Total Anomalous Pulmonary Venous Return

Anomalous Pulmonary Venous Connection refers to a condition where the pulmonary veins, which normally carry oxygenated blood from the lungs to the left atrium, drain instead into the right atrium or systemic venous circulation. This anomaly can be Total Anomalous Pulmonary Venous Return (TAPVR), where all pulmonary veins connect anomalously, or Partial Anomalous Pulmonary Venous Return (PAPVR), where only some veins connect anomalously. TAPVR is further classified based on where the veins drain: above the heart (supracardiac), to the heart (intracardiac), or below the heart (infracardiac). There is also a "fourth type," or mixed type, where veins drain to various locations.

Developmental Considerations and Classification

The development of the pulmonary veins is a complex process. The lungs and tracheal tree originate from the foregut, while the pulmonary vascular bed develops from the splanchnic plexus. Eventually, the splanchnic veins establish a connection with the common pulmonary vein, which is then incorporated into the left atrium. The precise site of the common pulmonary vein's development remains a subject of debate.

Pulmonary venous anomalies are broadly categorized as follows:

• Abnormal Connection: At least one pulmonary vein (partial anomalous) or all pulmonary veins (total anomalous) connect to a location other than the left atrium.

• Abnormal Drainage: This usually coincides with abnormal connection, but exceptions exist. For example, right pulmonary veins in a normal location may drain to the right atrium due to a deviated or displaced septum primum. Another scenario is hypoplastic left heart syndrome (HLHS) with mitral atresia and an intact atrial septum, where pulmonary veins connect normally but develop alternative pathways (levo-atrial cardinal veins) to the systemic venous circulation due to severe obstruction to flow from the left atrium. Conversely, abnormal connection can occur with normal drainage, seen when pulmonary veins form a confluence and connect to a left superior vena cava (LSVC) that then drains directly into the left atrium.

• Disease within the Pulmonary Veins: This includes pulmonary vein stenosis or atresia, and pulmonary veno-occlusive disease, which carry a very poor prognosis.

• Abnormal Common Pulmonary Vein Absorption: This leads to cor triatriatum, sometimes referred to as "divided left atrium".

It is important to differentiate between "venous drainage" and "venous connection." Connection refers to where the veins physically attach, while drainage refers to where the blood ultimately flows. For instance, in HLHS, the connection is normal to the left atrium, but drainage is abnormal because the blood cannot exit the left atrium normally.

Total Anomalous Pulmonary Venous Return (TAPVR)

TAPVR is a critical condition because it results in oxygenated blood mixing with deoxygenated blood, leading to cyanosis and, potentially, pulmonary hypertension. The presence of an atrial level shunt (e.g., patent foramen ovale or atrial septal defect) is essential for survival, allowing some oxygenated blood to reach the systemic circulation. The left atrium is underfilled and the right atrium receives the entire systemic and pulmonary venous return, leading to an obligatory right to left shunt at the atrial level. 

1. Supracardiac TAPVR (Above the Heart – Type 1). Supracardiac (approx. 45%): The vertical vein connects somewhere above the heart. The pulmonary veins typically form a horizontal confluence behind the LA. The vertical vein can connect to the innominate vein, right SVC, or a left SVC if present. Increased SVC flow is often observed. A "hemodynamic vice" can cause obstruction when the vertical vein passes between the right pulmonary artery (RPA) and the bronchus. If unobstructed, supracardiac TAPVC can lead to a "snowman appearance" on chest X-ray due to the dilated vertical vein, innominate vein, and SVC. In this type, pulmonary veins drain into a vertical vein that ascends to the innominate (or brachiocephalic) vein, then to the superior vena cava (SVC), and finally to the right atrium.

• Anatomical Characteristics:

  • The innominate vein is typically much larger than the ascending aorta because it carries a significantly larger volume of blood flow (pulmonary flow plus systemic flow).

  • The vertical vein is situated just in front of the brachiocephalic artery.

• Imaging Techniques:

  • Sagittal scan plane can reveal the vertical vein ascending from the heart into the brachiocephalic vein and then into the SVC and right atrium.

  • Subcostal coronal image is a useful technique to visualize the confluence of veins draining into the vertical vein.

  • The "crab view" from the suprasternal notch is a very effective way to see four (or more) pulmonary veins draining from below, with the right pulmonary artery and ascending aorta also visible.

