Heart Views

: 2007  |  Volume : 8  |  Issue : 2  |  Page : 52--61

Pulmonary atresia with ventricular septal defect: Systematic review

Duraisamy Balaguru1, Muhammad Dilawar2,  
1 Assistant Professor of Pediatrics, Tufts University School of Medicine, Boston, MA, USA
2 Consultant Pediatric Cardiologist, Cardiology & Cardiovascular Surgery Dept. Hamad Medical Corporation & Assistant professor of Pediatrics Weil Cornell Medical College, Doha, Qatar

Correspondence Address:
Duraisamy Balaguru
MD, MRCP (UK), FAAP, FACC, Children«SQ»s Heart Center, Children«SQ»s Hospital of New Jersey at Newark Beth Israel Medical Center, 201 Lyons Avenue, Newark, NJ 07112

How to cite this article:
Balaguru D, Dilawar M. Pulmonary atresia with ventricular septal defect: Systematic review.Heart Views 2007;8:52-61

How to cite this URL:
Balaguru D, Dilawar M. Pulmonary atresia with ventricular septal defect: Systematic review. Heart Views [serial online] 2007 [cited 2021 Oct 20 ];8:52-61
Available from: https://www.heartviews.org/text.asp?2007/8/2/52/63730

Full Text


Pulmonary atresia with ventricular septal defect (PA-VSD) is synonymous with Tetralogy of Fallot-pulmonary atresia and this defect may be considered as an extreme form of classic Tetralogy of Fallot. Classic Tetralogy of Fallot consists of right ventricular outflow tract stenosis, malaligned ventricular septal defect, overriding of aorta and right ventricular hypertrophy. In contrast, PA-VSD consists of atresia of right ventricular outflow tract along with remaining three features of classic Tetralogy of Fallot. Other synonyms for this defect are Type IV truncus and Pseudotruncus. PA-VSD has been proposed by the international nomenclature committee of Congenital Heart Surgery Nomenclature and Database Project as a unifying term [1] . The variabilities of pulmonary blood supply in PA-VSD make this defect heterogeneous and challenging for surgical repair. Relatively poorer outcome for PA-VSD compared to classic Tetralogy of Fallot stems from the complexity of its pulmonary blood supply. Strategies combining catheter-based therapies for rehabilitation of pulmonary arteries with appropriately-timed surgical repair have helped to achieve better results in recent years [2] .

 I. Epidemiology

Baltimore-Washington Infant Study3 (BWIS) recorded 4390 infants with cardiovascular malformations from 1981 - 1989. Of this, 296 (6.7%) were reported to be Tetralogy of Fallot. Sixty of 296 (20%) infants in the Tetralogy group were Tet-PA. Tet-PA accounted for 1.4% of all forms of congenital heart disease and 0.07 per 100 live births.

 II. Etiology

Genetic, environmental, and familial factors play a causative role in etiology of PA-VSD and therefore it remains multifactorial in nature. Baltimore-Washington infant study provides us with some pointers to the etiology of Tet-PA. In BWIS [3] , 73.3% of patients with PA-VSD did not have any associated extra-cardiac abnormalities. The remaining 26.7% of the patients with PA-VSD had chromosomal abnormality, a recognizable syndrome, or other single organ defects. PA-VSD occurs more often with DiGeorge syndrome and associated with Chromosome 22q11 microdeletion. Other recognizable syndromes associated with this lesion include VACTER, CHARGE and Alagille syndromes. Chromosomal anomalies such as Trosomy 13, Trisomy 21 and Deletion 5p have also been reported in babies with PA-VSD. A ten-fold higher incidence of PA-VSD has been reported in infants of diabetic mothers compared to non-diabetic mothers and the incidence is 20-fold higher if diabetes was severe enough to need treatment with insulin. Maternal intake of benzodiazepines was associated with congenital heart disease with an Odds ratio of 2.15.

