Hypoplastic left heart syndrome

Important Physiological Considerations

Blood enters the left atrium (LA) but encounters an obstruction at the LA/left ventricle (LV) level due to mitral valve (MV) atresia or stenosis. Consequently, flow to the right atrium (RA) depends heavily on the size and restriction of the inter-atrial shunt. If the shunt is restrictive or intact, these patients deteriorate very quickly after birth, often becoming pre-mortem. During fetal life, significant pulmonary venous congestion can develop despite low pulmonary blood flow (i.e.: high pulmonary vascular resistance in fetal life), leading to pulmonary vascular remodeling and congestion of lymphatic channels, which gives the lungs a "nutmeg" appearance on fetal MRI and sometimes on fetal echocardiography.

Post-natally, a septostomy may be necessary in the case of restrictive atrial septum (although very challenging since the left atrium is often severely underdevelopped, making the procedure often unachievable since it can be very difficult to either pass the balloon via the small inter-atrial opening or to even inflate the balloon in the extremely small LA to achieve a septostomy). Urgent cardiac surgery with surgical atrial septostomy may be necessary. 

Post-natally, as pulmonary vascular resistance (PVR) decreases, the Qp:Qs ratio progressively increases, raising the pulmonary venous return to the small LA. This increased pulmonary blood flow can cause the inter-atrial shunt to become more restrictive over time, progressively impeding post-capillary venous drainage and leading to pulmonary alveolar edema and ventilation-perfusion (V/Q) mismatch.

From the RA, blood flows into the right ventricle (RV) and then into the pulmonary artery (PA). Blood may either enter the pulmonary circulation or be shunted right-to-left through a patent ductus arteriosus (PDA) to supply the systemic circulation. Blood entering the systemic circulation will perfuse the lower body anterograde via the ductus, and feeding the transverse and ascending aorta retrograde (like in fetal life). As such, the small hypoplastic underdevelopped ascending aorta is supplied retrograde by the ductus arteriosus maintained patent by prostaglandins. The coronary arteries are also supplied retrograde and eventually their flow comes back to the right atrium via the coronary sinus. The balance between pulmonary and systemic blood flow (Qp and Qs) is determined by the PVR/SVR ratio (SVR; systemic vascular resistance). Pulmonary blood flow depends on pulmonary resistance, PDA size, and coronary blood flow, which is maintained by retrograde filling of the aorta through the PDA and feeds into the coronary sinus back to the RA.

As pulmonary blood flow increases at the expense of systemic flow (due to competition of PVR/SVR balance), the fraction of blood directed to systemic organs decreases, leading to a reduced volume fraction of systemic venous return. Consequently, the proportion of desaturated blood returning to the RA decreases, while the proportion of oxygenated blood returning to the LA increases (assuming no significant ventilation-perfusion mismatch leading to decreased pulmonary venous oxygen saturation). Therefore, rising systemic oxygen saturations in hypoplastic left heart syndrome (HLHS) indicate a relative decrease in systemic blood flow compared to pulmonary blood flow. As time passes, there can be significant pulmonary congestion and spilling within the pulmonary alveolis, leading to marked pulmonary edema. Pulmonary venous saturation will drop due to difficult passage of oxygen through the Alvelo-capillary membrane. The saturations may drop in this context. Hence, why, these patients are brought often for early first stage palliation to avoid excessive pulmonary flow at the expense of systemic ischemia. 

There are limited medical interventions available in the situation of Qp>>>>Qs in HLHS, but certain actions could inadvertently worsen the condition. It is crucial to avoid maneuvers that further reduce PVR relative to SVR. For mechanically ventilated patients (a situation that needs to be astutely monitored), CO₂ levels should be maintained within a range of permissive hypercapnia to avoid drop in PVR secondary to overventilation. Exposure to oxygen and the use of inhaled nitric oxide (iNO) should be avoided, as they are potent pulmonary vasodilators. In the past. the use of hypoxic mix was even considered to increase PVR - a practice that has been abandonned. See here.

Managing these patients is particularly challenging, as metabolic acidosis from decreased perfusion can lead to hyperventilation, which lowers CO₂ levels and further reduces PVR. In some cases, sedation may be used to prevent hyperventilation after intubation and mechanical ventilation. While this approach can help stabilize the PVR/SVR ratio, it may also reduce SVR, providing a temporary benefit. However, agents that increase SVR (vasopressors) could further compromise systemic blood flow and impair systemic ventricular function, especially in the presence of endocardial fibroelastosis (EFE) and tricuspid insufficiency.

