Introduction

For years now, the number of adults with congenital heart disease (ACHD) has outnumbered pediatric patients with congenital heart disease (CHD). However, for the last decade or so, we have seen steady growth in the proportion of ACHD patients with complex CHD, in particular, among long-term survivors with functionally univentricular hearts. These individuals pose unique challenges related to their underlying physiology.

It has been estimated that 1 in 3000 infants is born with a single ventricle [1]. In modern congenital cardiology practice, the vast majority of these individuals survive into adulthood. Those patients—individuals without a subpulmonary pumping chamber—are arriving in adult clinics and hospitals with increasing frequency and complex, unique medical demands.

This review focuses on the management of this fascinating group of patients. We will first discuss the long-term outcomes, and then focus on cardiac and extracardiac manifestations of patients who are not doing well, often labeled as the poorly defined “failing Fontan” physiology.

Population of Survivors

The Fontan operation, first reported in 1971 as a palliation for two cyanotic patients with tricuspid atresia, is now the final surgical step for many patients with functionally univentricular hearts [2]. It serves the purpose of separating the majority of systemic venous and pulmonary venous blood, such that inferior and superior caval flow is brought passively and directly to the pulmonary arteries.

While the single ventricle surgical pathway for most patients ends with the Fontan operation, the anatomic substrate of individual patients is quite varied. Many older Fontan patients have a morphologic left ventricle (LV) and pertained to either tricuspid atresia or double inlet left ventricle groups. With the advent of the Norwood operation as the initial surgery for patients with hypoplastic left heart syndrome (Fig. 1), adolescents and young adult Fontan patients increasingly include those with a morphologic right ventricle (RV) functioning as a systemic ventricle. Still, others with two good-sized ventricles have complex intracardiac anatomy that precludes biventricular repair and go on to Fontan palliation.

Fig. 1
figure 1

Staged reconstruction of hypoplastic left heart syndrome. a Stage 1, consisting of homograft patch reconstruction of aorta (asterisk), homograft patch on pulmonary artery, and Blalock-Taussig Shunt (dagger). b Stage 2, consisting of takedown of Blalock-Taussig Shunt and creation of bidirectional Glenn shunt (double dagger; end-to-side anastomosis of superior vena cava to right pulmonary artery and oversewing of superior vena cava stump). c Final step consisting of completion of Fontan, typically with intraatrial lateral tunnel or extracardiac conduit. RPA = right pulmonary artery, RA = right atrium, SVC = superior vena cava, LT = lateral tunnel

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Over time, the Fontan surgery itself has undergone many modifications (Fig. 2). Originally, it was described as a direct anastomosis of the right atrial appendage to the pulmonary artery known as an atriopulmonary (AP) Fontan. Many modifications later, most major congenital heart centers now offer either the extracardiac (EC) or lateral tunnel (LT) Fontan.

Fig. 2
figure 2

Variations of Fontan circulation (with permission from Springer: Valente AM, Landzberg MJ, Powell AJ: Adult congenital heart disease. Edited by Libby P. In Essential Atlas of Cardiovascular Disease. New York, New York: Springer; 2009:231–246) [3]

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Mortality

In a recent population study of >1000 Fontan patients in Australia and New Zealand, the 25-year freedom from death or transplant was 76 % in AP Fontan patients, while the LT and EC groups fared slightly better[4••]. Khairy and colleagues looked at a group of 261 Fontan patients from Boston and found that among survivors of the early postoperative period, the 20-year survival was 82.6 % and did not differ significantly among the various Fontan-types [5]. Reliable survival data beyond 20–25 years does not yet exist.

Morbidity

Morbidity, however, is a different story. In the same population study from Australia and New Zealand, freedom from late adverse events was only 29 % at 25 years [4••]. These late adverse events included the following: Fontan failure (defined as death/transplant, take down or Fontan conversion, or protein-losing enteropathy/plastic bronchitis), supraventricular tachycardia/pacemaker insertion, or stroke/pulmonary embolism.

