Embryology

Near the end of the first month of fetal life the primordial pulmonary buds have developed from the foregut. At this stage these structures are surrounded by the splanchnic plexus of the foregut and share drainage to the cardinal and umbilicovitelline veins. It is also at this time that this plexus begins the process of differentiation into the final pulmonic phenotype ( Fig. 48.1 ). Initially there is no direct connection of the pulmonary vascular plexus to the heart, but a common pulmonary vein eventually emerges from a combination of the evagination of left atrial tissue, the pulmonary venous plexus itself, and the surrounding mesoderm. The plexus of parenchymal pulmonary veins will eventually connect with this common pulmonary vein, which in turn connects with the sinoatrial portion of the heart. This connection will be incorporated into the left atrial wall, with the individual pulmonary veins draining independently into the chamber. The original connection to the systemic venous system will eventually involute, leaving the richly oxygenated blood draining directly to the systemic atrium. An anatomic defect occurs when the pulmonary venous plexus fails to connect to the systemic atrium and there is persistence of one or more of the early connections to the systemic venous circulation.

Normal development of pulmonary veins. (A) At approximately 4 weeks of gestation, the primordial lung buds are enmeshed by the vascular plexus of the foregut (the splanchnic plexus). At this stage there is no direct connection to the heart, with all the drainage to the splanchnic plexus. (B) By the end of the first month of gestation the common pulmonary vein (CPV) establishes a connection between the pulmonary venous plexus and the sinoatrial portion of the heart. (C) Next, the connections between the pulmonary venous plexus and the splanchnic venous plexus involute. (D) The CPV incorporates into the left atrium (LA) so that the individual pulmonary veins connect separately and directly to the LA. LCCV, Left common cardinal vein; LLB, left lung bud; RA, right atrium; RCCV, right common cardinal vein; RLB, right lung bud; UV, umbilical vein.

(From Allen HD, Shaddy RE, Penny DJ, et al. Anomalies of the pulmonary veins. In: Moss and Adams’ Heart Disease in Infants, Children, and Adolescents: Including the Fetus and Young Adult. 9th ed. Lippincott Williams & Wilkins, 2016:882.)

Classification

The most commonly used classification scheme was proposed by Craig, Darling, and Rothney. They classified this anomaly based on the drainage pattern of the pulmonary venous return to the systemic venous circulation. The supracardiac type occurs most frequently, occurring in 50% of cases in most published series. In supracardiac TAPVR all pulmonary veins enter a common confluence that subsequently connects to either the innominate vein or directly to the superior vena cava ( Fig. 48.2 ). The second most frequent type, termed infracardiac, occurs when the common confluence drains inferiorly to below the diaphragm to enter either the portal vein or the inferior vena cava directly ( Fig. 48.3 ). This type occurs approximately 25% to 30% of the time. The cardiac type occurs when the drainage of the confluence is to the coronary sinus or directly into the right atrium. Finally, the mixed type of TAPVR consists of a variable number of connections that drain directly to the heart or to an additional extracardiac structure. This classification scheme is most practical because it helps in surgical planning, postoperative management, and long-term care. An alternative classification scheme is that of Burroughs and Edwards, in which the anatomy is classified according to the embryologic basis of abnormal connection.

A volume-rendered image from a contrast-enhanced computed tomography angiogram of the chest as viewed from the anterior and slightly rightward projection. Most of the cardiac mass, except the right atrium, has been cropped out to easily visualize venous anatomy. Left superior and inferior pulmonary veins come to a confluence posterior to the left atrium. The confluence courses rightward posterior to the right atrium to enter the right chest. Here, after a tortuous course and picking up drainage from the right lower, middle, and upper veins, the venous confluence drains into the superior vena cava (SVC) from a posterior and lateral aspect.

A volume-rendered image from a contrast-enhanced computed tomography angiogram of the chest as viewed from the posterior projection. Right and left superior pulmonary veins come to a confluence posterior to the left atrium. As the confluence courses inferiorly, right and left inferior pulmonary veins drain into the confluence, which ultimately drains into portal circulation in the liver.