• Variants of HLHS:​

• MS-AS (45%): mitral stenosis – aortic stenosis​ - This form exhibits considerable variability in LV size, the amount of antegrade flow, and the degree of LV systolic and diastolic dysfunction, depending on the severity of obstruction caused by the combined effects of mitral and aortic stenosis. The ascending aorta is generally larger than in cases with aortic atresia. There is overlap in the spectrum with patients who have critical aortic stenosis, allowing some to be considered for a two-ventricle repair.

• MS-AA (25%): mitral stenosis – aortic atresia : risk factor for decreased survival after stage 1 palliation; coronary cameral fistulas in half (abnormal coronary – LV fistulas). ​ In this form, the ascending aorta is severely hypoplastic, and systemic output remains ductal-dependent. Depending on the degree of mitral stenosis, LV pressures may be sub-systemic, systemic, or even supra-systemic. The extent of ventricular hypertrophy is variable, but severe LV systolic dysfunction is typically present.

• MA-AA (30%): mitral atresia – aortic atresia​ - This is the most extreme form of hypoplastic left heart syndrome (HLHS). The left ventricle (LV) is either diminutive or absent, and the ascending aorta is severely hypoplastic. Systemic output is entirely ductal-dependent, with retrograde flow in the ascending aorta.

• Rare Variant – Mitral Atresia, Aortic Stenosis, and Ventricular Septal Defect (VSD): This rare variant involves mitral atresia with a VSD, allowing limited flow into the rudimentary LV, which may enable some forward flow in the aortic arch. These patients also present with aortic stenosis. Reference 1, Reference 2.

• Important considerations:​

• Restrictive atrial septum​ / Intact atrial septum​

• EFE outlines that the myocardium has been chronically undersupplied with oxygen and perfusion during fetal life, leading to chronic ischemia and collagen deposition due to secondary fibrosis. This leads to abnormal cardiac performance (systolic and diastolic function can be impaired). Coronary system is being supported by retrograde flow in the small underdevelopped descending aorta via the ductus. 

• In HLHS, tricuspid valve becomes main Atrio-ventricular valve of the future systemic chamber. Increasing severity of tricuspid regurgitation is associated with poorer prognosis. ​ ​ ​ ​

• Pulmonary valve and main pulmonary artery will become the major systemic outflow. 

• Pulmonary circulation will eventually be dependent on passive flow from the systemic venous return to the pulmonary arteries. As such, abnormal pulmonary vasculature may jeopardize the eventual Fontan circulation. Low pulmonary vascular resistance and normal pulmonary venous drainage is key in favouring the Fontan setup. 

• HLHS with highly restrictive (RS) or intact atrial septum (IAS) causes LA and pulmonary vascular hypertension (HTN) during growth​: “Muscularisation” of vessels during organogenesis ; Lymphangiectasia: dilation of lympathic vessels​

• ​HLHS-RS/IAS results in post-natal hemodynamic instability due to impeded LA flow & marked pulmonary venous HTN​

  1. Outcomes poor with > 50 % mortality in neonatal period​

  2. Surgical atrial septostomy, early Norwood, fetal balloon septoplasty, and transcatheter atrial septostomy, have been used with variable results ​

• ​Despite improvement in overall survival reported in different series for HLHS-RS/IAS carry a poor long-term prognosis​

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.

The systemic right ventricle is inherently different from a morphologic left ventricle. Its internal morphology, including its muscular bands, apex, and particularly its tricuspid valve, is uniquely altered depending on the specific underlying congenital heart disease. These morphological particularities likely play a significant role in the eventual dysfunction observed in systemic right ventricles. Furthermore, the conduction pathways and coronary blood supply are frequently abnormal, contributing to the complexity of these conditions. Learn more in the morphology section.

Definition

The term "Hypoplastic Left Heart Syndrome" was initially suggested in 1958 by Drs. John A. Noonan and Alexander S. Nadas to describe a group of anomalies with an obstructive lesion (atresia or stenosis) on the left side of the heart, building on the work of pathologist Dr Maurice Lev. Lev himself had used the term "hypoplasia of the aortic outflow tract complex". For consistent use in studies and databases, the International Paediatric and Congenital Cardiac Code (IPCCC) is recommended. This standardized international system provides definitions for paediatric and congenital cardiac terms and is used by major databases like the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS CHSD) and the European Congenital Heart Surgeons Association (ECHSA) Congenital Database. The European Association for Cardio-Thoracic Surgery (EACTS) and the Association for European Paediatric and Congenital Cardiology (AEPC) also provide guidelines for HLHS management, further detailing its anatomical definitions.

