Heparin, Unfractionated

Heparin is a complex mucopolysaccharide that effects anticoagulation by activating antithrombin III. Antithrombin III inactivates thrombin and the factors IX, X, XI, XII, plasmin, and kallikrein, and thereby prevents the conversion of fibrinogen to fibrin. The heparin is cleared primarily by the reticuloendothelial system and is not affected by decreased renal and hepatic function.

Heparin is administered by both intravenous and subcutaneous routes. Intramuscular administration causes large hematomas. Intravenous administration is initiated in the immediate postoperative period for newborns who have shunt-dependent pulmonary blood flow and infants and children who have prosthetic heart valves. When heparin is administered intravenously, it provides almost instant anticoagulation and has a half-life of about 90   minutes. Therefore, it is critical that hemostasis is established in the postoperative period before heparin therapy is initiated.

Subcutaneous heparin is used infrequently in children because of erratic absorption. It is used when an oral agent is contraindicated. The most frequent subcutaneous use occurs when a young woman with a prosthetic heart valve is pregnant or anticipating pregnancy. In these patients the oral agent, warfarin, is not used because of potential teratogenic effect.⁷³¹ Anticoagulation effects are monitored using the activated partial thromboplastin time (aPPT).

The dose for systemic heparinization may vary by cardiac surgeon, institution, or indication for anticoagulation. General guidelines include an initial loading doses range from 50 to 100   U/kg administered over 10   minutes, followed by a maintenance dose of 10 to 20   U/kg per hour. Infusion rates are titrated to maintain a desired aPTT level (usually 60-75   seconds). Heparin is neutralized by protamine. Long-term use can cause osteoporosis.^731,742,839

Warfarin

Warfarin is a vitamin K antagonist that has been used for 50 years and continues to be the most common oral anticoagulant used for the prophylaxis and treatment of thromboembolic disorders.^702,731 A coumarin derivative, warfarin acts by interfering with the hepatic synthesis of the vitamin K-dependent clotting factors, II, VII, IX, X, protein C, protein S, and protein Z. These factors decrease gradually depending on their half-life. Factor VII has a half-life of 6   hours, and factor II, prothrombin, has a half-life of 92   hours. Thus, the anticoagulation effect of warfarin is first seen around 8 to 12   hours and may persist for 1 to 5 days after the drug is stopped. A relatively steady state is reached 72   hours after the initial dose.

Warfarin may have a more antithrombotic effect (rather than a simple anticoagulant effect) by the reduction in prothrombin and factor X levels. This decreases the ability to generate thrombin, the main modulator of clot formation. Warfarin is readily absorbed orally with a peak concentration 90   minutes after ingestion. Food slightly slows the absorption.^731,742,839

Ninety percent of warfarin is bound to albumin. It is accumulated in the liver and then is metabolized and transformed by different pathways.

The suggested initial dose of warfarin for infants greater than 2 months of age and children is 0.2   mg/kg daily for 2 to 4 days and 0.1   mg/kg for those with liver disease. Older children and adults initially receive 5 to 15   mg daily for 2 to 4 days.⁸³⁹ Many factors influence this initial dose and subsequent doses in addition to liver disease. These factors include cardiac and renal output, especially perioperative cardiac function; nutritional status before surgery, which may be reflected in low serum albumin; acute and chronic disease; concurrent medications; and current diet, including type and amount of food and/or formula ingested.^{25,407,564,731,839}

Children are vulnerable to genetic and developmental factors that affect the hemostatic system and response to warfarin. Genetic factors may influence the response requiring as much as a 20-fold higher dose to achieve an anticoagulant effect.⁷⁴² At birth, the vitamin K clotting factors are approximately 50% of the adult levels.⁷⁴² Because of the immature hemostatic system of the neonate, warfarin is not used during the first 2 months of life.

Children frequently have acute bacterial or viral illnesses that require the initiation of medications or influence their dietary intake. Medication interactions with warfarin are listed in Box 8-20, A and B.

Different forms of dietary intake of vitamin K further influence warfarin effects. The two forms of vitamin K include vitamin K₁ (phylloquinones) and vitamin K₂ (menaquinones). Most of the vitamin K stores in the liver are menaquinones and are thought to originate from the diet rather than intestinal flora. Vitamin K₁ is found in green leafy vegetables, and vitamin K₂ occurs in various foods such as yogurt and organ meats, but is also produced by the bacterial flora of the colon and small intestine. Children with acute bacterial and viral illness do not eat in typical patterns and have frequent gastroenteritis. This significantly decreases the intake of vitamin K and production by bacterial flora, resulting in an increase in the prothrombin time-international normalized ratio (PT-INR).^702,731

Healthy infants and children often have significant changes in the vitamin K in their diets. Breastfed babies receive little dietary vitamin K, whereas formula-fed infants receive increasing doses of vitamin K as their daily intake of formula increases.^39,702,742

The risks of warfarin administration include serious and potentially fatal hemorrhage or necrosis and/or gangrene of the skin and other tissues. Warfarin is a known teratogen that causes midline defects in the fetus. A cardiologist and high-risk perinatologist must carefully follow women who are taking warfarin and become pregnant or plan to become pregnant. The best plan is to change the anticoagulation therapy to subcutaneous heparin.

Anticoagulation therapy using warfarin is monitored by the prothrombin time adjusted with the international normalization ratio (PT-INR). The target PT-INR is determined by the reason for anticoagulation. The frequency of monitoring is based on the time from the initiation of therapy, the PT-INR, concurrent illnesses, initiation of new medications or changes in doses of current medications, pending surgical or dental procedures, or changes in diet. Lifetime monitoring must continue at least monthly.

Increased PT-INR with symptomatic bleeding is treated with the administration of intravenous vitamin K and/or intravenous fresh-frozen plasma. Nonsymptomatic levels of PT-INR may be decreased by lowering the dose or by giving oral vitamin K. In the infant, several ounces of infant formula may be used.^731,742,839

Warfarin is available as a tablet in many strengths, from 1   mg to 10   mg. The daily dose of warfarin will change as a result of the PT-INR monitoring. Combining tablets as doses change helps to provide a consistent daily dose.

Aspirin

The effect of aspirin is mediated through inhibition of prostaglandin synthetase action. This prevents formation of the platelet-aggregating substance thromboxane A2. Therapy includes both low and high doses.^{622,731,742,839} Although the dose of aspirin is stated in the mg/kg format, it is generally dosed in fractions of the 81-mg chewable tablet.

Antiplatelet regimes differ at different pediatric cardiac centers. At Boston Children's Hospital, the dose is 40   mg/day for patients less than 10   kg and 81   mg/day for those greater than 10   kg. Patients less than 2.5   kg would take 40   mg every other day. At Miami Children's Hospital, all babies receive 21   mg/day (one quarter of an 81   mg tablet). Infants with bidirectional Glenn shunts generally take 40   mg/day. Children take 40 to 81   mg/day after Fontan surgery. The tablet should be chewed or crushed and taken with food or after eating to prevent direct irritation from the tablet on the gastric mucosa.

Dipyridamole

Dipyridamole inhibits platelet aggregation by inhibiting the activity of adenosine deaminase and phosphodiesterase. This may cause vasodilation, especially in coronary arteries. It may also stimulate release of prostacyclin. Dipyridamole is used in conjunction with warfarin to allow a lower PT-INR in higher-risk patients with thromboembolic disease. Patients with prosthetic heart valves are included in this category.^{622,731,742,839} The dose of dipyridamole is 3 to 6   mg/kg per day for children and 25 to 100   mg for adults. It is administered three to four times a day, making compliance more difficult.

Clopidogrel (Plavix)

Clopidogrel inhibits platelet aggregation by irreversibly modifying the platelet ADP receptor. The benefit of the addition of clopidogrel to conventional therapy following systemic to pulmonary shunts was recently evaluated in a multicenter, randomized, double-blind, placebo-controlled study.⁹⁴¹ The primary objective of the study was to determine if clopidogrel reduced the all-cause mortality and shunt-related morbidity in neonates or infants (less than 3 months of age) with cyanotic congenital heart disease palliated with a systemic-to-pulmonary artery shunt. A clopidogrel dose of 0.2   mg/kg per day was given once daily.⁹⁴¹ In this study, the addition of clopidogrel to aspirin therapy did not reduce all-cause mortality or shunt-related morbidity.⁹⁴¹

Pearls

Etiology

A patent ductus arteriosus (PDA) is persistence of the fetal structure, the ductus arteriosus, after birth (Fig. 8-30). The ductus arteriosus is derived from the left sixth embryologic aortic arch and connects the main pulmonary trunk (at the origin of the left pulmonary artery) to the descending aorta just below the left subclavian artery. When a right aortic arch is present, the ductus typically connects the right pulmonary artery with the right aortic arch. The ductus varies in length and is as large as or larger in diameter than the descending aorta in the fetus.^449,628

Fig. 8-30 Patent ductus arteriosus (PDA). The PDA extends from the bifurcation of the pulmonary trunk (PT) to the aorta (Ao), joining the aorta just beyond the origin of the left subclavian artery.