 III. Natural History of the disease

Early natural history reports did not address PA-VSD separate from Tetralogy of Fallot. Limited natural history information is available for PA-VSD group from two recent reports, though some patients in these studies underwent surgical repair. A cohort study of 26 adults managed at UCLA (UCLA adult congenital heart disease registry 1978 - 1992) was studied for outcome during a 14 year period [4] . At the time of referral as adults, 16 of them did not have any prior surgery and the remaining 10 have had some palliative surgery (mainly systemic to pulmonary artery shunting). All patients were symptomatic at the time of referral with cyanosis or functional limitation.

Twenty of these patients had aortic regurgitation by echocardiogram and 10 of them were classified as moderate or severe by semi-quantitative echocardiography. None of the patients survived beyond the third decade. This is a small group of self or naturally selected group of patients who have survived to adulthood with cyanosis and pulmonary blood supply supported by collateral arteries.

A recent European study [5] documents the outcome in 218 patients who were treated in two leading cardiac centers in London over a period of 26 years (1965 - 1991) and followed up to 40 years of age. This study sheds light on the course of the disease modified by state of the art surgical management that was available during the study period. It is notable that cardiac surgical therapy and catheterization techniques and the understanding of the disease itself had greatly improved during this study period. This study however helps to set the goals for future management planning.

Overall, 60% of infants survived to 1 year highlighting the greatest attrition that occurs during infancy with or without palliation. Of the patients who survived to 1 year, 65% lived to 10 years. Only 16% of these patients who lived up to 10 years were alive at 35 years of age. Cardiovascular complications included infective endocarditis (n = 17), stroke (n = 15) and RV failure (n = 16). Aortic regurgitation has been recognized in 62% of patients by the age of 30 years. Thirty one percent of patients who underwent definitive surgical repair died within 30 days of surgery and thirty eight percent of them died by 3 months. There was no difference in survival up to 2 years between the patients who underwent definitive repair versus no definitive repair. A difference was only noted after 5 years from definitive surgery.

Thus, the overall outcome in the first 3 decades of surgical approach to this lesion has not been encouraging despite significant progress in treatment of other complex congenital heart lesions. The survivors after definitive repair remain functionally well and are less symptomatic than the non-repaired patients. Evolution of newer management strategies in the past two decades appears to have considerably improved outcome. All patients face periodic re-operations and therapeutic catheterization procedures throughout their life time after complete repair, for replacement of RV - PA conduit and for correction of any residual obstruction in RVOT.

 IV. Pathology

Description of pathology of this defect falls under two categories namely intracardiac anatomy and pulmonary blood supply.

IV.1: Intracardiac anatomy

PA-VSD is characterized by atresia of both the pulmonary valve and a variable length of main pulmonary artery (MPA). Ventricular septal defect (VSD) is an integral part of the lesion and is typically large, malaligned, membranous type and can occasionally be of the infundibular type. There is variable degree of aortic override, and right ventricle (RV) hypertrophy develops as a consequence of hemodynamic effects.

It should be noted that PA-VSD is different from pulmonary atresia-intact ventricular septum (PA -IVS) in that the latter lesion has no VSD and is generally associated with hypoplastic tricuspid valve and RV, or dilated and dysfunctional RV with regurgitant tricuspid valve. Generally, pulmonary artery abnormalities are not seen in PA-IVS. Moreover, presence of coronary sinusoids is a significant issue in PA-IVS. Unlike tetralogy of Fallot, coronary arteries in A-VSD are usually normal with a prominent conal branch.

IV.2: Pulmonary blood supply

Abnormalities in pulmonary artery anatomy and pulmonary blood supply are significant features of PA-VSD that sets it apart from classic Tetralogy of Fallot. Variations in pulmonary blood supply makes each patient unique and warrant individualized planning of surgical and catheter-based strategies. Complexity in the management of Tet-PA stems from the complexity of pulmonary blood flow. The discussion of pulmonary blood flow in PA-VSD includes the extent of MPA atresia, patent ductus arteriosus, native pulmonary arteries, aortopulmonary collaterals and distal pulmonary vascular arborization.

