HLHS and Single Ventricles

Single Ventricle

1.Tricuspid atresia (dominant left ventricle (LV) or right ventricle (RV)) 2. Pulmonary atresia with intact ventricular septum, RV-dependent coronary circulation, and hypoplastic right ventricle (dominant LV) 3. Double inlet ventricle (dominant LV or RV) 4. Severely unbalanced atrioventricular (AV) canal defect (dominant LV or RV) 5. Straddling AV valve 6. l-loop transposition of the great arteries with pulmonary atresia and univentricular hypoplasia 7. Double outlet right ventricle with mitral atresia

Phenoxybenzamine 3

Management of Cardiopulmonary Bypass [Print Section] High-flow CPB guided by SvO2 provides the best organ perfusion and the least metabolic evidence of anaerobic metabolism. However, reconstruction of the aortic arch requires that blood flow be intermittently interrupted, and thus circulatory support for stage 1 palliation typically entails some degree of regional hypoperfusion. In addition to the usual invasive monitoring and venous oximetry on CPB, two-site NIRS has been identified as a useful adjunct to guide management of the determinants of oxygen delivery and consumption on CPB.

...

Mechanical Circulatory Support [Print Section] Mechanical circulatory support should be initiated before global or regional hypoxia results in organ damage or death. The threshold for brain lactate production occurs with cerebral rSO2 values around 40% (236,237) and the threshold for anaerobic metabolism appears to be at an SvO2 around 30% in this patient population (175). If manipulation of SVR, PVR, and inotropic state does not result in adequate systemic oxygen delivery, and if there is no issue with shunt size, patency, or other correctable anatomic limitations, then inotropic support should be aggressively escalated since individual dose-response effects are variable. Adequate oxygen delivery is the goal (220). Failure to achieve adequate organ oxygen delivery with sustainable inotropic support should prompt consideration of mechanical support. Elective mechanical support should be considered a defensible strategy and preferable over unplanned circulatory collapse and resuscitation (238). Traditional venoarterial extracorporeal membrane oxygenator (ECMO) support must be used if there is any question about shunt patency or lung function, and rapid-response ECMO can effectively salvage some infants who have severe hypoxia and cardiogenic shock. Management of the systemic-to-pulmonary artery shunt on ECMO has evolved. Historically, the shunt was mechanically clipped during ECMO support (207). This strategy was used because of a desire to limit ECMO flow and concerns about excessive pulmonary blood flow hypothesized to result in pulmonary dysfunction while on support. The result of a clipped shunt strategy was development of pulmonary dysfunction, which has been postulated P.1024 to be due to ischemia or more likely severe alveolar alkalosis that resulted from prolonged ventilation of underperfused lungs. Management with a patent shunt allows for gradual transition to pulmonary gas exchange while support flow is weaned (239). An alternative approach to mechanical support is to use the patient's lungs' total gas exchange, and a roller pump without oxygenator is interposed between atrial drainage and the aorta (240). This arrangement simplifies anticoagulation and requires maintenance of lung ultrastructure and function, which may be impaired by ECMO without pulmonary blood flow (234). Use of mechanical support to preserve end-organ function may improve outcomes (62,238,240). Problems with ECMO include bleeding, clotting, massive blood product requirements, lung "whiteout," acquired adult respiratory distress syndrome (ARDS) from ventilating an ischemic lung, and intracranial bleeding. We prefer a technique that maintains shunt patency allowing continuous transition of circulatory work and gas exchange between the patient and the machine. Critical attention to fluid and colloid administration with maintenance of central venous pressure (CVP) <10 is necessary if pulmonary and myocardial function are to recover. Continued management of SVR may be necessary to maintain adequate organ perfusion pressure and regional blood flow. CO2 is added to the inspired gas during ECMO to achieve an end-tidal CO2 of 40 torr to avoid hypocapnic lung injury (233,234) and acute increases in PVR with lung reperfusion (232). This strategy allows progressive weaning of mechanical support as native myocardial function improves.

Stage 3

tage 3: Completion Fontan [Print Section] For the patient with HLHS, the Fontan procedure is the last anticipated operation. The techniques and indications for surgery are not different from those for other single-ventricle patients, and indeed in many centers patients with HLHS make up the majority of patients undergoing the completion Fontan. For patients who have undergone a stage 2 procedure, either a P.1027 bidirectional Glenn shunt or hemi-Fontan, the timing of completion Fontan is not critical; in general, the operation is performed between 18 months and 4 years of age. The surgical goal is to route the blood from the inferior vena cava to the pulmonary arteries with as little energy loss as possible. Although interventional techniques to perform the completion Fontan using coated stents have been reported, much more commonly this is performed in the operating room using one of two techniques; a lateral tunnel or extracardiac conduit (Fig. 50.22). The lateral tunnel Fontan is commonly performed following the hemi-Fontan. As part of the hemi-Fontan, a dam is constructed between the pulmonary arteries and the right atrium. During the completion Fontan, this dam is removed and a section of prosthetic conduit is used to create a baffle to route the inferior caval blood return to the pulmonary artery. The baffle is not circumferential, and a portion of the tunnel is made up of the patient's atrium, therefore maintaining, in theory, potential for growth. Additional advantages include a low level of power loss as determined by computational fluid dynamic studies (258). Although controversial, some studies suggest a higher incidence of sinus node dysfunction following the lateral tunnel Fontan (259,260,261,262,263). Another potential disadvantage of the lateral tunnel Fontan involves the presence of prosthetic material exposed to the pulmonary venous portion of the atrium with the potential for thrombus formation and systemic embolization. The extracardiac Fontan is constructed by placing a prosthetic conduit between the inferior vena cava and the pulmonary arteries. The advantages include the ease of the operation and, although somewhat controversial, probably a lower incidence of sinus node dysfunction (259,260,261,262,263). In addition, no prosthetic material is placed in the pulmonary venous atrium, with potentially lower risk of thromboembolic complications. The principle disadvantage is the lack of growth potential. To this end, larger conduits, between 20 and 22 mm in diameter, are placed to accommodate growth. The larger and longer conduits may result in power loss, which, when combined with the potential for late revision for outgrowth, may impact the durability of the extracardiac Fontan. The postoperative course of patients following the Fontan procedure for HLHS is not substantially different from that of other single-ventricle patients with equivalent function. Patients with HLHS more commonly have decreased systolic and altered diastolic function, and they are at increased risk for postoperative complications including decreased cardiac output with elevated central venous pressure, pleural effusions, ascites, thrombosis, and arrhythmias. We routinely use a fenestration in the Fontan to permit right-to-left shunting, which decreases central venous pressure and improves single-ventricle preload and cardiac output, at the expense of some degree of desaturation. The use of a fenestration has resulted in excellent survival and shorter hospital stay (103). Additional strategies that minimize postoperative hospital stay include routine use of the diuretics including spironolactone, an aldosterone antagonist, and furosemide. Supplemental oxygen is used as a pulmonary vasodilator, and afterload reduction is given to improve cardiac output and lower single-ventricle filling pressures (264).

Fontan circuit and work of breathing

1.) Up to 1/ 3 of the cardiac output in the Fontan patient is directly attributable to the passive work of breathing 2.) Patients with a Fontan circulation may poorly tolerate positive pressure ventilation for this reason, as they are unable to drop intrathoracic pressure sufficiently to allow adequate increases in forward flow 3.) Several investigators have reported success in ventilating patients with cuirass negative pressure ventilation.

HLHS associated anomalies

1.) 80% of neonates with hypoplastic left heart syndrome will have evidence of a localized coarctation of the aorta, in addition to the typical ascending aorta hypoplasia and left ventricular hypoplasia 2.) Anomalous pulmonary venous return < 5% 3.) Persistence of a left SVC each occur in < 5% of patients 4.) Right AV valve dysplasia can occur in < 30% of patients and occurs more commonly in patients with patent mitral valves.

HLHS

1.) Aortic atresia with mitral valve atresia occurs in 36% to 46% of patients with HLHS 2.) AS/MS: 13% to 26 % 3.) 20% to 29% of patients have aortic atresia with a patent mitral valve.

Tricuspid Atresia

1.) Tricuspid Atresia: Type 1 - normally related great vessels Type 2 - d-transposed of the great arteries Type 3 - l-transposed of the great arteries 2.) Further classification depends on the presence or absence of ventricular septal defects and ventricular outflow tract obstruction.

SvO2

The range of SvO2 at any given SaO2 is shown in a model with variable total cardiac output and bounded by Qp/Qs as low as 0.5 and as high as 2. For any SaO2, a range of SvO2 is possible. The slope of the SaO2-SvO2 relationship, as total cardiac output changes, is determined by the Qp/Qs ratio.

Echo 4CV

Apical four-chamber view in a patient with hypoplastic left heart syndrome. The left atrium (LA) and left ventricle (LV) are much smaller than the right atrium (RA) and right ventricle (RV). The right ventricle clearly occupies the cardiac apex. Right ventricular function and tricuspid valve anatomy and competency are best assessed from the four-chamber view. Right ventricular systolic function may be depressed, especially in those neonates with ductal closure and acidosis. Tricuspid valve abnormalities are common and can include a bileaflet valve, tricuspid valve dysplasia/prolapse, and abnormal papillary muscle arrangement

NIRS

Actual SvO2 and values predicted from two-site near-infrared spectroscopy (NIRS) model. A neonate after the Norwood procedure performed with phenoxybenzamine has superior vena cava (SVC) SvO2 monitoring and NIRS probes over frontal cerebral and T10-L2 somatic (renal) sites. A linear model of NIRS data closely tracks actual SvO2 data. (Model SvO2 = 0.45*rSO2cerebral + 0.45* rSO2somatic.) CI, confdence interval; rSO2, regional oxygen saturation; SvO2, systemic venous saturation. (Adapted from Hoffman GM, Stuth EA, Berens RJ, et al. Two-site near-infrared transcutaneous oximetry as a non-invasive indicator of mixed venous oxygen saturation in cardiac neonates. Anesthesiology 2003;97:A1393 , with permission.)

