Infants with ductal dependent congenital heart disease require a “balanced” circulation to achieve adequate systemic and pulmonary blood flow. Those who present with severe cyanosis or shock, or require prolonged interhospital transport are tracheally intubated and mechanical ventilation is provided. Great care must be taken throughout the preoperative period to ensure that appropriate ventilation and oxygenation strategies are used to prevent an iatrogenic imbalance between systemic and pulmonary blood flow. In particular, in patients with ductal dependent systemic blood flow (e.g., HLHS or interrupted aortic arch), hyperventilation and provision of supplemental oxygen will decrease pulmonary vascular resistance, thereby promoting increased pulmonary to systemic flow ratio (Qp/Qs), and “steal” from the systemic and coronary circulations. Such patients will have inappropriately high systemic oxygen saturations (greater than 90%), poor systemic perfusion and are at risk of developing myocardial dysfunction as a result of volume overload and coronary ischemia, renal insufficiency, and/or NEC. Interventions that may be employed to increase pulmonary vascular resistance and improve the balance between systemic and pulmonary circulations, including subambiant FiO₂ and hypoventilation, are discussed below in the section on preoperative management of HLHS. Neonates with left ventricular outflow tract obstruction who are stable at presentation may be allowed to spontaneously breathe while awaiting surgical intervention, with close monitoring of their cardiopulmonary status. These neonates will typically have relatively high systemic oxygen saturations (greater than 90%) and “quiet tachypnea,” but will maintain adequate peripheral pulses, urine output, and low
lactate levels. Diuretics and low dose inotropic support are occasionally needed to alleviate pulmonary edema and to support the volume-loaded ventricular myocardium. In neonates with right ventricular outflow tract obstruction, the ductus arteriosus is often somewhat stenotic and takes a tortuous course from the aorta to the pulmonary artery, related to the in utero blood flow pattern, which typically will prevent torrential pulmonary blood flow. Thus marked pulmonary overcirculation is less of a clinical concern in ductal-dependent neonates with right ventricular outflow tract obstruction.

Inotropic support is occasionally necessary for neonates with congenital heart disease, particularly those with volume loaded single ventricles, but escalating inotropic or vasopressor requirements often signify a noncardiac problem or inadequate systemic cardiac output as a result of Qp/Qs imbalance. Inotropic agents are discussed in the postoperative section on low cardiac output.

The premature infant with critical congenital heart disease presents a significant challenge. Problems inherent to prematurity, including temperature instability, decreased nutritional reserve, intraventricular hemorrhage, respiratory distress syndrome, infection, and NEC, may develop during the pre- and postoperative course. In preterm infants with critical congenital heart disease, a management strategy of prolonged medical therapy to achieve weight gain prior to surgery is fraught with complications related to infection, heart failure and feeding intolerance (43,44). Advances in cardiopulmonary bypass techniques and miniaturization of surgical equipment allow for the safe conduct of open-heart surgery in these patients. Several reports depict the recent experience with palliative or definitive surgical intervention in premature infants with critical congenital heart disease. Reddy and associates reported the University of California at San Francisco experience with complete (two-ventricle) repair in 102 infants with significant congenital heart disease weighing less than 2,500 grams. These investigators found higher preoperative morbidity in the group of patients having delayed repair. The early and late mortalities were 10 and 8%, respectively, and no patient had postbypass intracranial hemorrhage (44). Investigators from the same center reported a series of 20 very low birth weight (LBW)(< 1,500 gm) infants with symptomatic congenital heart disease who underwent complete repair with only two deaths (10%) (45). Rossi and associates reported a series of infants weighing less than 2 kg, 73% of which were born prematurely. Hospital survival was 83%, and 24% of the patients had neurologic complications (46). Bacha and associates, in a study of 18 infants weighing less than 2 kg with coarctation of the aorta, found that repair can be accomplished with low operative mortality, but the residual or recurrent coarctation rate was 44% (47). Results for single ventricle palliation are less encouraging. The reported mortality for infants weighing less than 2.5 kg at the time of Norwood operation for HLHS or other single ventricle variants is 45% to 51% (48,49). Thus, although prematurity and LBW complicate the care of infants with significant heart disease, early intervention, including corrective surgery, can be performed with acceptable morbidity and mortality.

Although the enteral route is the preferred method for providing nutrition to infants in the intensive care unit, those with critical congenital heart disease awaiting intervention often have several pathophysiologic features that must be considered prior to initiation of enteral feedings. The combination of myocardial dysfunction, cyanosis and falling pulmonary vascular resistance, the later allowing increased diastolic runoff through the ductus arteriosus, may result in inadequate mesenteric oxygen delivery. In one large, retrospective study, approximately 3% of neonates admitted to a busy cardiac intensive care unit developed NEC (50). Independent risk factors for developing NEC were prematurity, a history of resuscitation from severe cyanosis or shock, HLHS, or the presence of diastolic runoff through the ductus arteriosus or other aorto-pulmonary connections (50). In part as a result of the absence of randomized studies, the use of enteral nutrition in infants with ductal-dependent congenital heart disease remains controversial and clinical practice varies widely. The risk-benefit ratio for providing enteral nutrition must be individually determined for each patient. One approach is to avoid enteral feeding in those infants who have one or more of the aforementioned risk factors. It is also reasonable to consider enteral feedings in those infants with an acceptable diastolic blood pressure despite the presence of a patent ductus arteriosus, provided that additional risk factors are not present.

Congenital complete heart block may be associated with structural heart disease including atrioventricular canal defects and complex lesions with ventricular inversion. In neonates with normal intracardiac anatomy, there is a high incidence of maternal autoimmune disease, particularly systemic lupus erythematosus (51). Congenital complete heart block is diagnosed electrocardiographically when atrioventricular dissociation is present with an atrial rate that is appropriate for age and a slow ventricular rate. The diagnosis may be made in utero by fetal echocardiography and may be associated with hydrops fetalis. Dual chamber epicardial pacemaker placement is indicated when third degree congenital atrioventricular heart block is associated with a wide QRS escape rhythm, complex ventricular ectopy, or ventricular dysfunction. A pacemaker is also indicated in an infant with a ventricular rate less than 50 to 55 beats per minute, or with congenital heart disease and a ventricular rate less than 70 beats per minute (52).

In neonates with critical pulmonary valve stenosis, the pulmonary valve leaflets are thickened and fused to a variable extent, and their mobility is decreased (Fig. 34-1, see also color plate). The pulmonary valve annulus is hypoplastic in severe cases. The pulmonary arteries are usually of normal size, but may be stenotic or dilated. The right ventricle is often hypertrophied and mildly hypoplastic. Significant tricuspid regurgitation, and a right to left atrial shunt are present (53). Infants with isolated critical pulmonary valve stenosis will develop significant cyanosis (See Color Plate) upon closure of the ductus arteriosus. Such infants are dependent on a PGE₁ infusion to maintain ductal patency for adequate pulmonary blood flow. Although open surgical valvotomy was routinely performed in the past to relieve right ventricular outflow tract obstruction, most of these infants are candidates for a balloon valvuloplasty in the cardiac catheterization laboratory. Balloon valvuloplasty is successful in approximately 60% to 80% of cases (53,54,55,56,57,58). Neonates who fail an attempted balloon valvuloplasty may have smaller right heart structures, and are referred for a surgical valvotomy +/- a systemic to pulmonary artery shunt (59,60).

