INTRODUCTION — The Fontan operation is a palliative surgical procedure performed in patients with a functional or anatomic single ventricle (also known as univentricular heart) [1,2]. The Fontan operation was originally described for patients with tricuspid atresia in 1971 [3]. In the past 50 years, the types of malformations for which the Fontan operation is utilized has expanded considerably, and it has become the most common operation performed for patients with any type of single ventricle [4]. Following the Fontan procedure, patients face substantial morbidity and mortality risks and require lifelong follow-up with a cardiologist experienced in the care of patients with complex congenital heart disease (eg, pediatric cardiologist or adult congenital heart disease specialist).
This topic will discuss management and prevention of complications in patients who have undergone a Fontan procedure. An overview of the management of patients post-Fontan procedure is presented separately. (See "Overview of the management and prognosis of patients with Fontan circulation".)
INDICATIONS FOR REINTERVENTION — During long-term follow-up, Fontan survivors commonly require catheter-based or surgical reintervention. Catheter-based interventions may include fenestration closure or creation, Fontan connection dilation/stenting, and pulmonary artery intervention. Surgical reinterventions include conversion surgery and reoperation to address complications.
Mechanical circulatory support and heart transplantation to treat advanced heart failure are discussed below. (See 'Management of advanced heart failure' below.)
In a series of 773 patients who underwent Fontan procedure, freedom from reoperation was 69 percent at 15 years and 63 percent at 20 years; the most common operations were permanent pacemaker placement and Fontan revision [5]. Freedom from catheter-based intervention was 53 percent at 15 years and 50 percent at 20 years.
Fontan conversion surgery — In selected patients with a history of atriopulmonary Fontan circulation, surgical total cavopulmonary conversion to an extracardiac conduit (or intracardiac lateral tunnel or intraatrial conduit) is considered [1,2,6,7].
The following are indications for evaluating the benefits and risks of Fontan conversion:
●Symptomatic refractory arrhythmias (eg, intraatrial reentry tachycardia, atrial fibrillation, or flutter). (See 'Arrhythmias' below.)
●Right atrial thrombosis. (See 'Thrombosis' below.)
●Fontan pathway obstruction not amenable to transcatheter intervention.
●Exercise intolerance.
●Pulmonary venous compression (particularly the right-sided pulmonary veins) by a very dilated right atrium in an old atriopulmonary connection Fontan.
In patients who present with symptomatic arrhythmias, total cavopulmonary conversion in conjunction with arrhythmia surgery (Maze procedure) has been shown to reduce the arrhythmia burden and improve exercise tolerance [8,9]. (See "Atrial fibrillation: Surgical ablation".)
Other reoperations — Other indications for reoperation after Fontan procedure include the following [1,2]:
●Residual atrial septal defect or other intracardiac shunt, resulting in symptomatic right-to-left shunt (with or without cyanosis) not amenable to transcatheter closure. (See 'Cyanosis and shunts' below.)
●Hemodynamically significant residual systemic-artery-to-pulmonary-artery shunt, residual surgical shunt, or residual ventricle-to-pulmonary-artery connection not amenable to transcatheter closure.
●Severe systemic atrioventricular (AV) valve regurgitation with symptoms, progressive ventricular dilation, or ventricular dysfunction. (See 'Atrioventricular valve regurgitation' below.)
●Subaortic obstruction with peak-to-peak gradient greater than 30 mmHg.
●Fontan pathway obstruction.
●Venous collateral channels or pulmonary arteriovenous malformation not amenable to transcatheter management. (See 'Cyanosis and shunts' below.)
●Pulmonary venous obstruction.
●Rhythm abnormalities such as complete heart block, requiring epicardial pacemaker/defibrillator insertion. (See 'Arrhythmias' below.)
●Indication for fenestration creation or closure not amenable to transcatheter intervention. (See "Overview of the management and prognosis of patients with Fontan circulation", section on 'Fenestration'.)
●Residual obstruction across atrial septum in hypoplastic left or right heart lesions in the presence of total cavopulmonary connection.
CARDIOVASCULAR COMPLICATIONS
Cyanosis and shunts — Patients with Fontan circulation generally have mild systemic arterial oxygen desaturation (oxygen saturation is most commonly 90 to 95 percent), but some patients have more marked oxygen desaturation [1]. Cyanosis in Fontan patients can be caused by persistent drainage of the coronary sinus into the systemic atrium and ventilation-perfusion mismatch; patients can also have right-to-left shunting via fenestrations or other intra- or extracardiac communications [10]. (See "Overview of the management and prognosis of patients with Fontan circulation", section on 'Fontan "physiology"'.)
Cyanotic Fontan patients (with oxygen saturation <90 percent at rest) who have not received intentional fenestration should undergo cardiac catheterization by a congenital cardiologist, including a search for systemic-venous-to-pulmonary-venous connection via venous collateral decompression, inadvertent fenestration, pulmonary arteriovenous malformations (PAVMs), Fontan circuit obstruction, and other potential right-to-left shunts (eg, atrial shunt; or inferior vena cava [IVC], superior vena cava [SVC], or innominate-vein-to-left atrial shunt) [1]. The development of PAVMs has been attributed to one or more hepatic factors not reaching the pulmonary vascular bed. Shunting of hepatic venous flow away from one lung (as seen in some forms of heterotaxy syndrome) can lead to development of PAVMs, and reestablishing hepatic venous flow to an affected lung can lead to improvement or resolution of PAVMs [1]. Obstruction can occur anywhere in the circuit (eg, IVC-to-pulmonary-artery conduit obstruction, branch pulmonary artery obstruction, or SVC/Glenn obstruction) and should be evaluated by advanced imaging (eg, computed tomography [CT], cardiovascular magnetic resonance imaging [CMR], or catheterization) in any cyanotic Fontan patient since it can be missed by echo-Doppler evaluation.
Venovenous collaterals (arising from the systemic venous vessels and draining to the pulmonary venous vessels) are among the potential causes of decreasing oxygen saturation following a Fontan operation. Venovenous collaterals are seen in 20 to 45 percent of patients undergoing catheterization after Fontan or Glenn operations [11,12]. These collaterals are thought to occur due to the chronically elevated central venous pressure. The collaterals act as a de facto right-to-left shunt, causing systemic desaturation and also posing a risk for paradoxical embolism. In the absence of cyanosis or symptoms, no treatment or surveillance for venovenous collaterals are required.
The presence of worsening systemic desaturation at rest or with exercise, or a history of an event attributable to the paradoxical shunt associated with the venovenous collaterals, are considered reasonable indications to proceed with collateral evaluation and potential occlusion. Comprehensive review and discussion are indicated prior to intervention for shunts; the benefits of closing (or altering) communications to improve oxygen saturation should be weighed against the potential risks of increased impedance to venous return, decreased cardiac output, and fall in oxygen delivery [1]. Limited data exist to guide decisions about whether to close a particular collateral vessel in the congenital cardiac catheterization laboratory [13]. In patients without intentional fenestration, persistent clinically significant venous collateral channels and other right-to-left shunts can be treated with transcatheter occlusion but often reoccur after intervention. However, venovenous fistula closure may adversely impact survival, particularly in patients with atriopulmonary type Fontan, heterotaxy, or Fontan pressure above 18 mmHg, so the potential risks and benefits should be carefully weighed [13]. Reoperation may be necessary to close an unintended residual atrial septal defect that results in cyanosis and is not amenable to transcatheter closure [2]. (See 'Other reoperations' above.)
