Morphological Approach

Important definitions

• Levocardia: the heart is located in the left hemithorax, with the apex pointing to the left. 

• Levoposition: the heart is located in the left hemithorax due to displacement by an external (extrinsic) structure.

• Dextrocardia: the heart is located in the right hemithorax, with the apex pointing to the right. 

• Dextroposition: the heart is located in the right hemithorax due to displacement by an external (extrinsic) structure.

• Mesocardia: the heart is located centrally in the thorax, with the apex pointing downward. 

• Mesoposition: the heart is centrally located due to displacement by an external (extrinsic) structure. 

• Left aortic arch: the aortic arch is located above the left main bronchus. 

• Right aortic arch: the aortic arch is located above the right main bronchus.

Normal Heart Anatomy

Right Atrium:

The right atrium receives the inferior and superior vena cavae, which are aligned with each other. Key anatomical features include:

• The right atrial appendage, which is of right morphology, has a wide implantation base, and a triangular shape.

• The characteristic anatomical feature of the right-morphology atrium is the pectinate muscles, which extend to the interatrial septum on the posterior wall.

• The interatrial septum has three components:

  • The fossa ovalis: A depression often covered by the septum primum.

  • The septum secundum: A muscular fold above the fossa ovalis, separating it from the superior vena cava. This is the third part of the septum to form embryologically, despite its name.

  • The vestibular septum: The lower part of the interatrial septum.

• The coronary sinus orifice, bordered by the Thebesian valve, also known as the valve of the coronary sinus, is also located here. The coronary sinus itself travels behind the left atrium.

• The Eustachian valve represents the vestigial remnant of the valve of the inferior vena cava.

Conduction Pathways and Nodes:

• The electrical impulse originates from the sinoatrial node, located at the base of the superior vena cava, within the crista terminalis.

• Conduction pathways then lead to the atrioventricular (AV) node.

• From the AV node, the bundle of His crosses the "cross of the heart" (behind the membranous septum) and divides into left and right branches. The right branch includes a part that goes into the moderator band.

• Surgical and interventional catheterization procedures require precise knowledge of the location of these nodes, especially the AV node. The AV node is situated at the apex of the Koch's triangle, which is formed by the coronary sinus, the tricuspid septal leaflet, and the tendon of Todaro (a fibrous continuation of the Eustachian valve (of the IVC) and the Thebesian valve (of the coronary sinus). Another reference point for the AV node is at the level of the commissure between the anterior and septal leaflets of the tricuspid valve.

  1. Electrophysiologists use Koch’s triangle to localize and avoid injury to the AV node during ablation procedures (e.g., for AVNRT). Surgeons are cautious around this area during tricuspid valve repair or congenital heart defect surgery to prevent conduction disturbances.

Left Atrium

The left atrium typically receives four pulmonary veins (two right, two left) that drain into its roof.

• The left atrial appendage (LAA) has a distinctive 'glove-finger' shape with a narrow base of implantation, in contrast to the broader and more pyramidal right atrial appendage. Its internal surface is characteristically crenellated or scalloped due to prominent pectinate muscles. This complex anatomy is important in imaging, particularly on transesophageal echocardiography (TEE) and cardiac CT, as it predisposes the LAA to blood stasis and thrombus formation—especially in (often adult) patients with atrial fibrillation.

• The internal surface of the left atrium is generally smooth, particularly the posterior wall, due to its embryological origin from the pulmonary veins. However, the anterior portion, especially within the left atrial appendage, contains muscular ridges called pectinate muscles. The left atrium also features openings for the pulmonary veins and the mitral valve, and a depression on the interatrial septum called the fossa ovalis (or its remnant).

• The posterior wall and generally the entire wall of the left atrium are uniformly smooth, lacking pectinate muscles, which are mostly confined to the left appendage.

• On the septal surface, the septum primum is visible, with its attachments to the muscular septum secundum, formed by the apoptosis of the embryological ostium secundum.

Ventricles

The ventricular mass comprises two ventricles separated by the interventricular sulcus, which houses the anterior interventricular artery (IVA), a branch of the left coronary artery. The interventricular sulcus is a groove or depression on the surface of the heart that separates the left and right ventricles. There are two interventricular sulci: the anterior interventricular sulcus, which is visible on the front of the heart, and the posterior interventricular sulcus, which is on the back. These sulci are important because they house major coronary blood vessels that supply the heart muscle.

Right Ventricle

• It is triangular in shape and is more anterior than the left ventricle.

• While often described as having coarser and fewer trabeculations than the left ventricle, these characteristics can vary greatly in congenital heart disease depending on pressure conditions and age.

• The primary anatomical distinction of the right ventricle is its muscular band system, which forms a quasi-complete circle interrupted by the anterior tricuspid leaflet. This system includes:

  • The parietal band and subpulmonary conus, collectively called the ventriculo-infundibular fold or supraventricular crest (Anderson's terminology). In a normal heart, the conus (the muscular band separating the AV valve from the arterial valve) is subpulmonary.

  • The septal band (trabecula septalis), which lies on the interventricular septum. It typically ends in a Y or V shape, with anterior and posterior limbs.

  • The moderator band, which is a continuation of the septal band, crosses the right ventricular apex and helps identify the right ventricle during echocardiography.

• The moderator band continues into the anterior papillary muscle of the tricuspid valve and the right ventricular trabeculations.

• The tricuspid valve has three leaflets: anterior, septal, and inferior/posteroinferior. The septal leaflet attaches directly to the septum or via small papillary muscles. Its septal attachments are visible on echocardiography. The tricuspid valve is described as "septophilic" because its attachments are lower on the septum than the mitral valve.

• The subpulmonary infundibulum (or conus) is the outflow tract of the right ventricle, located above the main ventricular mass.

Left Ventricle

• It is elongated, appearing smaller than the right ventricle from the anterior view because only its anterior third is visible.

• Its septal surface is characteristically smooth, lacking AV valve attachments or muscular bands. It has finer and more numerous trabeculations than the right ventricle.

• The mitral valve has anterior (great) and mural (posterior/inferior/small) leaflets, which attach to two distinct groups of anterolateral and posteroinferior papillary muscles via chordae. The mural leaflet makes up two-thirds of the mitral valve circumference.

  1. Officially, we name the mitral leaflefts: the anterior leaflet and the posterior leaflet. These leaflets are thin, strong flaps of tissue that open and close to regulate blood flow between the left atrium and left ventricle during each heartbeat. The leaflets attach to the papillary muscles of the left ventricle via the chordae tendineae, and also to the mitral annulus.

  2. Anterolateral Papillary Muscle (ALPM): Typically a single, larger muscle, arising from the anterolateral wall of the left ventricle. 

  3. Posteromedial Papillary Muscle (PMPM): Usually has multiple heads and arises from the posteromedial wall of the left ventricle.

• Unlike the right ventricle, the left ventricle lacks a conus; there is no muscle between the mitral valve and the aortic valve. Instead, there is a fibrous continuity between the mitral valve's anterior leaflet and the aortic valve. The mitral valve is "septophobe" because its attachments are further from the septum than the tricuspid valve.

Interventricular Septum

Viewed from its right face, the interventricular septum is divided into four main parts, corresponding to different types of ventricular septal defects (VSDs):

1. Trabecular septum: The largest part, extending to the apex.

2. Inlet/inflow (admission) septum: Extends posteriorly behind the septal leaflet of the tricuspid valve. This is the posteroinferior part.

3. Conal septum: Located between the two branches of the septal band's Y. In a normal heart, it is very small, just a few millimetres.

4. Membranous septum: The last part to form embryologically, a small fibrous, translucent zone. It is located at the commissure between the anterior and septal leaflets of the tricuspid valve on the right side, and between the antero-right and non-coronary cusps of the aortic valve on the left side.

Great Vessels

In a normal heart:

• The pulmonary artery originates from the right ventricle, and the aorta from the left ventricle.

• The pulmonary valve is anterior, to the left, and higher than the aortic valve. This is because the pulmonary valve is raised by the subpulmonary conus.

• The great vessels and their outflow tracts cross in a normal heart, indicating normal ventriculo-arterial concordance.

• The aortic arch normally forms to the left, with the descending aorta positioned to the left of the spine. The branches of the aortic arch typically include the brachiocephalic trunk (right subclavian and right carotid), followed by the left common carotid, and then the left subclavian artery.

• In some CHDs (e.g., Tetralogy of Fallot), the aortic arch can be right-sided, meaning the descending aorta is to the right of the spine. In such cases, the relative positions of the pulmonary and aortic valves remain the same (pulmonary anterior/left, aortic posterior/right), and the vessels still cross, but the neck vessel arrangement is mirrored.

Normal Variants and Common Misconceptions

• A subaortic conus can occasionally be present in a normal heart, though it is rare and usually small. The subpulmonary conus is almost always well-developed normally.

• The absence of mitral-tricuspid offset (where the mitral and tricuspid valves attach at the same level) is not a normal variant. It indicates a malformation like an atrioventricular canal septal defect . Normally, the tricuspid valve attachments are lower than the mitral valve attachments. There is a small RA-LV septum (atrio-ventricular septum - this area is also sometimes referred to as the membranous portion of the ventricular septum.). If a defect is there, we call it a Gerbode defect. 

• Marginal chordae of the mitral valve, if ruptured, typically do not cause significant mitral regurgitation, unlike principal chordae.

• False tendons in the left ventricle exist from birth and often correspond to conduction pathways. They may thicken and muscularize with age, becoming more visible in older children and adults, but they are not acquired.

"Simple" Congenital Heart Diseases

Atrial Septal Defects

ASDs involve a communication between the right and left atria.

• Categories:

  1. Defects of the interatrial septum itself: True "holes" in the septum, including PFO, ostium secundum, and ostium primum defect.

  2. Other interatrial communications: Involve an orifice that is normally present (like the coronary sinus) or abnormally created (like sinus venosus), but where the true interatrial septum is intact.

True Atrial Septal Defects:

• Foramen Ovale (PFO): A normal fetal structure that usually closes within the first days or weeks of life. It remains patent in 30-40% of normal individuals. It can be "forced" or enlarged in certain CHDs (e.g., pulmonary atresia with intact septum) where right atrial pressure is higher. A PFO allows blood clots to migrate from right to left.

• Ostium Secundum CIA: The most common type, located in the fossa ovalis. They are defects of the septum primum resulting from excessive or ectopic apoptosis during embryological development. Most are closed percutaneously, requiring sufficient septal borders for prosthesis attachment. Double ASDs can occur with two apoptosis zones. A multiperforated or cribriform septum primum describes multiple small holes.

• Inferior Sinus Venosus-type Defect: A rarer ASD type whose exact nature is not fully understood, located below the fossa ovalis. It lacks an inferior caval border, making percutaneous closure impossible.

• Ostium Primum ASD: Technically part of the atrioventricular septal defect family rather than simple CIAs. It represents the persistence of the embryological ostium primum.

Other Interatrial Communications (Intact Septum):

• Sinus Venosus ASD:

  • Can be superior (most common) or inferior (very rare).

  • Mechanism: Involves an abnormal fusion and subsequent apoptosis of the walls of the superior right pulmonary vein and the superior vena cava, creating a communication. This communication is located above the septum secundum, not within the septum itself.

  • This anomaly pulls the superior vena cava towards the left, causing it to "straddle" the interatrial septum. It is typically associated with partial anomalous pulmonary venous return (PAPVR) of the right lung to the superior vena cava.

• Coronary Sinus ASD:

  • A communication between the atria through the orifice of the coronary sinus.

  • This requires the coronary sinus itself to open partially or totally into the left atrium. This occurs when the left horn of the embryological sinus venosus fails to involute.

  • If the anterior wall (roof) of the coronary sinus is "unroofed" (absent), blood can pass from the left atrium into the coronary sinus and then into the right atrium.

  • This can be associated with a persistent left superior vena cava (which normally drains into the coronary sinus). Dilatation of the coronary sinus is not always present; it depends on the extent of unroofing and the presence of a left superior vena cava.

Ventricular Septal Defects

VSDs are the most frequent CHDs (around 50% in newborns), though many close spontaneously. Historically, VSD classification has been highly controversial, with various nomenclatures causing confusion.