Tetralogy of Fallot, the most common cyanotic congenital heart lesion, is comprised of an anterior malalignment VSD in a heart with two ventricles and aortic to mitral fibrous continuity. Anatomic details that need to be clarified at the time of diagnosis include the severity and location of right ventricular outflow tract obstruction, the pulmonary artery anatomy, the presence of additional VSDs, the sidedness of the aortic arch (rightward in 25%), and the coronary artery anatomy. The left coronary artery may arise from the right coronary artery and cross the right ventricular outflow tract in 5% of cases. Complete anatomic information is usually obtainable by transthoracic echocardiogram (33). If uncertainty exists about the coronary artery anatomy, some surgeons may request a cardiac catheterization, as great care must be taken not to injure the coronary vessels during right ventricular outflow tract reconstruction. Chromosome 22q11 deletion is present in 15% of patients with tetralogy of Fallot, and those with a right aortic arch are at higher risk (41).

In neonates with tetralogy of Fallot, a wide spectrum of presentation exists, depending in large part upon the degree of malalignment of the conal septum into the right ventricular outflow tract. Infants with a minimal degree of obstruction to pulmonary blood flow, commonly referred to as “pink tets,” are usually asymptomatic and fairly well oxygenated (systemic saturations > 85%) soon after birth. They are commonly observed in the hospital until the ductus arteriosus closes and then sent home to await surgical repair within the first 6 months of life. Occasionally a “pink tet” will mimic the pathophysiology of an infant with a large VSD and develop congestive heart failure within the first few months of life as pulmonary vascular resistance falls. More commonly these patients develop progressive right ventricular outflow tract obstruction and cyanosis. The exact timing of repair varies depending
upon several variables including the development of increasing cyanosis, hypercyanotic spells (“TET spells”), and institutional preference (2,61). Infants with tetralogy of Fallot and more severe right ventricular outflow tract obstruction or pulmonary atresia will develop excessive cyanosis (oxygen saturation < 75%-80%) upon closure of the ductus arteriosus. Such patients will require surgical intervention during the initial hospitalization. Either a complete repair or a systemic to pulmonary shunt is performed, depending on the details of the anatomy and surgeon preference (62).

Hypercyanotic episodes, or “TET spells,” are potentially life-threatening events notable for significant desaturation and irritability as a result of an acute decrease in pulmonary blood flow. The precise etiology of these spells is unclear but has been attributed to spasm of the infundibular conus, an imbalance between the systemic and pulmonary vascular resistances, increased systemic venous return, and/or tachycardia, all of which may lead to a progressive cycle of decreased pulmonary blood flow, increased cyanosis, and eventually metabolic acidosis. Although TOF spells can occur at any age, the incidence seems to increase after 4 to 6 months of age, which is one of the reasons that early complete repair before this age is commonly recommended. TET spells can be triggered by medical procedures including placement of intravenous catheters and cardiac catheterization. Infants with tetralogy of Fallot have a fixed component of obstruction to pulmonary blood flow, and thus will normally develop transient desaturation with agitation and feeding as a result of increased oxygen consumption and cardiac output. Clinical judgment is required to differentiate a true TET spell from these common and benign desaturation episodes. The absence of a murmur during a true TET spell, signifying a substantial reduction of blood flow across the right ventricular outflow tract, may be useful in this regard. Treatment strategies are implemented with the goal of decreasing patient agitation and heart rate, increasing systemic vascular resistance and pulmonary blood flow, and correcting metabolic acidosis (Table 34-4). Prompt surgical intervention is indicated once an infant has had a TET spell.

Absent pulmonary valve syndrome, identified by the presence of rudimentary pulmonary valve leaflets and free pulmonary insufficiency, is a relatively rare lesion, present in approximately 3% of all patients with tetralogy of Fallot. This lesion is most notable for in utero development of aneurysmal dilation of the pulmonary arteries, which may occur as a result of the lack of a ductus arteriosus or as a result of the pulsatile blood flow pattern across the right ventricular outflow tract. When compared with infants with typical tetralogy of Fallot, there may be a higher incidence of chromosome 22q11 deletion in those with absent pulmonary valve (63). A nearly pathognomonic to-and-fro (“sawing wood”) murmur is heard as a result of pulmonary annulus stenosis and free pulmonary insufficiency (Fig. 34-2, see also color plate). Such patients may have minimal if any respiratory symptoms and behave much like a “pink tet,” or present with severe problems with oxygenation and ventilation soon after birth as a result of compression of the bronchi by the dilated pulmonary arteries (64). Intubation, mechanical ventilation (with judicious use of positive end-expiratory pressure), and deep sedation may be life saving in neonates with symptomatic airway obstruction. Prone positioning may be advantageous as gravity will allow the pulmonary arteries to fall off the mainstem bronchi, thus permitting adequate gas exchange (65). Prompt surgical repair is indicated in symptomatic neonates.

Infants with pulmonary atresia, VSD and MAPCAs represent a challenging subset of infants with pulmonary atresia. This lesion is also referred to as tetralogy of Fallot, pulmonary atresia and MAPCAs. In addition to the anatomic features of tetralogy of Fallot as described above, the true pulmonary arteries are often diminutive or absent, and a variable number of aortopulmonary collaterals arise from the aorta or bracheocephalic vessels to supply pulmonary blood flow. Infants with this lesion will present with either cyanosis or congestive heart failure, depending upon the cardiac anatomy (66). The physical examination may be notable for the presence of a widely radiating continuous murmur produced by the aortopulmonary collateral blood flow. These infants are generally not dependent upon prostaglandin infusion unless a major aortopulmonary
collateral vessel arises from the ductus arteriosus. Cardiac catheterization is required to identify all sources of pulmonary blood flow. Surgical strategy must then be individualized depending upon the pulmonary artery and collateral vessel anatomy. True pulmonary arteries, MAPCAs, or both may supply blood to individual segments of the lungs. The ultimate goal is to encourage true pulmonary artery growth and incorporate as many arterial blood vessels and lung segments into the repair as possible to maximize the effective pulmonary arterial vascular bed, and thus minimize right ventricular hypertension following VSD closure. In situations in which dual blood supply to a lung segment exists, the MAPCAs are coil occluded in the cardiac catheterization laboratory or ligated at the time of surgery to eliminate left to right shunting. As with other conotruncal defects, these infants should undergo genetic testing for chromosome 22q11 deletion.

