Advances in Neonatal Cardiac Surgery

Abstract

After completing this article, readers should be able to: Advances in the surgical and medical management of children who have congenital heart disease (CHD) have led to a dramatic improvement in overall survival and reduced the long-term sequelae of open-heart surgery. With improved survival and decreased morbidity over the past 2 decades, the early complete repair of complex congenital heart problems in preterm and low-birthweight neonates has gained wider acceptance. Cardiologists and cardiothoracic surgeons now consider and perform complete neonatal repair more frequently than palliative surgery in this patient population.The treatment of hypoplastic left heart syndrome (HLHS) best illustrates the evolution of management strategies to improve survival and long-term outcome. A recent modification of the Norwood operation that involves a right ventricle-to-pulmonary artery conduit has led to much improved early postoperative stability and, in many centers, improved survival to a stage II superior cavopulmonary connection. A multidisciplinary team approach is required to provide the necessary care for this complex patient population.In 1938, Robert Gross at Children’s Hospital in Boston successfully ligated a patent ductus arteriosus, and this procedure—performed against the wishes of surgeon-in-chief William Ladd—opened the era of surgery for CHD. (1) Gross and Hufnagel performed detailed animal experiments to develop a technique for treatment of coarctation of the aorta that involves excision and end-to-end anastomosis. (2) Clarence Craaford of Stockholm, Sweden, had visited Gross to observe his experimental work, and in October 1944, Craaford and Nylin were the first to repair aortic coarctation successfully in a patient. (3)Helen Taussig at Johns Hopkins observed that some children who had cyanotic heart disease became progressively more cyanotic with closure of the ductus arteriosus and proposed creating an artificial ductus to improve pulmonary blood flow. Alfred Blalock, based on experimental work with Vivien Thomas, performed the first shunt procedure for tetralogy of Fallot in November of 1944 and published their early experience in 1945. (4) In this procedure, the end of the subclavian artery was connected directly to the side of the ipsilateral pulmonary artery. This shunt (Blalock-Taussig shunt) and its many modifications revolutionized the treatment of children who had cyanotic heart disease.Before the 1950s, only palliative surgeries, such as the aortopulmonary shunt, were available to treat a minority of patients who had CHD. Bigelow and colleagues introduced experimental work on hypothermia, indicating that whole-body hypothermia produced by surface cooling might be useful in cardiac surgery. (5) The development of techniques to provide circulatory and pulmonary support was necessary to allow intracardiac repair. Innovative techniques such as surface cooling with inflow occlusion to repair the first atrial septal defect (6) and cross-circulation (7) created excitement and interest in developing a safe means of cardiopulmonary bypass. These techniques ushered in the exciting era of open-heart surgery but were impractical and risky.In the late 1930s, John Gibbon, Jr, began pioneering experimental work that culminated in the first successful operation using cardiopulmonary bypass. (8) In 1953, he repaired an atrial septal defect in a young woman using a pump-oxygenator. (9) After this initial success, Gibbon had multiple subsequent patient deaths, prompting him to place a moratorium on his own program. John Kirklin at the Mayo Clinic performed a series of operations with the Mayo-Gibbon pump-oxygenator, based on technology developed in conjunction with IBM. (10) The reproducible method of entering the heart made an increasing number of intracardiac lesions amenable to repair. The introduction of deep hypothermia with circulatory arrest by Barrett-Boyes and colleagues in New Zealand allowed for the operative treatment of most complex congenital lesions amenable to repair, even in smaller infants. (11)Over the last 4 decades, many have contributed to the morphologic characterization of all types of congenitally malformed hearts, which has led to a safer surgical approach and improved outcome. For example, a thorough understanding of the conduction system in the various cardiac defects has decreased the incidence of postoperative complete heart block to less than 4%. Improvements in cardiopulmonary bypass and surgical technique have included strategies for better myocardial and cerebral protection. The development of the cardiac intensive care unit and an interdisciplinary team approach followed the realization that care of the patient who has CHD requires focused, specialized attention that is provided best by subspecialists in pediatric cardiac surgery, cardiology, anesthesia, critical care, and nursing.Surgical advances also have coincided with tremendous improvements in diagnostic capabilities, preoperative