The Fontan circulation: Beyond hemodynamics to a unified disease paradigm

The Fontan operation is one of the most significant, transformative milestones of congenital cardiac surgery, which enabled patients born with single-ventricle physiology to survive into adulthood. However, the physiological trespass of the absence of a subpulmonary ventricle unveiled a more complex reality: the Fontan circulation is not a cure, but a chronically stressed physiological state with inevitable long-term consequences. With time, it became clear that the current challenge is no longer survival, but understanding and managing the progressive, multisystem nature of Fontan failure. In this issue of the journal, six articles deal with various aspects of this challenging circulation. The surgical way of creating the Fontan circulation has also undergone many changes, with extracardiac (EC) Fontan being the current most popular way of doing it. A meta-analysis and systematic review by Fakhri et al. in this issue of Annals of Pediatric Cardiology analyzed 12 studies with 6280 patients and concluded that EC Fontan had 60% lower odds of arrhythmia (Odd Ratio OR 0.38).1 Classical Fontan patients, who also had the highest arrythmia load, were included in the non-EC group; nonetheless, EC Fontan considerably outperformed lateral tunnel Fontan (OR 0.5). The overall incidence of 15%–60% of important arrhythmias, mainly atrial, is noteworthy. It is fairly intuitive that with no atrial incision, less scarring, and less re-entry circuits, EC Fontan performed better. The inclusion of classic Fontan patients in the non-EC group probably is the reason for such high arrhythmia burden, and the conclusion needs to be absorbed with caution. EC Fontan is associated with lower long-term arrhythmia risk, but arrhythmias remain a universal problem in all Fontan patients. At its crux, the Fontan circulation represents a fundamentally altered hemodynamic construct, characterized by the absence of a subpulmonary ventricle, passive pulmonary blood flow, chronically elevated systemic venous pressure, and reduced cardiac output. While these features are well recognized, their measurement remains surprisingly imprecise. Conventional methods of cardiac output assessment – including Fick, thermodilution, and Doppler-based techniques – are inherently limited in this physiology, often producing inconsistent or unreliable results. Cardiac magnetic resonance imaging provides the most accurate non-invasive assessment but is limited by cost, availability, need for patient cooperation or sedation, and inability to provide real-time or frequent monitoring. This persistent inability to accurately quantify the most fundamental parameter of cardiovascular function underscores a critical gap in Fontan care: we are managing a circulation that we cannot reliably measure. Shah et al. describe impedance cardiography as a promising non-invasive alternative.2 This technology allows bedside, continuous, and repeatable estimation of cardiac output without the risks of invasive procedures. However, its application in Fontan patients is inadequately validated currently. Factors such as thoracic fluid accumulation, low-flow physiology, and the presence of collaterals may affect measurement accuracy. Beyond hemodynamics, the Fontan circulation is increasingly recognized as a multisystem disorder. Chronic venous congestion and low cardiac output exert a sustained burden on multiple organ systems, leading to hepatic fibrosis, renal dysfunction, lymphatic abnormalities, and impaired exercise capacity. Nawara-Węgrzyn et al.’s article in this issue of the journal showed that protein-losing enteropathy (PLE) is a serious complication of the Fontan circulation, affecting about 12% of patients.3 Reduced cardiac output, intestinal inflammation, and possible gut microbiome changes further contribute to the disease. Management is multimodal, including optimization of Fontan hemodynamics, medications (diuretics, steroids, and heparin), and nutritional therapy (high-protein and medium chain triglyceride diet). Newer lymphatic interventions offer promising targeted treatment, whereas heart transplantation remains the definitive option in refractory cases. Similarly, structural issues such as conduit calcification highlight the long-term effect of prosthetic materials, altered flow dynamics, and vascular biology, reinforcing the need for lifelong surveillance. These observations collectively emphasize that no version of the Fontan circulation is free from long-term risk. A study by Cao et al. examines the calcification of EC Fontan (Expanded Polytetraflouroethylene ePTFE) conduits using computed tomography imaging more than 5 years after surgery.4 It shows that conduit calcification is common and progressively associated with narrowing, as reflected by a reduction in cross-sectional area over time. A key finding is that calcification is not uniform; it is significantly greater along the lesser curvature of the conduit, likely due to abnormal flow dynamics. Over long-term follow-up, the proportion of patients maintaining adequate conduit size declines substantially, indicating progressive conduit degeneration, which may remain clinically silent. In spite of being considered an inert material, EPTFE conduits used in EC Fontan conduits do undergo progressive, asymmetric calcification, especially along the lesser curvature, highlighting the need for long-term imaging surveillance. A recent therapeutic innovation, transcatheter Fontan completion, has been promoted by interventional cardiologists in high-risk patients. Sivakumar et al. report a case series in this issue of the journal describing a combination of multiple additional catheter-based interventions to optimize hemodynamics.5 After creation of a conduit by placement of a covered stent between the inferior vena cava and pulmonary arteries, the authors describe atrial septostomy, closure of antegrade pulmonary flow (pulmonary artery PA band/ Patent ductus arteriosus PDA), Blalock–Taussig shunt closure, collateral occlusion, PA stenting, and creation of fenestrations as additional procedures to optimize hemodynamics. This issue of the journal also has a review article by Shah which highlights that failing Fontan circulation is a progressive, multisystem disorder with no proven disease-modifying therapy.6 While survival has improved, most patients eventually develop low cardiac output, high venous pressure, and multiorgan complications, including liver disease, PLE, lymphatic disorders, and exercise intolerance. Current medical therapies (angiotensin-converting enzyme inhibitors, beta-blockers) have little evidence of benefit, while pulmonary vasodilators show modest, inconsistent improvements. Emerging research focuses on new pathophysiological insights, particularly metabolic and biochemical abnormalities such as elevated bile acids and altered lipid metabolism, which may open new therapeutic targets. Several promising strategies are under investigation, including SGLT2 inhibitors (metabolic and heart failure modulation), bile acid-targeted therapies, exercise and rehabilitation programs, an lymphatic interventions for complications like PLE. Failing Fontan is a complex multisystem condition with no established therapy yet, but emerging metabolic, pharmacologic, and interventional strategies offer hope for future treatment. In addition, the pendulum of EC Fontan controversies has been swinging with no solid evidence about routine fenestration of Fontan circuits for better outcomes or the use of therapeutic agents like vasopressin routinely for reducing the morbidity of prolonged pleural effusion.7,8 Our own studies did not show any benefit of routine fenestration or use of vasopressin in low-risk, routine Fontan subsets.9,10 What emerges from this evolving body of evidence is not a lack of progress, but a lack of integration of therapies. The hemodynamic, structural, metabolic, and clinical aspects of the Fontan circulation are still approached in silos, lacking a cohesive framework to link them. This fragmented approach limits our ability to fully understand disease progression, identify early markers of failure, and develop targeted interventions. The way forward requires a fundamental shift in perspective. The Fontan must be redefined; not as the endpoint of surgical palliation, but as the beginning of a chronic, systemic condition requiring lifelong, multidisciplinary management.11 Until we move toward a unified, systems-based understanding of Fontan circulation, it will remain not only a remarkable achievement but an unfinished journey.