Pulmonary atresia is characterized by a membranous or plate-like obstruction of the right ventricular outflow tract at the level of the pulmonary valve, with variable degrees of hypoplasia of the tricuspid valve and right ventricle, and occasional coronary artery fistulous connections to the right ventricle. Systemic venous return to the right atrium flows through an obligatory atrial communication to the left atrium. Infants with pulmonary atresia and intact ventricular septum will manifest with significant cyanosis upon closure of the ductus arteriosus, and are thus dependent on prostaglandin infusion. Intervention in these patients depends on two key issues: the adequacy of the right ventricular size to support a two-ventricular circulation, and on the presence of “right ventricle dependent coronary circulation.” The right ventricle must have adequate size to support the entire right heart circulation if these patients are to be considered for a two-ventricle repair. The size of the tricuspid valve annulus plays an important role in the decision making process (67). Infants with pulmonary atresia and intact ventricular septum, particularly those with small tricuspid valve annulus size, may have significant fistula communications between the right ventricle and the coronary circulation, known as coronary-cameral fistulae, which may be identified by echocardiogram and further characterized by cardiac catheterization (68,69). If coronary stenoses exist such that a significant amount of coronary blood flow to the myocardium is derived from and dependent upon the coronary cameral fistulae, then “right ventricular dependent coronary circulation” is present. If the right ventricular outflow tract obstruction is relieved in an infant with “right ventricular dependent coronary circulation,” coronary perfusion pressure falls and the patient may develop a myocardial infarction. Thus, if the right ventricle is not of adequate size, or if “right ventricle dependent coronary circulation” exists, these patients are referred for a systemic to pulmonary artery shunt in anticipation of an eventual Fontan operation. If a complete two-ventricle repair is deemed appropriate, this may be performed as a primary operation in the neonatal period, although more commonly a systemic to pulmonary artery shunt and right ventricular outflow tract decompression is initially performed to encourage right ventricular growth, with complete repair in later infancy (70). Some infants with membranous pulmonary atresia and intact ventricular septum who meet criteria for a two ventricular repair may undergo perforation of the pulmonary valve using a stiff wire, a radiofrequency ablation catheter, or a laser catheter, followed by balloon valvuloplasty (54,58,71). In well-selected patients, the use of transcatheter intervention
may eliminate the need for surgical intervention. The decision to attempt transcatheter intervention is made considering patient size, co-morbidities, anatomic details, and institutional experience.

Ebstein’s anomaly of the tricuspid valve is a malformation in which the septal and posterior leaflets of the tricuspid valve are displaced to a variable extent into the anatomic right ventricle, and the anterior leaflet, although not inferiorly displaced, is redundant. Tricuspid regurgitation of variable severity occurs (Fig. 34-3, see also Color Plate). One or more accessory connections may be present at the tricuspid valve annulus, creating the necessary substrate for atrio-ventricular reentrant tachycardia. The clinical presentation is usually one of right-sided congestive heart failure and arrhythmias in adolescence or early adulthood. A small subset of infants with Ebstein’s anomaly, those with severe tricuspid regurgitation, a large “atrialized” portion of the right ventricle, severe cardiomegaly, and pulmonary hypoplasia are critically ill soon after birth and have a high mortality (72). These neonates will present with severe cyanosis as a result of functional right ventricular outflow tract obstruction, and right to left shunting at the atrial level. Infants with significant cyanosis should be started on PGE₁, and judicious use of positive end-expiratory pressure is required to re-expand the lungs, which are compressed by the generous heart size (73). Additionally, standard measures including inhaled nitric oxide should be employed to decrease pulmonary vascular resistance and cyanosis. In many of these patients, as pulmonary vascular resistance falls over time, forward flow increases across the right ventricular outflow tract, cyanosis decreases, and surgery can be deferred. For those neonates with refractory cyanosis, referral is made for either a primary complete repair, consisting of a reduction atrioplasty, fenestrated closure of the atrial septum and tricuspid valvuloplasty, or palliation toward the Fontan pathway starting with a systemic to pulmonary artery shunt (73,74,75).

Isolated congenital aortic valve disease may present in a variety of ways, depending primarily upon the severity of stenosis. A bicuspid aortic valve without stenosis or insufficiency may be an incidental finding in an otherwise healthy patient. At the other extreme, newborns with critical aortic valve stenosis develop shock upon closure of the ductus arteriosus. The murmur is typically softer than expected as a result of the low cardiac output state, and the gradient estimated by echocardiography may not correlate with the severity of the stenosis. Initiation of PGE₁ infusion allows blood from the right ventricle to provide systemic perfusion until an intervention can be performed (76). Once the infant is stabilized, echocardiographic information must be carefully reviewed to predict whether the left ventricle is of adequate size to sustain the systemic circulation following a two-ventricle repair (77). Infants thought to be suitable for a two-ventricle repair usually will be referred for a balloon aortic valvuloplasty; although a surgical aortic valvotomy is an acceptable option (78,79,80). If hypoplasia of multiple left sided structures suggests that the left ventricle will not be able to support the circulation, then a Norwood operation or heart transplantation may be considered.

A coarctation of the aorta is present when a significant narrowing exists in the thoracic aorta just distal to the left
subclavian artery. A “posterior shelf” is present opposite the insertion site of the patent ductus arteriosus. Coarctation of the aorta may exist in isolation or can be associated with aortic arch hypoplasia, a VSD, or other complex intracardiac lesions. When present in isolation, coarctation of the aorta is “critical” when ductal dependent systemic blood flow exists, which represents only about 10% of cases. Neonates with isolated critical coarctation of the aorta also will present with shock if the diagnosis is not made before significant constriction of the ductus arteriosus occurs (Fig. 34-4). Prior to the development of shock, the diagnosis should be suspected by the detection of a brachial-femoral pulse discrepancy, which can be confirmed by measuring an arm-leg blood systolic pressure gradient. A systolic blood pressure gradient between the upper and lower extremities of greater than 10 mm Hg is clinically significant. In approximately 5% of infants with isolated coarctation of the aorta, the right subclavian artery will arise aberrantly from the descending thoracic aorta, distal to the coarctation. Thus it is important to palpate pulses and measure blood pressure in both upper extremities in all infants with suspected coarctation. Occasionally differential cyanosis will be present as the lower body is being perfused by deoxygenated blood from the ductus arteriosus. PGE₁ infusion will almost always reopen the ductus arteriosus and allow recovery of end-organ function prior to surgical repair (76). In the absence of data from randomized clinical trails, the method of nutritional support for these patients should be individualized and deserves comment. Those neonates with critical coarctation who present in shock with metabolic acidosis and laboratory evidence of end-organ dysfunction should be maintained on bowel rest prior to surgery, and nutritional support is provided with total parenteral nutrition. However, enteral feeds may be considered in the subset of infants who are diagnosed prior to the development of shock, started on PGE₁, and subsequently have reasonable femoral pulses and diastolic blood pressure distal to the coarctation.

HLHS exists when there is severe mitral and aortic valve stenosis or atresia, a diminutive left ventricle, ascending aorta, and aortic arch, and often a juxtaductal coarctation of the aorta. Following birth there are two key communications that need to remain open to permit cardiopulmonary stability. A patent ductus arteriosus (PDA) is necessary to allow blood flow from the pulmonary artery to reach the systemic circulation, and shock will develop once the ductus arteriosus constricts. An adequate ASD is also necessary to allow egress of the pulmonary venous
blood flow from the left atrium to the right atrium. The 5% of infants with HLHS who have a severely restrictive or intact atrial septum will develop profound cyanosis, pulmonary edema, and shock almost immediately following delivery.