(From Perloff M: Clinical recognition of congenital heart disease, ed 5, Philadelphia, 2003, Saunders. Fig. 20-1.)

During fetal life the ductus arteriosus diverts blood away from the (high-resistance) pulmonary circulation to the descending aorta and toward the low-resistance placental circulation. The ductus carries 55% to 60% of the combined ventricular output.⁶²⁸

The intimal layer of the ductus arteriosus is thicker and more mucoid than the intimal layer of the pulmonary artery and the aorta. The smooth muscle in the medial layer of the ductus is arranged in both leftward and rightward patterns with an increased amount of hyaluronic acid; this facilitates constriction and closure of the ductus after birth. By comparison, the medial layer of the wall of the pulmonary artery and aorta consists of circumferential layers of muscle fibers.

The precise mechanisms of ductal closure are not fully understood. Functional closure occurs in two phases. In the first phase, immediately after birth, contraction and cellular migration of the medial smooth muscle produce shortening and thickening of this layer and protrusion of the media into the ductal lumen with thickening of the intimal layer. These thickened cushions or mounds result in functional closure of the ductus within about 12   hours of birth. Infolding of the endothelium; disruption and fragmentation of the elastic fibers; and cellular proliferation, hemorrhage, and necrosis in the subintimal layers result in replacement of the muscle fibers with fibrotic connective tissue to form the ligamentum arteriosum within about 2 to 3 weeks after birth.⁶²⁸

The increase in the partial pressure of oxygen (PaO₂) that normally occurs after birth stimulates constriction of the ductus arteriosus. However in preterm infants the ductus is not constricted at even high levels of oxygen tension. Prostaglandins play an important role in ductal patency or constriction. Prostaglandins dilate the ductus, and a normal fall in endogenous prostaglandins after birth contributes to constriction of the ductus. Administered prostaglandin inhibitors (e.g., indomethacin) can cause ductal constriction.^449,628 Other vasoactive substances (bradykinin, acetylcholine, and endogenous catecholamines) also contribute to ductal constriction and closure.

The PDA accounts for about 5% to 10% of all congenital heart defects in full-term infants.⁶⁸⁶ The incidence is much higher in premature infants (8 of 1000 premature infants have a PDA), particularly those with pulmonary disease and varies inversely with birthweight. Hemodynamically significant PDA is noted in almost 80% of infants with a birthweight of less than 1000   g, because ductal constrictive response to oxygen is related to gestational age.⁶²⁸

Ductus closure may be delayed if the neonate's arterial oxygen tension does not rise normally after birth. For example, the incidence of PDA is about 30% higher at high altitudes (i.e., 4500-5000   m [about 14,700-16,000 feet] above sea level), and neonates with cyanotic congenital heart disease characteristically demonstrate delayed closure of the ductus. A PDA also may be present as part of the rubella syndrome, and it may be seen occasionally in otherwise healthy, normal full-term infants.

A functionally closed ductus may reopen if the arterial oxygen tension falls, such as occurs with asphyxia, meconium aspiration, or pneumonia. It may also reopen in response to administered prostaglandin (e.g., for infants with cyanotic congenital heart disease or lesions with ductal-dependent systemic perfusion).⁶²⁸

Pathophysiology

With a PDA, several factors impact the magnitude of the left-to-right shunt: the diameter and length of the ductus, the pressure difference between the aorta and pulmonary artery, and the relative resistances in the systemic and pulmonary circulations.⁶²⁸ With the first breaths after birth, alveolar oxygenation improves and pulmonary vascular resistance begins to fall; as a result, the pulmonary to systemic flow through the ductus decreases dramatically.⁴⁴⁹ Once the umbilical cord is clamped, the systemic vascular resistance becomes slightly greater than the pulmonary vascular resistance, so any flow through the ductus initially becomes bidirectional and then ultimately reverses so it flows from the aorta into the pulmonary circulation.

As noted, the diameter and length of the ductus influences the magnitude of the left-to-right shunt. If the ductus is long and narrow the small diameter and the length add to the resistance to flow. By comparison, a short, wide ductus will offer little resistance to blood flow and allow a large shunt that will increase pulmonary blood flow. In addition, a short, wide ductus allows the blood to flow from the aorta into the pulmonary artery under relatively high pressure. The magnitude and pressure of the pulmonary blood flow through a PDA is likely to increase as pulmonary vascular resistance continues to fall over the first 2 months of life.⁶²⁸

There are several compensatory mechanisms, including the Frank-Starling law, adrenergic response, and myocardial hypertrophy that all help maintain cardiac output and systemic perfusion despite high-output heart failure. However, these mechanisms may not be as well developed or expressed in the neonate and particularly the premature neonate as they are in the older infant or child.⁶²⁸ Even at term the newborn's myocardial structure has higher water content and fewer contractile elements than the myocardium of adults.³⁰ Neonatal myocardium—especially the myocardium of the preterm neonate—has a more modest response to stretch, so there is limited ability to increase stroke volume in response to volume administration and increased ventricular end-diastolic pressure. All result in decreased ability to compensate for increased ventricular end-diastolic volume and pressure. In addition, sympathetic nervous innervation of the left ventricle is not complete until term or just after birth.

Myocardial perfusion is also affected by a large PDA. Higher left ventricular diastolic pressure, faster heart rates with shorter diastolic filling time, and lower aortic pressures from ductal flow (runoff) all can compromise coronary artery blood flow. Physiologic anemia also affects myocardial function. Lower hemoglobin concentrations in newborns (even lower in premature newborns) and fetal hemoglobin affect oxygen delivery to the myocardial tissue.⁶²⁸ In addition to decreased myocardial perfusion, the decrease in systemic blood flow may compromise other organ systems, with resulting renal insufficiency, necrotizing enterocolitis, and intraventricular hemorrhage.³⁰

Increased pulmonary blood flow through the PDA is associated with a variety of pulmonary complications, including increased pulmonary interstitial water, increased work of breathing, and decreased diaphragm blood flow. Reduced diaphragm blood flow probably substantially reduces the effectiveness of ventilation. Pulmonary edema may be observed in neonates with only a moderate ductal shunt because capillary permeability is higher in neonates than in older infants.⁶²⁸

The high pressure, high volume pulmonary blood flow that can result from a PDA (particularly a short, wide PDA) creates a risk of pulmonary vascular disease. The systemic and pulmonary arterial pressures can become equal. This high pulmonary vascular pressure can prevent the normal postnatal regression of medial smooth muscle in the pulmonary arteries. If the ductus remains open, true pulmonary vascular disease may develop with increased medial smooth muscle, intimal damage with cellular proliferation and hyalinization, and ultimately thrombosis and fibrosis of the small pulmonary arteries.⁶²⁸

With some congenital heart defects, flow through the ductus arteriosus is required for pulmonary or systemic blood flow; these defects are called ductal-dependent defects. Defects such as pulmonary atresia have ductal-dependent pulmonary blood flow. This means that blood flow from the aorta to the pulmonary artery provides the only source of pulmonary blood flow. When the ductus begins to constrict after birth, the newborn develops profound hypoxemia. Defects such as hypoplastic left heart syndrome have ductal-dependent systemic blood flow. With such defects, blood flow from the ductus into the aorta supports systemic blood flow. When the ductus begins to constrict after birth, systemic perfusion is compromised and shock develops.

Clinical Signs and Symptoms

Clinical features vary depending on the volume and pressure of the left-to-right shunt and the age of the patient. In the preterm infant with no lung disease a systolic murmur may be heard at 24   hours of age. The widespread use of surfactant has reduced severe respiratory disease, so the symptoms of a PDA appear earlier than when severe disease is present. As lung disease resolves and oxygenation improves, vasodilation causes pulmonary vascular resistance to fall, increasing the left-to-right shunt.³⁰ As the magnitude of the left-to-right shunt increases, the systolic murmur becomes louder and extends into early diastole. A middiastolic flow rumble may be heard at the apex.

If the shunt is small, a murmur may be the only sign of a PDA.^30,628,686 The classic continuous so-called “machinery murmur” heard in an older infant or child with a moderate PDA is not initially heard in the premature or term infant. With an increasing shunt the murmur is louder in all affected patients and may be accompanied by a suprasternal thrill. The pulmonic component of the second heart sound may be increased, especially in the infant with pulmonary disease. The precordium will be active, and the peripheral pulses bounding (because aortic flow runs off into the pulmonary artery).

