurring bradyarrhythmias are estimated at around 10–77% after the ILT and 0–29% after the ECC (Table 1).

Early tachyarrhythmias have been described to occur in 2–38% of patients after ILT and 0–11% after the ECC [7, 8, 17, 18, 23]. Most of the attention has been on late tachyarrhythmias as this is a key determinant of long-term outcome [22, 29]. Late tachyarrhythmias have been shown to occur in 4–33% of the ILT group and 0–9% of the ECC group [4,5,6,7,8, 15, 17, 18, 20, 23]. Again, direct comparison of these two surgeries has been complicated by the fact that the ILT procedure was described earlier and therefore the ILT cohort tends to be older and undergone longer follow-up, and so the current data may be underestimating the incidence of the late arrhythmias in the ECC cohort. Larger scale studies [17, 19, 20] do show a trend for a lower incidence of arrhythmias in the ECC group, and is a difference from smaller scale studies [7, 10, 18], which have shown a less significant reduction; however, further follow-up of the ECC cohort remains necessary to fully evaluate the efficacy of this surgery on reducing the incidence of arrhythmia.

Etiology and pathophysiology

Bradyarrhythmias

Bradyarrhythmias, especially sinus node dysfunction, is an important post-operative problem. Extensive dissection in the region of the sinus node and its arterial supply either at the Fontan or at the earlier-stage operations (particularly the Glenn operation) can result both in immediate (early) or late severe sinus node dysfunction [7, 11]. Heart block due to atrioventricular (AV) node dysfunction is less common, although the patients’ underlying anatomy may be a factor. For example, patients with single ventricles associated with heterotaxy syndromes and with L-looped ventricles have been well described to have a predisposition to the development of de novo heart block [9].

Transient sinus node dysfunction with the need for temporary pacing can often be seen in the post-operative period and can resolve spontaneously without the need for a permanent pacemaker [17, 19]. Early atrial arrhythmia has also been shown to be associated with late tachy and bradyarrhythmias, likely due to an additive effect of disruption to nodal tissues with progressive atrial dilation [23••].

Late bradyarrhythmia

Sinus node dysfunction and less commonly AV block are common longer term problems in Fontan patients. Bradyarrhythmias are associated with decreased ventricular function and found to have freedom from decreased ventricular function at 15 years of only 46% [20••]. There is no significant difference found between the ILT and ECC patients in regard to incidence of late bradyarrhthmia [17, 18]. Sinus node dysfunction remains a major cause of pacemaker placement in this population and has been reported to occur in 6–12% of patients [4, 15, 17, 19, 20].

Tachyarrhythmias

Tachyarrhythmias, especially supraventricular tachycardias (SVT) in the APC, are thought to be primarily due to the extensive suture lines in the atrium, which set up the substrate for atrial reentry tachycardia. The obligatory increase in right atrial (RA) pressure predisposes the APC Fontan patients to develop severe RA dilation, which further stretches the surgical scars, creating the toxic combination of factors that result in a high incidence of arrhythmias [4, 22, 29, 30].

Of all the arrhythmias that occur, the most important from a prognostic viewpoint is the issue of late occurring tachyarrhythmias. The most common tachyarrhythmia seen in younger patients is a reentry arrhythmia around scars (called IART or intra-atrial reentry tachycardia), although cavo-tricuspid (or typical) atrial flutter and ectopic (or focal) atrial tachycardia (EAT) are also often seen, especially in the longer term [1, 15, 21]. As Fontan patients become older, a higher incidence of atrial fibrillation is noted and this will likely prove to be the major electrical problem as these patients survive to old age. Indeed “brady begets tachy” is a familiar electrophysiological dictum and an estimated 21% of Fontan patients develop both brady and tachyarrhythmias [20••]. Tachyarrhythmias, by the phenomenon of overdrive suppression, can lead to “weakening” of the intrinsic pacemakers such that when the tachyarrhythmia terminates (sometimes spontaneously, sometimes by medical intervention), there is severe bradycardia and potentially even asystole. This is an important aspect to be borne in mind when treating these patients.