Initially, most patients with HLHS (assuming an unrestrictive or mildly restrictive atrial communication) will be hemodynamically stable following the initiation of a PGE₁ infusion. Over several days, however, as pulmonary vascular resistance falls, the ratio of pulmonary to systemic blood flow (Qp/Qs) will increase, leading to an increase in arterial oxygen saturation. Poor systemic circulation may manifest, and the neonate may develop right ventricular volume overload, and coronary and end-organ ischemia. The Qp/Qs may be calculated by the following equation which is derived from the Fick principle: Qp/Qs =(SaO₂-SvO₂)/(PvO₂-PaO₂), in which SaO₂ =aortic saturation; SvO₂ =mixed venous saturation (estimated by the superior vena cava oxygen saturation); PvO₂ =pulmonary venous oxygen saturation (assumed to be > 95% if not directly measured); and PaO₂ =pulmonary artery oxygen saturation (assumed equal to the aortic saturation). Most preoperative neonates will not have a catheter positioned in the superior vena cava to measure SvO₂, and thus the Qp/Qs cannot be precisely calculated. Determination of an absolute value for Qp/Qs is of less importance than having an appreciation for the physiologic disturbance that develops as these neonates become progressively over circulated. Theoretical computer models of newborns with HLHS demonstrate that, beyond a certain point, slight increases in arterial oxygen saturation are associated with significant decreases in oxygen delivery, and that maximal oxygen delivery occurs at a Qp/Qs less than 1 (Fig. 34-5 and 34.6) (81,82). This model also demonstrates that a SvO₂ less than 40%, or a SaO₂-SvO₂ difference of more than 40%, is likely associated with a severe derangement in systemic oxygen delivery, related to either a high Qp/Qs or low cardiac output (82).

In the typical neonate with HLHS, interventions that lower the pulmonary vascular resistance, such as supplemental oxygen and hyperventilation, may increase Qp/Qs and should be avoided. Patients with pulmonary over-circulation (high Qp/Qs) and evidence of poor end-organ perfusion (e.g., poor urine output, rising lactate levels, diminished peripheral pulses) may be treated with sub-ambient FiO₂, obtained using supplemental inhaled nitrogen to increase pulmonary vascular resistance and thus restore the balance between systemic and pulmonary blood flow (83,84). The supplemental nitrogen may be delivered through the endotracheal tube or through a nasal cannula in neonates who are spontaneously breathing. Pulmonary vascular resistance may also be increased in such patients using supplemental inspired carbon dioxide (CO₂) (85). In a prospective, randomized, crossover study, the impact of hypoxia (17% FiO₂) vs. hypercarbia (2.7% FiCO₂) on systemic oxygen delivery in preoperative neonates with HLHS was evaluated (86). All patients were receiving mechanical ventilation, deep sedation or anesthesia, and
neuromuscular blockade. The study found that both hypoxia and hypercarbia were effective in reducing Qp/Qs ratio (Fig. 34-7). Hypercarbia increased cerebral oxygen saturation, mean arterial blood pressure, oxygen delivery and, although not directly measured, cardiac output, whereas hypoxia did not change these variables, suggesting that hypercarbia may be the preferred therapy (Fig. 34-8) (86,87). However, administration of supplemental CO₂ requires the concurrent use of sedation and paralysis, thus limiting its applicability for most neonates with HLHS prior to surgery.

Neonates with HLHS and myocardial dysfunction should receive inotropic support to improve cardiac output and systemic oxygen delivery. However, care should be taken to avoid inotropic agents that increase systemic vascular resistance because this will favor pulmonary blood flow over systemic blood flow. Low-dose dopamine or milrinone are good inotropic agents for neonates with HLHS and myocardial dysfunction.

The neonate with HLHS and a severely restrictive or intact atrial septum will present with profound cyanosis and shock immediately after birth as a result of obstruction of blood egress from the left atrium. The short- and long-term outlook for such infants has historically been poor, regardless of whether they undergo the Norwood operation or are listed for heart transplantation, due in large part to the in utero development of pulmonary venous hypertension and lymphatic abnormalities that persist following birth (88,89,90). The immediate management of these critically ill neonates involves prompt intervention to decompress the left atrium. Emergent surgical intervention, involving either open atrial septectomy or a Norwood procedure, has usually resulted in early death. A Brockenbrough atrial septoplasty (transcatheter, trans-septal needle puncture followed by serial balloon dilation of the new ASD and possibly stent placement) will serve to decompress the left atrium, increase pulmonary venous return and pulmonary blood flow, and alleviate cyanosis (35). Following this procedure, the patient may be medically managed for a few days with a PGE₁ infusion and diuretics to allow pulmonary vascular resistance to fall and pulmonary edema to improve prior to the Norwood operation. This multidisciplinary approach to the neonate with HLHS and severely restrictive or intact atrial septum has resulted in a contemporary 53% survival rate following the Norwood operation, which is better than results obtained with other management strategies for this lesion, but remains poor when compared with the outcome of neonates without atrial obstruction who undergo the Norwood operation (91). Theoretically, alleviation of the left atrial hypertension in utero may improve outcome in patients with HLHS and a severely restrictive or intact atrial septum. Fetal intervention to dilate the atrial septum using percutaneous, transcatheter needle puncture of the atrial septum followed by balloon dilation appears to be feasible and is associated with minimal maternal risk, but technical improvements and additional experience will be required before this procedure is widely adopted (92).

Initial reports suggested that severe tricuspid regurgitation was a significant risk factor for infants with HLHS (93,94). However, in the preoperative infant with HLHS, the severity of tricuspid regurgitation may be in part related to a high Qp/Qs, with right ventricular volume overload and stretching of the tricuspid valve annulus. Following the Norwood operation, the Qp/Qs may decrease as a result of the fixed resistance to pulmonary blood flow provided by the shunt, and subsequently the degree of tricuspid regurgitation may diminish. Thus, clinical judgment and an appreciation of tricuspid valve morphology are required in such cases.

Several centers have recently reported overall survival rates of more than or equal to 90% following initial surgical palliation for HLHS (Fig. 34-9) (4,95). Contemporary risk factors contributing to higher mortality following the Norwood operation include prematurity, the presence of multiple congenital anomalies, and an intact atrial septum (48,88). Although palliative care is still offered at some centers for neonates with HLHS, fewer clinicians and parents are opting for no intervention given the improving surgical results (96). Some centers offer heart transplantation as a primary option for HLHS (97). Problems with this strategy include the high morbidity and mortality incurred while waiting for a heart to become available from a very limited donor pool, suboptimal neurologic outcome in many patients, and complications inherent to heart transplant (98,99,100). For these reasons, many pediatric cardiology centers recommend the Norwood operation as the initial surgical intervention in neonates with HLHS, and heart transplantation is typically reserved for the small subset that develop subsequent irreversible myocardial failure.

An interrupted aortic arch (IAA) is most commonly associated with a VSD, but also is seen with a variety of other congenital cardiac malformations, including truncus arteriosus and TGA (101). If a VSD is not present in a patient with an IAA, an aorto-pulmonary window is likely to be found. IAA is classified by the location of the arch interruption in relation to the bracheocephalic vessels (Fig. 34-10) (102). IAA type B is the most common subtype (>50% of cases), and type C is rare. Chromosome 22q11 deletion is present in approximately 60% of neonates with IAA type B (41). The infant with an unrecognized IAA will present with shock, similar to a critical coarctation, upon closure of the ductus arteriosus. Infants with IAA are dependent upon ductal patency to maintain blood flow to the lower body, and
preoperative management strategies to balance the systemic and pulmonary circulations mimic those used in infants with HLHS. Early surgical intervention is warranted.