Anesthetic Management

Anesthetic Management [Print Section] Stage 1 Palliation Trauma and surgical stress induce a neurohumoral and cytokine response, the magnitude of which is associated with organ dysfunction and death (212). Anesthetic techniques that reduce the magnitude of biologic markers of stress are associated with decreased mortality (213). Because of the extent of surgical trauma and the use of profound hypothermia with or without circulatory arrest, anesthetic techniques that use high doses of synthetic opioids to reduce the stress response and preserve the limited neonatal cardiac reserve are rational and associated with improved outcome (142,214). Typically, profound analgesia and adequate blunting of the stress responses can be accomplished with 30 to 60 μg/kg of fentanyl before cardiopulmonary bypass (CPB) and a continuous fentanyl infusion of 10 μg/kg/hour throughout the procedure and into the postoperative period (142,215). Low-dose volatile anesthetics (0.25 to 0.5 minimum alveolar concentration [MAC]) or benzodiazepines (lorazepam 100 to 200 μg/kg) for hypnosis and to further limit autonomic responses, particularly to CPB, are routinely used. Some patients may require dopamine at 2 to 5 μg/kg/minute or epinephrine at 0.02 to 0.05 μg/kg/minute to counterbalance the reduction in sympathetic outflow resulting from unconsciousness, and such inotropic support will usually improve systemic flow to vital organs (216). Afterload Reduction [Print Section] Anesthetic drugs alone cannot completely eliminate the stress response to profound hypothermia (142). Because increases in SVR as part of the stress response can impair systemic oxygen delivery, strategies to control Qp/Qs have been critical in the management of these infants. Medical gas management aimed at elevation of PVR with inspired CO2 or hypoxic gas mixtures allow control of PVR independently of minute ventilation (161,167,171). Management based on modulating PVR guided by SaO2 as an indicator of Qp/Qs does not eliminate early hemodynamic collapse, and autonomic influences on SVR remain active.

A4Chamber

Apical Four-Chamber View The apical four-chamber view is often critical for definitively evaluating left ventricular size and function. If a large portion of the cardiac apex is occupied by the right ventricle (Fig. 50.6), it is unlikely that the left ventricle can support P.1012 the systemic circulation. The four-chamber view also provides an excellent window to see the entire mitral apparatus, including the subvalvar and supravalvar areas. Mitral valve anatomy and annulus size should be reassessed, especially in cases of borderline left ventricular size.

Approach to Qp:Qs balance

As an alternative approach to obtain Qp/Qs balance, pharmacologic interruption of systemic vasoconstrictor responses using alpha-adrenergic blockade was popularized by Poirier et al. (217). Such an approach has been shown to increase systemic oxygen delivery (173) and is associated with improved survival (173,174). The basic physiologic premise is that pharmacologic clamping of SVR in conjunction with clamping the total PVR with a resistive shunt will reduce the variability in systemic oxygen delivery through reduced variability in Qp/Qs. The importance of shunt size in limiting Qp/Qs extremes has been modeled, and smaller shunts make pulmonary overcirculation less likely (170). However, fourfold elevations in SVR are possible in the stressed neonate, making variable Qp/Qs unavoidable if the capacity for vasoconstriction is not blocked or at least reduced. Treatment with phenoxybenzamine, a long-acting irreversible alpha-adrenergic receptor blocker improved systemic oxygen delivery as signaled by SvO2 (172,218). The improved SvO2 occurred during the early postoperative course, the time typically associated with critical reductions in systemic oxygen delivery (219,220). The relationship between blood pressure and SvO2 was fundamentally altered in patients receiving phenoxybenzamine, suggesting that SVR was both lower and less variable (Figs. 50.16 and 50.17). With SVR effectively clamped by reducing autonomic influences, phenoxybenzamine largely eliminated the deterioration of systemic oxygen delivery at high SaO2 and fundamentally changed the relationship between SaO2 and SvO2 in the postoperative parallel univentricular circulation, as depicted in Figure 50.18 (176). This has simplified management by reducing the extremes in Qp/Qs variability. The required total cardiac output to meet systemic oxygen requirements is less at Qp/Qs closer to one, and the cycle of increasing SVR resulting in falling oxygen delivery is interrupted. We routinely use 0.25 mg/kg phenoxybenzamine at the initiation of CPB, with a selective postoperative infusion of 0.25 mg/kg/day limited to infants who demonstrate reactive SVR despite fentanyl and benzodiazepine treatment. A similar effect was not achieved with milrinone and nitroprusside. The benefits of phenoxybenzamine result from its pharmacologic effect, alpha-blockade, and from its duration of action, which commits the patient to a treatment strategy that both promotes and requires high systemic blood flow.

Cardiac Catheterization

Cardiac Catheterization [Print Section] Indications for cardiac catheterization in patients with HLHS may be interventional or may be elective diagnostic studies performed prior to Stage 2 palliation or prior to the Fontan connection. Ruiz et al. (265) and Gewillig et al. (266) reported on the use of transcatheter stent placement within the ductus arteriosus in newborns with HLHS. This was performed in a group of patients who were listed for cardiac transplantation. This intervention allowed for avoidance of long-term PGE1 therapy and its inherent complications including apnea, increased secretions, and chronic edema during the weeks' to months' wait for a donor heart. Transcatheter atrial septostomy is also used in patients with HLHS and an intact atrial septum or highly restrictive atrial septal defect. It is likely that many in this group of patients have irreversible PVR changes that may not respond to intervention after birth. As a result, a few centers are currently performing fetal interventional procedures including balloon atrial septostomy and aortic balloon dilation in select patients with HLHS. Interventional procedures after stage 1 palliation may be indicated to further palliate the infant prior to stage 2 palliation. Indications include excessive cyanosis as a result of stenosis of either the systemic-to-pulmonary artery shunt, stenosis of the right ventricle-to-pulmonary artery conduit, or recurrent arch obstruction. Cardiac catheterization is routinely performed prior to stage 2 palliation in many centers. Information obtained includes measurement of pulmonary artery or pulmonary vein wedge pressure, pulmonary capillary wedge pressure, right ventricular systolic and diastolic pressures, and ascending and descending aortic pressures. Additionally, the pulmonary artery anatomy, the adequacy of the atrial septal defect, neoaortic arch obstruction, P.1028 atrioventricular valve function, right ventricular function, and superior vena cava anatomy are assessed. Two recent studies suggest that in select patients in whom clinical or anatomic concerns are absent by history, physical exam, and improved echocardiography technology, cardiac catheterization may not be necessary prior to stage 2 palliation (267,268). Catheterization is also performed prior to the completion Fontan operation. At this study, determination of pulmonary artery pressure, pulmonary capillary wedge pressure, and ventricular end-diastolic pressure is performed. Additionally, pulmonary artery anatomy, neoaortic arch anatomy, and the presence of venovenous or aortopulmonary collaterals are assessed. Some centers use three-dimensional CT scanning or MRI to determine vascular anatomy. Finally, the completion Fontan operation itself has been performed via catheter intervention (269). For patients with planned Fontan completion via interventional catheterization, a modification of the hemi-Fontan procedure is performed and includes a restrictive band placed at the superior vena-cavoatrial junction. A transseptal needle perforation is undertaken through the banded SVC-right atrial junction with the subsequent placement of a covered stent from the IVC to the pulmonary artery. In a report of five patients who underwent the Fontan operation with this technique, all returned home in 24 hours. However, several patients have required subsequent intervention for baffle leaks (192). The covered stent is presently under FDA evaluation and is not presently approved for use in the United States.

Transplantation

Cardiac Transplantation [Print Section] Primary Transplantation [Print Section] Some centers have chosen cardiac transplantation as the preferred primary therapeutic approach to HLHS (303,304,305,306,307,308,309,310,311,312,313,314). Bailey et al. (305) reported the results of neonatal transplantation for HLHS. Between 1985 and 1996, 176 infants with HLHS were listed for cardiac transplantation. Nineteen percent of this group died prior to the identification of a donor heart. One hundred forty two patients underwent transplantation between 1.5 hours and 6 months of life (median 29 days). Actuarial survival of patients who underwent transplant at 1 month, and at 1, 5, or 7 years of age were 91%, 84%, 76%, and 70%, respectively. Actuarial survival did not take into account the group of patients who died prior to an available donor heart. Intermediate-term follow-up of this group of patients has shown good growth and development (305). Evidence of neurodevelopmental delay has been noted in 11% with normal psychomotor development in 91% and a normal developmental index in 96% (305,315). Donor availability continues to be a limiting factor to primary transplantation with the donor shortage resulting in 25% to 30% mortality while on the waiting list. Alternative strategies to reduce pretransplant mortality include ABO-incompatible neonatal transplantation. West et al. (316,317) have demonstrated promising results in patients who underwent ABO-incompatible transplantation with a concomitant decrease in mortality in those patients awaiting primary transplantation. Transplant for Failed Palliation [Print Section] Cardiac transplantation has been used at most centers for patients with HLHS who have failed or are poor candidates for staged palliation. Indications include severe, symptomatic right ventricular dysfunction and/or tricuspid valve regurgitation at any stage of repair. Additionally, cardiac transplantation should be considered for the patient with severe, intractable PLE that is refractory to the usual therapeutic maneuvers, occasionally seen after the completion Fontan operation. Transplantation required in the course of staged palliation may be complicated by immunologic sensitization as a result of previous surgical interventions and the inherent need for blood transfusion, in addition to exposure to nonvalved allograft materials used for stage 1 repair (318). This sensitization may require prospective cross-matching of donor and recipient to find a suitable donor. This strategy has the potential to prolong the period of time that the patient may need to wait for transplantation. This group of patients generally has a higher risk for serious rejection after transplantation. Several centers have reported their results for heart transplantation in patients with previous Fontan operations. Gamba et al. (319) reviewed results from 1990 to 2002 in 14 patients who underwent heart transplantation after a previous Fontan operation. Mean age at the time of Fontan was 7.3 ± 2.8 years with the mean age at transplantation of 17.2 ± 6.3 years. The indication for transplantation was PLE in seven patients, arrhythmia with ventricular dysfunction in five patients, and heart failure in two patients. Late survival was reported in 10 of 14 patients at a mean follow-up of 64 ± 42 months with patients in New York Heart Association class I category. Actuarial survivals at 1, 5, and 10 years were 86% ± 9%, 77% ± 12%, and 62% ± 17%, respectively (319). Michielon et al. (320) evaluated the incremental risk factors for early mortality after heart transplantation. Between 1988 and 2002, 25 patients underwent heart transplantation, 15 of whom had a functional right ventricle and 10 of whom had a functional left ventricle. Twenty-two patients (88%) had a previous completion Fontan operation. Transition to heart transplantation occurred from a shunt in ten patients, a P.1030 bidirectional cavopulmonary anastomosis in nine patients, and after Fontan failure in six patients. Overall 30-day survival was 68% with no additional mortality up to 14.1 years. Heart transplantation following bidirectional cavopulmonary anastomosis exhibited 100% long-term survival as opposed to 68% after systemic-to-pulmonary artery shunt and 33% following the failing Fontan circulation. Michielon concluded that heart transplantation for patients with single-ventricle physiology is associated with substantial early mortality whereas the bidirectional cavopulmonary anastomosis provides the best transition to heart transplantation (320).