Classification Controversy:

• Geographical Approach: Divides the interventricular septum into regions (e.g., van Praagh's zones). This approach is older, more intuitive for clinicians and echocardiographers, and has strong embryological links, influencing prenatal diagnosis and associated chromosomal abnormalities.

• Borders Approach: Promoted by Robert Anderson, this approach classifies VSDs based on whether their margins are fibrous or muscular. Its primary interest is for surgeons, as it indicates the vulnerability of conduction pathways. However, it leads to overlapping categories (e.g., perimembranous VSDs by this definition could include geographic perimembranous, inlet, or outlet VSDs).

• Consensus: After extensive debate, the international nomenclature group for CHDs decided to prioritize the geographical approach due to its widespread use and intuitive nature for clinical practice.

Geographic Classification of VSDs (based on right ventricular septal surface landmarks):

1. Central Perimembranous VSD 

   • Location: At the membranous septum. They are posterior and inferior to the outlet VSDs, situated behind the upper part of the tricuspid septal leaflet. They are centered on the attachments of the conus papillary muscle and the commissure between the tricuspid anterior and septal leaflets.

   • Features: Always involve a fibrous continuity between the aortic valve leaflets and the tricuspid septal leaflet. They tend to extend posteriorly or inferiorly. There is no septoaortic malalignment (the conal septum is normally positioned).

   • Spontaneous Closure: Often partially covered by bulging tricuspid septal leaflet tissue, forming what is incorrectly called an "aneurysm of the membranous septum". This can lead to spontaneous closure.

2. Outlet VSD:

   • Location: Geographically, they are always situated between the two branches of the septal band's Y.

   • Embryology: Result from a defect in the growth and fusion of the conal septum. The conal septum normally forms between the great arteries and descends to insert between the septal band limbs. If this descent is incomplete, a hole forms.

   • Types of Malalignment:

     • Anterior Malalignment: The conal septum does not descend sufficiently, staying above the right ventricle. This leads to an overriding aorta (aorta partially positioned over the right ventricle). This is common in conotruncal heart diseases like Tetralogy of Fallot. It can result in pulmonary stenosis or, if wide, a defect like the "Eisenmenger type" without pulmonary stenosis.

     • Posterior Malalignment: Rarer, this involves an excessive movement of the conal septum to the left, positioning it above the left ventricle. This creates an obstruction in the subaortic outflow tract, leading to associated left heart obstacles like coarctation or interrupted aortic arch.

     • Juxta-Arterial (Doubly Committed or Supracristal) VSD: In these cases, the conal septum is severely underdeveloped or absent, leading to a fibrous continuity between the pulmonary and aortic valves (no muscle between them). Blood can flow into both arteries.

3. Inlet VSD:

   • Location: Located behind the tricuspid valve's septal leaflet and extending along its length. This corresponds to a rectangular area of the posteroinferior septum that fails to muscularize or form properly.

   • Associations: The most frequent inlet VSDs are associated with atrioventricular canal defects (CAV). Other types exist without such malalignment.

   • Malalignment: Can occur due to malalignment between the interatrial and interventricular septa, leading to the tricuspid valve "straddling" the VSD and inserting into the left ventricle. This can be associated with a hypoplastic and stenotic "parachute" mitral valve.

4. Muscular/Trabecular VSD:

   • Location: Can occur anywhere within the large muscular part of the septum, classified as mid-septal, apical, anterosuperior (anterior dihedral), or posteroinferior.

   • Appearance: Can be multiple, creating a "Swiss cheese" appearance. They have entirely muscular borders.

Atrioventricular Septal Defect (AVSD)

The defining characteristic of all AVSDs is a common atrioventricular (AV) junction. This means that instead of distinct mitral and tricuspid valves, there is a single AV valve annulus. On echocardiography, this manifests as an alignment of the AV valves (no offset), unlike the normal heart. All AVSDs also feature a defect in the formation of the inlet septum, leading to a characteristic "scooped out" appearance.

Spectrum of Anatomical Types:

1. Complete AVSD:

   • Features: A single, common AV valve orifice with a single annulus and a single valve. There is a communication at both the atrial level (an ostium primum ASD) and the ventricular level (an inlet VSD). The valve typically has five leaflets, including superior and inferior "bridging leaflets" that pass over the septal defect.

   • Rastelli Classification: For complete AVSDs, this classifies based on the attachments of the anterior bridging leaflet to the septal crest:

     • Type A: The anterior leaflet has attachments to the septal crest (most common).

     • Type B: Rare, the anterior leaflet bridges the septum and attaches to an abnormal papillary muscle in the right ventricle.

     • Type C: The anterior leaflet has no attachments to the septal crest (free-floating).

   • The posterior bridging leaflet is always attached to the septal crest.

   • The "scooped-out" appearance of the inlet septum is prominent, as the septal crest is free and not fused with the bridging leaflets.

2. Partial AVSD:

   • Features: Still has a single common AV annulus. However, the superior and inferior bridging leaflets have fused with the septal crest, thereby closing the ventricular communication (no inlet VSD).

   • Communication: Only an ostium primum ASD remains.

   • Valve Morphology: The left component of the AV valve (analogous to the mitral valve) often presents with a characteristic cleft and may have three leaflets.

3. Intermediate AVSD:

   • Features: Essentially a complete AVSD where the inlet VSD is restrictive due to near-complete fusion of the bridging leaflets to the septal crest, leaving only small residual communications. Physiologically, this can resemble a partial AVSD.

4. Isolated Inlet VSD of AVSD Type:

   • Features: A common AV junction with an inlet VSD but without an ostium primum ASD (the interatrial septum is intact). The AV valve leaflets have fused with the interatrial septal crest.

5. AVSD without Shunt:

   • Rarely, there can be a AVSD with an aligned common AV junction but no significant shunting between chambers, often due to linear insertion of the AV valves.

Consequences and Associated Features of AVSD:

• "Scoped-Out" Inlet Septum: This fundamental defect in the inlet septum leads to a longer and narrower subaortic outflow tract in the left ventricle, predisposing patients to subaortic stenosis ("goose-neck deformity"). This risk is higher in partial AVSDs due to the complete fusion of leaflets.

• Conduction System Displacement: The atrioventricular node and bundle of His are displaced inferiorly due to the septal defect. This explains the prolonged PR interval often seen on ECG in AVSDs.

• Ventricular Dominance/Hypoplasia: AVSDs can be associated with hypoplasia of either the right or, more rarely, the left ventricle.

• Double Orifice of AV Valve Components: Duplication of the orifices of the right or left AV valve components can occur.

• Parachute Valve: The left component of the common AV valve (or a mitral valve in general) is considered a "parachute valve" when its chordae attach to a single papillary muscle or group of papillary muscles, instead of the normal two.

Right Heart Obstacles

Pulmonary Valvular Stenosis

This involves a narrowing at the level of the pulmonary valve.

• Forms:

  • Tricuspid Pulmonary Valve with Dysplastic Leaflets: The valve leaflets are thickened and malformed, leading to limited opening and a "doming" appearance on echocardiography. This is common in Noonan syndrome and usually requires surgical valvectomy as it does not respond well to balloon dilation.

  • Unicuspid Pulmonary Valve: A critical form seen in newborns, where the three commissures are fused, resulting in a single leaflet with a pinpoint opening ("jet opening"). This is often treated with percutaneous balloon dilation.

Subvalvular Pulmonary Obstacles

These obstructions are rarely isolated and often associated with other CHDs.

• Infundibular Ostium Stenosis: A fibrous band develops at the entrance of the subpulmonary infundibulum (the outflow tract of the right ventricle). This is a frequent complication of restrictive perimembranous VSDs, where the VSD jet impacts the base of the infundibulum, causing a fibrotic reaction. It requires surgical resection.

• Double-Chambered Right Ventricle: A much rarer anomaly caused by an abnormally positioned moderator band or an abnormal muscular band that divides the right ventricle into two chambers.

Left Heart Obstacles

Shone’s Complex is a congenital heart disease characterized by multiple levels of left-sided obstructive lesions and should be called "multiple levels of left-sided obstruction". It was first described by Dr. John D. Shone in 1963. It indicates an association of multiple left heart obstructions.

• Definition: Characterized by at least one inlet  obstacle combined with at least one outlet obstacle.

• Inlet Obstacles: Anomalies of the mitral valve or a supramitral membrane.

• Outlet Obstacles: Subaortic stenosis, aortic valvular stenosis, supravalvular aortic stenosis, or aortic coarctation.

• Exclusions: This syndrome excludes hypoplastic left heart syndrome (HLHS) with mitral and aortic atresia, and outlet VSDs with posterior conal septum deviation.

• Cardiopathy of Flow (Domino Effect): A crucial concept for left heart obstacles is "cardiopathy of flow". Abnormal fetal blood flow through one part of the left heart can lead to a cascade of anatomical malformations or stenoses further downstream. For example, a supramitral membrane can reduce flow through the mitral valve, leading to reduced flow in the left ventricular outflow tract, potentially causing a bicuspid aortic valve to stenose, and ultimately resulting in coarctation of the aorta.

• Heredity: There's a notable familial recurrence rate (under 10%).

• Often has a combination of: 

  1. Supravalvular mitral membrane

  2. Parachute mitral valve

  3. Subaortic stenosis (fibromuscular ridge or tunnel)

  4. Coarctation of the aorta

Obstacles to Left Ventricular Filling (Inlet Obstacles)

Intra-Atrial (Left Atrium) Obstacles:

• Supramitral Membrane: A fibroelastic tissue ring that forms above or sometimes within the mitral valve. It is distinguished from Cor Triatriatum by its location below the left appendage orifice. Cor triatriatum is above the LA appendage. 

• Massive Dilation of Coronary Sinus: If the coronary sinus is significantly dilated (often due to a persistent left superior vena cava draining into it), it can bulge into the left atrium and obstruct up to half of the mitral valve. This can be associated with other left heart obstacles.

Mitral Valve Anomalies: Many types of mitral valve anomalies exist, often making surgical repair challenging due to diverse and combined lesions.

• Parachute Mitral Valve: Instead of two separate papillary muscle groups, the myocardium condenses into a single papillary muscle receiving all chordae.

• Arcade Mitral Valve: Two papillary muscles are present but connected by a thickened, fibro-muscular free edge of the valve, leading to severe stenosis and few chordae.

• Hammock Mitral Valve: Characterized by numerous papillary muscles and dysplastic mitral tissue with fused free edges, creating multiple small, restrictive openings.

• Funnel-shaped Mitral Valve (Pilier Commissure Syndrome): The annulus size is normal, but there is fusion of the interchordal spaces, leading to a severely stenotic funnel-shaped orifice.

Obstacles to Left Ventricular Outflow tract 

Subvalvular Aortic Stenosis:

• Fibrous Diaphragm (Subaortic Membrane): A fibroelastic tissue that encircles the subaortic outflow tract, often attaching to the anterior mitral leaflet. Crucially, this is an acquired lesion, not congenital, developing and progressing after birth. It is frequently associated with a bicuspid aortic valve.

• Morphological Substrate: The most common congenital predisposition for a subaortic membrane is a particular orientation of the left ventricular outflow tract, specifically an acute septoaortic angle. This angle causes blood to impact the septum during systole, leading to scar tissue formation and progressive fibrosis.

• Associated Mitral Anomalies: Abnormal mitral valve structures (e.g., muscularization of the anterior leaflet, accessory mitral tissue "bleb," abnormal chordae, axial rotation or anomalous insertion of papillary muscles onto the septum) can also promote subaortic membrane development.

• Muscular (Subaortic Tunnel): Can be caused by an abnormal anterolateral muscular bundle of the left ventricle, known as Moulaert's muscle. This muscle, a remnant of the heart's internal curvature, can hypertrophy and become obstructive, forming a subaortic ridge or tunnel. While it exists in 30-40% of normal hearts without being pathological, in some cases it becomes obstructive.

Valvular Aortic Stenosis:

• Often associated with a bicuspid aortic valve (BAV). A critical form is the unicuspid aortic valve, resulting from the fusion of all commissures.