The preterm, term infant, and child with a significant left-to-right shunt is dyspneic, tachypneic, and tachycardic. (For further information regarding auscultatory findings, see Table 8-25.)

Table 8-25 Clinical, Radiographic and Electrocardiographic Characteristics of Acyanotic Congenital Heart Defects

If the neonate is receiving mechanical ventilator support for lung disease, increased support requirements (including increased inspiratory pressure or increased supplementary oxygen requirements) may indicate the development of a shunt through the PDA. The murmur may only be heard between breaths or when the neonate is briefly removed from ventilator support (e.g., for suctioning).⁶²⁸

Evidence of left ventricular hypertrophy often is noted on clinical examination and by electrocardiographic criteria in the older infant and child (Table 8-26). The echocardiogram usually documents evidence of a large shunt, and an increase in the ratio of left atrial size/aortic size. The chest radiograph may be normal in asymptomatic patients with a small shunt, but cardiomegaly and increased pulmonary vascular markings are generally identified if a large shunt and congestive heart failure are present. Pulmonary interstitial edema also may be apparent. The main pulmonary artery may be prominent (for further information, see, also, Table 8-25).

Table 8-26 Characteristic 12-Lead Electrocardiographic (ECG) Patterns in Congenital Heart Disease

If the clinical presentation is typical and if no additional abnormality is suspected, the diagnosis is made on the basis of clinical examination, chest radiograph, and echocardiogram. Cardiac catheterization is commonly used as an intervention to close the duct, using one of several devices. If the clinical presentation is atypical or if the presence of other cardiac anomalies is suspected, a cardiac catheterization may be performed. The catheterization will reveal an increase in oxygen saturation in the pulmonary artery. Right ventricular and pulmonary artery pressures will be elevated if pulmonary hypertension is present. Aortic contrast injection will demonstrate the shunt into the pulmonary artery.

If pulmonary hypertension develops, the patent ductus arteriosus murmur may decrease in intensity or be absent. The pulmonary component of the second heart sound will be increased.

If pulmonary vascular resistance is approximately equal to systemic vascular resistance, the child may develop bidirectional shunting through the PDA. This causes arterial oxygen desaturation; the child may demonstrate cyanosis, particularly of the lower extremities and when the infant cries.

If the neonate has ductal-dependent pulmonary blood flow (i.e., cyanotic congenital heart disease with pulmonary blood flow occurring only through the ductus arteriosus), profound hypoxemia and cyanosis will develop when the ductus begins to constrict. The hypoxemia is not relieved with oxygen administration (refer to Hypoxemia in the second section of this chapter and Cyanotic Defects later in this section of the chapter).

If the neonate has ductal dependent systemic blood flow, signs of poor systemic perfusion will develop when the ductus begins to constrict. Without treatment, these signs will progress to circulatory collapse (see section, Obstructive Lesions, Single Functioning Ventricle).

Management

Treatment of a PDA is aimed at closing the ductus. In the asymptomatic older child and adult with a PDA presenting only with a murmur, the need for PDA closure remains controversial.^399,628 Before echocardiography was available, the natural history of the PDA included some spontaneous closure, but also included high infant mortality, and risk of bacterial endocarditis, heart failure, and pulmonary vascular disease with a mortality rate of 60% before 60 years of age. However, the widespread use of echocardiography enables early identification and evaluation of the ductal shunt.

With current therapy and closure at the time of diagnosis the complications of the ductal shunt are eliminated.⁴⁴⁹ The PDA may be closed pharmacologically, it may be closed surgically, and it can be closed using a device in older infants and young children. The timing and method of ductal closure in the premature infant remain open to debate. Before the ductus is closed in the preterm infant, medical management includes the maintenance of adequate hemoglobin concentration and hematocrit, normal serum electrolytes, adequate blood glucose, and nutritional support. To provide peripheral oxygenation and improve cardiac output, the hematocrit should be maintained greater than 45%. Management of congestive heart failure includes careful management of intravascular volume, diuretic administration, fluid restriction, and possible sodium restriction. Digitalis is not administered in the preterm infant because complications are high and therapeutic effect is minimal.⁶²⁸ For further information, see Common Clinical Conditions, Congestive Heart Failure.

Surgical Intervention

Early surgical ligation of a PDA in premature neonates was shown to reduce the duration of mechanical ventilatory support and the length of the hospital stay.⁶²⁸ Therefore prompt surgical PDA ligation is recommended if pharmacologic ductal closure fails.

Closed-heart surgery may be performed thorascopically or through a left, lateral thoracotomy. Although there is risk of recannulation, ligation (tying of the ductus) is favored over division (cutting and oversewing) for the smallest premature neonates (less than 1000   g) because it minimizes the dissection required and shortens the time required for lung retraction and anesthesia. Most surgeons clip the ductus to minimize the need for dissection and the risk of vocal cord dysfunction associated with dissection.^628,757 For all others the ductus is divided and oversewn. If the ductus is calcified, hypertensive, and fragile (generally this occurs only in elderly patients) the procedure is performed with cardiopulmonary bypass on standby.

Morbidity and mortality for surgical elimination of the ductus are typically extremely low (less than 1% mortality). The neonatal myocardium is very sensitive to afterload, and the change in afterload with ligation of the ductus arteriosus will affect the myocardial performance index and cardiac output of the premature neonate. To maintain cardiac output, inotropic support, usually with dopamine, is required for approximately 24   hour postoperatively.⁶⁵⁶

The highest surgical risk is observed in children and adults with PDA who have developed pulmonary hypertension and Eisenmenger syndrome (a left-to-right shunt becomes a right-to-left shunt as the result of the development of pulmonary hypertension). These patients require careful evaluation and diagnostic studies preoperatively.²⁷⁵ PDAs have been successfully closed using devices in adult patients with pulmonary hypertension.

Postoperative complications of PDA surgical repair (see Table 8-27)^851-853 include those of a thoracotomy (bleeding, atelectasis, hemothorax, and pneumothorax). In addition, phrenic or recurrent laryngeal nerve injury may occur.^851-853 Vocal cord paralysis may be associated with recurrent laryngeal nerve injury; this complication is relatively uncommon and is observed almost exclusively in very small neonates.

Table 8-27 Summary of Surgical Repair of PDA, 2009-2010^851-853

Advanced concepts regarding the care of the child with a PDA are presented in Box 8-22.

Box 8-22 Advanced Concepts: Patent Ductus Arteriosus

• Heart failure from a left-to-right shunt is “high output” failure.

• Patent ductus arteriosus appears earlier in the preterm infant when surfactant is used to prevent pulmonary disease.

• The preterm infant has less compensatory mechanisms to handle the increased volume load from the left-to-right shunt.

• The symptoms of a PDA in a neonate during mechanical ventilation for lung disease may include requirement for increased pressure and/or oxygen support.

• Abrupt closure of the PDA with surgical ligation in the preterm infant will decrease myocardial performance and require inotropic support.

Etiology

An aortopulmonary window is a defect between the ascending aorta and the pulmonary artery. With this defect, there must be two distinct semilunar valves.⁴⁴⁵

Septation of the fetal truncus arteriosus is influenced by neural crest cells. However, embryologic studies demonstrate that the neural crest cells do not affect the development of an aortopulmonary window. Studies also demonstrate that the aortopulmonary window is not associated with DiGeorge syndrome or any other chromosomal deletions in 22Q11.³⁰

Aortopulmonary window accounts for 0.2% to 0.6% of all congenital heart defects. Nearly half of these patients have associated anomalies; the most common include interrupted aortic arch, anomalous origin of the coronary arteries, and anomalous origin of right pulmonary artery. Although these associated anomalies are found in the same area in the heart, they appear to be embryologically unrelated.⁶²⁸

Pathophysiology

The physiologic effects of an aortopulmonary window are similar to the left-to-right shunt of a large patent ductus arteriosus (PDA) or a ventricular septal defect. Once the pulmonary vascular resistance falls in the first days to weeks of life, blood is shunted from the aorta across the defect into the pulmonary circulation. These defects are discrete, most commonly large and unrestrictive, and are positioned between the semilunar valves and the bifurcation of the pulmonary artery as illustrated in Fig. 8-31.

Fig. 8-31 Aortopulmonary window. The defect between the aorta and pulmonary artery produces a left-to-right shunt from the aorta into the pulmonary circulation. Shunting of blood occurs during both systole and diastole. If the defect is large, the volume of the shunt will be large and under high pressure.

These defects typically produce early congestive heart failure. Without repair, pulmonary vascular disease often develops, perhaps as early as 1 year of age.⁴⁴⁵ This defect does not close spontaneously. Prompt surgical repair is indicated when the diagnosis is made.^30,686

Clinical Signs and Symptoms

Clinical signs and symptoms of an aortopulmonary window vary with the size of the defect and the associated anomalies. A very small defect may not produce signs or symptoms other than a systolic ejection murmur.