If cyanosis cannot be corrected (or is accepted in a patient with intentional fenestration), standard management for patients with cyanotic heart disease should be instituted (such as meticulous intravenous line care) to avoid air embolism. (See "Medical management of cyanotic congenital heart disease in adults".)
Systemic anticoagulation therapy is recommended for all Fontan patients with cyanosis (with oxygen saturation <90 percent at rest) related to fenestration or collateral formation due to the risk of paradoxical systemic thromboembolism in this setting if benefits outweigh risks.
Due to limited data on direct oral anticoagulants, vitamin K antagonist is currently preferred in this patient population. (See 'Thrombosis' below.)
Arrhythmias — By 10 years after Fontan operation, more than 20 percent of patients have supraventricular tachyarrhythmia, and arrhythmias occur in over 50 percent of patients with prior atriopulmonary Fontan procedure [14]. The incidence of atrial tachycardia appears to be significantly lower after total cavopulmonary connection (eg, lateral tunnel Fontan or extracardiac conduit Fontan), compared with the older atriopulmonary connection Fontan [15]. Intraatrial reentry tachycardia and atrial flutter are the most common arrhythmias following atriopulmonary Fontan procedure [16]. Sinus node dysfunction is also commonly observed in patients with Fontan circulation and may result in impaired heart rate response to exercise.
Patients with arrhythmias following Fontan operation may present with palpitations, hemodynamic deterioration, nonspecific functional decline, embolic events, and occasionally they may be asymptomatic. Atrial arrhythmia episodes, including intraatrial reentry tachycardia, can cause hemodynamic compromise and clot formation.
Consultation with an experienced congenital heart disease electrophysiologist and prompt appropriate management are recommended for patients with atrial or ventricular arrhythmias following Fontan operation, given the risk of significant morbidity [1,2].
●New atrial arrhythmias in a patient with prior Fontan procedure warrant comprehensive assessment for an underlying cause such as electrolyte disorder, thyroid disorder, sleep apnea, or a structural problem such as Fontan obstruction or ventricular or valve dysfunction. Secondary complications such as intracardiac thrombus and heart failure should be identified and treated.
●Systemic anticoagulation is recommended for all Fontan patients with atrial arrhythmias [2,17]. Due to limited data on direct oral anticoagulants, vitamin K antagonist (eg, warfarin) is currently the preferred therapy. (See 'Thrombosis' below.)
Sustained arrhythmia associated with hemodynamic compromise is a medical emergency; electrical cardioversion is the treatment of choice and is usually effective. Transesophageal echocardiography is generally recommended for all Fontan patients undergoing elective cardioversion for atrial arrhythmias, even when on anticoagulation, due to a high risk of atrial thrombus. The most common sites for thrombus are right atrium, Fontan conduit, left atrial appendage, and pulmonary vein orifices.
Patients with infrequent (<once per year), promptly recognized, and well-tolerated intraatrial tachycardia may be treated with a chronic AV-node-blocking agent (eg, digoxin, beta blocker, or calcium channel blocker) to limit the rate of ventricular response, anticoagulation, and periodic cardioversion. If episodes of intraatrial tachycardia are frequent, symptomatic, not promptly recognized by the patient, or are associated with atrial thrombus formation, treatment to prevent recurrences is indicated.
Treatment to prevent recurrent atrial arrhythmias, including intraatrial reentry tachycardia, is a major challenge and includes the following options:
●Class III antiarrhythmic agents (eg, sotalol and amiodarone) are used to treat symptomatic atrial flutter not related to Fontan obstruction. These agents should be started in the hospital under cardiovascular monitoring.
●Catheter ablation is used as an adjunctive strategy or first-line strategy in young patients who prefer to avoid lifelong antiarrhythmic therapy [18]. This procedure should be performed at a specialized center by an electrophysiologist experienced with the management of patients with complex congenital heart disease and prior Fontan procedure. (See "Atrial fibrillation: Catheter ablation" and "Overview of atrial flutter" and "Overview of catheter ablation of cardiac arrhythmias".)
●Customized pacemaker (eg, antibradycardia or antitachycardia) therapy has been suggested as a means of improving arrhythmia management in patients following Fontan operation. Dual-chamber epicardial antitachycardia pacemakers are often used after Fontan conversion [19].
●Surgical conversion to a total cavopulmonary connection with arrhythmia surgery is suggested for select patients with features of Fontan obstruction not amendable to other treatments or refractory arrhythmias despite medical- or catheter-based therapy (figure 1).
Serial exercise testing may identify impaired heart rate response, which may require treatment with an atrial rate responsive pacemaker in selected patients [1]. When a permanent pacemaker is indicated, AV synchrony should be preserved when feasible since ventricular pacing may negatively affect cardiac output and quality of life [1].
Standard indications for implantable cardioverter-defibrillator apply to patients with Fontan circulation. Data are lacking on the use of epicardial or subcutaneous implantable cardioverter-defibrillator placement for primary prevention in patients with Fontan circulation. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".)
Heart failure — Heart failure is defined as a common clinical syndrome with symptoms caused by impaired ability of one or both ventricles to meet resting and exercise demands at a normal pressure due to a structural or functional cardiac disorder. Given this definition, all patients with Fontan circulation have chronic heart failure with elevated systemic venous pressure and low cardiac output. Additional conditions that contribute to heart failure in some Fontan patients include systemic ventricular systolic and/or diastolic dysfunction, AV valve regurgitation, rhythm disorders, volume-loading shunts, Fontan obstruction, and pericardial restraint/constriction. (See 'Atrioventricular valve regurgitation' below and 'Arrhythmias' above and 'Other reoperations' above.)
Symptoms and signs of heart failure in Fontan patients include fatigue, dyspnea, central nervous system symptoms similar to superior vena cava syndrome, end-organ dysfunction (eg, renal insufficiency and liver dysfunction), edema, and ascites.
General management — The management of heart failure in Fontan patients includes medical therapy for heart failure, selective use of biventricular pacing, and selective use of pulmonary vasodilator therapy.
The approach to management of heart failure is similar to that for non-Fontan patients but requires caution given the risk of precipitating a low-output state. Diuretics to treat volume overload should be used with caution since diuresis may decrease edema but can exacerbate low-output symptoms by decreasing systemic venous pressure.
