Single Venricle and Considerations

Univentricular heart, also known as a single ventricle, are a group of complex congenital heart defects characterized by the presence of a single functional ventricle. While considered rare, they are relatively frequent in hospital settings specializing in congenital cardiology. The prevalence of these conditions is evolving, with a significant proportion of patients now surviving into adulthood, forming a new population of adult congenital heart disease patients with specific challenges.

Definitions of Univentricular Cardiopathies

The term "univentricular" refers to a functional state where only one ventricle is effectively pumping blood to both the systemic and pulmonary circulations, regardless of the anatomical presence of two ventricular chambers. Univentricular heart conditions can be defined in two ways: anatomically and physiologically. 

1. Anatomical Definition: This definition describes the structural characteristics of the heart. It refers to a heart with only one ventricular cavity into which blood from one or both atria flows. From this single ventricle, there is one or two outflow tracts.

   • Atrioventricular (AV) Valve Configurations:

     • Two AV valves: Both mitral and tricuspid valves are present and open into the single ventricular chamber. In univentricular hearts, the atrioventricular (AV) valve morphology may not conform to the classic definitions of "mitral" or "tricuspid" valves. In such cases, it is more accurate to describe the valves based on their anatomical location and relationships rather than traditional nomenclature. Terms such as left-sided AV valve, right-sided AV valve, anterior or inferior AV valve, or descriptors like mural leaflet (abutting the ventricular free wall) are used to provide a detailed and anatomically appropriate description of valve position and structure. This approach is essential for accurate communication, particularly in complex univentricular or heterotaxy anatomy, where valve morphology and orientation may vary significantly from normal segmental anatomy. It is also important to evaluate the attachments of the AV valve(s), including both the number and location of supporting structures such as papillary muscles or chordal pillars. Configurations may include a parachute valve (with all chordae attaching to a single papillary muscle) or multiple attachments. Special attention should be given to the relationship of these attachments to the underlying ventricular anatomy, particularly in cases where the valve straddles a non-committed ventricular septal defect (VSD) or is malaligned relative to the interventricular septum. These structural relationships have significant implications for ventricular balance, flow distribution, and surgical planning in patients with complex or univentricular physiology. 

       • Straddling refers to an anatomical condition in which the chordal attachments of an AV valve cross the interventricular septum and attach to both ventricles, rather than being confined to the ventricle associated with that valve. Normally, the mitral valve inserts into the left ventricle, and the tricuspid valve into the right ventricle. In straddling, the valve leaflets or chordae tendineae attach to papillary muscles or septal structures in both ventricles, meaning the valve is “shared” or partially committed to the contralateral ventricle. This often occurs in association with a VSD, where the valve bridges or "straddles" the defect. Straddling AV valves are often associated with unbalanced ventricles or single-ventricle physiology. They may complicate surgical repair, especially in biventricular vs. univentricular decision-making. They may be associated with malalignment of the septum, atrioventricular canal defects, or heterotaxy syndromes.

       • Overriding AV Valve: The valve annulus is positioned directly over or across the interventricular septum. This differs from straddling in that it's the valve orifice (not just the chordal attachments) that is committed to both ventricles. Can occur with tricuspid, mitral, or common AV valves. Common in AV canal defects and some double outlet ventricles.

       • Parachute AV Valve: All chordae tendineae attach to a single papillary muscle. Most commonly seen with parachute mitral valve. Often associated with mitral stenosis or part of "Shone’s complex". May lead to obstruction due to limited mobility and narrowed orifice.

       • Cleft AV Valve Leaflet: Often a cleft in the anterior leaflet of the mitral valve or in the left component of a common AV valve. Common in partial AVSDs (in which case we do not call it a "mitral" or a "tricuspid" valve). May lead to significant regurgitation. Must be distinguished from normal commissures.

       • Double-Orifice AV Valve: Two separate orifices within a single AV valve annulus. Can affect either mitral or tricuspid valves. May cause stenosis or regurgitation, depending on orientation and flow dynamics.

       • Absent or Imperforate AV Valve: Rare, but seen in tricuspid atresia or mitral atresia. The valve is either completely absent or replaced by an imperforate membrane. Always associated with univentricular physiology. By definition, a ventricle has an "inlet". Without an inlet, we would often call the residual chamber an "accessory chamber". The hole between the main ventricle and this accessory chamber is often termed "bulbo-ventricular foramen". 

       • Ebsteinoid Malformation: Typically affects the tricuspid valve, with apical displacement of the septal and posterior leaflets. Can be seen in isolation or in heterotaxy. May mimic features of Ebstein anomaly and is associated with atrialization of the RV and tricuspid regurgitation.

       • Malaligned AV Valve: Seen in association with malaligned AV septal structures or ventricular imbalance. Leaflets may insert in abnormal planes, creating functional obstruction or regurgitation.

     • One AV valve: One AV valve is present, with the other being atretic (closed). Examples include mitral atresia (no left ventricle connection) or tricuspid atresia (no right ventricle connection). As such, when one of the AV valves is atretic (closed; or extremely stenosed), there is underdevelopment of the corresponding ventricle. Examples include tricuspid atresia, where only the left ventricle develops, and mitral atresia, where the right ventricle might be the dominant one

     • Common AV valve: A single shared AV valve, often associated with an atrioventricular canal defect.

