Five decades of Fontan palliation: What have we learned? What should we expect?

Abstract

The Fontan procedure is the final palliative surgery in a series of staged surgeries to reroute the systemic venous blood flow directly to the lungs, with the ventricle(s) pumping oxygenated blood to the body. Advances in medical and surgical techniques have improved patients’ overall survival after the Fontan procedure. However, Fontan-associated chronic comorbidities are common. In addition to chronic cardiac dysfunction and arrhythmias, complications involving other organs such as the liver, lungs, intestine, lymphatic system, brain, and blood frequently occur. This narrative review focuses on the immediate and late consequences in children, pregnant women, and other adults with Fontan circulation. In addition, we describe the technical advancements that might change the way single-ventricle patients are managed in future.

Introduction

Single-ventricle heart defects are congenital heart defects characterized by either severe stenosis or atresia of the atrioventricular and/or semilunar valves, hypoplastic ventricles, or cardiac anatomy not favorable for biventricular repair. As a result, a single ventricle is responsible for pumping blood both to the lungs and into the systemic circulation while also receiving input from both sources. This abnormality often requires a physiological shunt to allow mixing of oxygenated and deoxygenated blood to sustain life.

The present narrative review focuses on application of the Fontan procedure to help palliate these anatomic abnormalities, the long-term implications of having Fontan circulation, and some of the complications that commonly arise. We identified relevant literature using the PubMed, Scopus, and Web of Science databases. We reviewed all relevant publications since 1971, the year in which the Fontan procedure was introduced to 15 August 2023. The following terms were used for the search: Fontan OR Fontan circulation OR single ventricle OR univentricular heart AND outcome OR complications.

Single-ventricle palliation using Fontan procedure

One method of palliating single-ventricle heart defects is staged reconstruction of the heart. The goal of this intervention is to separate deoxygenated and oxygenated blood while allowing the single working ventricle to operate without volume overload. Patients undergo staged reconstruction with stage 1 and 2 palliations followed by the Fontan procedure.

Surgical palliation: Stage 1, stage 2, and Fontan procedure

The Fontan procedure was first described in 1971 by Francis Fontan et al.^1,2 In these revolutionary reports, they discussed a new procedure that was initially directed at correcting tricuspid atresia. They described an operation in which the heart underwent staged repair to redirect all vena caval blood to the pulmonary arteries (PAs), and the blood then passively returned to a single ventricle (termed the systemic ventricle). This ventricle was responsible for supplying oxygenated blood to the rest of the body. This was initially accomplished by anastomosing the superior vena cava (SVC) to the right PA and the inferior vena cava (IVC) to the left PA via the right atrium (RA), then closing off any remaining connections with the systemic ventricle. This minimized any mixing of oxygenated and deoxygenated blood. ¹ Today, a similar staged repair is used to address single-ventricle heart defects, albeit with some modifications. ³

Stage 1 of reconstruction, termed the Norwood procedure, is usually performed within a few days after birth. The goal is to correct any life-threatening abnormalities to allow survival until the next stage of reconstruction can be attempted. This usually involves three primary endpoints. First, atrial septectomy allows oxygenated blood from the left atrium to reach the systemic ventricle. Second, a neo-aorta is constructed to restore flow to the systemic circulation. Finally, a systemic-to-pulmonary artery shunt is created to supply blood from the aorta to the lungs. This is termed the modified Blalock–Thomas–Taussig shunt and is usually created by placing a shunt between the subclavian or innominate artery to the branch PA. The patent ductus arteriosus is surgically closed. The shunt ensures that a controlled amount of blood reaches the pulmonary circulation, preventing overload. ⁴ In some cases, an alternative shunt termed the Sano shunt can also be utilized. ⁵ This involves the placement of a conduit between the systemic ventricle and main PA. In particularly high-risk patients, an alternative to the Norwood procedure is the hybrid procedure.^6,7 This involves placement of bilateral PA bands while keeping the patent ductus arteriosus open either by stenting or use of prostaglandin infusion. For some single-ventricle heart defects with pulmonary overcirculation but reliable systemic blood flow and intracardiac blood mixing, PA banding is maintained until stage 2 palliation.