●Some experts treat Fontan patients with heart failure with reduced ejection fraction (HFrEF; left ventricular ejection fraction [LVEF] ≤40 percent) or asymptomatic ventricular dysfunction (LVEF ≤40 percent) with a renin-angiotensin system inhibitor (eg, angiotensin converting enzyme [ACE] inhibitor or angiotensin receptor blocker) or angiotensin receptor-neprilysin inhibitor (ARNI). Use of renin-angiotensin inhibitor therapy in this setting is based upon indirect evidence in non-Fontan patients with HFrEF or asymptomatic left ventricular systolic dysfunction, as there is scant evidence in Fontan patients [20]. (See "Initial pharmacologic therapy of heart failure with reduced ejection fraction in adults" and "Management and prognosis of asymptomatic left ventricular systolic dysfunction".)
●Similarly, selected beta blockers (eg, metoprolol succinate, carvedilol, or bisoprolol, the beta blockers with established benefit for HFrEF generally) (see "Initial pharmacologic therapy of heart failure with reduced ejection fraction in adults") are used with caution in select Fontan patients with HFrEF or asymptomatic ventricular dysfunction. Use of beta blockers in this setting is based on indirect evidence in non-Fontan patients. Beta blocker use to treat atrial arrhythmias is discussed above (see 'Arrhythmias' above). Monitoring of chronotropic competence is important when beta blockers are used in this population. Negative inotropic drugs are otherwise generally avoided in patients with single-ventricle dysfunction.
Biventricular pacing is an option for selected patients with persistent low output despite optimized medical therapy [21-23]. This device should be placed by an experienced congenital electrophysiologist with knowledge of the anatomic challenges. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system".)
Pulmonary vasodilator therapy — For Fontan patients with high indexed pulmonary vascular resistance (PVRI; >2 Wood units x m2), we suggest pulmonary vasodilator therapy. This is an area of ongoing investigation, as there are limited data to support this approach. An observational study identified the combination of high PVRI and low cardiac index (defined as <2.5 L/minutes/m2) as an independent risk factor for Fontan failure (defined as all-cause mortality, listing for heart transplantation, or initiation of palliative care; hazard ratio [HR] 1.84, 95% CI 1.09-2.85) [24]. Agents commonly used in Fontan patients with elevated PVRI include an endothelin receptor antagonist (ERA; eg, bosentan) or a phosphodiesterase type 5 inhibitor (eg, sildenafil). Calcium channel blockers are generally not tolerated in this setting and are generally avoided.
●Support for use of an ERA in this setting comes from the TEMPO trial in which 75 adolescents and adults were randomly assigned to 14 weeks of treatment with bosentan or placebo [25]. There were greater improvements in New York Heart Association (NYHA) functional class (nine improved in the bosentan group versus none in the placebo group), peak oxygen consumption, and cardiopulmonary exercise test time in the bosentan group. Side effects were mild and generally similar in the two groups.
●In an uncontrolled study of eight children, eight adolescents, and eight adults with Fontan circulation with PVRI ≥2 Wood units x m2 and treated with an ERA (bosentan in minors, macitentan in adults) for six months, declines in PVR were observed in all three age groups, and increases in cardiac output were observed in adolescents and adults [26].
●Use of phosphodiesterase type 5 inhibitor in this setting is supported by a randomized crossover trial in 28 patients with Fontan circulation in which sildenafil (20 mg three times daily for six weeks) improved ventilatory efficiency compared with placebo [27]. Flushing was more frequent with sildenafil (5 of 27 versus 0 of 28 patients). A small study has reported on the use of tadalafil in patients with Fontan circulation as well [28].
Management of advanced heart failure — Limited options are available for the complex Fontan patient with end-stage heart failure. Mechanical circulatory support with a ventricular assist device and/or cardiac transplantation is considered in patients following Fontan operation who have refractory low-output symptoms despite optimized medical and device therapy as a bridge to transplantation [29,30]. (See "Treatment of advanced heart failure with a durable mechanical circulatory support device" and "Management of long-term mechanical circulatory support devices".)
Early experiences with outpatient ventricular assist device use in patients post-Fontan were limited to small case series at single centers [29,31,32] (see "Treatment of advanced heart failure with a durable mechanical circulatory support device"). In a report from the ACTION network of 45 Fontan patients supported by ventricular assist devices, at one year after device implantation, 70 percent of patients had been successfully transplanted, while 21 percent of patients had died [33]. Adverse events were common and occurred in 67 percent of patients, with neurologic events the most common type of adverse event.
Although medical issues in Fontan patients complicate and/or preclude isolated cardiac transplantation in some cases, it remains an option for many patients. Factors limiting isolated heart transplant candidacy include severe hepatic dysfunction (including cirrhosis and risk of hepatocellular carcinoma), chronic kidney disease, pulmonary insufficiency (including single functional lung), infection risk (particularly in patients with protein-losing enteropathy [PLE] and asplenia), and presensitization. Heart-liver transplant is a treatment option for some patients. Due to multiple prior blood transfusions and/or the use of homograft material in the palliative surgeries, patients can develop preformed antibodies to donor human leukocyte antigens. This can increase the risk of graft rejection and vasculopathy post-transplant. (See "Heart transplantation in adults: Indications and contraindications" and "Heart transplantation in adults: Prognosis" and "Liver transplantation in adults: Patient selection and pretransplantation evaluation".)
Because of these many comorbidities, mortality on the heart transplant waiting list is higher for Fontan patients compared with most other diagnoses. Risk factors for death on the transplant waiting list for all patients include a diagnosis of congenital heart disease (specifically hypoplastic left heart syndrome), being on extracorporeal membrane oxygenation (ECMO) or ventilator support, and a history of dialysis [34-36].
Accepted indications for heart transplant in patients after Fontan operation include:
●Ventricular systolic or diastolic dysfunction with class III or IV symptoms
●PLE
●Plastic bronchitis
●Cyanosis with associated decline in functional status
●Refractory arrhythmias in a patient who is not a candidate for Fontan conversion in conjunction with arrhythmia surgery
Recommended personnel for cardiac transplantation evaluation and management in adult Fontan patients are not well established. Some centers have all of these patients receiving transplants through the pediatric program, while others perform these transplants at adult centers with the assistance of adult congenital heart disease experts.
For Fontan patients undergoing cardiac transplantation, the in-hospital mortality remains higher than patients with other diagnoses, primarily related to preoperative risk factors discussed above (although this varies by center due to selection bias) and late referral in many cases [35,37,38]. Studies comparing longer-term mortality rates post-transplant in Fontan patients with other congenital heart disease patients have yielded mixed results. A study of 488 patients (mean age 14.8 years, range 6 months to 62 years) transplanted for congenital heart disease found that Fontan patients faced higher mortality rates at one and five years compared with non-Fontan patients (29 versus 17 percent and 40 versus 26 percent). In contrast, a meta-analysis of 351 Fontan patients (mean age 14 years, range 7 to 24 years) undergoing cardiac transplantation reported a one-year mortality rate of 20.7 percent and a five-year mortality rate of 28.8 percent, results similar to other patients with congenital heart disease [39]. Notably, studies have reported improved post-transplant survival of Fontan patients in the last 10 years, compared with the prior era [40].