Embryology

HLHS is considered an acquired disease of fetal life by Dr Robert Anderson (see Youtube Video below). This means the developmental insult that causes the condition occurs most likely after the closure of the embryonic intraventricular communication, rather than being a primary malformation of initial heart formation. The exact insult that stops the left ventricle from growing is currently unknown. The underlying cause is likely multifactorial. While often sporadic, some familial forms of left-sided heart obstruction exist, where certain family members might have conditions like coarctation or bicuspid aortic valves, and others exhibit HLHS. Rarely, specific genetic mutations, such as those in the NOTCH gene (also associated with bicuspid aortic valves), have been described, but monogenic deletions are not typically found in the majority of cases. A crucial factor in the abnormal development of the left heart chambers is the reduction of normal blood flow to the left cavities during prenatal development. A cavity needs normal blood flow to develop properly in the prenatal period. Thus, both genetics and insufficient blood flow are believed to contribute to the abnormal development of the left heart. In a fetus with HLHS, the left ventricle is unable to effectively support systemic circulation. The right ventricle takes over as the dominant ventricle. Blood from the pulmonary trunk passes through the arterial duct (ductus arteriosus) to supply the descending aorta. From there, blood flows retrogradely into the aortic arch to perfuse the coronary arteries and brain. Before birth, affected babies are generally not in hemodynamic distress.

In the extreme form of Mitral Atresia - Aortic Atresia, 100% of the combined foetal blood flow is directed to the right ventricle, with the left ventricle being virtually non-existent (0% flow). Despite this, foetal physiology ensures the preservation of organ blood supply. Pulmonary blood flow (7%) remains unchanged, and the descending thoracic aorta is normally perfused via a significantly enlarged ductus arteriosus. Due to the aortic atresia, the aortic isthmus is notably wider than in a normal heart because of the large flow from the PA to the Aorta via the ductus. There is typically no coarctation in this form of HLHS. There is, however, coarctation possibly in forms involving a "small left ventricle" (mitral stenosis). The ascending aorta is miniscule because it is fed retrograde via the ductus and the flow through it is very limited. This condition serves as a clear demonstration of how morphogenesis is directly linked to the absence of a ventricle (due to absence of flow from the absence of a mitral valve opening) and the resulting altered blood flow reducing significantly the size of the ascending aorta. If there is a small left ventricle (not completely atretic, with a patent mitral and aortic valve but reduced flow), the physiology differs significantly. For example, if 25% of the combined foetal blood flow goes to the left ventricle, and only 1% reaches the isthmus after perfusing the brain and coronaries, this can lead to quasi-atretic isthmus, a nearly interrupted aortic arch of type A, or a very severe coarctation. This illustrates how the presence or absence of flow fundamentally shapes the structure.

Pathophysiology & Hemodynamics

HLHS involves a spectrum of anatomical anomalies, primarily affecting the left ventricle (LV), mitral valve (MV), aortic valve (AoV), and aorta (Ao).

• Definition: HLHS is a heterogeneous group of congenital cardiac anomalies characterized by a hypoplastic or virtual left ventricle, which typically does not form the apex of the heart, along with hypoplasia or atresia of the aorta and/or mitral valve.

• Functional Single Ventricle: A key feature of HLHS is that the heart functions as a single ventricle, with the morphologically right ventricle (RV) supporting the entire systemic circulation.

• Systemic Circulation: In severe forms, such as mitral atresia (MA) and aortic atresia (AA), or mitral stenosis (MS) and aortic atresia (AA), the systemic blood flow (Qs) is entirely dependent on the right ventricle and retrograde flow through the ductus arteriosus (DA) to perfuse the aortic arch and ascending aorta.

• Crucial Postnatal Structures: For postnatal survival, the ductus arteriosus must remain open (patent), and there must be adequate mixing of blood at the atrial level.

• Restrictive Atrial Septum: A significant pathological feature is a restrictive or closed foramen ovale (FO) or an intact atrial septum (IAS). This prevents adequate left-to-right shunting of oxygenated blood from the pulmonary veins into the right atrium, leading to:

  • Left atrial hypertension.

  • Pulmonary venous congestion and pulmonary edema.

  • Severe hypoxemia.

  • Abnormal lung development, including pulmonary cystic lymphangiectasia and muscularization of the pulmonary veins, which can persist postnatally. This can result in unacceptably high pulmonary vascular resistance (PVR).

  • Three distinct patterns of atrial cavity and septum have been recognized in cases with intact or restrictive FO:

    • Type A: Characterized by a relatively large left atrium (LA), a thick septum secundum, a thin septum primum (often deviated leftward and posteriorly), and massively dilated pulmonary veins. Decompression pathways to the innominate vein, right superior vena cava (SVC), and right atrium (RA) are typically unobstructed.

