Surgical Treatment of Pediatric Hypoplastic Left Heart Syndrome Treatment & Management

Initial medical support in infants with hypoplastic left heart syndrome (HLHS) requires a specific medical regimen. The goals of preoperative management are to maintain ductal patency and to provide the appropriate balance between the systemic and pulmonary vascular resistances. Intravenous prostaglandin E is infused at 0.05 mcg/kg/min to maintain patency of the ductus arteriosus. This dose may be titrated to keep the ductus arteriosus open while minimizing the risk of apnea.

Oxygen saturation is monitored by pulse oximetry. Acidosis is rapidly reversed using sodium bicarbonate. The fraction of inspired oxygen (FIO₂) is adjusted to maintain a relative hypoxemia (oxygen saturation 75-80%), which aids in preventing the pulmonary vasodilatation associated with high oxygen concentrations. Even in the neonate who is being resuscitated because of circulatory collapse, ventilation with a high concentration of oxygen is avoided because it may only further decrease pulmonary vascular resistance and systemic blood flow.

Blood transfusion should be performed to maintain the hematocrit at 40-45%. Mechanical ventilation is avoided when possible, but infants on ventilation may require sedation with intravenous fentanyl to prevent tachypnea. In patients with significant pulmonary overcirculation, hypoventilation to maintain a mild respiratory acidosis (partial pressure of carbon dioxide [PCO₂] of 45-55 mm Hg) and elevation of pulmonary vascular resistance may be used. Occasionally, inhaled nitrogen or carbon dioxide can be added to reduce the FIO₂ to 16-18% to increase pulmonary vascular resistance, although the use of the latter has been cautioned because of adverse effects on splanchnic blood flow. ^[33] Inotropic support may be necessary in patients with depressed right ventricular function.

Nourishment is usually provided via intravenous hyperalimentation, which avoids the added risk of necrotizing enterocolitis prior to surgery. Diuretics are added, as necessary, when pulmonary congestion becomes apparent. This regimen simulates the fetal balance of pulmonary and systemic vascular resistance, stabilizing the infant while deciding on therapeutic options.

Parents of children with hypoplastic left heart syndrome (HLHS) are presented with the following 3 options: (1) supportive therapy only (leading usually to rapid demise), (2) staged reconstruction, and (3) orthotopic cardiac transplantation. Each institution must assess its results with the various modes of therapy and counsel the parents accordingly. As outcomes of palliative procedures and heart transplantation in patients with HLHS have improved, even surpassing therapies for other complex forms of congenital heart disease in some patients, the first option of supportive therapy only has been challenged. The techniques and results of staged reconstruction are discussed below.

The goal of staged reconstruction is a Fontan procedure, creating separate pulmonary and systemic circulations supported by a single (right) ventricle. The initial stage must provide unobstructed systemic blood flow from the right ventricle to the aorta and coronary arteries, relieve any obstruction to pulmonary venous return, and limit pulmonary blood flow by virtue of an appropriately sized systemic–to–pulmonary artery shunt or right ventricle–to–pulmonary artery shunt (RVPAS).

As a result of the relatively high pulmonary vascular resistance present in the newborn period, a systemic shunt is necessary, and the right ventricle performs the increased volume of work of both the pulmonary and systemic circulations. Preservation of right ventricular function has been aided by using smaller initial aortopulmonary shunts to limit right ventricular volume overload, by using an RVPAS, and by using an interim procedure between the Norwood and Fontan operations. This staging procedure, either a bidirectional Glenn anastomosis or a hemi-Fontan procedure, is usually performed at age 4-6 months.

As introduced above, the use of an RVPAS as an alternative to the traditional modified Blalock-Taussig shunt (MBTS) has been revisited. In 2002, Sano and colleagues described their experience with the Norwood procedure, with improvements in hospital survival from 53-89% when compared with historical controls. ^[34] Several other groups also reported similar improvements in outcomes, based on historical controls. A comparison using nonrandomized, but contemporary, controls by Tabbutt and colleagues revealed no difference in hospital survival. ^[35]

The general trend in the literature has been that centers that have had difficulties in achieving optimal survivals with the Norwood procedure have found a benefit to using the RVPAS, whereas institutions that have had better success with the Norwood procedure have found no improvement. Each source has inherent advantages and disadvantages, and the long-term effects are unknown. The MBTS results in significant diastolic run-off and potential coronary steal. The RVPAS avoids this run-off but adds the undesirable need to place an incision on the right ventricle.