Stage 2 of reconstruction involves the hemi-Fontan ⁸ or bidirectional Glenn procedure ⁹ and is usually performed between 4 and 6 months of life. The goal of both of these interventions is to offload the systemic ventricle and redirect blood flow into the pulmonary circulation. In the hemi-Fontan procedure, this is accomplished by creating an anastomosis between the SVC and central/branch PAs, allowing SVC blood to flow directly into the PAs. A homograft stopper is then placed in the SVC to increase blood flow into the pulmonary circulation. Alternatively, patients can undergo the bidirectional Glenn procedure, which involves disconnecting the SVC from the RA and attaching it to the right PA. In both procedures, the Blalock–Thomas–Taussig or Sano shunt is removed. ⁴ Patients who initially underwent a hybrid procedure undergo comprehensive stage 2 palliation including neo-aortic reconstruction, atrial septectomy, and PA debanding in addition to the bidirectional Glenn procedure. ¹⁰

Stage 3 of reconstruction, termed the Fontan procedure, is performed at 2 to 3 years of age. The goal of this procedure is to separate the arterial and venous circulation and prevent mixing of oxygenated and deoxygenated blood. This either involves detaching the IVC from the RA and reconnecting it to the previously created SVC and right PA anastomoses via a conduit (extracardiac Fontan) or placing a conduit from the IVC to the SVC through the RA (lateral tunnel Fontan). In patients with high pulmonary vascular resistance (PVR), a fenestration of the conduit can be performed with the common atrium to allow shunting of blood from the venous to arterial circulation. ⁴

Interstage care of single-ventricle patients

Interstage care refers to the time between stage 1 and stage 2 of single-ventricle palliation. ¹¹ This period is characterized by high morbidity and mortality rates because these infants are discharged from the hospital. ¹² Specifically, the goal of interstage care is to reduce mortality by educating parents and implementing in-home surveillance to detect changes in physiology, which may occur immediately prior to decompensation. ¹¹

Patients’ parents must be counseled on common red flags prior to patient discharge. These red flags involve noting any acute changes in the patient’s status, either by observing their vitals or by using easily attainable objective data. Almost all patients receive home oxygen monitoring devices to ensure that their oxygenation remains appropriate. Because the blood is mixed between the atria, normal oxygen saturation is not expected; however, it should not fall below 75%. ¹³ Other important markers include appropriate weight gain, absence of weight loss, good oral intake, and absence of cyanosis and fever. Patients should also be monitored for new diarrhea or vomiting, respiratory distress, and increased sweating or irritability.

In addition to proper education, families must receive the appropriate home equipment before hospital discharge. This includes a pulse oximetry device and a digital infant scale to monitor weight. Close follow-up is critical to ensure the infant is doing well and will be healthy enough for the next stage of cardiac repair.

Transition to adult healthcare

Because of advancements in the management of children with congenital heart disease, such as development of the Fontan procedure, more children now live into adolescence and then adulthood. This has gradually given rise to a unique population of adult patients with congenital heart disease. As these children reach adolescence, there is a need to transfer their care from pediatric cardiologists to an adult congenital heart disease team. ¹⁴ This transition is critical to ensure continued care throughout the patient’s lifetime, especially as they begin developing medical problems primarily seen in adulthood. Successful transition is dependent on the pediatric team, the patient’s primary care physician, and the adult congenital heart disease specialist all working closely together to ensure that no information is lost between clinics and that continuity of care is maintained. ¹⁵

Adults with Fontan circulation

The Fontan procedure has been perfected over the years, and the currently estimated 30-year survival rate after completion is approximately 85%. As of 2018, an estimated 40% of patients were surviving to >18 years of age, a number that is likely to continue growing every year. ³ As more patients survive into adulthood, we have begun to better understand the long-term effects of Fontan circulation and its limitations. The long-term impacts of this circulation include chronic heart failure, limited exercise capacity, high-risk pregnancy, increased thrombotic risk, and arrhythmias.