The defect characteristically produces a loud, systolic murmur at the upper left sternal boarder or a machinery murmur, similar to that produced by a patent ductus arteriosus. Additionally, there may be a mid-diastolic murmur at the apex caused by the flow of the large volume of pulmonary venous return across the mitral valve. The second sound may have a louder pulmonary component from pulmonary hypertension. An ejection click may also be heard in the pulmonary area.^445,628 A right ventricular impulse may be felt along the left sternal boarder, and a thrill may be present at the upper left sternal border. Pulses may be bounding, or if the defect is associated with an interrupted aortic arch, femoral pulses may be markedly decreased when the patent ductus arteriosus closes.

Signs of congestive heart failure often are present, and left ventricular hypertrophy may be apparent on the clinical examination, the chest radiograph, and the ECG. Signs of right ventricular hypertrophy will be present if pulmonary vascular disease develops.

Echocardiography can accurately diagnose an aortopulmonary window and associated anomalies. The defect can also be identified by a fetal echocardiogram.⁶²⁸ Cardiomegaly and increased pulmonary vascular markings are typically apparent on chest radiograph, unless the defect is very small.

Cardiac catheterization is usually not necessary but will document elevated pulmonary pressures, usually equal to systemic pressures. Contrast injection into the aorta will reveal the shunt into the pulmonary artery. Small defects have been successfully closed with a device during catheterization.^445,628

Management

Closure of the defect is indicated in virtually all cases. Surgical closure is usually planned as soon as the diagnosis is made. If signs and symptoms of heart failure are severe, preoperative treatment of congestive heart failure (e.g., diuretics) is helpful to reduce pulmonary congestion. Newborns with an aortopulmonary septal defect and interrupted aortic arch may require prostaglandin E₁ to maintain ductal patency to support systemic blood flow preoperatively.

Recommended surgical treatment of an aortopulmonary window requires a median sternotomy with hypothermic cardiopulmonary bypass. Best outcomes are achieved with patch closure through an aortic incision under direct visualization.²⁷⁵ Postoperative complications include bleeding, low cardiac output, pulmonary hypertension, and congestive heart failure.¹⁵⁶

Pearls

Etiology

An atrial septal defect is any opening in the atrial septum other than a competent foramen ovale.⁷⁰⁸ Atrial septal defects result from improper septal formation early in fetal cardiac development. Most occur sporadically. However, some occur with genetic syndromes, most commonly Holt-Oram syndrome, Down syndrome, and Noonan syndrome. The incidence of atrial septal defects is 1 per 1000 live births,⁴⁵⁸ but ASDs are found in about 30% to 50% of children with other forms of congenital heart disease.⁶⁸⁶

ASDs are classified into three major types, according to their location relative to the fossa ovalis (Fig. 8-32 illustrates the three types of ASDs: the ostium secundum, ostium primum, and sinus venosus).

Fig. 8-32 Atrial septal defect (ASD). A, Typical oxyhemoglobin saturations observed in the cardiac chambers and great vessels when an ASD is present. B, Common types of ASD, and their relationship to the superior vena cava (SVC), the inferior vena cava (IVC) and the mitral and tricuspid valves.

(From Kambam J: Patent ductus arteriosus. In Kambam J, editors: Cardiac anesthesia for infants and children. St Louis, 1994, Mosby.)

The ostium secundum is the most common type of ASD, accounting for 50% to 70% of all ASDs. It is located in the region of the fossa ovalis (the foramen ovale). Historically, a patent foramen ovale has not been included in this category unless atrial dilation occurs from increased volume, and the flap closing the foramen ovale becomes incompetent, allowing a left-to-right or a right-to left shunt.⁷⁰⁸ Although functional closure of the fetal foramen ovale may occur at birth, anatomic closure of the foramen ovale does not occur in 25% to 30% of the population. This failure is thought to be responsible for paradoxic emboli (from a right-to-left shunt across the foramen ovale) associated with cryptogenic stroke and decompression illness.¹⁶⁹ Migraine headaches have also been linked to patent foramen ovale.

The ostium primum defect accounts for about 30% of ASDs. This defect is located anterior to the fossa ovalis where the atrial septum originates from the endocardial cushion. It usually is associated with a defect in ventricular septal tissue as well as with anomalies of one or both atrioventricular valves. (See section, Atrioventricular Septal Defects/Endocardial Cushion Defects.)

The sinus venosus ASD is located posterior and superior to the fossa ovalis, typically near the junction of the superior vena cava and the right atrium. This defect can also occur at the junction of the inferior vena cava and right atrium. It often is associated with partial anomalous pulmonary venous return (PAPVR). With PAPVR, some of the pulmonary veins empty directly into the right atrium or superior vena cava instead of into the left atrium.

Anomalies of the atrioventricular valves may be associated with ASDs. As noted, ostium primum ASDs are often associated with anomalies of one or both atrioventricular valves. Mitral valve prolapse is present in about 20% of patients with either a secundum or sinus venosus ASD.^458,686

Less common forms of ASDs include Chiari network, characterized by multiple fenestrations in the atrial septum that allow a left-to-right shunt (from left-to-right atrium), and a coronary sinus septal defect at the expected site of the coronary sinus as an “unroofed” coronary sinus. When the coronary sinus is unroofed, coronary sinus (i.e., venous) blood flows into the left atrium (a form of right-to-left shunt). Thus, this defect results in bidirectional shunting of blood at the atrial level, with resulting hypoxemia and cyanosis. This unusual form of ASD typically is associated with persistent left superior vena cava.⁴⁵⁸

A common atrium is the most severe form of ASD. The septum primum, septum secundum, and the atrioventricular canal septum are all absent. A common atrium is usually associated with heterotaxy syndrome⁴⁵⁸ (for further information, see section, Essential Anatomy and Physiology, Fetal Development of the Heart and Great Vessels).

A patent foramen ovale may serve as a necessary channel for shunting of blood between the right and left atria. This is most commonly observed in patients with obstruction to right atrial flow (tricuspid atresia), obstruction to right ventricular flow (pulmonary atresia), transposition of the great arteries, or obstruction of left ventricular flow (hypoplastic left heart syndrome).³⁶²

Pathophysiology

The resistance (and compliance) of the ventricles and the ventricular outflow tracts determine the magnitude and direction of shunt across an ASD.^458,708 At birth, the right ventricle is thicker and less compliant than the left ventricle. Pulmonary vascular resistance begins to fall with the first few breaths following birth, but the right ventricle takes weeks to remodel and for resistance to decrease.³⁰ Therefore, a significant shunt does not typically develop for the first weeks of life.

This defect usually is tolerated well and often produces no symptoms during childhood. An occasional neonate with ASD will develop symptoms of heart failure. Such newborns typically have extracardiac anomalies and developmental delay but do not have hemodynamic changes that are different from newborns without heart failure.⁷⁰⁸ Heart failure may also develop in neonates with ASD and additional cardiac defects, such as ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, or those with myocardial dysfunction, an anatomically small left ventricle and systemic hypertension.⁴⁵⁸

If an ASD remains unrepaired to adulthood, significant right atrial and right ventricular dilation and hypertrophy can develop, producing atrial arrhythmias (e.g., atrial fibrillation), congestive heart failure, and possible paradoxic emboli. The risk of pulmonary vascular disease is low in the child with an uncomplicated ASD. However, pulmonary vascular disease is reported in 5% to 10% of all adults with unrepaired ASD, although it usually does not occur before the patient is 20 to 30 years of age.⁴⁵⁸ This complication should decrease in frequency because most ASDs greater than 7 to 8 mm in children more than 6 years of age are now closed when they are discovered. The risk of bacterial endocarditis in association with an uncomplicated ASD is virtually zero.⁷⁰⁸

When the child has cyanotic congenital heart disease, an ASD may provide an important shunt that allows mixing of oxygenated and venous blood within the atria. In this case the size of the ASD can influence the degree of mixing as well as the arterial oxygen saturation.

Clinical Signs and Symptoms

Most children with secundum or sinus venosus ASD are asymptomatic. (See Atrioventricular Septal Defects for information about ostium primum atrial septal defects.) The characteristic heart murmur associated with an ASD is a soft systolic ejection murmur heard over the left second intercostal space and an early to mid-diastolic murmur at the lower left sternal border. This systolic murmur results from increased blood flow across an otherwise normal pulmonary valve; this causes a “relative stenosis” because when a larger than normal volume passes through a normal (not larger than normal) valve orifice, turbulence results. The diastolic murmur results from increased flow from the right atrium across the tricuspid valve into the right ventricle.