Extent of pulmonary valve atresia varies from only a plate-like atresia of the pulmonary valve to absence of both valve and a variable length of MPA. Extension of MPA atresia to its bifurcation results in non-confluent central pulmonary arteries (PAs). Presence or absence of confluent PAs significantly influences surgical outcome. At birth, PDA becomes an essential source of pulmonary blood flow when confluent pulmonary arteries are present. In PA-VSD, PDA typically originates from either the undersurface of the arch (67%) or from the undersurface of the innominate artery (33%). Unilateral PDA is usually associated with confluent PAs, while PDA can be bilateral as is usual with non-confluent PAs. When PDA is present, PAs are confluent in 80% of cases. All patients with PDA have central Pas [6] . Notably, PDA is absent in 1/3 of cases and is associated with absent central Pas [6] .

Aortopulmonary collaterals (APCs) are muscular arteries until they enter the lung parenchyma, but the muscular layer is gradually replaced by elastic lamina that resembles true pulmonary arteries. APCs are seen in 30 - 65% of patients with PA - VSD [7] and are usually 2 - 6 in number. Known sites of origin of APCs include descending thoracic aorta at the level of carina, subclavian arteries, abdominal aorta, and coronary arteries. Sixty percent of APCs have stenosis either at diagnosis or it develops over a period of time during follow up.

The differentiation between PDA and APCs is important in newborns, who have balanced pulmonary blood flow and therefore, are candidates for a relatively late definitive repair. In such patients, a reliable source of pulmonary blood flow is necessary until cardiac repair is performed. PDA is considered a less reliable source beyond the first few days of life due to its tendency to close. Though APCs are also prone for stenosis over a period of weeks to months, they remain patent more reliably than PDA until surgical repair is performed at few months of age. Color Doppler flow studies have been shown to be reliable in making this distinction between PDA and APCs based on the direction of blood flow in the proximal mediastinal segment of Pas [6] . Furthermore, PDA is straight and do not branch while APCs in general, are tortuous and may branch. .

 V. Classification

The anatomic spectrum varies from atresia of pulmonary valve, presence of MPA and confluent normal sized PAs that are supplied by a PDA; to atresia of MPA with diminutive and/or non-confluent PAs, absent PDA and pulmonary blood supply solely provided by multiple APCs and bronchial arteries. There are several degrees of severity in between these two extremes of the spectrum. Consequently, it has been difficult to classify this lesion and compare the outcome. A practical classification has been proposed by Congenital Heart Surgeons Society based on complexity of pulmonary blood supply which in turn indicates the complexity of surgical repair [1] [Figure 1].

Type A: Native PAs present, pulmonary vascular supply through PDA and no APCs.

Type B: Native PAs and APCs present

Type C: No native PAs, pulmonary blood supply through APCs only.

Surgical approach for type B and C is similar except that more extensive unifocalization of APCs will be needed in Type C, before the total repair is achieved.

 VI. Evaluation of a child with PA-VSD

VI.1: Clinical presentation

Approximately 65% of Tet-PA patients present to a cardiac center during infancy. The remainder presents later presumably because of high enough pulmonary blood flow which lead to clinically undetectable cyanosis during the early months of life. Overall, the modes of presentation in Tet-PA consisted of cyanosis (50%), heart failure (25%) or murmur with mild cyanosis with or without failure to thrive (25%) [5] .

Newborns present with cyanosis with or without a heart murmur. Such newborns have duct dependent pulmonary circulation. The presentation occurs when the duct starts to constrict. Severe hypoxia, acidosis and shock ensues closure of PDA. If the babies had gone home by this time, they present to the emergency department in extreme shock and acidosis. Typical age of presentation in this group is 3 - 7 days. Sepsis, congenital adrenal hyperplasia, other duct-dependent congenital heart diseases or severe illnesses affecting other systems comprise the differential diagnosis.