To better understand the effects of Fontan circulation in adulthood, we must first discuss how Fontan circulation changes normal hemodynamics. In a normal heart, the right ventricle (RV) serves to offload the venous system and overcome pulmonary resistance. This helps to keep the RA pressure lower than the left atrial pressure, preserving a pressure gradient that facilitates transfer of blood flow from the venous to arterial circulation. This is further assisted by the RV, which can overcome reasonable pulmonary resistance exerted by the pulmonary vasculature. ³ In Fontan circulation, there is no subpulmonic ventricle; instead, all blood drains passively to the lungs. This results in several long-term issues such as higher systemic venous pressure. Overall vascular resistance and ventricular afterload is increased after the Fontan operation because blood must traverse the systemic arterial system, systemic venous system, Fontan pathway, and pulmonary venous system before returning to the ventricle. ¹⁶ The right systemic ventricle is not designed to pump against these higher systemic pressures, and filling pressures will continue to rise over time. This results in increased pulmonary vascular congestion and systemic venous congestion, which is transmitted to the systemic ventricle as pressure it must pump against, completing a negative feedback loop that continues until the ventricle can no longer function adequately. ³ Some have termed this physiologic negative-feedback loop the “Fontan paradox.”^16,17 In this context, we will now discuss common medical issues that arise in patients with Fontan circulation.

Pregnancy in patients with Fontan circulation

One common question that has arisen because of increased survival after the Fontan procedure is whether pregnancy is safe. Pregnancy is considered moderate- to high-risk in any patient with Fontan circulation who otherwise does not have active medical problems, although pregnancy is not contraindicated. ¹⁸ Because of the limited number of patients of child-bearing age who have this unique physiology, there are few data that accurately reflect the risk of pregnancy complications in patients with Fontan circulation. However, some systematic reviews have been conducted to help clarify expectations. One such study published in 2018 showed that almost 70% of pregnancies resulted in pregnancy loss, most (45%) of which were due to miscarriages. The most common cardiovascular complications were arrhythmia (supraventricular arrythmia) and heart failure. The most common obstetric complications were postpartum hemorrhage and premature birth. No maternal deaths were reported. ¹⁹ Although this study was a meta-analysis, it only included 255 pregnancies in 133 women. Further data are needed to better understand the complications that may arise with pregnancy in a Fontan patient.

Anticoagulation in patients with Fontan circulation

Long term anticoagulation in patients with Fontan circulation has been a topic of debate for many years. Before we discuss anticoagulation strategies, it is important to understand why Fontan patients are at higher risk for thrombosis. This can be easily discussed in the context of Virchow’s triad of thrombosis: coagulopathy, endothelial injury, and disturbed blood flow.

Most Fontan patients have abnormal levels of coagulation proteins, ²⁰ presumably secondary to chronic hepatic congestion and subsequent liver dysfunction. Endothelial dysfunction is also an important contributor to increased thrombosis.^21,22 Studies have also shown increased platelet reactivity in patients with Fontan circulation. ²³ These patients experience chronic hypoxia, have undergone surgical manipulation that often involves artificial intravascular material, and have inherently abnormal blood flow due to the Fontan circulation design. Stasis of blood flow often occurs where the cardiac anatomy has been altered (PA stump), and elevated systemic venous pressure promotes thrombogenesis. All these factors are thought to contribute to an increased risk of thrombosis.