and postoperative care, and catheter-based intervention. A detailed review of these advances is beyond the scope of this article. Cardiac catheterization, first developed in the 1940s, still provides critical hemodynamic assessment, anatomic confirmation, and therapeutic intervention. Balloon dilation of critical aortic and pulmonary valve stenosis, dilation of recurrent aortic coarctation, and device closure of appropriate secundum atrial septal defects are current first-line therapies. In pulmonary atresia with an intact ventricular septum, percutaneous valve perforation and balloon dilation of the pulmonary valve may facilitate staging to a biventricular circulation. (12)Bedside echocardiography has become the primary diagnostic tool used to identify cardiac lesions and confirm the anatomy. The advancement of fetal echocardiography and reliable, accurate prenatal diagnosis has made it possible to counsel the family appropriately, transfer the fetus in utero to a tertiary care center, and plan for immediate postnatal intervention when necessary. Intraoperative transesophageal echocardiography provides immediate postoperative feedback and assesses surgical results and cardiac function. Other diagnostic tools, such as cardiac computed tomography scan and magnetic resonance imaging, rapidly are becoming mainstays of preoperative and postoperative diagnostic evaluation and assessment.Coincident with the tremendous medical advances was a transition in philosophy from palliative approaches to early, complete repair when possible. For example, the treatment of truncus arteriosus initially was confined to pulmonary artery banding, and the earliest repairs were performed in older children. Delaying surgery resulted in significant pulmonary hypertension and cardiac decompensation. Paul Ebert and colleagues (13) achieved excellent results in infants younger than 6 months of age, providing a basis for early intervention to prevent cardiac failure, pulmonary artery hypertension, failure to thrive, and a high mortality rate.Treatment of complete transposition of the great arteries (D-TGA) also illustrates the change in philosophy and management to earlier repair and the establishment of a normal circulation pattern. In the 1950s, Blalock and Hanlon developed a closed technique for removing the atrial septum, which allowed for mixing of systemic and pulmonary venous blood. (14) Partial atrial level switch procedures (“partial physiologic correction”) were introduced by Lillihei and Varco. (15) In this procedure, the right pulmonary veins were connected to the right atrium and the inferior vena cava was redirected to the left atrium. The Baffes procedure is a modification, using a homograft to connect the inferior vena cava to the left atrium. (16) These procedures carried a substantial risk of mortality. Introduction of the balloon atrial septostomy by Rashkind and Miller revolutionized the palliative treatment of complete transposition. (17)In 1959, Ake Senning used creative flaps of atrial septum and right atrial wall to perform the first successful atrial or venous level switch procedure. (18) Finally, deoxygenated systemic venous blood passed through the lungs, albeit via a morphologic left ventricle, and oxygenated pulmonary venous blood coursed through the aorta via the morphologic right ventricle. This procedure was difficult for most surgeons to reproduce with acceptable mortality. In 1963, William Mustard introduced an atrial level switch procedure that used autologous pericardium to baffle the blood within the atria. (19) The Mustard procedure was adopted more widely than the Senning procedure, largely because of its reproducibility. Nevertheless, the Mustard procedure was not successful in the neonate and small infant, and newborns underwent a palliative atrial septostomy prior to proceeding with the atrial level switch. Despite the success of these procedures to provide physiologic correction, numerous long-term complications developed, such as obstruction of intra-atrial pathways, systemic right ventricular dysfunction, sick sinus syndrome, atrial tachyarrhythmia, and sudden death.In an attempt to establish a normal circulation in patients who had D-TGA, Mustard performed an arterial level switch operation, but he only translocated the left coronary artery. (20) Adib Jatene performed the first successful arterial switch operation in a patient who had D-TGA and a ventricular septal defect, and this operation soon became the procedure of choice for these types of patients. (21) Contributions by Radley-Smith and Yacoub in London, (22) Quaegebeur in Holland, (23) and Castaneda in Boston (24) demonstrated the safety of performing the arterial switch operation in the neonate who has an intact ventricular septum. The treatment of D-TGA, thus, has completed a philosophical and practical transition from early palliative approaches to complete repair in the neonatal period. Over the last 2 decades, techniques have been developed to handle even the most difficult