Potential shortcomings of the RVPAS are the right (systemic) ventriculotomy, right ventricular volume overload from the nonvalved conduit insufficiency, and decreased branch pulmonary artery growth because of the lack of diastolic flow, although its long-term effects on the right ventricle in the setting of HLHS are not known. ^{[36, 37]}

Because of the important implications of shunt selection on Norwood procedure outcomes, the National Heart, Lung, and Blood Institute (NHLBI)–funded Pediatric Heart Network began a multi-institutional, randomized controlled trial (Single Ventricle Reconstruction or SVR trial) in 2005 to rigorously and objectively compare the RVPAS with the MBTS. ^[38] The primary outcome measure was a combined outcome of death or cardiac transplantation 12 months after randomization. Secondary outcomes that were investigated were postoperative morbidity after the Norwood and stage II procedures, right ventricular function and branch pulmonary artery growth at stage II, and neurodevelopmental outcomes at age 14 months.

The 1-year primary and secondary outcome results for the SVR trial were reported in 2010 by Ohye and colleagues for the Pediatric Heart Network. ^[1] From May 2005 to July 2008, 555 neonates were enrolled, of which 549 subjects (275 in the MBTS arm and 274 in the RVPAS arm) underwent a Norwood procedure and were included for study from 15 North American sites. Subjects in the RVPAS group had a 74% transplantation-free survival versus 64% for the MBTS group (P =.01).

Importantly, right ventricular function as measured by ECG was similar in both groups at 14 months. However, when all available data were analyzed at a longer mean follow up of 32±11 months, a statistically significant transplant-free survival advantage of the RVPAS group did not persist. (P =.06). The RVPAS group required more unplanned cardiovascular interventions, which included catheter and surgical procedures to address narrowing or obstruction in the shunt, branch pulmonary arteries, or neoaorta, as compared to the MBTS group (92 vs 70 per 100 infants, P =.003).

Whichever source of pulmonary blood flow is selected, these procedures provide adequate pulmonary blood flow while decreasing volume overload to the right ventricle and improving effective pulmonary blood flow until the patient can undergo a completion Fontan procedure. As described in detail in Second-stage palliation: Hemi-Fontan or bidirectional Glenn anastomosis, the hemi-Fontan procedure is a modification of the bidirectional Glenn procedure. The hemi-Fontan procedure involves (1) a side-to-side connection between the superior vena cava (SVC)/right atrial junction and the pulmonary arteries, (2) routine augmentation of the branch pulmonary arteries, and (3) temporary patch closure between the pulmonary arteries and the right atrium.

As mentioned above, a newer alternative method of staged repair is the hybrid procedure. ^{[39, 40]} The hybrid procedure provides the essential elements of the Norwood procedure, namely, providing unrestricted systemic output from the right ventricle and controlling pulmonary blood flow without the need for an open heart procedure with cardiopulmonary bypass. For the hybrid procedure, the invasive cardiologist and the congenital cardiac surgeon work in concert. Generally, the surgeon opens the chest and places an introducer into the pulmonary artery. The cardiologist then places a stent in the patent ductus arteriosus to provide systemic output from the right ventricle. Concurrently or at interval, the atrial septal communication is assured by balloon septostomy ± stenting and pulmonary artery blood flow is controlled with the use of bilateral pulmonary artery bands.

The second stage, the so-called comprehensive stage II procedure, involves an aortic reconstruction as in the Norwood procedure and a hemi-Fontan or bidirectional Glenn as described above.

First-stage palliation: Norwood procedure

Through a midline sternotomy, cardiopulmonary bypass (CPB) is established via arterial cannulation of the patent ductus arteriosus and venous cannulation of the right atrium. A snare is engaged around the patent ductus arteriosus to prevent flow into the pulmonary arteries. A minimum of 20 minutes of cooling to a core temperature of 18°C is begun for deep hypothermic circulatory arrest. Alternatively, some groups have reported the use of regional low-flow cerebral perfusion in lieu of deep hypothermic circulatory arrest (see below).

Regardless of the technique used, the septum primum is completely excised (atrial septectomy). The ductus is ligated and divided. The main pulmonary trunk is divided just proximal to the bifurcation of the pulmonary arteries. The resultant opening in the pulmonary artery is closed with a patch of pericardium, polytetrafluoroethylene, or homograft. The remaining ductal tissue (on the undersurface of the aortic arch) is completely excised, and the incision is extended at least 10 mm further down the descending aorta into a normal-appearing and normal-caliber aorta (see following image).