The first heart sound is louder at the left lower sternal boarder, and the second heart sound is heard best at the left upper sternal border. The pathognomonic auscultatory finding of an ASD is the presence of fixed splitting of the second heart sound. This split does not vary with respirations and it results from prolonged right ventricular ejection, caused by the increased blood flow into the right atrium, right ventricle and the pulmonary circulation (see Table 8-25). If pulmonary hypertension develops, the split narrows and the pulmonary component of the second heart sound increases.

Right ventricular hypertrophy may produce a sternal lift on clinical examination and right ventricular hypertrophy may be apparent on the ECG (see Table 8-26). A two-dimensional echocardiogram will demonstrate the position as well as the size of the atrial septal defect. It will also demonstrate the effects of the left-to-right shunt, including right ventricular and right atrial enlargement as well as a dilated pulmonary artery. Color-flow Doppler studies will enhance the evaluation of the shunt.

In adolescents and children who are overweight, the transthoracic echo may not provide clear visualization, and a transesophageal echocardiogram is needed. Echocardiographic studies may be augmented by “bubble” studies. During this study agitated normal saline is injected into a peripheral vein, and contrast bubbles are visualized in the left atrium.^458,686,708

The chest radiograph may be normal, or it may demonstrate cardiomegaly and increased pulmonary vascular markings. The main pulmonary artery is often prominent on the chest radiograph (see Table 8-25).

Cardiac catheterization is necessary only when device closure is planned, if other defects are present, or if pulmonary vascular disease has developed. During cardiac catheterization of the patient with pulmonary vascular disease, pulmonary pressures are measured directly and effects of pulmonary vasodilators, including medications, nitric oxide, and oxygen on pulmonary vascular resistance are evaluated. These studies help to determine the risks associated with surgical or device closure of the ASD.^708,892

Cyanosis may be present if the coronary sinus is unroofed. Patients with this form of ASD are at risk for development of systemic consequences of chronic hypoxemia, including cerebral thromboembolic complications and brain abscess formation (see Hypoxemia).

Management

Management of an atrial septal defect is determined by the type of defect and presence of symptoms.

Surgical Intervention

Surgical closure of the ASD most frequently is completed through a median sternotomy incision on cardiopulmonary bypass. To reduce visible scarring, other surgical approaches can be used. The most frequent alternative approach is a “mini-sternotomy” through an incision on the lower half of the sternum.⁴⁵⁸ Other approaches include a limited right lateral thoracotomy with the incision starting below the scapula and ending at the mid axial line.^11,800 Thorascopic approaches have also been used.

A secundum ASD is closed directly with sutures (primary closure) or with autologous pericardium or prosthetic patch material (patch closure). Mortality is virtually zero, and hospital stay is normally less than 3 days. Complications include bleeding, arrhythmias, and post-pericardiotomy syndrome.⁴⁵⁸

Surgical repair of a sinus venosus defect is more complicated, especially if anomalous pulmonary veins are present. An intracardiac patch may be required as a baffle or the superior vena cava may be translocated to direct pulmonary venous return to the left atrium. If the defect is an inferior sinus venous defect, the procedure becomes more complex to direct hepatic venous return or anomalous pulmonary venous return to the appropriate atrium.

Repair of a coronary sinus ASD is tailored to the anatomy. If a left superior vena cava (SVC) is present, it may be ligated if a bridging vein to the right superior vena cava exists, or flow from the left SVC will be baffled (directed under a patch) to the right atrium. Postoperative mortality is less than 4%.

Complications following repair of a sinus venosus or coronary sinus ASD include arrhythmias, such as heart block, and postoperative obstruction to venous return. If cyanosis is noted in the postoperative period, reevaluation of pulmonary or systemic drainage is required.

Long term followup from surgical closure of ASDs in children with low pulmonary artery pressures shows excellent results (Table 8-28),^851-853 with a 95% survival rate compared with a matched population survival rate of 98%.⁷⁰⁸ Surgical closure usually alleviates symptoms, and residual defects are rare. Occasional patients demonstrate persistent arrhythmias or develop late arrhythmias. Cardiomegaly as evident on a preoperative chest radiograph or ECG may be evident for months or years postoperatively.⁴⁵⁸

Table 8-28 Summary of Surgical Repair of ASD, 2006-2010^851-853

Advanced concepts regarding atrial septal defects are listed in Box 8-23.

Box 8-23 Advanced Concepts: Atrial Septal Defect

• The direction of blood flow across an atrial septal defect is determined by the resistance or compliance of the ventricles.

• A significant shunt from an atrial septal defect usually does not develop in the newborn because it takes the right ventricle weeks to months to remodel and resistance to decrease.

• Because the defect is well tolerated and a significant number of secundum atrial septal defects close spontaneously, closure can wait until the child is 4 to 6 years of age.

• The primary reason to close an atrial septal defect is to prevent pulmonary vascular disease and other complications (e.g., atrial arrhythmias). Such complications usually do not develop until the second decade of life or later.

Pearls

Etiology

A ventricular septal defect is the most common congenital heart defect, accounting for 15% to 20% of all congenital heart defects.⁶⁸⁶ It occurs as frequently as 2.5 in 1000 live births, although only about one in five or fewer of the defects require closure, either during catheterization or surgery.⁴⁵⁷

A VSD results when the interventricular septum fails to close after the first 7 weeks of fetal life. The reasons for this failure are not clear and are felt to be multifactorial. Although these defects are the most common present in many genetic and chromosomal syndromes, including trisomy 13, 18, and 21, Holt-Orem and Cornelia de Lange syndromes, the vast majority of VSDs are not associated with any defects.^457,597,686 They are, however, more common in premature and low-birthweight neonates.

VSDs can occur as a single defect, as multiple defects, in association with another defect, or as a component of more complex congenital heart disease. Physiologic consequences range from trivial to severe. VSDs are classified by location in the ventricular septum.⁵⁹⁷

Although many terms have been used to classify VSD location, the current terms for the four major locations are: perimembranous, outlet, inlet, and muscular. A summary of the four classifications is presented in Table 8-29, and locations are illustrated in Fig. 8-33.

Table 8-29 VSD Classification

Fig. 8-33 Ventricular septal defect (VSD). A, Typical intracardiac pressures (systolic, diastolic and mean [m]) and oxyhemoglobin saturations (in circles). Note step-up in oxyhemoglobin saturation from the right atrium (66%) to the right ventricle (86%) indicating left-to-right shunt at the ventricular level. Right ventricular pressure (60/5) is elevated compared with the normal right ventricular pressure, but is less than the left ventricular pressure (90/5), indicating that the VSD in this illustration is restrictive. The pulmonary artery pressure is elevated as well. (From Nichols DG. Critical heart disease in infants and children, ed 2, St Louis, 2006, Mosby (Fig. 24-8). B, Classification of ventricular septal defects (VSDs) and potential locations: atrioventricular canal (inlet) type; muscular VSDs (anterior [1], midventricular [2], posterior [3], and apical [4]); conoventricular septal defect, which includes perimembranous and malalignment conoventricular septal defects; and conal septal (outlet) defects. The orifice of the pulmonary artery (pulmonary a.) is indicated.

(From Sellke F: Sabiston and spencer's surgery of the chest, ed 8, Philadelphia, 2009, Saunders; Fig. 117-4.)

Perimembranous VSDs, also called membranous conoventricular and infracristal defects, are the most common type of VSD, accounting for 70% to 80% of all VSDs.^597,686 The membranous septum is a small area just below the aortic valve. Defects in this area include the muscular tissue adjacent to the membranous septum. The membranous septum overlaps a small segment of the right atrium, and defects occasionally occur in this area.

Outlet (conal) VSDs account for 5% to 7% of all VSDs with several-fold higher incidence in Far Eastern countries. Outlet VSDs have also been called supracristal, conal, subpulmonary, or subarterial VSDs.^457,686 The outlet defect is located in the conal septum just below the pulmonary valve. Because of its location, a cusp of the aortic valve can prolapse into this defect, causing aortic valve insufficiency.

The third type of ventricular septal defect, an inlet defect, occurs in 5% to 8% of all VSDs. It is located posterior and inferior to the membranous septum below the septal leaflet of the tricuspid valve. This form of a VSD may also be referred to as an endocardial cushion defect or AV canal defect, but unlike the atrioventricular septal defects, it usually does not involve either of the atrioventricular valves.⁵⁹⁷

The fourth type of VSD is the muscular defect, located in the muscular septum. Muscular VSDs constitute 5% to 20% of all VSDs. The defect may be single when viewed from the left side but appears to be multiple when viewed from the right ventricle because the shunted blood flows around trabeculations (criss-crossing muscular and fibrous tissue strands) that form the right ventricular walls. Muscular defects are found in the apex, in the central or mid-muscular region, or in the anterior or marginal region of the septum. Multiple defects involving all components of the ventricular septum are usually referred to as a “Swiss cheese” septum.