There may or may not be a murmur which is typically continuous in nature representing aortopulmonary collateral artery flow if present. Immediate resuscitation with prostaglandin E1 (PGE1) infusion will help to stabilize the patient. This is the type with good-sized native PAs which are supplied by a duct. Usually, these patients do not require unifocalization and are good candidates for neonatal repair with right ventricle to pulmonary artery (RV-PA) conduit. However, babies with more complex pulmonary blood flow tend to be less dependent on ductal flow since the proportion of pulmonary blood flow derived via native PAs is much less than that derived via the APCs. If the pulmonary blood flow is adequate and well-balanced, these babies will only have mild cyanosis and will escape detection as a newborn.

Presentation in early infancy occurs when the baby has "balanced circulation" with adequate pulmonary blood flow via APCs. These babies often present after 4 - 6 weeks of age either with increasing cyanosis or signs of heart failure. Development of stenosis in APCs progressively reduces pulmonary blood flow causing progressive cyanosis. Alternatively, pulmonary over circulation occurs from the physiologic reduction in pulmonary vascular resistance as the newborn gets older and leads to heart failure. These infants may have only mild cyanosis and escape recognition until later.

There is yet another subset of patients with adequate and "balanced" pulmonary blood flow throughout early infancy and may present during late infancy. Such patients may present with a heart murmur that was heard during routine physical examination and cyanosis or heart failure was not clinically obvious. As a general rule, in complete mixing lesions such as pulmonary atresia, systemic oxygen saturation of 85% is achieved by Qp/Qs of at least 2.5 (mixed venous saturation 60%). Symptoms of heart failure in childhood imply a Qp/Qs ≥ 4. The so-called "balanced circulation" with asymptomatic infants occurs when Qp/Qs ranges between 2.5 and 4 during infancy [5] .

Failure to thrive in the absence of heart failure has been reported as a presenting symptom but the mechanism is unclear and can be secondary to underlying genetic abnormality.

Adult patients, either unoperated since they were deemed inoperable or had undergone only a palliative procedure, are infrequently seen in the current era. In a recent report of 26 adult patients [4] , all were cyanotic (mean oxygen saturation of 85%) and polycythemic (mean hematocrit 57%) at presentation. They were all symptomatic with signs of heart failure such as effort dyspnea or decreased exercise tolerance and were NYHA functional class II or III.

VI.2: Physical examination

The severity of cyanosis depends upon the amount of pulmonary blood flow. Close clinical follow up with regular measurement of oxygen saturations is essential until surgical repair is accomplished. On the other hand, fall of pulmonary vascular resistance during early infancy allows increase in pulmonary blood flow leading to heart failure and present with feeding difficulty, failure to thrive, signs of respiratory distress, tachypnea, tachycardia and hepatomegaly. A bounding pulse in these infants is usual and signified large pulmonary blood flow with run-off from systemic arteries through APCs. Auscultation reveals the absence of pulmonary component of second heart sound and therefore, a single S2. Continuous bruit of the flow through APCs could be heard over the chest wall. As the infancy progresses, cyanosis usually worsens and polycythemia and clubbing may develop.

VI.3: Chest X ray

Boot shaped heart: The left heart border on chest X-ray from above downwards is constituted of aortic arch, main pulmonary artery, left atrial appendage and left ventricular apex. In Tetralogy of Fallot with or without pulmonary atresia, the main pulmonary artery segment is small or absent creating a concavity below the aortic arch. The right ventricular hypertrophy leads to upward pointing of the cardiac apex from the right dome of the diaphragm. The combination of concavity at the upper mid part of the left heart border with the uplifting of the cardiac apex creates a boot shape appearance of the cardiac silhouette on chest X-ray. Right aortic arch (25 - 50%), is more common in this lesion than classic Tetralogy of Fallot (20 - 25%) and can be diagnosed on chest X-ray and more precisely by echocardiogram. Pulmonary vascular markings have a typical reticular pattern when there are multiple collaterals supplying the lungs. Overall extent of pulmonary vascular markings will depend on the extent of pulmonary blood flow.