CPB 2

Cardiopulmonary bypass strategies vary by institutional philosophy and patient-specific anatomy as well as the intended operation. Both cannula placement and perfusion strategy are interdependent factors. Most commonly, a single venous cannulation is used. Direct cannulation of the proximal pulmonary artery trunk or ductus arteriosus permits high-flow bypass to commence with the intent of whole-body cooling to 18°C to 20°C prior to circulatory arrest, after which time the arterial cannula is repositioned in the neoaortic trunk (104,221). Alternatively, the innominate artery can be cannulated either directly or via a synthetic graft that will later become the source of pulmonary blood flow. This approach permits continuous cerebral perfusion with enough access to the arch to permit reconstruction and also provides measurable descending aortic blood flow (177,178,221,222). By manipulation of pump flows, temperature, and pCO2, significant somatic blood flow may be maintained during regional perfusion via the innominate artery (177,178,223). Avoidance of somatic arrest and profound hypothermia has also been achieved with bifurcated aortic cannulation to the innominate and descending thoracic aorta (224). Management of blood flow, hematocrit, temperature, and pCO2 on CPB surrounding the time of circulatory arrest has been extensively investigated. Evidence suggests that cooling until jugular venous saturation is near 100%, at which time EEG silence occurs, maximally preserves cerebral oxygenation during subsequent ischemia. Neurologic outcomes are presumably improved with longer cooling time, pH-stat management during cooling, higher hematocrit before and after deep hypothermic circulatory arrest (DHCA), and by providing more metabolic suppression from hypothermia with more oxygen delivery (225). Questions remain whether metabolic suppression from hypercapnia is additionally beneficial. The absolute safe time for DHCA in any individual patient remains unknown, although risk is clearly increased after 30 to 40 minutes at 18°C to 22°C (226). Neurologic injury, however, may occur despite all CPB parameters in the usual safe range. Recently, Anttilla et al. (227) have shown that combinations of hematocrit, pCO2, temperature, and flow rate could produce ischemic injury, which was consistently identified by a lower brain oxygen saturation by NIRS. Based on the premise that hypoxia is the major cause of cerebral injury in the perioperative period, it is hypothesized that strategies that provide continuous or near-continuous cerebral perfusion (228) may avoid the complications attributable to DHCA (229). A post-cardiopulmonary bypass period of increased risk of decreased cerebral perfusion has been identified (Fig. 50.19). A recent randomized prospective study of patients with single-ventricle anatomy undergoing arch reconstruction comparing continuous cerebral perfusion and DHCA failed to identify a difference in neurodevelopmental outcome at 1 year of age (230). Because techniques are continuously evolving, and neurologic outcome assessment is best performed many years after neonatal surgery, a formal outcome study will not likely speak directly to current management.

Cardiovascular Reflexes and Shock

Cardiovascular Reflexes and Physiology of Shock Efficient delivery of oxygen to meet metabolic demand occurs through regional and global circulatory controls. Global cardiac output is affected by preload, afterload, rate, rhythm, contractility, and the presence of aortopulmonary shunts. Regional resistance is determined by the interaction of neurohumoral factors related to inflammation and the sympathetic nervous system, and local factors related to autoregulation. The total systemic vascular resistance (SVR) is thus determined by the net effect of regional resistances. Oxygen delivery (DO2) is systemic cardiac output (Qs) multiplied arterial oxygen content (CaO2), which is determined by the hemoglobin (Hb) concentration, oxygen saturation (SaO2), and oxygen tension (PaO2): The sympathetic stress response as described with hypo-volemic-septic shock (123,124,125) is activated in all shock states to redistribute blood flow to the brain and heart (126,127,128). The distribution of cardiac output can be significantly altered by stress responses, with the mesenteric and splanchnic circulations being at risk for silent ischemia during compensated shock (129,130,131,132). Circulatory reflexes to hemorrhage or hypotension will increase baroreflex gain to raise contractility, heart rate, and SVR, and decrease venous capacitance (133,134,135,136). These responses may be immediately protective in the face of hemorrhagic shock but often impair systemic flow in the face of myocardial dysfunction (137,138). These responses are also activated by cold stress, pain, and anxiety, and thus are not specific to hypovolemia (139,140,141,142). The vigor of the vascular component of the stress response may actually cause blood pressure to be elevated in the face of low cardiac output in the stressed neonate or child (143). The predominant profile of shock in pediatric patients is low cardiac output and very high SVR (144). The organs in the splanchnic circulation are the first to suffer ischemic injury because sympathetic outflow and innervation is rich in these regions (131,145,146,147,148) and because of the selective effects of angiotensin (149,150). Ischemic organ damage may occur even in the presence of normal global oxygen economy if regional vascular resistance is sufficiently elevated (129,130,151,152,153). There now exists compelling evidence that splanchnic/mesenteric ischemia is a frequent common pathway for multisystem organ dysfunction and death (154,155,156,157). Regional cellular oxygen deficit is underrecognized, underdiagnosed, and undertreated (158). Strategies targeting earlier detection and treatment of shock could improve outcome significantly.

Stage 2 palliation

Connection of the superior vena cava to the pulmonary arteries and takedown of previous systemic-to- pulmonary artery shunts constitutes the stage 2 procedure. Two surgical techniques are commonly used. A: The bidirectional Glenn shunt is a direct anastomosis of the superior vena cava to the central pulmonary artery. The principle advantage of the bidirectional Glenn shunt is the ease of construction; it can even be accomplished without the use of cardiopulmonary bypass in selected cases. B: In a hemi-Fontan procedure, the superior vena cava is connected to the confluent pulmonary arteries without disconnecting it from the atrium; the atrial end of the superior vena cava is closed with a patch. Although a more extensive operation than the bidirectional Glenn shunt, the hemi-Fontan allows for expeditious performance of a completion Fontan.

Cerebral perfusion

Changes in cerebral and somatic saturation during the Norwood procedure performed with continuous cerebral perfusion. Frontal cerebral and T10-L2 flank (renal-somatic) regional saturation (rSO2) from continuous near-infrared spectroscopy (NIRS) monitoring during the Norwood procedure. Cerebral oxygenation is well maintained during continuous regional cerebral perfusion (RCP) via the innominate artery, but somatic saturation falls. After weaning from cardiopulmonary bypass (CPB), the cerebral saturation falls, although somatic oxygenation is maintained. (Adapted from Hoffman GM, Stuth EA, Jaquiss RD, et al. Changes in cerebral and somatic oxygenation during stage 1 palliation of hypoplastic left heart syndrome using continuous regional cerebral perfusion. J Thorac Cardiovasc Surg 2004;127:223-233 , with permission.)

Diagnosis

Diagnosis [Print Section] Physical examination in the neonate with a severely restrictive atrial septum will be most notable for intense cyanosis with respiratory distress. In contrast, the infant with a nonrestrictive atrial defect may appear relatively pink. The infant with ductal closure is often lethargic and has respiratory distress, cool extremities, and pallor. Auscultation is generally benign, especially in comparison with a sometimes dramatic clinical picture. The second heart sound is single and loud, reflecting the absence of the aortic valve component and the associated pulmonary artery hypertension. A third heart sound may be heard, especially in the presence of ventricular dysfunction. Murmurs are uncommon, although a soft systolic ejection murmur may be generated from increased flow across the pulmonary valve. A louder S1 coincident murmur may be heard if there is significant tricuspid regurgitation. The upper- and lower-extremity pulses are palpable and symmetric early but are reduced later as ductal closure ensues. Hepatomegaly is common and is generally seen in infants with a delayed presentation. Chest radiographs are generally nondiagnostic but typically reflect the degree of atrial level restriction. In the infant with a severely restrictive atrial septum, the heart size may be relatively normal; however, there is significant pulmonary edema. The radiographic findings may be misinterpreted as lung disease, leading to a delay in diagnosis. In contrast, if the atrial septum is nonrestrictive, there is pulmonary overcirculation with cardiomegaly. The right atrial border may be prominent with absence of the ascending aortic shadow. The electrocardiogram does reflect the underlying pathology; however, it is nondiagnostic. Right axis deviation and right ventricular hypertrophy are common, but not distinctly different from the normal electrocardiogram of the neonate. Tall, peaked p waves, indicative of right atrial enlargement, have been reported in 30% to 40% of patients (7,8). With diagnostic two-dimensional echocardiography readily available, the need for cardiac catheterization in an infant with HLHS has dramatically decreased. Cardiac catheterization is generally used as an adjunct tool when trying to better identify pulmonary venous anomalies, or possibly, coronary anomalies. Also, in the setting of a severely restrictive atrial septum, catheter intervention may be lifesaving. P.1011

CBP 3

During rewarming and reperfusion, oxygen consumption increases and may require adjustment of flow by physiologic parameters. Titration of hypnotic drugs may be necessary to limit both oxygen consumption and vascular responses. Ultrafiltration during rewarming should aim to raise the hematocrit to 40%. Uniform rewarming to a bladder temperature of 36°C is necessary to avoid thermoregulatory metabolic responses after separation from CPB, which will be imposed at the most critical point for oxygen delivery. Additional targets include an SVR of about 12 Wood units and anesthetic and inotropic support at a steady state. Before separation from CPB, milrinone (50 μg/kg load plus infusion of 0.5 μg/kg/minute) is routinely used for inodilation (231). For additional inotropy, epinephrine in the 0.03 to 0.3 μg/kg/minute range is titrated to systolic function and heart rate (163,220). With pump flow of 3.2 L/m2/minute, an organ perfusion pressure of 40 mm Hg (mean arterial pressure [MAP] - central venous pressure [CVP]) is targeted while the systemic to pulmonary artery shunt is still occluded. This translates into an SVRI of 12 Wood units. Anesthetic depth is evaluated, but analgesic/hypnotic withdrawal is not used to raise SVR. Specifically, low-dose vapor or hypnotic infusion is maintained during rewarming, separation from CPB, and closure. If the SVR is low, as is typical with the use of phenoxybenzamine, norepinephrine is infused at 0.03 to 0.3 μg/kg/minute. If SVR is high, additional sedative/hypnotic, alpha-blockade, or, rarely, nitroprusside is administered. If phenoxybenzamine has been administered on CPB, then additional epinephrine often reduces SVR because of unopposed β-adrenergic activity in the face of α-adrenergic blockade.