coronary artery anomalies, including intramural coronaries (those that travel within the aortic wall) and single coronary artery.Similar dramatic story lines are reported in the surgical history of many other lesions, including atrioventricular septal defect, truncus arteriosus, interrupted aortic arch with ventricular septal defect, tetralogy of Fallot, and pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. The common theoretical denominator is that earlier, complete repair results in better long-term outcome.The initial surgical treatment of single ventricle anatomy relies on various palliative surgeries, with the ultimate goal of achieving a Fontan circulation. In a Fontan circulation, the superior and inferior vena caval blood is directed into the pulmonary arteries, and the single ventricle serves as a systemic pump; there is no “pulmonary” ventricle. Originally described by Fontan and colleagues in 1971 for tricuspid atresia, (25) it has evolved to a staged approach to either lateral tunnel (26) or extracardiac conduit Fontan. (27) In the lateral tunnel repair, inferior caval blood is directed to the pulmonary arteries via an intra-atrial tunnel, while a tube graft (outside of the heart) is used in the extracardiac Fontan. Compared with other modifications such as the lateral tunnel Fontan, the extracardiac conduit Fontan is advantageous because it can be performed with partial or no cardiopulmonary bypass and is associated with less arrhythmias.The advances of neonatal cardiac surgery are best summarized by the ability to perform more complex surgical repairs safely on smaller neonates and infants. This is possible because of the development of precise finer equipment, better cardiopulmonary bypass technology, and improved cerebral and myocardial preservation techniques. Small-volume cardiopulmonary bypass circuits with improved membrane oxygenators provide the necessary cardiopulmonary support during surgery. The smaller priming volumes used in these circuits has reduced the requirement for blood products and is associated with a decreased inflammatory response. Modified ultrafiltration performed after cardiopulmonary bypass reduces the degree of fluid overload and the inflammatory markers present after cardiac surgery. Ultrafiltration improves the cardiac systolic function and diastolic relaxation, with a decreased requirement for inotropic support in the early postoperative period (28) and a decreased need for the transfusion of blood products.Modification of warming techniques has led to an improvement in the overall neurologic outcome after cardiac surgery. Hyperthermia is associated with cognitive dysfunction and, therefore, closely monitored gradual rewarming is essential to reduce the risk of neurologic injury and cognitive impairment.Closure of the sternotomy with absorbable sutures has resulted in a decreased risk of developing sternal wound infections, sternal dehiscence, and mediastinitis.The improvement in accurate diagnosis, surgical techniques, and cardiopulmonary bypass has led to earlier surgical repairs, and most patients avoid palliative temporary procedures. Surgical repair is successful even in low-birthweight infants, with no benefit achieved by delaying surgery. In fact, delaying surgery may be associated with a higher preoperative morbidity. (29)(30) After the surgery, postoperative care is in a designated cardiac intensive care setting by a multidisciplinary team that includes surgeons, intensivists, neonatologists, and cardiologists as well as designated nursing staff, respiratory therapists, pediatric pharmacists, and social workers.Although used infrequently in the neonatal population, minimally invasive thorascopic ligation of the patent ductus arteriosus is gaining recognition. This has been performed safely in preterm neonates as small as 640 g with no evidence of residual ductal flow. (31)The recent advances in neonatal cardiac surgery as a discipline can be illustrated best by using the example of a single congenital defect. For this review, we describe the management of various aspects of HLHS.HLHS or HLHS variant refers to a group of malformations marked by a hypoplastic left ventricle and ascending aorta. Morphologically, there is either aortic stenosis or atresia associated with mitral stenosis or atresia, and the ascending aorta and arch can be extremely small (even <2 mm in diameter), usually with a juxtaductal coarctation. Physiologically, the systemic circulation depends on the right ventricle, the only substantial pumping chamber, and there is complete mixing of the pulmonary and systemic venous blood at the atrial level. This cardiac defect is present in 7% of infants who have CHD and, therefore, represents approximately 0.16 per 1,000 live births. There is a two thirds male predominance, with about 10% of patients manifesting extracardiac malformations. If not diagnosed prenatally, most affected patients develop respiratory distress, tachycardia, and cyanosis. Approximately 50% of patients who have HLHS present