As a term, “Fontan failure” means different things to different clinicians. As such, variable definitions have been used in the literature, including some combination of death or transplant, Fontan conversion, signs and symptoms of poor cardiac output in setting of preserved ventricular function, lymphatic complications (protein-losing-enteropathy (PLE)/plastic bronchitis), New York Heart Association (NYHA) class III–IV symptoms, etc. What is consistently reported is that adults who have undergone a Fontan operation face challenges and are at risk for all of the above issues.

Cardiac Manifestations

If we define Fontan failure as a clinical syndrome of circulatory dysfunction that can involve multiple organ systems [6], we must first consider the central role that the heart plays. Broadly, patients with Fontan failure can be divided into two categories: those with poor ventricular function and those with preserved ventricular function.

Systolic Dysfunction

A subset of univentricular patients with Fontan palliation has poor systemic ventricular function, and speculation persists regarding whether this can be attributed to differences in systemic RV versus LV morphology. In the multicenter Pediatric Heart Network (PHN) study of 546 Fontan patients with a mean age of 11.9 years, RV morphology was associated with worse systolic function compared to LV morphology, though the differences were small (56 vs. 60 %)[7]. RV morphology has also been associated with increased hazard of heart failure death [5]. In nearly 500 single-ventricle patients, those with RV-dominant ventricles had a hazard ratio of 2.2 for death, but only as children prior to the bidirectional Glenn stage (Fig. 1b) [8].

In adults, there has been no definitive evidence of significantly different outcomes between those with RV and LV morphology [9]. This may be related to some survival bias among those patients who reach ACHD clinics. The historical differences in terms of anatomic substrate for Fontan palliations accounts for larger groups of single morphologic LV in modern ACHD practice, so the final answer as to whether systemic RV patients have worse systolic long-term function remains uncertain.

Lacking large randomized controlled trials, the management of Fontan patients with systolic dysfunction is largely extrapolated from the literature of systolic heart failure in adults. Patients with hypertension should be carefully evaluated for any anatomic obstruction, such as residual coarctation or arch obstruction in cases of prior Norwood operation. Afterload reduction with angiotensin converting enzyme-inhibitors or beta-blockers seems reasonable, and diuretics are used mainly for symptoms of congestion and fluid retention.

Atrioventricular Valve Regurgitation

One issue tied closely to systolic function is the degree of atrioventricular (AV) valve regurgitation. In particular, a systemic RV with its tricuspid AV valve appears more prone to regurgitation [10]. In the PHN study, patients with a systemic RV tended to have more AV valve regurgitation following Fontan completion than those with a systemic left ventricle [7]. Liu and colleagues examined over 500 patients and found that nearly 10 % required AV valve surgery prior to, at the time of, or following Fontan surgery [11]. Many of those required subsequent reoperation of the AV valve: at 10 years postoperation, only 48.9 % were free from repeat AV valve surgery or cardiac transplantation. AV valve regurgitation may be a particularly challenging issue for those with heterotaxy and unbalanced complete AV canal with a common AV valve.

Regardless of cause, significant AV valve regurgitation in an individual with a univentricular heart is poorly tolerated over the long term. Data for medical treatment of this condition is lacking. Most centers aggressively target significant AV valve regurgitation by surgical means—AV valve repair or replacement—at the time of Fontan and in long-term survivors, although surgical AV interventions remain a risk factor for poor outcomes [12, 13••].

Diastolic Dysfunction

As many as two - thirds of adult Fontan patients who die or require heart transplantation maintain preserved systolic function [14]. Over time, patients with a single ventricle are exposed to hemodynamic stressors that predispose to elevated filling pressures. Many ACHD patients had palliative shunts and later Fontan operations compared to a modern cohort, subjecting their single ventricle to more significant and prolonged volume loading. Indeed, operation in an early surgical era (prior to 1991) is one known risk factor for worse long-term outcomes [13••]. By the time they reach adulthood, these patients have undergone many surgical procedures requiring cardiopulmonary bypass.

Hebson et al. showed that adults with Fontan palliations and symptoms had higher systemic ventricular end diastolic pressure compared to asymptomatic pediatric Fontans (13 vs. 10 mmHg, respectively, p = <0.01) [15]. Given that systemic venous pressure in a Fontan circulation must be higher than the ventricular filling pressure, it follows that these adult patients also have higher Fontan pressures compared to their pediatric cohort and, thus, more postsinusoidal hypertension of the Fontan liver (see section below).