In general, patients transplanted for congenital disease (or undergoing retransplantation) have higher early mortality rates compared with patients transplanted for cardiomyopathy [41]. However, patients with congenital heart disease able to survive the early post-transplant period have the highest conditional survival and overall survival beyond 5 to 10 years [41]. Importantly, both PLE and plastic bronchitis appear to resolve within three to six months after transplant in most patients. (See "Heart transplantation in adults: Indications and contraindications" and "Heart transplantation in adults: Prognosis".)
Some patients with Fontan palliation and multiple comorbid conditions are considered for multiorgan transplantation. These procedures are performed at only a few centers worldwide due to the complexity of the procedure and preoperative and postoperative care.
Atrioventricular valve regurgitation — Moderate or greater AV valve regurgitation is common in patients with Fontan circulation. In a series of 1199 Fontan patients, the cumulative incidence of AV valve failure (eg, development of moderate or greater regurgitation or need for valve repair or replacement) at age 25 years was 56 percent for patients with common AV valve, 46 percent for those with single tricuspid valve, 8 percent for those with single mitral valve, and 26 percent for those with two AV valves. [42]. AV valve failure occurred both pre- or post-Fontan.
Patients with prior Fontan operation and AV valve regurgitation may be asymptomatic or present with progressive dyspnea, ventricular dilation, ventricular dysfunction, or arrhythmias. AV valve regurgitation may be caused by structural valve abnormalities (particularly of the tricuspid valve), ventricular and/or annular dilation, or impaired ventricular systolic function [1]. Moderate or greater AV valve regurgitation is a risk factor for increased long-term mortality in patients with Fontan circulation [1]. Fontan failure (defined as death, heart transplantation, Fontan takedown, Fontan conversion, plastic bronchitis, PLE, or NYHA functional class III or IV) is twice as frequent among those with AV valve failure compared with those without valve failure (23 versus 9 percent at 10 years post-Fontan and 46 percent versus 23 percent at 20 years) [42].
Annual echocardiographic imaging is recommended to assess ventricular size/function and valve function in all patients following Fontan operation.
Medical management of Fontan patients with AV valve regurgitation may include afterload reduction and diuretic therapy. Diuretics may be beneficial for Fontan patients with features of volume overload, but these agents should be used with caution since they can cause excessive fall in preload with decreased cardiac output. Afterload reduction therapy is often used in patients with single ventricle, but there are no prospective data to support the use of these agents to treat ventricular dysfunction or AV valve regurgitation in patients with Fontan circulation.
Patients with Fontan circulation, severe AV valve regurgitation and symptoms, progressive ventricular dilation, or ventricular dysfunction are evaluated for surgical valve repair or replacement. However, these patients face high risks of operative mortality, recurrent regurgitation following valve repair, and persistent ventricular dysfunction after valve repair or replacement [43]. Observational data on AV valve surgery in Fontan patients suggest that systemic mitral valve repair may be more durable than systemic tricuspid valve or common AV valve repair [42,44]. Data are lacking on the use of transcatheter interventional procedures for patients with native AV valve regurgitation following Fontan operation, with only limited case reports available [45].
Thrombosis — Patients with Fontan circulation are at risk for systemic and pulmonary thromboembolic events given low flow in the Fontan circuit and associated alterations in levels of clotting and fibrinolysis factors. The reported prevalence ranges from 2 to 33 percent (overall 11 percent), depending on the mode of detection [46,47]. The risk of stroke is approximately 0.3 to 0.5 percent per year. Systemic thromboembolic events occur with greater frequency in patients with fenestrations (communication between right atrium/Fontan connection and left atrium). Pulmonary thromboembolic events can reduce cardiac output due to increases in pulmonary vascular resistance and thus can also be life threatening. (See "Overview of acute pulmonary embolism in adults" and "Overview of the management and prognosis of patients with Fontan circulation", section on 'Fenestration'.)
Risk factors for thrombus or low flow in the Fontan circuit include right-atrial-to-pulmonary-artery connection, Fontan connection with secondary right atrial dilation (figure 1), reduced cardiac output, Fontan obstruction, presence of foreign material (eg, stents), and atrial arrhythmias. In addition, some patients may have a concurrent thrombophilia (eg, protein C or protein S deficiency). By echocardiography, low flow in the Fontan circuit may appear as spontaneous echo contrast (a smoke-like pattern of blood flow), especially in patients with the right-atrial-to-pulmonary-artery connection; thrombus may also be identified incidentally on imaging assessment (image 1) [48].
Thrombosis occurs not only in the right heart but also may occur in the left atrium and pulmonary veins. Transthoracic echocardiography lacks the sensitivity of transesophageal echocardiography (TEE) for intracardiac thrombus identification, so TEE is recommended to assess for thrombus in a patient presenting with systemic thromboembolism following Fontan. Cardiac CT and CMR may also identify or confirm intracardiac thrombus in Fontan patients.
Management of the thromboembolic risk in Fontan patients includes anticoagulation, maintenance of sinus rhythm, and treatment of Fontan obstruction when identified. We suggest low-dose aspirin (75 to 100 mg daily) for all Fontan patients [49]. For Fontan patients with a history of thromboembolism, right atrial thrombus, right atrial blood stasis, fenestration, atrial arrhythmias, or ventricular ejection fraction less than 40 percent, we suggest anticoagulation with a vitamin K antagonist or rivaroxaban. Data are lacking on the safety and efficacy of direct oral anticoagulation agents in Fontan patients [17]. If thrombus in the Fontan patient persists despite adequate anticoagulation, surgical removal and Fontan conversion are suggested. There are limited data on thrombolytic therapy for thrombus and thromboembolic complications in patients with prior Fontan operation [50].
The best therapeutic approach for preventing thromboembolism in post-Fontan patients has not been established. Limited data are available on use of vitamin K antagonist (eg, warfarin) or rivaroxaban in this setting:
●Vitamin K antagonist – A randomized trial comparing aspirin (5 mg/kg/day) and warfarin (goal international normalized ratio [INR] 2 to 3) in 111 patients with Fontan circulation found that rates of thrombosis (combined clinical and subclinical) were similar in the two treatment groups (21 and 24 percent) at two years [51]. Patients treated with warfarin with subtherapeutic INR levels had higher risks of thrombosis compared with patients on warfarin with therapeutic INR levels and those on aspirin (HR 3.53, 95% CI 1.35-9.20) [52].
●Rivaroxaban – The UNIVERSE Study randomly assigned 112 children to either rivaroxaban or aspirin for 12 months following Fontan operation [53]. The safety profile in the two treatment groups was similar, with clinically relevant nonmajor bleeding in 6 percent of participants on rivaroxaban versus 9 percent on aspirin. The rate of thrombotic events was similar in the two groups: one participant on rivaroxaban had a pulmonary embolism (2 percent overall event rate); on aspirin, one participant had ischemic stroke and two had venous thrombosis (9 percent overall event rate). Rivaroxaban is now approved by the US Food and Drug administration for both children and adults following the Fontan operation.
Bleeding — Management of bleeding complications includes evaluation for underlying cause, discontinuation of antithrombotic agents such as aspirin or vitamin K antagonists, and correction of any coagulopathy or bleeding lesion (eg, esophageal varices, hemorrhoids). Little is known about the impact of bleeding complications on these patients and how they affect long-term outcomes.