   • Accessory Ventricle: In cases with only one functional ventricle, an "accessory ventricle" or "rudimentary ventricle" may be present. This is often a small, hypoplastic chamber, sometimes reduced to its apex, primarily functioning as an outflow tract as it lacks an inlet valve. As mentioned, in the absence of an inlet component, the remaining chamber is often referred to as an "accessory chamber" because to be a ventricle, you technically need an "inlet". The communication between the main ventricle and this accessory chamber is commonly called the "bulbo-ventricular foramen", although there is controversy about its nomenclature. To call it a "ventricular septal defect, technically you would need two "ventricles". Other terms sometimes used: Conoventricular foramen, Outflow tract–ventricular connection, Infundibulo-ventricular connection, trabecular gap, etc. In other words, there is a "hole" or a communication between the main ventricle and this accessory chamber, which is often connected to an outflow tract. This accessory ventricle does not receive an AV valve input and primarily forms the outflow tract and its apex may be minimal. If the communication with the main ventricle is large enough that flow was able to enter this chamber during fetal life, there may have been some growth. While it might appear as a separate chamber with a communication to the main ventricle, it is not considered a true functioning ventricle as it lacks a direct AV valve connection

2. Physiological Definition: This definition focuses on the clinical management strategy. It includes malformations where it is not possible to repair the heart as a two-ventricle system, therefore necessitating a univentricular management/palliation pathway (the Fontan pathway).

   • Anatomically Univentricular Hearts: This category includes conditions like tricuspid atresia or single ventricle with double inlet (example: DILV), which by definition have only one functional ventricle.

   • Hearts with Two Ventricles that Cannot Be Repaired Biventricularly: Despite having two anatomically distinct ventricles, biventricular repair is impossible due to severe functional limitations. Examples include:

     • Multiple, very large interventricular communications: The septal defect(s) is too extensive to allow for a partition.

     • Highly asymmetric ventricles: One ventricle is too small (hypoplastic) to adequately perform its function. This includes:

       • Hypoplasia of the left heart (HLHS): Various degrees of underdeveloped left-sided structures, often including mitral atresia (with a communication between the RV and the accessory left-sided chamber), mitral stenosis-aortic atresia, etc.

       • Hypoplasia of the right heart: Various degrees of underdeveloped right-sided structures. Often seen in Pulmonary Atresia Intact Ventricular Septum.

       • Certain double outlet right ventricles: Where the left ventricle is small or the great vessels are misaligned relative to the VSD (ventricular septal defect).

       • Imbalanced atrioventricular septal defects: Where one ventricle is significantly smaller.

       • Straddling atrioventricular valves: One AV valve extends into both ventricles through a VSD, making biventricular repair difficult or requiring sacrifice of a valve.

These various anatomies ultimately fall under a spectrum of anomalies in atrioventricular junction development. The heart's segmentation (atrial looping, ventricular looping) and the positioning of rudimentary ventricles (e.g., in d-loop or l-loop configurations, or with atrioventricular discordance) contribute to the wide range of presentations. Despite the anatomical complexity, the goal for all these conditions is the same: a univentricular surgical repair strategy.

Epidemiology

The epidemiological characteristics of functionally univentricular cardiopathies are distinctive.

• Frequency: They account for 5% to 7% of all congenital cardiopathies. However, there is a lot of factors influencing the occurence of these conditions within a particular context, such as prenatal decisions by the family.

• Associated Anomalies: There is a high frequency of association with chromosomal anomalies and extracardiac malformations. This association can significantly increase the risk of mortality. Heterotaxy syndromes, while not always univentricular, often require a univentricular repair strategy due to high proportions of cases not amenable to biventricular repair.

• Prenatal Diagnosis: The diagnosis is made before birth in over 90% of cases. This is often due to the readily apparent major imbalance of the 4-chamber view during fetal echocardiography.

• Pregnancy Interruption: Due to the severity of these malformations, families may choose to interrupt the pregnancy depending on the gravity and other societal/personal choices. This impacts the number of live births of children with univentricular CHD compared to theoretical numbers.

• Neonatal Presentation: For cases not diagnosed prenatally, the condition is typically identified within the first week of life, and virtually all within the first month. Often diagnosed within the first few days, this is due to cyanosis (obligatory mixing) - especially with universal pulse oxymetry screening. These are therefore considered neonatal presentations. 

• Chromosomal anomalies are found in approximately 15% or more of cases. If parents consent, amniocentesis is performed. Extracardiac malformations (affecting other organs) are present in about one in five cases.

• Mortality: Despite advances in treatment, infant mortality remains high - especially for complex anatomies (could be up to 60% in some cohorts). However, there is an increasing number of survivors with Fontan palliation and long-term transplantation in some settings. A non-negligeable portion of the mortality is attributed to compassionate care decisions by parents who, after declining pregnancy termination, choose not to pursue the challenging surgical palliation pathway.

Echocardiographic and Clinical Findings

The clinical presentation of univentricular CHDs is diverse due to the varied anatomical forms and associated obstacles (pulmonary, subaortic, aortic, coarctation, etc.). However, a common feature is cyanosis, as the blood inevitably mixes due to the single ventricular circuit.

Echocardiography is crucial for diagnosis and characterization:

• Double Inlet Single Ventricle: Two AV valves opening into a single, often dominant, ventricular cavity, sometimes with a rudimentary septum or pillars. Usually of left-sided conformation (DILV), it can rarely be a DIRV (although this is extremely rare as the RV forms usually later in the embryological development).

• Single Atrioventricular Valve: A single AV valve feeding the dominant ventricle.