Surgical Treatment of Pediatric Hypoplastic Left Heart Syndrome. The main pulmonary artery and ductus arteriosus have been divided. Dashes indicate the line of incision on the hypoplastic ascending aorta. Image courtesy of Edward L. Bove, MD.

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This incision is proximally extended under the transverse arch and down the diminutive ascending aorta until the level of the previously divided main pulmonary trunk is reached (see following image).

Surgical Treatment of Pediatric Hypoplastic Left Heart Syndrome. The ascending aorta is opened and sutured to the adjacent proximal main pulmonary artery. A patch of pulmonary homograft is fashioned to create the neoaorta (inset). Image courtesy of Edward L. Bove, MD.

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A cryopreserved pulmonary allograft is trimmed to fashion a patch that serves to enlarge the aorta and allow anastomosis to the proximal main pulmonary trunk (see inset in image above). The remainder of the aorta is attached to the pulmonary allograft, proximally incorporating the main pulmonary trunk. The cannulae are replaced to begin bypass and commence systemic rewarming to 37°C.

A polytetrafluoroethylene shunt is placed from the innominate artery to the central pulmonary artery during rewarming (see image below). A 4-mm shunt is used in patients who weigh more than 3.5-4 kg; smaller patients receive a 3.5-mm shunt. The distal end of the shunt is centrally placed on the pulmonary arteries, rather than onto the right pulmonary artery, to promote even distribution of blood flow to both lungs. Alternatively, the RVPAS can be placed. These polytetrafluoroethylene grafts are generally either 5 mm or 6 mm in diameter.

Surgical Treatment of Pediatric Hypoplastic Left Heart Syndrome. Completed Norwood procedure showing reconstructed neoaorta and modified Blalock-Taussig shunt from the innominate artery to the confluence of the branch pulmonary arteries. Image courtesy of Edward L. Bove, MD.

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Several groups routinely use regional cerebral perfusion for aortic arch reconstruction in lieu of deep hypothermic circulatory arrest. For this technique, the proximal anastomosis of the modified Blalock-Taussig shunt is performed prior to instituting CPB. Then, the arterial cannula can be placed into the shunt, and perfusion is administered to the innominate artery. Whether these techniques improve perioperative survival rates or long-term neurodevelopmental outcomes has yet to be determined. Publications have failed to demonstrate any improvement in outcome with regional cerebral perfusion. ^{[41, 42, 43]}

Second-stage palliation: Hemi-Fontan or bidirectional Glenn anastomosis procedure

The hemi-Fontan operation or a bidirectional Glenn anastomosis is typically performed in infants aged 3-10 months to minimize the period of time during which the right ventricle is subject to volume overload. Cardiac catheterization is performed prior to this procedure to evaluate pulmonary vascular resistance, pulmonary artery anatomy, tricuspid valve regurgitation, and right ventricular function.

To perform a bidirectional Glenn procedure, CPB is achieved with neoaortic arch cannulation and separate right-angle IVC and right-angle SVC cannulae. The aortopulmonary shunt is ligated and divided when CPB is initiated. If any stenosis of the pulmonary artery secondary to the prior shunt or patch is present, the stenosis is repaired with patch augmentation. The azygous vein is ligated and divided. The SVC is transected and anastomosed in an end-to-side fashion to the superior aspect of the right pulmonary artery. The cardiac end of the transected SVC is oversewn. Some groups routinely perform the bidirectional Glenn procedure without CPB, with or without an SVC-to–right atrial temporary shunt, during the anastomosis to minimize high cerebrovenous pressures.

The hemi-Fontan procedure has the same physiologic factors as a bidirectional Glenn anastomosis but includes an anastomosis of the pulmonary arteries to an incision in the atriocaval junction. The cavopulmonary connection may be performed under a brief period of deep hypothermic circulatory arrest. Alternatively, cannulation of the IVC and high on the SVC can be used to perform the procedure entirely during CPB.

Whether the procedure is performed under circulatory arrest or during CPB, the remainder of the procedure is the same. The aortopulmonary shunt is divided, and the pulmonary arteries are mobilized from the right to the left upper lobe. The azygous vein is ligated. The right atrium is opened along the superior aspect of the appendage, and a corresponding incision is made transversely along the confluence of the branch pulmonary arteries (see upper left of image below). The posterior aspect of the right arteriotomy is anastomosed to the inferior aspect of the pulmonary arteriotomy (see upper right of following image).