    • Type B: Features a small, muscular LA with circumferential thickening of the atrial walls and a thick, "spongy" muscular atrial septum, without clear distinction between septum primum and secundum. Pulmonary veins are usually small.

    • Type C: Presents with a giant LA and a thin, rightward-bulging septum (with identifiable septum primum and secundum), often in the setting of severe mitral regurgitation. Pulmonary veins are typically large.

• Coronary Circulation Anomalies:

  • The coronary arteries are typically normal in origin but can be affected by retrograde flow.

  • In cases of MS/AA, ventriculocoronary connections or fistulas may be observed. These are hypothesized to occur due to a hypertensive LV.

  • Microscopic fistulous communications between the ventricular cavities and coronary arteries are reported in 90% of cases upon histological examination.

  • Overt, ectatic coronary arteries with fistulous communications are considered a very bad prognostic feature.

Classification

• Mitral Atresia (MA) / Aortic Atresia (AA): This represents one of the most severe forms of HLHS. In this configuration, the LV is often "slit-like" with a flattened appearance, and there is typically no endocardial fibroelastosis (EFE) because no blood flows into the ventricle. 

• Mitral Stenosis (MS) / Aortic Atresia (AA): In this subtype, the aortic outflow tract is atretic, but the mitral valve is stenotic, allowing some blood to enter the hypoplastic left ventricle. This can be associated with overt fistulous communications between the left ventricle cavity and the coronary circulation. 

• Mitral Stenosis (MS) / Aortic Stenosis (AS): This involves stenosis of both the mitral and aortic valves. In such cases, there may be a "small LV cavity with a thick parietal wall," where EFE is often recognizable as a firm, whitish layer on the LV endothelial surface, contributing to the stiffness of the LV. 

• Mitral Atresia (MA) / Aortic Stenosis (AS) + Ventricular Septal Defect (VSD). 

• Hypoplastic Left Heart Complex (HLHC): This is considered the milder end of the HLHS spectrum. It is characterized by underdevelopment of the left heart structures, including a significantly hypoplastic LV and hypoplasia of the aortic valve or mitral valve (or both), without intrinsic valvar stenosis or atresia of these valves. The valves are described as "minute" but not intrinsically stenotic. In HLHC, the miniaturized aortic and mitral valves are commensurate in size with the left ventricle. The potential for biventricular repair is greater in these cases compared to other HLHS subtypes. 

• Conditions Excluded from the HLHS Definition 

  • It is important to note that certain conditions, even if they involve a small left ventricle, are generally not included in the definition of classical HLHS according to the International Nomenclature Committee and guidelines from professional associations. These exclusions typically include: Double outlet right ventricle (RV) with a small LV; Double Discordance ("Congenitally corrected transposition of the great arteries") with a large VSD and a small LV; Unbalanced atrioventricular septal defect (AVSD) with a small LV; Long-segment subaortic AS with AS, VSD, and Ao arch hypoplasia; Cases that might have transposition.

Clinical Findings & Diagnosis

The diagnosis of HLHS is most frequently made prenatally, but also presents clinically after birth.

• Prenatal Diagnosis:

  • Timing: HLHS is very often diagnosed during the 20th-week fetal ultrasound due to visible asymmetry of the cardiac cavities. While classic forms with severe LV hypoplasia can be detected as early as 11-14 weeks, they are more commonly identified during the standard 18-22 week fetal anatomy screening.

  • Fetal Echocardiography: This is the primary diagnostic tool. Key views for assessment include:

    • Four-chamber view: Demonstrates size discrepancy between the right and left heart chambers.

    • Outflow tract views and three-vessel tracheal view: Allow comparison of pulmonary artery, ductal arch, and aortic arch sizes, which can reveal early markers of evolving HLHS.

  • Associated Findings: Fetal HLHS cases tend to be smaller than normal, with declining growth rates in late gestation. Evaluation for extracardiac abnormalities and chromosomal anomalies is also important.

• Postnatal Presentation:

  • Newborns with HLHS are typically born at term. They are often smaller babies, weighing around 2.8-2.9 kg.

  • The clinical condition postnatally depends on the patency of the ductus arteriosus, the quality of pulmonary vein drainage, coronary and cerebral perfusion, and the function of the right ventricle and tricuspid valve.

  • Initial Stability: Babies may appear stable at birth because the ductus arteriosus is still open, allowing systemic blood flow. However, as the DA naturally constricts and pulmonary vascular resistance falls in the first few days of life, an imbalance in blood flow occurs, leading to low systemic output.