The astute clinician caring for adult Fontans will review potentially reversible causes for diastolic dysfunction. Cardiac catheterization may be helpful to treat arch obstruction or any aortopulmonary collaterals resulting in a significant left to right shunt. Medical management is usually based on symptoms. In cases of severe dysfunction and Fontan failure, some have advocated working toward a Fontan ventricular assist device that would serve to power the passive circuit, decrease systemic venous pressure, and increase preload and cardiac output [16, 17]. Ultimately, some of these patients may be considered for cardiac transplantation.

Two reports have suggested that Fontan patients who are referred for cardiac transplant with preserved ventricular function do worse than similar patients with decreased ventricular function [18, 19]. Simpson and colleagues showed that Fontan patients with preserved ventricular function had more episodes posttransplant of primary graft failure, requirement for mechanical circulatory support, and infections [18].

Pulmonary Vasculature

Lacking a subpulmonary ventricle, the cardiac output in Fontan patients is intimately tied to resistance across the pulmonary vascular bed. Given this, there has been a great deal of interest in applying newer drugs directed at lowering pulmonary vascular resistance (PVR) toward improving Fontan hemodynamics.

One must first ask: what is a normal PVR in a patient who has undergone Fontan palliation? In patients who have multiple sources of pulmonary blood flow (e.g., classic Glenn and AP Fontan to the left pulmonary artery), it is not possible to accurately calculate the PVR. Some have suggested using transpulmonary gradient as a surrogate. Still, the non-pulsatile flow inherent to the Fontan may not accurately reflect the true PVR. For example, one study found a mean increase in transpulmonary gradient of 6.8 mmHg when it was assessed and calculated before and after heart transplantation [20].

A recent randomized, placebo-controlled, double-blinded study examined exercise parameters in response to bosentan, an endothelin receptor antagonist [21•]. Compared to placebo, a small but significant increase in peak VO2 (1.4 cc/kg/m2) was seen with bosentan. Patients who received bosentan also had an improvement in NYHA function class. Goldberg and colleagues studied exercise parameters in young adult Fontan patients who received sildenafil [22]. While they found no difference in VO2 max, they did find improved ventilatory efficiency. Additionally, they reported improved oxygen consumption at anaerobic threshold in patients with a morphologic LV or mixed ventricle group or those with elevated baseline brain natriuretic peptide [22].

While most experts do not routinely use pulmonary vasodilators, the threshold for use of such drugs in adult Fontan patients is certainly lower. These drugs may play an important role for those with significant functional impairment yet preserved systolic function, or those with elevated Fontan pressure who also have elevated transpulmonary gradient. They also may play a role for the rare group of Fontan patients that develop protein-losing enteropathy or plastic bronchitis (see below) [23•].

Fontan Pathway/Pulmonary Artery Architecture

One key follow-up issue in Fontan patients is the architecture of pulmonary artery (PA) anatomy and serial observation for obstruction. Banka et al. reviewed 175 single-ventricle patients under 5 years of age at pre-Fontan catheterization and found that 64 % required interventions, 7 % of which were related to pulmonary artery plasty [24]. In the setting of non-pulsatile flow, small narrowings may have a large impact on flow through the Fontan. Three-dimensional cardiac imaging and/or cardiac catheterization are critical tools for surveillance of adequate PA growth and early detection of anatomic obstruction.

Thrombosis, obstruction, and the potential for thromboembolism in the Fontan pathway are major long-term issues [25]. Almost all adults are on some form of antiplatelet or anticoagulation therapy, though data have yet to define the optimal treatment strategy [26]. At a minimum, adult Fontan patients should be on an antiplatelet agent in the absence of contraindications; warfarin is a reasonable choice for higher-risk patients, such as those with a prior history of thrombus or significant arrhythmia burden.