• Mitral Atresia/Hypoplastic Left Heart Syndrome (HLHS): A closed mitral valve, a hypoplastic or absent left "ventricle" (chamber), often with an underdeveloped aorta. The right ventricle becomes the systemic pumping chamber. The hypoplastic ventricle may show increased echogenicity of the endocardium (endocardial fibroelastosis, outlining that the walls of this chamber have fibrosed/scar and are likely with significantly reduced contractile capacity).

• Tricuspid Atresia/Hypoplastic Right Heart: A closed tricuspid valve/inlet, with a hypoplastic right ventricle. The left ventricle becomes the systemic pumping chamber. The size of the rudimentary right accessory chamber depends on the blood flow through the communication and pulmonary outflow obstruction. Tricuspid atresia may have normally-related great vessels or d-transposition of vessels (may present as well with systemic outflow tract obstruction and unobstructed pulmonary outflow tract). See Tricuspid Atresia section.

• Straddling Valves: An AV valve (e.g., mitral valve) can insert partially into a hypoplastic ventricle and partially into the dominant ventricle, making biventricular repair unfeasible.

• Criss-Cross Heart: A complex anomaly where the ventricular chambers are crossed relative to each other, leading to unusual alignment of AV valves and great vessels, often making biventricular repair impossible despite the presence of two ventricles and two AV valves. There is an abnormal spatial rotation of the ventricular mass, such that the inflow axes of the right and left ventricles cross each other. This results in the AV valves being oriented in an unusual oblique fashion, often with one valve positioned superiorly and the other inferiorly. Despite the unusual alignment, each atrium typically connects to its corresponding ventricle, but the crossed inflow streams create a twisting appearance of the ventricular chambers. Criss-cross heart is frequently associated with other congenital defects such as transposition of the great arteries, ventricular septal defects, or univentricular physiology, and echocardiographic imaging in multiple planes is essential for accurate diagnosis and surgical planning.

• Outflow Tracts: The great vessels (aorta and pulmonary artery) can arise differently from the main and accessory ventricular cavities, with varying degrees of subvalvular or valvular obstruction.

Double Inlet Left Ventricle (DILV) with two atrioventricular (AV) valves draining into a morphologic single left ventricle (LV). An accessory rudimentary chamber is located on the right side of the main ventricular cavity and communicates with it via a defect. There is ventriculo-arterial (VA) discordance: the pulmonary artery (PA) arises from the dominant morphologic LV, while the aorta originates anteriorly and to the right from the accessory chamber and receives flow through the defect. As such, there is transposition of great arteries with the aortic orifice anterior right with respect to pulmonary orifice. Hypoplastic right ventricle supporting the aorta. Large confluent ventricular septal defect (VSD). Large unrestrictive interatrial communication (ASD). 

Hypoplastic left Heart Syndrome with Mitral Atresia. There is some insufficiency of the right-sided atrio-ventricular valve (systemic AV valve). 

Criss-Cross Heart

Other nomenclature: Twisted atrioventricular connection, superior-inferior ventricles, and upstairs-downstairs ventricles. In this condition, the ventricles are positioned in a superior-inferior or upstairs-downstairs relationship, with the ventricular septum lying in a horizontal plane. Although most hearts categorized with "functionally one ventricle" have two ventricular chambers, one large and dominant and the other smaller and rudimentary, criss-cross hearts often fall into this functional classification. The distinctive anatomical features of a criss-cross heart include: 

• Atrioventricular (AV) Junction and Valve Orientation: The AV junction can be twisted in either a clockwise or counter-clockwise direction. A defining characteristic is that the axes of the atrioventricular (AV) valves cross each other, rather than being approximately parallel as in a normal heart. This crossing angle can be significantly large, reaching up to 150 degrees, contrasting sharply with the normal angle of less than 10 degrees.

• Ventricular Position: In most cases, the right ventricle (RV) is located superior ("upstairs") to the left ventricle (LV), which is inferior ("downstairs"). This spatial arrangement results in the ventricular septum typically lying in a horizontal plane. 

• Ventricular Septum: A large ventricular septal defect (VSD), commonly a perimembranous VSD with inlet extension, is frequently observed. Echocardiographic imaging can demonstrate the atrial septum in a perpendicular plane relative to the horizontally oriented ventricular septum, illustrating the criss-cross alignment.

The Fontan Pathway: Surgical Treatment Strategy

The ultimate goal for patients with univentricular CHDs is the Total Cavopulmonary Derivation (TCPC), also known as the Fontan circulation. This surgical strategy aims to connect the systemic venous return directly to the pulmonary arteries, completely bypassing the right side of the heart. The single systemic ventricle (or the functionally dominant ventricle) then solely pumps blood to the systemic circulation. This makes the pulmonary circulation motorless, relying on systemic venous pressure to push blood through the lungs. In a Fontan, the single ventricle drives the systemic circulation, and the venous return (deoxygenated blood) must traverse both systemic and pulmonary capillary beds using the energy primarily generated by this single ventricle.

Historical Context

The Fontan procedure was pioneered by Dr. Francis Fontan in Bordeaux in the 1970s. Early techniques, such as the atrio-pulmonary anastomosis (connecting the right atrium to the pulmonary artery), were abandoned due to complications like atrial dilation, thrombosis, and arrhythmias. Modern techniques usually involve extracardiac conduits (made of gore-tex).

Physiology of Fontan Circulation

In a Fontan circulation, the systemic ventricle must not only ensure adequate systemic arterial pressure and cardiac output but also drive blood through the entire pulmonary vascular bed without the assistance of a dedicated pumping chamber. The patient relies on passive flow through the lungs, driven by the pressure gradient between the systemic venous system and the left atrium. The single ventricle must also manage its own filling pressures.