Surgical Treatment of Pediatric Hypoplastic Left Heart Syndrome. Hemi-Fontan procedure. The modified Blalock-Taussig shunt is ligated, and incisions are made in the right atrial appendage and pulmonary arteries (upper left). The posterior aspect of the right atriotomy is anastomosed to the inferior aspect of the pulmonary arteriotomy (upper right). A patch of polytetrafluoroethylene is placed to prevent the superior vena cava return from entering the right atrium. The cavopulmonary connection is roofed with a patch of pulmonary homograft (lower). Image courtesy of Koji Kagasaki, MD.

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A patch of pulmonary allograft tissue is fashioned to augment the pulmonary arteries. The allograft patch is begun at the left upper lobe, incorporating a separate end-to-side anastomosis for a left SVC, if necessary (see lower portion of above image). A patch is placed within the right atrium, which isolates SVC return into the pulmonary arteries and provides an unobstructed pathway for connection of IVC return during the Fontan procedure (see lower portion of above image). The atrial septal defect is inspected and enlarged, if necessary, which is completed best by cutting back the coronary sinus into the left atrium. Tricuspid valve repair is also performed as needed.

The advantage of the hemi-Fontan is that it shortens the length of time of CPB and dissection required for the completion Fontan procedure, which requires only the removal of the intra-atrial patch and placement of a lateral tunnel in the right atrium from the IVC to the SVC. In addition, routine augmentation of the branch pulmonary arteries helps optimize the anatomy for the completion Fontan procedure.

Third-stage palliation: Fontan procedure

The completion Fontan procedure is usually performed in children aged 18-24 months. The infant is evaluated using cardiac catheterization prior to surgery. The Fontan technique used by the authors for HLHS anatomy is the technique termed total cavopulmonary connection with a lateral tunnel. After achieving CPB, the right atrium is opened.

If a hemi-Fontan procedure has been performed, the intra-atrial baffle is resected. In bidirectional Glenn anastomosis, a right atrium–to–pulmonary artery anastomosis is created. A baffle of polytetrafluoroethylene is fashioned and placed inside of the right atrium to convey the IVC return to the cavopulmonary connection (see image below). This technique minimizes the possibility of obstruction of the pulmonary venous return, which can be caused by an atriopulmonary anastomosis. Fenestration of the baffle may help prevent complications in high-risk patients and shorten the period of pleural drainage. Some centers opt for an extracardiac, instead of an intracardiac, lateral tunnel Fontan.

Surgical Treatment of Pediatric Hypoplastic Left Heart Syndrome. Fontan procedure. Through a right atriotomy, the polytetrafluoroethylene (PTFE) patch has been removed. A new PTFE patch is placed to baffle the inferior vena cava return to the cavopulmonary connection constructed during the hemi-Fontan procedure (left). The arrows indicate the systemic venous return bypassing the right heart to directly enter the pulmonary arteries (right). Image courtesy of Edward L. Bove, MD.

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First-stage palliation: Hybrid procedure

The hybrid procedure is performed either in an operating room with cardiac catheterization capability or in a cardiac catheterization suite. A median sternotomy is performed and bilateral pulmonary artery bands are placed at the take off of the left pulmonary artery and on the right pulmonary artery between the aorta and superior vena cava. The bands are constructed by cutting a 1- to 2-mm ring from a 3.5-mm polytetrafluoroethylene tube graft (GoreTex). A 3.0-mm graft is used for patients weighing less than 2.5 kg.

Bands are adjusted to achieve a mean distal pulmonary artery pressure of 17-20 mm Hg with some pulsatility. ^[44] An introducer sheath is then placed through the main pulmonary artery via a pursestring suture. A stent is deployed in the patent ductus arteriosus to provide unrestricted systemic blood flow. Just prior to discharge, a balloon atrial septostomy, and, if necessary, a stent are performed to maintain the atrial communication.

Second-stage palliation: Comprehensive stage II procedure

Via a median sternotomy, cardiopulmonary bypass is initiated with cooling for deep hypothermic circulatory arrest or regional cerebral perfusion at the discretion of the surgeon. The pulmonary artery bands are removed and the arteries are augmented as needed. The stent is removed and the aortic reconstruction is performed as in a Norwood operation. A bidirectional Glenn or hemi-Fontan is performed, depending on surgeon preference.