with symptoms within the first 48 hours after birth, as the ductus arteriosus begins to close. Therapeutic measures, especially a prostaglandin (PGE1) infusion to maintain ductal patency, are instituted urgently to prevent rapid progression to cardiocirculatory collapse. Without intervention, most children die in the first 6 postnatal weeks. The defect always should be suspected in patients who present in the first two postnatal weeks with evidence of poor femoral pulses, cardiovascular collapse, or pulmonary edema. Fortunately, obstetricians and fetal echocardiologists now diagnose the condition more frequently on prenatal fetal ultrasonography, allowing for appropriate initiation of medical therapy soon after birth.On physical examination in the newborn period, the second heart sound is single, and there is a pulmonary ejection click that reflects the presence of pulmonary hypertension with a dilated pulmonary artery. There is often a pansystolic murmur of tricuspid regurgitation. Hepatomegaly may be present in a patient who has cardiovascular collapse. Palpation of the femoral pulses is variable but usually reveals weak femoral pulses. In the presence of prograde aortic blood flow, an oxygen saturation differential may be seen, with a higher right arm oxygen saturation.Right axis deviation and right ventricle hypertrophy are evident on electrocardiography. There is prominent right voltage with usually poor left ventricular forces. Chest radiography reveals evidence of moderate or severe cardiomegaly, a globular cardiac silhouette, and right atrial enlargement. The ascending aorta may be absent. There is a variable pattern of pulmonary vascular markings, ranging from normal pulmonary vascular markings to evidence of pulmonary edema and significant pulmonary overcirculation.Echocardiography is the diagnostic tool of choice for confirming the anatomy and defining the various elements of the defect. The left ventricle is hypoplastic or absent, and the aortic and mitral valves are atretic or hypoplastic. The degree of prograde flow across the aortic or mitral valve is assessed and confirmed by echocardiography and may alter management and prognosis. The aortic arch anatomy and its branching are delineated completely, and the degree of patency of the ductus arteriosus is assessed. The patent ductus arteriosus provides systemic blood, and its closure causes early clinical deterioration in affected newborns. The ductus arteriosus may be closing in a patient presenting with cardiovascular collapse. The right ventricle usually is dilated, and often there is evidence of tricuspid regurgitation. The atrial septal communication (atrial septal defect or patent foramen ovale) should be evaluated to establish that pulmonary venous return is unrestricted.Cardiac catheterization usually is not indicated for patients who have HLHS because the diagnosis can be made on echocardiography. In certain situations, a patient who has a severely restrictive atrial septum may be referred for cardiac catheterization and balloon septostomy to relieve the pulmonary venous obstruction and to improve the cardiac output. After stabilization for 2 to 3 days, the child can undergo palliative surgery.For patients who have HLHS, a restrictive atrial septum is a poor prognostic factor and may lead to fetal demise.Appropriate preoperative management is essential to improve systemic perfusion, correct metabolic acidosis, and optimize end-organ function. The management strategy includes initiation of prostaglandin therapy to maintain ductal patency as well as maneuvers to optimize systemic perfusion while controlling the pulmonary blood flow. Pulmonary circulation increases at the expense of the systemic and coronary circulation. In this preoperative period, other medical conditions or extracardiac manifestations, such as renal anomalies, neurologic problems, and genetic syndromes, should be considered and evaluated.When the diagnosis is made or considered, PGE1 therapy is initiated at 0.05 to 0.1 mcg/kg per minute to maintain patency of the ductus arteriosus. PGE1 also can cause significant pulmonary vasodilation, with a concomitant increase in pulmonary blood flow at the expense of the systemic and coronary blood flow. In the absence of lung disease, oxygen concentration of 35 to 45 mm Hg usually represents a well-balanced circulation with adequate pulmonary and systemic circulation.Typically, multiple measures are instituted to help balance the pulmonary and systemic blood flows. Avoiding supplemental inspired oxygen is critical to control the pulmonary blood flow and to prevent pulmonary overcirculation. Patients may require intubation and mechanical ventilation for controlled ventilation. This may be necessary to achieve appropriate elevation in the carbon dioxide, thereby increasing the pulmonary vascular resistance and decreasing pulmonary blood flow. A decrease in oxygen concentration also controls the pulmonary vasodilation and increases the pulmonary pressure. Therefore, oxygen is weaned to room