In d-TGA, the aorta arises from the anatomic right ventricle and the pulmonary artery arises from the anatomic left ventricle. Approximately 40% of neonates with TGA have an associated VSD, which occasionally is a malalignment type defect. If anterior malalignment exists, there may be associated right ventricular outflow tract obstruction, aortic valvar stenosis, coarctation of the aorta or rarely an IAA. A posterior malalignment VSD is associated with left ventricular outflow tract obstruction, pulmonary stenosis or atresia. Coronary artery branching abnormalities are present in approximately 30% of cases.

In this unique parallel circulation, deoxygenated systemic venous blood returns to the right heart and is pumped back to the systemic arterial circulation, and oxygenated pulmonary venous blood passes through the left heart and is pumped back to the lungs. Unless there is adequate mixing between these parallel circulations, severe cyanosis, metabolic acidosis and death will occur. Such intercirculatory mixing represents effective pulmonary and systemic blood flows, and may take place at the atrial, ventricular, or great artery level (Fig. 34-11). Infants with TGA and an intact ventricular septum typically have a patent foramen ovale (PFO) or ASD that allows some mixing at the atrial level. However, a PGE₁ infusion is usually necessary to open or maintain patency of the ductus arteriosus, which will increase effective pulmonary blood flow, provided that the pulmonary vascular resistance is lower than the systemic vascular resistance and that there is an adequate atrial communication.

Occasionally infants with TGA may develop severe cyanosis and shock following the initiation of PGE₁ infusion, as a result of increasing blood volume returning to the left atrium and functional closure of the foramen ovale. If this occurs, or if the PFO is restrictive, as assessed by echocardiography, and excessive cyanosis is present, an emergent balloon atrial septostomy should be performed to enlarge the atrial communication (Fig. 34-12, see also Color Plate) (34). The balloon atrial septostomy may be performed at the bedside using echocardiographic guidance, or in the cardiac catheterization laboratory (103). Excessive cyanosis may persist despite a technically successful balloon atrial septostomy. High pulmonary vascular resistance may limit effective pulmonary blood flow, and measures should be taken to lower pulmonary vascular resistance. Because the majority of systemic blood flow comes from the systemic venous circulation in TGA, neonates who remain excessively cyanotic following a balloon atrial septostomy will also improve following maneuvers that will increase the mixed venous oxygen saturation. These include interventions to decrease oxygen consumption, such as sedation and paralysis, and improve oxygen delivery, such as correcting anemia and administering inotropic agents. To summarize, infants with TGA and intact ventricular septum who remain excessively cyanotic despite the initiation of PGE₁ require a balloon atrial septostomy, and if necessary, interventions to lower pulmonary vascular resistance and increase systemic venous oxygen saturation.

Many clinicians recommend that a semi-elective balloon atrial septostomy be performed in nearly all patients with TGA and intact ventricular septum, even those without
excessive cyanosis. Once the atrial septum is enlarged, the PGE₁ can usually be safely discontinued, thus avoiding complications related to that medication and a large ductus arteriosus, such as apnea and NEC. Furthermore, the left atrium is decompressed following a balloon atrial septostomy, which may allow the pulmonary vascular resistance to fall prior to surgery. Finally, the infant may be transferred from the ICU to the general ward to initiate feedings and await surgery. The major risks associated with the performance of a balloon atrial septostomy include myocardial perforation or avulsion of the inferior vena cava from the right atrium during pullback of the balloon, both of which rarely occur. Following initial stabilization of the neonate with TGA and intact ventricular septum, an early arterial switch operation is required before the left ventricle becomes deconditioned.

Infants with TGA and moderate to large VSD generally are well oxygenated and do not require a PGE₁ infusion provided that the ventricular outflow tracts are unobstructed. Early congestive heart failure typically develops, and surgical repair is indicated within the first few weeks of life. A malalignment-type VSD may be associated with clinically significant left or right ventricular outflow tract obstruction. Patients with sub-aortic obstruction may have an associated coarctation of the aorta or an IAA. Such an infant may present with the very unique finding of reverse differential cyanosis, with low oxygen saturation in the right arm and high oxygen saturation in the leg. A PGE₁ infusion is needed, followed by early surgical intervention. Infants with d-TGA and VSD who are referred for surgery after the first few months of life (typically from underdeveloped nations) are at risk for having developed pulmonary vascular obstructive disease. These patients may require a cardiac catheterization to evaluate their pulmonary vascular resistance prior to surgery.

Tricuspid atresia is present when there is agenesis of the tricuspid valve and an absent communication between the right atrium and right ventricle. The presentation of infants with this lesion is variable and depends primarily upon the presence and size of a VSD, whether the great arteries are normally related or transposed, and the degree of ventricular outflow tract obstruction (Table 34-5) (104,105). These factors determine which of these neonates will be dependent on a PGE₁ infusion. All of the systemic venous blood must pass through an obligate atrial communication to the left atrium, in which it mixes with the pulmonary venous blood. In the presence of normally looped ventricles and normally related great arteries, the left ventricle then ejects blood to the aorta, and through the VSD, if present, to the pulmonary artery. If the great arteries are transposed, the left ventricle pumps blood to the pulmonary artery (unless pulmonary atresia is present), and through the VSD to the aorta. Although all infants with tricuspid atresia eventually require a Fontan palliation, the type of initial operation depends upon the extent of cyanosis or systemic outflow obstruction. For example, infants with tricuspid atresia, normally looped ventricles and normally related great vessels, a large VSD and no or minimal right ventricular outflow tract obstruction (type I-C) will be well oxygenated and develop early heart failure. In the neonatal period, they require placement of a pulmonary artery band or transection of the pulmonary artery and placement of a systemic to pulmonary artery shunt. Those with a moderate size VSD and a moderate degree of right ventricular outflow tract obstruction (type I-B) will have a balanced circulation with an acceptable amount of cyanosis. Such infants may be discharged home with the expectation of a bi-directional
Glenn or hemi-Fontan operation within the first six months of life. Infants with tricuspid atresia and a small or absent VSD (type I-A or I-B) will have significant cyanosis and thus be dependent on a PGE₁ infusion until a systemic to pulmonary artery shunt is performed. Infants with tricuspid atresia and transposed great arteries, a small or absent VSD (type II-A or II-B) will develop shock unless ductal patency is maintained. These infants require a Damus-Kaye-Stansel operation (aortopulmonary anastomosis) or a modified Norwood operation with a systemic to pulmonary artery shunt.