Arrhythmia

Atrial arrhythmias, most typically intraatrial macroreentrant tachycardias, are the most common cardiac complication affecting individuals after Fontan operation. Factors contributing to the high risk of atrial arrhythmias include extensive atrial suture lines, atrial hypertension, and atrial dilation and hypertrophy. The incidence increases steadily from the time of Fontan completion but varies depending on the type of Fontan connection. In patients who underwent the classic AP connection, nearly half have experienced atrial arrhythmia 15 years following Fontan surgery. While the experience with LT and EC Fontan operations is shorter, the incidence of atrial arrhythmias in patients with either of these Fontan types has been significantly lower than at comparable time points after AP Fontan [27].

Unfortunately, atrial arrhythmias are poorly tolerated by single-ventricle patients, even when the ventricular rate is “well - controlled.” If sustained, patients may experience congestive heart failure, intracardiac thrombus, stroke, hypotension, or even sudden death. Thus, while “rate control” is a frequently used strategy in the anatomically normal patient with atrial arrhythmias, patients with Fontan physiology who are found to be in a persistent atrial arrhythmia frequently warrant urgent cardioversion with appropriate precautions taken to minimize stroke risk.

Once atrial arrhythmias manifest, treatment is dictated by the arrhythmia burden and patient symptomatology. This often serves as the impetus to advance patients from aspirin to warfarin therapy. In cases of less frequent, well-tolerated arrhythmias, conservative use of beta-2 adrenergic antagonists or a class III antiarrhythmic agent (e.g., sotalol, dofetilide, amiodarone) may be sufficient to control events. Often, radiofrequency catheter ablation can be useful, but the presence of multiple reentrant pathways and atrial hypertrophy result in overall lower success rates compared to other forms of CHD [28]. Many patients will undergo two or more attempts at catheter ablation before resorting to more aggressive measures to control arrhythmia, such as Fontan conversion, which consists of resection of the enlarged right atrium in an individual with an older, atriopulmonary Fontan; placement of an intracardiac or extracardiac conduit as is standard in contemporary Fontan operations; and performance of an atrial maze operation.

The flipside to atrial arrhythmias is sinus node dysfunction and chronotropic incompetence. The occurrence of this complication in patients with Fontan circulation is likely due to injury to the sinus node or its arterial supply at the time of surgery or as a result of postoperative atrial remodeling. While less common than tachyarrhythmia, the hemodynamic consequences of too slow a heart rate in an individual with Fontan circulation can be equally profound [29, 30]. In such cases, placement of a pacemaker—hardly a straightforward task in the Fontan anatomy—can be beneficial.

Extracardiac Manifestations

As a paradigm for heart failure, the Fontan circulation is unique in its chronicity. Whereas half of heart-failure patients die within 5 years of diagnosis, transplant-free survival post-Fontan operation has reached nearly 85 % at 20 years according to some studies [5]. The magnitude and chronicity of hemodynamic disturbance seen in the Fontan circulation may be one explanation for the high prevalence of other organ system dysfunction.

Although cardiologists may not be accustomed to thinking about and assessing other organ systems, it has become clear that dysfunction of extracardiac organ systems is an important component of Fontan failure. Even in the absence of overt symptoms of heart failure, such as edema, ascites, or exertional dyspnea, the development of systemic complications must be seen as an indication of failure of the Fontan circulation. Indeed, it is often these complications that become the primary determinant of patient prognosis and management.

Plastic Bronchitis

Plastic bronchitis is a very rare entity characterized by rubbery, fibrin casts of the bronchial tree that result in progressive airway obstruction and, potentially, asphyxia and death, with an estimated prevalence of 4–14 % in Fontan patients [31]. Most cases of plastic bronchitis occur within the first 4–5 years after Fontan completion, but it has been reported to occur as late as 15 years out [32•].

Although understanding of the pathophysiology of plastic bronchitis remains incomplete, one plausible theory is that decreased cardiac output results in mucosal injury, permitting leakage of proteinaceous and cellular material into the airways. Because cast formation is commonly described in the context of respiratory infections, airway inflammation likely plays a role as well.

The immediate priority is alleviation of symptoms. In the case of more significant respiratory compromise, early bronchoscopy is indicated for diagnosis and therapeutic removal of casts. Inhaled tissue plasminogen activator has been demonstrated to be beneficial in both clinical and ex vivo studies. Bronchodilators, mucolytics, and aggressive pulmonary toilet all facilitate expectoration of casts. Response to inhaled corticosteroids and anti-inflammatory agents has also been reported.