• Bicuspid Aortic Valve Classification (Sievers):

  • Type 0: Two cusps with no raphe, considered a true bicuspid valve. 

    1. Type 1: One raphe present, fusing two cusps. Type 1 with raphe: Fused commissures, with right-left cusp fusion being the most frequent (3/4 of cases). Further subdivided into: 

       1. 1 L-R: Left and right cusp fusion. (RL fusion (~70–80%))

       2. 1 R-N: Right and non-coronary cusp fusion. 

       3. 1 L-N: Left and non-coronary cusp fusion. 

    2. Type 2: Two raphes present, fusing three cusps.

Aortic Coarctation: A narrowing of the aorta, typically at the aortic isthmus (distal to the left subclavian artery, near the ductus arteriosus insertion).

• Neonatal/Infant Form: Characterized by a hypoplastic and tubular aortic arch. The descending aorta is often supplied by the ductus arteriosus. This form is often associated with other significant intracardiac anomalies because reduced fetal flow through the horizontal aorta leads to hypoplasia (e.g., stepped left heart obstacles, VSDs with posterior conal septum malalignment).

• Older Child/Adult Form: A localized isthmic stenosis with a normal, well-developed horizontal aorta. The descending aorta is normally supplied. This form is typically isolated or associated with minor intracardiac anomalies like a bicuspid aortic valve. It is primarily caused by an extension of ductal tissue (from the ductus arteriosus) into the aortic isthmus. This tissue can extend around the origin of the left subclavian artery, potentially causing its stenosis. Clinically, this can manifest as diminished or absent left brachial pulses.

Reference: Cours DU CPC M3C Necker Anatomie du Coeur normal et des cardiopathies simples by Dr Lucil Houyel

Van Praagh Classification (Boston)

Since 1964, the van Praagh classification has been a segmental approach to describing congenital heart defects. It is based on a systematic analysis of the heart’s anatomy using the following principles: 

• Situs: Determination of the position of the atria and viscera (e.g., solitus, inversus, ambiguous) 

  • Refers to the location of the atria and abdominal/thoracic organs. Determines whether the arrangement is normal (situs solitus), mirror-image (situs inversus), or ambiguous (isomerism or undefined lateralization)

• Segmental alignment: The sequential relationship between the atria, ventricles, and great arteries 

  • Describes the progressive, sequential connection between heart segments: Which atrium connects to which ventricle (atrioventricular alignment)? Which ventricle gives rise to which great artery (ventriculo-arterial alignment)?

• Connections between segments: How each segment connects to the next (AV and VA connections: concordant, discordant, double outlet, etc.) 

  • Refers to the status, nature, and morphology of the junctional segments: 

    • Atrioventricular junction: the anatomical and functional characteristics of how the atria connect to the ventricles (e.g., normal valves, atresia, straddling, double inlet). 

    • Ventriculo-arterial junction: the anatomical and functional characteristics of how the ventricles connect to the great arteries (e.g., normal outflow tracts, double outlet, truncus arteriosus). 

    • This assessment includes whether the junctions are concordant, discordant, atretic, overriding, or malpositioned, and is essential for defining the complexity and type of congenital heart defect.

• Spatial relationships: Orientation of cardiac structures in space (right/left, anterior/posterior, etc.) 

  • Right, left, anterior, posterior, superior, inferior

• Associated anomalies: Structural or functional abnormalities that coexist with the segmental arrangement (e.g., VSD, outflow tract obstructions, etc.) 

  • Any congenital heart defect can be described using the segmental coding system, ensuring that the description includes both the **segmental alignments** and the **status of the connections** between segments.

This method provides a comprehensive anatomical framework for describing both normal and complex congenital heart anatomies.

References: 

1. Van Praagh R. The segmental approach to diagnosis in congenital heart disease. Birth Defects;1972:8:4. 

2. Van Praagh R. Editorial. Terminonlogy of congenital heart disease. Glossary and Commentary. Circulation 1977;56:139-143

Three cardiac segments (anatomical building blocks in the van Praagh classification): 

• Atria (oreillettes) - Atrial Situs:

  • S (Solitus): Normal arrangement. S: Situs solitus — the right atrium is on the right and the left atrium is on the left

  • I (Inversus): Mirror-image arrangement. I: Situs inversus — the right atrium is on the left and the left atrium is on the right 

  • A (Ambiguous): Indeterminate arrangement. A: Ambiguous atrial situs — uncertain atrial lateralization; bilateral "viscero-atrial symmetry" Can be associated with right isomerism (asplenia) or left isomerism (polysplenia).

  • The atrial situs usually corresponds to the abdominal and thoracic visceral situs. Segmental notation: { S, _ , _ } or { I , _ , _ } or { A , _ , _ } 

  • Note: Van Praagh did not support the concept of pure cardiac isomerism, unlike Anderson, who did.

• Ventricular Looping:

  • D (D-loop): Rightward looping; morphologic right ventricle on the right. D: d-loop — rightward cardiac loop; typically, the right ventricle is on the right and the left ventricle is on the left; 

  • L (L-loop): Leftward looping; morphologic right ventricle on the left. L: l-loop — leftward cardiac loop; typically, the left ventricle is on the right and the right ventricle is on the left

  • { _ , D , _ } or { _ , L , _ }. 

• Great vessels (gros vaisseaux) — i.e., the aorta and pulmonary artery 

  • Normal conus: The relative position of the great vessels (GV) is preserved, with the aortic valve (AoV) posterior to the pulmonary valve (PV). There is fibrous continuity between the AoV and atrioventricular (AV) valves. 

    • {_,_,S} (Solitus): AoV is posterior and to the right of the PV 

    • {_,_,I} (Inversus): AoV is posterior and to the left of the PV 

  • Abnormal conus: The aorta is anterior, indicating an abnormal position of the GV. There is discontinuity between the AoV and AV valves. 

    • {_,_,D} (Dextro): AoV is anterior and to the right of the PV, or both valves are side-by-side with AoV on the right 

    • {_,_,L} (Levo): AoV is anterior and to the left of the PV, or both valves are side-by-side with AoV on the left 

    • {_,_,A} (Anterior): AoV is directly anterior to the PV

• Two connecting segments (junctional components): 

  • Atrioventricular junction (canal atrioventriculaire) — connects the atria to the ventricles. Atrioventricular (AV) alignment – 5 types: 

    • AV concordance {S,D,_} or {I,L,_}: The right atrium connects to the right ventricle, and the left atrium to the left ventricle 

    • AV discordance {S,L,_} or {I,D,_}: The right atrium connects to the left ventricle, and the left atrium to the right ventricle 

    • Atresia of an AV valve: One AV valve is absent (e.g., tricuspid or mitral atresia) 

    • Overriding or straddling AV valve: An AV valve is positioned above and connected to both ventricles (overrides the septum) 

    • Double inlet ventricle (DIV): Both atria drain into the same ventricle (usually a morphologic left ventricle, but sometimes RV)

  • Infundibulum or conus arteriosus — connects the ventricles to the great arteries. Ventricular-Arterial junction.

    • Ventriculo-arterial (VA) alignment – 4 types: 

      • VA concordance {_,D,S} or {_,L,I}: The right ventricle gives rise to the pulmonary artery, and the left ventricle gives rise to the aorta — normal arrangement. 

      • VA discordance {_,D,D} or {_,L,L}: The right ventricle gives rise to the aorta, and the left ventricle gives rise to the pulmonary artery — as seen in transposition of the great arteries. 

      • Double outlet ventricle: Both great arteries arise from the same ventricle: DORV (Double Outlet Right Ventricle), DOLV (Double Outlet Left Ventricle) 

      • Single outlet ventricle: Only one great artery exits the heart, e.g., common arterial trunk (truncus arteriosus).

These segments and their connections are described in sequence to define the architecture and anomalies of the heart in congenital disease.

Each segment has distinct anatomical features that help identify it. For example: Atrial appendages and the moderator band (RV) are key distinguishing structures. The connection of veins is not reliable for identifying atrial morphology, as venous connections can be anomalous. However, the right atrium can often be identified by the opening of the coronary sinus, according to Stella van Praagh. In general (but not always), atrial situs and abdominal visceral situs are concordant.

Examples:

• {S,D,S}: Normal heart configuration

• {S,D,D}: Classic Dextro-Transposition of the Great Arteries (d-TGA)

• {I,L,I}: Mirror-image normal heart (situs inversus totalis and dextrocardia)

• {S,D,S}: A tricuspid atresia without transposition of the great arteries is still classified as {S,D,S}, because the segments are in their normal positions, but there is an anomaly at the right atrioventricular (AV) junction — specifically, absence of the tricuspid valve. Although the right atrium (RA) and right ventricle (RV) are aligned (S,D), they do not communicate. The same concept applies to pulmonary atresia: the RV is aligned with the pulmonary artery, but there is no flow due to atresia of the pulmonary valve. Key point: AV or VA concordance means that the segments are correctly aligned anatomically, but this does not guarantee functional communication between the structures.

• {S,D,D}: A classic double outlet right ventricle (DORV) with TGA physiology (Taussig-Bing anomaly) is also classified as {S,D,D}. This means: S: Situs solitus (normal atrial arrangement); D: D-loop (rightward ventricular looping — morphologic right ventricle on the right); D: Dextro-malposition of the great vessels. In this case: Both great arteries (the aorta and pulmonary artery) arise from the right ventricle (transposition of the great vessels). The aortic valve (VAo) is positioned anterior and to the right of the pulmonary valve (VP), indicating abnormal spatial arrangement.

• {S,L,L}: TGA {S,L,L} or l-TGA (Double discordance / congenitally corrected transposition of the great arteries): Situs solitus Levocardia (heart on the left with apex pointing left); Atrioventricular discordance (right atrium connects to left ventricle, left atrium to right ventricle); Ventriculo-arterial discordance (left ventricle connects to pulmonary artery, right ventricle to aorta); Aortic valve anterior and to the left of the pulmonary valve. This results in a physiologically corrected circulation despite the anatomical discordances.

• {S,L,L}: A single left-type ventricle classified as {S,L,L} is characterized by situs solitus and levocardia, with a morphologic left ventricle receiving inflow from both atria (double inlet configuration). The right ventricle is hypoplastic or replaced by a small outlet chamber, and there is ventriculo-arterial discordance, meaning the great arteries arise abnormally. Specifically, the aortic valve is positioned anterior and to the left of the pulmonary valve, originating from the outlet chamber. A ventricular septal defect (VSD) or bulbo-ventricular foramen (BVF) is typically present, allowing blood flow between chambers. This anatomical configuration results in a functionally univentricular circulation, with the left ventricle serving as the dominant systemic pump.

Anderson Classification (London)

This is the classification we locally use. We follow as well the international nomenclature. Anderson classification focuses on identifying the concordance or discordance between cardiac segments (atria, ventricles, great arteries). It is a highly descriptive approach that emphasizes the detailed morphology and connections of each cardiac structure. 

Key principles: 

• Rather than relying on a segmental code, it provides a structural description of: 

  • Atrial situs 

  • Ventricular topology (right/left morphology) 

  • Atrioventricular and ventriculo-arterial connections 

  • Valve morphology (e.g., separate vs. common AV valves, valve anomalies) 

This approach is particularly useful for surgical planning and for understanding complex congenital heart disease, as it focuses on the actual anatomy and not just segmental position.

Atrial segment

• Atrial situs solitus: the right atrium is on the right, and the left atrium is on the left (normal arrangement). 

• Atrial situs inversus: the right atrium is on the left, and the left atrium is on the right (mirror-image arrangement). 

• Right isomerism: both atria have the morphological features of a right atrium (often associated with asplenia). 

• Left isomerism: both atria have the morphological features of a left atrium (often associated with polysplenia).