Many (30% to 40%) membranous and muscular VSDs may close spontaneously. Spontaneous closure occurs more frequently in small defects and during the first 6 months of life. Defects do not enlarge with age, so they may become relatively smaller as the infant grows. Inlet and outlet defects do not close spontaneously.

Pathophysiology

The primary variable that determines the hemodynamic consequences of a VSD is the size of the defect. Small to medium defects restrict the volume and the pressure of the left-to-right shunt. However, large defects (approaching the size of the aortic orifice) do not restrict flow, so the magnitude of the shunt is determined by the difference between pulmonary and systemic vascular resistances.⁵⁹⁷

Immediately after birth, pulmonary vascular resistance normally falls rapidly as the small, muscular pulmonary arteries change from vessels with small lumens and thick medial muscle walls to vessels with larger lumens and thinner walls.³⁰ When pulmonary vascular resistance falls normally, right ventricular pressure decreases and approaches adult levels by 7 to 10 days of life.⁵⁹⁷

The normal postnatal decline in pulmonary vascular resistance may be delayed if a large VSD is present, and this will, in turn, delay development of symptoms of the shunt. The increase in pulmonary blood flow resulting from a VSD will increase left atrial and pulmonary venous pressure and slow the normal decline in pulmonary vascular resistance, so it may take weeks to fall. When pulmonary vascular resistance eventually falls, the left-to-right shunt through the VSD increases. Increased pulmonary blood flow causes increased pulmonary venous return to the left side of the heart with resultant left atrial and ventricle enlargement and development of congestive heart failure, usually at 2 to 8 weeks of age.⁵⁹⁷ If signs of congestive heart failure develop at this age, blood flow to the pulmonary arteries is typically at least twice the systemic blood flow or more.⁴⁵⁷

When the VSD is large, the volume of the shunt into the pulmonary circulation is large. Left ventricular hypertrophy develops rapidly in response to the volume load resulting from increased pulmonary venous return. In addition, when the VSD is large, the pressures in the right ventricle and the pulmonary circulation increase, and right ventricular hypertrophy and failure and pulmonary hypertension can develop.

Increased pulmonary blood flow can cause changes in the pulmonary vessels; these changes are more likely to develop and can develop more rapidly when the increased pulmonary blood flow is under high pressure. Medial hypertrophy and intimal proliferation can eventually cause pulmonary vascular obstructive disease.⁵⁹⁷ Such pulmonary vascular obstructive disease may be permanent as early as 12 months of age.

Once pulmonary vascular resistance approaches systemic vascular resistance, the shunt flow through the VSD decreases. If the shunt flow reverses as the result of development of pulmonary hypertension, this is called Eisenmenger syndrome. If Eisenmenger syndrome develops, the defect is irreparable, because acute right heart failure is likely to develop if the defect is closed.⁴⁵⁷ For this reason, children with moderate to large VSDs are followed closely with surgical intervention planned before the development of pulmonary hypertension.⁶⁸⁶ For further information, see Common Clinical Conditions, Pulmonary Hypertension.

Several factors may cause the newborn with a VSD to develop signs of congestive heart failure within the first few days of life rather than at several weeks of age. In a rare form of membranous defect, the left ventricle ejects directly to the right atrium. This defect produces a significant shunt and substantial increase in pulmonary blood flow. Other factors that promote early signs of congestive failure include additional cardiac anomalies (particularly any defect that increases resistance to left ventricular or systemic blood flow), respiratory infection, anemia, other congenital anomalies, and prematurity. Left heart abnormalities, including aortic stenosis, coarctation of the aorta, and interrupted aortic arch, can contribute to left ventricular failure and pulmonary edema, and they also magnify the difference between pulmonary and systemic resistance and increase the magnitude of the left-to-right shunt. Mitral valve stenosis or any pulmonary venous obstruction will substantially increase pulmonary venous congestion and pulmonary hypertension.⁵⁹⁷

Other factors may affect the pulmonary or systemic blood flow in patients with a VSD. In a membranous defect the great arteries may be malaligned, either to the right or left and the malalignment may obstruct right or left ventricular outflow. Such malalignment may affect the direction, volume, and pressure of the shunt flow. Tetralogy of Fallot and double outlet right ventricle with a subaortic VSD and pulmonary stenosis are examples of malaligned VSD associated with obstruction to pulmonary blood flow and a right-to-left shunt through the VSD (see section, Tetralogy of Fallot, Double Outlet Right Ventricle).⁴⁵⁷

In an outlet defect the right coronary cusp of the aortic valve may prolapse into the defect, because the defect in the ventricular septum results in inadequate support for the aortic root. In addition, a venturi effect on the valve leaflets can contribute to development of aortic insuffiency.^361,597 Once aortic insufficiency develops it is likely to increase with age.⁵⁹⁷ The right or noncoronary cusp of the aortic valve may also prolapse into a membranous defect; this may reduce flow through the defect but obstruct the right ventricular outflow tract.⁶⁸⁶

The risk of bacterial endocarditis in infants and young children with VSD is low, rarely occurring before the age of 2 years.⁵⁹⁷

Clinical Signs and Symptoms

Moderate and large VSDs typically produce signs and symptoms of heart failure as early as 2 weeks of age. The infant will develop signs of pulmonary venous congestion, with tachypnea and respiratory rates as high as 80 to 100 breaths per minute with retractions. Systemic venous congestion produces hepatomegaly and systemic edema.⁴⁵⁷ These infants have difficulty feeding; as symptoms of congestive heart failure worsen, the infant takes a progressively longer time to take less formula, and fails to gain weight. Adrenergic stimulation produces tachycardia, peripheral vasoconstriction, decreased urine output, and diaphoresis.

Infants with a moderate to large VSD and congestive heart failure frequently present with respiratory infection. The respiratory infection makes it difficult to determine if the respiratory distress is caused by the left-to-right shunt or the infection.⁵⁹⁷

The murmur of a moderate VSD is harsh and holosystolic, and is usually associated with a thrill. When pulmonary blood flow is twice systemic blood flow, a third heart sound may be heard, with a mid-diastolic rumble. This sound is best heard at the apex and results from increased flow of pulmonary venous return across the mitral valve. The second heart sound is split with the pulmonary component at normal intensity.^457,597,686

With large shunts, increased precordial activity is apparent over both the right ventricular (parasternal) and left ventricular (apical) areas. The high volume of pulmonary blood flow and pulmonary venous return increase left ventricular volume, resulting in a hyperdynamic precordium. The systolic murmur is S1 coincident and is heard best along the left sternal border; it may end before the second heart sound. The second heart sound is narrowly split and has a loud pulmonary component. Some patients with VSDs have an early diastolic murmur indicating mild pulmonary or aortic valve insufficiency. Either condition indicates increased pathology: the pulmonary valve insufficiency indicates increased pulmonary artery pressure and the aortic valve insufficiency indicates prolapse of the aortic valve cusp. There is also a third heart sound, and a diastolic rumble can be heard at the apex.^457,597

Infants with infundibular pulmonary stenosis may develop cyanosis from a right-to-left shunt pathology similar to tetralogy of Fallot. Cyanosis may also be seen in the older child with a large VSD and pulmonary hypertension (i.e., pulmonary vascular disease with Eisenmenger syndrome—see section, Common Clinical Conditions, Pulmonary Hypertension).

The chest x-ray and electrocardiogram also vary with the size of the ventricular septal defect (see Tables 8-25 and 8-26). If the VSD is small the ECG and chest x-ray may be normal.⁶⁸⁶ With a moderate VSD there is increased pulmonary venous return to the left ventricle, resulting in left ventricular hypertrophy (LVH) on the ECG. Cardiomegaly, increased pulmonary vascular markings, and an enlarged main pulmonary artery segment will be visible on the chest radiograph.⁵⁹⁷ In young infants with large VSDs, right ventricular hypertrophy may not be as marked on the ECG as in older infants who have pulmonary hypertension. When the right ventricular pressure equals the left ventricular pressure, biventricular hypertrophy is apparent on ECG and the left atrial enlargement may produce a biphasic P wave.

Cardiomegaly will be present on chest radiograph and results from enlargement of both ventricles and the left atrium. Increased pulmonary vascular markings (increased pulmonary blood flow) will also be present.^597,686

Two-dimensional echocardiography accurately identifies the defect anatomy and any associated anomalies, including overriding atrioventricular valves, prolapse of the aortic valve cusp, aortic valve regurgitation, and ventricular outflow tract obstruction. Color-flow Doppler studies provide information regarding restriction of flow through the defect and allow assessment of pulmonary and right ventricular pressures. Measurement of left atrial and ventricular diameters provides information about shunt volume.