All patients presenting with plastic bronchitis should undergo rigorous evaluation of the Fontan circulation to identify potential inefficiencies in the circuit that may be driving worsened venous hypertension and decreased cardiac output (Table 1). Catheter-based or surgical interventions to address treatable conditions may result in decreased cast formation. If PVR is increased, pulmonary vasodilators such as phosphodiesterase type 5 (PDE-5) inhibitors or endothelin antagonists may be used. If there is inadequate response to the above approaches, creation of a Fontan fenestration may allow for improved cardiac output and decreased venous congestion (Fig. 3). In more dire cases, takedown of the Fontan, ventricular assist device implantation, and/or transplant may need to be considered.

Table 1 Important contributors to consider in the evaluation of the failing Fontan patient
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Fig. 3
figure 3

Angiographic stills before (a) and after (b) fenestration of the atrial septum in an 18-year-old patient who developed persistent ascites and pleural effusions 15 years after undergoing an atriopulmonary Fontan operation. Arrow shows approximate site of newly created fenestration. Aortic saturation decreased from 90 to 81 %. There was a modest immediate decrease in Fontan pressure from 23 to 21 mmHg. On follow-up catheterization, Fontan pressure had decreased further to 15 mmHg. RA = right atrium, MPA = main pulmonary artery, LA = left atrium

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More recently, there has been speculation that plastic bronchitis is related to abnormal lymphatic drainage, whether congenital or acquired as a result of elevated central venous pressure, adhesions, and trauma at the time of surgery. Ligation of the thoracic duct to limit lymphatic flow has been reported to help, as has diversion of the innominate vein to the atria [33].

Protein-Losing Enteropathy

Protein-losing enteropathy is estimated to affect 5–15 % of the Fontan population, and has a tendency to occur later after Fontan surgery than does plastic bronchitis (mean 3.5 years, but can happen as much as 27 years after surgery)[23•]. Some authors have observed two distinct peaks, one occurring early after Fontan completion and the second in late adolescence and early adulthood.

PLE is characterized by excessive gastrointestinal loss of serum proteins, resulting in hypoproteinemia. In older patients, PLE generally presents with edema, pleural and pericardial effusions, and loose stools. In younger patients, the nutrient malabsorption and protein loss can lead to failure to thrive. It has been reported that mortality reaches 50 % by 5 years after initial diagnosis [34], but more contemporary data shows current survival to be 88 % at 5 years, with higher Fontan pressure, decreased ventricular function, decreased NYHA class, higher PVR, and lower cardiac index being risk factors for poor outcomes. Death is due to heart failure, thromboembolism, arrhythmia, or sepsis [23•].

Increased vascular impedance has been seen in Fontan patients with PLE compared to those without [35]. This, in combination with increased venous pressures, results in decreased systolic and diastolic blood flow, potentially compromising the integrity of gut epithelium and allowing increased protein losses. In addition, several reports have pointed to potential genetic predisposition in some individuals with reduced enterocyte heparan sulfate [36, 37].

Once diagnosed, consultation with a gastroenterologist is needed to rule out other conditions such as malnutrition, impaired hepatic protein synthesis, or intestinal causes. The Mayo group recently proposed a treatment algorithm based on the suspected multifactorial nature of PLE [23•]. This includes intestinal direct therapies such as low fat/high protein diet, medium chain triglycerides, subcutaneous heparin, oral budesonide, or octreotide. Patients who develop PLE earlier seem to better respond to oral budesonide than those who present later. In this group, chronic hypertension within the lymphatic system may play more of a role. Diuresis and albumin infusion can also be used to treat symptoms.

As with plastic bronchitis, a rigorous search for factors that decrease cardiac output and/or increase venous pressures should be undertaken. This should include non-cardiac contributors such as anemia, thyroid dysfunction, or sleep apnea. Also as with plastic bronchitis, case reports of response to PDE-5 inhibitors have been published [38]. PLE is considered an indication for transplant post-Fontan as transplantation is often curative.