• Hemodynamic and Obstruction:

  • This is a significant complication, occurring in approximately 60% of Type 1 TAPVR cases.

  • Cause: Obstruction occurs when the vertical vein drains behind the pulmonary artery and in front of the bronchus, creating a "hemodynamic vice".

  • Consequences: Leads to severe obstruction, pulmonary edema (visible on X-ray), and an undulating clinical course in infants, often misdiagnosed as primary pulmonary hypertension. The cardiac output falls when obstruction is severe, causing pulmonary pressure to drop, which temporarily relieves the vice, leading to a cycle of improvement and worsening.

  • Doppler Findings: Expect to see high-velocity, continuous flow (e.g., 1-2 meters per second) at the site of obstruction, whereas normal pulmonary venous flow is low velocity. A pullback from low to high velocity confirms the obstruction.

• Variations:

  • Azigos Vein Drainage: Some patients have drainage into the azigos vein, which then drains into the SVC. This is an important observation, as it is commonly found with right isomerism (asplenia). The "Tauzik sign" (floppy, mobile heart due to lack of anchoring by pulmonary veins) can be observed with this variation.

  • Levoatrocardial Vein: Often associated with hypoplastic left heart complex. This "vertical vein" typically comes off the origin of the left pulmonary artery. It is considered a misnomer, with "left vertical vein" being a more accurate term. Mild obstruction in this vein can lead to persistent pulmonary hypertension.

2. Intracardiac TAPVR (To the Heart – Type 2). Cardiac (approx. 25%): Usually drains directly to the coronary sinus, but occasionally directly to the right atrium. When draining to the coronary sinus, it appears markedly dilated with a characteristic "whale's tail" appearance. Pulmonary veins drain directly into the heart, most commonly to the coronary sinus or, less frequently, directly to the right atrium.

• To the Coronary Sinus:

  • Anatomy: The pulmonary veins drain into an enlarged coronary sinus, which then empties into the right atrium. This enlarged coronary sinus often bulges into and indents the left atrium, making it appear extremely small.

  • Echocardiographic Recognition: Easily recognized from subcostal coronal imaging. A characteristic sign is the "whale tail sign," where the enlarged coronary sinus resembles a whale's tail from the back of the heart.

  • Obstruction: Obstruction is very rare in this type of TAPVR, making it generally not a surgical emergency.

• Directly to the Right Atrium:

  • This condition is less common and often found in patients with isomeric conditions.

  • It can be misdiagnosed as an atrial septal defect (ASD) (specifically, ostium secundum ASD) if a surgeon finds the veins draining to the right atrium and simply patches them into the right atrium without full recognition of the anomaly.

  • The key differentiator from a true ASD is that in TAPVR, the pulmonary veins are not draining into the left atrium, and the right-to-left shunt occurs across the oval fossa (foramen ovale).

  • Sagittal imaging is an important complement to coronal imaging for complete analysis.

3. Infracardiac TAPVR (Below the Heart – Type 3). Infracardiac (approx. 20%): The vertical vein connects somewhere below the diaphragm, typically to the ductus venosus, portal system, or gastric vein. It does not connect directly to the IVC. The pulmonary veins often form a vertical confluence in an "upside down Christmas tree" formation. This form is commonly obstructed due to the closure of the ductus venosus after birth, constriction as the vertical vein passes through the diaphragm, or obstruction from the length and tortuosity of the vertical vein. In this type, pulmonary veins drain below the diaphragm, typically into the portal venous system or inferior vena cava (IVC). This type is by definition obstructed.

• Drainage Pattern:

  • Veins generally do not drain to a single confluence but rather in an "inverted Christmas tree" or "fern" appearance.

  • They drain into a vertical vein, then into the porta hepatis, and further through the ductus venosus or directly through the liver into the inferior vena cava (IVC), often via the left hepatic vein.

• Imaging:

  • Subcostal sagittal cut is the easiest way to recognize this condition. The hallmark feature is a vertical vein carrying blood away from the heart, running parallel to the pulsating descending aorta, appearing like a "little sausage". Saline contrast will not fill this vein.

  • Suprasternal notch view is also very effective, showing the pulmonary veins draining down into the vertical vein and then to the porta hepatis.

