eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Cardiology

Tetralogy of Fallot With Pulmonary Atresia

Author: Michael Pettersen, MD, Director of Echocardiography, Division of Cardiology, Children's Hospital of Michigan; Associate Professor of Pediatrics, Wayne State University School of Medicine
Coauthor(s): Aparna Kulkarni, MBBS, MD, Fellow, Department of Cardiology, Children's Hospital of Michigan
Contributor Information and Disclosures

Updated: Nov 24, 2008

Introduction

Background

Tetralogy of Fallot (TOF) is comprised of a malaligned ventricular septal defect (VSD), anterior shift of the aorta over the VSD (overriding aorta), obstruction of the right ventricular outflow tract, and right ventricular hypertrophy. Pulmonary atresia (PA) with VSD is considered the extreme end of the anatomic spectrum of tetralogy of Fallot. Tetralogy of Fallot with pulmonary atresia is worthy of separate consideration. Because of the wide variability of pulmonary blood supply, diagnosis and surgical management of tetralogy of Fallot with pulmonary atresia is more difficult than that of classic tetralogy of Fallot.¹

Embryology

The lungs develop from the foregut and carry their nutrient supply from the paired dorsal aortae. The paired sixth aortic arches also give rise to branches that form an anastomosis with the pulmonary vascular tree at 27 days' gestation. Over time, the branches from the descending thoracic arch become smaller, and the sixth aortic arch becomes larger.

The aorta and pulmonary arteries form from the distal bulbus cordis and the truncus arteriosus, which are positioned above the right ventricle. The bulbotruncal ridges separate the great arteries, and the aortic component posteriorly rotates. However, faulty rotation of the bulbus-truncus in tetralogy of Fallot results in incomplete transfer of the aorta above the left ventricle. Malalignment of the infundibular septum to the trabecular septum is present, resulting in a malalignment VSD. Anterior displacement of the bulbotruncal region has been postulated to cause the infundibular stenosis. Another theory that has been suggested to cause tetralogy of Fallot is underdevelopment of the subpulmonic infundibulum that results in maldevelopment of the conal septum. Little or no evidence supports this hypothesis.

Anatomy

Anatomy of the pulmonary arteries and the source of pulmonary artery blood supply may widely vary in tetralogy of Fallot with pulmonary atresia. Persistence of descending thoracic branches accounts for the abnormal pulmonary arterial supply in this condition. Major aortopulmonary collateral arteries may anastomose at any site in the pulmonary vascular tree. Most frequently, the right and left pulmonary arteries are patent and maintain free communication with each other; they are termed confluent pulmonary arteries. The pulmonary arteries may also be hypoplastic and nonconfluent. No antegrade blood flow is present from the right ventricle to the pulmonary arteries. The ductus arteriosus (DA) is often an important source of blood supply, although occasionally it is absent.²

Classification of pulmonary atresia with VSD depends on the predominant source of blood supply to the bronchopulmonary segments. These range from the native confluent pulmonary arteries supplied solely by the DA to nonconfluent pulmonary arteries with multiple major aortopulmonary collaterals supplying pulmonary blood flow. Rare sources of pulmonary blood flow include an aortopulmonary window, a persistent fifth aortic arch, and coronary–to–pulmonary artery fistulae. Identification of the pulmonary arterial supply is essential in planning the type of surgical repair.

Pathophysiology

Clinical presentation in tetralogy of Fallot with pulmonary atresia depends on the source and volume of pulmonary blood flow. This usually occurs via the DA and/or aortopulmonary collaterals. The newborn infant, in whom the DA is the sole source of pulmonary blood flow, becomes increasingly cyanotic as the DA closes. Early recognition of the diagnosis along with prompt institution of prostaglandin E1 (PGE1) infusion is life saving in this instance. Conversely, when the aortopulmonary collaterals constitute the source of pulmonary blood flow, the clinical presentation may vary from cyanosis with inadequate pulmonary blood flow to no cyanosis with increased pulmonary blood flow. Uncommonly, pulmonary blood flow is sufficiently increased to cause symptoms due to pulmonary overcirculation. Older infants and children commonly present with cyanosis. Hypoxia usually progresses further as the child outgrows the source of pulmonary blood flow. Early surgical intervention has improved survival in these patients.

Frequency

United States

The Baltimore Washington Infant study reported an incidence of 0.07 cases per 1000 live births. This condition accounts for 1.5% of all forms of congenital heart disease and 20% of all forms of tetralogy of Fallot.³

Mortality/Morbidity

Survival before the advent of modern surgical techniques rarely occurred, with less than 5% of patients reaching age 25 years.^4,5  In patients with operable pulmonary arteries, survival rates with satisfactory quality of life now reach 90%.