Most thrombotic events in Fontan patients occur within the venous circulation, resulting in caval thrombosis or pulmonary embolus (81%). ²⁴ Antithrombotic prophylaxis is recommended in all Fontan patients because they are at high risk of thromboembolic events. Recent studies have shown that low-dose aspirin, warfarin, and non-vitamin K antagonist oral anticoagulants are all effective for thromboprophylaxis in Fontan patients. ²⁵ On the basis of the UNIVERSE study data, the U.S. Food and Drug Administration approved rivaroxaban for thromboprophylaxis in children aged >2 years with Fontan physiology. ²⁶ Anticoagulation in Fontan patients remains highly controversial, and management is dependent on the individual provider’s practice, the patient’s clinical factors including his or her thromboembolic risk profile, and institutional guidelines.

Arrythmias in patients with Fontan circulation

Arrythmias in Fontan patients are relatively common. A recent retrospective study of 683 patients showed that 15% had an arrhythmic event prior to reaching the age of 16 years and that 20% had an event afterward. ²⁷ These arrhythmias were supraventricular in nature, most commonly supraventricular tachycardia, atrial flutter, and atrial fibrillation in that order. Only 6% of patients required permanent pacemakers; the rest were managed with the conventional approach to their respective arrhythmia. The incidence and types of arrythmia are secondary to the significant atrial manipulation that occurs while creating Fontan circulation. Patients with Fontan circulation and atrial tachycardia are prone to develop an RA thrombus, heart failure, and ventricular dysfunction and to require hospitalization. ^{28 – 32}

Heart failure in patients with Fontan circulation

As discussed above, at completion of the Fontan circulation, the heart enters a state of chronic and progressive heart failure. ^{33 – 36} Cardiac output is determined by systemic vascular resistance as well as PVR. Because both systolic and diastolic dysfunction can occur, therapies are targeted toward treating the respective dysfunction, as in a normal heart. The main difference in management is the targeted approach to treatment of PVR. Even small elevations in PVR can decrease ventricular preload while increasing afterload. Treatment of pulmonary hypertension has been shown to result in some improvement in exercise capacity and heart failure, but there are no conclusive data to prove its benefits in all patients.^37,38

Mechanical circulatory support and cardiac transplantation in patients with Fontan circulation

Heart failure is progressive, and transplantation will eventually be needed. However, a donor is not immediately found for most patients, which brings into question the role of mechanical circulatory support (MCS) for patients with Fontan circulation. Traditional devices used for MCS are designed for hearts with normal anatomy and biventricular circulation. No device that can meet the unique physiologic needs of patients with Fontan circulation has yet been designed. The primary role of MCS in patients with Fontan circulation is prevention of heart failure secondary to systolic dysfunction; however, Fontan patients who are decompensating often have preserved systolic function. Although MCS has been successfully used as a bridge to transplantation, the failure rate is high and outcomes are relatively poor. The role of MCS is currently limited to a bridge to transplantation in patients with end-stage heart failure characterized by systolic heart failure.^3,39

The difficulty with transplantation in Fontan patients is the lack of consensus on the indications and contraindications for transplantation and the optimal timing of transplantation. Currently, patients with Fontan circulation who have no complications have a better prognosis than transplantation can afford. However, such patients do not need transplantation. The most common diagnoses among patients listed for transplantation are protein-losing enteropathy (PLE) and ventricular dysfunction.^40,41 Once the need for transplantation has been established, the next hurdle is procuring a donor heart. Among children, those with congenital heart disease are prioritized for transplantation, and the highest level of priority is given to any patient with congenital heart disease who has dilated cardiomyopathy, MCS, or mechanical ventilation. This prioritization reflects current transplantation practice, as most patients with congenital heart disease receive transplantation as children, with 40% being <1 year of age. ³ Very few transplantations occur in adulthood, and even if patients are listed for transplantation, they have difficulty procuring an organ. One reason is that congenital heart disease does not award any prioritization. Additionally, the usual therapies that prioritize patients, such as MCS and inotropes with pulmonary catheters, are not commonly used for Fontan patients. As a result, it can be difficult for these patients to find a donor organ in a timely manner, and they also have minimal options to bridge them to transplant.