Echocardiography

Echocardiography [Print Section] The diagnosis of HLHS can be readily made by two-dimensional echocardiography, with additional important hemodynamic information provided by Doppler echocardiography (75,89,90,91,92,93,94,95,96). The intracardiac anatomy and physiology should be investigated using a standard echocardiographic approach and should include multiple imaging views (long-axis, short-axis, apical four-chamber, subcostal coronal, subcostal sagittal, suprasternal notch) with repeated Doppler assessments.

Phenoxybenzamine

Effect of phenoxybenzamine on 48-hour SvO2 trend. Mean and 95% confidence intervals of SvO2 from neonates following the Norwood procedure with and without phenoxybenzamine. Phenoxybenzamine increases SvO2 and reduces variability. SvO2, systemic venous saturation. (Adapted from Tweddell JS, Hoffman GM, Fedderly RT, et al. Phenoxybenzamine improves systemic oxygen delivery following the Norwood procedure. Ann Thorac Surg 1999;67:161-168 , with permission.)

CPB

Effect of phenoxybenzamine on SaO2-SvO2 relationship. Real time (hourly) SaO2 and SvO2 values and best-fit polynomial equations in neonates after the Norwood procedure with and without phenoxybenzamine. The SaO2-SvO2 pattern in control patients reveals variable Qp/Qs and a systemic-to-pulmonary flow tradeoff at high SaO2; a critical peak of SvO2 occurs at an average SaO2 of 77%. In contrast, the SaO2-SvO2 relationship follows the pattern of variable total output and relatively constant Qp/Qs with phenoxybenzamine treatment, with no evidence of systemic-to-pulmonary flow tradeoff. However, individual SvO2 cannot be predicted from SaO2 in either group. Qp, pulmonary blood flow; Qs, systemic blood flow; SaO2, oxygen saturation; SvO2, systemic venous saturation. (Adapted from Hoffman GM, Tweddell JS, Ghanayem NS, et al. Relationship between arterial and venous saturation following the Norwood procedure: Sustained afterload reduction prevents hemodynamic deterioration at high arterial saturation. J Thorac Cardiovasc Surg 2004;127:738-745 , with permission.)

Phenoxybenzamine 4

Effect of phenoxybenzamine on SaO2-SvO2 relationship. Real time (hourly) SaO2 and SvO2 values and best-fit polynomial equations in neonates after the Norwood procedure with and without phenoxybenzamine. The SaO2-SvO2 pattern in control patients reveals variable Qp/Qs and a systemic-to-pulmonary flow tradeoff at high SaO2; a critical peak of SvO2 occurs at an average SaO2 of 77%. In contrast, the SaO2-SvO2 relationship follows the pattern of variable total output and relatively constant Qp/Qs with phenoxybenzamine treatment, with no evidence of systemic-to-pulmonary flow tradeoff. However, individual SvO2 cannot be predicted from SaO2 in either group. Qp, pulmonary blood flow; Qs, systemic blood flow; SaO2, oxygen saturation; SvO2, systemic venous saturation. (Adapted from Hoffman GM, Tweddell JS, Ghanayem NS, et al. Relationship between arterial and venous saturation following the Norwood procedure: Sustained afterload reduction prevents hemodynamic deterioration at high arterial saturation. J Thorac Cardiovasc Surg 2004;127:738-745 , with permission.)

Phenoxybenzamine 2

Effect of phenoxybenzamine on SvO2-blood pressure relationship. Real-time (hourly) values of SvO2 and mean arterial blood pressure and linear fit equations from neonates after the Norwood operation. In neonates managed without phenoxybenzamine, blood pressure and systemic oxygen delivery are inversely related because blood pressure is determined mainly by systemic vascular resistance (SVR). In neonates who received phenoxybenzamine, blood pressure and oxygen delivery are positively related because blood pressure is determined mainly by cardiac output and SVR remains relatively constant. SvO2, systemic venous saturation. (Adapted from Tweddell JS, Hoffman GM, Fedderly RT, et al. Phenoxybenzamine improves systemic oxygen delivery following the Norwood procedure. Ann Thorac Surg 1999;67:161-168 , with permission.)

Fetal Intervention

Fetal Intervention [Print Section] It is important to remember that most fetuses with severe left ventricular outflow tract obstruction will survive gestation. Therefore, fetal cardiac intervention in this setting does not serve as a lifesaving procedure, but rather a procedure that may improve postnatal surgical options. More specifically, it is hoped that successful intervention in the fetus with left ventricular outflow tract obstruction (LVOTO) will lead to a biventricular circulation at the time of birth. This possible benefit must be weighed against the risks of the procedure, which, even in the setting of technical success, may result in fetal death or extreme prematurity. Since the risk/benefit ratio of fetal cardiac intervention in the setting of severe LVOTO is presently unknown, it is not surprising that these procedures are not universally accepted. Some centers have advocated fetal cardiac intervention only when it is felt to be a lifesaving procedure, such as in the setting of critical aortic stenosis with fetal hydrops. In the year 2000, Kohl et al. (50) reported the world experience of fetal aortic balloon valvuloplasty. The small early clinical experience (n = 12), was quite poor, with only one "long-term" survivor. More encouraging data were recently reported by Lock (51) at the 2005 World Congress of Pediatric Cardiology and Cardiac Surgery meetings. As part of an innovative protocol at the Children's Hospital of Boston and the Brigham and Women's Hospital, fetal aortic valvuloplasty was offered to 40 mothers whose fetuses had aortic stenosis and were thought to be at risk for the development of HLHS. Thirty-four fetuses underwent aortic valvuloplasty, with technical success in 27. Fetal complications included in utero death, death related to prematurity, bradycardia, and pericardial effusion. Maternal complications were rare, although the procedure itself required laparotomy in 50% of mothers. Of the 22 liveborn infants status postvalvuloplasty, 6 had a biventricular circulation and 16 had HLHS. The authors described a learning curve, with a significant improvement in technical success since September 2003. These preliminary data support the hypothesis that some forms of HLHS may be preventable with in utero intervention. In utero therapy for HLHS with a severely restrictive or intact atrial septum has also been described. Although technical successes have been reported, there has been no significant clinical impact, with continued significant mortality after Norwood palliation (52,53,54). Anatomy [Print Section] Various cardiac malformations characterized by variable degrees of underdevelopment of the left ventricular cavity are referred to as HLHS. Most broadly, HLHS includes any number of lesions with a dominant right ventricle and systemic outflow obstruction that are not amenable to two-ventricle repair. Underdevelopment of the Left Ventricle Outflow-Aorta Complex [Print Section] Underdevelopment of the left ventricle-aorta complex, resulting in critical aortic valve stenosis or aortic valve atresia with an intact ventricular septum is the most recognized form of HLHS (55,56,57) (Fig. 50.2). A spectrum of abnormalities includes aortic valve atresia with mitral atresia, aortic valve atresia with a patent mitral valve, and aortic stenosis with a patent mitral valve. This final group with aortic stenosis and a patent mitral valve blends smoothly into critical aortic stenosis. The general unifying etiologic explanation is that the growth and development of vascular structures are dependent to some degree on the relative quantity of blood flow during fetal development. As mentioned earlier, fetal echocardiographic observations have confirmed the progression from aortic stenosis to HLHS (31). In addition to these observations, supporting data for underdevelopment of the left ventricle outflow-aortic complex as the inciting event are provided by the fact that with an intact P.1008 ventricular septum, additional lesions, particularly mitral valve hypoplasia, are always less severe than the degree of left ventricular outflow obstruction (58). The ascending aorta is hypoplastic; among patients undergoing surgery for HLHS, the mean aortic diameter was 3.3 ± 1.7 mm; 40% to 55% of patients had an ascending aorta of <2 mm (59,60). Blood flow in the arch is retrograde, and in aortic atresia, the ascending aorta serves only as a conduit for the retrograde flow of blood into the coronary arteries. A localized coarctation of the aorta is present in 80% of patients (9,61). Aortic stenosis with mitral stenosis makes up 23% to 26% of patients undergoing stage 1 palliation, whereas 36% to 46% have aortic atresia with mitral atresia and 20% to 29% have aortic atresia with a patent mitral valve (62,63,64).