  • Signs of Deterioration:

    • Poor perfusion: Pale, poorly perfused newborn with high heart rate and low-volume pulses.

    • Respiratory distress: Tachypnea (rapid breathing), particularly with high oxygen saturation (>93%), can indicate severe heart failure.

    • Cyanosis: Deep cyanosis and respiratory distress are immediate signs if there is a highly restrictive FO/IAS or obstructed total anomalous pulmonary venous drainage (TAPVD).

    • A medium-frequency murmur and hyperactive precordium may occur with heart failure-related tricuspid regurgitation.

• Differential Diagnosis:

  • HLHS must be differentiated from other common left-sided obstructions such as aortic stenosis, coarctation of the aorta, or interrupted aortic arch.

  • Sepsis often presents with very similar symptoms to HLHS, and misdiagnosis is common initially.

  • Echocardiography is the gold standard for definitive diagnosis and differentiation from other conditions.

Echocardiography Findings

Echocardiography is the essential imaging modality due to its non-invasive nature and availability. A full sequential segmental echocardiographic examination is crucial.

• Left Ventricular Morphology: Four main patterns are recognized:

  • "Slit-like ventricle": A flattened, virtual LV in the posterior ventricular mass, often identified by coronary vessels encircling it. This is typically associated with mitral atresia (MA) and aortic atresia (AA). No valve tissue or endocardial fibroelastosis (EFE) is detected, and the atrioventricular (AV) junction is muscular.

  • "Miniature LV": Has a nearly normal size and wall thickness but does not form the cardiac apex. Associated with anatomically normal (small but not stenotic) aortic and mitral valves, as seen in MS and AS cases. Sometimes termed Hypoplastic Left Heart Complex (Dr C. Tchervenkov). Hypoplastic Left Heart Complex: This specific subgroup, characterized by a small left ventricle but proportionally sized mitral and aortic valves, may offer a rare opportunity for biventricular repair

  • "Small LV cavity with a thick parietal wall": Typically associated with a range of aortic valve malformations (stenotic or atretic) and mitral stenosis. EFE is usually recognizable as a firm, whitish layer on the LV endocardial surface, contributing to LV stiffness.

  • LV "Dilation": Associated with mitral regurgitation, leaflet redundancy, a thin LV parietal wall, and a giant left atrium that can compress the right heart chambers.

• Mitral Valve (MV):

  • In MA, the MV may appear as a nodule of white tissue.

  • In MS, the valve can have thick leaflets, short thick chordae, and small papillary muscles, often coated with EFE. Dysplasia of leaflets is common.

• Aortic Valve (AoV):

  • In AA, an imperforate membrane typically guards the hypoplastic annulus, though three well-formed commissures might still be identifiable.

  • Congenital aortic stenosis (AS) shows restricted cusp excursion and often post-stenotic dilation of the ascending aorta. It can present as a dysplastic tricuspid valve, bicuspid valve, or a unicuspid severely stenotic valve with annular hypoplasia.

• Aortic Arch & Ascending Aorta:

  • The ascending aorta (Asc Ao) and aortic arch are typically hypoplastic to varying degrees, reflecting the amount of blood flow through the left heart. They are consistently narrower than the pulmonary trunk.

  • The ascending aorta and aortic arch are narrowest in MA/AA subtypes.

  • Coarctation of the aorta (CoA) is a very common associated anomaly, coexisting in at least 80% of affected infants.

• Atrial Septum:

  • Assessment of the atrial septum is critical, as a restrictive FO (r-FO) is reported in 25% of cases and an intact atrial septum (IAS) in 1-6% of series.

  • Indicators of restriction include high-velocity Doppler flow, leftward bowing of the atrial septum, and dilation of the left atrium and pulmonary veins.

  • "A-wave reversal" (flow from the atrium into the pulmonary veins during atrial contraction) on pulmonary vein Doppler assessment is a significant sign of severe restriction.

• Coronary Arteries:

  • Coronary arterial origins are typically normal.

  • Coronary artery-to-ventricular cavity fistulas (ventriculocoronary connections) can be observed, particularly in the MS/AA subtype where the LV is often globular. These are best visualized by lowering the color Doppler scale.

• Right Ventricle (RV) and Tricuspid Valve (TV):

  • The RV is typically well-developed as it handles the entire systemic circulation in HLHS.

  • Poor RV function is a predictor of mortality throughout surgical palliation.

  • The tricuspid valve can show some degree of leaflet dysplasia and subvalvular apparatus abnormalities. Significant tricuspid regurgitation (TR) is a poor prognostic factor, especially if noted prenatally.