Clinical Presentation

In a comprehensive, population-based study from several European countries the most common signs and symptoms at the time of presentation in children with TAPVR were cyanosis (43%), respiratory distress (31%), failure to thrive (11%), circulatory collapse (4.5%), a murmur (0.5%), or supraventricular tachycardia (0.5%). Patients not diagnosed prenatally will often present early with findings similar to those observed with a large atrial septal defect (ASD), although mild cyanosis is present. The infants initially appear well. Over time they will develop signs of congestive heart failure such as tachypnea, tachycardia, and hepatomegaly. They may present with recurrent pneumonias and failure to thrive. Physical examination will reveal a hyperactive RV impulse, split and fixed S ₂ , systolic ejection murmur at the upper left sternal border, and a middiastolic rumble at the left lower sternal border. Electrocardiograms will demonstrate right axis deviation, RV hypertrophy, and right atrial enlargement. Chest radiography will show cardiomegaly with increased pulmonary venous markings. In children greater than 4 months of age a prominent vertical vein may create the appearance of the “snowman” sign on chest radiographs.

For children with pulmonary venous obstruction (PVO), rapid progression to metabolic acidosis, cardiac failure, and death may occur shortly following birth. If the child survives the initial 24 hours, tachycardia, poor peripheral perfusion, and hypotension can occur. They may develop lactic acidosis, arrhythmias, and end-organ dysfunction related to cardiogenic shock. Cardiac auscultation findings are minimal and may include a loud S ₂ and gallop rhythm. Chest radiography reveals pulmonary edema with a small heart. Electrocardiograms will show right axis deviation and RV hypertension.

Diagnostic Assessment

The diagnosis of TAPVR can be difficult on prenatal ultrasonography. In the series by Seale and colleagues, only 1.9% of cases were diagnosed prenatally. This observation suggests that an increased awareness of this diagnosis should occur at the early stages of evaluation of any child with suspected congenital heart disease. A recent paper from Tongsong and colleagues presented a comprehensive set of guidelines for increasing the number of accurate prenatal diagnoses at the time of initial imaging. In this work the authors recommend further imaging studies when the initial ultrasonogram does not depict the entry of the pulmonary veins into the left atrium when one of these additional conditions is met: (1) the presence of a vascular confluence in the space behind the heart, (2) abnormal spectral waveforms in the pulmonary veins, (3) a smooth posterior wall of the left atrium, (4) increased retroatrial space, (5) a dilated coronary sinus, or (6) a dilated superior vena cava. In a review of 26 fetuses with a prenatal diagnosis of TAPVR, Ganesan and colleagues described several consistent ultrasonographic findings, including the lack of visible pulmonary venous connections to the left atrium and the presence of a visible venous confluence on axial four-chamber views. The presence of an additional vertical venous channel on three-vessel or axial abdominal views was also sometimes noted. A high index of suspicion is required to avoid a false-negative or false-positive echocardiographic study. When there is doubt, it may help to have an experienced cardiologist review echocardiographic images.

The differential diagnoses of these children can be grouped according to the child’s age at presentation. Patients with severe obstruction are first seen as neonates and will often be mistaken for having other more common severe illnesses of the newborn associated with acidosis and hypoxia, including persistent pulmonary hypertension of the newborn, sepsis with pneumonia, and hyaline membrane disease. For this reason it is recommended that all such critically ill newborns undergo careful echocardiography to rule out structural heart disease. Neonates beyond the first few days of life will have clinical findings similar to those seen with a large ventricular septal defect, atrioventricular septal defect, truncus arteriosus, or patent ductus arteriosus. Children beyond the neonatal period must be distinguished from patients with a large ASD, a common atrium, and partial anomalous pulmonary venous return.

Echocardiography is an important initial diagnostic tool for patients with suspected TAPVR. The distinguishing echocardiographic features include RV diastolic volume overload, an absence of the pulmonary venous connections to the left atrium, and identification of an alternative drainage site of the pulmonary veins. The objectives of preoperative echocardiography are to do the following :

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  Identify the drainage of individual pulmonary veins

  
  
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  Identify the position of the confluence in relation to the left atrium

  
  
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  Identify the presence and degree of obstruction to pulmonary venous flow

  
  
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  Assess if there is obstruction at the level of the atrial septum

  
  
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  Estimate RV pressure

  
  
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  Identify any associated cardiac lesions

Multiple echocardiographic views and methods should be used to comprehensively evaluate suspected TAPVR. Two-dimensional echocardiography provides good anatomic information and can be validated by color Doppler side-by-side comparison ( Fig. 48.4 ). The pulsed Doppler technique provides important physiologic information before surgical intervention. A transthoracic echocardiogram is the starting point and should suffice in most situations. Use of transesophageal views for diagnosis has been described, but at most institutions this is limited to intraoperative evaluation.

Two pulmonary veins, one from either side (green arrows) , drain into the coronary sinus (CS), as visualized from subcostal coronal echocardiographic view. This appearance has sometimes been likened to the tail of a whale (“whale tail sign”). The yellow star shows right-to-left flow across the foramen ovale.