Ventricular segment

• Biventricular heart: has two distinct ventricles with either right or left topology

• Univentricular heart: only one functional ventricle, which can be: Right-type (morphologic right ventricle); Left-type (morphologic left ventricle); Indeterminate (ventricle does not clearly resemble either morphology)

Atrioventricular junction

• Myocardial junction (Atrioventricular connection types): 

  • Biventricular AV connection: Both atria connect to separate ventricles 

    • Can be: Concordant (normal alignment); Discordant (atria connect to the opposite ventricles); Ambiguous (unclear or mixed features) 

  • Univentricular AV connection: Both atria connect to a single ventricle 

    • Can present as: Double inlet (both atria empty into one ventricle); Absence of one AV connection (either right or left AV valve is missing); 

  • Biventricular and uni-atrial connection: One atrium connects normally to a ventricle. The other atrium has no direct connection, and instead the permeable AV valve overrides or straddles the ventricular septum, connecting to both ventricles.

• Valvular Morphology

  • Right and left AV valves separated. Possible morphological abnormalities include: 

    • Stenotic: narrowed valve 

    • Imperforate (atretic): valve is completely closed or absent 

    • Regurgitant: valve is incompetent and allows backflow 

    • Overriding: valve is positioned over both ventricles 

    • Straddling: valve chordae and attachments extend into both ventricles

  • Common AV valve:

    • Stenotic, imperforate (atretic) right or left component, regurgitant, straddling.

Ventricular-Arterial junction

• Ventricular-arterial connection:

  • Concordant, discordant, double outlet ventricle, single outlet ventricle

  • Valvular morphology: 

    • Aortic and pulmonary valves separated: Stenotic, Imperforate, Regurgitant, Overriding 

    • Single semilunar valve: Stenotic, Regurgitant, Overriding

    • There is no straddling for semilunar valves, as they do not have chordae tendineae.

A normal heart has atrioventricular and ventriculo-arterial concordance; a mirror-image heart does as well. A classic transposition of the great arteries (TGA) has atrioventricular concordance but ventriculo-arterial discordance. This model recognizes isomerism—for example, a person can have two morphologically right atria.

Physiological classification

• Left-to-right shunt lesions 

  • Communication between the two circulations can occur at the atrial, ventricular, or arterial level. This promotes the flow of blood from the systemic to the pulmonary circulation, whether during systole, diastole, or continuously. Over time, this leads to increased pulmonary venous return, resulting in volume overload of the left heart chambers. However, in the case of an atrial septal defect (ASD), the right-sided chambers become overloaded, as the shunt occurs during diastole at the atrial level. Symptoms typically develop gradually and are often clinically silent in the immediate neonatal period. A murmur may become audible as pulmonary vascular resistance decreases.

  • Diastolic shunt: seen in atrial septal defect (ASD) 

  • Systolic shunt: seen in ventricular septal defect (VSD) 

  • Systolic–diastolic shunt: seen in patent ductus arteriosus (PDA), common arterial trunk (truncus arteriosus), complete atrioventricular canal (CAVC), and aortopulmonary window 

  • Symptoms typically emerge as pulmonary vascular resistance (PVR) decreases. In complete AV canal defects (CAVC), there may be early desaturation when elevated PVR promotes right-to-left shunting during the initial neonatal period.

  • Examples: Atrial septal defect, ventricular septal defect, atrioventricular canal, double outlet right ventricle without pulmonary stenosis, d-transposition of the great arteries with a large VSD, patent ductus arteriosus, common arterial trunk, aortopulmonary window.

• Cyanotic lesions 

  • Communication between the two circulations combined with an obstruction of the pulmonary outflow tract promotes the passage of blood from the pulmonary to the systemic circulation at the atrial or ventricular level, and rarely at the arterial level. 

  • Right-to-left shunting at the arterial level is generally due to pulmonary hypertension. 

  • These lesions cause obligatory mixing of the two circulations. 

  • They are typically recognized in the neonatal period by desaturation, with or without a murmur.

  • Atrial level: ASD/PFO with severe pulmonary stenosis, Ebstein anomaly 

  • Arterial level: Patent ductus arteriosus (PDA) with pulmonary hypertension 

  • Lesions causing obligatory mixing of the two circulations: d-Transposition of the great arteries (d-TGA), total anomalous pulmonary venous return (TAPVR), tricuspid atresia, single ventricle physiology

  • Examples: Tetralogy of Fallot, severe pulmonary stenosis with ASD or VSD, d-transposition of the great arteries, severe Ebstein anomaly, double outlet right ventricle with pulmonary stenosis, single ventricle with pulmonary stenosis, total anomalous pulmonary venous return, tricuspid atresia, persistent left superior vena cava draining into the left atrium, any congenital heart defect combining a VSD with obstruction of the pulmonary outflow tract.

• Obstructive lesions 

  • Lesions with partial obstruction to blood flow at the level of a valve, above a valve, or below a valve. 

  • They are rarely symptomatic unless the obstruction is severe or critical. 

  • In the neonatal period, they are typically identified by the presence of a heart murmur.

  • Examples: Mitral or supramitral stenosis, aortic stenosis (valvular, subvalvular, supravalvular), coarctation of the aorta, pulmonary stenosis (valvular, subvalvular, supravalvular), tricuspid stenosis (rare)

• Lesions with univentricular physiology 

  • Only one ventricle is well developed.

  • There is obligatory mixing of the pulmonary and systemic circulations at the atrial and/or ventricular level.

  • This condition is typically identified in the neonatal period by possible desaturation, a murmur, and often a hyperdynamic precordium.

  • Palliative surgeries will eventually be required to separate the two circulations and use the well-developed ventricle as the systemic pump. Ultimately, systemic venous return will be diverted away from the heart and connected directly to the pulmonary arteries.

  • Example: DORV with hypoplastic left or right ventricle, single left-type ventricle or DILV, hypoplastic left heart syndrome, pulmonary atresia with intact ventricular septum and hypoplastic right ventricle, tricuspid atresia, unbalanced atrioventricular canal.

• Low cardiac output lesions 

  • CO = SV x HR

  • SV influenced by preload, contractility, afterload

  • Increased afterload: Obstruction of the systemic ventricle, including: Hypoplastic left heart syndrome; Severe aortic stenosis; Severe coarctation of the aorta; Restrictive VSD in certain lesions. 

  • Decreased contractility: Myocarditis, dilated cardiomyopathy (DCMP) 

  • Decreased preload: Hypovolemia, cardiac tamponade, severe mitral stenosis, or restrictive ASD in certain conditions

  • Examples of low cardiac output lesions: Critical aortic stenosis, severe coarctation of the aorta, interrupted aortic arch, severe mitral stenosis, hypoplastic left heart syndrome, obstructed total anomalous pulmonary venous return (TAPVR), single ventricle with restrictive VSD, dilated cardiomyopathy. Restrictive ASD may be equivalent to mitral stenosis in certain lesions. 

  • TAPVR can be obstructed at the site of venous connection—most commonly in the infracardiac (infradiaphragmatic) type, and less frequently in the supracardiac type. Obstruction can also occur at the foramen ovale. In that case, the pulmonary venous return is not obstructed per se, but there is a reduction in left ventricular preload.

• PDA dependent lesions:

  • Lesions with systemic circulation dependent on the ductus arteriosus 

  • Lesions with pulmonary circulation dependent on the ductus arteriosus

  • For pulmonary circulation:

    • Any severe obstruction of the pulmonary outflow tract in the absence of significant aortopulmonary collaterals. In these cases, the ductus arteriosus supplies pulmonary blood flow from the aorta via a left-to-right (L→R) shunt.

    • Examples: Critical pulmonary stenosis, pulmonary atersia with TOF or without VSD, severe TOF, Tricuspid atresia with severe pulmonary stenosis or with a very restrictive ventricular septal defect (in the absence of TGA), double outlet right ventricle (DORV) with severe pulmonary stenosis.

  • For systemic circulation: Any severe obstruction of the left ventricular outflow tract. Here, the ductus arteriosus provides systemic blood flow from the pulmonary artery via a right-to-left (R→L) shunt. It is essential to maintain elevated pulmonary vascular resistance (PVR) to promote this shunting. This is referred to as a vicariant ductus (serving as an alternative route).

    • Examples: Hypoplastic left heart syndrome, critical aortic stenosis, severe coarctation of the aorta or interrupted aortic arch, tricuspid atresia with TGA and a very restrictive VSD or severe aortic stenosis and/or coarctation of the aorta, double outlet right ventricle (DORV) with aortic stenosis and/or severe coarctation.

A single lesion can be classified into two different categories based on its physiological characteristics.

Conus - Infundibulum

The conus, also known as the infundibulum, is a muscular band located within a ventricle that serves to separate an atrioventricular valve (e.g., tricuspid valve) from an arterial valve (e.g., pulmonary valve). It can also be referred to as the ventriculo-infundibular fold or supraventricular crest.

In a normal heart:

• A subpulmonary conus is typically well-developed. This conus elevates the pulmonary valve, causing it to be positioned anteriorly, to the left, and higher than the aortic valve.

• There is normally no subaortic conus, which allows for direct fibrous continuity between the mitral and aortic valves.

• The great vessels and their outflow tracts cross in a normal heart.

The conal septum, which is distinct from the conus muscle, originates from the endocardial cushions of the outflow tract and is intimately linked to the position of the aortic and pulmonary valves. Its proper rotation and insertion are crucial for forming the interventricular septum.

Anomalies of the Conus and Conal Septum

Anomalies related to the conus and conal septum are often due to issues during the "wedging" process—the septation and rotation of the outflow tracts during embryonic development. These malformations can represent approximately 40% of serious congenital heart defects. Neural crest cells play a significant role in the formation of the outflow tract and conal septum. Some examples of conus and conal septum anomalies:

1. Abnormal Conal Septum Position or Malalignment:

   • This is a hallmark feature of conotruncal cardiopathies.

   • Tetralogy of Fallot: This condition is characterized by an anterior deviation or malalignment of the conal septum. This leads to:

     • An overriding aorta (dextroposition of the aorta), where the aorta straddles both ventricles.

     • Subpulmonary stenosis, an obstruction of the pulmonary outflow tract.

     • A ventricular septal defect (VSD), typically located between the two branches of the septal band's "Y".

   • Posterior Malalignment of the Conal Septum: A less common anomaly where the conal septum is malaligned posteriorly. This can obstruct the subaortic outflow tract, restricting blood flow and potentially leading to associated conditions such as coarctation of the aorta or interrupted aortic arch.

   • Double Outlet Right Ventricle (DORV): In this condition, both great vessels originate from the right ventricle. It is characterized by the persistence of two conuses: one subaortic and one subpulmonary. The specific malalignment of the conal septum determines the type of associated outflow obstruction.

2. Abnormal Conus Presence or Absence:

   • Transposition of the Great Arteries (TGA): In TGA, the conus is typically located under the aorta, resulting in a discontinuity between the mitral and aortic valves. The right ventricular outflow tract, which ejects into the aorta, is vertical and rectilinear instead of the normal oblique orientation. The great vessels are also parallel and do not cross. TGA is considered a laterality anomaly of the "wedging" process rather than a conotruncal defect directly involving neural crest cells.

   • Congenitally Corrected Transposition of the Great Arteries (ccTGA): In ccTGA, the conal septum is often malaligned, contributing to the complexity of the malformation and frequently resulting in anomalies of the conduction system.

   • Persistence of a Subaortic Conus: Although a small subaortic conus can rarely persist in normal hearts, its presence is generally considered an anomaly, as it should normally be absorbed.

   • Complete Absence of Conus: The complete absence of conus structures is another described anomaly.

3. Other Related Anomalies:

   • Juxta-Arterial VSDs (also known as supracristal, conal, or infundibular VSDs): In these cases, the conal septum may be entirely absent or severely underdeveloped. This leads to a fibrous continuity between the pulmonary and aortic valves, allowing blood to flow into both vessels indiscriminately through the VSD.

   • Muscle of Moulaert: This is a muscular remnant resulting from the incomplete absorption of the embryonic conus that normally occurs during the formation of the left ventricular outflow tract. If it persists, it can sometimes create an obstruction.

   • Coronary Artery Anomalies: In conotruncal cardiopathies, the position and course of the coronary arteries can be abnormal due to a malformed "repulsive domain" around the pulmonary artery.