Management

The management of HLHS typically involves a staged palliative surgical approach aiming for a functional single ventricle circulation, though in rare cases, biventricular repair or heart transplantation may be considered.

• Prenatal Intervention:

  • Fetal Atrial Septostomy/Stent Implantation: For fetuses with HLHS and a severely restrictive FO or IAS, fetal intervention can be offered to decompress the left atrium. Criteria include FO diameter <1mm, pulmonary venous Doppler patterns consistent with high atrial pressure (e.g., to-and-fro flow), and A-wave duration >90 ms. While successful in a good proportion of cases, long-term outcomes can still be poor due to irreversible pulmonary vascular changes.

  • Fetal Aortic Valvuloplasty: For fetuses with critical aortic stenosis and evolving HLHS (where there is potential for LV growth), this procedure aims to decompress the LV and augment flow across left-sided structures, potentially improving the likelihood of a biventricular circulation at birth.

• Postnatal Stabilization (Prior to Surgery):

  • The primary goal is to stabilize the newborn and prepare for reconstructive surgery.

  • Prostaglandin E1 (PGE1) infusion: Essential to maintain patency of the ductus arteriosus, which ensures systemic blood flow. The lowest effective dose (0.005 to 0.02 mcg/kg/min; 5–20 ng/kg/min) is typically used to avoid side effects like apnea when initiated from birth. Much higher dosages are needed when the diagnosis is post-natal and the ductus is restrictive, closing, or closed.

  • Avoid excessive oxygen and intubation/ventilation (if stable): These measures can excessively lower pulmonary vascular resistance, leading to high pulmonary blood flow at the expense of systemic circulation, and are linked to higher complications.

  • Promote Systemic Blood Flow: This is critical to optimize systemic oxygen delivery. An ideal arterial oxygen saturation (SaO2) range of 75% to 85% is targeted. Pulmonary vasodilation is discouraged and avoided. As such, iNO, pulmonary vasodilators, systemic vasoconstrictors (may favour less Right to Left ductal shunt), low CO2, high pH, alkalosis (bicarbonate), and oxygen may favour lower PVR with more systemic steal. 

  • Emergency Interventions: Newborns with restrictive DA, r-FO, TAPVD, or high Qp may require immediate transcatheter or surgical intervention for stabilization. For instance, balloon atrial septostomy or stent placement can be performed for r-FO/IAS.

• Staged Surgical Palliation:

  • Stage 1: Norwood Procedure: This is typically performed within the first week of life. It involves:

    • Aortic Arch Reconstruction: The hypoplastic ascending aorta and main pulmonary artery (MPA) are conjoined to create a new, larger "neoaorta" to supply the systemic circulation (DKS - Damus-Kaye-Stansel - procedure). Excision of ductal tissue is important to prevent re-stenosis of the reconstructed arch.

    • Systemic-to-Pulmonary Shunt Creation: To provide controlled pulmonary blood flow, a shunt is created. Two main types:

      • Modified Blalock-Taussig-Thomas shunt (MBTTS): Connects a systemic artery (e.g., innominate artery) to a pulmonary artery.

      • Right Ventricle-to-Pulmonary Artery (RV-PA) conduit (Sano shunt): Connects the right ventricle directly to the pulmonary artery.

      • Read more on this in the single ventricular section.

    • Atrial Septectomy: A wide resection of the septum primum or creation of an adequate interatrial communication is performed to ensure unobstructed mixing of oxygenated and deoxygenated blood.

  • Hybrid Stage 1 Palliation (h-S1P): This approach avoids cardiopulmonary bypass (CPB) and open-heart surgery in the neonatal period. It is often used for high-risk neonates or to delay complex surgery. Components include:

    • Bilateral Pulmonary Artery Banding (b-PAB): Bands are placed on both pulmonary arteries to restrict blood flow to the lungs and prevent pulmonary overcirculation. This is done in expert centers with experience as the banding may distort architecture of the pulmonary arteries, or lead to excessive banding with resultant decreased pulmonary vascular growth (a big concern for the single ventricular montage). 

    • Ductus Arteriosus Stenting (DAS): A stent is placed in the ductus arteriosus to maintain its patency and ensure systemic blood flow.

    • Atrial Septal Manipulation: Can be performed to ensure adequate interatrial communication.

  • Interstage Management (IS-1): This is the period between Stage 1 palliation (Norwood or hybrid) and the next surgical stage. Home monitoring programs (or sometimes hospital-based monitoring for high-risk scenarios) are crucial to reduce the high risk of sudden interstage mortality. Optimal growth and development through adequate nutrition are key goals.