Key Requirements for a Successful Fontan

The success and longevity of a Fontan circulation depend on specific anatomical and physiological conditions. Ideal Conditions for Fontan: Include perfect pulmonary arteries (no stenosis, hypoplasia, low resistance, low transpulmonary gradient), a strong single ventricle with competent valves, sinusal cardiac rhythm, and consistently low or normal systemic atrial pressures.

1. Good Quality Pulmonary Vascular Bed:

   • No evidence of diffuse hypoplasia

   • Absence of localized stenosis (whether native or iatrogenic)

   • Low pulmonary vascular resistance: Crucially, pulmonary vascular resistance must be low to allow passive blood flow. This requires healthy pulmonary arterioles and no significant native or iatrogenic stenoses or asymmetries in the pulmonary artery branches. Protection from high pressure and hyper-perfusion is essential.

   • Low transpulmonary gradient. Pulmonary blood flow must be precisely calibrated in infancy to ensure proper oxygenation and growth of the pulmonary arteries without causing hypertension.

   • No Obstruction to Pulmonary Venous Return: Any obstruction (e.g., restrictive interatrial communication, anomalous pulmonary venous return) must be corrected to prevent post-capillary pulmonary hypertension.

2. Preserved Ventricular Function: The single ventricle must have good systolic and diastolic function.

   • Normal systolic and diastolic function 

   • Functional Atrioventricular Valve(s): At least one AV valve must be free from significant stenosis or regurgitation.

   • No Obstruction to Systemic Ejection: Conditions like coarctation or subaortic stenosis must be corrected to ensure normal afterload on the systemic ventricle.

   • Maintain integrity of systemic venous return (avoid cathethers in the SVC). Minimize atrial and ventricular scarring .

   • Stable Sinus Rhythm: Any arrhythmia can significantly compromise Fontan circulation.

   • Low left atrial pressure

   • Low Systemic Atrial Pressure: Low filling pressures of the single ventricle are desirable.

   • The ventricle's afterload must remain normal, meaning no aortic or subaortic obstructions. Diastolic overload must be minimized by carefully calibrating pulmonary flow to avoid excessive venous return. Atrioventricular valve regurgitation must be prevented or addressed, as it significantly compromises long-term Fontan success. Surgical procedures should aim to minimize cardiac arrest time and intracardiac manipulations to prevent myocardial damage and scarring.

Certain anatomical features are associated with a better prognosis (presumed but evidence still in evolution) : a single left ventricle (as in tricuspid atresia) often has a better outcome than a single right ventricle (as in HLHS). The absence of aortic obstruction, and the presence of native pulmonary stenosis or atresia (avoiding the need for surgical banding), are also favourable. Normal, native pulmonary branches of good calibres and the absence of pulmonary venous obstruction or restrictive foramen ovale at birth are also beneficial.

Stages of Fontan Pathway

The Fontan pathway is typically a multi-stage surgical process:

Neonatal Management (First Stage): 

This initial stage stabilizes the infant and prepares the heart for future surgeries, depending on the specific physiology. Addresses immediate ductus-dependent circulation needs

1. • Ductus-Dependent Pulmonary Circulation (e.g., Pulmonary Atresia): Prostaglandin is administered to keep the ductus arteriosus open. This is followed by either a Blalock-Taussig-Thomas (BTT) shunt (a surgical connection between a systemic artery and a pulmonary artery to provide blood flow to the lungs) or ductal stenting (hybrid).

   • Ductus-Dependent Systemic Circulation (e.g., Aortic Atresia, severe Aortic Stenosis): This requires a variant of the Norwood procedure. 

     1. Damus–Kaye–Stansel procedure — a surgical technique used primarily in single ventricle physiology or complex congenital heart defects involving systemic outflow tract obstruction. It connects the main pulmonary artery (MPA) to the ascending aorta to bypass or relieve obstruction in the left ventricular outflow tract (LVOT). The pulmonary artery is used to create a new, larger aorta

     2. Source of systemic blood flow:

        1. Modified BTT shunt: A gore-tex tube from the subclavian artery to the pulmonary artery. (The class BTT shunt was connecting the subclavian artery to the native PA).

           1. Theoretical advantages of the Modified BTT Shunt: 

              1. No ventriculotomy required – Unlike the Sano shunt, it avoids incision into the right ventricle, preserving myocardial integrity and reducing risk of ventricular dysfunction or arrhythmia (systemic ventricle). 

              2. Simpler to revise – Easier to access and revise if stenosis or thrombosis occurs. 

              3. Avoids distortion of pulmonary arteries – Especially when the shunt is well-positioned, it minimizes asymmetric pulmonary artery growth. 

              4. Widely used and well understood – Long history of clinical use with extensive institutional experience. 

              5. Potentially less risk of shunt obstruction from dynamic compression – No conduit crossing the sternum or surrounded by contracting myocardium.

           2. Disadvantages of the Modified BTT Shunt: 

              1. Diastolic runoff → systemic coronary steal – Pulmonary blood flow continues during diastole, lowering aortic diastolic pressure and potentially impairing coronary perfusion, especially critical in HLHS where the coronary arteries are perfused retrograde from the neoaorta. 

              2. Less pulsatile pulmonary flow – Compared to the Sano shunt, which is directly connected to the RV, resulting in more physiologic flow patterns. 