Unfortunately, outcomes also reflect the difficulty in obtaining a transplant. Currently, pediatric patients with Fontan circulation who undergo transplantation have a 1-year survival rate of 89%, which is not significantly different from that of patients who do not have Fontan circulation. Adults with Fontan circulation who undergo the same procedure have a 1-year survival rate of only 65%. ⁴²

Fontan-associated liver disease

Fontan-associated liver disease refers to liver fibrosis and cirrhosis that occurs following establishment of Fontan circulation. The immediate result is centrilobular hepatic congestion due to elevated caval pressures and lymphatic overflow/congestion. ⁴³ Ultimately, this can progress to hepatocellular carcinoma, but whether the risk of developing this is any higher than that in the general population with cirrhosis of other causes remains unclear. Despite the presence of abnormal biological markers, imaging findings, or histopathological changes, the functional reserve of the liver may be quite satisfactory. ⁴⁴ Rarely, patients may progress to decompensated cirrhosis, but no special tools are currently employed for risk stratification of these patients compared with patients who have decompensated cirrhosis of other causes. ^{45 – 47} All patients with Fontan circulation are recommended to undergo regular hepatic screening. Measurement of the biomarker α-fetoprotein is recommended in older patients who are at high risk for hepatocellular carcinoma. Medical therapy is usually targeted at reducing hepatic congestion by reducing pulmonary or systemic vascular resistance; however, no data have yet proven that this is of concrete benefit. ³

Neurodevelopmental outcomes in single-ventricle patients

Studies of the neurodevelopmental outcomes in patients with congenital heart disease have identified a high prevalence of cognitive, neuropsychological, and behavioral deficits in patients with Fontan circulation. ^{48 – 50} Several impairments have been recognized particularly in single-ventricle patients, including the general intelligence quotient (IQ). One-fourth to one-third of patients have moderate to severe impairment (IQ of <85), with one-fifth of them having severe impairment (IQ of <70). Further deficits involve impairments in visual and spatial integration, fine and gross motor skills, language, memory, and executive function. Impulsive behavior and impaired emotional control may also be present. ⁵¹ These data have been obtained from cross-sectional studies; few longitudinal studies have been conducted. As a result, studies in adults are limited. The few studies that have been conducted show that these impairments often persist into adulthood and do not improve over time.

The etiology of these impairments is multifactorial and cumulative, but the most frequently associated risk factor is preoperative ischemic brain injury.^52,53 Such brain injury is present in approximately 45% of all patients who have hypoplastic left heart syndrome, a common indication for the Fontan procedure. ⁵⁴ Much of the remaining etiologies are thought to be due to innate patient factors including sex, birth weight, socioeconomics, and genetics. Complications from correction of congenital heart disease account for <5% of the variance observed in early neurodevelopment. ⁵⁵

Cardiovascular imaging in patients with Fontan circulation

Imaging of the Fontan circulation can be difficult because of the abnormal anatomy and surgical correction. The most frequently used imaging modalities include echocardiography, cardiac computed tomography (CT), and cardiac magnetic resonance imaging (CMR). Echocardiography is commonly performed annually. It allows for inexpensive routine assessment of cardiac function and can show early valve dysfunction. ⁵⁶ However, high imaging quality can be difficult to obtain because of the positioning of the heart or poor acoustic windows. Additionally, echocardiography does not allow visualization of the collateral circulation, which can be critical in a Fontan patient. An alternative to echocardiography is CMR, ⁵⁷ which is an excellent tool for examining the volumetry and functional capacity of a single ventricle. CMR has excellent resolution and allows visualization of collaterals and estimations of shunting. This is considered the gold standard for imaging examination of patients with significantly abnormal anatomy such as Fontan circulation. However, CMR has some limitations; it is expensive and takes a long time to complete, requiring patients to follow specific instructions while multiple images are taken. Additionally, it is only available at academic centers.