  • Stage 2: Bidirectional Cavopulmonary Shunt (BCPS) / Glenn Procedure: Typically performed around 3-6 months of age. The superior vena cava (or, if more than one SVC, superior caval veins) is (are) connected directly to the pulmonary arteries, directing deoxygenated blood passively to the lungs.

  • Stage 3: Fontan Operation: Ideally performed around 3-5 years of age. This completes the functional single ventricle circulation by connecting the inferior vena cava (and/or hepatic veins) to the pulmonary arteries, thus fully separating systemic and pulmonary circulations.

• Left Ventricular Recruitment/Rehabilitation: In milder forms of HLHS or HLH complex where the LV has some potential, strategies like resection of endocardial fibroelastosis (EFE), restriction of atrial septal defects (to increase LA filling pressure and LV end-diastolic pressure, leading to stenting of the LV cavity), and management of aortic/mitral stenosis may be attempted to promote LV growth and allow for a biventricular repair. However, success is variable, especially if EFE is extensive and deep within the myocardium.

• Heart Transplantation: Can be a primary treatment option if single ventricular palliation is failing or difficult to achieve based on various factors, or as a "fourth stage" for Fontan failure in older patients.

Prognosis & Prognostic Factors

Untreated HLHS is universally fatal. With modern surgical and medical management, outcomes have significantly improved, but it remains a condition with higher morbidity and mortality.

• Overall Survival: HLHS is reported to account for 23% of neonatal deaths from congenital heart malformations. Survival rates vary significantly based on initial anatomy, associated anomalies, and surgical strategies. Long-term survivors of the Fontan operation may eventually require a heart transplant due to Fontan failure.

• Negative Prognostic Factors:

  • Intact or Highly Restrictive Atrial Septum (IAS/r-FO): This is a very severe risk factor for early and late death. It is associated with pulmonary vascular disease, pulmonary lymphangiectasia, and high perinatal/perioperative mortality (exceeding 50% in some series).

  • Obstructed Totally Anomalous Pulmonary Venous Drainage (TAPVD): This is also a severe risk factor, with significantly higher mortality rates.

  • Ventriculocoronary Artery Fistulas: Particularly associated with the MS/AA variant, these connections have been linked to worse outcomes, though some data conflict.

  • Impaired Right Ventricular Function and Significant Tricuspid Regurgitation (TR): Both are poor prognostic factors, significantly increasing mortality and morbidity during staged palliation and potentially preventing Fontan completion. Severe TR at birth is particularly challenging. Tricuspid valve is the systemic atrio-ventricular valve. 

  • Small Ascending Aorta Diameter (<2mm): This carries a slight to moderate increased risk for death following Stage 1 palliation (Norwood procedure).

  • Genetic or Chromosomal Abnormalities: These are strong and consistent risk factors for poor outcomes, both in-hospital and late. 

  • Low Birth Weight (<2.5 kg): This is a risk factor for Stage 1 palliation, posing technical and physiological challenges.

  • Need for Extracorporeal Membrane Oxygenation (ECMO) Post-Stage 1 Palliation: Indicates severe post-operative instability and is a highly significant risk factor for postoperative death, with predicted hospital survival of only 25-30% in these circumstances.

  • Shunt Type (in Norwood): The Single Ventricle Reconstruction Trial (SVRT) found that Stage 1 palliation with a modified Blalock-Taussig-Thomas shunt was associated with a higher interstage mortality risk than with an RV-PA conduit, especially in patients with no or mild TR.

  • Endocardial Fibroelastosis (EFE): Its presence points towards functional univentricular repair as opposed to biventricular repair. The extent and depth of EFE in the myocardium can affect the feasibility and success of LV rehabilitation.

Epidemiology

HLHS is a relatively rare but significant congenital heart defect.

• Prevalence: It represents 1% to 3.8% of all congenital heart defects. In Canada and the USA, the phenotype occurs in approximately 0.016% to 0.036% of live births. Estimates for Germany, Croatia, and Belgium show similar incidences.

• Mortality Impact: Despite its lower prevalence compared to other heart defects (2-9% of congenital heart disease cases), HLHS accounts for a disproportionately high percentage of neonatal deaths, specifically 23% of neonatal deaths from congenital heart malformations.

• Trends: There has been a tendency towards a lower prevalence of HLHS over the last decade in some regions. This is largely attributed to the increasing prevalence of accurate fetal diagnosis, which allows for decisions regarding termination of pregnancy.

The "levocardinal" vein, which is neither levo or cardinal.