Reference:

https://thoracickey.com/infundibuloarterial-situs-equations-how-normally-and-abnormally-related-great-arteries-are-built-and-the-importance-of-infundibuloarterial-situs-concordance-and-discordance/ 

The Right Ventricle

The right ventricle (RV) is a unique and relatively recent development in evolution, appearing approximately 180 million years ago, significantly later than the left ventricle (LV) which dates back about 500 million years. This evolutionary "newcomer" status has led to the hypothesis that the majority of congenital heart diseases affecting the right ventricle might be linked to its more recent evolutionary arrival. In terms of cardiac development, the primitive cardiac tube initially only contains the left ventricle, with the right ventricle being added subsequently by the second anterior cardiac field. Early in development, the right ventricle is positioned superior to the left ventricle, only later adopting its definitive position to the right of the left ventricle due to looping.

Key Anatomical Characteristics of the Normal Right Ventricle:

• Size and Mass: The normal right ventricle is 10% to 15% larger in volume than the left ventricle. However, its mass is significantly less, ranging from 1/3 to 1/6 of the left ventricular mass.

• Wall Thickness: The anterior wall of the right ventricle is very thin, measuring 3-5 mm in a normal adult heart. This thinness makes the anterior wall extremely fragile, which is an important consideration for procedures like biopsies (i.e. in transplant).

• Histology:

  • The cardiomyocytes (myocardial cells) of the right ventricle are smaller than those in the left ventricle.

  • There is a higher proportion of collagen fibers.

  • The right ventricular walls are composed of two cellular layers, in contrast to the three layers found in the left ventricle.

    • A superficial layer consists of fibers parallel to the atrioventricular junction, accounting for 25% of the right ventricular myocardial fibers.

    • A deep subendocardial layer consists of longitudinal fibers.

  • This two-layer architecture dictates the right ventricle's contraction mode.

  • There is a continuity between the circumferential fibers of the right and left ventricles, highlighting the ventricular interdependence (RV-LV interdependence).

• Overall Shape and Position:

  • The normal right ventricle is anterior to the left ventricle.

  • It has a triangular shape with its base at the atrioventricular junction and its apex.

  • The right ventricle wraps around the left ventricle.

  • It is classically described as tripartite, comprising:

    • An inlet zone ("admission"/"inflow" zone), extending to the base of the papillary muscles (theoretically to the moderator band).

    • A trabeculated zone that reaches the apex and extends up to the outflow tract.

    • An outflow tract (infundibulum).

Distinctive Internal Structures and Features:

When a right ventricle is opened from the apex to the pulmonary artery, several key structures are observed:

• Trabeculations: These are often considered a distinctive mark of the right ventricle (by Dr Anderson) compared to the left ventricle. However, they are highly variable and can be effaced by conditions like increased pressure.

• Muscular Arc of the Right Ventricle: This is a more crucial distinguishing feature than trabeculations and includes:

  • Parietal band ("Bande pariétale"). The parietal band originates from the RV septum and extends across the tricuspid orifice onto the anterior wall, fading out near the anterior papillary muscle. It is a muscular band located within the basal part of the RV. The parietal band courses from the ventricular septum beneath the right pulmonary valve cusp to the anterior free wall of the right ventricle. In Tetralogy of Fallot (TOF), the parietal band of the crista supraventricularis forms the anterior boundary of the ventricular septal defect (VSD). This muscle also separates the aortic valve from the tricuspid valve and is sometimes referred to as the ventriculo-infundibular fold.

  • Subpulmonary Conus ("Conus sous-pulmonaire"): This muscular structure separates the pulmonary valve from the tricuspid valve. Together with the parietal band, it forms the supraventricular crest (crête supraventriculaire).

  • Y-shaped Septal Band (Bande septale): This structure has an anterior branch and a postero-inferior branch. The conal septum is embedded between these two branches. The septal band (septo-marginal trabeculation) divides into an antero-superior limb and a postero-inferior limb; the latter courses towards the RV free wall, where it merges with the parietal band (septo-parietal trabeculation)

  • Moderator Band (Bande modératrice): This band continues from the septal band, traverses the apex, and continues into the anterior papillary muscle. It is considered the primary criterion for distinguishing a right ventricular morphology in echocardiography. However, it is absent in 8% of normal hearts and is variable in size and thickness. Its origin is debated, though it is likely formed in conjunction with the septal band and anterior papillary muscle from the tricuspid infundibulum during development. The absence of the septal band and moderator band is observed in tricuspid atresia, supporting this developmental link. It also houses a segment of the right bundle branch of the His bundle.

• Tricuspid Valve:

  • It has three leaflets: an anterior leaflet, a septal leaflet (which attaches to the septum), and a postero-inferior leaflet.

  • The anterior and septal leaflets insert onto the papillary muscle of the conus and the postero-inferior branch of the Y-shaped septal band.

  • The tricuspid valve is an integral part of the right ventricle.

  • Its formation is linked to the tricuspid infundibulum, a muscular funnel that forms in the postero-inferior part of the primitive annulus and contributes to the formation of the tricuspid valve, septal band, moderator band, and anterior tricuspid papillary muscle. Infants with tricuspid atresia will not have this muscular funnel during embryogenesis and an absent inflow portion. 

• Apex: Located beyond the tricuspid papillary muscles, the apex is the site of trabeculations, which are typically few and thick. Abnormalities in the apex (filled, absent, or hypoplastic) are common in congenital heart diseases.

• Right Ventricular Outflow Tract (RVOT) / Infundibulum:

  • This is a funnel-shaped muscular sleeve that elevates the pulmonary valve above the right ventricle.

  • It is related to the right ventricle but is considered independent of the main body of the right ventricle.

  • Its formation involves the transfer of the aortic valve to the left ventricle during rotation, with the conal septum (formed by the endocardial cushions of the outflow tract) following the aortic valve's rotation. The conal septum moves to the interventricular septum, embedding itself between the two branches of the Y-shaped septal band. This original proximal part of the outflow tract diminishes in size during development.

  • The normal RVOT has a characteristic orientation from right to left, with the great vessels crossing in a normal heart.

• Interventricular Septum (IVS):

  • The interventricular septum has a fragile zone circumferentially where it contacts the left ventricle and the aorta. Only the central zone of the septum is robust.

  • The conal septum is not normally visible in a dissecting heart unless it is disjoint from the septal band. Its dissociation from the septal band is the mechanism behind many ventricular septal defects (VSDs) of the outflow tract, such as those seen in Tetralogy of Fallot where there is an anterior deviation of the conal septum. The highest and most anterior part of the septum is located between the two branches of the Y-shaped septal band.

  • The membranous septum is the last part of the interventricular septum to become sealed during development. It is located under the subpulmonary conus, behind the posterior branch of the Y-shaped septal band, and behind the septal leaflet of the tricuspid valve, centered on the anteroseptal commissure of the tricuspid valve.

"Right-Handed" Morphology Convention:

The particular anatomy of the right ventricle leads to the convention of describing it as "right-handed". This means that a right hand can be placed on the interventricular septum from the right ventricular side, with the thumb in the tricuspid valve (inlet) and the fingers in the pulmonary valve (outlet). This "right-hand on a right-morphology ventricle" indicates a normal position (d-loop). If a right-morphology ventricle is situated on the left, a left hand would be applied to the septal surface, with the thumb in the inlet and fingers in the outlet.

Coronary Vascularization and Conduction Pathways:

• Vascularization: The right ventricle is primarily supplied by only one coronary artery, the right coronary artery, whereas the left ventricle has two. This results in a weaker myocardial blood supply for the right ventricle.

• Conduction Pathways: The right branch of the His bundle travels within the septal band, then the moderator band, and finally the anterior papillary muscle of the tricuspid valve. Due to this proximity, it is common for children undergoing surgery via the right ventricle to experience branch blocks.

In conclusion, the right ventricle's unique internal architecture, particularly its muscular bands, is largely tied to the formation of its atrioventricular valve, the tricuspid valve, and the tricuspid infundibulum. Its distinct outflow tract, apex, and myocardial structure differentiate it significantly from the left ventricle, impacting its functional characteristics.

The Systemic Right Ventricle

When the right ventricle (RV) operates in a systemic circulation, it adapts to the elevated systemic pressures by undergoing significant hypertrophy. This considerable hypertrophy can affect both the RV wall and its trabeculations, potentially leading to chronic ischemia, fibrosis, and dysfunction. This is exacerbated by the fact that the RV naturally has a poorer coronary vascularization compared to the left ventricle. The RV becomes systemic in various congenital heart diseases, including:

• Transposition of the Great Arteries (TGA), particularly after Mustard or Senning procedures.

• Double Discordance (also known as congenitally corrected TGA, SLL type).

• Double Inlet Right Ventricle.

• Mitral Atresia with Double Outlet Right Ventricle.

• Hypoplastic Left Heart Syndrome (HLHS), especially after the Norwood procedure.

While the RV adapts to its systemic role, its morphology is distinctly particular to each specific cardiopathy, which likely contributes to its eventual dysfunction. It is crucial to understand that a systemic right ventricle is not morphologically equivalent to a left ventricle.

I. Transposition of the Great Arteries (TGA)

In uncomplicated TGA, the morphologic right ventricle may initially appear relatively normal with its characteristic structures:

• A conus.

• A septal band, including its Y-shaped configuration.

• A papillary muscle of the conus.

• A moderator band.

• An anterior papillary muscle.

• An apparently normal tricuspid valve.

However, key anatomical distinctions exist in the outflow tract:

• In normal hearts, the right ventricular outflow tract (RVOT) is oriented from right to left, and the great vessels cross.

• In TGA, the great vessels do not cross, and there is no rotation of the aortic valve or the outflow tract.

• Consequently, the RV infundibulum, which ejects into the aorta, is vertical and rectilinear, unlike the normal oblique orientation.

However, in the rarer form of S,D,L Transposition of the Great Arteries (Situs Solitus, D-loop, L-transposition of the Great Arteries): This specific form of TGA, representing 5-6% of all transpositions, shows a higher incidence of intrinsic RV anomalies:

• The aorta remains above the RV but is positioned to the left of the pulmonary artery. Instead of the normal position where the aorta is to the right and posterior to the pulmonary artery. 

• The outflow tracts cross distal to the arterial valves, although the vessels themselves remain parallel.

• Studies have shown significant RV anomalies in these cases, including:

  • 50% incidence of right ventricular hypoplasia.

  • 23% incidence of ventricular malpositions, such as superior-inferior ventricles, which can result in a horizontal interventricular septum.

  • A higher rate of "criss-cross" heart configuration.

Tricuspid Valve Anomalies in TGA: The tricuspid valve, which is developmentally inseparable from the RV, is also frequently abnormal in TGA:

• It is anomalous in 20% of TGAs with an intact septum.

• This figure dramatically rises to 64% when an associated ventricular septal defect (VSD) is present.

• Observed anomalies include:

  • Straddling and overriding of the tricuspid valve.

  • Dysplasias.

  • Double orifices.

  • Abnormal attachments to the septum or conal septum.

  • Anomalies of the tricuspid subvalvular apparatus.

II. Double Discordance (SLL)

Double Discordance is characterized by a defect in laterality and an abnormal cardiac (L-)loop, leading to both atrioventricular and ventriculo-arterial discordance. In this condition, the morphologic right ventricle is situated on the left side, often described as a "left-handed" RV morphology.

The RV morphology in double discordance is always abnormal, a consensus shared by experts like Van Praagh and Anderson:

• It does not simply present as a mirror image of a normal RV; the septal band can appear "bizarre".

• Anomalies typically affect the inlet, the tricuspid valve, and often the RV apex, which is frequently hypoplastic.

• There can be a constriction at the junction of the outflow tract and the admission chamber, often due to abnormal tricuspid attachments to the septum or septal band, making recognition of the septal band difficult.

• The septal band is frequently abnormal: specifically, the postero-inferior branch of the Y-shaped septal band is often virtually absent, leaving predominantly an anterior branch.

• Despite the ventriculo-arterial discordance, studies have shown that the orientation of the outflow tract and septal band in double discordance is similar (though mirrored) to a normal heart, in contrast to TGA where it is rectilinear. This suggests a degree of outflow tract rotation may occur in double discordance, unlike TGA. This finding underscores why the term "double discordance" is preferred over "congenitally corrected TGA," as the defining feature is the atrioventricular discordance.