              3. Potential for excessive pulmonary blood flow (Qp) – Can lead to volume overload, ventricular dilation, and diastolic dysfunction, particularly if pulmonary vascular resistance (PVR) drops rapidly. 

              4. Risk of subclavian artery "steal" – Can affect perfusion of the ipsilateral arm or brain, especially in small neonates. 

              5. May contribute to uneven pulmonary artery growth – Especially if anastomosed to one pulmonary artery without adequate flow redistribution.

        2. RV-PA conduit (Sano procedure). The Sano shunt is a right ventricle-to-pulmonary artery (RV-PA) conduit, typically made of Gore-Tex (PTFE), that provides pulmonary blood flow after the Norwood operation.

           1. Theoretical advantages: More stable diastolic blood pressure (less diastolic runoff into pulmonary circulation), Improved coronary perfusion, More pulsatile pulmonary flow, Potentially better early postoperative hemodynamics.

           2. Theoretical disadvantages: Risk of right ventricular injury (from ventriculotomy), Stenosis or narrowing of the conduit over time, Higher risk of arrhythmias or conduit thrombosis.

        3. Hybrid: A non-bypass Stage I palliation that includes: 

           1. Bilateral pulmonary artery banding (PAB) – Surgically placed to restrict pulmonary blood flow and prevent volume overload to the lungs. Banding the pulmonary arteries avoids too much pressure and flow transmission.

           2. Ductal stenting – A stent is placed in the ductus arteriosus to maintain systemic perfusion (replacing the Norwood neoaorta construction). The Aorta, cerebral circulation and coronary arteries are perfused retrograde via the stented ductus. 

           3. Atrial septostomy (if needed) – Balloon or blade septostomy to ensure unrestricted atrial mixing.

           4. Theoretical Advantages of the Hybrid Procedure 

              1. Avoids cardiopulmonary bypass in the neonatal period – Particularly valuable in high-risk infants (e.g., low birth weight, prematurity, comorbidities, sepsis, severe ventricular dysfunction). 

              2. Shorter initial recovery – Less postoperative inflammation and shorter ventilation duration in some cases. 

              3. Staged flexibility – Allows time for somatic growth before committing to complex surgery. 

              4. Reduced ischemic time – No ischemic arrest or prolonged hypothermic bypass in the neonatal period. 

              5. Possible bridge to transplantation or Norwood – Provides stabilization and buys time for decision-making.

           5. Theoretical Disadvantages of the Hybrid Procedure 

              1. Technically complex and requires hybrid team coordination – Needs a center with close collaboration between interventional cardiologists and surgeons. 

              2. More intensive imaging and follow-up – Ductal stent may require re-intervention due to restenosis or migration; close surveillance needed. 

              3. Potential for uneven pulmonary artery growth – Due to banding, may result in distortion or hypoplasia of pulmonary arteries, complicating later Fontan staging, which is dependent on pristine pulmonary vasculature. 

              4. Increased need for catheter-based re-intervention – E.g., re-dilation or restenting of ductus, arch re-coarctation, or PA branch stenosis. 

              5. Delayed Norwood-type reconstruction or comprehensive Stage II – Second-stage surgery (often called comprehensive Stage II) is more complex and combines arch reconstruction, Partial Cavopulmonary Anastomosis ("Glenn"), and stent removal.

   • High Pulmonary Blood Flow/pressure transmission: A pulmonary artery band is placed to restrict blood flow to the lungs and protect the pulmonary vasculature from damage due to excessive flow and pressure. However, pulmonary vasculature does require enough flow to grow appropriately and harmonously. As such, expertise is needed to gage the "amount" of banding. 

   • Pulmonary Venous Obstruction: An atrial septostomy or enlargement of the interatrial communication may be performed to decompress the left atrium and pulmonary veins.

Partial/Bidirectional Cavopulmonary Derivation ("Glenn Shunt" - Second Stage of single ventricular palliation): 

This procedure, also known as the "Bidirectional Glenn" typically performed around 3 to 6 months of age, connects the superior vena cava (SVC) directly to the pulmonary artery. This delivers deoxygenated blood from the upper body directly to the lungs, reducing the volume load on the single ventricle.

1. • The original Glenn shunt (1958) was a unidirectional connection between the superior vena cava (SVC) and the right pulmonary artery (RPA). The RPA was disconnected from the LPA, which remained connected to the neo-aorta via the BTT shunt. The original Glenn operation involved sectioning the right pulmonary artery. It then performed a terminal-to-terminal anastomosis between the superior vena cava and the right pulmonary artery. This technique has fallen into disuse since it led to significant complications such as atrial dilations, risks of thrombosis, and arrhythmias, and were hydrodynamically less efficient.

   • The modern Partial Cavopulmonary Anastomosis (Bidirectional "Glenn") connects the SVC to the right and left pulmonary arteries, allowing blood from the upper body to flow passively to both lungs, bypassing the heart. The RPA is still connected to the left pulmonary artery. It is a termino-lateral connection. The superior vena cava is separated from its original connection to the right atrium, and that opening in the right atrium is then sutured. A critical step is the sectioning of the azygos vein to ensure that blood arriving in the superior vena cava is directed effectively into the pulmonary artery, preventing it from taking an easier, less effective path by descending into the inferior vena cava. During the procedure, if a BTT shunt was previously placed, it is typically cut (sometimes, a mixed source of blood flow is kept where a BTT shunt may be maintained to a part of the pulmonary arteries to favour its growth, and the origin of the RPA is banded to allow only the flow from the partial cavopulmonary anastomosis to feed it). 