Total anomalous pulmonary venous return (TAPVR) is a congenital heart defect in which all four pulmonary veins drain to a systemic vein or the right atrium. TAPVR results from a failure of the common pulmonary vein to fuse with the posterior surface of the left atrium early in fetal life. The pulmonary veins then decompress via the coronary sinus or primitive venous structures, which eventually lead to the right atrium, in which mixing occurs with the systemic venous blood. An anatomic classification system divides TAPVR into supracardiac, cardiac, infracardiac, and mixed, depending upon which primitive venous pathways are employed. Supracardiac TAPVR exists when all of the pulmonary veins come to a confluence behind the left atrium and drain via a vertical vein to the innominate vein or superior vena cava. Occasionally the vertical vein is obstructed as it passes between the left mainstem bronchus and left pulmonary artery. Cardiac TAPVR exists when the pulmonary veins drain to the coronary sinus or right atrium. Obstruction is uncommon in cardiac TAPVR. In infracardiac TAPVR, the pulmonary venous confluence drains inferiorly through the diaphragm and into the portal or hepatic veins, in which obstruction is common. Patients with mixed TAPVR have drainage to more than one site. For example, the left sided pulmonary veins may drain through a vertical vein to the innominate vein, although the right pulmonary veins drain to the right atrium. An obligatory intracardiac (usually atrial) communication exists in neonates with TAPVR to allow some oxygenated blood to reach the left heart and systemic arterial circulation. TAPVR may be associated with significant intracardiac disease as is seen in patients with heterotaxy syndrome, or may exist as an isolated lesion.

The presentation of isolated TAPVR is primarily based upon the presence and degree of obstruction between the pulmonary veins and the right heart. Most patients with infracardiac TAPVR and some with supracardiac TAPVR will have obstructed pulmonary venous pathways that result in pulmonary edema, pulmonary hypertension, cyanosis, and significant respiratory distress soon after birth. The clinical presentation and CXR may mimic those seen with neonatal pneumonia or respiratory distress syndrome, leading to delays in diagnosis. If a venous blood gas is drawn from an umbilical venous catheter positioned just above the liver in a cyanotic newborn, and the oxygen saturation level is in the high 90s, the diagnosis of infracardiac TAPVR should be suspected, as the sample is reflective of pulmonary venous return. The umbilical venous catheter should be removed so that it does not further obstruct pulmonary venous flow and cause clinical decompensation. Stabilization for the neonate with obstructed TAPVR involves mechanical ventilation, sedation and urgent surgical intervention (106). Hypoxemia may be abated somewhat by interventions that increase mixed venous oxygen saturation, including pharmacologic paralysis, correction of anemia, and inotropic support. Although neonates with obstructed TAPVR may be quite cyanotic, measures to lower pulmonary vascular resistance, including the use of hyperventilation and nitric oxide (NO), are usually not beneficial. The use of PGE₁ infusion in such patients is controversial, but generally is discouraged. Some physicians feel that PGE₁ may maintain patency of the ductus venosus in infants with infracardiac obstructed TAPVR, thus allowing for better drainage back to the right heart. Other clinicians believe that maintaining patency of the ductus arteriosus may allow left to right shunting at the arterial level (if the pulmonary vascular resistance is less than the systemic vascular resistance) and thus exacerbate pulmonary edema.

Infants with unobstructed isolated TAPVR and an adequate atrial communication will be mildly hypoxemic without overt clinical cyanosis at birth but develop congestive heart failure (CHF) within a few weeks to months. Surgical repair is performed within the first few days to weeks of life.

Truncus arteriosus is present when a single (common) arterial trunk gives rise to the aorta, at least one coronary artery, and at least one pulmonary artery. A single semilunar (“truncal”) valve is always present, and an unrestrictive VSD is almost always present. About one-third of patients with truncus arteriosus have a 22q11.2 microdeletion (DiGeorge syndrome) that can be diagnosed with florescent in-situ hybridization (FISH) (107). Several classification systems exist that may be used to describe the origins of the pulmonary arteries from the arterial trunk and the presence or absence of an IAA (108). Newborns with truncus arteriosus who present with mild cyanosis do not require a PGE₁ infusion unless an IAA (about 10% of cases) or ductal origin of one of the pulmonary arteries is present.

Infants with truncus arteriosus usually develop too much pulmonary blood flow and congestive heart failure within a few weeks after birth as pulmonary vascular resistance falls and systemic vascular resistance increases, unless stenosis is present at the origin of the pulmonary arteries from the aorta. Supplemental oxygen should be avoided to minimize the risk of decreasing pulmonary vascular resistance. Congestive heart failure is exacerbated in the presence of significant truncal valve insufficiency, which occurs in 50% of cases, or significant truncal valve stenosis (less common). For this reason, and to prevent the development of pulmonary vascular obstructive disease before surgery and minimize the incidence of pulmonary hypertension crises postoperatively, complete surgical repair is generally performed prior to discharge from the nursery (8,109,110).

ASDs may be present in isolation or with nearly any other type of congenital heart defect. ASDs are categorized by location and include secundum, ostium primum and sinus venosus types. The most common type is the secundum ASD, which exists when there is a deficiency in the septum primum in the central portion of the atrial septum. Although secundum ASDs may become smaller and close spontaneously, particularly those that are less than 5 mm in diameter, the ostium primum and sinus venosus defects will always require surgical intervention. The ostium primum defects are located in the inferior region of the atrial septum, and are almost always associated with an additional endocardial cushion abnormality. The sinus venosus defects usually occur at the junction between the superior vena cava and the right atrium, and are almost always associated with partial anomalous pulmonary venous return.

Isolated ASDs only rarely cause symptoms in infants, as significant left to right shunting does not occur until right ventricular compliance falls below left ventricular compliance, and this often takes years to occur. Likewise it is uncommon for patients with large ASDs to require oral medications (digoxin or diuretics). However, clinical judgment regarding the medical management and timing of surgical intervention is required in the neonate with a large ASD and additional medical problems (e.g., chronic lung disease) that complicate the clinical picture. The primary indication for surgery in infancy is the presence of symptoms secondary to left to right shunting. Toddlers require intervention if they have an ostium primum or sinus venosus ASD, or a secundum ASD with evidence for volume overload of the right ventricle. Intervention is indicated in early childhood in asymptomatic patients with significant left to right atrial shunts to prevent late complications including pulmonary vascular obstructive disease, thromboembolic events, arrhythmias, and right heart failure. A variety of devices exist that are used to close secundum ASDs in the catheterization laboratory, but the majority of clinical experience thus far exists with older children (111).

VSDs may be found in a variety of complex congenital heart lesions, or may exist in isolation. VSDs are categorized by location and size. VSDs may be located in the perimembranous, muscular, inlet or conal (outlet, subarterial, supracristal) regions of the ventricular septum, and there may be more than one VSD present. Malalignment of the conal septum may exist, resulting in variable degrees of right or left ventricular outflow tract obstruction. Conal VSDs often develop involvement of the aortic valve over many years (112). The size may be determined by an estimation of the diameter of the VSD in relation to the aortic annulus, and by degree of restriction to blood flow as estimated by Doppler echocardiogram. Perimembranous and muscular VSDs may become smaller or close with time, particularly if the initial diameter of the VSD is less than 5 mm (113). In patients with isolated moderate to large VSDs, congestive heart failure develops over time once an imbalance exists between systemic and pulmonary vascular resistance and a significant left to right shunt develops. Neonates with large VSDs will typically develop pulmonary overcirculation, left ventricular volume overload, and symptoms of congestive heart failure within the first several weeks to months of life as pulmonary vascular resistance falls. Any associated left ventricular outflow tract obstruction, such as coarctation of the aorta, will exacerbate this problem. Premature infants with left to right shunting at the ventricular or great artery level may develop congestive heart failure sooner as a result of decreased musculature in the pulmonary arterioles that allows for a precipitous drop in pulmonary vascular resistance.