Transesophageal echocardiography is used preoperatively to further define the defect. It may also be used intraoperatively to evaluate closure of the defect(s).^457,597

Because echocardiography provides precise details of the anatomy and allows assessment of pulmonary and ventricular pressures and shunts, cardiac catheterization is rarely necessary unless device closure is anticipated. Cardiac catheterization is used to evaluate pulmonary vascular disease (see section, Common Clinical Conditions, Pulmonary Hypertension).

Management

Surgical Closure

Palliative surgery using a pulmonary artery band is no longer used, even for small infants with significant left-to-right shunts. Indications for early surgery include uncontrolled congestive heart failure with failure to thrive. Surgical repair is successfully performed within the first few months of life in infants as small as 2   kg. Additional indications for closure include large defects even without symptoms, defects with elevated pulmonary pressures, defects producing a pulmonary-to-systemic shunt ratio greater than 2:1, and defects with associated aortic cusp prolapse. Defects associated with elevated pulmonary pressure and signs of pulmonary hypertension are repaired as soon as signs of pulmonary hypertension are noted or before 2 years of age to prevent pulmonary vascular disease.^457,597

VSDs are closed surgically through a median sternotomy on hypothermic, cardiopulmonary bypass. Muscular, perimembranous, and inlet defects are closed from the right atrium through the tricuspid valve (i.e., without a ventriculotomy). Subpulmonary defects are closed through the pulmonary valve (so the incision is made in the pulmonary artery). Outlet and perimembranous defects that involve prolapse of the aortic valve cusps require careful attention to support of the aortic valve cusp and avoiding injury to the conduction system.^275,457 Multiple defects, especially near the ventricular apex, may require a small apical ventriculotomy or device closure. The device may be placed intraoperatively.⁴⁵⁷

A variety of materials are used to close VSDs, including autologous pericardium, woven Dacron, or homograft material, and selection is determined by surgeon preference.²⁷⁵ Intraoperative echocardiography and color flow Doppler are used to determine residual shunts or additional defects before the patient is removed from cardiopulmonary bypass or before the patient leaves the operating room.

Postoperative complications include congestive heart failure and arrhythmias. Right bundle branch block is usually present postoperatively if surgery is performed in patients less than 6 months of age. If closure of an apical ventricular septal defect required a ventriculotomy, postoperative myocardial dysfunction is likely.⁴⁵⁷ Postoperative complications are likely in infants with respiratory infections before surgical repair.⁵⁹⁷

Long-term survival of patients with VSD is good. Spontaneous closure of small defects is almost 80%. Ninety-four percent of symptomatic infants with moderate defects who respond to medical treatment and do not require surgical or catheter intervention continue to do well 15 years after initial diagnosis. Most infants with large, symptomatic VSDs who require surgery within the first year have excellent results with normal growth, development, and activity. Limited longitudinal studies show that pulmonary hypertension is rare; sinus node dysfunction is also rare; but progressive aortic valve insufficiency is more common. Children repaired after 2 years of age may demonstrate increased postoperative pulmonary resistance that may be progressive.^597,759

In the discharge mortality data (Table 8-30) from the STS Congenital Heart Surgery Data Summary,^851-853 mortality for surgical closure of VSD is highest in neonates. Infant discharge mortality is twice that of the child, but is just slightly greater than 1%. Therefore it appears that repairing symptomatic infants in the first year of life is the best management of large symptomatic ventricular septal defects.

Table 8-30 Summary of Surgical Repair of VSD, 2006-2010^851-853

Advanced concepts for the nurse caring for the infant or child with VSD are provided in Box 8-24.

Box 8-24 Advanced Concepts: Ventricle Septal Defect (VSD)

• The primary determinant of a left-to-right shunt and the pulmonary artery pressure is the size of the defect; once it is approximately half the size of the aortic outflow tract, it allows a relatively unrestricted shunt. Location of the defect also influences shunt volume and pressure.

• If the defect is large, the relative difference between pulmonary and systemic outflow tract resistance (including any subvalvular or valvular stenosis or pulmonary artery or aortic narrowing and resistances in the vascular bed) determines the volume of a left-to-right shunt.

• The presence of a loud murmur and a thrill does not indicate a significant left- to-right shunt.

• Closure of a ventricular septal defect is indicated for

Uncontrolled congestive heart failure and failure to thrive

Signs and symptoms of increased pulmonary resistance

Signs and symptoms of aortic valve prolapse

Pearls

• Atrioventricular septal defects are a group of abnormalities with a common finding—absence of atrioventricular septum. There are two forms of AVSDs—partial and complete.

With partial AVSD the mitral annulus and the tricuspid valve annulus are separate and complete

With complete AVSD, the mitral and tricuspid valve share some tissue—there is a single atrioventricular valve annulus.

• AVSDs do NOT close spontaneously. All require surgical repair.

Etiology

Atrioventricular septal defects (AVSD) are a group of abnormalities of the atrioventricular septum and atrioventricular valves.¹⁵⁰ The one common finding in this group of abnormalities is the absence of the atrioventricular septum; therefore the term atrioventricular septal defect is used for this group of defects.³⁰ AVSDs are mainly derived from faulty fetal development of the atrioventricular septum and the embryologic endocardial cushion tissue; thus, they are also called endocardial cushion defects.

Atrioventricular septal defects occur in 4% to 5% of all congenital heart defects. The estimated incidence is 0.19 in 1000 live births. An AVSD is the most common defect identified on fetal echocardiography,^150,686 and the most common congenital heart defect in children with Down syndrome (see section, Essential Anatomy and Physiology, Etiologies of CHD: Noninherited and Genetic Factors). Patients with Down syndrome and AVSD rarely have associated cardiac defects. Children with AVSD but no Down syndrome may also have heterotaxy syndrome with asplenia and polysplenia.⁵⁷⁵ A common atrium is associated with Ellis-van Creveld syndrome.¹⁵⁰

The AVSDs are divided into two forms: partial and complete (Fig. 8-34). In the partial form there are two distinct atrioventricular valve annuli: the tricuspid valve (with possible cleft) and a cleft mitral valve. In the complete form of AVSD there is a common atrioventricular valve annulus.

Fig. 8-34 Diagram of the atrioventricular (AV) valve(s) and cardiac septa in partial and complete atrioventricular septal defects (AVSDs). A, Normal AV valve anatomy with no septal defect. B, Partial AVSD with an ostium primum atrial septal defect (ASD) (solid arrow showing left to right atrial shunt) and clefts in the mitral and tricuspid valves. C, Complete AVSD. An ostium primum ASD (solid arrow indicates resulting atrial shunt) and an inlet ventricular septal defect (open arrow indicates ventricular shunt) are present. There is a common AV valve with large anterior and posterior bridging leaflets. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

(From Park MK. Pediatric cardiology for practitioners, ed 5, Philadelphia, 2008, Elsevier, Fig. 12-15.)

A typical partial AVSD includes a primum atrial septal defect (ASD) with a cleft in the anterior leaflet of the mitral valve. The tricuspid valve may also have a cleft in the septal leaflet.

The complete form of AVSD includes a persistent fetal common atrioventricular canal. It is composed of a primum atrial septal defect that is contiguous with an inlet ventricular septal defect (VSD). When the common atrioventricular valve is open, the valve and the septal defects form a “canal” in the center of the heart, hence the name atrioventricular canal defect.^150,575,686

In both partial and complete forms of AVSD there is downward displacement of the left atrioventricular valve so that both valves are on the same plane. This creates a deficiency in the length of the ventricular septum from the inlet portion to the apex and increases the length from the apex to the aortic valve. The result is an elongated and narrowed left ventricular outflow tract, commonly called a “gooseneck” deformity as illustrated in Fig. 8-35.

Fig. 8-35 Left ventricular angiograms depicting characteristic features of atrioventricular septal defects (AVSDs). A, The injection of contrast into the left ventricle creates a silhouette of the large cleft in the mitral valve (large black arrow). During systole, contrast material can be seen flowing back into the left atrium through the insufficient mitral valve. The downward displacement of the mitral valve creates a characteristic elongation of the left ventricular outflow tract (the “gooseneck” deformity), which is outlined by five small (black and white) arrows. B, This complete atrioventricular canal defect can be identified, because injection of contrast material into the left ventricle outlines both the mitral and tricuspid valve orifices (TV and MV); these valve rings are not separate and complete. A small indentation in the contrast material (single large arrow) is created by some ventricular septal tissue, but the contrast material reveals the ventricular level shunt. The elongation (“gooseneck” deformity) of the left ventricular outflow tract (four small arrows) is apparent.