   • In the modern Glenn procedure (also called bidirectional cavopulmonary anastomosis), the distal end of the SVC is surgically connected to the RPA, usually near its confluence with the left pulmonary artery (LPA). This allows deoxygenated blood from the upper body (draining through the SVC) to: Flow passively into the right pulmonary artery, and also cross into the left pulmonary artery, thanks to the continuity between the two branches. Thus, blood flows in both directions — right and left — into the lungs. This contrasts with the original (unidirectional) Glenn described in 1958, which connected the SVC only to the right pulmonary artery, supplying only one lung.

   • It is essential to thoroughly assess the anatomy of the systemic venous return. In the presence of a persistent left-sided superior vena cava, the left SVC is typically incorporated into the cavopulmonary circulation at the time of the second-stage procedure, alongside the right SVC.

   • This step allows the upper body flow to come back passively to the pulmonary vasculature, while having the lower body blood flow coming back to the atrium and single ventricle. As such, the systemic ventricle receives the pulmonary venous return, as well as the systemic venous return from the lower body. 

   • In cases where there is interruption of the inferior vena cava (IVC) with azygos continuation, the surgical planning for the bidirectional cavopulmonary anastomosis (Glenn procedure) becomes more complex. In this anatomical variant, the inferior vena cava (IVC), which normally carries deoxygenated blood from the lower body to the right atrium, is interrupted. Instead, the systemic venous return from the lower body drains via an enlarged azygos or hemiazygos vein, which then empties into the superior vena cava (SVC). This anomaly is particularly important to identify pre-operatively because it can complicate cardiac catheterization and venous cannulation during surgery. It is often associated with polysplenia syndrome (left atrial isomerism).

     1. This anatomical variant results in systemic venous return from both the upper and lower body draining through the azygos vein into the superior vena cava (SVC). Consequently, performing a Glenn in early infancy would redirect approximately 75–80% of the total systemic venous return to the pulmonary circulation, creating a substantial volume load on the lungs. 

     2. Kawashima procedure: A bidirectional cavopulmonary anastomosis (Glenn) is performed as usual. The SVC is connected to the pulmonary arteries, bypassing the heart. Because the azygos system carries IVC flow into the SVC, this connection now diverts nearly all systemic venous return (except hepatic venous blood) directly to the lungs. This effectively functions like a Fontan circulation, but without including the hepatic veins. Since hepatic venous blood still flows into the heart, pulmonary arteriovenous malformations (PAVMs) may develop over time. This happens because the pulmonary endothelium is thought to require “hepatic factors” to suppress abnormal vessel growth. Completion Fontan A later procedure connects the hepatic veins (via a conduit or tunnel) to the pulmonary circulation, completing the total cavopulmon

   • Pre-Glenn Evaluation: Before this stage, the pulmonary arterial bed and ventricular function are thoroughly assessed (via echocardiography, MRI, or cardiac catheterization) to ensure favourable hemodynamic and anatomical conditions. Any pulmonary artery stenoses may be addressed at this time.

Long-Term Complications of Fontan Circulation (Failing Fontan)

Despite initial success, the Fontan circulation is inherently non-pulsatile and places chronic demands on the single ventricle and systemic venous system, leading to potential complications over time. This progressive deterioration is often referred to as "Failing Fontan".

The pathophysiology of a Failing Fontan involves a vicious cycle:

• Initially, the univentricular heart is volume-overloaded from both systemic and pulmonary circulation, leading to ventricular dilation and hypertrophy.

• After Fontan completion, the sudden reduction in preload can lead to systemic vasoconstriction. While this vasoconstriction maintains systemic pressure, it increases the afterload on the systemic ventricle.

• Elevated filling pressures of the single ventricle can impede passive flow through the pulmonary vascular bed, further reducing cardiac output. Indeed, poor diastolic function elevates filling pressures in the systemic atrium, which in turn raises pulmonary pressures, further reducing the passive flow through the lungs and ultimately decreasing cardiac output.

• The combination of reduced preload and increased afterload leads to ventricular remodeling, impairing both systolic and, critically, diastolic function.

• This creates a cycle where decreased cardiac output leads to further reductions in preload, perpetuating a decline in ventricular function.

Common and significant long-term complications include:

1. Heart Failure: This can be due to:

   • Systolic or diastolic dysfunction of the single ventricle.

   • Increased pulmonary vascular resistance (PVR) or atrial draining pressure (if adverse systemic ventricular compliance or atrio-ventricular valve insufficiency), which impedes passive flow and increases Fontan pressures.

   • Chronic thromboembolic disease, where recurrent small emboli to the lungs further reduce the pulmonary vascular bed, increasing PVR.

   • Arrhythmias (atrial and/or ventricular)

2. Thromboembolic Complications: There is a high risk of thrombosis within the Fontan circuit, primarily due to venous stasis in the non-pulsatile flow.

   • Risk Factors: Atrial arrhythmias, absence of anticoagulation, elevated right atrial/Fontan pressures, and a history of previous thrombus are significant risk factors.

   • Consequences: Thrombi can lead to paradoxical emboli (if a fenestration is present or if there is a clot that forms in the atrium or systemic ventricle due to hypokinesia or arrythmias) causing ischemic events in systemic territories (e.g., stroke). They can also obstruct the pulmonary vasculature, increasing PVR.

   • Prevention: Studies are ongoing to evaluat the best strategy to prevent thrombo-embolic events, such as the use of anticoagulation or anti-platelet aggregation. Most centers will expose their patients with Fontan palliation to one of these strategies. 