An alternative to CMR is cardiac CT.^58,59 Cardiac CT is more widely available, and the examination itself is significantly shorter than CMR. It is also better for assessing stents and the coronary arteries. However, it is not useful for examining tissue, valve function, or overall hemodynamics. Moreover, it requires exposure to radiation. Cardiac CT is primarily used as a substitute for CMR when CMR is unavailable, but it does have some benefits over CMR in the right context.^60,61

Lymphatics in patients with Fontan circulation

Because the Fontan circulation requires elevated systemic venous pressure to drive the pulmonic circulation and thus enhance the RV preload, normal drainage of the lymphatics into the venous system is interrupted. ⁶² The increased pressure gradient causes backup of blood in the capillary network, resulting in accumulation of fluid in the interstitial space. This is further exacerbated by reduced plasma oncotic pressure secondary to protein deficiencies such as hypoalbuminemia. It is important to understand this pathophysiology because it leads to specific pathologies in Fontan patients such as diffuse edema, ascites, pleural effusion, PLE, and plastic bronchitis (PB). ⁶³

Protein-losing enteropathy and plastic bronchitis

PLE occurs in 5% to 15% of patients after Fontan palliation.^64,65 PLE is important to identify because it is associated with high mortality. The proposed pathophysiologic mechanism is that systemic venous congestion results in lymphatic congestion, resulting in spilling of lymph-rich fluid into the lower-pressure intestinal tract. This occurs in the context of abnormal lymphatic vessels throughout the gastrointestinal tract. Loss of protein results in declining serum oncotic pressure, causing systemic edema. Edema of the intestinal wall results in malabsorption and worsening protein loss, creating a negative-feedback cycle. Over time, this results in diffusely worsening edema as well as predisposition to infection with the loss of immunoglobulins and white blood cells. The gold standard diagnostic finding is an elevated α-1 antitrypsin clearance rate in a 24-hour stool collection. ⁶⁶ Alternatively, an elevated α-1 antitrypsin clearance rate in a stool sample within the context of serum hypoalbuminemia and systemic edema can also be diagnostic. No targeted treatment is currently recommended; instead, treatment is limited to supportive care. Occasionally, heart transplantation can be pursued. Although this does seem to improve outcomes, patients with PLE are also often malnourished and deconditioned, making successful heart transplantation difficult. This is reflected in the high mortality rate of patients who undergo transplantation. ⁶⁷

PB occurs in up to 5% of patients with Fontan circulation, and it develops by a mechanism similar to that proposed for PLE.^68,69 In PB, leakage of lymph into the airways results in formation of thick casts, which subsequently cause hypoxemia and airway obstruction. Diagnosis is confirmed by histopathologic examination of an airway cast. Definitive treatment is clearance of the airway by bronchoscopy. Medical therapies such as dietary modifications (low-fat diet) are also pursued to help prevent recurrence. Traditionally, definitive treatment was heart transplantation. With removal of the Fontan circulation, the disease resolves. More recently, catheter-based intervention to eliminate lymphobronchial communications has resulted in disease remission with good outcomes. ⁷⁰ However, this does nothing to correct the underlying pathology, and the disease will eventually recur. ³

Cyanosis in patients with Fontan circulation

Cyanosis is associated with increased late morbidity and mortality rates in patients with Fontan circulation. ⁷¹ Some degree of cyanosis is always expected to be present in patients with Fontan circulation. Although the goal of the operation is to separate the venous and arterial circulation, some mixing still occurs. Most commonly, the systemic arterial oxygen saturation ranges from 90% to 95%. This is predominantly due to three main mechanisms: drainage from the coronary sinus, ventilation–perfusion mismatch in the lungs, and surgically created fenestration.^3,72