Numerous studies have shown that atrial tachyarrhythmias are common among Fontan patients with prevalence of up to 60% at 20 years after initial Fontan surgery [4, 21,22,23], with one report describing a 100% incidence in the APC Fontan patients at 26-year follow-up [1]. In all Fontan patients who develop an atrial tachycardia, IART and EAT are the most common forms occurring in 40–60% [31]. Atrial flutter and atrial fibrillation have an estimated incidence of 21–66% [20, 21, 23], with some reports citing an even higher incidence of up to 83% in APC Fontan patients [22••]. Atrial fibrillation has an incidence of 2–40% [4, 20,21,22]. Ventricular tachycardias are the least frequent of the tachyarrhythmias in the Fontan population with a cited incidence of 3–10% [23, 32]. In patients with an APC Fontan presenting for an atrial arrhythmia ablation, the most common arrhythmia induced was IART (93%) with atrioventricular re-entrant tachycardia and atrioventricular nodal re-entrant tachycardia occurring in ~ 4% [33]. As the ILT and ECC cohorts age, the incidence of the subtypes of arrhythmias will be better elucidated and the efficacy of these surgical modifications can be better compared with the APC.

Clinical presentation

The presentation of arrhythmias in the Fontan population can vary from the subtle (vague or mild symptoms of fatigue and respiratory distress) to the catastrophic (syncope or rarely, cardiac arrest). Arrhythmias, which can cause stasis of blood, combined with the presence of patch material make them a higher risk for acute thromboembolic events [34,35,36]. While underlying structural problems such as poor ventricular function, and valve regurgitation predispose to arrhythmias, in turn, arrhythmias often lead to Fontan failure and deterioration, with 40% of patients developing decreased ventricular function following the first onset of an arrhythmia [1, 20]. Atrial arrhythmias have been associated with a sixfold increase in transplantation and death [29]. Sinus node dysfunction has also been implicated in the development of plastic bronchitis and protein-losing enteropathy in Fontan patients [37••]. The decrease in ventricular filling time and dyssynchronous contractions is poorly tolerated in patients with single ventricles and any imaging or clinical signs of poor function should raise a high suspicion for arrhythmia in this population given the wide range of clinical presentation [34, 37, 38]. Given the significant morbidity and mortality associated with arrhythmias, a significant amount of attention has been directed in routinely evaluating the rhythm in these patients and this will likely continue in the future care of these patients.

Sudden death

Arrhythmias with severe cardiac compromise and even sudden cardiac death are also a major problem in this population [39,40,41]. Sudden death alone has been noted to have an incidence of 5–10% and occur at an average age of 20.5 years. An underlying arrhythmia was found in 65% of Fontan patients who developed sudden death. Additionally, risk factors for sudden death included AV valve replacement at the time of Fontan operation and post-bypass Fontan circuit pressure greater than 20 mmHg. Pre-operative presence of sinus rhythm has been found to be a protective factor [23••]. Further studies into the mechanism of sudden death in this population are needed with particular attention to identifying which subgroup of patients would benefit from ICD placement.

Summary

The development of any bradyarrhythmia or tachyarrhythmia is an independent predictor of a poor clinical outcome. A study on long-term outcomes after first-onset arrhythmia in Fontan patients showed that the 15-year survival following the development of any arrhythmias was only 70% and freedom from Fontan failure was only 44% [20••]. Tachyarrhythmias are especially associated with increased Fontan failure, sudden cardiac death, and mortality [1, 4, 20, 23, 32]. In APC patients, 83% of those with a dilated atrium also had a documented arrhythmia, and this was associated with increased risk of heart failure and death [22••]. This phenomenon was a concern posed by Dr. Francis Fontan during his initial description of the procedure in 1971 and has instigated the development of modifications to the initial procedure [29]. Thus far, the ILT and more recently the ECC have shown some promising results in regard to the incidence of arrhythmias [18, 19]. A systemic review and meta-analysis by Li et al. [42••] in 2017 showed that ECC Fontan patients have a twofold lower risk of late arrhythmias compared with ILT patients. This needs to be taken in the context of changes in a surgical era in addition to the other factors impacting the incidence of late atrial tachycardias including age at the time of Fontan surgery (irrespective of Fontan type) [1], heterotaxy or atrial isomerism, and presence of ventricular-dependent coronary circulation [19,20,21, 24, 43]. Dennis et al. [4] describes that for all Fontan types prior to age 16, only 15% had experienced arrhythmic events, which is consistent with the arrhythmias being mostly a burden as these patients age into adulthood. Further studies will continue to inform the true impact of surgical techniques and other factors in regard to the incidence of arrhythmias and their impact in this vulnerable population.