Tricuspid Valve Anomalies in Double Discordance: The tricuspid valve is always anatomically abnormal in double discordance:

• It can be dysplastic, with leaflets appearing fused or atypical (e.g., the anterior leaflet appearing as two fused leaflets), leading to potential regurgitation.

• Epstein-like anomalies are common, though often they involve a displacement or verticalization of the tricuspid annulus rather than a true absence of leaflet delamination. While true Epstein's (with delamination absence) can occur, they are not the majority of "Epstein-like" valves seen.

• The posterior wall does not undergo atrialization; it remains muscular despite being thinner.

Conduction System Anomalies: The conduction pathways are also abnormal in double discordance:

• An anterior atrioventricular node is typical.

• The His bundle courses along the anterior border of an associated VSD (if present), or within the septal band, often in proximity to the pulmonary valve in the morphologic left ventricle.

III. Double Inlet Right Ventricle (DIRV)

Double Inlet Right Ventricle is a very rare and developmentally complex malformation. In this condition, the morphologic right ventricle is never normal.

• The only reliable criterion for identifying a morphologic right ventricle in DIRV is the presence of trabeculations.

• Crucially, in DIRV, the RV often lacks both a septal band and a moderator band, and frequently there is no discernible interventricular septum at all.

• Two atrioventricular (AV) valves are present, which are often similar in appearance and may have three leaflets, but their attachments are very frequently abnormal. In cases of heterotaxy, a common AV valve is often observed.

• DIRV is always associated with Double Outlet Right Ventricle (DORV) and a bilateral conus.

• Specific morphological characteristics observed include: no septal band, no moderator band, very prominent septoparietal trabeculations on both sides of the outflow tract, and thick trabeculations.

• DIRV is often accompanied by a hypoplastic or even absent morphologic left ventricle. If no other ventricular chamber is identifiable, some experts consider the main ventricle to be "indeterminate" rather than definitively right-morphology.

IV. Mitral Atresia with Double Outlet Right Ventricle (MA-DORV)

In mitral atresia with double outlet right ventricle, the systemic right ventricle is predictably hypertrophied.

• It can be very challenging to recognize typical RV structures.

• While a conus may be present, the septal band can appear as an abnormal muscular band with unusual attachments.

• A moderator band might be present, but the septal band itself remains atypical.

• The aortic valve is often positioned posteriorly, maintaining continuity with the tricuspid valve, while the pulmonary artery is anterior.

• The tricuspid valve itself is commonly abnormal and often requires surgical plastic repair.

V. Hypoplastic Left Heart Syndrome (HLHS)

In Hypoplastic Left Heart Syndrome, where the left ventricle is underdeveloped, there is no anatomical reason for the systemic right ventricle to be normal; indeed, it is significantly altered.

• There is considerable hypertrophy of the RV free wall and its trabeculations.

• The septal band, moderator band, and anterior papillary muscle are typically present.

• The tricuspid valve is frequently abnormal:

  • It can exhibit dysplastic zones that prolapse into the right atrium.

  • Anatomical studies have shown that tricuspid dysplasia occurs in 15% of HLHS cases with both mitral and aortic atresia, but this figure rises to 50% when there is mitral hypoplasia combined with aortic atresia or hypoplasia.

  • A rare Epstein-like anomaly can occur, which specifically affects only the septal leaflet, showing partial delamination and a focal insertion of the anterior papillary muscle. Only a handful of such cases have been published in literature.

Coronary Circulation Peculiarities: Even if the coronary arteries follow normal pathways, their blood supply is compromised:

• They are fed retrogradely from a filiform (thread-like) ascending aorta.

• This abnormal perfusion significantly increases the risk of myocardial ischemia in these hearts.

Reference: 

1. Anatomie macroscopique normale du ventricule droit Lucile Houyel - M3C Academy - YouTube Link

2. Particularités du VD dans les TGV, doubles discordances etc Lucile Houyel - M3C Academy - YouTube Link

Malformations of the Right Ventricle

Defining Right Ventricular Malformations

The concept of right ventricular (RV) malformations, particularly in isolation, presents a complex subject in pediatric cardiology. A fundamental question arises: do isolated malformations of the right ventricle truly exist, or are anomalies primarily contingent on other factors? Most observed anomalies are considered contingent or secondary, meaning their presence or proportion depends on factors not directly tied to the development of the right ventricle itself. Instead, they are often linked to abnormal development of the RV's inlet (entry) or outlet/outflow tract (exit), or to earlier disruptions in the formation of the cardiac loop. These malformations can be broadly separated into contingent/secondary types and rarer, specific developmental anomalies of the ventricle itself. Contingent malformations are those that are secondary to issues like abnormal positioning of the right-morphology ventricle, or anomalies in fetal physiology that either deplete the ventricle's preload, compromising its growth and size, or constrain the ventricle during systole. In such cases, the right ventricle adapts in a normal way to a malformation that is not primarily an RV malformation. The interplay between the constraining anomaly and the ventricular development is a key area of discussion.

Semantic Challenges in Naming Ventricular Structures

A significant challenge in understanding right ventricular malformations lies in the very definition and naming of cardiac structures. A ventricle is usually characterized by the presence of its inlet. This definition creates semantic problems in various congenital cardiac anomalies where an inlet may be absent, raising questions about whether the downstream structure should legitimately be called a "ventricle". The right ventricle presence can only be legitimately discussed once the tricuspid infundibulum has formed.

• Structures without an inlet: If a cardiac structure lacks an inlet/inflow, its classification as a true ventricle is questionable.

• Interventricular Communications: In some anomalies, it is difficult to name the communication between the left ventricle (often with a double inlet) and an ejection pathway as an "interventricular communication" or "bulbo-ventricular foramen" if the accessory cavity is not definitively a right ventricle. It might not yet have a name at that stage of development. The terminology "with outlet chamber" may be more appropriate. An example can be found as Case 2 in the section on Double Inlet Left Ventricle.

• Straddling Tricuspid Valve: Even when a small structure is called a right ventricle in cases of a straddling tricuspid valve, if there has not been sufficient displacement for the tricuspid infundibulum to form properly, its designation as a true right ventricle is debated. This could be an arrest of embryonic development.

• Systemic Right Ventricle: While referred to as a "right ventricle in systemic position," its development and anatomy differ significantly from a normally positioned right ventricle, despite retaining some characteristics. This also presents a semantic problem.

• Hypoplastic Right Ventricle in Atrioventricular Septal Defect or "Canal": In univentricular congenital cardiac conditions with an atrioventricular septal defect and a small right ventricle, it is often called an "unbalanced AV canal" predominantly affecting the right ventricle. However, there is doubts about whether it should be precisely called a "hypoplastic right ventricle".

Classification of Right Ventricular Malformations

Based on their origins, malformations involving the right ventricle can be broadly categorized:

• Contingent/Secondary Malformations: These are the most common and arise due to external factors affecting the RV, rather than a primary defect within the ventricular muscle or structure itself. Examples include:

  • Anomalies of ventricular positioning.

  • Anomalies of right morphology.

  • Anomalies of fetal cardiac physiology, such as issues with preload or afterload, which can compromise the RV's growth and development or constrain it.

  • Anomalies of the RV's inlet/inflow or outlet/outflow tract.

• Specific Developmental Anomalies: These are much less common and are believed to be direct developmental defects of the right ventricle. They are often less symptomatic or asymptomatic and may be less challenging to repair and/or manage.
  
  

Specific Types of Right Ventricular Malformations

Anomalies of Position

Most univentricular congenital heart defects, whether with a double inlet or with a double inlet but a variation in one of the valves, arise from anomalies in the formation of the cardiac loop. These highly varied anatomical CHD share the same underlying mechanism: the relative spatial position of structures. Example: double inlet univentricular heart with an outlet chamber.

Atrioventricular Inlet and Ventricular Morphology Issues

• Tricuspid Atresia: In this condition, there is never a tricuspid valve, and thus never an inlet to the right ventricle. The structure from which a vessel exits is considered an accessory cavity, similar to what is seen in double-inlet ventricles. Many of the morphological characteristics of a true right ventricular structure, such as certain bands, are absent. Therefore, these are not considered specific right ventricular malformations but rather more global malformations where the right side of the heart did not develop.

• Ebstein's Anomaly: This is a condition where the right ventricle may be small, but it does possess an inlet. However, the inlet is malformed, leading to a destructured right ventricle. Both the inlet and potentially the outlet can be abnormal, and the structure referred to as the right ventricle may be reduced to primarily an ejection pathway in some cases.

Pulmonary Atresia with Intact Septum (PA/IVS)

• It may be a primitive malformation of the outflow tract that obstructs the right ventricle, preventing its development. This idea conflicts with the observation of secondary hypertrophy. Another hypothesis is that PA/IVS as a primitive anomaly of the right ventricle that restricts it in diastole, leading to outflow tract anomalies. 

• Certain morphological anomalies of the right ventricle, such as its coronary vascularization and the presence of sinusoids, might indicate that PA/IVS is a primitive malformation of the right ventricle, at least in some cases, rather than a secondary one due to outflow tract anomalies. This condition often involves a mix of developmental and constraint anomalies.

Isolated Hypoplasia of the Right Ventricle

This is one of the rare anomalies specifically of the right ventricle. It is characterized by no anomalies of the inlet or the outlet.

• Trabeculated Chamber: It often involves a severely reduced or absent apical trabeculated chamber of the right ventricle.

• Physiological Impact: This leads to restrictive behavior of the right ventricle and a right-to-left shunt via an atrial septal defect.

• Management: It is typically managed with common strategies, most often a "1.5 ventricle" repair. Or, tolerating desaturated patients that are in generating sufficient output while there is remodelling / growth of the RV with tight surveillance. 

• Mechanism: The mechanism behind this specific developmental anomaly of the trabeculated chamber remains mysterious.

Anomalies of the Intracavitary Bands

Abnormally developed bands within the right ventricle, such as the moderator band, can create intraventricular obstacles and stenoses.

• Double-Chambered Right Ventricle: When these bands are very prominent, they can lead to a condition known as a double-chambered right ventricle. This creates successive chambers: a high-pressure proximal chamber and a low-pressure distal chamber.

• Etiology: This anomaly is relatively rare in isolation but can also be recognized once a concomitant ventricular septal defect (VSD) closes while being apriori unnoticed.

Anomalies of the RV Wall

• Aneurysms and Diverticula: While aneurysms and diverticula are more frequently observed in the left ventricle, diverticula of the right ventricular wall can be found incidentally.

  • Clinical Presentation: These can be seen in fetal images and may be discovered fortuitously during examinations for unrelated issues, such as a heart murmur.

  • Functionality: They often contract synchronously with the rest of the ventricular wall and may not cause immediate problems.

  • Concerns: The primary concern with these diverticula is the potential for future arrhythmias (or clots), though reported cases rarely show them.

  • Location-Specific Associations: Apical diverticula are often associated with midline anomalies, such as Pentalogy of Cantrell, though they most commonly affect the left ventricle. 

    1. Cantrell syndrome, also known as Pentalogy of Cantrell, is a rare congenital condition characterized by five primary defects: a midline supraumbilical abdominal wall defect, a defect of the lower sternum, an anterior diaphragmatic defect, a defect in the diaphragmatic pericardium, and various congenital heart malformations. These defects are thought to result from abnormal development of the mesoderm during embryonic development.

  • Rarely, a diverticulum of the RV apex can extend through the diaphragm into the abdomen, creating two parts to the ventricle – one in the thorax and one in the abdomen.

  • Association with other Malformations: Diverticula can also be associated with other congenital heart malformations, such as a large basal RV diverticulum in Tetralogy of Fallot or a lateral RV wall diverticulum in an atrioventricular canal. The mechanism of their development in these complex malformations is a subject of ongoing inquiry.

Specific Wall Diseases

Some specific anomalies of the ventricular wall blur the line between malformative and degenerative pathologies.

• Arrhythmogenic Right Ventricular Dysplasia (ARVD): This condition involves a thin right ventricular wall with adipocytic and fibrous replacement. The bands within the ventricle become more visible due to ectatic dilatation. ARVD is linked to mutations in cardiomiopathy genes, most commonly desmosomal junction proteins, but other genes can also cause this type of anomaly. Notably, ARVD can affect both the right and left ventricles.