• Patients with inadequate pulmonary blood flow and marked cyanosis develop complications affecting multiple organ systems, including hematologic, skeletal, renal, and neurologic, causing significant morbidity and mortality.
• In patients with large aortopulmonary collaterals and excessive pulmonary blood flow, congestive heart failure (CHF) may result in failure to thrive.
• Patients with tetralogy of Fallot and nonconfluent pulmonary arteries are subject to increased morbidity and mortality related to the frequent need for multiple cardiac surgeries. The risks of cardiopulmonary bypass and anesthesia are present at each stage of the repair.

Race

No race predilection is known.

Sex

No specific male or female preponderance of tetralogy of Fallot with pulmonary atresia has been noted.

Age

Tetralogy of Fallot with pulmonary atresia becomes symptomatic at birth in most cases. Diagnosis usually occurs at this time.

Clinical

History

Clinical presentation widely varies and largely depends on the source and volume of pulmonary blood flow.

• An infant with tetralogy of Fallot with pulmonary atresia (TOF-PA) is often symptomatic within the first hours to days of life.
  • Severe cyanosis becomes apparent immediately after birth as the ductus arteriosus (DA) begins to close. In the presence of significant aortopulmonary collaterals, cyanosis may be mild to moderate. If adequate collaterals or additional sources of pulmonary blood flow are lacking, closure of the DA may produce hypoxemia too severe for survival.
  • On rare occasions, patients with well-developed aortopulmonary collaterals or persistent patency of the DA may present with heart failure. Symptoms develop several weeks after birth as pulmonary vascular resistance decreases and pulmonary blood flow increases.
  • The older infant and child with adequate pulmonary blood flow supplied by aortopulmonary collaterals presents with a history of cyanosis. Impaired exercise tolerance and growth failure may occur.
• Patients who have undergone palliative surgical procedures may present with variable symptomatology.
  • Most palliative procedures are intended to augment pulmonary blood flow by placement of systemic-to-pulmonary artery shunts. These shunts may distort the pulmonary vasculature or may cause stenosis and result in hypoxia.
  • Elevated pulmonary vascular resistance has been noted in the presence of large systemic-to-pulmonary connections. This problem was prevalent with the Waterston (direct anastomosis of the ascending aorta to the pulmonary artery) and the Potts (direct anastomosis of the descending aorta to the pulmonary artery) shunts, both of which have been largely abandoned.

Physical

Physical findings vary according to the source and volume of pulmonary blood flow.

• Obvious profound cyanosis may be noted in the neonatal period. This becomes severe as the ductus narrows. Patients with significant aortopulmonary collaterals may be mildly cyanotic initially but become increasingly cyanotic if they outgrow their source of pulmonary blood flow.
• Peripheral pulses and blood pressures are usually normal during the first few days of life. Patients with increased pulmonary blood flow may be noted to have bounding pulses.
• Auscultation reveals a normal first heart sound with a single second heart sound. A systolic murmur may be present at the left lower sternal border. The typical right ventricular outflow tract murmur of classic tetralogy of Fallot is not heard. A soft continuous murmur from the DA may occur at the left base. A continuous murmur from the aortopulmonary collaterals may be heard in the back.
• Growth and development are often delayed.

Causes

• Many patients with tetralogy of Fallot with pulmonary atresia have associated syndromes and extracardiac malformations.
  • Conotruncal cardiac malformations associated with a chromosome arm 22q11 deletion have been incorporated under an acronym of CATCH22 (cardiac defect, abnormal face, thymic hypoplasia, cleft palate, hypocalcemia, microdeletion of band 22q11). Patients with tetralogy of Fallot with pulmonary atresia have a higher incidence of this syndrome than patients with classic tetralogy of Fallot. The prevalence of deletion 22q11 is 16% in tetralogy of Fallot with pulmonary atresia with confluent pulmonary arteries and 41% in patients with tetralogy of Fallot with pulmonary atresia and multiple aortopulmonary collateral arteries.⁶
  • Other syndromic associations include the vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, and renal and radial anomalies (VATER) syndrome; the coloboma, heart disease, atresia choanae, retarded growth and retarded development and/or CNS anomalies, genital hypoplasia, and ear anomalies and/or deafness (CHARGE) syndrome; Alagille syndrome; cat's eye syndrome; Cornelia de Lange syndrome; Klippel-Feil syndromes; and trisomy 21.⁷
  • Maternal diabetes mellitus; maternal phenylketonuria; and maternal ingestion of retinoic acid, trimethadione, or sex hormones increase the risk of conotruncal abnormalities. Infants of mothers with diabetes mellitus have a 20-fold higher risk than infants of mothers without diabetes mellitus.
• The recurrence risk of siblings with tetralogy of Fallot is 3-4%. The recurrence risk increases further if syndromic variants are present.
• Variable patterns of inheritance may be observed.

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