First-stage palliation: Norwood procedure

After weaning from CPB, an atrial-monitoring catheter is placed to measure central venous pressure, and infusion of inotropes is initiated. University of Michigan medical staff routinely use continuous infusions of milrinone and low-dose dopamine, adding epinephrine in doses of 0.02-0.06 mcg/kg/min if hypotension is significant. Ventilation, with an initial FIO₂ of 100% to achieve a PCO₂ of approximately 35 mm Hg, is initiated and adjusted depending on the systemic arterial oxygen saturation and the systemic perfusion. If poor peripheral perfusion with systemic saturation in excess of 80-85% is noted, the FIO₂ and minute ventilation are decreased to avoid excess pulmonary vasodilatation. The opposite maneuvers are used if systemic oxygen saturation is less than 70-75%.

Postoperative management is aimed at maintaining the delicate balance between the systemic and pulmonary vascular resistances and, therefore, relative systemic and pulmonary blood flow. Many regimens of ventilation, inotropic support, and vasodilatory support have been used, and multiple indicators of perfusion adequacy (mixed venous oxygen, lactate) have been measured with varying degrees of success.

Ideally, systemic arterial saturation should be maintained at 75-80%, which usually indicates that an optimal pulmonary-to-systemic blood flow ratio of less than 1 has been achieved. However, measurements of mixed venous oxygen saturation and pulmonary venous oxygen saturation are necessary to accurately assess the ratio of pulmonary blood flow (Qp) to systemic blood flow (Qs). The authors have found that serial lactate measurements provide an excellent indication of low cardiac output, and they rely on these determinations rather than mixed venous oxygen saturations.

Second- and third-stage palliation: Hemi-Fontan and Fontan procedures

For second- and third-stage operations, maintaining a low pulmonary vascular resistance is paramount. The pulmonary blood flow no longer is driven by an arterial shunt (or systemic RV, in cases of RVPAS), but by central venous pressure. Volume infusion used to increase central venous pressure is thus commonly needed. Hypoxia and acidosis, which increase pulmonary vascular resistance, are avoided. Although mild respiratory alkalosis may be beneficial for pulmonary vascular resistance, a pH higher than 7.45-7.5 decreases cerebral blood flow and, hence, SVC return. After the hemi-Fontan procedure is performed, this decrease in SVC return decreases pulmonary blood flow. Inhaled nitric oxide (NO) may also be used to decrease pulmonary vascular resistance but is infrequently needed. Positive-pressure mechanical ventilation can also impair Fontan physiology, and, thus, ventilator pressures are minimized and patients should be extubated early.

After discharge from the hospital, regular cardiovascular evaluations are important. The child should be carefully observed for aortic arch obstruction, tricuspid insufficiency, and increasing cyanosis secondary to a limited atrial septal defect, shunt stenosis, or pulmonary artery distortion. Inter-stage I and II home monitoring, which follows patient weight gain and oxygen saturation, is being used more frequently, and single-center studies have demonstrated an improvement in survival. ^[45] For other long-term concerns, see Complications and Outcomes and Prognosis.

Complications that result from a procedure of the magnitude of the Norwood palliation are fairly common. Complications may include bleeding, low cardiac output syndrome, and arrhythmia in the immediate postoperative period. Aggressive correction of thrombocytopenia and coagulation factors is warranted. Poor peripheral and end-organ perfusion may represent poor cardiac output or pulmonary overcirculation, which may be treated by inotropic support or manipulation of relative pulmonary and systemic resistances. Common arrhythmias include junctional ectopic tachycardiac, which can be treated either with surface cooling to 35-36°C and pacing or with amiodarone infusion.

Incidence of unexplained sudden death, both in the immediate postoperative period and after discharge, remains problematic. In the postoperative period, the authors found that serial serum lactate determinations demonstrating failure to clear lactic acidosis have been helpful in predicting patients who will do poorly despite an apparently stable clinical condition.

Shunt complications, such as thrombosis, can occur. All patients are started on low-dose aspirin when they begin enteral nutrition. Other causes of increasing cyanosis during the postoperative period include pulmonary artery stenosis or distortion and restriction at the level of the atrial septal defect.

Evaluation prior to the hemi-Fontan procedure may reveal pulmonary artery stenosis, particularly of the left branch or at the insertion of the shunt. These stenoses are managed with patch augmentation during the hemi-Fontan procedure. Residual coarctation should be rare if the initial homograft patch is brought sufficiently onto the descending aorta during the Norwood procedure. Postoperative coarctation can usually be managed with balloon dilatation or, if necessary, surgical augmentation.