A trial of medical management is usually indicated in infants with moderate to large VSDs. Provision of adequate nutrition and administration of medications including
loop diuretics and sometimes digoxin and/or angiotensin converting enzyme inhibitors (ACE inhibitors) can often allow surgery to be deferred for a few months (114). Supplemental oxygen and hyperventilation should be avoided, as they will cause pulmonary vascular resistance to fall, and Qp/Qs to rise. Infants who continue to have failure to thrive despite these measures are referred for surgical repair, or in selected cases, transcatheter intervention (115).

The presence or absence of a common atrioventricular valve oriface and the relative size of the physiologic VSD characterizes the different types of atrioventricular septal defects, also known as endocardial cushion defects. In patients with an incomplete atrioventricular canal, an ostium primum ASD exists along with a cleft in the mitral valve. There is no physiologic VSD present. A transitional atrioventricular canal defect has an ostium primum ASD, dense attachments of the atrioventricular valve leaflets to the crest of the ventricular septum such that two functionally separate atrioventricular valves exist, and a small physiologic VSD. A complete atrioventricular canal defect has a primum ASD, a common atrioventricular valve and a large inlet VSD. Associate anomalies include a left superior vena cava to the coronary sinus, additional VSDs, and aortic arch obstruction. Uncommonly, right ventricular outflow tract obstruction is seen, and such patients have features of tetralogy of Fallot and an atrioventricular canal (116). In most cases the ventricles are balanced, such that both are of adequate size to support the full cardiac output following surgery. Occasionally one of the ventricles is hypoplastic (“unbalanced”), precluding a two ventricular repair. Such patients may be considered for a one and a half ventricular repair, the single ventricle pathway, or heart transplantation.

Infants with complete atrioventricular canal defects typically develop congestive heart failure within the first few weeks to months of life. The congestive heart failure will be exacerbated if significant atrioventricular valve regurgitation or aortic arch hypoplasia is present. There is an increased incidence of Down syndrome (trisomy 21) in patients with endocardial cushion defects, and such patients are predisposed to the early development of pulmonary vascular obstructive disease. A trial of medical management is indicated in symptomatic infants, as discussed above for patients with large VSDs. Surgical repair is required within the first three to six months of life to eliminate the symptoms of congestive heart failure, prevent the development of pulmonary vascular obstructive disease and minimize the incidence of postoperative pulmonary hypertensive crises. Surgical repair is not commonly performed in the newborn period as a result of the difficulty with suturing the paper-thin atrioventricular valve leaflets.

Infants with incomplete or transitional atrioventricular canal defects often follow the clinical course of patients with isolated ASDs, and these lesions are typically repaired sometime between 6 months and 4 years of age.

The ductus arteriosus normally is functionally closed within the first hours to days of life. PDAs may exist in isolation or with many other types of congenital heart disease. An isolated, large PDA will cause symptoms of congestive heart failure once the pulmonary vascular resistance falls, allowing a left to right shunt from the aorta to the pulmonary artery. Left atrial and left ventricular volume overload are present and pulmonary edema may occur. Diastolic runoff exists leading to a “steal” from systemic blood flow, which may contribute to mesenteric ischemia and the development of NEC. PDAs are more common and cause more symptoms in premature infants. Small PDAs typically do not cause symptoms but are a long-term risk for bacterial endocarditis. Symptoms of congestive heart failure may be treated with diuretics, digoxin and the provision of adequate nutrition. Approximately two-thirds of PDAs in premature infants will close following a course of indomethacin or ibuprofen (117). Surgical ligation is indicated for PDAs that do not respond to medical therapy in premature infants, and for PDAs in any symptomatic term infant. Older children with a continuous murmur but no symptoms should have the PDA closed surgically or in the cardiac catheterization laboratory to minimize the risk of endocarditis.

An aortopulmonary window is an uncommon, usually large communication between the ascending aorta and pulmonary artery in the presence of two semilunar valves. This lesion usually exists in isolation, but may be associated with IAA, VSD, or other congenital heart defects (118,119). Infants with large aortopulmonary windows will usually develop congestive heart failure at several weeks of life. Prompt surgical repair is indicated in most cases to eliminate the symptoms of congestive heart failure, prevent the development of pulmonary vascular obstructive disease and minimize the incidence of postoperative pulmonary hypertension.

A multidisciplinary team, lead by the intensivist, a cardiologist with expertise in heart failure and transplantation, and a congenital heart surgeon, is required to answer several key questions for each infant who presents with a severe cardiomyopathy: What is the primary cause for the cardiomyopathy? Is it treatable or reversible? What level of medical or mechanical support is required? Is the infant a candidate for heart transplantation?

Infants may develop a severe cardiomyopathy from a wide variety of causes, including infection, structural heart disease, chronic arrhythmia, metabolic disorders, and primary myopathies. The broad differential diagnosis for infantile
cardiomyopathies is covered in detail in Chapter 33 and will not be repeated here. However, several conditions that may present with severe cardiomyopathy, are difficult to diagnose and are sometimes erroneously referred for heart transplantation, yet are readily treatable deserve comment. Infants born with anomalous left coronary artery from the pulmonary artery (ALCAPA) develop coronary ischemia when the pulmonary artery pressures fall after birth. These patients typically present in the first few weeks to months of life with severe left ventricular dysfunction, mitral regurgitation (as a result of papillary muscle ischemia), and pulmonary edema. The diagnosis may be suspected by the presence of characteristic findings on the electrocardiogram, and confirmed by echocardiography with careful examination of the coronary anatomy and blood flow pattern (120,121). Following reimplantation of the left coronary artery in the aorta, the vast majority of infants with ALCAPA recover left ventricular and mitral valve function (122). Infants with incessant arrhythmias, such as automatic atrial tachycardia, may present with severe cardiomyopathy. The initial rhythm may be thought to be sinus tachycardia secondary to the cardiomyopathy, but the correct diagnosis may be made by careful examination of the P wave morphology on the electrocardiogram. Myocardial function will recover once the arrhythmia is controlled with medications or ablation. Severe viral myocarditis is another condition that may be difficult to differentiate from a primary cardiomyopathy. Myocardial biopsy may provide clarity but is not without risk in sick infants. Many infants with viral myocarditis will recover ventricular function over time with supportive care (123).

Infants with cardiomyopathy may present with congestive heart failure or shock. Many of the principles for supporting cardiac output and monitoring of patients with severe cardiomyopathy are discussed below in the “postoperative care” section, and thus will not be reiterated. Mechanical support, typically with venoarterial extracorporeal membrane oxygenation (ECMO) in infants, may be used as a bridge to recovery or transplantation and is discussed further below. Indications for mechanical support in an infant with severe cardiomyopathy include worsening end-organ function and metabolic acidosis despite maximal medical support.