  • CT scans are excellent for defining these anomalies in 3D space.

• Sites of Obstruction: This type has multiple potential sites of obstruction:

  • Where the vein passes through the diaphragm.

  • Within the porta hepatis or portal vein.

  • At the ductus venosus, which can constrict.

  • The liver itself can become a site of obstruction, leading to "huge sinusoids" within the liver if patients present late.

• Urgency: Infracardiac TAPVR is a surgical emergency. If clear imaging is obtained, the patient should be sent to surgery without delay, as contrast studies can exacerbate the obstruction.

4. Mixed TAPVR (Type 4). Some pulmonary veins drain to one place, and others drain to a different place. This type carries a much worse prognosis, with a higher risk of reintervention and lower survival rates compared to other TAPVC forms. It is crucial for the surgeon to know if mixed veins are present. The smaller size of individual veins in mixed types may contribute to higher obstruction rates. In this scenario, different pulmonary veins drain to different anomalous sites (e.g., some above the heart, some below, or some to the coronary sinus).

• Characteristics: Patients with mixed veins can exhibit features of all other types of APVC.

• Diagnosis: Requires multiple echocardiographic cuts to identify all anomalous drainage pathways.

• Scimitar Syndrome: An example of a mixed pattern, or a partial anomaly sometimes resembling it. In this syndrome, right pulmonary veins drain anomalously into the inferior vena cava (IVC) in the supradiaphragmatic portion. It may be associated with extralobar sequestration.

  • Imaging: Seen from subcostal view. Echocardiographically, one must lower the Doppler scale (e.g., to 23 cm/s) to visualize the low-velocity flow in veins, even when obstructed.

5. Lethal Form (Vertical Vein Atresia): No vertical vein or vertical vein atresia. Patients are immediately severely cyanotic at birth and are often transferred to tertiary care with suspected severe pulmonary hypertension. This is an unsurvivable anomaly due to the tiny, sclerotic confluence and severe lung damage. These patients may have connections between pulmonary veins and bronchial veins that provide minimal, inefficient blood flow.

Key Echocardiographic Findings in TAPVC:

• Obligatory right-to-left shunting at the atrial level: This is because it's the only way blood can get to the left side of the heart. If this is not observed, TAPVC is not present. This communication must be adequately sized as it determines the entire cardiac output from the left ventricle. Unlike primary pulmonary hypertension (PPHN), which often shows bi-directional atrial flow, TAPVC almost always has obligatory right-to-left shunting.

• "Bald" or small left atrium (LA): The LA appears small and lacks the "Mickey Mouse ears" appearance in the four-chamber view because pulmonary veins do not connect to it. The aorta may also be displaced posteriorly due to this.

• Dilated right ventricle (RV): Often, the RV is significantly dilated, especially if there is obstruction to venous flow.

• Flattening or bowing of the ventricular septum: Due to high pressures reflecting back to the pulmonary vascular bed.

Partial Anomalous Pulmonary Venous Return (PAPVR)

PAPVR occurs when one or more, but not all, pulmonary veins drain anomalously. These cases may not present as urgent surgical emergencies in neonates unless significant obstruction or hemodynamic compromise is present.

• Common Sites:

  • Left upper pulmonary vein to innominate vein: This is a very common subtype.

  • Directly to the coronary sinus: Typically involving left veins. To the Coronary Sinus: Similar to TAPVR, but only partial drainage. An enlarged coronary sinus due to PAPVR can be mistaken for an unroofed coronary sinus (coronary sinus septal defect). Misdiagnosis and closure can lead to obstruction of the pulmonary veins, highlighting the importance of accurate pre-operative diagnosis.

  • Scimitar Syndrome: A constellation of findings where one or more right pulmonary veins (usually the right lower pulmonary vein) connect directly to the inferior vena cava (IVC). Associated findings include right lung hypoplasia (causing mesocardia or dextrocardia), an aortic pulmonary collateral to the right lung, and pulmonary sequestration in the right lung. Mesocardia (apex pointing midline) or dextrocardia (heart shifted to the right) should raise suspicion for Scimitar syndrome, especially in a newborn with pulmonary hypertension.

  • Right pulmonary veins to the superior vena cava (SVC): This can occur in isolation or with a sinus venosus defect. Right pulmonary veins draining to the SVC or the SVC-right atrial junction is also a common site for isolated anomalous pulmonary venous anomalies. It acts like a left to right "ASD" shunt.