VI.4: Electrocardiogram

The EKG findings depends on the age of the patient. Right axis deviation, right ventricular hypertrophy and possibly right atrial enlargement are usual features. Biventricular hypertrophy is noted in patients with increased pulmolnary blood flow. In newborns, presence of right ventricular hypertrophy differentiates it from PA-IVS which has diminutive RV forces in the anterior chest leads. However, there is less emphasis on EKG findings in the era of advanced echocardiographic technology.

VI.5: Echocardiography

Echocardiography is the key diagnostic modality for the diagnosis of congenital heart diseases. While echocardiography has supplanted diagnostic catheterization studies to a considerable extent in the evaluation of infants with PA-VSD, creative use of other non-invasive modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) are increasingly used to define pulmonary blood flow. Echocardiography is the gold standard to delineate intracardiac defects but has limitations for the extracardiac vascular structures. Direction of blood flow in central PAs helps to differentiate PDA from APCs. The blood flow by color Doppler typically is antegrade if the source is PDA since PDA joins the PA in the mediastinum while the collateral arteries join PAs in the lung hilum, and hence, the flow in the central PAs will be retrograde. In general, if there is evidence of significant APCs, a diagnostic catheterization angiography or CT/MR angiography is generally performed to define the precise anatomy and distribution of blood flow in the APCs.

VI.6: Cardiac Catheterization

The technological advances in echocardiography with color Doppler imaging over the past 2-3 decades, have diminished the indications for diagnostic catheterization. The focus of catheterization has shifted from making the diagnosis to filling in missing information in the diagnosis such as the hemodynamic data regarding pulmonary blood supply. Other specific questions unanswered by echocardiography such as: 1) coronary anatomy; 2) aorto-pulmonary collateral arteries (number, size, distribution, any stenosis and blood pressure in each collateral vessel) [Figure 2]: A, B; 3) confirmation of presence or absence of native PAs and a retrograde pulmonary vein wedge injection if needed to identify their presence if not clear on aortography; 4) number of lung segments connected to native Pas; and 5) lung segments with dual blood supply.

VI.7: CT / MR angiography

CT/MR angiography provides an alternative modality to conventional angiography to define RVOT, MPA, branch PAs and APCs [8] .

VI.8: Nuclear perfusion scan

Quantitative lung perfusion scan using nuclear scintigraphy is useful in defining relative distribution of RV output to each lung and to individual lung segments. Such lung perfusion scans help to guide and gauge interventional catheterization therapy during pulmonary arterial rehabilitation postoperatively and is generally not helpful preoperatively in the presence of APCs.

VI.9: Evaluation of adequacy of pulmonary arteries

The complexity of pulmonary blood supply determines the extent of surgical exploration necessary to perform unifocalization. Eligibility for complete repair is dependent on this since the RV-PA conduit needs to be placed to the vessel which is connected to maximum possible pulmonary vascular bed. Furthermore, closing the VSD at the time of placement of RV - PA conduit needs to be determined. Adequacy of the pulmonary vascular bed and the pulmonary vascular resistance are the determinants of postoperative RV pressure which in turn has been closely correlated with surgical outcome. At least 10 - 16 lung segments need to be connected to the RV-PA conduit in order to have satisfactory hemodynamic result after complete repair [9] . If the central native PAs were not identified on echo, it is prudent to demonstrate them angiographically. Furthermore, a simultaneous contrast injection into the proximal stump of the pulmonary artery and the pulmonary vein wedge injection will help to define the length of discontinuity that need to be "bridged" surgically during repair [10] .