Following Fontan operation, patients are also at risk for bleeding complications. A report described bleeding complications in 412 Fontan patients during long-term (mean 11.2 years) follow-up: 13 patients (3 percent) had hemoptysis, and cerebral bleeds occurred in three patients (1 percent) [54]. These bleeding events were associated with having a Fontan operation later than usual and the preoperative use of medications blocking the renin-angiotensin system (eg, ACE inhibitors, angiotensin receptor blockers).
Venous insufficiency — The prevalence of chronic venous insufficiency and venous reflux is significantly greater in the Fontan population compared with healthy controls [55,56]. Patients with venous insufficiency present with lower-extremity edema, venous varicosities, stasis changes, and venous ulcers. (See "Diagnostic evaluation of lower extremity chronic venous insufficiency" and "Overview of lower extremity chronic venous disease".)
Factors associated with severe chronic venous insufficiency in one series included increased numbers of catheterization procedures with groin venous access, lower-extremity itching, and deep venous thrombosis [55]. Venous reflux in Fontan patients appears to be related to single right ventricle, use of antiarrhythmic drugs, and family history of venous disease [56]. Management of chronic venous insufficiency is discussed separately. (See "Overview of lower extremity chronic venous disease".)
RESPIRATORY COMPLICATIONS — Patients post-Fontan commonly have restrictive lung disease and may develop plastic bronchitis.
Restrictive lung disease — Patients with a history of Fontan operation have been shown to have a restrictive pattern on pulmonary function testing associated with reduced exercise capacity [57], likely related to multiple sternotomies [58], and perhaps also due to concomitant scoliosis [59]. This is functionally important, and patients with reduced forced vital capacity and breathing reserve also have poorer functional capacity on cardiopulmonary exercise testing.
They also may have differences in diffusing capacity related to the manner of passive blood flow into the lungs [60]. Regular chest radiography is typically recommended for lung disease surveillance. (See "Overview of the management and prognosis of patients with Fontan circulation", section on 'Follow-up recommendations'.)
Plastic bronchitis — Plastic bronchitis is estimated to occur in 3 to 4 percent of patients after Fontan procedure [61] and is associated with similar risk factors as protein-losing enteropathy (PLE) [62]. In plastic bronchitis, there is formation of mucofibrinous bronchial casts, resulting in marked airway obstruction. Patients will often expectorate these large casts or require urgent removal by bronchoscopy, and life-threatening events may occur in up to 40 percent of affected patients [63]. Initial management of patients with active plastic bronchitis is similar to that of PLE, including optimization of Fontan hemodynamics and ensuring there is no alternate reversible cause of elevated central venous pressure. Proposed treatment options include inhaled or systemic steroids, aerosolized mucolytics, and aerosolized fibrinolytics such as tissue plasminogen activator [64]. There are limited available data on survival; a study of 25 patients reported a median transplant-free survival of 8.3 years after diagnosis [62].
Observational studies suggest that plastic bronchitis results from intrapulmonary lymphatic overload or leakage. In a case series, retrograde lymphatic flow from the thoracic duct to the lung parenchyma was observed in patients with plastic bronchitis, and selective embolization of the culprit lymphatic vessels was followed by symptomatic improvement [65,66]. Lymphatic embolization has also been used in the setting of acute decompensation in the setting of plastic bronchitis [67]. While early evidence is very promising, long-term follow-up will be required to determine the safety and durability of the intervention.
Cardiac transplantation appears to be effective as a long-term option for treating plastic bronchitis. In a multicenter study, all patients who survived 30 days post-transplant had full resolution of their plastic bronchitis [68]. (See "Heart transplantation in adults: Indications and contraindications", section on 'Congenital heart disease'.)
GASTROINTESTINAL COMPLICATIONS
Protein-losing enteropathy — Protein-losing enteropathy (PLE) has been reported to affect 3 to 18 percent of patients following the Fontan operation in various series [1,69-72]. In the largest reported multicenter series, studying >3000 Fontan patients and risk factors for developing PLE, an incidence of 3.7 percent was reported [71]. PLE can present weeks to years after Fontan operation, with the average reported time around 3.5 years after Fontan [71].
Commonly presenting symptoms and signs of PLE include diarrhea, peripheral edema, abdominal pain and bloating, pleural effusions, pericardial effusions, and ascites. The intestinal protein loss seen in PLE along with nutrient malabsorption lead to hypoalbuminemia, lymphopenia, hypogammaglobulinemia, coagulation abnormalities, impaired growth, and decreased bone density. Mortality after PLE diagnosis is high, with only 46 to 59 percent of PLE patients surviving for more than five years after diagnosis in the largest studies. Death can be due to heart failure, hypocalcemia, thromboembolism, arrhythmia, and infections, with sepsis as a particular risk due to chronic hypogammaglobulinemia [71,72]. (See "Protein-losing gastroenteropathy".)
A multifactorial hypothesis for the development of PLE after the Fontan operation has been described [1,65,70]. The primary insult is often chronic venous congestion-induced lymphatic overload and low cardiac output with poor perfusion of the gastrointestinal mucosa. Mesenteric vascular impedance is markedly increased in patients with PLE, which in combination with vascular congestion due to elevated venous pressures, results in abnormal enterocyte function [73]. PLE patients have been shown to have specific loss of heparin sulfate and syndecan-1 proteoglycans, which is felt to worsen in the presence of inflammation or elevated central venous pressure, affecting intestinal epithelial barrier function [74]. It is likely that chronic inflammation and an undefined genetic predisposition play a role in determining which patients develop PLE after Fontan [70,71,75]. It is unclear how many of the abnormal abdominal lymphatic vessels are present at birth or whether they occur as a result of the Fontan and associated operations.
The gold standard for diagnosis of PLE is a combination of clinical features (eg, diarrhea, peripheral edema, abdominal pain and bloating, ascites, and pleural or pericardial effusions) combined with laboratory confirmation (eg, low albumin and increased 24-hour clearance of alpha-1-antitrypsin). Patients with no or minimal clinical symptoms of PLE who demonstrate laboratory features consistent with the diagnosis are occasionally identified. Diagnostic laboratory testing includes 24-hour stool alpha-1-antitrypsin clearance study. Random "single-sample" analysis of stool for alpha-1-antitrypsin level is not as accurate as the formal 24-hour clearance study. However, a low "single-sample" alpha-1-antitrypsin stool concentration, coupled with normal plasma protein levels, may serve as a convenient surveillance method for asymptomatic patients in whom clinical suspicion for PLE is low [76,77]. The diagnosis and evaluation of PLE are discussed further separately. (See "Protein-losing gastroenteropathy", section on 'Diagnosis'.).