  • Ipsilateral pulmonary veins: Seen in left isomerism (polysplenia form of heterotaxy), where right pulmonary veins drain to the right-sided atrium and left pulmonary veins to the left-sided atrium.

  • Isolated anomalous pulmonary vein draining to a vertical vein (similar to Type 1 TAPVR but not all veins). These isolated anomalies can enlarge over time and may necessitate surgical closure later in life.

  • Drainage to the azigos vein.

Echocardiographic Tips for PAPVC Detection:

• Always suspect PAPVC when the right ventricle (RV) is dilated but there is no atrial communication.

• Sinus venosus defects are almost always associated with PAPVC.

• If one anomalous pulmonary vein is found, always look for others.

• Be vigilant for vertical veins at the limits of the mediastinum, particularly in patients with Turner syndrome, who have a high rate of missed PAPVC.

• The subcostal sagittal view can be excellent for identifying the right upper pulmonary vein connecting to the left atrium, thereby ruling out its anomalous connection.

Management of PAPVC:

• If right pulmonary veins drain high into the SVC, a Warden procedure may be required. This involves baffling the right pulmonary veins directly to the left atrium, dividing the SVC, and connecting the portion above the right pulmonary veins to the right atrial appendage. Post-procedure, the SVC may be at risk for obstruction.

• In older patients, covered stents can be used to direct SVC blood to the right atrium and pulmonary venous blood to the left atrium.

Diagnostic Considerations and Challenges

Accurate and timely diagnosis of APVC is crucial for effective management.

• Echocardiography - Effective echocardiography for pulmonary venous anomalies requires meticulous technique:

  • Urgent Situations (Sick Neonate): In an emergency, the recommended approach is to start with subcostal coronal and sagittal cuts to look for a vertical vein, especially if it drains below the diaphragm, as this signals a need for immediate surgery. This should be followed by suprasternal or transmanubrial views to identify any vertical veins.

  • Saline Contrast Echocardiography: If a right-to-left atrial shunt is detected, it strongly suggests either obstructed APVC, pulmonary hypertension, or a combination. The absence of such a shunt makes obstructed APVC highly unlikely.

  • Doppler Settings: For clear visualization of venous flow, which is typically low velocity, it is essential to lower the Doppler color scale (e.g., to 23 cm/s).

  • Comprehensive Analysis: A complete echocardiographic analysis is vital to define the anomaly, especially to account for all pulmonary veins (there may be five or six) and ensure no other anomalous drainage sites are missed.

• Lower the Nyquist limit: Venous flow velocities are typically low (under 20 cm/s), so the Nyquist limit on the echo machine should be lowered, often below 40 cm/s, to accurately visualize flow. Modern machines tend to default to higher Nyquist limits to increase frame rates, so conscious adjustment is necessary.

• Systematic Examination: Always examine the entire heart and integrate all findings.

• Prioritize 2D Imaging: Attempt to identify pulmonary veins using 2D imaging first before relying on colour Doppler.

• Utilize Multiple Views:

  • The subcostal view (particularly sagittal) is excellent for initial assessment and for identifying the right upper pulmonary vein connecting to the left atrium.

  • The apical four-chamber view is crucial, especially for observing the "bald" left atrium.

  • The suprasternal "crab" view is a classic view for visualizing the pulmonary veins and confluence.

  • Parasternal views are also valuable.

• Differentiate from Other Vessels: Be careful not to confuse pulmonary veins with other vessels like the supreme intercostal vein (which drains into the innominate vein and has different Doppler flow patterns) or pulmonary arteries.

• Saline Contrast Echocardiography: A "bubblegram" can confirm right-to-left atrial shunting in TAPVC and may highlight venous structures.

• Fetal Echocardiography: This condition is frequently missed during fetal echocardiography, leading to increased morbidity postnatally. Careful attention to venous drainage in the fetus is paramount.

• Advanced Imaging: For non-emergency situations or when echocardiographic views are inconclusive, CT angiography (CTA) or magnetic resonance angiography (MRA) can provide excellent three-dimensional imaging of the venous anatomy, aiding precise surgical planning. Ancillary Imaging (CT/MRI): While echocardiography can diagnose most pulmonary venous diseases, cross-sectional imaging (CT or MRI) is considered when:

• Not all pulmonary veins are clearly visible by echo.