Liver Disease

Liver disease is one of the most vexing complications after Fontan. Although the overall incidence is still being investigated, it appears that liver disease is all but inevitable in patients with Fontan physiology and may begin immediately after Fontan completion, if not before then [39, 40]. Manifestations range from modest hepatic congestion in the mildest cases to severe fibrosis with nodular regeneration (cardiac cirrhosis).

Coexisting liver disease has presented a barrier to heart transplant in many patients with Fontan physiology. In other cases, unappreciated liver dysfunction may contribute to increased postoperative mortality. More recently, reports of hepatocellular carcinoma among older patients with Fontan physiology 2–3 decades after Fontan have been generating concern [41–45].

The precise cause of liver disease in individuals with Fontan circulation is still not completely understood. Factors that are associated with more advanced liver disease vary. There appears to be a correlation with poorer hemodynamics and increased time after Fontan, but these findings have been inconsistent [39, 40, 46–48]. Hepatic fibrosis associated with congestive heart failure has long been recognized and is generally understood to be a primarily sinusoidal process with portal tract involvement in only the most advanced cases. This type of hepatopathy is thought to be mediated by increased central venous pressure, which induces hepatic injury through sinusoidal stasis, stromal stretch, and compression of adjacent hepatocytic plates. Fibrosis in the portal distribution is more typically associated with inflammatory liver diseases such as viral hepatitis, toxic injury related to alcohol or medications, or non-alcoholic fatty liver disease (NAFLD), but studies consistently show portal involvement in patients with Fontan circulation at all stages of sinusoidal fibrosis, suggesting that factors other than central venous hypertension may be contributing to liver injury.

Most routine blood testing has been shown to be insensitive for detecting liver disease. While biopsy is still generally considered to be the gold standard, correlation between biopsy and outcomes appears to be poor, suggesting that diagnostic utility may be limited by heterogeneous liver involvement [48]. Thus, liver imaging with CT or MRI may be the best method for routine hepatic surveillance.

In cases where liver disease is identified, efforts should be undertaken to identify and eliminate sources of obstruction or decreased output, and consultation with a hepatologist familiar with Fontan liver disease is essential. Although increased hepatic vein pressure gradients are rarely found at catheterization, findings associated with portal hypertension such as esophageal varices, ascites, thrombocytopenia, and splenomegaly can be seen and predict adverse outcomes [14].

Nadolol is the standard treatment for esophageal varices in liver disease patients and may be considered for affected Fontan patients, but reduction of venous congestion through diuresis may reduce varices as well. Transjugular intrahepatic portosystemic shunts are sometimes considered for patients with cirrhotic patients but probably do not play a role for Fontan patients unless an increased hepatic vein pressure gradient is demonstrated. Ascites is presumably related to a combination of heart failure and liver disease. Diuresis with loop diuretics and spironolactone is the mainstay of treatment, but paracentesis may be needed if symptomatic ascites develop.

Hepatocellular carcinoma (HCC) is perhaps the most dreaded complication of chronic liver injury, but the risk factors are not clear. In the general population, HCC is rare in the absence of cirrhosis. Because making a diagnosis of cirrhosis remains problematic in the Fontan population, anyone with more advanced fibrosis probably warrants imaging and alpha-fetoprotein measurement every 6–12 months for surveillance.

Once diagnosed, even more challenges arise with regard to the appropriate management of HCC in the Fontan population. Due to the high risk of reoccurrence, liver transplantation is generally considered the treatment of choice for HCC, but in the Fontan population, this would only be feasible in the context of a combined heart-liver transplant [49].

Renal Disease

While the need for hemodialysis is rare among individuals with Fontan circulation, abnormal renal function probably remains under-recognized in this population. Reduced glomerular filtration rate and increased creatinine is common and is likely a consequence of decreased cardiac output and venous congestion. Those with concomitant cyanosis are at particularly high risk for renal disease. However, even a modest reduction in renal function is an important predictor of adverse outcomes [50].