The coronary sinus normally drains deoxygenated blood to the RA, from where it is pumped through the RV into the PA. In Fontan circulation, the atria contain oxygenated blood returning from the pulmonary circulation, and this blood is then mixed with deoxygenated blood coming from the coronary sinus. In normal pulmonary perfusion, the RV assists perfusion of all the lung fields. Because Fontan circulation is dependent on passive perfusion of the lungs, gravity plays a larger role, and the bases of the lungs therefore tend to be more perfused than the upper segments. Because aeration favors the upper lobes, this can create ventilation–perfusion mismatch. Finally, some Fontan patients may require the creation of a shunt during palliation to help offload the pulmonary circulation. This is accomplished by fenestration of the RA with the conduit carrying venous blood flow from the IVC to the PA system. This forms a right-to-left shunt from the venous system directly into the RA, allowing mixing of oxygenated and deoxygenated blood. This fenestration exists to prevent volume overload of the pulmonary circulation. ³

Outside of the normally expected mixing of blood in Fontan circulation, abnormal vessels may exist, causing a pathologic decrease in systemic arterial oxygenation. These abnormal vessels include venovenous collaterals, which allow blood to bypass the pulmonary blood flow, ⁷³ as well as pulmonary arteriovenous malformations (PAVMs), which connect the PAs and pulmonary veins. ⁷⁴ Both types of vessels result in right-to-left shunting, which may worsen systemic arterial oxygenation. Venovenous collaterals are thought to arise secondary to overload of the pulmonary circulation and function as pop-off valves to allow decompression of the circulation. The mechanism underlying the creation of PAVMs is not well understood, but these malformations are thought to be secondary to loss of the ability of hepatic factor (created in the liver) to reach the pulmonary vascular bed. Hepatic factor is theorized to prevent formation of PAVMs. Treatment of venovenous collaterals is straightforward, simply involving catheter-based plugging of abnormal vessels. However, this can result in elevated pulmonary pressures and may subsequently diminish cardiac output, and it should not be pursued without careful consideration. PAVMs are not easily treated, and targeted therapy has not been well studied. Heart transplantation can lead to regression of PAVMs.^3,75

Atrioventricular regurgitation in patients with Fontan circulation

Among patients with Fontan circulation, those with atrioventricular regurgitation have higher morbidity, mortality, and Fontan failure than those without regurgitation. Atrioventricular valve regurgitation is present in up to 75% of patients with Fontan circulation. ⁷⁶ Patients who have moderate or severe regurgitation or require referral for an atrioventricular valve operation have twice the risk of Fontan failure (endpoint of death or transplantation) than the base population. ⁷⁷ This risk is correlated with the degree of regurgitation. Poor outcomes are due to elevated central venous pressure and decreased cardiac output, which potentiates other complications of Fontan circulation such as liver disease, renal dysfunction, heart failure, and PLE, all of which have been discussed in greater detail above. ⁷⁸

Exercise in patients with Fontan circulation

Reduced exercise capacity is expected in patients with Fontan circulation given the lack of a subpulmonic ventricle, impaired chronotropic response, and limited pulmonary vascular reserve. These factors significantly reduce the preload reserve available for the RV, resulting in low cardiac output that is not able to keep up with oxygen demand during exercise. This raises the question of whether it is safe for Fontan patients to exercise regularly. Fontan patients were historically recommended to avoid moderate to vigorous physical activity. However, recent data suggest that exercise training is both safe ⁷⁹ and the single most effective noninvasive therapy to improve exercise capacity. ⁸⁰ Exercise training also has the benefit of improving the innate ability of the skeletal muscle to help return blood to the heart, which becomes critical in patients who are otherwise unable to pump blood through the pulmonary vasculature. ^{81 – 83} Data has shown that regular exercise is effective in improving mental health, perceived health, and quality of life in patients with Fontan circulation. ⁸⁰

Innovations and advancements for future Fontan care

Although Fontan circulation was indeed a revolutionary advancement in the management of congenital heart disease, it still has many limitations. The Fontan procedure traditionally revolved around performing an identical procedure for all patients; however, patients may have differing anatomies. Additionally, there will always be an increased risk of thrombosis when any foreign material is in contact with the circulation. Finally, there is the Fontan paradox, the physiologic negative-feedback loop that results in heart failure over time. ¹⁷