3. Fontan-Associated Liver Disease (FALD) - Hepatic Complications: The elevated systemic venous pressure in the Fontan circulation leads to chronic passive congestion of the liver. This can result in:

   • Nodular remodeling of the liver and potentially portal hypertension.

   • Regenerative nodules, arterialized nodules, fibrosis, and ultimately cirrhosis.

   • Varices (e.g., esophageal, gastric) due to portal hypertension. Development of arterialized liver nodules and esophageal varices, similar to cirrhosis. 

   • Increased risk of hepatocellular carcinoma in adulthood.

   • These patients require long-term surveillance for liver disease.

4. Lymphatic Complications (Cardiology-Lymphology): The chronically elevated central venous pressure directly translates to increased lymphatic pressure (arterial duct draining into the passive venous circulation which may be under higher pressure than usual), leading to lymphatic system abnormalities and  to lymph leakage. This is an emerging field with new diagnostic and therapeutic approaches, such as the use of lymphangiograms.

   • Extravasation of lymph can result in effusions under the skin or in serous cavities.

   • Lymphatic Dilatation: Widespread dilatation of lymphatic vessels (seen on lymphatic MRI). Lymphangiectasias. 

   • Chylous Effusions: Accumulation of lymphatic fluid in body cavities (pleural effusions, ascites).

   • Protein-Losing Enteropathy (PLE): Lymphatic fluid leaks into the gastrointestinal tract, causing loss of lymphocytes (lymphopenia) and proteins (hypoalbuminemia, hypogammaglobulinemia). This makes these patients immunosuppressed or prone to infections. It also leads to to edema, undernutrition, dehydration (which may impact preload) and hypoalbuminemia (which worsens tissue edema). Patients experience chronic diarrhea and edema.

   • Plastic Bronchitis: Lymph leaks into the airways, coagulates, and forms casts that obstruct bronchi, leading to acute respiratory distress and atelectasis. Indeed, lymph leaks into the bronchial tree, forming casts that can obstruct airways and cause severe respiratory distress.

   • Management: Interventional lymphangiography techniques, such as stenting of the thoracic duct (if stenotic) or lymphatic embolization of leaking lymphatic vessels (using glue) in the abdomen or chest, can reduce lymphatic leakage. While these offer significant symptomatic relief, they are often transient as the underlying high venous pressure persists. Severe, irreducible PLE may necessitate transplantation, though reversibility post-transplant is not guaranteed.

5. Collateral Vessel Development:

   • Systemic-to-Pulmonary Collaterals: Arterial collaterals can form from systemic arteries (e.g., internal mammary artery) to supply the lungs, often due to non-pulsatile or insufficient flow. These are typically closed before the Fontan procedure. 

   • Systemic Venous Collaterals: If venous pressures rise (e.g., due to poor flow in the Glenn), collateral veins can develop, shunting deoxygenated blood back to the systemic circulation (e.g., persistent left superior vena cava re-opening), leading to increased cyanosis. These are often closed. They signify that there is possibly increased venous pressure in the circuit, which is not an ideal sign for the 3rd-stage.

   • Pulmonary Arteriovenous Fistulas (PAVFs): These are abnormal connections between pulmonary arteries and veins within the lung, causing deoxygenated blood to bypass the capillaries. There can be 100s to 1000s of them, making it near impossible to close them, but some of the major ones could be considered for embolization. They result in cyanosis and are generally irreversible. The cyanosis is because there is right to left shunting within the lungs. 

6. Other Complications:

   • Sudden death: A risk, particularly in adults, requiring careful rhythm management.

   • Terminal ventricular arrhythmias that may require a defibrilator. 

   • Renal complications: Rare before adulthood.

Management of Failing Fontan

Managing a failing Fontan involves a multi-faceted approach. Indeed, the main mechanisms of disease, which can be targeted, include: 

1. Vasoconstriction: A compensatory mechanism to maintain blood pressure.

2. Increased Afterload: This vasoconstriction increases the resistance the ventricle must pump against. 

3. Ventricular Remodelling: The ventricle adapts to these altered conditions, leading to changes in its structure and function, particularly affecting its diastolic (filling) and systolic (pumping) capabilities.

4. Increased Filling Pressures: Altered diastolic function can lead to elevated pressures within the systemic atrium and subsequently in the pulmonary circulation. This is especially true if there is atrio-ventricular valve(s) insufficiency. 

5. Increased Pulmonary Resistance: Difficulties in blood flowing through the pulmonary vascular bed further reduce the preload to the unique ventricle, leading to a decrease in cardiac output.

Management

• Initial steps involve assessing the quality and patency of the surgical montage to rule out any mechanical obstructions (e.g., stenoses, emboli in pulmonary arteries). Indeed, the initial step in managing Fontan failure is to investigate the integrity of the Fontan circuit itself. This involves checking for: 

  • Obstacles: Such as blockages or narrowings in the pulmonary arteries or the Fontan conduit.

  • Pulmonary Emboli: These can obstruct blood flow through the lungs, contributing to increased pulmonary resistance and worsening Fontan physiology. These can be very difficult to diagnose and may require: CT, MRI, Lung/Perfusion scans and sometimes catheterization.

  • Collateral Circulation: The development of collateral vessels or re-permeabilization of a left superior vena cava can increase cyanosis by shunting deoxygenated blood directly back into the systemic circulation, bypassing the lungs.