Long-term complications following the Fontan operation include atrial arrhythmia, thromboembolic events, and protein-losing enteropathy. Atrial arrhythmias are less common with the current techniques of cavopulmonary connections and may be treated with standard antiarrhythmic therapy. All of the authors' patients who undergo the Fontan procedure are maintained on aspirin therapy, whereas others have advocated low-dose warfarin as prophylaxis against thromboembolism. Patients in whom the classic atriopulmonary connection Fontan procedure is performed with a dilated right atrium may benefit from conversion to a lateral tunnel or extracardiac Fontan operation to treat both arrhythmia and thrombosis.

Protein-losing enteropathy remains a difficult problem, affecting as many as 5% of patients who undergo the Fontan procedure. Treatment with intravenous infusions of albumin and immunoglobulin are supportive but not curative. Several other methods, including intravenous heparin, Fontan takedown, and cardiac transplantation, have been used with varying success.

A 2020 systematic review of interventions and neonatal outcomes of 118 fetuses with hypoplastic left heart syndrome (HLHS) and congenital diaphragmatic hernia found mortality remains high with surgical intervention. ^[46]  Sixty-two of the 118 patients underwent surgery (51%), of whom 36 (59%) survived to discharge. Factors that may affect outcomes include age at surgery, pulmonary function, and the use of extracorporeal membrane oxygenation (ECMO). ^[46]

A 2018 retrospective study (2001-2014) evaluated the prognostic value of of troponin in 70 infants with hypoplastic left heart syndrome between stage I and II of palliation and reported findings such as the following ^[47] :

• Those who underwent Norwood I procedure had significantly higher troponin levels than those who underwent the hybrid approach.
• There was a 39% overall mortality (n = 22): 54% post-Norwood survival (n = 22) and 73% post-hybrid intervention (n = 16).
• Independent of the approach used, nonsurvivors had significantly higher levels of maximum troponin and initial lactate values relative to survivors (median troponin: 9 mcg/L vs 3.5 mcg/L, respectively; median lactate: 3.7 mmol/L vs 2.9 mmol/L, respectively).
• Reinterventions were necessary in 30% of patients overall (n = 17): 11% (n = 4) after Norwood procedure and 59% (n = 13) post hybrid procedure
• There did not appear to be any correlation between the need for reintervation and troponin levels in the interstage period.

First-stage palliation

Bove et al studied first-stage palliation of HLHS from January 1990 to August 1995 in 158 patients. ^[48] All patients had classic HLHS, defined as right ventricle–dependent circulation, in association with atresia or severe hypoplasia of the aortic valve. Patients were subdivided into standard-risk (n=127) and high-risk (n=31) groups. High-risk patients included those undergoing the Norwood procedure after age 1 month, patients with severe obstruction to pulmonary venous return, and patients with significant noncardiac congenital conditions (ie, prematurity, low birth weight, chromosomal anomalies). Hospital survivors numbered 120 (76%). The hospital survival rate was significantly better in the 127 standard-risk patients (86%) than in the high-risk group (42%). Risk factor analysis failed to reveal any effect on outcome by morphologic subgroup, ascending aorta size, shunt size, initial pH at hospital presentation, or duration of circulatory arrest.

Among 151 patients at The Children's Hospital of Philadelphia in a report by Norwood et al, 42 (28%) early deaths and 9 (5%) late deaths occurred. ^[49]

In a Children's Hospital Boston series reported by Jonas et al, 78 neonates underwent palliative reconstructive surgery from 1983-1991. ^[50] Hospital deaths numbered 29 (37%). Analysis of deaths revealed a greater risk of hospital death for infants with aortic atresia and mitral atresia, especially those with ascending aortic dimensions of less than 2 mm.

However, in the authors' experience, these conditions have not been associated with increased risk. The results for the hospital survival for the Norwood procedure has continued to improve. In 2002, Tweddell and colleagues reported a 93% hospital survival in 81 patients undergoing a Norwood procedure for HLHS. ^[51] Galantowicz and colleagues published their results with the hybrid approach. ^[40] The hospital survival rate was 97.5%.