Management of PLE generally includes comprehensive evaluation to address underlying cause(s) (as outlined below), close clinical surveillance, and individualized therapy, depending on patient characteristics and response to therapy. All of our patients undergo cardiac catheterization to exclude Fontan obstruction and define hemodynamics to guide management. Therapy is individualized but generally involves a multifaceted dietary, medical, and occasionally interventional approach (see "Protein-losing gastroenteropathy", section on 'Management'):
●Consultation with gastroenterologist with knowledge of the Fontan operation. Other causes of gastrointestinal symptoms (eg, sprue) should be excluded.
●Exclusion of other causes of hypoalbuminemia and reversible mechanical causes of elevated central venous pressure such as Fontan circuit obstruction (if present, consider percutaneous or surgical intervention), significant AV valve regurgitation, restrictive interatrial septum, or left ventricular outflow tract or aortic arch obstruction. Aortography should be performed to identify aortic-pulmonary collateral vessels causing increased resistance to pulmonary flow.
●Optimize general management, including the following:
•Minimize anemia or iron deficiency [78].
•Diet modification with caloric augmentation.
-A high protein, high medium-chain triglyceride, reduced sodium, low-fat diet is often recommended. The clinician should monitor serum markers of nutritional status such as albumin. The primary concern with this treatment is compliance, as the diet is not easy to follow.
●Improve symptoms (eg, careful diuretic therapy to treat symptoms of volume overload). Examples of diuretics used include:
•Loop diuretic – Furosemide is commonly used in this setting to treat volume overload; pediatric dosing is 1 mg/kg by mouth twice daily; adult dosing is 20 to 80 mg by mouth once to twice daily or by intravenous infusion. Torsemide, another loop diuretic, is often used for maintenance therapy in adults. Dosing is adjusted as needed based on symptoms. The clinician will need to check serum electrolytes as the dose is titrated (eg, hypokalemia, other disturbances).
•Mineralocorticoid receptor antagonist – For spironolactone, pediatric dosing is 2 to 4 mg/kg/day by mouth divided twice daily; adult dosing is 50 to 100 mg per day dosed daily or split into twice daily doses. Dosing is adjusted as needed. Serum electrolyte monitoring is similarly required (eg, hyperkalemia, other disturbances). Gynecomastia has been reported as a common side effect. If a patient develops endocrine side effects on spironolactone (eg, gynecomastia), then eplerenone is an alternative.
●Albumin infusions may also be utilized to improve serum albumin, enhance diuretic effect, and improve symptoms, though these are temporary measures. Pediatric dosing is 0.5 to 1 g/kg of 25 percent albumin IV, up to adult dosing. For adult/teen dosing, we suggest 50 g of 25 percent albumin IV; repeat weekly to monthly with titration to effect (eg, symptoms, serum albumin). The primary side effects are edema and infection from repetitive access. Furosemide is often used in combination with IV albumin to help treat edema.
●Improve cardiac output using:
•Afterload reduction – This is accomplished with a renin-angiotensin system inhibitor (eg, ACE inhibitor or angiotensin II receptor blocker [ARB]), although direct evidence of efficacy in this setting is lacking.
•Fenestration – This creates a right-to-left shunt and "off-loads" the Fontan circulation [10]. The benefits and risks of fenestration are discussed separately. (See "Overview of the management and prognosis of patients with Fontan circulation", section on 'Fenestration'.)
•Pacing – If indications for a pacemaker are present, this should be performed while preserving AV synchrony when feasible. The primary risks involved are related to the procedure itself (often epicardial) and the risk of lead or generator complications.
•Reduce pulmonary arteriolar resistance using pulmonary vasodilator.
-Sildenafil – Pediatric dosing is 0.5 to 1 mg/kg/dose by mouth three times daily up to adult dosing of 20 mg by mouth three times daily. Primary side effect concerns are hypotension and priapism. Other phosphodiesterase type 5 inhibitors may be used.
For children weighing 8 to 20 kg, 10 mg three times daily; for those weighing over 20 kg, 20 mg three times daily. For children weighing less than 8 kg (including neonates), a typical starting dose of 0.5 mg/kg three times daily is generally used. This can then be increased as tolerated or to effect, up to a maximum of 2 mg/kg/dose every 6 hours [79].
-Bosentan – Infants and children <12 years: Initial dose is 1 mg/kg/dose twice daily; increase to a target dose of 2 mg/kg/dose twice daily; maximum dose: 125 mg/dose;
Children ≥12 years and >20 to 40 kg: initial: 31.25 mg twice daily; increase to a target dose of 62.5 mg twice daily;
Children ≥12 years and >40 kg are dosed as adults.
Adult dosing: Initial dose is 62.5 mg twice daily; if patient weighs ≥40 kg, this is titrated up to 125 mg twice daily.
●Reduce gastrointestinal protein loss. (See "Protein-losing gastroenteropathy", section on 'Management'.)
•Case reports have described resolution of PLE with heparin therapy [80,81]. An observational study found that heparin therapy led to subjective improvement in PLE symptoms but did not increase the rate of PLE remission [82]. Unfractionated heparin (UFH) is the preferred form (low-molecular weight heparin has been reported on in very limited case reports but may not be as effective) [80-82]. Pediatric dosing for UFH is 100 units/kg subcutaneously daily, up to adult dosing of 5000 units subcutaneously daily, with adjustments as needed, guided by anti-Xa assay. Side effects are bleeding and issues related to chronic injections.
•Limited case reports have described using octreotide to reduce gastrointestinal protein loss [83]. When used, it is given as a three-times-daily subcutaneous injection or as a monthly intramuscular depot injection. Pediatric dosing is 1 to 10 mcg/kg/day to start, up to adult dosing of 150 mcg subcutaneously three times daily or 20 mg monthly intramuscular depot injection. If any new abdominal pain occurs on octreotide, cholelithiasis needs to be ruled out.
•Observational studies suggest that oral glucocorticoid therapy (eg, prednisone or budesonide) may reduce gastrointestinal protein loss in patients post-Fontan with PLE, but systemic side effects can limit treatment. Patients with liver disease are particularly intolerant of budesonide [84].
-Prednisone – Pediatric dosing is 1 to 2 mg/kg/day by mouth; adult dosing is 5 to 60 mg/day by mouth initially. Dosing is adjusted for effect and tolerance. Primary side effects include hyperglycemia, hypertension, adrenal suppression, and osteopenia.
-Budesonide – Dosing (adult and pediatric) is 6 to 9 mg/day by mouth, increased by increments of 3 mg. Primary side effects include hepatotoxicity, hyperglycemia, hypertension, and adrenal suppression. Systemic steroid side effects of budesonide may be increased in the presence of significant liver disease and portosystemic shunts as the first-pass effect of the liver is diminished.
•Evidence continues to suggest that abnormal hepatic lymphatic vessels are present in patients with PLE and may be the cause of much of the protein loss. Thus, targeting these vessels via selective embolization is an attractive therapeutic target [65,66,85]. The optimal timing and long-term outcomes of this intervention remain unclear, but isolated case reports suggest resolution of some of the complications related to PLE in treated patients.
●PLE is considered an indication for cardiac transplantation post-Fontan. (See 'Management of advanced heart failure' above and "Heart transplantation in adults: Indications and contraindications", section on 'Congenital heart disease'.)