HLHS: Epidemiology and Genetics

Epidemiology and Genetics [Print Section] Hypoplastic left heart syndrome (HLHS) makes up 1.4% to 3.8% of congenital heart disease. Despite its low incidence, 0.016% to 0.036% of live births, HLHS causes 23% of cardiac deaths during the first week of life and 15% of cardiac deaths within the first month of life (1,2,3,4,5,6). A male predominance has been reported for HLHS (55% to 67%) (1,2,7,8,9). The recurrence risk in families with one affected child is 0.5% to 2%. Additionally, the recurrence risk for other forms of congenital heart disease in families with one affected child with HLHS is 2.2% to 13.5% (10,11,12). Although a multifactorial mode of inheritance is likely, the recurrence risk among siblings suggests transmission via an autosomal recessive mode. In addition, pedigree analyses have demonstrated a 12% prevalence of cardiac abnormalities involving the left ventricular outflow tract in first-degree relatives of patients with HLHS (13). Lewin et al. (14) studied 278 first-degree relatives of 113 patients with nonsyndromic left ventricular outflow obstruction and found that 4.6% had a bicuspid aortic valve; an additional 11.5% of relatives had anomalies of the aorta, aortic valve, left ventricle, or mitral valve. P.1006 Extracardiac anomalies and genetic syndromes have been recognized in patients with HLHS with a reported incidence of 15% to 30% (15,16,17,18). Identified syndromes include Turner syndrome, Noonan syndrome, Smith-Lemli-Opitz syndrome, Holt-Oram syndrome, Ellis-van Creveld syndrome, oral-digital-facial syndrome and CHARGE syndrome (1,19,20,21,22,23,24,25). Additionally, several chromosomal abnormalities have been identified in patients with HLHS, including trisomy 13, trisomy 18, trisomy 21, duplication of short arm of chromosome 12, 2q-, a balanced 3:7 translocation, 4q-, 4p-, 7q-, 11q-, duplication of 16q and 18p- (1,24,26). Recognized extracardiac abnormalities associated with HLHS include congenital diaphragmatic hernia, duodenal atresia, biliary atresia, malrotation, omphalocele, and cystic fibrosis. Ongoing research in the area of molecular genetics may allow a better understanding of the causes of HLHS. Mutations in the signaling and transcription regulator, NOTCH1, have been noted to cause an early developmental defect in the aortic valve in mice (27). The discovery of isolated mutations in genes such as the dHAND gene or the HRT1 and HRT2 genes and their involvement in downstream NOTCH signaling and cardiac gene expression have been implicated in familial forms of HLHS (28,29,30). These studies suggest that proteins such as the HRT proteins may regulate specific sets of cardiac genes by modulating the function of cardiac transcriptional activators in a signal-dependent manner. Future work in the area of molecular genetics, along with large population registry information, may allow determination of the cause of HLHS and prevention.

Forms of HLHS with VSD

Forms of Hypoplastic Left Heart Syndrome with a Ventriclular Septal Defect [Print Section] There are various forms of HLHS that have in common a ventricular septal defect. This may include forms that otherwise resemble those described above except that they have a ventricular septal defect that can be in any part of the septum. If these defects are small, the cause and development of HLHS may not be significantly different than in patients with HLHS and an intact septum. In this group, mitral atresia with a patent left ventricular outflow may be present and suggests that inflow obstruction may be the source of development of HLHS. Within this group are forms of double-outlet right ventricle including double-outlet right ventricle with mitral atresia without obstruction to aortic outflow and unbalanced endocardial cushion defects. Although this latter group could arguably be placed outside HLHS, there are forms with undeniable hypoplasia of the left ventricle. Additional Anatomic Considerations [Print Section] Abnormalities of systemic venous return are uncommon in the patient with HLHS. Persistent left superior vena cava (SVC) P.1010 occurs in <5% (8,57). Abnormal pulmonary venous connection or drainage occurs in 5% of patients (75). Anomalous pulmonary venous connection may occur with an intact atrial septum or severely restrictive atrial septal defect. Frequently there is a persistent levocardinal vein that drains to the innominate vein (76). Rare cases of anomalous pulmonary venous connection directly to the right atrium also exist. Important coronary abnormalities are rare. Anomalous origin of either of the coronary arteries from the right pulmonary artery has been described (77,78,79,80). Coronary-cameral fistulas have been observed in patients with aortic atresia and a patent mitral valve. Additionally, patients with aortic atresia and a patent mitral valve have been observed to have tortuous epicardial coronaries with increased medial thickness (81). Despite the origin of the coronary arteries from the small ascending aorta, the coronary ostia and proximal coronary artery calibers are normal (82). Premature closure of the patent foramen ovale has been postulated as a cause of HLHS. Because the foramen ovale is the source of left ventricular preload in the fetus, one would expect that closure of the foramen ovale would starve the left ventricle of preload and result in hypoplasia. Premature closure of the foramen ovale may also occur as a secondary event to left ventricular outflow obstruction. As mentioned earlier, LVOTO will result in increased left atrial pressure, and increased left atrial pressure results in apposition of the fossa ovalis flap valve against the septum secundum. Premature closure or restriction of the foramen ovale might occur along with LVOTO and contribute to development of HLHS. Among patients with an intact ventricular septum, premature closure of the foramen ovale was associated with endocardial fibroelastosis and indicates that LVOTO with elevated left ventricular end-diastolic pressure and subendocardial ischemia was present (83). Among patients with premature foraminal closure and a ventricular septal defect, fibroelastosis was absent, indicating that premature closure was perhaps a primary event in the development of left ventricular hypoplasia.

Glenn and Fontan

In patients with hypoplastic left heart syndrome, all cardiac output is ejected to the pulmonary artery. Systemic output is dependent on flow from the pulmonary trunk to the aorta by way of the ductus. Although the ductus is open, pulmonary blood flow is increased and the heart may be enlarged. Oxygen therapy may worsen pulmonary overcirculation and steal flow from the aorta. This lesion is an admixture lesion. All venous return mixes in the right ventricle. Qp/Qs determines arterial saturation, so patients with this lesion are seldom markedly desaturated at birth. On ductus closure, shock ensues. The heart dilates, and pulmonary overcirculation may worsen despite severe acidosis. In an occasional patient, the foramen ovale is small and obstructs pulmonary venous return, causing pulmonary edema and severe desaturation.

interstage monitoring

Initiation of interstage monitoring in September 2000 marked another milestone in the palliation of HLHS with improved interstage survival from 84% to 99% in a cohort of 139 patients who underwent stage 1 palliation with 95% early survival. Just over half of the monitored patients breached surveillance criteria with most patients presenting before 100 days of age. Worsening hypoxemia was the most common reason parents sought medical care. Shunt stenosis, outgrowth of the shunt, and innominate artery narrowing represented the cardiac diagnoses that led to interstage hypoxemia. Extracardiac causes of desaturation from baseline included viral illness, anemia, and dehydration. Isolated inappropriate weight change or generally poor weight gain occurred in a third of patients who breached surveillance criteria and was the result of recurrent arch obstruction, sepsis, poor oral intake necessitating gastrostomy tube placement, failure to adequately adjust gastrostomy tube feeds for weight gain, or progressive heart failure (205).

HLHS Interstage death

Interstage Management and the Timing of Stage 2 Palliation [Print Section] After recovery from stage 1 palliation, acute care is transitioned to chronic therapies that allow preservation of organ function and somatic growth. As such, interstage management should include pharmacologic therapy targeted at optimizing the inefficient parallel circulation inherent to HLHS after stage 1 palliation, vigilant monitoring of physiologic variances as a means to identify destabilizing pathology, and ensuring adequate nutrition and somatic growth. Prescribed Medical Therapy Pharmacologic therapy between stages 1 and 2 palliation remains variable among institutions and potentially includes chronic afterload reduction, diuretics, and/or digoxin for support of the cardiovascular system, and anticoagulation. At our institution, chronic afterload reduction with an angiotensin-converting enzyme (ACE) inhibitor is introduced in patients who have a pulmonary-to-systemic flow ratio (Qp/Qs) >2 in the early postoperative period, greater than mild atrioventricular valve insufficiency, evidence of congestive heart failure, or noninvasive evidence of elevated SVR. If SVR is suboptimally controlled with ACE-inhibitor therapy, we add transdermal clonidine to the regimen. Afterload reduction is titrated with caution to avoid worsening hypoxia from excessive lowering of the Qp/Qs ratio and diastolic hypotension that could result in impaired coronary flow. For patients with evidence of pulmonary overcirculation or heart failure, chronic diuretic therapy with furosemide is prescribed. Caution is taken to avoid intravascular volume depletion that might reduce total cardiac output as well as increase the risk of shunt thrombosis owing to hyperviscosisty. Prophylactic antiplatelet therapy with aspirin 20 mg daily is uniformly administered to our patients unless there is evidence of atrial or venous clot, at which time subcutaneous low-molecular-weight heparin is prescribed with a therapeutic goal of 0.7 to 1.2 anti-Xa IU/mL. Finally, patients at our institution are expected to maintain SaO2 >80% while awake and asleep, and if unable to do so, are placed on supplemental oxygen via nasal cannula. Any one of these prescribed therapies will likely require outpatient adjustments during the interstage period. Risk Factors for Interstage Death The limited circulatory reserve inherent in a volume-loaded single ventricle with parallel circulation and cyanosis places the infant with HLHS at risk for late morbidity and mortality. The incidence of sudden death in the interstage period has remained fairly constant at approximately 5% to 15% and does not seem to have been eliminated despite the introduction of perioperative surgical, medical, and monitoring strategies that have dramatically improved early inpatient survival (62,173,208,249). Multiple risk factors and causes have been proposed for interstage death. Escalated risk of interstage mortality has been linked to anatomic diagnosis and residual or recurrent lesions. Specifically, the diagnosis of aortic atresia with a di-minutive ascending aorta represents an anatomic subtype of HLHS presumably with the lowest physiologic reserve and has been associated with an increased risk of late death (198,217,250). The presence of a restrictive atrial communication, arch obstruction, obstructed shunt flow, pulmonary artery distortion, and atrioventricular valve insufficiency have also been associated with interstage mortality (194,196). Commonly P.1025 acquired childhood gastrointestinal or respiratory diseases that result in hypovolemia and/or acute hypoxemia have also been implicated as causes for interstage death (60,196). After successful stage 1 palliation, any of the above-mentioned pathologic processes can lead to increased metabolic demands and an unfavorable oxygen supply/demand relationship, placing the infant with minimal myocardial reserve at even greater risk for mortality until progression to cavopulmonary anastomosis. Therefore, transitioning infants to home after stage 1 palliation warrants ongoing vigilance well beyond the initial early postoperative period and requires continued collaboration among caregivers, including parents. Interstage Monitoring To improve late outcomes, we developed an interstage monitoring program of SaO2 and weight designed for home use as a means to identify modifiable risk factors that might fatally tax the inefficient circulation intrinsic to HLHS after stage 1 palliation (60). The monitoring program was based on the hypothesis that earlier recognition of decreased SaO2 from baseline, poor weight gain, or weight loss might foretell the presence of serious anatomic lesions or a developing intercurrent illness and subsequently allow for lifesaving intervention during the interstage period. In infants with HLHS after stage 1 palliation, arterial desaturation from baseline might be indicative of anemia, respiratory illness, and myocardial dysfunction resulting from falling cardiac output, or limited pulmonary blood flow from shunt stenosis or outgrowth. Hypoxemia alone, however, might not occur early in an acute illness that results in elevation in SVR, with consequent reduced systemic flow and increased Qp/Qs. Specifically, dehydration that results in hypovolemic shock from increased fluid loss as seen with gastroenteritis or decreased intake might mimic such a clinical scenario and be reflected only by failure to have expected weight gain or even weight loss. To detect acute hypoxemia, dehydration, or growth failure between stages 1 and 2 palliation, patients are discharged home with a digital infant scale and pulse oximeter as part of an interstage monitoring program, and parents obtain daily weights and oxygen saturations. Criteria for which parents are instructed to notify a member of the cardiac team are SaO2 <75% or >90%, weight loss of 30 grams, failure to gain 20 grams of weight over 3 days, or enteral intake <100 mL/kg/day. Breach of criteria prompts investigation to rule out an intercurrent illness or anatomic lesion as the cause of physiologic variance.