There is wide variability among AVSDs with many variations of the atrial and ventricular septal defects and of atrioventricular valve anomalies. These variations provided the basis for complex terminology used in previous classifications. The current trend is to use the generic term AVSD and then describe the anatomy and shunting present.^150,575

Pathophysiology

The physiology seen in this group of defects may be similar to that observed with an atrial septal defect (ASD), ventricular septal defect (VSD), or both, with the possibility of atrioventricular valve regurgitation (refer to Atrial Septal Defect and Ventricular Septal Defect, above). Every possible variation is seen with anatomic differences in both the size of the defect(s) and/or the degree of atrioventricular valve incompetence.⁵⁷⁵

Clinical Signs and Symptoms

Management

The management of the child with AVSD is determined by the child's symptoms, anatomy, and presence of pulmonary vascular disease. Surgical intervention is ultimately required because the defects do not close spontaneously and are not amenable to catheter closure.

Repair of Complete AVSD

For the child with complete atrioventricular septal defect preoperative management includes medical therapy for congestive heart failure using diuretics and afterload reduction (see section, Common Clinical Conditions, Congestive Heart Failure). Medical management also includes nutritional support to minimize failure to thrive (see section, Common Clinical Conditions, Altered Nutrition and Potential Gastrointestinal Complications).

To prevent permanent development of pulmonary vascular obstructive disease and to treat congestive heart failure, surgical repair for uncomplicated complete AVSDs is typically performed in early infancy (at about 2 to 4 months).⁵⁷⁵

The goals of surgical repair of an infant with a balanced, complete AVSD include complete closure of the atrial and ventricular septal defects and effective use of the available atrioventricular septal valve tissue to create two competent atrioventricular valves. In an uncomplicated complete AVSD this may be accomplished in infants in the neonatal period, including those weighing as little as 3   kg.^45,492 The critical component of this repair is the repair of the valve, particularly the left atrioventricular or mitral valve. Dysfunction of the right-sided atrioventricular (tricuspid) valve is much better tolerated than dysfunction of the left atrioventricular valve.^275,575

A pulmonary artery banding is a palliative procedure performed through a left thoracotomy, without cardiopulmonary bypass. A “band” of synthetic material is placed around the pulmonary artery in an attempt to reduce pulmonary blood flow, decrease the severity of congestive heart failure, and reduce the risk of pulmonary vascular disease. This band on the pulmonary artery may cause distortion of the pulmonary valve or artery.¹⁵³

Only in extreme cases—including complex anatomy, sepsis or respiratory illnesses such as respiratory syncytial virus or pneumonia—is palliative surgery with placement of pulmonary artery band considered.^145,150,153 Some centers report successful outcomes with pulmonary artery banding for infants less than 1 month of age and less than 5   kg who exhibit significant congestive heart failure unresponsive to medical treatment. Successful banding has also been reported for infants with significant associated anomalies. However, the combined reported mortality rate (for banding and later debanding with complete repair) is as high as 15%.^150,686

For complete correction of AVSD the defect is approached through a median sternotomy incision and repaired during hypothermic, cardiopulmonary bypass. The repair is performed through an incision in the right atrium. Based on the preference of the surgeon, either a single patch or double patch technique is used to close the atrial septal defect and ventricular septal defect and reconstruct the atrioventricular valve (Fig. 8-36).^{41,145,150,275,575,623}

Fig. 8-36 Surgical correction of atrioventricular septal defect. A patch is used to close the atrial septal defect (pericardium is usually used). When a complete AVSD is present (as shown), a second woven patch (usually Dacron) can be used to close the ventricular septal defect. The patches are placed to divide common atrioventricular valve tissue, particularly the bridging anterior leaflet. Clefts in the mitral valve are sutured to prevent significant postoperative mitral insufficiency while avoiding the creation of mitral stenosis.

(From Bender HW, et al: Repair of atrioventricular canal malformation in the first year of life. J Thorac and Cardiovasc Surg 84:518, 1982.)

In the single patch technique repair of AVSD, autologous pericardium is used to close the defects. In the double patch procedure, a Dacron patch is used to close the VSD and autologous pericardium is used to close the ASD. Usually the cleft in the left atrioventricular valve is sutured to form a bi-leaflet valve. Chordal attachments of the atrioventricular valve must be identified preoperatively with a surface echocardiogram or in the operating room with a transesophageal echocardiogram. The surgeon visually confirms the anatomy and makes the appropriate adjustments in patch placement. The abnormal location of the conduction system makes it critically important that the surgeon place the sutures to avoid the conduction tissue. Direct injury to the conduction tissue or edema around the sutures can cause postoperative heart block, including complete atrioventricular block.²⁷⁵

Postoperative complications following repair of complete AVSDs include persistent mitral valve regurgitation, low cardiac output, pulmonary hypertension, elevated left atrial pressures, and arrhythmias such as heart block and junctional atrial tachycardia. Because the atrioventricular valve has been reconstructed and risk of persistent AV valve regurgitation remains, volume loading to increase cardiac output should be avoided if at all possible for the first 24 postoperative hours. Volume loading may put tension on the site of valve sutures and can increase AV valve regurgitation. Atrial filling pressures should be maintained at lower values with inotropic support used to increase cardiac output, as needed. If either a residual ventricular septal defect or significant AV valve regurgitation is thought to be present, aggressive afterload reduction is needed.¹⁵³

Postoperative mortality is related to pulmonary hypertension. It is important to recognize any anatomic causes of pulmonary hypertension, such as severe left atrioventricular valve stenosis or regurgitation, or a residual ventricular septal defect.¹⁵³ The trend toward earlier age of repair has decreased the risk of pulmonary hypertension. When correction is performed at less than 3 months of age, fixed elevated pulmonary vascular resistance is rare and outcomes are good. If surgical repair occurs at 6 months of age or older, pulmonary vascular resistance may be elevated and postoperative pulmonary arterial hypertensive crises may be observed postoperatively.⁵⁷⁵ (For additional information, please refer to Common Clinical Conditions, Low Cardiac Output and Common Clinical Conditions, Pulmonary Hypertension, as well as the third section of this chapter, Postoperative Care and Anticoagulation.)

Postoperative arrhythmias may be problematic following repair of complete AVSD. As noted, the conduction tissue is in an abnormal position at the rim of the septal defect. Sinoatrial dysfunction may be present preoperatively, and complete heart block may be present postoperatively. When dysfunction of the sinoatrial node is present, cardiac output may be improved with atrial pacing. The preferred treatment of complete heart block is AV sequential pacing. Atrioventricular valve regurgitation may increase if ventricular (ventricular sensing, pacing inbited, or VVI) pacing is provided, rather than atrioventricular pacing.¹⁵³

The mortality rate following repair of AVSD averages 3% to 10%. The surgical mortality is the same for patients with and without Down syndrome. Increased mortality risk for complete repair of an AVSD is associated with very young age at operation, severity of preoperative atrioventricular valve regurgitation, hypoplasia of the left ventricle, increased or fixed pulmonary vascular resistance, and severity of preoperative symptoms.^150,686

If additional defects are present they can increase the operative risk. Patients with complex forms of atrioventricular septal defects include unbalanced AVSD (surgical risk is highest for right ventricular dominant defect; this means left ventricular hypoplasia is present) and when the defect is present in combination with tetralogy of Fallot, transposition of the great arteries, and double outlet ventricles. Please refer to those associated defects discussed in the following sections.

Surgical repair of AVSDs is one of the great success stories in the past several decades of congenital cardiac surgery.¹⁵⁰ In the STS Congenital Heart Surgery Data Summary, partial AVSD repairs in children have a postoperative mortality of 0%, and infant repairs of complete AVSD repairs has a mortality of 2% (Table 8-31).^851-853 Long-term survival is excellent. Reoperation is required for 2.5% of patients, most often indicated for progressive left atrioventricular valve regurgitation or for relief of left ventricular outflow tract obstruction.¹⁵⁰ Endocarditis remains a long-term postoperative risk for most patients, so antibiotic prophylaxis is recommended for periods of increased risk of bacteremia (see section, Bacterial Endocarditis).

Table 8-31 Summary of Surgical Repair of AVSD 2006-2010^851-853

Care of the infant or child with AVSD is both challenging and rewarding. Advanced concepts regarding atrioventricular septal defects are listed in Box 8-25.

Box 8-25 Advanced Concepts: Atrioventricular Septal Defect (AVSD)

• Atrioventricular septal defects are the most common defects in patients with Down syndrome.

• The degree of atrioventricular valve regurgitation determines the onset of symptoms in both forms of AVSDs.

• A delay in the onset of symptoms past 2 months may indicate persistent pulmonary hypertension.

• Surgical repair of complete AVSD is performed before 6 months of age to prevent pulmonary vascular obstructive disease.

• Abnormal development of the conduction system is an important risk factor for postoperative arrhythmias, especially complete heart block.