Important Comorbidities

While not necessarily a result of the Fontan circulation, an increased prevalence of disease in still other organ systems can contribute to Fontan failure. Recognition of these interrelationships is important to ensure appropriate surveillance and early intervention in well Fontan patients.

Lung Disease

Due to the lack of a pump “energizing” the Fontan circuit upstream from the pulmonary vascular bed, a healthy pulmonary and pulmonary vascular system is an important factor in the long-term success of the Fontan circulation. Unfortunately, patients with Fontan physiology often have restrictive lung disease on pulmonary function testing related to prior thoracotomies and abnormal diffusing capacity related to the unusual distribution of pulmonary blood flow in the Fontan circulation [51, 52]. Better understanding of cardiopulmonary mechanics may yield novel strategies for maintaining the Fontan circulation.

Hematology

Many potential sources of right-to-left shunting exist in the Fontan patient, from surgically created fenestrations at the time of Fontan completion to pulmonary arteriovenous malformations in patients where inferior vena caval return streams preferentially to one lung. Although erythrocytosis is a normal compensatory response to decreased systemic oxygen saturations, it is important to monitor iron levels and hematocrit. While it can be easy to overlook iron deficiency anemia in patients with erythrocytosis, it may be particularly problematic in this cohort of patients with limited ability to augment cardiac output.

Overview of Clinical Approach

At any time of a decline in functional status, it is prudent to consider a rigorous evaluation of potential exacerbating factors (Table 1). Echocardiography, MRI, and/or cardiac catheterization are useful to identify potential inefficiencies in the Fontan circuit that may be driving venous hypertension and decreased cardiac output. Potential issues to rule out include Fontan obstruction due to thrombus or stenosis, pulmonary vascular disease, valvular regurgitation or stenosis, ventricular dysfunction, pericardial constriction, restrictive ventricular filling, coarctation, or aortopulmonary collaterals.

Medical therapy is usually directed at the underlying symptoms. Manifestations of congestion and heart failure can be treated with diuretics, with close attention paid to the underlying ventricular function. In some cases, typical adult CHF therapies such as afterload reduction with ACE-I may be harmful in the setting of Fontan failure, liver failure, and low systemic vascular resistance state. Arrhythmias often require rapid interventions to restore sinus rhythm, with a focus on rhythm control. Antiarrhythmics and beta-blockers are often only temporizing solutions. If PVR is increased, pulmonary vasodilators such as PDE-5 inhibitors or endothelin receptor antagonists may be considered.

Catheter-based or surgical interventions to address reversible issues are critical and time-dependent. For example, patients with a classic atriopulmonary Fontan and high arrhythmia burden or other complications might benefit from Fontan conversion to an LT or EC Fontan, though even at experienced centers, mortality for this operation ranges between 5 and 10 %[53, 54]. In selected cases, ventricular assist devices—either as a support for the single ventricle with poor systolic function or as a Fontan support—may be considered [16]. Cardiac transplantation, with or without concomitant liver transplant, may be an option for some [55].

There is a growing recognition of the Fontan circulation as an altered physiology, which has a remarkably broad, adverse impact on the long-term health of single-ventricle patients. Given the high rate of Fontan morbidity and mortality and the myriad ways that Fontan failure can manifest, it is essential to adopt a proactive approach for the evaluation and surveillance of anticipated issues.

Current consensus guidelines recommend lifelong care with an ACHD specialist [56]. However, cardiologists alone are inadequately trained to provide for the numerous extracardiac care needs of single-ventricle patients. In many cases, care for this group requires collaboration and partnership between subspecialty cardiologists and specialists in other organ systems.

Conclusions

It has been 45 years since the initial publication of a Fontan’s strategy to palliate cyanotic patients with functional univentricular hearts. We are now witnessing the triumph of survival into adulthood of these complex patients, and the challenges—both cardiac and extracardiac—that can occur in the face of chronic, fundamentally abnormal hemodynamics.

It is essential for clinicians to remember that not all patients with Fontans are the same. There is great anatomic heterogeneity, varied historical surgical strategies, and different hemodynamic pitfalls for “failure” along the way. To better understand this group, it will be critical to find a common classification scheme for Fontan failure and focus on multi-institutional collaboration to combine resources and study this rare group of patients.