air and may be decreased to subambient concentrations of 17% to 18% with the use of nitrogen or carbon dioxide. Decreasing the Fio2 and increasing the Pco2 with inspired carbon dioxide may be better than administering nitrogen to achieve and maintain a low inspired Fio2. (32) These measures are performed to prevent pulmonary overcirculation and optimize systemic and coronary blood flow.Inotropes must be used judiciously when there is evidence of ventricular dysfunction because their effect on Qp/Qs (the ratio of pulmonary to systemic blood flow) is unpredictable. High doses of dopamine and epinephrine increase systemic vascular resistance and can have detrimental effects on Qp/Qs. Inodilators, such as milrinone, can be added to enhance cardiac output and systemic perfusion. Obstruction to flow at the level of the atrial septum is analogous to obstructed pulmonary venous drainage and should be addressed emergently soon after birth. Urgent surgery with a Norwood procedure or controlled balloon septostomy is performed to relieve the obstruction to the venous return and improve oxygenation in these critically ill neonates. If a balloon septostomy is performed, infants are allowed to stabilize over the ensuing several days prior to proceeding with a modification of the Norwood procedure. Infants who have restrictive atrial septa experience an almost 50% mortality regardless of whether emergent surgery or a balloon septostomy is the initial procedure. (33)Approximately 10% of patients who have HLHS have extracardiac manifestations and as part of the preoperative evaluation and management, renal ultrasonography, cranial ultrasonography, and baseline laboratory tests to evaluate renal and hepatic function are warranted. Chromosomal analysis is essential specifically in females, who may have Turner syndrome that is associated with poor prognostic implications.Fortunately, with the development of prenatal diagnosis by ultrasonography, HLHS is diagnosed prenatally in as many as 28% of affected patients. (34) There is a 40% association of karyotype and extracardiac malformations in patients in whom HLHS is diagnosed prenatally. Prenatal diagnosis necessitates complete evaluation of the fetus for associated genetic and extracardiac malformations, which also allows for appropriate, detailed counseling of parents. (35) Other advantages of prenatal diagnosis include safer intra utero transport of the fetus to a tertiary cardiac center and early appropriate therapy to avoid circulatory compromise and end-organ dysfunction. Early fetal diagnosis also allows close monitoring of the atrial septum for evidence of restriction. Surprisingly, until recently, prenatal diagnosis of HLHS has not had a positive impact on long-term fetal outcome. However, in a recent review of patients in whom HLHS was diagnosed prenatally, all survived the surgery compared with only 25 of 38 diagnosed postnatally. (36) Patients diagnosed prenatally also had a lower incidence of preoperative acidosis, tricuspid regurgitation, and ventricular dysfunction and better early postoperative survival.Fetal interventions have been attempted, but experience remains limited. In a recent series from Boston Children’s Hospital, fetal balloon aortic valvuloplasty procedures were attempted, which improved prograde aortic flow in 25 of the 26 fetuses. (37) Infants who have HLHS and an intact or very restrictive atrial septum have a 50% chance of surviving the neonatal period. In this patient population, an atrial septostomy for left atrial decompression has been attempted at 26 to 34 weeks’ gestation. (38) Under ultrasonographic guidance, the atrial septum was perforated successfully and dilated in most of the patients. There were no maternal complications, but one fetus died after the procedure. Four of the seven fetuses died in the neonatal period. Histologic and autopsy studies of patients who have restrictive atrial septa reveal abnormalities of the pulmonary venous vasculature, which contributes to the poor prognosis.In 1983, Norwood and colleagues (39) were the first to describe neonatal palliation that led to achievement of a subsequent successful Fontan circulation among infants who had HLHS. The technical principles of the “conventional” Norwood procedure are critical to achieving a successful Fontan circulation. The initial stage must provide unobstructed systemic blood flow into the reconstructed aorta and coronary arteries, a widely patent atrial septum (common atrium), and a secure “controlled” source of pulmonary blood flow. The outcome depends on multiple pre- and postoperative variables as well as the details of the operative procedure. Improved outcome is expected with the larger ascending aorta, preferably in the presence of prograde aortic flow, good right ventricular (systemic ventricular) function, and adequate tricuspid valve function with absence of significant tricuspid regurgitation.Reconstruction of the ascending aorta and aortic arch requires connection of the pulmonary trunk to the aorta, allowing