The levoatrial cardinal vein, also sometimes referred to as the levocardinal vein, is a specific type of collateral venous channel that can develop in individuals with hypoplastic left heart syndrome (HLHS). It acts as an overflow pathway for an obstructed left atrium, especially when the atrial septum is restrictive or intact.

Here's a breakdown of what the sources and our conversation indicate about the levoatrial cardinal vein:

• Function and Anatomy

  • In cases of HLHS, particularly when there is an intact atrial septum (IAS) or a restrictive foramen ovale (r-FO), the left atrium (LA) can become obstructed because blood struggles to pass into the hypoplastic left heart structures.

  • The levoatrial cardinal vein serves as a collateral venous channel that originates from the roof of the left atrium, travels through the mediastinum, and terminates in the superior caval vein (SVC), providing an alternative drainage route for the LA.

  • Its presence suggests a lack of normal communication between the atria.

• Clinical Significance in HLHS

  • A restrictive foramen ovale (r-FO) or intact atrial septum (IAS) can lead to left atrial hypertension and abnormal lung development, including pulmonary cystic lymphangiectasia and pulmonary vein muscularization. The levoatrial cardinal vein helps to decompress the left atrium in such scenarios.

  • If retrograde flow is observed in a levoatrial cardinal vein, it is a strong indicator to suspect an r-FO or IAS. This is particularly relevant in the context of HLHS with IAS, which is associated with maldevelopment of the pulmonary vasculature and a very high mortality rate.

  • While the presence of such a vein can provide an overflow for the obstructed left atrium, it can also be associated with obstruction of pulmonary venous drainage, which has prognostic importance for pulmonary vascular resistance (PVR).

• Detection

  • Superiorly directed flow from the LA through a persisting levoatrial cardinal vein should be actively sought during echocardiographic assessment.

• Nomenclature Debate

  • Levo- means "left". "Cardinal": Cardinal veins are a pair of major venous channels present in early vertebrate embryos and primitive adult vertebrates. They are crucial for draining blood from the developing body, with anterior cardinal veins handling drainage from the head and posterior cardinal veins handling drainage from the trunk.

  • There is a recognized issue with the name "levoatrial cardinal vein". It is "neither levo atrial nor cardinal". It is simply a "collateral channel" or "collateral pulmonary to systemic venous channel," but the term persists in common usage.

References:

• M3C-Carpedem. DIU 2020 C OVAERT Hypo VG [Video]. https://youtu.be/iAyvBJkKxsM?list=TLGG2og_3UK4_N8yMDA3MjAyNQ 

• Congenital Heart Academy. HYPOPLASTIC LEFT HEART SYNDROME [Video]. https://youtu.be/dSyoEkMg0TA?list=TLGGHARrTYx3ClwyMDA3MjAyNQ 

• Congenital Heart Academy. Hypoplastic Left Heart Syndrome [Video]. https://youtu.be/I19B31MGcDQ?list=TLGGme8s9IhdhQ4yMDA3MjAyNQ 

• Alphonso N, Angelini A, Barron DJ, Bellsham-Revell H, Blom NA, Brown K, et al. Guidelines for the management of neonates and infants with hypoplastic left heart syndrome: The European Association for Cardio-Thoracic Surgery (EACTS) and the Association for European Paediatric and Congenital Cardiology (AEPC) Hypoplastic Left Heart Syndrome Guidelines Task Force. Eur J Cardiothorac Surg. 2020;58:416–99. doi:10.1093/ejcts/ezaa188.

Guidelines for the management of neonates and infants with hypoplastic left heart syndrome: The European Association for Cardio-Thoracic Surgery (EACTS) and the Association for European Paediatric and Congenital Cardiology (AEPC) Hypoplastic Left Heart Syndrome Guidelines Task Force

Echocardiography examples

Example 1

Example 2

Example 3

Some restriction at the level of the inter-atrial septum with a mean gradient of 6.5 mmHg. The Peak by CW-Doppler gives 15 mmHg. This patient requires early stage-1 with atrial septal opening, or an atrial septostomy if the surgery must be delayed. 

Example 4

Example 5

In this one there is a hypoplastic left ventricle (non-apex forming), a hypoplastic mitral valve annulus and a hypoplastic aortic valve and arch. Although the 4 cavities are formed, we can appreciate how this LV will have difficulties handling the entire pulmonary venous return preload and sustain eventually systemic afterload, and generate sufficient output. Many of these patients will require a single ventricular palliation. 

Presentation by Dr Sariya Sahussarungsi (NH Fellow) and Laila Wazneh (NNP) - 2024

Presentation on HLHS by Shiran Moore and Laila Wazneh - 2021