Preoperative evaluation of adequacy of pulmonary artery size is difficult because of under filling of PAs and therefore, the potential size of these PAs after surgical repair is unpredictable. However, several pulmonary artery indices have been developed by several investigators:

1) McGoon's ratio: McGoon's ratio is calculated by dividing the sum of the diameters of RPA (at the level of crossing the lateral margin of vertebral column on angiogram) and LPA (just proximal to its upper lobe branch), divided by the diameter of aorta at the level above the diaphragm [DRPA /DDTAO)+( DLPA / DDTAO)]. An average value of 2.1 was noted in normal subjects. Ratio above 1.2 is associated with acceptable postoperative RV systolic pressure in Tetralogy of Fallot. Ratio below 0.8 is deemed inadequate for complete repair of PA - VSD. VSD closure is deferred in such patients at the time of repair or they underwent aortopulmonary shunt procedure as first stage [11],[12] . However, this ratio tends to overestimate the adequacy of the size of PAs since this is derived using the diameter of descending thoracic aorta at the level of diaphragm which is frequently smaller in patients with PA-VSD.

2) Nakata index: Nakata PA index is calculated from the diameter of PAs measured immediately proximal to the origin of upper lobe branches of the respective branch Pas [13] . The sum of the cross sectional area (CSA) of right and left PAs is divided by the body surface area of the patient [Nakata index = CSA of RPA (mm2) + CSA of LPA (mm2)/ BSA (m2)]. A Nakata index of >150 mm2/m2 is acceptable for complete repair without prior palliative shunt14. While Nakata index is widely used in preoperative assessment of adequacy of pulmonary vascular bed, it is not useful in patients with multifocal pulmonary blood supply, who are evaluated for single-stage repair of PA - VSD. UCSF group had proposed a total Neo-pulmonary artery index for use in patients with such complex lesions.

3) Total Neo-pulmonary artery index (TNPAI): Nakata index is of limited use for evaluation of the adequacy of PAs in single stage repair strategy where unifocalization of several APCs is followed by total repair at the same operation. In Nakata index, there is no provision for the additional vascular bed that will be added by unifocalization. A composite index of native PAs and the APCs that will be unifocalized was needed, in order to determine whether the VSD could be closed at surgery.

The UCSF group proposed TNPAI in order to help preoperative planning in these patients15. Nakata PA index was measured as described above. Then, APCs index was calculated by addition of CSA of all significant APCs divided by the BSA. CSA of each APC was calculated from diameter of the respective vessels measured on preoperative cineangiogram. The sum of total APC index and PA index is called TNPAI. A TNPAI index >200 mm2/m2 correlated well with low postoperative RV/LV pressure ratio and identified patients who were clear candidates for VSD closure at the time of single-stage surgical repair. These indices are limited in value since they are based on the size of the proximal vessels only. The nature of the distal pulmonary vascular bed and pulmonary vascular resistance are not expressed in these calculations. Since these latter factors play an important role in postoperative RV pressure and in turn the hemodynamic outcome of surgical repair, an intraoperative method to assess the adequacy of pulmonary vascular bed has been proposed [15] .

 VII. Management

VII.1: General principles of surgical therapy of PA-VSD:

Heterogeneity of pulmonary blood supply in PA-VSD precludes uniformally applicable management to all the patients. However, certain guiding principles of management have evolved over the past 3 decades based on earlier observations in these patients. Connecting as many lung segments as possible to the blood flow from RV during early infancy is essential since early attrition of these patients occurs during infancy and significant histologic changes occurs in pulmonary vasculature during young age [5],[9] . Development of pulmonary vascular occlusive disease from unrestricted pulmonary blood flow from APCs can develop as early as 4 weeks [16] . Recruitment of lung segments into RV-PA conduit supply is more successful when blood flow to it is restored early in life and complete repair should be attempted within weeks to months during infancy. Therapeutic catheterization procedures such as balloon angioplasty help to rehabilitate pulmonary arteries with stenosis and should be combined with surgical repairs to optimize the overall outcome.