• There is suspicion of mixed total veins, as the prognosis is worse and surgical planning requires precise anatomical detail.

• Concern for pulmonary vein stenosis exists, as CT/MRI provides superior detail on the location and length of the stenosis for interventional planning.

• Caution: In patients with obstructed TAPVC, taking them to CT for imaging can be dangerous due to radiation exposure and the volume load from contrast, which can exacerbate their critical condition. These patients are surgical emergencies where rapid diagnosis by echo and immediate intervention are paramount.

• Chest X-ray Findings:

• Obstructed TAPVC (early diagnosis): May show a "white out" of the lungs due to severe pulmonary venous congestion, making it hard to distinguish the lungs from the heart.

• Unobstructed Supracardiac TAPVC (late diagnosis): Can present with the characteristic "snowman appearance," caused by the dilated vertical vein, innominate vein, and SVC forming a silhouette above the cardiac silhouette.

• Scimitar Syndrome: May show a shift of the heart (mesocardia or dextrocardia) and hypoplasia of the right lung.

• Differential Diagnoses:

  • Pulmonary Hypertension: TAPVR, especially Type 1 with obstruction, can mimic primary pulmonary hypertension, leading to potential misdiagnosis and inappropriate treatment.

  • Hypoplastic Left Heart Syndrome (HLHS): There is a historical misconception that TAPVR often presents with a hypoplastic left ventricle, leading to confusion with HLHS. However, the left ventricle in TAPVR is typically dynamically small due to altered loading conditions (reduced preload and afterload). After surgical correction, the left ventricle's volume significantly increases and it looks normal as loading conditions normalize. True HLHS involves an intrinsically small aorta and a fixed hypoplastic ventricle, making it a different "kettle of fish".

  • Cor Triatriatum: Differentiating from an enlarged coronary sinus can be challenging. In cor triatriatum, an obstructive membrane is typically present within the left atrium, often thickened and highly echoreflective, which may be pushed into the mitral valve funnel by pressure. Blood flow will eventually find a way back to the left side of the heart, often through a perforation in the membrane.

  • Azigos Vein vs. Anomalous Pulmonary Vein: The azigos vein typically runs higher in the mediastinum, over the bronchovascular bundle on the right side, serving as a landmark. Anomalous pulmonary veins generally do not drain beyond the azigos vein.

Obstruction in TAPVC:

• Obstruction can occur in any type of TAPVC.

• Signs include a dilated and poorly functioning RV, right-to-left ductus arteriosus shunting (indicating very high pulmonary vascular resistance), and accelerated flow (with a mean gradient by Doppler) at the point of obstruction.

• Obstructed TAPVC is a surgical emergency; there are no medical treatments, and patients require urgent transfer to the operating room or ECMO support. The longer the delay in diagnosis and treatment, the poorer the outcome.

• The Pulmonary Venous Variability Index (PVI), calculated as (maximum velocity - minimum velocity) / mean velocity, is a sensitive tool to predict significant obstruction.

Post-operative Obstruction Risk Factors in TAPVC:

• Single ventricle physiology.

• Need for additional procedures at the time of TAPVC repair.

• Mixed type TAPVC (worst survival).

• Pre-operative obstruction.

Surgical Considerations

Surgical intervention is the definitive treatment for APVC, especially obstructed forms.

• Surgical Urgency: Obstruction in Type 1 (supracardiac) and Type 3 (infracardiac) TAPVR constitutes a surgical emergency. Type 2 (intracardiac) TAPVR rarely involves obstruction and thus is typically not an emergency.

• Repair Techniques: For veins draining directly to the right atrium, surgeons can simply patch the opening to redirect flow to the left atrium. For cases of surgical obstruction in pulmonary veins, sutureless techniques might offer a better anastomosis.

• Post-operative Pulmonary Vein Stenosis: This is a major concern post-surgery. It is often intrinsic to the disease (e.g., "venitis") rather than solely a surgical complication, making it difficult to predict pre-operatively. Patients with this complication face high morbidity and mortality.