the right ventricle to pump into the aorta. The aorta is either augmented with a patch (usually homograft material) or by direct anastamoses of the ascending aorta, arch, and proximal descending aorta to the proximal pulmonary artery, with excision of the ductal and coarctation tissue. (40)(41)In the modified Norwood procedure, an adequate source of controlled pulmonary blood flow is achieved by placement of a 3.0- or 3.5-mm expanded polytetrafluorethylene central shunt between the right innominate or subclavian artery and the right pulmonary artery. In the immediate postoperative period, patients have a significant risk of death prior to the second-stage surgery, a superior cavopulmonary connection. Most of the risk relates to the diastolic runoff from the shunt, which results in a lower diastolic blood pressure and, therefore, the potential for coronary ischemia.A recent modification of the operation, the Sano procedure, addresses this physiologic concern. In this operation, a prosthetic conduit is placed between the right ventricle (RV) and the pulmonary artery (PA) instead of a central shunt. (42) Numerous single-center studies have documented improvements in early survival and survival to stage II (superior cavopulmonary connection) using an RV-to-PA conduit instead of a central shunt. The RV-to-PA conduit leads to higher diastolic pressures and, therefore, a lower risk of coronary ischemia. There appears to be better control of pulmonary blood flow, with a resultant benefit on systemic output. A recent single-center study compared Norwood procedures using either a central shunt or an RV-to-PA conduit. (43) Although this study did not reveal any significant difference in overall mortality at a median follow-up of 18 months, a higher percentage of high-risk patients who had aortic atresia had been referred for an RV-to-PA conduit.The Norwood procedure typically has been performed using a period of hypothermic circulatory arrest, during which the pump is turned off when adequate systemic hypothermia (18 to 22°C) has been achieved. After the entire procedure is performed, the pump is restarted to resume circulatory support. This technique depends on hypothermia alone to protect the brain and other organs during this period of “no flow.” Although this technique still is employed by many centers with excellent early results, concern has been growing about the effects of circulatory arrest on the brain. (44) Techniques have been developed to perform this procedure with low-flow continuous cardiopulmonary bypass because “some flow” should be better than “no flow.” For example, the left common carotid artery can be cannulated directly or the central shunt can be sewn to the innominate artery and then cannulated directly to provide inflow during the initial part of the operation. If an RV-to-PA conduit is planned, the innominate artery can be cannulated directly (the preferred technique at our center). These techniques permit continuous flow at low temperatures and likely provide better cerebral protection than hypothermic circulatory arrest. Nevertheless, more laboratory and clinical data are necessary to document the superiority of one technique over another in terms of neurologic morbidity and improving long-term outcome.Surgical stage I palliation for low-birthweight and preterm infants who have HLHS has been performed in infants whose birthweights were as low as 1.5 kg with an increased but acceptable surgical risk. Low birthweight and prematurity are not considered contraindications for surgery in many centers. (45)(46)As noted previously, postoperative care requires an interdisciplinary approach that integrates input from cardiac surgeons, cardiologists, intensivists, neonatologists, and anesthesiologists as well as specialized nursing staff and respiratory therapy. Balancing the pulmonary and systemic circulation is essential to ensure adequate oxygenation and ventilation, coronary and systemic perfusion, and cerebral oxygenation. Measures to promote afterload reduction, such as milrinone and sodium nitroprusside, promote systemic perfusion. The pulmonary vascular resistance is adjusted via alterations in the acid-base balance, the degree of alveolar oxygenation, correction of anemia, sedation, and vasodilators. Inotropic support (predominantly epinephrine) is necessary in the early postoperative period to support the systemic right ventricle. Maintenance of normal sinus rhythm is essential and may require temporary pacing using epicardial wires implanted at the time of surgery. A low Qp/Qs ratio (eg, 1.5:1) should be targeted for an optimal course early after first-stage Norwood palliation. (47)Use of the RV-to-PA conduit seems to obviate the need for vigilant attention to balancing the pulmonary and systemic resistances. After either operation, a continuous venous oximetry catheter placed in the SVC monitors the systemic perfusion closely. Recently, near-infrared spectroscopy has been used to monitor cerebral perfusion and as an indirect measure of systemic