VII.2: Components of surgical repair:

Regardless of the surgical strategy that is used for a given patient, the components of total repair of PA-VSD consist of (a) placement of RV - PA conduit, (b) unifocalization of APCs and (c) VSD closure. These components are performed in one-stage, or at different operations depending on the anatomy and institutional policy.

a) RV - PA conduit placement: Typically a cadaveric, cryopreserved homograft is used to connect right ventricle to available central pulmonary arteries. In complex cases, where a central pulmonary artery is absent or the pulmonary blood flow is multifocal, unifocalization of the diminutive native pulmonary arteries and APCs will be performed before RV - PA conduit is placed [Figure 3].

b) Unifocalization of APCs: It was shown in the mid seventies that unifocalization will enable connecting more lung segments to central Pas [17],[18] , and the current practice is to unifocalize significant APCs during the first 3 months of life. Median sternotomy is the preferred method especially if single stage repair is planned. In multi stage surgical approach, unifocalization is done through lateral thoracotomies. During unifocalization, APCs are ligated at the origin and mobilized to maximize their length with creative rerouting. Such mobilized vessels are anastomosed in the mediastinum before being connected to RV-PA conduit.

c) VSD closure: Closure of VSD at the time of initial repair is desirable in order to avoid the need for further surgery. However, if there were any concerns about the adequacy of the pulmonary vascular bed, it is customary to defer VSD closure. Leaving the VSD unrepaired, helps to avoid supra-systemic RV pressure in the immediate postoperative period by allowing RV to decompress through the VSD. Over a period of months, pulmonary vascular development occurs and the VSD can be closed safely with sub-systemic RV pressure. The strategy of delayed VSD closure has reduced the operative mortality.

With the single stage surgical repair strategy it is important to ensure that pulmonary vasculature is adequate, both in diameter of proximal pulmonary vessels and development of distal pulmonary vascular bed, for the safe closure of VSD. Preoperative PA indices mentioned earlier help to assess the adequacy of PA size and the nature of distal pulmonary vascular bed that is connected to central PAs.

However when a single-stage repair strategy is adopted with unifocalization of APCs at the same operation, preoperatively-determined PA indices will not be able to predict the level of pulmonary vascular bed added by unifocalization of APCs. Therefore, an intraoperative method to evaluate adequacy of pulmonary vascular bed was proposed by the UCSF group [15] . After completion of unifocalization and distal anastamosis of RV - PA conduit, a perfusion cannula and a PA catheter are inserted from the proximal end of the conduit and left atrial vent is placed. The conduit is connected to the bypass machine. The bypass machine is run at increasing flow rates to 2.5 L/min/m2 and the PA pressure is monitored. VSD is closed if the mean conduit pressure is [15].

 VIII. Multi-stage versus single-stage approach

VIII.1: Multi-stage approach: A multi-stage correction evolved from the early surgical experiences. Inevitably, the strategy changed based on individual patient's anatomy and clinical features. Traditional approach consisted of a palliative shunt in all patients (patients with "good size", confluent central PA in particular) during neonatal period or early infancy to relieve cyanosis and allow for growth of distal pulmonary arteries. However, with diminutive PAs, RV - PA continuity is established by placing a RV - PA conduit. This provides catheter access to peripheral PAs to perform balloon angioplasty of the pulmonary arteries. The VSD is typically left open at this first stage. Any possible unifocalization of APCs will also be performed.

A subsequent operation will be done to close the VSD, relieve any residual right ventricular outflow tract obstruction and place a valved conduit. With absent mediastinal PAs, the surgical approach is further complicated. Two modified Blalock Taussig shunts are performed to each PA via bilateral thoracotomies. Unifocalization of any significant APCs will be preformed. Each thoracotomy is done during the same hospitalization but separated by few days. This will relieve cyanosis and allow growth of native pulmonary arteries. The babies would have catheter evaluation prior to next operation. The second operation will consist of RV - PA homograft, connection of all branches of PA with or without VSD closure. Modifications to above mentioned generalized outlines will be made dependent upon individual patient's condition.