Liver disease — Patients post-Fontan are at risk for liver disease (known as Fontan-associated liver disease), although the overall incidence of liver disease in patients following the Fontan operation is unknown. A retrospective study evaluated 195 patients who had liver imaging or liver biopsy after Fontan operation. Of these, 40 of 195 (21 percent) had a diagnosis of cirrhosis. The mean duration from Fontan operation to a diagnosis of cirrhosis was 23±6 years. The freedom from cirrhosis in this cohort was 99, 94, and 57 percent at 10, 20, and 30 years, respectively. However, these data should be interpreted cautiously, as this is a retrospective cohort with a high degree of selection bias [86].
After a patient has a Fontan procedure, the liver is subjected to a chronic low-cardiac output state combined with increased mesenteric resistance and chronic venous congestion [70,73,87]. As a substantial amount of blood flow to the liver is dependent on the mesenteric circulation, the elevated central venous pressure and mesenteric resistance seen in Fontan patients may result in further abnormalities of blood supply to the liver [87].
Patients post-Fontan with liver fibrosis or cirrhosis are most often asymptomatic, with abnormalities found on screening blood work such as elevated liver enzymes, reduced platelet count, or radiologic abnormalities on liver ultrasound, magnetic resonance imaging (MRI), or CT. Serum liver enzymes (with progressive increase, particularly of gamma-glutamyl transpeptidase) and serum bilirubin levels are commonly elevated. Variable degrees of hepatomegaly, hepatic congestion, liver fibrosis, and cirrhosis are seen. The degree of cirrhosis may be heterogeneous and patchy within the liver. Most concerning is the increased risk of hepatocellular carcinoma in Fontan patients, particularly those with cardiac cirrhosis [88].
Patients with Fontan circulation should be advised to avoid hepatotoxins given the potential risk of liver disease. Routine liver surveillance is advised, particularly given the risk of hepatocellular carcinoma. The most effective method and frequency of surveillance for liver disease in Fontan patients are uncertain. We suggest routine liver imaging (eg, ultrasound, MRI, or CT) every three to five years in asymptomatic patients who are five or more years out from their Fontan operation. Patients with features of fibrosis or cirrhosis require close monitoring, including twice-annual laboratory surveillance (alpha-fetoprotein level) and annual imaging due to an increased risk of developing hepatocellular carcinoma. MRI and CT offer superior sensitivity for detection of hepatocellular carcinoma compared with ultrasound. Magnetic resonance elastography or ultrasound-based elastography of the liver appear promising for the noninvasive screening of patients after Fontan procedure for liver pathology; however, further research is required before these become the standard screening tools [89-91]. Routine laboratory markers such as liver enzymes are rarely helpful for screening this cohort of patients since blood tests do not adequately distinguish patients with normal, noncirrhotic changes from cirrhosis [92,93]. (See "Clinical features and diagnosis of hepatocellular carcinoma", section on 'Imaging'.)
Routine liver biopsy has been proposed for all patients 10 years after Fontan operation to establish the degree of liver fibrosis/cirrhosis [87]. However, the sensitivity of liver biopsy in these patients with heterogeneous liver findings is unclear, as is the availability of treatment modifications based on results. In the event of a liver mass on ultrasound, MRI, or CT, however, biopsy remains the gold standard to investigate a specific lesion for possible malignancy, as radiologic features of HCC are not pathognomonic.
Consultation with a hepatologist who has experience in hepatocardiac disorders and patients with Fontan operation is recommended for those with evidence of liver disease. Noncardiac causes of cirrhosis (eg, viral hepatitis, inherited, or autoimmune disorders) should be excluded. Patients with cirrhosis should be referred for upper endoscopy to identify esophageal varices. Prognostic stratification can be performed by assessing patients for features of portal hypertension using modifications of current criteria such as MELD-XI score [94,95]. (See "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis", section on 'Diagnosis' and "Primary prevention of bleeding from esophageal varices in patients with cirrhosis", section on 'Endoscopic evaluation'.)
RENAL COMPLICATIONS — Patients with a Fontan circulation are at risk for developing reduced glomerular filtration rate (GFR), proteinuria, and albuminuria, which may reflect end-organ dysfunction caused by low cardiac output and venous congestion [1,96]. Renal dysfunction has been observed longitudinally in at least 10 percent of children with Fontan circulation, with increasing prevalence in adolescence and adulthood [1]. Renal resistive index has emerged as a powerful predictor of late outcomes [97]. Patients who suffer acute kidney injury (AKI) at the time of Fontan operation are at higher risk of both late renal dysfunction and all-cause mortality [98].
Consultation with a nephrologist who is familiar with the Fontan operation is suggested for patients post-Fontan with evidence of kidney disease. Evaluation should include exclusion of treatable renal inflow or outflow obstruction. Cyanosis and hypotension appear to adversely impact renal function.
Management includes surveillance for kidney disease (particularly prior to any procedures) and renal protective measures including control of blood pressure (eg, treatment of hypertension and avoidance of hypotension, control of blood sugar, and counseling the patient to stay hydrated, avoid smoking, limit sodium intake, and avoid overweight/obesity) [1]. Patients with chronic kidney disease should avoid or minimize use of nephrotoxins, including nonsteroidal antiinflammatory drugs and radiographic contrast dye. (See "Overview of the management of chronic kidney disease in adults" and "Dietary recommendations for patients with nondialysis chronic kidney disease".)
Dialysis or ultrafiltration (ie, renal replacement therapy [RRT]) may be required for patients with Fontan operation with renal failure or volume overload that does not respond to standard therapy, either immediately following the Fontan operation or over long-term follow-up. In the largest study published of patients undergoing Fontan operations, 11 percent suffered AKI, with around half requiring RRT. Both in-hospital mortality and long-term all-cause mortality were higher in patients who had AKI at the time of their Fontan operation compared with those who did not have AKI.
RRT was needed in <4 percent of patients following Fontan conversion at one experienced center [7]. In another surgical series, 4 of 23 consecutive patients required RRT after Fontan revision with total cavopulmonary surgery [99]. Three of the four patients treated with RRT died at a median of three months; thus, RRT requirement portends a higher mortality risk after Fontan revision or conversion. There are limited data on the outcome of patients that require chronic RRT related to progressive decline in renal function late after Fontan procedure.
SOMATIC GROWTH ISSUES
Impaired physical development — Patients with Fontan circulation tend to have short stature, and deficits in height are associated with reduced functional health status [1,100]. Measures to prevent or treat short stature in this population have not been established. Optimizing treatment of heart failure has been proposed as one possible means of reducing the risk of short stature [1].
Many patients with Fontan circulation have decreased vitamin D levels, increased levels of parathyroid hormone, low lean muscle mass, and decreased cortical bone mineral density [1]. Heart failure may be a factor in impaired growth as suggested by an observed inverse relationship between B-type natriuretic peptide level (a marker of heart failure) and mediators of growth hormone insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) in children and young adults with Fontan circulation [101]. The diagnostic approach to children and adolescents with short stature is discussed separately. (See "Diagnostic approach to children and adolescents with short stature" and "Causes of short stature".)