Interstage growth

Interstage growth among survivors of the stage 1 palliation calculated using >1,400 observations of weights. The regression line and 95% confidence intervals are indicated. Normal growth is depicted in the shaded area, with the dashed line representing 50% for age. The curve indicates the limited growth potential of the patient following the first stage of palliation. In this group of patients, growth into later infancy is limited, unlike a normal infant whose continued growth is expected. From Ghanayem NS, Tweddell JS, Hoffman GM, et al. Optimal timing of the second stage of palliation for hypoplastic left heart syndrome facilitated through home monitoring, and the results of early cavopulmonary anastomosis. Cardiol Young 2006;16(Suppll):61-66 , with permission.

Late Concerns

Late Fontan Concerns [Print Section] Staged palliation for single ventricle physiology has undergone a series of surgical revisions that have reduced early postoperative Fontan mortality from 20% to <2% (270,271). In late follow-up studies, 11% of Fontan survivors were found to have clinically significant morbidity including atrial dysrhythmias, protein-losing enteropathy (PLE), liver dysfunction, congestive heart failure, progressive ventricular dysfunction, or stroke at a median age of 8 years (range 1 to 25 years). Despite the significant morbidities associated with the Fontan operation, overall late mortality (range 4 months to 18 years) continues to decrease from 25% in the early experience to 5% in the recent era (271,272). Although long-term outcome data are sparse for isolated HLHS, when compared with other single-ventricle lesions with Fontan circulation, late mortality is comparable regardless of ventricle morphology (103,273). Over the recent decades, indications for successful Fontan have been modified from the initial "Ten Commandments" described by Choussat and Fontan (274). From this list, specific physiologic risk factors for a failing Fontan prevail and relate to ventricular performance, atrioventricular and aortic valve function, and pulmonary circulation (275). Small pulmonary artery size, PVR >4 Wood units, preoperative pulmonary artery pressure >15 mm Hg, or the presence of venovenous collaterals constitute a high-risk group of patients (272,276). Additionally, more complex anatomy that requires main pulmonary artery-to-ascending aorta anastomoses or ventricular septal defect enlargement, both indicators of ventricular outflow obstruction, have been identified as risk factors for late morbidity. Ventricular Dysfunction Volume unloading provided by staged palliation results in reduction in ventricular size and wall thickness that in turn increases contractility and ventricular performance. Ventricular dilation, however, may persist in some patients owing to early volume overload, as well the presence of aortopulmonary collaterals that are common in patients with chronic cyanosis. Regardless of the early success with staged palliation, late ventricular dysfunction after the Fontan operation may ensue because of morphologic/structural features of the single right (systemic) ventricle, residual obstructive lesions, and/or atrioventricular valve insufficiency. The failing systemic ventricle after staged palliation can be attributed to systolic dysfunction, diastolic dysfunction, or both (276,277,278,279). Systolic dysfunction is characterized by reduced contractility and an ejection fraction of <50%. Diastolic dysfunction is more difficult to define, but is evident by increased ventricular end-diastolic pressure and the rate of ventricular relaxation (280,281). As a result, late ventricular dysfunction and subsequent failure of Fontan circulation become clinically evident with symptoms of lower functional class, exercise intolerance, dyspnea, fatigue, and syncope (282,283). Hypoxemia Slight hypoxemia with SaO2 in the low 90s is common after Fontan completion even when residual atrial level shunts are absent (275,284). This desaturation is thought to result from coronary sinus blood return to the pulmonary venous atrium, arteriovenous shunts, or ventilation/perfusion imbalances within the lung. Desaturation also commonly occurs in patients with residual anatomic shunts such as persistent atrial level shunt or acquired collateral circulation within the lung. In a study by Triedman et al. (285) in which the prevalence and risk factors for aortopulmonary collateral vessels were assessed, collateral vessels were present in more than one third of patients who underwent either a bidirectional cavopulmonary anastomosis or Fontan procedure, and were most prevalent in patients with a history of a Blalock-Thomas-Taussig shunt. Most collateral vessels originated from the internal mammary arteries and thyrocervical trunk, with fewer vessels originating from the brachiocephalic vessels (285). Venovenous collaterals that drain directly into the left atrium or pulmonary venous circulation can also serve as a source of arterial desaturation after Fontan palliation. The collateral circulation that forms after Fontan palliation plays no role in gas exchange, produces right-to-left intrapulmonary shunts, and might contribute to progressive ventricular dysfunction as a source of chronic volume overload (286). Hence, the impact of intrapulmonary collateral circulation on oxygen saturation is variable but is often most pronounced in the presence of progressive ventricular dysfunction. Protein-Losing Enteropathy Protein-losing enteropathy, a phenomenon of hypoalbuminemia through intestinal protein loss, occurs in 3% to 15% of patients with Fontan circulation and has a reported mortality as high as 30% at 2 years and 50% at 5 years after diagnosis (287,288,289). Onset of PLE can be as early as 1 month to nearly two decades after Fontan palliation but occurs most commonly 2 to 3 years following the Fontan procedure (290). The pathogenesis of PLE remains elusive despite increased understanding of univentricular physiology. Chronically elevated systemic venous/right atrial pressures with subsequent increased IVC and portal vein pressures have been implicated as the primary cause of PLE. This elevation in abdominal venous pressures presumably leads to intestinal congestion, lymphatic obstruction, and enteric protein loss (90). Diastolic dysfunction that results in low cardiac output in the face of elevated venous pressures, or even with venous pressures considered normal for Fontan physiology (<15 mm Hg), predisposes the patient to P.1029 mesenteric ischemia and subsequent intestinal mucosal injury leading to the onset of enteric protein losses (275,290). Finally, inflammation owing to infection or unexplained causes can result in epithelial membrane injury that may result in PLE despite the absence of hemodynamic derangements (291,292,293). In a large retrospective multicenter study that included >3,000 patients with Fontan circulation in whom the incidence of PLE was 3.7%, ventricular anatomy other than dominant left ventricle and an elevated preoperative ventricular end-diastolic pressure were risk factors for the development of PLE (290). Other large single-center studies have confirmed these findings but also identified heterotaxy, polysplenia, anomalies of systemic venous drainage, increased pulmonary arteriolar resistance, and longer CPB time at Fontan palliation as risk factors for the development of PLE (275,287,288). Thromboembolism Patients with Fontan circulation have a lifelong risk of thromboembolic complications, particularly stroke and pulmonary embolism. In a large series by Coon et al. (294), the reported prevalence of thrombus formation as detected by transthoracic echocardiography was 8.8% with most thrombi detected within the first year of Fontan palliation (mean 2.3 months, range 1 day to 163 months). In a smaller series, the diagnosis of thrombus formation was more common with transesophageal echo with a reported prevalence of 17% to 30% (295). The high rate of thrombus formation is postulated to be predominately secondary to venous stasis and impaired cardiac output that is inherent to single-ventricle circulation. No difference has been observed between patients who received a lateral tunnel or those who received an atriopulmonary Fontan (294). Several studies report the presence of arrhythmias at the time of thrombus detection (294,295,295,296,297). Finally, liver dysfunction and coagulation factor deficiency, particularly protein C deficiency, have been identified in patients who were thought to have good outcomes after the Fontan operation. These appear to be time-related phenomena that resolve (298,299). Arrhythmias Late atrial arrhythmias have a reported incidence of 10% to 45% in patients with Fontan physiology (272,275,281,282,300). Sinus node dysfunction, presence of atrial suture lines, and increased atrial pressure have all been implicated in the etiology of late arrhythmias. In recent years, the surgical approach for the Fontan has been modified from the lateral tunnel to the extracardiac Fontan with the goal of reducing the incidence of atrial arrhythmias. The extracardiac Fontan has theoretic advantages in achieving this objective as this approach minimizes atrial suture lines and lessens the atrial hypertension that is expected with the lateral tunnel Fontan. Several series have reported this outcome with a decreased incidence of atrial tachyarrhythmias or pacemaker insertion for sinus node dysfunction in patients who underwent the extracardiac Fontan when compared with lateral tunnel Fontan patients (260,301,302). Conversely, Cohen et al. (262) reported no early benefit with either approach after the Fontan operation.