Heart transplantation is a widely accepted option for many infants with severe congenital heart disease and irreversible cardiomyopathies. Approximately 100 infant heart transplants are reported annually to the registry of the International Society for Heart and Lung Transplantation. Seventy-five percent of these transplants are for congenital heart disease, and the majority of the remainder are for cardiomyopathies (124). Heart transplantation is considered a primary option in some institutions for infants with complex congenital heart disease if surgical intervention is believed to result in an unacceptably high mortality rate (Table 34-6). Transplantation is also an option if uncorrectable anatomical issues and/or irreversible myocardial dysfunction are present following initial surgical intervention. The donor pool is very limited, and as a result as many as 25% of infants will die while waiting for a heart to become available. If more institutions adopted a policy of primary transplantation for the lesions listed in Table 34-6, particularly HLHS, the mortality while waiting for a donor heart to become available would certainly increase. Recent experience with ABO incompatible transplantation has shortened the wait times at a few centers (125). Relative contraindications to heart transplantation include high, fixed pulmonary vascular resistance (>6-8 Woods units per m²), recent or recurrent malignancy, serious infection, significant systemic disease, other organ system disease (e.g., hepatic, renal, or neurological), and chromosomal, metabolic or genetic abnormalities with a poor long-term prognosis.

Although the 1-year survival following heart transplantation in infancy is lower than that reported for older children, the long-term survival appears to be better, perhaps related to immune tolerance or better compliance with medications (124). The 10-year survival following infant heart transplantation is approximately 60%. Infants who have a successful heart transplant face potential long-term complications related to immunosuppression (i.e., renal insufficiency, infection, diabetes mellitus, and malignancy), transplant coronary artery disease, and rejection (124). In depth conversations about these issues
with parents are always required before an infant is listed for transplantation.

Comprehensive supportive care is required to maintain patients who are awaiting transplantation in the ICU. An appropriate level of cardiopulmonary support is required to maintain end-organ function. This often entails the use of inotropic agents, vasodilators, and diuretics. Mechanical support, usually ECMO in infants, is occasionally required (126).

Mechanical ventilation may be beneficial to minimize oxygen consumption, and positive end-expiratory pressure will reduce wall stress and thus provide afterload reduction for a failing systemic ventricle. Close attention must also be given to the prevention of infection and the provision of adequate nutrition. Anticoagulation may be indicated for infants with severe myocardial dysfunction to minimize the chance of luminal clot formation.

Management of the infant with HLHS awaiting transplantation deserves comment. Ductal patency is maintained with a low dose PGE₁ infusion, and occasionally these infants can be discharged to home while awaiting transplantation (127). Infants with HLHS awaiting heart transplantation tend to develop pulmonary overcirculation as pulmonary vascular resistance falls over time, which further volume overloads the right ventricle and may exacerbate tricuspid regurgitation. The extended use of subambiant FiO₂, achieved using supplemental inspired nitrogen, to increase pulmonary vascular resistance and limit pulmonary blood flow has been reported in this patient population (84,127). Limitation of pulmonary blood flow by banding of the pulmonary artery, either surgically or using innovative transcatheter techniques, has also been reported (128).

Selected pediatric cardiac surgical procedures may be performed without the use of CPB such as modified Blalock-Taussig shunt or repair of coarctation of the aorta. However, the majority of cardiac operations performed require CPB. Thus, physicians caring for these patients must be familiar with the equipment and techniques used to perform CPB, its sequelae on end-organ function, and several intraoperative strategies used to minimize the associated morbidities. The primary function of CPB is to temporarily replace the major functions of the heart and lungs while surgical interventions are performed on these organs. A typical CPB circuit used to perform these functions includes venous cannula(s) that drain systemic venous blood from the vena cavae or systemic venous atrium, a reservoir, a heat exchanger, a membrane oxygenator, a roller pump, a filter, and an arterial cannula to return blood to the aorta. Before initiation of CPB, the circulated blood must be modified to provide an appropriate composition of oxygen, carbon dioxide, pH, temperature, hematocrit, oncotic pressure, electrolytes, and glucose (129). The circuit is “primed” with standardized quantities of crystalloid solution, albumin, mannitol, sodium bicarbonate, heparin, calcium, and packed red blood cells. The patient is anticoagulated with heparin for the duration of CPB time, and cooled to a variable extent to minimize metabolic needs and oxygen consumption. Because hypothermia causes increased viscosity and red cell rigidity, hemodilution is used during hypothermic cardiopulmonary bypass.

To obtain a motionless heart for intracardiac repairs, the aorta is cross-clamped and a potassium-rich cardioplegia solution is injected into the proximal ascending aorta. Asystole develops once the cardioplegia solution perfuses the coronary circulation. The combination of cardioplegia and hypothermia provides myocardial protection for several hours. Following placement of the aortic cross clamp, blood from aortopulmonary collaterals will continue to return to the left atrium. To eliminate the left atrial blood return and facilitate certain complex left heart operations, deep hypothermic circulatory arrest (DHCA) may be used. Deep hypothermia refers to cooling of the core temperature to 18°C to 20°C. During circulatory arrest the CPB pump is shut off. In addition to the absence of blood returning to the left atrium, the perfusion cannula may be removed from the surgical field, creating optimal conditions for an accurate repair. Due to concerns about neurologic outcome following DHCA, regional perfusion techniques have recently been designed to minimize or avoid the use of circulatory arrest (130). The neurologic sequelae of CPB and DHCA are discussed in the section on neurologic complications later in this chapter. Following rewarming, weaning and separation from CPB, protamine is administered to reverse the effect of heparin (129). Additional blood components may be required to control bleeding immediately following CPB.

A number of adverse effects from CPB will impact on the postoperative course. During CPB, formed elements of the blood are exposed to artificial surfaces and sheer stress. Ischemia reperfusion injury occurs, as does microembolization of gas bubbles and particulate matter. Hemodilution may cause problems with oxygen delivery and dilution of clotting factors. These events trigger a complex neurohumoral and inflammatory response. CPB is associated with the release of endogenous catecholamines, vasopressin, endothelin, and activation of the renin-angiotensin-aldosterone axis, all of which contribute to elevation of systemic and pulmonary vascular resistances and fluid retention (131,132,133,134,135,136,137,138,139,140,141,142). A generalized inflammatory response occurs following CPB, and the complement, coagulation and fibrinolytic systems are activated (143,144,145,146). Capillary leak also occurs, related to fluid retention, the inflammatory response, and dilution of plasma proteins. White blood cells and platelets are also activated, leading to additional release of inflammatory mediators and proteolytic enzymes (147,148,149). Pulmonary leukosequestration occurs, as does oxygen free radical generation (150,151). Platelet counts
fall following CPB, and clotting factors are diluted (140,152). Myocardial systolic dysfunction also occurs following CPB in infants and children (153). The end result of these processes is a clinical picture of end-organ dysfunction of variable severity. The cardiovascular, pulmonary, hematologic and renal systems tend to be the most severely affected. Myocardial dysfunction, elevated systemic and pulmonary vascular resistance, abnormal gas exchange and decreased pulmonary compliance, bleeding and fluid retention all may be present in the early postoperative period.