With the advent of multidetector computed tomography (CT) scanning, detailed images of the pulmonary venous drainage, including inflow and runoff vessels from the confluence, can be achieved. Image interpretation is aided by the use of advanced postprocessing techniques. Volume-rendered three-dimensional reconstruction of the vascular bed provides a global overview for rapid identification of pathology. The combination of axial and three-dimensional images in helical CT angiography (CTA) is helpful in the assessment of TAPVR containing the individual pulmonary vein. Maximum-intensity projection and multiplanar reformat images provide views similar to or better than traditional angiography. Measurements on CTA may be used for objectively assessing the degree of stenosis. In an adult coronary artery disease model, high interreader, intrareader, and interstudy reproducibility for a given scanner has been established. Distortion-free detailed interrogation is performed with thin-section multiplanar reformats, which can be oriented to any desired plane. Axial two-dimensional source data are used when other techniques are inconclusive. In the setting of TAPVR, CTA is ideal when surgically pertinent anatomic and physiologic information cannot be obtained by echocardiography. CTA helps in surgical planning by delineating stenosis or obstruction, the site(s) of abnormal connections, and the course of the anomalous vein in relation to the left atrium. CTA provides accurate diagnosis with very short scan times, obviating the need for sedation, and has become the modality of choice in critically ill neonates. Recurrent pulmonary vein obstruction is a common postoperative morbidity associated with early repair of TAPVR. CTA can demonstrate the type of stenosis and the entire course of the individual veins to better effect than echocardiography.

Currently available magnetic resonance imaging (MRI) scanners and cardiovascular imaging software from all manufacturers provide high-resolution angiographic images without patient exposure to radiation. In TAPVR with PVO, when emergent intervention is required, CTA is preferred for these reasons. Patients undergoing MRI for pulmonary venous assessment and evaluation of associated cardiovascular anomalies must remain still in the scanner for up to 20 to 60 minutes to minimize motion artifact; therefore children under 6 years of age typically require sedation or anesthesia. Infants younger than approximately 6 months may fall into a natural sleep after being fed and swaddled comfortably. For children greater than 6 months of age, some institutions prefer to employ general anesthesia with mechanical ventilation via endotracheal intubation or laryngeal mask airway. Respiratory motion artifact can be eliminated by holding breaths for brief periods (8 to 15 seconds) after a few seconds of hyperventilation. It is important to have communication of expected anatomy, duration of study, and cardiorespiratory risk factors between the anesthesiologist and the radiologist before the start of and throughout the MRI.

Measurement of quantitative flow to each lung, the fractional flow to each lung in patients with pulmonary vein stenosis, can be obtained with phase-contrast imaging. It is worth noting that the US Food and Drug Administration has not yet approved the use of gadolinium (Gd)-based contrast agents for pediatric cardiac MRI. However, judicious off-label use of different Gd-based MRI contrasts is used at most centers, with a reasonably good safety profile. Dynamic-contrast MR angiography with a Gd-based contrast agent under sedation is very useful for evaluation of the thoracic vessels of infants and small children in the preoperative and postoperative states.

Diagnostic cardiac catheterization is reserved for patients in whom echocardiography or CT imaging is not satisfactory or when associated lesions need to be further defined. Cardiac angiography is performed after direct cannulation of the anomalous pulmonary vein or selective PA angiography. A delay in contrast transit through the pulmonary bed and small caliber of the pulmonary veins at insertion suggest obstruction to pulmonary venous return. Catheterization can be particularly helpful in case of atresia of the common pulmonary vein when echocardiography and CT are not able to visualize pulmonary veins. Pulmonary arteriograms in this situation show persistence of contrast medium in the pulmonary arteries, and the left atrium, the great veins, and the right heart chambers are not opacified. Another diagnostic hallmark of TAPVR is that oxygen saturations from the right and left atria are nearly the same as those in the PA and aorta, because the right atrium is a common mixing chamber. Because of streaming of blood flow along fetal patterns, there could be minor differences in the left and right oxygen saturations depending on the type of TAPVR. Again depending on the drainage site, high oxygen saturations can be noted in the portal vein, coronary sinus, superior vena cava, and innominate vein.

Preoperative Pathophysiology

Children with TAPVR have an obligatory left-to-right shunt from the pulmonary veins to the right heart and an intracardiac right-to-left shunt across an atrial communication. The specific physiology will depend on the degree of PVO, which can be severe in up to 25% of the cases, and on the amount of pulmonary blood flow. When the obstruction is severe, significant pulmonary edema and pulmonary hypertension will occur immediately. This will result in an increase in the right-to-left intracardiac shunt and subsequently worsening systemic cyanosis. The condition will rapidly progress with worsening acidosis and low cardiac output.

