The Fontan operation for single-ventricle hearts alleviates cyanosis but creates a hemodynamically fragile circulation.¹ Without a right ventricle, pulmonary flow is driven by venous pressure, making it the limiting factor for cardiac output.¹ Furthermore, the obligatory rise in central venous pressure leads to hepatic and splanchnic congestion.¹ Consequently, long-term consequences include Fontan failure (FF) and hepatic congestion resulting in Fontan-associated liver disease (FALD).¹

Francis Fontan proposed that sinus rhythm was a requirement for successful operative outcome. Unfortunately, the Fontan operation is associated with sinus node dysfunction (SND).¹ SND often leads to an escape junctional rhythm (JR), which results in loss of atrial contribution and a significant reduction in cardiac output.² The impact of SND/JR on outcomes is poorly characterized and forms the basis of this Viewpoint.

The association between SND/JR and FF/FALD is poorly understood. Large studies of Fontan outcomes have largely omitted cardiac rhythm as a model covariate.¹ This is partly explained by the absence of clear definitions and, accordingly, accurate identification of SND/JR. SND/JR can occur insidiously, and patients may remain relatively asymptomatic. There are few studies on the incidence of FF after the onset of SND/JR. The Australia鈥揘ew Zealand Fontan registry reported that 74 of 1034 patients had a bradyarrhythmia and experienced a significant hazard of FF of 41% at 10 years.³ This compares unfavorably with those with a normal rhythm in the same registry.

Cardiac output after the Fontan operation is dependent on ventricular preload, which is regulated by atrial relaxation, diastolic and systolic function of the single ventricle, atrioventricular valve function, and heart rate and rhythm. During sinus rhythm, pulmonary blood flow occurs during ventricular systole.^1,4 JR disrupts this fragile balance. During JR, intact retrograde atrial activation promotes simultaneous atrial and ventricular contraction, with flow reversal in the pulmonary veins⁴ (Figure). Cardiac magnetic resonance鈥揹erived flow patterns have demonstrated retrograde flow in the entire Fontan circulation during JR.⁵ This flow reversal temporarily increases hepatic and splanchnic venous pressures and when persistent, worsens congestion. In Fontan, increased pulmonary artery wedge pressure predicts poor outcomes, including end-organ dysfunction and mortality.¹ Conversely, atrial pacing (AP) in patients with JR after the Fontan operation is associated with an acute improvement in cardiac index (CI) by鈥塧pproximately鈥�25%.^6,7

In patients with JR, AP restores atrioventricular synchrony.¹ Although pacing has been shown to worsen outcomes in patients who have the Fontan procedure,¹ most studies fail to distinguish between atrial, ventricular, and dual-chamber pacing.¹ This is critical, as ventricular pacing is poorly tolerated after the Fontan procedure, whereas AP improves hemodynamics including higher CI, lower left atrial pressure, and lower pulmonary artery pressure.⁸

The timing and approach to AP is controversial because implantation of an atrial pacemaker after the Fontan procedure is rarely straightforward.¹ Endocardial, transvenous AP is only applicable to patients with the atriopulmonary and the lateral-tunnel Fontan, in whom atrial tissue is present inside the Fontan circuit. The extracardiac Fontan conduit bypasses the right atrium, and therefore, there is no atrial tissue to be approached endocardially.¹ Unfortunately, the extracardiac Fontan is currently favored by most cardiac surgeons.¹ AP in this situation, therefore, requires either thoracotomy or other innovative approaches reported by a few centers.⁹ Endocardial pacing can also promote thrombus formation around the lead with embolization to the lungs or the systemic circulation.¹ Pacemaker implantation, therefore, carries significant morbidity and, potentially, mortality. The decision to pursue AP is often challenging and undertaken only after much deliberation.

The impact of SND/JR on outcomes (FF and FALD) needs study. Further, the detection and quantification of JR burden by ambulatory monitoring needs improvement using automated software. Finally, SND needs better definition, especially in children. As JR can be intermittent, the association between JR burden and clinical outcomes requires study (much like the impact of the burden of premature ventricular contractions and ventricular pacing).

Current guidelines state that 鈥溾��permanent atrial or dual-chamber pacemaker implantation is reasonable for patients with congenital heart disease and impaired hemodynamics due to sinus bradycardia or loss of atrioventricular synchrony.鈥�^10(p1896) The potential negative impact of JR on Fontan hemodynamics would be adequate justification for further studies (including cardiac catheterization) in patients with JR on electrocardiogram. If JR is shown to compromise hemodynamics, AP could be considered. However, this remains challenging at present. Not only are the long-term adverse consequences of JR ambiguous, but the standard treatment approach (ie, pacemaker implantation) is risky. Existing guidelines are, therefore, ill-equipped to guide contemporary treatment for those who have the Fontan procedure in the setting of such clinical equipoise.

Absent a curative solution for single ventricle, optimizing the Fontan circulation offers the best hope for patients. Preliminary evidence suggests that SND and JR are detrimental in patients who have the Fontan procedure. A persistently decreased cardiac output of almost 25% combined with elevated left atrial, and Fontan pressures cannot be considered benign for this fragile circulation. SND and JR may be significant, yet underappreciated, arrhythmias that silently accelerate the progression to FF and FALD. However, many critical, unanswered questions remain, and empirical proof is lacking, especially regarding JR burden and FF/FALD. Further studies are required to define the JR burden associated with poor outcomes. These, in turn, will require improved methodology for the quantification of JR by ambulatory monitoring.

We believe that future investigations should focus specifically on the detection and quantification of asymptomatic patients with SND/JR after the Fontan procedure as well as the long-term outcomes among this rapidly growing pediatric and adult population. Only then will we answer the issue of whether SND/JR is an innocent bystander to be disregarded or a silent killer to be apprehended on recognition.

Corresponding Author: Seshadri Balaji, MBBS, MRCP, PhD, Pediatric Cardiology, Oregon Health & Science University, 707, SW Gaines St, Mailcode: CDRC:P, Portland, OR 97239 (balajis@ohsu.edu).

Published Online: April 24, 2024. doi:10.1001/jamacardio.2024.0689

Conflict of Interest Disclosures: Dr Balaji reported receiving grants from Medtronic and personal fees from Milestone Pharmaceuticals and Altathera Pharmaceuticals. Dr Moore reported serving as a consultant for Altathera Pharmaceuticals and Biosense-Webster (Johnson & Johnson). No other disclosures were reported.