Second-stage palliation

Hospital records of 114 patients undergoing the hemi-Fontan procedure for HLHS between August 1993 and April 1998 at the University of Michigan Medical Center were reviewed by Douglas et al. ^[52] The overall hospital survival rate was 98% (112 patients). Sinus rhythm was present in 92% of patients. At the time of publication, 79 of the patients had undergone the completion Fontan procedure, with 74 survivors (94%). A similar study by Forbess et al from the Children's Hospital Boston also revealed that a cavopulmonary anastomosis performed as a second-stage procedure for HLHS reduced mortality and improved intermediate survival rates. ^[53]

Lee and colleagues reported results with 557 second-stage palliation procedures between 1998 and 2010 at the University of Michigan C.S. Mott Children’s Hospital (Michigan Congenital Heart Center), of which 89% were performed using the hemi-Fontan technique described above. ^[54] The overall hospital mortality rate was 4.7%. Sinus rhythm was present in 98.2% by hospital discharge. Risk factors for poor outcomes identified with multivariate analysis included ventricular dysfunction, atrioventricular valve regurgitation, and unbalanced atrioventricular septal defect anatomy. The authors recommended that any significant atrioventricular valve regurgitation should be addressed at the time of the hemi-Fontan procedure.

Galantowicz and colleagues also reported their overall results with the 40 patients who had undergone the hybrid procedure as referenced above. ^[40] There were 2 interstage deaths (5%), 2 reoperations, and 12 reinterventions in the catheterization laboratory. Thirty-six patients underwent comprehensive stage II procedures with 3 deaths (8%).

Results of the SVR trial

The 1-year primary and secondary outcome results for the SVR trial were reported in 2010 by Ohye and colleagues for the Pediatric Heart Network. ^[1] From May 2005 to July 2008, 555 neonates were enrolled of which 549 subjects (275 in the MBTS arm and 274 in the RVPAS arm) underwent a Norwood procedure and were included for study from 15 North American sites.

Subjects in the RVPAS group had a 74% transplantation-free survival versus 64% for the MBTS group (P =.01). The 2 highest-risk periods were during hospitalization for the Norwood procedure and in the interstage period between the Norwood and the stage II surgery.

Importantly, right ventricular function as measured by ECG was similar in both groups at 14 months. However, when all available data were analyzed at a longer mean follow up of 32±11 months, a statistically significant transplantation-free survival advantage of the RVPAS group did not persist (P =.06). The RVPAS group required more unplanned cardiovascular interventions, which included catheter and surgical procedures to address narrowing or obstruction in the shunt, branch pulmonary arteries, or neoaorta, as compared with the MBTS group (92 vs 70 per 100 infants, P =.003).

While consistent pathological examinations were not available, the deaths in the SVR trial were investigated further with specific attention given to the causes and timing. ^[55] Most of the deaths occurred in the study hospital (74%), while the rest occurred in a non-SVR hospital (13%) or at home (13%). Most of the hospital deaths occurred in the ICU. Twenty-nine (18%) deaths were considered unexpected (13% died at home, while 5% made it to a hospital and died there). Twelve of these deaths were preceded by a prodrome. These prodromes included poor oral intake and vomiting (n=4); diarrhea (n=2); cyanosis (n=1); combination of poor oral intake, fussiness, and diarrhea (n=1); and combination of fever and increased work of breathing (n=1). Three of these patients with prodromes were evaluated by a physician. It is not known how many of these patients were part of a home-monitoring program.

Tabbutt et al analyzed the events during the Norwood hospitalization of subjects in the SVR trial. ^[56] Not surprisingly, those who needed extracorporeal membrane oxygenation (ECMO), CPR, or emergent resuscitation with ECMO had inferior survival compared with those who did not need ECMO. Genetic abnormality, low center volume, low surgeon volume, open sternum, and higher number of post-Norwood operations were the most common independent risk factors for the post-Norwood morbidities.

Frommelt et al analyzed ECG measurements obtained early after the Norwood procedure, just before the stage II procedure and at 14 months post randomization. ^[57] Average right ventricle ejection fraction was abnormally low in both groups and identical at all time intervals, except after the Norwood procedure, for which it was higher in the RVPAS group (49 vs 44%). These findings indicate that the ventriculotomy required to perform the RVPAS does not have significant untoward effects, at least up to 14 months. It is also interesting that an advantage in right ventricular function in the RVPAS group coincided temporally with the interstage period, in which there was a survival advantage in this group as well.

Aiyagari et al analyzed the hemodynamic parameters of 389 SVR patients undergoing a pre-stage II cardiac catheterization. ^[58] These investigators found that smaller size, lower aortic and superior vena cava oxygen saturation, and higher right ventricle end-diastolic pressure were associated with worse 12-month transplantation-free survival. The MBTS group had significantly lower coronary perfusion pressure and greater pulmonary blood flow/systemic blood flow ratio. The MBTS group also had fewer shunt and severe left pulmonary artery obstruction and larger branch pulmonary arteries, suggesting better preparation for the Fontan circulation.