• Uhl's Disease: This is considered more likely a malformative condition. Unlike ARVD, it only affects the right ventricular wall; left ventricular involvement is not observed. The wall is replaced by a fibrous structure with very few, if any, muscle cells, making the coronary network visible through transparency. It can be detected in fetal life and is considered congenital rather than degenerative, despite its anatomical proximity to ARVD. These are extremely rare diseases.

  1. Uhl's disease, also known as Uhl's anomaly or parchment heart, is a rare congenital heart condition characterized by a thin, often translucent, right ventricular free wall due to a near-complete or complete absence of the myocardium (heart muscle) in that area. This can lead to right ventricular dysfunction, heart failure, and arrhythmias.

The right ventricle is frequently involved in congenital cardiac malformations. These involve anomalies of the cardiac loop, and issues related to fetal cardiac preload and afterload, affecting both the inlet and the outflow tract. Conditions like pulmonary atresia with intact septum are examples where developmental anomalies and physiological constraints both play a role. In contrast, isolated anomalies of the right ventricle are rare. Beyond these, there are exceptional and very rare diseases that specifically affect the right ventricular wall, which are seldom encountered in clinical practice.

Reference: Les malformations du ventricule droit by Dr Damien Bonnet

Cardiac Embryology

The heart is the first organ to form in humans, developing very early during embryology. Its formation spans from the 2nd to the 7th week of intra-uterine life, or between 4 to 10 weeks of amenorrhea. This rapid development means that by six weeks, the embryo has acquired all the necessary anatomical structures for the heart to be fully formed and functional. This rapid and precise chronolgy is crucial, as any issues can lead to congenital cardiac defects.

• Day (D)18-D23: Precursor cells gather to form the primitive cardiac tube. This is followed by the fundamental looping stage, where the tube takes on a helical shape, aligning the ventricles and establishing the right-left axis.

• D40: The convergence stage follows looping, allowing for the creation of the right atrioventricular (AV) junction and the alignment of the atrial and AV septa.

• D45: The wedging stage involves the positioning of the great vessels, the aorta, and the pulmonary artery, with the aorta undergoing rotation.

• D60: Heart formation is largely complete with the connection of coronary arteries to the aorta, along with the formation of AV and arterial valves and the proper alignment of all segments.

Early Embryonic Development and Heart Precursors

To understand heart development, it is essential to begin with fundamental embryology.

• Gastrulation and Mesoderm Formation: At the end of the 2nd week of intra-uterine life (4 weeks amenorrhea), the embryo consists of two cellular populations: the epiblast and hypoblast, arranged in a bilaminar disk. Through a process called gastrulation, a third cellular layer, the mesoderm, forms between the epiblast and hypoblast. The heart, specifically, derives from the lateral part of the mesoderm.

• Embryonic Axes: From this early stage, the embryo establishes its fundamental axes:

  • Right-Left Axis: Influenced by Hensen's node and cilia movement. (The Hensen’s node, also known as the primitive node, is a key structure in early human embryonic development. It is located at the anterior end of the primitive streak and plays a critical role in gastrulation—the process by which the three germ layers (ectoderm, mesoderm, and endoderm) form.)

  • Antero-Posterior Axis: Defined by cellular invagination at the cranial level.

  • These axes are crucial for the proper alignment of cardiac structures.

• Cardiogenic Region: Cells from the lateral mesoderm differentiate into cardiac cells in response to signals from the underlying endoderm, forming the cardiogenic plate. Initially, these precursors are symmetrical, with a cardiogenic plate on both the left and right sides of the midline.

• Heart Fields: These precursor cells migrate towards the cranial end of the embryo and the midline to form the cardiac fields.

  • First Heart Field (FHF): This initial population of cells fuses to form the primitive cardiac tube. For a long time, it was believed that the FHF gave rise to the entire heart. However, it is now known that the FHF primarily forms the left ventricle.

  • Second Heart Field (SHF): Discovered in the early 2000s, the SHF is a pool of progenitor cells located posteriorly and surrounding the heart. The SHF is crucial for heart growth, providing new cells and forming the right ventricle, atria, and outflow tract (the part of the great vessels derived from the heart itself). It constitutes almost three-quarters of the cells added to the heart during its formation.

    • Arterial Pole (Anterior SHF): Gives rise to the right ventricle and the beginning of the outflow tract.

    • Venous Pole (Posterior SHF): Gives rise to the atria, pulmonary veins, and cardinal veins.

• Other Cell Populations:

  • Neural Crest Cells: These cells, originating from the neural tube, migrate to the heart and contribute to the formation of a part of the great vessels and arterial valves, playing a significant role in outflow tract septation and smooth muscle cells of the vessels and aortic arches.

  • Epicardial Cells: These cells contribute to the formation of the coronary arteries.

• Genetic Regulation: Several critical genes regulate these early developmental stages, setting up the embryonic and cardiac axes:

  • Nodal and Pitx2: Important for establishing the right-left axis.

  • FGF8, Tbx5, CYP26: Involved in the antero-posterior axis.

    • Retinoic Acid Signalisation Pathway (Vitamin A): Crucial for determining anterior and posterior orientation in many organs. Interference with this pathway can cause severe malformations (e.g., isotretinoin use during pregnancy).

  • Cardiac differentiation gene: BMP/Isl1 genes.

  • Nkx2.5: The only gene expressed in pre-cardiac cells across all vertebrates. First described in flies. Its absence leads to no heart in flies, abnormal looping in mice, and conduction problems or rare malformations in humans. ASD, TOF and conduction problems have been described in relationship to this gene. 

Key Stages of Heart Morphogenesis

The heart's formation is a highly orchestrated process involving three fundamental stages: Looping, Convergence, and Wedging.

1. Cardiac Looping (D18-D23)

The primitive cardiac tube, initially straight, undergoes a fundamental transformation into a looped structure.

• Mechanism: The straight cardiac tube is fixed at its anterior (arterial) and posterior (venous) poles within the embryo. As the tube grows rapidly, its fixed ends force it to bend and fold, acquiring a specific helical, rightward looping shape (dextro-loop). This aligns the right and left ventricles in a horizontal plane, with the right ventricle positioned to the right and the left ventricle to the left.

  • Initially, the right ventricle is superior to the primitive left ventricle, which is important for understanding congenital heart defects.

• Right-Left Asymmetry: This crucial process is dictated by the primitive node, a structure expressing genes like Nodal and Pitx2. Cilia within the node rotate in a specific direction, creating a fluid flow that sends signals primarily to the left side of the embryo, establishing the left-right axis. This early signaling informs cardiac precursor cells on the left that they are "left" cells and those on the right that they are "right" cells. This information is transmitted to the Second Heart Field, enabling the creation of fundamental right-left asymmetry for cardiac anatomy.

• Clinical Relevance - Looping Anomalies: Problems with cilia function or left-right signaling can lead to laterality defects.

  • L-Loop (Levocardia): If the cardiac loop turns to the wrong side (leftward), the right ventricle will be on the left and the left ventricle on the right, which is an embryological L-loop.

  • Heterotaxy Syndromes: These are problems of laterality, often linked to genes that dictate left-right signaling.

    • Situs Inversus Totalis: Occurs when cilia are immobile (e.g., Kartagener syndrome) and the right-left formation is randomized. All organs are inverted but otherwise well-formed.

    • Heterotaxy Syndrome (Global Randomization): Leads to malformations of multiple organs (heart, colon, spleen) due to incorrect left-right signals. Must rule our primary ciliary dyskenesia. 

    • Partial Randomization: Anomalies of left-right signaling contained within the heart itself, such as doubly discordant atrioventricular connections, where atria are in situs solitus (normal position), but ventricles are inverted (L-loop), leading to atrioventricular discordance and often malpositioned great vessels.

• Primitive Heart Post-Looping: After looping, the primitive heart consists of a larger primitive left ventricle, a smaller primitive right ventricle, an outflow tract, and a nearly unique atrium that communicates only with the left ventricle through the atrioventricular canal.

2. Convergence (D40)

Convergence is a series of morphological displacements that follows looping, crucial for aligning heart segments and establishing proper septation.

• Key Transformations:

  • Ventricular Growth: The right ventricle grows faster than the left, leading to the alignment of both ventricles. This growth is driven by the rapid addition of myocardial cells from the Second Heart Field, differentiating under the influence of specific genes. Ventricles grow downwards via "ballooning".

  • Right AV Junction Formation: The atrioventricular canal initially connects only to the left ventricle. During convergence, the right AV junction (future tricuspid valve) is created by the expansion and excavation of the primitive annulus, moving into the right ventricle. This process explains the muscular vestiges seen in the right ventricle, like the moderator band and septal band, which are remnants of this muscular primitive annulus.

  • Outflow Tract Repositioning: The growth of the right ventricle allows the outflow tract to be repositioned more medially, contributing to segment alignment.

• Transition Zones: The primitive heart tube has transition zones that become critical structures:

  • Atrioventricular Canal: Becomes the future AV valves (mitral and tricuspid).

  • Primitive Annulus: Becomes the future interventricular septum.

  • Conotruncus: Becomes the future aortic and pulmonary outflow tracts.

  • Internal Curvature: Acts as a pivot for organizing AV and ventriculo-arterial junctions.

• Clinical Relevance - Convergence Anomalies: These anomalies are typically severe due to early developmental arrest.

  • Univentricular Heart: Results from a failure of ventricular growth or alignment, leading to a single functional ventricle, often with a double-inlet left ventricle. These are functionally univentricular and require palliative surgeries (e.g., Fontan).

  • Tricuspid Atresia: Occurs when the right AV junction fails to form, resulting in no communication between the right atrium and the "right ventricle", which is not really a ventricle because there is no inlet, but rather a "chamber".

  • Straddling/Overriding Tricuspid Valve: If tricuspid valve formation arrests partially, the valve can override both ventricles.

  • Double Inlet Right Ventricle (DIRV): This is a rarer and more complex malformation, difficult to explain solely by convergence anomalies. The genesis of DORV is complex and can arise from issues at multiple embryological stages, including looping, convergence, or wedging, or malformations of situs.

3. Septation

Once the heart segments are aligned after convergence, septation—the formation of internal divisions—begins. Proper septation requires aligned cavities and specific cellular populations like the Second Heart Field cells and endocardial cushions.

• Atrial Septation:

  • Venous Incorporation: Initially, the common atrium receives systemic veins symmetrically. The right horn of the sinus venosus is incorporated into the right atrium, forming the superior and inferior vena cava. The left horn involutes, leaving the coronary sinus, which usually drains into the RA-inferior vena cava area. If the left horn fails to involute, a persistent left superior vena cava can form, draining into the coronary sinus. Similarly, the left atrium is largely formed by the incorporation of the pulmonary veins, not just from the primitive atrium.

  • Atrial Septum Development:

    1. The septum primum descends from the roof of the common atrium towards the endocardial cushions of the AV canal. An opening, the foramen primum, initially exists at its lower edge.

    2. Apoptosis occurs in the superior part of the septum primum, forming the ostium secundum.

    3. Concurrently, the septum secundum (a thicker, more fibrous septum) grows downwards from the atrial roof, overlapping the ostium secundum.

    4. The space between the septum primum and septum secundum forms the foramen ovale, allowing blood to shunt from right to left in fetal circulation. At birth, increased left atrial pressure causes the septum primum and secundum to fuse, closing the foramen ovale.

  • Clinical Relevance - Atrial Septal Defects (ASDs):

    1. Ostium Primum ASD: Results from a failure of the septum primum to fuse completely with the endocardial cushions.

    2. Ostium Secundum ASD: Caused by excessive apoptosis in the septum primum (leading to a too-large ostium secundum) or an underdeveloped septum secundum.

    3. Sinus Venosus ASD (unroofing of a pulmonary vein into the SVC (superior) or IVC (inferior), by definition a partial anomalous pulmonary venous return): Less common, resulting from different embryological mechanisms.