• Medical Management for Cardiac Insufficienc/Pharmacological Treatment:

  • Traditional heart failure medications like ACE inhibitors/ARBs (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers) have shown negative results in clinical trials for Fontan patients and are generally not recommended preventatively when there is no systolic dysfunction. While potentially useful in the immediate post-operative period to counteract vasoconstriction (which is usually a temporary phenomenon) caused by ventricular de-loading, their long-term benefit is limited as afterload tends to normalize relatively quickly.

  • Diuretics must be used cautiously, as reducing preload can worsen the "vicious cycle" of Fontan failure, ase these patients can be very sensitive to preload. Used only if the patient has fluid overload (e.g., ascites or oedema).

  • Beta-blockers may be considered to prolong diastole and improve ventricular filling. They may have some inherent negative inotropy effects, making them tricky in Fontant patients with a fragile systemic ventricle. They may be used to prolong diastole and improve ventricular filling, but there is limited high-quality evidence from controlled trials demonstrating their efficacy.

• Improving Pulmonary Blood Flow and Ventricular Filling

  • Physical Activity: Regular physical activity and training are strongly encouraged and are fundamental. This helps preserve pulmonary vascular resistance and improve ventricular preload, offering more benefit than many medications. Regular physical activity, at least one hour daily, is considered the most effective intervention for improving functional capacity by enhancing pulmonary vascular resistance.

  • Pulmonary vasodilators (used for pulmonary arterial hypertension) may be beneficial in situations of elevated PVR in Fontan patients to promote the passive forward flow into the pulmonary arteries and diminish the central venous pressure and stasis. As such, if exercise alone is insufficient, pulmonary vasodilators (similar to those used for pulmonary hypertension) may be prescribed, though compelling evidence of their long-term efficacy in this population is scarce.

  • Lusitropic Medications: To address difficulties in ventricular filling due to impaired compliance of the unique ventricle, lusitropes may be considered. Guanylate cyclase stimulators, such as riociguat—used in pulmonary hypertension—and vericiguat—used in chronic heart failure—may occasionally be considered in this patient population, but that is lacking on their effects in this population. There is lack of data for these agents in the single ventricular population.

    1. These agents stimulate soluble guanylate cyclase (sGC), an enzyme in the nitric oxide (NO) signaling pathway. sGC activation increases the production of cyclic guanosine monophosphate (cGMP), theoretically leading to: vasodilation, reduced vascular resistance, anti-fibrotic and anti-remodeling effects, improved myocardial and endothelial function. Contraindications include: pregnancy (teratogenic), concurrent use with PDE-5 inhibitors (e.g., sildenafil) due to risk of hypotension.

• Anticoagulation/antiplatelet management: As discussed, this is essential to prevent thrombotic complications. Hematology/Thrombosis should be involved in managing these patients in a single ventricular program. They must be at least on one of the agents for anti-aggregation of platelets (aspirin) or anti-coagulation (Non–Vitamin K Oral Anticoagulants (Rivaroxaban) or Warfarin).  These three treatments have shown equivalent efficacy in preventing thrombosis, and patients should always receive one of these treatments. 

• Cardiac Arrhythmias: Can be life-threatening and contribute to ventricular dysfunction. Management may involve antiarrhythmic medications, defibrillator implantation, or pacemaker placement.

• Interventional Lymphangiography: For lymphatic complications, targeted lymphatic interventions are an emerging and beneficial treatment.

• Organ Surveillance: Continuous monitoring for liver (and less commonly, renal) complications is necessary due to the chronic venous congestion.

• Transplantation: When medical and interventional strategies fail to manage the failing Fontan circulation, cardiac transplantation (or heart-lung transplantation, especially if there are significant pulmonary issues) remains the ultimate treatment option. This is particularly true for patients with intractable exudative enteropathy. Access to transplantation can be challenging. While transplantation offers hope for reversal of complications like exudative enteropathy, success is not always guaranteed.

Prognosis and Pregnancy

Patients with Fontan circulation require lifelong, comprehensive follow-up due to the progressive nature of complications. While medical and interventional advances have improved outcomes, it is currently difficult to imagine that patients with a Fontan circulation will achieve a normal life expectancy, as complications are considered almost inevitable. At the MUHC, we have a team of congenital cardiologists with Maternal Fetal Medicine, Obstetrical Medicine, and Neonatology that would follow these patients very closely during their pregnancy. Fetal Cardiology would also evaluate these patients to evaluate the fetus as there is a higher rate of CHD in these pregnancies as well. 

Pregnancy in women with Fontan circulation is not an absolute contraindication, but it carries significant risks for both the mother and the fetus. These risks are primarily related to the unique hemodynamics of the Fontan circulation, specifically the high venous pressure and the limited ability of the single ventricle to adapt to the increased cardiac output demands of pregnancy, especially in the third trimester.

• Fetal Risks: High incidence of prematurity, intrauterine growth restriction, and fetal death.

• Maternal Risks: Increased maternal morbidity and mortality are concerns. Pregnancy in Fontan patients requires strict, multidisciplinary management and careful case-by-case assessment. Anticoagulation (often with heparin during pregnancy) and careful planning of delivery timing and location are crucial. This contrasts with conditions like Eisenmenger syndrome, where pregnancy is formally contraindicated due to prohibitively high maternal mortality.

Reference:

• DU CPC Université de Paris Damien Bonnet Cardiopathies Univentriculaires - M3C Carpedem - Dr Damien Bonnet

• DU CPC 2022 23 Université de Paris Cardiopathies univentriculaires Damien Bonnet

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Selected Review Articles In Open Source