• Dynamic Nature of Heart Structures: Surgeons and echocardiographers alike must appreciate the dynamic and plastic nature of cardiac structures. The size and appearance of ventricles, great vessels (like the aorta), and even coronary arteries can change significantly once abnormal loading conditions are corrected. For example, a "hypoplastic" left ventricle in TAPVR will normalize post-repair, and an enlarged right coronary artery in anomalous coronary artery cases will shrink after re-implantation.

• For unobstructed TAPVC, repair can be elective, usually within the first few weeks of life. The confluence is anastomosed to the left atrium, and the vertical vein is typically ligated.

• For cardiac TAPVC to the coronary sinus, the coronary sinus is unroofed, and its ostium is closed to the left atrium. Inadequate unroofing can lead to significant obstruction.

• Mixed TAPVC may require a combination of surgical strategies.

• Post-repair, the heart often undergoes significant remodeling: the dilated RV becomes smaller, and the compressed left ventricle (LV) becomes larger and normally filled. The LV is almost always adequate and recoverable, as its "hypoplasia" is often a loading condition rather than an anatomical deformity.

• Surgeons often prefer sutureless pulmonary vein repair in re-operations because pulmonary veins are very sensitive to being touched. Challenges can arise in repairing veins that are small or travel in an "unfavourable" direction, such as in Scimitar syndrome.

Anomalous pulmonary venous connection is a diverse group of congenital heart defects with varying anatomical patterns and clinical presentations. A thorough understanding of its classifications, characteristic imaging features, and potential for obstruction is vital for accurate diagnosis and timely management. The dynamic nature of cardiac structures, particularly the left ventricle's response to corrected loading conditions in TAPVR, highlights the need for a nuanced diagnostic approach beyond static anatomical measurements. Close collaboration between echocardiographers, surgeons, and other specialists is essential to optimize outcomes for these complex patients.

Heterotaxy (Isomerism) and Pulmonary Veins

Heterotaxy syndromes are associated with unique pulmonary venous anomalies and often complex heart disease.

• Left Isomerism (Polysplenia): The most common anomaly is ipsilateral pulmonary veins, where right pulmonary veins enter the right-sided atrium and left pulmonary veins enter the left-sided atrium. This is thought to occur because the patient theoretically has two left atria.

• Right Isomerism: Patients have "two right atria". Total anomalous pulmonary venous connection is common and frequently obstructed in this context. It is often associated with other complex heart diseases, such as double outlet right ventricle, right ventricular aorta with pulmonary atresia, and single ventricle. The risk for these patients is extremely high, and surgical outcomes for pulmonary vein repair in right isomerism have historically been very poor, with low long-term survival rates. When pulmonary atresia or severe pulmonary stenosis is present with TAPVC, it indicates a severe problem with both inflow and outflow to the lungs, leading to likely abnormal pulmonary vasculature and a high risk of subsequent pulmonary vein stenosis.

Description of various clips of TAPVR

Total anomalous pulmonary venous return (TAPVR) is a condition where the pulmonary veins will connect to the right atrium, instead of the left atrium. As such, there is an obligatory right to left shunting. The pulmonary venous return may become obstructed in the post-natal life, which is a neonatal emergency. TAPVR has variants, depending on where the pulmonary veins are draining into. Read more on TAPVR here.

Total Anomalous Pulmonary Venous Return presentation by Carolina Michel Macias and Cowzhiya Ravisingam

Case 1: Intracardiac location of TAPVR to coronary sinus non-obstructed

• Intracardiac location of totally anomalous pulmonary venous connection to coronary sinus non-obstructed.

• Large secundum atrial septal defect (ASD) shunting right to left.

• Moderate to severe right ventricular dilation.

• Underfilled left ventricle.

• Straight ventricular septum in systole (right ventricular pressure overload).

• Large nonrestrictive patent arterial duct (PDA) measuring 0.45 cm shunting bidirectionally.

Case 2: Supracardiac location of TAPVR to left-sided vertical vein non-obstructed

• Supracardiac location of totally anomalous pulmonary venous connection(s) to left-sided vertical vein non-obstructed.

• Moderate unrestrictive secundum atrial septal defect (ASD) within oval fossa shunting right to left.

• Severe right ventricular dilation with straight ventricular septum.

• Small anterosuperior trabecular muscular ventricular septal defect (VSD) shunting right to left.

• Small restrictive patent arterial duct (PDA) shunting left to right