Abstract
This chapter describes the disease spectrum of pulmonary atresia with intact ventricular septum (PA/IVS). It reviews the embryology, anatomy, physiology, treatment algorithms, and surgical techniques and outcomes. PA/IVS is a highly variable continuum of severe congenital heart disease. The severity of this disease ranges from patients with simple plate-like pulmonary atresia with relatively normal right ventricular anatomy and geometry who can undergo a biventricular treatment pathway, to those patients with “hypoplastic right heart syndrome” who must undergo single-ventricle palliation. Patients with right ventricular sinusoids and coronary artery fistulae with right ventricular–dependent coronary circulation have an associated high rate of early mortality. Many programs have adopted a primary transplant strategy for these fragile patients. For those patients whose anatomy allows for potential one-and-one-half- or two-ventricle pathways we have adapted a hybrid treatment strategy for early palliation followed by completion of biventricular repair or one-and-one-half-ventricle repair, usually within the first year of life with excellent early and midterm results. Outcomes for the treatment of PA/IVS have improved significantly over the past several decades. Quality of life for these patients is subjectively good; however, when measured objectively, many of them continue to have limited exercise capacity. Those patients with borderline anatomy for a two-ventricle repair, as evidenced by small tricuspid valve z scores, may have better exercise capacity when treated with one-and-one-half-ventricle palliation or single-ventricle palliation.
Key Words
Pulmonary Atresia, Intact Septum, Hypoplastic Right Heart
In 1783, Hunter described membranous or muscular atresia of the right ventricular outflow tract. This deformity was revisited by Peacock in 1869 and then again by Robert Freedom in 1989. They described remarkable heterogeneity of the right ventricular inlet and functional size, as well as the subepicardial connections between the diminutive RV chamber and the coronary artery circulation. The span of almost 100 years between these published investigations speaks to the difficulty in understanding this particular form of heart disease. Pulmonary atresia with intact ventricular septum (PA/IVS) is anatomically and functionally a left-sided heart with normal atrial relations (situs solitus), concordant atrioventricular and ventriculoarterial connections presenting with obstruction to RV outflow that can range from a relatively normal RV chamber and tricuspid valve size with an imperforate membrane in the location of the pulmonary valve at one end of the spectrum, to “hypoplastic right heart syndrome” with a diminutive tricuspid valve, a tiny RV cavity and often RV to coronary artery connections associated with a long area of muscular infundibular atresia at the other end of the spectrum. The ventricular septum is intact. Because of the absence of antegrade flow across the RV outflow tract, PA/IVS is a “ductal dependent” lesion. The patent ductus arteriosus (PDA) supplies pulmonary blood flow, and multiple aortopulmonary collaterals and nonconfluent pulmonary arteries are uncommon. Approximately 20% of patients have subendocardial fistulous connections, frequently called “sinusoids.” Infants born with this disease usually present with cyanosis shortly after birth when their PDA begins to close.
Poor development of the tricuspid valve is a result of the abnormal, highly pressured right ventricle (that has no outlet), and the degree of tricuspid regurgitation appears to correlate with the severity of the defect. Fetal loss may account for an underestimated incidence and prevalence of the defect, which is estimated at 0.6/10,000 live births. Consequently, the real incidence of this defect is speculated as being up to ten times higher. The prenatal echo is a postnatal prognosticator, with an emphasis on the tricuspid valve Z score as well as on the anatomy of the RV chamber—with attention to the presence of a well-developed inlet, apical trabecular, and outlet (tripartite) portions of the right ventricle. There have been attempts to characterize muscular hypertrophy with the proposal that intervention may cause regression of the hypertrophy with a real versus perceived growth of ventricle. This has been the rationale for fetal intervention for this disease. Figure 61.1 provides a schematic representation of the spectrum of defects in PA/IVS.
Because of this wide spectrum and variability in disease severity, mainly related to tricuspid valve size, RV chamber anatomy, and coronary artery anomalies, complex algorithms for treatment are required to ensure optimum outcomes for these often fragile patients. These algorithms have resulted in improved survival in patients diagnosed with PA/IVS, particularly in the more severe forms of the spectrum.
This chapter reviews the embryology, anatomy, physiology, treatment strategies, and outcomes for this diverse group of patients.
Embryology
The embryologic cause of PA/IVS to this day remains unknown. Identifiable genetic syndromes and other cardiac and noncardiac malformations are less common in PA/IVS than in other forms of congenital heart disease. There are currently no known genetic causes, although there are reports of familial cases of PA/IVS with an autosomal dominant inheritance pattern with incomplete penetrance. A single-gene theory has also been proposed in a sibling pair, suggesting that an autosomal recessive pattern may have a role. However, based on these somewhat conflicting sources, evidence is insufficient to establish a consistent genetic association for PA/IVS
The failure of the separation of the pulmonary valve leaflets leads to decreased flow through the tricuspid valve and RV, which leads to RV muscular hypertrophy and hypoplasia of the RV cavity in utero. It has been proposed that this perturbation in fetal blood flow may occur after cardiac septation, which may explain the normal size of the proximal main pulmonary artery in most cases of PA/IVS when compared with pulmonary atresia with ventricular septal defect (PA/VSD).
The later fusing of the pulmonary valve leaflets may be related to viral infection or inflammatory disease in midterm gestation, as opposed to the atresia occurring in PA/VSD, which is felt to be an early developmental event. However, there has been no relationship established between PA/IVS and maternal rubella, despite the suggested association between pulmonary stenosis and maternal rubella. Additionally, there are most often no other associated findings of cardiac inflammation that would indicate this is a systemic or at the very least cardiac inflammatory process.