  • Anomalous Pulmonary Venous Return (APVR): Often associated with a small left atrium because it does not receive the myocardial contribution from the pulmonary veins necessary for its proper growth.

• Atrioventricular Septation:

  • The endocardial cushions and vestibular spine at the AV canal are crucial for septation.

  • Failure of these structures to develop correctly leads to defects affecting both atrial and AV septation.

  • Clinical Relevance - Atrioventricular Septal Defects (AVSDs): These malformations arise from deficiencies in the endocardial cushions/vestibular spine. They range from partial (e.g., primum ASD with a unique AV valve) to complete AV canal (large primum ASD, large VSD, and a common AV valve).

• Interventricular Septation:

  • The interventricular septum (IVS) is composed of four parts:

    1. Inlet Septum: Formed by the endocardial cushions of the AV canal. Defects lead to inlet VSDs.

    2. Muscular Septum (Trabecular): The largest part, formed by compaction of the myocardium from the primitive annulus. Defects result from abnormal myocardial compaction.

    3. Conal Septum (Outflow Septum): Involved in the wedging process, initially large and then narrowing. Defects lead to conal VSDs (or outlet VSDs) and are associated with conotruncal anomalies (think of DiGeorge; example; TOF).

    4. Membranous Septum: A small, fibrous part that connects the other three septal components. It forms only if the other septa develop correctly. Perimembranous VSDs are the most common VSD type and are often extensions of defects in one of the other septal components.

4. Wedging (D45-D60)

Wedging is a pivotal stage where the great arteries (aorta and pulmonary artery) are properly positioned and septated, ensuring the correct outflow from the ventricles.

• Aortic Rotation and Septum Formation:

  • Initially, the outflow tract (future aorta and pulmonary artery) arises solely from the right ventricle.

  • The aorta, initially situated to the right, undergoes a rotation to align with the left ventricle, creating the aortic-mitral continuity (a direct fibrous connection between the aortic and mitral valves). In the normal heart, the aorta does not have a conus. The Pulmonary artery has a conus. 

  • Simultaneously, the pulmonary artery remains aligned with the right ventricle. This rotation causes the great vessels to cross normally.

  • The conal septum (also called aortopulmonary septum or outflow septum) forms concurrently with this rotation, separating the future aorta from the pulmonary artery. It fuses with the interventricular septum, closing the interventricular communication.

• Cellular Contributions to Wedging:

  • Cardiac Neural Crest Cells: These cells migrate from the neural tube into the outflow tract. They are essential for the septation of the outflow tract. Experimental ablation in chick embryos leads to the absence of outflow tract septation, resulting in a common arterial truncus. Partial ablation can lead to malalignment of the conal septum, causing defects like Double Outlet Right Ventricle (DORV) and Tetralogy of Fallot.

    • DiGeorge Syndrome: A human condition linked to deletions in the region where neural crest cells originate, characterized by conotruncal heart defects, thymic hypoplasia, and parathyroid issues, highlighting the crucial role of these cells.

  • Anterior Second Heart Field (ASHF): This population is vital for the elongation of the outflow tract. Without sufficient elongation, the outflow tract cannot properly rotate and align, leading to malformations. The ASHF also contributes to the formation of the conal septum.

  • Interaction: Neural crest cells and ASHF interact, and a defect in one can affect the other, exacerbating malformations.

• Outflow Tract Septation Mechanism: The outflow tract, initially a single tube, septates through:

  • Fusion of Cushions: Endocardial cushions within the outflow tract fuse like a "zipper" from proximal (ventricular) to distal (aortic arch).

  • Muscularization: The fused cushions muscularize to form the septum.

  • Spiraling: The great vessels undergo a spiraling rotation, ensuring they cross normally.

  • Connection to Aortic Sac: The distal part of the outflow tract connects to the aortic arch sac, which forms the 4th (aorta) and 6th (pulmonary artery, ductus arteriosus) aortic arches. Failure of the distal septum to close can result in an aortopulmonary window.

• Clinical Relevance - Conotruncal Defects (Wedging Anomalies): These are characterized by abnormal positioning and septation of the great vessels.

  • Tetralogy of Fallot (TOF): This complex defect (VSD, overriding aorta, pulmonary stenosis, right ventricular hypertrophy) is explained by a single embryological anomaly: anterior deviation of the conal septum. This malposition causes the aorta to override the VSD, obstructs the pulmonary outflow, and leads to right ventricular hypertrophy.

  • Truncus Arteriosus (TA): A severe defect characterized by a single great artery arising from the heart, with a large VSD, due to complete absence of outflow tract septation (no conal septum) and nearly absent wedging.

  • Pulmonary Atresia with VSD: Often on the severe end of the TOF spectrum.

  • Double Outlet Right Ventricle (DORV): This means both great arteries (aorta and pulmonary artery) arise entirely or predominantly from the right ventricle. DORV can have various embryological origins:

    • Early Looping Anomalies: Severely complex DORV, often associated with heterotaxy and AV septal defects.

    • Convergence Defects: DORV with uncommitted VSDs, often affecting left ventricular and mitral valve development.

    • Wedging Anomalies:

      • Insufficient Wedging (Fallot-type DORV): Aorta fails to position over the left ventricle, remaining dextroposed over the VSD (which is subaortic). This is seen as a less complete wedging than TOF.

      • Laterality Problem in Wedging (Transpo-type DORV): The pulmonary artery descends abnormally, resulting in a VSD (which is subpulmonary) under the pulmonary artery. The great vessels remain parallel.

  • d-Transposition of Great Arteries (d-TGA): In TGA, the aorta arises from the right ventricle and the pulmonary artery from the left ventricle, with parallel circulation. One hypothesis suggests it is an anomaly of wedging related to left-right laterality signaling rather than an arrest of rotation. The pulmonary valve might receive the wrong signal and position itself over the left ventricle, while the aorta remains over the right ventricle, and the vessels do not cross.

5. Valve Formation

Heart valves, both atrioventricular (AV) and semilunar (arterial), derive primarily from endocardial cushions, which are localized proliferations of cardiac jelly.

• General Valve Development:

  • Cardiac Jelly Transformation: The cardiac jelly, initially separating the myocardium and endocardium, largely disappears except at the transition zones (AV canal and outflow tract).

  • Epithelial-Mesenchymal Transition (EMT): Endocardial cells at these sites undergo EMT, transforming into mesenchymal cells that invade the cardiac jelly, forming the endocardial cushions.

  • Signaling: These cushions respond to signals from the myocardium and other populations like neural crest cells and epicardial cells, leading to muscularization and septation, as well as valve formation. Each leaflet of a valve has a specific embryological origin from different cushions.

• Semilunar Valves (Aortic and Pulmonary):

  • Identical Origin: A key feature is that the aortic and pulmonary valves are morphologically identical because they derive from the same principal cushions in the outflow tract and intercalated cushions. This anatomical similarity allows for procedures like the Ross intervention (replacing the aortic valve with the patient's own pulmonary valve).

  • Sculpting Process: They form by a combination of excavation (hollowing out) of the cushion mass and proliferation of peripheral cells. Apoptosis plays a critical role in sculpting the leaflets and forming the sinuses of Valsalva.

• Atrioventricular Valves (Mitral and Tricuspid):

  • Tricuspid Valve: Its formation is intimately linked to the "tricuspid funnel".

    • It involves excavation of the primitive annulus within the right ventricular muscle, pulling the endocardial cushions into the ventricle.

    • Leaflets form successively, with the anterior leaflet appearing first, followed by the posterior-inferior, and lastly the septal leaflet.

    • Unlike the anterior leaflet, the posterior-inferior and septal leaflets form by delamination (detachment) from the ventricular wall. This delamination explains why muscular vestiges are often found in the right ventricle.

    • Clinical Relevance - Ebstein's Anomaly: Results from an arrest in the delamination process of the tricuspid valve, where the septal and posterior leaflets remain partially attached to the ventricular wall, leading to apical displacement and tricuspid regurgitation.

  • Mitral Valve:

    • Forms differently from the tricuspid, without a funnel-like invagination.

    • The mural (posterior/inferior) leaflet delaminates from the ventricular wall, while the aortic (anterior) leaflet develops in continuity with the aorta and has no muscular component.

    • Its formation is linked to the wedging process and the establishment of aortic-mitral continuity.

    • Ebstein-like anomalies of the mitral valve are rare and involve the mural leaflet.

  • Papillary Muscles and Chordae Tendineae: Papillary muscles derive from the myocardium of the ventricular walls, while chordae tendineae are fibrous structures that develop from the valve leaflets.

    • Clinical Relevance - Parachute Mitral Valve: An anomaly of papillary muscle formation, where they are abnormally positioned, affecting valve function.

6. Aortic Arch and Coronary Artery Formation

• Aortic Arches:

  • Symmetrical Origin: The aortic arches begin as a symmetrical system of six pairs of arches connecting the ventral and dorsal aortae.

  • Remodeling: During the 5th week, these arches undergo significant remodeling, with some disappearing and others developing into the great vessels we recognize. For example, the 3rd arch forms the carotid arteries, the 4th arch forms the aortic arch and subclavian arteries, and the 6th arch forms the pulmonary arteries and ductus arteriosus.

  • Clinical Relevance - Aortic Arch Anomalies: These arise from abnormal involution or persistence of certain arches. Examples include double aortic arch (persistence of both 4th arches) or retro-esophageal subclavian artery (abnormal involution of parts of the arch system). Neural crest cells are implicated in their formation.

• Coronary Arteries:

  • Complex Origin: Unlike previous beliefs, coronary arteries do not sprout from the aorta but develop independently and then connect to it. They originate from three main populations: the pro-epicardium (located at the venous pole), the endocardium, and the sinus venosus.

  • Development Pathway: Cells from the pro-epicardium interact with the myocardium, undergo EMT, and invade the myocardium, then differentiate into endothelial cells to form vessels. These vessels then extend into the subepicardial space.

  • Connection to Aorta: The connection to the aorta is guided by precise molecular signals. A repulsive domain around the pulmonary artery prevents coronary arteries from connecting there, while a likely attractive domain in the aortic wall guides them to connect appropriately, usually at right angles within the sinuses of Valsalva.

  • Clinical Relevance - Anomalous Coronary Connections: If the repulsive domain around the pulmonary artery is absent or malformed, coronary arteries can connect abnormally, often to the pulmonary artery. These anomalies are often found in conotruncal heart defects because the degree of rotation of the outflow tract affects the development of these signaling domains. The neural crest also plays a role in guiding coronary artery trajectories.

7. Conduction System Formation

The heart's electrical conduction system, responsible for its rhythmic beating, also develops from specific embryological structures.

• Origin: The conduction system derives from the transition zones identified earlier:

  • The sinus venosus gives rise to the sinoatrial node (pacemaker) and intra-atrial conduction pathways.

  • The primitive annulus (between atria and ventricles) gives rise to the atrioventricular node and intraventricular conduction pathways.

• Early Function: The primitive cardiac tube begins contracting very early, but these contractions are slow and different from the mature heart's rhythm.

• Clinical Relevance: For the conduction system to form correctly, proper septation and alignment of heart segments are essential. Malformations, such as those found in doubly discordant hearts (where segments are misaligned) or severe septal defects, can lead to conduction abnormalities.

Reference: CPC M3C Necker Université de Paris Embryologie cardiaque et des malformations congénitales by Dr Ségolène Bernheim

• Rudolph AM. Congenital Diseases of the Heart: Clinical-Physiological Considerations. 3rd ed. Hoboken (NJ): Wiley-Blackwell; 2009. 

• Alboliras ET, Hijazi ZM, Lopez L, Hagler DJ, editors. Visual Guide to Neonatal Cardiology. Hoboken (NJ): Wiley; 2018.

Morphology of Atriums

• Rudolph AM. Congenital Diseases of the Heart: Clinical-Physiological Considerations. 3rd ed. Hoboken (NJ): Wiley-Blackwell; 2009. 

• Alboliras ET, Hijazi ZM, Lopez L, Hagler DJ, editors. Visual Guide to Neonatal Cardiology. Hoboken (NJ): Wiley; 2018.

Diagnostic Hierarchy of Congenital Heart Defects by the IPCCC