VIII.2: Single-stage approach: Current surgical approach attempts to perform APCs unifocalization and cardiac repair at the same operation, through median sternotomy. The choice between multi-stage and single-stage repair is dependent on various factors: Nature of PAs (small vs. good size), (duct-dependent or collateral-dependent PBF), age of the patient at presentation, status of APCs, and availability of surgical skills and results of the institution. Newborns with no PDA and adequate collateral dependent pulmonary blood supply with acceptable systemic oxygen saturations, are the typical candidates for elective single-stage unifocalization and cardiac repair that is performed at about 3 months of age.

VIII.3: Comparison of outcome between multi and single-stage repair: Several theoretical advantages of the single-stage approach over the more traditional multi-stage approach exist. Single stage repair allows for early normalization of cardiovascular physiology by recruitment of all possible lung segments into RV derived circulation as early in life as possible. This alleviates cyanosis and polycythemia during infancy. Early repair also preserves pulmonary vascular bed and avoids development of pulmonary vaso-occlusive disease in the lung segments exposed to systemic pressure via APCs, and hypoplasia of the distal pulmonary vasculature in under-perfused lung segments. There is also evidence to suggest that long term cardiac function is preserved by avoiding ventricular dysfunction from prolonged cyanosis and arrhythmias [19] . When we compare outcome between patients treated in same surgical era [20], [21] , the ultimate results are comparable but patients in the single stage group undergo one or two operations less than the patients in multi-stage group do.

 IX. Complementary role of interventional catheterization

Interventional catheterization has assumed an important complementary role in rehabilitation of pulmonary arteries in the management of patients with PA - VSD by the use of balloon angioplasty and stent placements [22] . Catheterization helped avoiding surgery in case of stenosis in proximal segments of the PAs and by being able to reach distal stenosis within lung parenchyma that are inaccessible to the surgeon. Coil occlusion of APCs, stent placement in RVOT and palliative stenting of stenotic APCs are some of the other procedures that interventional catheterization has to offer to the patients with PA - VSD.

 X. Long term sequelae/outcome

Many of the long term sequelae have been mentioned earlier under the natural history section. Patients who were unsuitable for complete surgical repair and therefore were palliated with systemic to pulmonary artery shunts only, develop progressive cyanosis and polycythemia as they survive into adulthood. Aortic regurgitation (AR) develops in a significant number of patients with or without complete surgical repair. Development of AR occurs more often with patients who had palliative shunts only since they add to the LV volume overload and therefore LV dilatation. The resultant aortic annular dilatation worsens aortic regurgitation. Infective endocarditis affecting aortic valve is another mechanism of AR. Progressive LV dilatation due to volume overload from AR, systemic to pulmonary artery shunt or collateral flow eventually leads to LV dysfunction.

In patients who have had complete repair, there is a gradual deterioration of conduit function [23] from loss of luminal diameter, calcification, peel formation and from the deterioration of valve function. The valve in the conduit is prone for calcification, stenosis and regurgitation. Pulmonary regurgitation worsens with any residual stenosis in distal pulmonary arteries. While pulmonary regurgitation is well tolerated for years, RV dilatation and hypertrophy eventually ensues leading to RV dysfunction [24] . There is evidence that RV dilatation with dysfunction can eventually impact LV function by ventricle-ventricle interaction. However, optimal timing of re-operation either to replace the deteriorated conduit or implantation of pulmonary valve to stop pulmonary regurgitation is still unclear. Development of ventricular arrhythmias has been documented after tetralogy repair. This is thought to account for the relatively high incidence of sudden deaths noted in patients long after tetralogy repair. Co-existing poor hemodynamic parameters such as high RV pressure is thought to be a risk factor for arrhythmias. Correction of hemodynamic abnormalities by pulmonary valve implantation or replacement of RV - PA conduit is expected to help reduce this risk [25] . The outcome from the current modified approach combining surgery and therapeutic cardiac catheterization techniques has improved the outcome and long term studies in future will provide proof of such improved outcome.


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