In children with no obstruction to the pulmonary venous connection the physiology is similar to that of other patients with significant left-to-right shunts and will likely go undetected in the neonate if not diagnosed on routine prenatal ultrasound examinations or postnatal screening. With time, as pulmonary vascular resistance (PVR) decreases, pulmonary blood flow will increase, resulting in right heart enlargement and clinical signs of heart failure including tachypnea, tachycardia, and failure to thrive. Mild cyanosis will occur but is often not noticeable, especially in children with darker skin complexions.

Children frequently present with a combination of excessive pulmonary blood flow and mild PVO. These findings are often seen in the supracardiac type with drainage of the confluence to the left side of the innominate vein via a vertical venous connection. In a number of these cases there could be an increase in pulmonary blood flow to three to five times systemic levels, leading to obvious symptoms and signs of congestive heart failure. Pulmonary artery pressure may range from mildly to severely elevated depending on the degree of PVO and PA blood flow. PVO most often occurs at the level of the vertical vein as it courses between the left PA and left bronchus. These children can become critically ill from viral respiratory infections and often demonstrate failure to thrive.

When PVO is severe, neonates are critically ill with pulmonary venous hypertension resulting in pulmonary edema, reflex pulmonary arterial vasoconstriction, and pulmonary arterial hypertension with associated decreased pulmonary blood flow. Right-to-left shunting occurs at the ductal and atrial levels. This physiology causes marked hypoxemia. Additionally, decreased pulmonary venous return to the left atrium and impingement of the septal wall on the LV cavity by the RV result in impaired LV filling and function with decreased cardiac output. Severely affected neonates present with cyanosis, respiratory distress, and hemodynamic compromise with hypotension and poor perfusion.

Preoperative Critical Care

The level of preoperative support required will reflect the pathophysiologic state of the patient and depends on the degree of PVO and pulmonary blood flow. Critical care management of infants with TAPVR and severe PVO is supportive and focuses on stabilization, optimization of oxygen delivery, and prevention of pulmonary hypertensive crisis. Of neonates and infants presenting with TAPVR, approximately one-third have severe PVO requiring mechanical ventilation and inotropic support, and 2% to 4% are moribund upon presentation. Due to tenuous and potentially inadequate oxygen delivery, intubation and mechanical ventilation should be instituted promptly. Deep sedation and neuromuscular blockade may be beneficial to decrease metabolic demands and agitation-related elevations in PVR, as well as to promote stable minute ventilation and avoid hypercarbia-related elevations in PVR. Inotropic support with dopamine or epinephrine may be useful to improve cardiac output while awaiting surgery. Initially, sodium bicarbonate may be of benefit to mitigate severe metabolic acidosis while the interventions discussed previously are instituted to improve perfusion. This should be used as a temporizing measure while the operating room (OR) is being prepared and the patient is being transported for operative correction.

Standard lines and monitoring include umbilical artery catheter, umbilical venous catheter (UVC), and regional oxygen saturation monitoring via near-infrared spectroscopy (NIRS). In infants with infracardiac TAPVR, one may prefer to avoid UVC placement in favor of alternative central venous access. Therapeutic goals include normoventilation without excessive ventilator pressures or volumes and adequate oxygen delivery and cardiac output as indicated by central venous oxygen saturation and regional oxygen saturations, lactate levels, and end-organ function. Though an increasing percentage of neonates with TAPVR are diagnosed prenatally, others present in a shock-like state and may initially be treated for sepsis, respiratory distress syndrome, or other conditions before TAPVR diagnosis. It is important to be aware that previously implemented therapies may not be indicated for TAPVR. Pulmonary vasodilators such as inhaled nitric oxide (iNO) have not been of demonstrated benefit preoperatively and may result in increased pulmonary edema. Similarly, attempts to increase pulmonary blood flow with hyperoxygenation, aggressive hyperventilation, or sodium bicarbonate–induced alkalosis are not indicated. Prostaglandin E ₁ (PGE ₁ ) is not routinely recommended due to similar risks, though some authors have described the cautious use of PGE ₁ in select patients with low cardiac output syndrome (LCOS) in an attempt to provide right-to-left shunting to the systemic circulation or to relax the ductus venosus in infracardiac TAPVR. Diuretic use should be employed with caution because the noncompliant RV may benefit from higher filling pressures