Improving the Fontan circulation for future generations currently revolves around addressing these key issues. Advancements in imaging now allow surgeons to model and optimize surgical reconstruction prior to intervention, facilitating individualization of circuits to each patient’s unique anatomy. ⁶⁰ To mitigate the risk of clotting, research is currently underway to develop tissue-engineered components that resemble normal endovascular epithelium. Finally, to address the Fontan paradox, research is being performed to develop a pump that can be placed within the Fontan conduit. This is termed a cavopulmonary assist device in a Fontan-implantable blood pump. This pump would increase the PA pressure and decrease the intracaval venous pressure, replicating the normal function of a subpulmonic ventricle and effectively increasing pulmonary perfusion while offloading the systemic ventricle. These studies are still in their infancy, and much more research is required before implementation of such devices in the real-world setting.^17,84

Noninvasive ventilation in Fontan patients

Inspiration normally increases return of blood to the RA, increasing preload. In Fontan circulation, however, the RA is absent and blood returns to the total cavopulmonary connection (TCPC), which is the point at which the SVC and IVC anastomose with the PAs. The blood flow through the TCPC can be characterized using CMR and echocardiography. This flow is divided into two categories: net forward flow and flow pulsatility within the TCPC. As with normal physiology, inspiration appears to increase venous return to the TCPC. However, because the TCPC functions via passive venous flow, expiration results in decreased venous return. This results in no significant net increase in flow with inspiration as is seen with normal physiology. ⁸⁵ However, a similar phenomenon does not seem to be present for pulsatility. Fontan patients have 70% to 90% higher flow rates during inspiration compared with 20% in healthy controls. This is thought to be secondary to decreased central venous pressure due to the fenestration between the Fontan circulation and the RA.

A thorough understanding of the effects of respiration on Fontan circulation is important to facilitate successful treatment of these patients when they require ventilation. Traditionally, negative-pressure ventilation has been thought to improve pulmonary blood flow by decreasing intrathoracic pressure, resulting in increased venous return to the heart. However, recent research shows that biphasic positive airway pressure ventilation may offer greater benefit and is superior to negative-pressure ventilation. The current theory is that whereas negative-pressure ventilation only alters the inspiratory phase, biphasic positive airway pressure ventilation augments venous return throughout the respiratory cycle. Reduced intrathoracic pressure during inspiration and increased intra-abdominal pressure during exhalation have a greater effect on augmenting blood flow. This results in increased pulmonary blood flow and increased cardiac output. Although further research involving larger patient cohorts is needed, there does appear to be a short-term benefit of using biphasic positive airway pressure ventilation in patients with Fontan circulation. ⁸⁶

Peripheral venous pressure as a surrogate for invasive central venous pressure in Fontan patients

Patients with Fontan circulation often need right heart catheterization to determine their pressure gradients and whether their circulation is problematic. The peripheral venous pressure can be noninvasively assessed in the outpatient setting. Recent research has shown that the peripheral venous pressure is strongly correlated with the central venous pressure and can be calculated using the following equation in adult Fontan patients: central venous pressure = (0.86 × peripheral venous pressure) +1.3. ⁸⁷ A similar correlation has been seen in pediatric Fontan patients.^88,89 Although this number is a good estimate at best, it does allow us to make conclusions about the overall function of the Fontan circulation in an outpatient setting and determine whether further workup is needed.

Conclusions

The Fontan procedure remains a critical component of palliating certain congenital heart diseases, providing patients who previously had only months to years to live with the possibility of decades. However, this unique circulation has specific caveats. As more patients with Fontan circulation reach adulthood, our understanding of their unique physiology and subsequent complications will continue to be better understood, and we can continue to make advancements in their care.