The development of coronary fistulae (sinusoids) does not appear to be an inflammatory process but rather seems to be due to myointimal hyperplasia in the presence of a rich background of glycosaminoglycans. There are mild degrees of medial-intimal thickening due to a loss of normal wall with replacement of the wall by fibrocellular material. Of note, this process does not occur in thin-walled low pressure systems.
Anatomic Considerations
Pulmonary Artery Anatomy
Complete fusion or absence of the pulmonary valve cusps is the hallmark of PA/IVS. Often the main pulmonary artery is only mildly hypoplastic, and frequently it is normal in size. The pulmonary valve sinuses are often normally developed, and the leaflets may, in milder forms, be fairly thin. However, usually the cusps are quite misshapen and even cartilaginous in their appearance.
Ventricular Anatomy
The RV ranges in size and form from a well-developed tripartite RV (with an inlet, trabecular, and outlet portion) to a severely hypoplastic diminutive inflow chamber. Bull et al. in 1982 showed that RV hypertrophy led to decreased apical trabecular chamber and inflow size. Both by angiography and autopsy they showed that hearts with obliterated infundibular and trabecular cavities had thicker walls and smaller tricuspid valves than those in which the normal three portions of the ventricular cavity were represented. This original tripartite classification is helpful in determining treatment strategy for these patients. Typically the left ventricular anatomy is normal in size and geometry.
Tricuspid Valve Anatomy
The tricuspid valve itself exhibits a high degree of variability in form and function, ranging from severe stenosis to massive regurgitation. The anatomic size of the tricuspid valve also determines or is correlated with RV morphology. The patients with the smallest tricuspid valves tend to have absence or attenuation of the trabecular and outlet portions of the ventricle. These patients are the ones least likely to have a tripartite RV.
Ebstein anomaly of the tricuspid valve is an unusual component of PA/IVS seen in approximately 10% of cases. It can pose a significant challenge in the management of patients who present with this tricuspid valve anatomy.
Coronary Artery Anomalies
Coronary artery anomalies represent the most likely reason for patients succumbing to this disease entity. Ischemic events related to abnormal coronary anatomy and abnormalities in the arterial wall are common in the more severe forms of the disease. Coronary artery anomalies in patients with PA/IVS include (1) RV-to-coronary artery fistulae, (2) coronary artery stenoses, and (3) coronary occlusions. In some, a substantial part of the coronary blood supply may depend on the RV. This RV-dependent coronary circulation may determine survival after RV decompression (RVD): RVD may cause RV “steal” in the presence of fistulae alone and ischemia, coronary isolation, or myocardial infarction in the presence of coronary stenoses ( Fig 61.2 ).
Microstructural abnormalities of the coronary arterial wall are also common and can lead to ischemic areas of myocardium with subsequent fibrosis even if aorta coronary continuity exists.
Fetal Diagnosis
PA/IVS can be diagnosed in utero and this can help with educating the family and preparing the medical and surgical team for eventual treatment options, including having the baby delivered at a center where prostaglandins can be started and transfer to a cardiac center initiated.
The true value of fetal echocardiography in the diagnosis of PA/IVS lies in predictive factors, and the ability to develop postnatal plans. Some of the morphologic and physiologic predictors for the postnatal surgical pathway include a combination of z-scores of fetal cardiac measurements and tricuspid/mitral valve (TV/MV) ratios, the presence of coronary fistulae, the right atrial pressure (RAP) based on the patent foramen ovale, the tricuspid valve dimension and competency and the ductus venosus Doppler. The combination of these variables can predict a biventricular circulation (at 26 weeks gestation) with a 92% specificity. The tricuspid valve z-score is a good predictor at all gestation. The best predictive scores for specific gestations include the pulmonary z-score (23 weeks) and the median tricuspid z-score (26 weeks) with a combination of median PV z-score and TV/MV ratio (26 to 31 weeks), and a combination of median TV z-score and median TV/MV ratio (31 weeks). The RAP score and the presence of coronary fistulae are good independent predictors with a RAP score >3 predicting a biventricular repair (83%) and the presence of coronary artery fistulae usually predicting a single ventricle route.
Physiology
Due to the atretic pulmonary valve and absence of flow from the RV to the pulmonary arteries, the physiology is dependent on left-to-right ductal flow for pulmonary circulation. Prostaglandin infusion is the mainstay of medical treatment in these newborns and allows time for further workup and planning. Systemic venous return to the right atrium requires a nonrestrictive ASD to allow right to left shunting to support cardiac output.
Treatment Strategies
Preprocedural Care and Evaluation
Patients are maintained on prostaglandin infusion after birth, and standard workup for newborns with complex congenital heart disease is undertaken. Imaging with echocardiogram and cardiac catheterization, including aortic root injection to determine aortocoronary continuity, is standard. This allows adequate and accurate categorization of risk, as well as surgical planning.
PA/IVS is a rare form of complex congenital heart disease with significant morphologic heterogeneity. Because of the significant morphologic heterogeneity seen in PA/IVS, repair or palliation strategies have a wide variation, from single-ventricle palliation to complete biventricular repair. The likelihood of significant coronary artery abnormality is related to tricuspid valve Z score ( Figure 61.3 ). the smaller the tricuspid valve, the greater the likelihood of need for staging to the single ventricle or transplant pathways.