Third-stage palliation

One hundred consecutive patients with classic HLHS underwent a Fontan procedure at the University of Michigan between February 1992 and April 1998. ^[59] The survival rate in patients (n=52) undergoing surgery in the second half of the study and treated with a prior hemi-Fontan procedure at second-stage palliation was 98%. No deaths have occurred in patients undergoing the last 125 consecutive Fontan procedures for HLHS. Several other centers also have reported significant improvements in survival rates following the Fontan procedure in patients with HLHS.

Currently, numerous groups are advocating the use of an extracardiac conduit to complete the Fontan procedure. This technique may offer significant advantages; however, patients may be exposed to the risks of thromboembolic complications inherent in prosthetic conduits in the venous system. Lack of growth is also of concern. The literature does not have a consensus that favors one technique over the other. The results of the hybrid approach through the Fontan procedure were also reported by Galantowicz et al. ^[40] One interstage mortality occurred and 15 patients had undergone Fontan completion while 17 awaited Fontan. Among the 15 patients who underwent Fontan completion, no mortalities occurred.

Neurodevelopmental outcomes

Newburger and colleagues evaluated neurodevelopmental outcomes in 321 SVR trial subjects at 14 months post randomization. ^{[60, 61, 62]} Neurodevelopment was assessed by the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Development-II. Shunt type, cardiac anatomy, and intraoperative strategies did not affect PDI or MDI scores. Average PDI and MDI scores for the entire cohort were below normal values. ^{[60, 61, 62]} The neurodevelopmental impairment in HLHS patients who have undergone the Norwood procedure is likely due to inherent patient factors rather than intraoperative factors. The authors recommended against elective deliveries prior to 39 weeks, as well as optimizing developmental support after Norwood hospitalization discharge.

Similar findings were reported in a 2020 pilot study that evaluated cognitive function and attention in 20 patients aged 8 to 16 years with HLHS using the Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V) and NIH Toolbox Cognition Battery (NTCB). ^[63] Parents also completed the Child Behavior Checklist. The children had medium to large lower scores on the WISC-V and NTCB scales, and large, significant attention problems. There was also an association between child age and lower visual spatial scores. ^[63]  

Despite the initial innovation of the Norwood procedure and single-ventricle palliation for hypoplastic left heart syndrome (HLHS), mortality still remains high for this group of patients. As mentioned above, although the SVR trial demonstrated early differences in survival favoring the right ventricle–to–pulmonary artery shunt (RVPAS), longer follow-up has demonstrated a loss of this survival advantage. The SVR trial did reveal a wide variation of mortality rates across centers, and thus some clinicians and researchers are now focusing on improving the outcomes of inferior-performing centers by identifying best practices in centers that have superior outcomes.

Variations in practice have been also seen as areas of controversy in this field: RVPAS versus MBTS, hypothermic circulatory arrest versus regional cerebral perfusion, hybrid versus conventional Norwood, hemi-Fontan versus bidirectional Glenn, and extracardiac conduit versus lateral tunnel Fontan. As small single-center studies have provided conflicting results, these major practice variations are best compared in large multicenter trials and will likely require very long-term follow-up to determine superiority (which may be statistical but not clinical in magnitude) of one approach versus another.

Another concept developed from the SVR trial that is receiving attention is that of “failure (or ability) to rescue,” with superior-performing centers, not surprisingly, having a better ability to rescue a patient in extremis. Using SVR data, and ultimately additional prospective trials, it will be possible to determine whether high-performing centers have fewer complications compared with standard-performing centers, or similar rates of complication, but an enhanced ability to successfully manage complications when they occur, as has been seen in other patient populations. ^[64]

It is likely that patients with a circulation powered by a single right ventricle with relatively low preload will have decreased life expectancy, but it is not known whether current results have reached this physiological ceiling yet. As considerable efforts are devoted towards achieving this ceiling with a single right ventricle, other efforts of restoring a normal amount of mechanical power input to the total body circulation (systemic plus pulmonary) may have the potential of reestablishing normal life expectancy to these patients with HLHS and functional single-ventricle heart defects. Current examples of these strategies include mechanical circulatory support and cardiac transplantation; however, each has its own obstacles and shortcomings that make these options far from the ideal replacement of the autologous left ventricle.