Parallel Circulation

Monitoring the Parallel Circulation [Print Section] The first successful approaches to monitoring and managing the patient with HLHS emphasized the central importance of SaO2 in detecting and guiding treatment of unbalanced pulmonary-to-systemic blood flow ratio and total cardiac output (161). Generalization of this approach was based on circulatory models that assumed either a constant arteriovenous oxygen difference (of typically 25%) or a constant mixed SvO2 (of typically 50%). In either model, an SaO2 of 75% would then result from mixing equal parts systemic venous and (fully saturated) pulmonary venous blood; deviations of SaO2 from 75% in these models would result from, and be diagnostic of, deviations of Qp/Qs from 1. These approaches also assumed adequate total cardiac output to meet oxygen delivery needs if Qp/Qs is optimized. Under these conditions, systemic oxygen delivery generally increases as SaO2 approaches 75% to 80% and falls at higher saturation owing to increasing Qp/Qs imbalance. However, in the perioperative period, total cardiac output and metabolic demand may frequently be mismatched as a result of the inherent instability of parallel circulation as described above, and variability of Qp/Qs, Qt, and VO2 occurs (162,163,164). Inspection of Table 50.1 reveals that assertions about the Qp/Qs from a single measured SaO2 value are unreliable unless either SvO2, or VO2 and Qt, are known. A target SaO2 of 75% can result from a range of Qp/Qs and SvO2 conditions, which may include inadequate systemic flow if Qt or VO2 is variable. In a circulatory model that allows for variation in both total cardiac output and Qp/Qs, a wide range of tissue/venous saturation can result at any given SaO2, shown graphically in Figure 50.12. The resulting domain of SvO2 shows that severely impaired systemic oxygen delivery can occur with SaO2 closely maintained in the target 75% to 80% range.

...

Multichannel recording of early intensive care unit (ICU) course after Norwood procedure without phenoxybenzamine, showing severe deterioration in systemic oxygen delivery without significant changes in other conventionally monitored parameters. Continuously recorded data are from a single neonate arriving in the ICU after the Norwood procedure, performed without phenoxybenzamine. A life-threatening hemodynamic deterioration is clearly shown with SvO2 monitoring despite SaO2 in the 75% to 80% range. An initial deterioration in SvO2 (arrow a) was partially corrected with additional analgesia (arrow b) but did not prevent a subsequent critical deterioration in systemic oxygen delivery (arrow e), which was effectively treated with a combination of additional analgesia/anesthesia and increased inotropic and vasodilator infusions. Conventional parameters (arterial blood pressure and SaO2) show only subtle changes that provide neither an early warning of the critical situation nor feedback about the effectiveness of corrective measures. ART, mean arterial blood pressure; FiO2, fraction of inspired oxygen; PetCO2, end-tidal carbon dioxide; SaO2, arterial saturation; SvO2, systemic venous saturation. Reprinted from Hoffman GM and Stuth EA. Hypoplastic left heart syndrome in Pediatric Cardiac Anesthesia, 4th ed., Eds. Lake CL and Booker PD. 2005. With kind permission of Lippincott Williams & Wilkins.

Neurodevelopmental Outcomes

Neurodevelopmental Outcomes and Quality of Life [Print Section] Relative to other forms of congenital heart disease, the diagnosis of HLHS may impose one of the highest risks of neurodevelopmental and behavioral abnormalities for survivors of this complex lesion. Neurologic outcomes are influenced by congenital anomalies as well as preoperative, perioperative, and long-term risk factors. The collective effect of the multiple risks faced by subjects with HLHS results in a complex, multifactorial impact on development (321). Some factors known to impact neurodevelopment such as congenital brain anomalies or intrauterine brain injury (15,322,323,324,325), genetic syndromes and polymorphisms (326,327), prenatal versus postnatal diagnosis (328), socioeconomic status, and parental achievement (329,330) are not modifiable. Nevertheless, they should be taken into consideration when counseling parents or investigating the causes of an identified delay. Neurocognitive disorders in patients with uncorrected cyanotic heart disease and neurologic injury following deep hypothermic circulatory arrest (DHCA) point to the vulnerability of brain to both global and focal ischemia (331). Pathologic evidence of neurologic injury in HLHS has been associated with hypoglycemia and hypoxia but not hypercarbia or acidosis (16). Recently implemented strategic approaches to care for infants and children with HLHS may have a positive influence on factors such as hemodynamic stability before, during, and after surgery (169,177,229,332,333); perioperative neuroprotection (229,334); reduction of seizures and embolic events (335); and the effects of CPB (222,336,337,338,339). These may result in a cumulative reduction of neurologic risk. Treatment modalities for HLHS have evolved dramatically in a relatively short period of time, making it difficult to generalize conclusions from historical cohorts to today's patients. It is hoped that today's vastly improved understanding of the physiology of HLHS, optimal treatment choices, and reduction of the overall profile of risk for these patients will result in improved long-term neurodevelopmental outcomes for infants with HLHS born today. Early studies of neurodevelopmental outcomes in children with HLHS demonstrated major delays in multiple areas of functioning and raised awareness of the importance of long-term monitoring in this population (340,341). More recently, research has demonstrated that children with HLHS often demonstrate overall IQ within the low range of normal but that they manifest important delays in visual-motor integration, executive functioning, and motor development as well as a higher than expected incidence of behavioral abnormalities, particularly attention deficits (329,330,335,341,342,343,344,345). IQ alone does not fully represent the spectrum of outcomes in this patient group, increasing the importance of multidisciplinary follow-up. A range of outcomes for children with HLHS has been reported in the literature. In the study by Mahle et al. (335) of school-aged children with HLHS, 79% of parents rated their child's health as good to excellent. Eighty-eight percent reported minimal activity limitations, and 84% rated school performance as average or above average. Despite these encouraging parental perceptions, one third of these children were receiving special education services and the median full-scale IQ was 86 with 18% of subjects demonstrating mental retardation (IQ <70). Goldberg et al. (330) found that neurodevelopmental outcomes for Fontan patients were within the normal range; however, children with HLHS demonstrated lower overall intelligence, verbal scale and performance scale scores than non-HLHS patients (93.8, 98.9, and 89.7 vs. 107, 110, and 101.9, respectively). Scores for adaptive behavior and behavior problems did not differ between HLHS and non-HLHS subgroups. Ikle et al. (315) reported very similar neurodevelopmental outcomes for children with HLHS who were treated with cardiac transplantation between 1993 and 1998. In this study, subjects had a median overall IQ of 89. Longer waiting time prior to transplantation was found to have a negative effect on later neurocognitive outcomes. Mahle et al. (346) have recently confirmed these findings in a multicenter study. Surgical approaches, staged palliation versus transplantation, were not associated with any measure of developmental outcome in a group of 47 school-aged children representing four institutions. For the entire cohort, mean full-scale IQ was 86 ± 14. Lower full-scale IQ, verbal, and math performance was associated with longer hospital stay at the time of initial surgery. Wernovsky and Newburger (347) postulated that these similar findings, despite dramatically different treatment strategies, are evidence of the important impact of genetic factors, congenital brain abnormalities, and insults incurred during the preoperative and perioperative period for which these children are at risk despite the treatment method chosen. Hoffman et al. (245) demonstrated a significant relationship between SvO2 in the first 48 hours following the Norwood procedure and developmental and behavioral outcomes in children with HLHS assessed at 4.5 years of age. Postoperative SvO2 values of <40% were independently associated with poorer developmental outcomes. In a multivariate model, SvO2, circulatory arrest time, CO2 tension, and mean arterial blood pressure accounted for 79% of the variation in the outcome measures assessed. These studies have evaluated children at multiple different ages and stages of repair. Generalization to today's child undergoing care for HLHS is difficult; however, these preliminary data emphasize the need for comprehensive follow-up and evaluation of developmental progress for these subjects. Further multicenter research involving thorough longitudinal assessment of children with HLHS is needed to better understand neurodevelopmental risks and to optimize outcomes for these children. Several important studies including those of the Pediatric Heart Network, the Congenital Heart Surgeons Society, the Pediatric Heart Transplant Study Group, and individual investigators are carefully examining outcomes for the modern cohort of children with HLHS. Their findings will serve as a guide for future care and provide important information for counseling children, families, educators, and other health care practitioners. The intensive focus on improving outcomes for children with HLHS has allowed our specialty to begin to look beyond survival at some of the long-term psychosocial implications of this complex congenital heart disease. In 1996, Caplan et al. (348) P.1031 reported the results of a survey on the management of HLHS in 93 neonatology sections across the United States. At that time, 36% offered comfort care only, 26% offered surgery only, using either staged palliation or cardiac transplant, and 38% offered both surgery and comfort care. Responders cited the lack of long-term outcome data on quality of life (QOL) for survivors as one of the major reasons for the lack of a unified approach and the continued use of a "no treatment" option. While there is much yet to be learned, there is increasing awareness about QOL, functional outcomes, and impact on the families of children living with HLHS. Children and families living with HLHS experience a roller coaster of uncertainty about long-term prognosis, chronic medication use, persistent symptoms, the prospect of developmental delay, and repeated interventions. It would be inappropriate to propose that the combination of these factors has no impact on QOL. However, it is equally wrong to assume that bad outcomes are inevitable. QOL is a highly subjective, multidimensional concept that includes not only the impact of disease but also personal perceptions, expectations, satisfaction, and other factors (349,350). Although cultural differences in approaches to care for HLHS exist (351), health care professionals universally hope that patients realize quality of life versus quantity alone. The definition of quality, however, can be provided only by the children and families living the experience. It has been demonstrated repeatedly in congenital heart disease and other pediatric chronic illnesses that severity of illness is not a reliable predictor of QOL (352,353,354). It cannot be assumed that children with HLHS will experience a poor quality of life. Access to large cohorts of survivors of HLHS has been limited; therefore, few studies have examined psychosocial outcomes in this population exclusively. However, several studies have addressed these outcomes in groups representing survivors of various forms of single-ventricle heart disease. In studies by Casey et al. (355,356) of 26 children with various single-ventricle lesions, it was found that 80% of parents underestimated the exercise tolerance of their children. Parents reported their children to have more social problems and decreased activities, and to be more withdrawn than healthy children. Teachers also reported single-ventricle children to be more withdrawn in the classroom setting. The physical symptoms most commonly reported included breathlessness, a high rate of respiratory infections, and leg cramps. Sixty-five percent of these children were attending full-time school, and 27% attended half-time or more. School adjustment in the children was found to be significantly related to both family strain and exercise tolerance. The impact of the child's chronic condition on the family appeared to be a more important predictor of behavioral adjustment than the symptoms the children experienced. Saliba et al. (357) examined adults with single-ventricle heart disease ranging in age from 17 to 49 years and found that reported QOL was similar to that of healthy controls. Younger patients in the sample reported better overall QOL. In a study focusing exclusively on children with HLHS, Williams et al. (358) reported a cross-sectional evaluation of the impact of HLHS in children at various stages of surgical palliation. QOL was rated as normal after stage 1 surgery; however, the lowest QOL reports were in children following stage 2 palliation. QOL was not related to the degree of developmental delay identified; however, longer circulatory arrest times were found to have a negative impact on QOL indicators. The authors speculated that differences in parental expectations during early childhood may account for these different responses. QOL, functional status, and impact on the family were evaluated in a cohort of 55 children with single-ventricle heart disease including 29 with HLHS at a mean age of 6 years (359). Parents reported QOL that was significantly lower than a healthy normative sample for overall, physical, social, and school functioning. Emotional functioning was rated the same as healthy controls. Reports of QOL for children with single-ventricle heart disease were equal or better in all of the domains assessed in contrast to a normative sample of children with other chronic illnesses such as diabetes, arthritis, and limb deficiencies. QOL scores were not found to be correlated with gender, socioeconomic status, total number of operations, or time since surgery. There was, however, a negative correlation between age and QOL scores. Functional status in the domains of physical activity, pain, emotional function, and school function demonstrated moderate positive correlations with overall QOL (r = 0.33 to 0.39, p <0.05). Impact on the family was rated as less than that reported by a normative sample of mothers of children with chronic illness (p <0.05). The perception of negative impact overall and in the areas of financial, social, personal strain, and siblings was significantly correlated with lower QOL (r = -0.26 to -0.58, p <0.05). The Pediatric Heart Network recently reported outcomes of a cross-sectional study of 544 children with Fontan physiology in which QOL, heart rhythm, exercise tolerance, and data on other physical morbidities were collected (360,361,362). It was theorized that QOL may provide a proxy indicator of physical function. The study identified scores for quality of physical health that were approximately one standard deviation below normal and scores for psychosocial health that were one-half standard deviation lower than normative values for the Child Health Questionnaire. QOL in these Fontan survivors was less than that of healthy children; however, it was clearly influenced by multiple factors, not only those related to medical outcomes. These findings once again emphasize the inherent disconnect between physiologic variables and subjective variables such as QOL.