perfusion. (48)(49)The routine use of postoperative mechanical ventricular assist has been advocated by some centers that report improved hospital survival and cerebral oxygenation, leading to improved neurologic outcome. (50) Most centers selectively use extracorporeal membrane oxygenation (ECMO) for low cardiac output state or evidence of progressive end-organ dysfunction (eg, increasing lactate concentrations). The survival to discharge for infants who have single-ventricle physiology is about 60%, and ECMO support for greater than 72 hours is a poor prognostic factor in this patient population. (51) ECMO may be initiated in the operating room if there is difficulty in weaning of cardiopulmonary support.In many centers, the sternum is left open in the immediate perioperative period to prevent early postoperative cardiac dysfunction due to myocardial edema. Aggressive early diuresis is important to reduce chest and abdominal wall edema as well as to improve myocardial function. The sternum usually can be reapproximated in the intensive care unit 2 to 5 days postoperatively. Diuresis and elimination of extravascular fluid is also necessary to improve ventilatory mechanics and allow decreased ventilatory support and earlier extubation. A consistent and titratable diuresis can be achieved best by a continuous infusion of furosemide to avoid the hypotension that may be seen with bolus dosing. A low dose can be started (0.2 mg/kg per hour) and increased as required and tolerated. In some centers, peritoneal dialysis catheters are inserted at the time of surgery to allow passive fluid drainage and the ability to perform peritoneal dialysis if required. With new perfusion techniques and the use of ultrafiltration during and after cardiopulmonary bypass, peritoneal catheters and dialysis rarely are required. In our center, a dialysis catheter is placed if there is poor urine output unresponsive to diuretic therapy, evidence of progressive renal dysfunction, or intra-abdominal fluid causing an abdominal compartment syndrome.Early nutrition support is of paramount importance, especially because these children may require prolonged intubation and inotropic support. Recognition of feeding difficulties in patients who have HLHS is increasing, but the mechanisms have not been fully elucidated. If initiation of gastric feeding is delayed due to hemodynamic instability, hyperalimentation and small-volume gastric trophic feedings usually are initiated within 48 hours.Cardiac transplantation is considered for neonates who have HLHS in certain surgical centers and for patients who have poor prognostic anatomic factors such as aortic atresia. Limitations include the paucity of available organs and a prolonged waiting time with the associated risks of sepsis and the complications of prolonged PGE1 therapy. In a recent multicenter study, of the 262 patients who had HLHS and were listed for transplantation, 25% died while waiting for a suitable organ, with 50% of the deaths due to cardiac failure. (52) Of the 175 patients who underwent cardiac transplantation, survival was 68% at 3 months and 54% at five years. The authors concluded that cardiac transplantation offers good early survival for infants who have HLHS. The long-term results for transplantation are influenced by the development of coronary artery disease, the risk of posttransplant lymphoproliferative disorder, and the progression of cardiac systolic and diastolic dysfunction after cardiac transplantation. Because of a shortage of organs as well as much improved results with the Norwood palliation en route to Fontan circulation, most centers favor proceeding with Norwood palliation.Overall 1-year survival after the Norwood procedure for HLHS is 60% to 75%. Noncardiac abnormalities and low birthweight remain risk factors for patients who have single-ventricle physiology. (53)A recent single institutional report described a 12-year experience with staged surgical management of HLHS in 333 patients and attempted to identify the factors that influenced the outcome. (54) Actuarial survival was 58% at 1 year and 50% at 5 and 10 years. On multivariable analysis, five factors influenced early mortality after the Norwood procedure (P<0.05). Supply of the pulmonary blood flow by an RV-to-PA conduit, arch reconstruction with pulmonary homograft patch, and an increased operative weight improved early mortality. Increased periods of cardiopulmonary bypass and deep hypothermic circulatory arrest increased early mortality. This study suggested improved outcome after the Sano RV-to-PA conduit.Malnutrition is common in infants who have HLHS after stage I palliation. An aggressive approach, with the early use of parenteral nutrition and high-calorie enteral feedings, has been associated with improved nutritional status. (55) However, affected neonates are at high risk (41%) of developing gastrointestinal complications after the initial Norwood procedure, including necrotizing enterocolitis (18%), prolonged hospital stay for nutritional