In some patients, growth hormone therapy may be used to treat short stature, depending on bone age and other clinical features. This should only be done under the guidance of an endocrinologist with experience in treating patients with complex congenital heart disease.
Obesity — Avoidance of obesity is an important component of management of patients with Fontan circulation since obesity increases the risk of some complications [1]. Evidence suggests that a body mass index <25 kg/m2 may be optimal for cardiovascular health in the general population [102], and this target may also be helpful for patients with Fontan circulation [1]. Obesity and overweight are highly prevalent in patients with Fontan circulation, similar to the general population, but obesity poses particularly hazardous effects in patients with Fontan circulation [1]. At the time of Fontan surgery, an estimated 10 percent of patients are overweight or obese, increasing to 20 to 30 percent by 12 years of age and 38 to 50 percent in adults [1]. Recommendations for exercise are discussed separately. (See "Obesity in adults: Overview of management" and "Healthy diet in adults" and "Overview of the management and prognosis of patients with Fontan circulation", section on 'Exercise'.)
Risks associated with obesity include heart failure, nonalcoholic liver disease, obstructive sleep apnea, and increased risk of cancer including hepatocellular carcinoma. (See 'Heart failure' above and 'Liver disease' above.)
NEUROLOGIC COMPLICATIONS — Patients with congenital heart disease are at increased risk of neurodevelopmental disorders, disabilities, developmental delay [103], and abnormalities in executive function. Following Fontan operation, functional and developmental status can range from normal to severely limited. Limitations may be due to genetic or developmental issues and perioperative or postoperative insults (including hypoxic-ischemic injury, macroemboli, and microemboli) [1]. Since individuals with Fontan circulation have a prothrombotic state and are at risk for developing atrial arrhythmias, they are at increased risk for embolic complications, including stroke. Brain MRI studies have demonstrated widespread abnormalities in white and gray matter [1,104].
Early neurodevelopmental and neuropsychiatric evaluations of children with Fontan circulation are warranted to identify those who may benefit from targeted intervention [1]. Developmental limitations warrant genetic and neurologic assessment to identify and address treatable causes.
PSYCHIATRIC DISORDERS — In one study comparing 156 adolescents after Fontan operation with 111 healthy controls, the Fontan patients had a higher rate of any lifetime psychiatric diagnosis (65 versus 22 percent) [105]. Fontan patients also had higher rates of any lifetime anxiety disorder or adult deficit/hyperactivity disorder and scored lower on the Children's Global Assessment scale, a common measure of psychosocial function. Concerns for any psychiatric illness in a Fontan patient warrant full assessment by psychology or psychiatry specialists. Social work support is beneficial for many Fontan patients and their families and caregivers.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Congenital heart disease in adults" and "Society guideline links: Arrhythmias in adults".)
SUMMARY AND RECOMMENDATIONS
●Complications in patients with Fontan circulation include cyanosis, arrhythmias, heart failure, atrioventricular valve regurgitation, thrombosis, venous insufficiency, lung disease, protein-losing enteropathy (PLE), liver disease, kidney disease, somatic growth disorders, neurologic complications, and psychiatric disorders. (See 'Cardiovascular complications' above and 'Respiratory complications' above and 'Gastrointestinal complications' above and 'Renal complications' above and 'Somatic growth issues' above and 'Neurologic complications' above and 'Psychiatric disorders' above.)
●Conversion from atriopulmonary Fontan to an extracardiac conduit is considered in selected patients with symptomatic refractory arrhythmias, Fontan pathway obstruction, or marked exercise intolerance attributed to abnormal Fontan flow. (See 'Indications for reintervention' above.)
●Patients with Fontan circulation generally have mild systemic arterial oxygen desaturation (oxygen saturation most commonly 90 to 95 percent), but some patients have more marked arterial oxygen desaturation. Cyanotic Fontan patients (with oxygen saturation <90 percent at rest) who have not received intentional fenestration should undergo cardiac catheterization by a congenital cardiologist, including a search for systemic-venous-to-pulmonary-venous connection via venous collateral decompression, inadvertent fenestration, pulmonary arteriovenous malformations, and other potential right-to-left shunts (eg, atrial shunt, or inferior cava, superior cava, or innominate-vein-to-left-atrial shunt). (See 'Cyanosis and shunts' above.)
●Patients with atrial or ventricular arrhythmias following Fontan operation require consultation with an experienced congenital electrophysiologist and urgent and aggressive management given the risk of significant morbidity, including intracardiac thrombus and heart failure. (See 'Arrhythmias' above.)
●All patients with Fontan circulation have chronic heart failure with elevated systemic venous pressure and low cardiac output. Additional conditions that contribute to heart failure in some Fontan patients include systemic ventricular systolic and/or diastolic dysfunction, atrioventricular valve regurgitation, rhythm disorders, volume-loading shunts, and Fontan obstruction. The management of heart failure in Fontan patients includes medical therapy for heart failure, selective use of biventricular pacing, and selective use of pulmonary vasodilator therapy. (See 'Heart failure' above.)
●For Fontan patients with indexed pulmonary vascular resistance >2 Wood units x m2, we suggest pulmonary vasodilator therapy (Grade 2C). Agents commonly used in this setting include an endothelin receptor antagonist (eg, bosentan) or a phosphodiesterase type 5 inhibitor (eg, sildenafil). (See 'Pulmonary vasodilator therapy' above.)
●Management of thromboembolic risk in Fontan patients includes anticoagulation, maintenance of sinus rhythm, and recognition/treatment of Fontan obstruction. For all Fontan patients, we recommend antithrombotic therapy (Grade 1B). The choice of antithrombotic therapy depends on the risk of thromboembolic complications. For patients at high risk (eg, cyanosis related to fenestration or collateral formation, atrial thrombus, right atrial blood stasis, fenestration, atrial arrhythmias, venovenous collaterals, ventricular ejection fraction less than 40 percent, or history of thromboembolism), we suggest anticoagulation (Grade 2C). In this setting, anticoagulation options are vitamin K antagonist (eg, warfarin) or rivaroxaban (approved by the US Food and Drug Administration for this indication). For Fontan patients not at high risk of thromboembolism, low-dose aspirin (75 to 100 mg daily) is sufficient. (See 'Thrombosis' above and 'Cyanosis and shunts' above.)
●PLE can present weeks to years after Fontan procedure. Five-year survival after PLE diagnosis is around 50 percent. Management includes exclusion of reversible mechanical causes of elevated central venous pressure, medical therapy, and in select cases catheter-based or surgical intervention, including heart transplantation. (See 'Protein-losing enteropathy' above.)
●Patients post-Fontan are at risk for liver disease, although the overall incidence is unknown. The most effective method of surveillance for liver disease in Fontan patients is uncertain. We suggest liver imaging (eg, magnetic resonance imaging or computed tomography) every three to five years in patients who are five or more years out from their Fontan operation. Patients with features of cirrhosis require close monitoring due to high risk of developing hepatocellular carcinoma. (See 'Liver disease' above.)