support (8%), and requirement for a home feeding tube (18%). (56) Therefore, it is necessary to balance the risk of early feeding and mesenteric ischemia with the risk of malnutrition.With the balanced single-ventricle circulation seen after a Norwood operation, special attention must be paid to any factors that may alter the relative systemic and pulmonary circulations. For example, fever, anemia, or dehydration may lead to an imbalance in the systemic and coronary perfusions. In a neonate who has a classic Norwood procedure and a central shunt, vomiting can lead to dehydration and an increased risk of shunt thrombosis. Patients who have had a successful Norwood procedure usually are discharged from the hospital on afterload-reducing agents and low-dose aspirin for antiplatelet effect with or without diuretics. Oxygen saturation usually is in the 80s on room air, and patients require a higher-than-expected hemoglobin for oxygen-carrying capacity. Therefore, iron therapy frequently is prescribed to avoid the physiologic anemia of infancy. Patients are monitored closely, with regular clinical follow-up and echocardiography by cardiologists.Residual cardiac defects or intercurrent illnesses are responsible for significant mortality between the Norwood procedure and second-stage surgery. Therefore, recent programs have been developed that focus on outpatient daily monitoring of weight and oxygen saturation in the attempt to identify early signs that require intervention. (57) Close attention is paid to the development of aortic coarctation, neoaortic stenosis, systemic (right ventricular) dysfunction, tricuspid regurgitation, or worsening cyanosis. These factors, combined with arrhythmias or sinus node dysfunction, are poor prognostic factors for long-term results after a single-ventricle palliation. Even mild coarctation of the aorta may cause significant obstruction to the single ventricle and can lead to a failing single ventricle. In general, patients are referred for cardiac catheterization at about 3 to 4 months of age prior to undergoing superior cavopulmonary connection. At the second stage, a bidirectional Glenn shunt or a hemi-Fontan is performed, depending on whether the center favors extracardiac conduit or lateral tunnel Fontan, respectively. At about 2 years of age, the Fontan (total cavopulmonary anastomosis) is completed if there are no significant hemodynamic abnormalities noted on a repeat catheterization. At any stage before or following the completion of the Fontan procedure, any evidence of recoarctation of the aorta or any abnormal collateral vessels must be addressed surgically or in the cardiac catheterization laboratory to eliminate the risk of developing cardiac dysfunction or pulmonary hypertension.Developmental delay (intelligence quotient <70) has been reported in 18% of patients who have HLHS and have had a staged palliative approach. (58)To avoid the risk of the neonatal Norwood operation predominantly related to the aortic arch reconstruction, several groups have developed innovative hybrid techniques that combine both surgical and catheter-based approaches for neonatal palliation. In this approach, the ductus is stented by catheterization to ensure patency, and bilateral pulmonary artery bands are placed surgically. Also, a balloon septostomy can be performed if needed. This innovative strategy creates a circulation similar to that seen after stage I Norwood palliation. The arch repair is deferred until the child is ready for cavopulmonary shunt at 3 to 6 months of age. (59) The second procedure entails removal of pulmonary artery bands, pulmonary artery reconstruction, aortic arch reconstruction, and bidirectional cavopulmonary connection. The Fontan can be completed in the catheterization laboratory with transcatheter completion of the cavopulmonary anastomosis. This approach offers the potential for complete palliation for patients who have HLHS with only one cardiopulmonary bypass procedure and hopefully better neurologic and cardiopulmonary outcome. This strategy is in its early stage of development, and long-term outcome is unknown. It is currently not the recommended approach for most patients who have HLHS.The treatment of CHD continues to evolve as investigators search for better strategies for the wide variety of congenital heart defects. Although tremendous advances have been made over the last several decades, minimally invasive surgery, catheter-based techniques, and hybrid approaches should improve the long-term outcome further for children who have heart disease. Other fields, such as gene therapy, stem cell biology, robotic surgery, and fetal intervention, are even “younger” in their development and likely will provide great advances in the future.See also Rudolph AM. Historical perspectives: history of surgery for congenital diseases of the heart.NeoReviews. 2005;6:e447–e453 and Kipps A, Silverman NH. Historical perspectives: the introduction of ultrasonography in neonatal cardiac diagnosis.NeoReviews. 2005;6:e315–e325.