...

Nutritional Support and Somatic Growth Scrutiny of weight change during early infancy provided invaluable somatic growth data for this patient population. From >1,400 patient weight observations, a growth curve was generated for infants who survived the interstage period. Unlike the healthy infant who usually doubles the birthweight by 5 months of age, the patient with HLHS appears to have limited growth potential with a plateau phase of weight gain between 4 and 5 months of age (Fig. 50.20). Early growth velocity was generally <20 g/day whereas normal infant growth is 30 g/day. These initial data prompted a greater focus on ensuring adequate caloric intake prior to hospital discharge and increased attention to outpatient growth and nutrition. In an attempt to optimize adequate growth, infants are expected to take 110 to 130 kcal/kg/day with formula or breast milk fortified to 24 to 27 calories per ounce. Approximately 25% of our patients have undergone open gastrostomy tube placement because of inability to consume adequate calories with oral feeding alone. Increased attentiveness to nutritional intake has P.1026 resulted in improved somatic growth in monitored patients that nearly parallels normal infant growth with a growth velocity >25 g/day regardless of feeding method. Attentiveness to nutritional support also provided insight on optimal timing for stage 2 palliation. When comparing interstage monitored patients with those patients who were not subjected to frequent monitoring of weight and saturation, monitored patients had similar weights to nonmonitored patients (5.5 ± 0.8 vs. 5.7 ± 1.3 kg) despite the younger age at stage 2 palliation in the monitored group (4.2 ± 1.4 vs. 5.6 ± 2.1 months, p <0.01). This observation along with the demonstrable flattening in growth velocity beyond 4 to 5 months of age call into question the benefit of arbitrarily delaying stage 2 palliation until after 6 months of age.

CBP 4

Once the target SVR has been achieved and vasoactive infusions are constant, the lungs are reinflated and mechanical ventilation is resumed. Usual initial ventilator settings include a fiO2 >0.5, inflating pressure of 25 to 28 cm H2O, inspiratory P.1023 time of 0.6 to 0.8 seconds, PEEP of 3 to 4 cm H2O, and a rate of 10 to 20 breaths per minute to achieve normal alveolar ventilation without atelectasis. Prolonged ventilation without lung perfusion is avoided to reduce the likelihood of acute changes in PVR and lung injury (232,233,234). Shunt adequacy is evaluated with a test opening; a rise in end-tidal CO2 to the 30-torr range and a drop in mean arterial pressure of >10 mm Hg are suggestive of adequate shunt flow. An oximetric catheter is placed in the SVC for post-CPB monitoring. Weaning from CPB is attempted over 30 to 45 seconds. The total cardiac output must double with shunt opening; preload must be carefully titrated to avoid ischemia and generally is optimal at an initial central venous pressure of 10 to 12 mm Hg. Inotropic support may need further adjustment during this time. As pump flow decreases, the arterial and venous saturation falls. Generally, an organ perfusion pressure of 40 mm Hg is adequate. Real-time knowledge of Qp/Qs and SvO2 drive physiologic adjustment of SVR and myocardial performance. SvO2 or other measures of oxygen supply/demand become the primary hemodynamic target, with appropriate attention to coronary perfusion pressure and evidence of ischemia. Successful separation from CPB is likely if arteriovenous saturation difference remains normal (20% to 30%) and SvO2 remains above the anaerobic threshold of 30% to 35%. Modified ultrafiltration usually increases SvO2 and apparent myocardial performance (235). A low SvO2 (<40%) with high SaO2 (>80%) indicates high Qp/Qs, and reduction in SVR is attempted. Increasing PaCO2 may redistribute systemic blood flow to the brain but has little effect on Qp/Qs in the postoperative period in the presence of a relatively restrictive systemic to pulmonary shunt. Low SvO2 and balanced Qp/Qs indicate inadequate total oxygen delivery. Increasing the inotropic state, preload optimization, increasing hemoglobin, and metabolic suppression can be used. High SVR must be addressed and may be present even if blood pressure is not high because of the accompanying reduction in systemic perfusion. Management based on SvO2 (or NIRS as a surrogate) is shown in Table 50.2. After separation and completion of modified ultrafiltration, cannulae are removed and heparin reversal is achieved. Modification of Qp/Qs by PVR modulation is now less effective than manipulation of SVR because of the large fixed resistance imposed by the systemic-to-pulmonary artery interposition shunt and the potential lability in SVR. Lung management targets the usual goals of maintenance of functional residual capacity, avoidance of atelectasis, and fully saturated pulmonary capillary blood. In the presence of a restrictive shunt, adjustment of CO2 will have more effect on the distribution of SVR than on total pulmonary resistance (170), and increasing the fiO2 will usually increase oxygen delivery without adverse effect on Qp/Qs (171). Increases in SaO2 are not deleterious in the presence of intense afterload reduction (176). Anticipating changes in SVR, sympathetic outflow, and oxygen consumption with volatile anesthetic withdrawal should prompt appropriate transition to intravenous hypnotic analgesics and occur before transfer to the intensive care unit (ICU).

...

Other Adjunctive Therapies The hypoxic patient with inefficient single ventricle physiology benefits from increased oxygen carrying capacity. Increasing the hematocrit to 50% will benefit the patient with limited Qp or Qt. Other means to improve systemic perfusion include therapies that attenuate sympathetic vascular tone. Specifically, for the stressed neonate with increased SVR, low-dose morphine can be used to reduce agitation and work of breathing. Because of the variable SVR, falling PVR, and potential for systemic hypoperfusion, we avoid enteral feeding during the preoperative period. Parenteral nutrition is provided with volume administration that is generally 10% to 20% higher than in the healthy neonate to account for the capillary leak that is expected with PGE1 therapy. Diuretic therapy is reserved for those patients who demonstrate respiratory insufficiency from increased interstitial lung edema related to either pulmonary overcirculation or restrictive pulmonary venous return. Any of the proposed preoperative management strategies can be used in isolation or combination to balance pulmonary-to-systemic flow, optimize systemic perfusion, and preserve organ function. However, each should be embarked on only with sufficient monitoring as they can pose potential risks to the neonate awaiting staged palliation for HLHS. Surgical Management [Print Section] Stage 1 Palliation The goals of stage 1 palliation include relief of ductal-dependent systemic flow, provision of unrestricted coronary artery flow, creation of a nonrestrictive atrial septal defect to prevent pulmonary venous hypertension, and provision of a reliable but restricted source of pulmonary blood flow (Fig. 50.15). Surgical strategies are varied, and recently the introduction of the hybrid procedure revisits early strategies of Litwin and Van Praagh to accomplish the goals of stage 1 palliation without the use of cardiopulmonary bypass (190,191,192,193).

...

Oxygen Flux in Single-Ventricle Parallel Circulation With univentricular parallel anatomy, both the pulmonary circulation and the systemic circulation are fed by arterial blood that is only partially saturated with oxygen. Because arterial saturation (SaO2) is reduced by mixing, and because Qs may be reduced by various factors, a reduction in DO2 is typically encountered in patients with HLHS, with a resulting higher risk of cellular hypoxia as a major physiologic vulnerability. Applying the Fick principle (equality of systemic oxygen consumption and pulmonary oxygen uptake) to the patient with HLHS yields the following relationships between oxygen consumption (VO2), pulmonary blood flow (Qp), systemic blood flow (Qs), SaO2, systemic venous saturation (SvO2), and pulmonary venous saturation (SpvO2), which allows estimation of the pulmonary-to-systemic flow ratio (Qp/Qs) in the parallel circulation: Optimal systemic oxygen delivery in univentricular models occurs at the lowest total cardiac output when Qp/Qs equals 1 (159). This economy occurs with the total ventricular output (Qt) being twice the normal output of an in-series systemic ventricle, to yield normal values for both Qs and Qp. With a Qp/Qs of 1 and an arterial-venous saturation difference (SaO2 - SvO2) of 25%, oxygen uptake/consumption equilibrium will occur when the pulmonary capillary-arterial saturation difference (SpvO2 - SaO2) also equals 25%, resulting in an SaO2 of 75% and an SvO2 of 50%, assuming that pulmonary venous blood is fully saturated. If SaO2 is >75%, a higher Qp is necessary to maintain the same pulmonary O2 uptake; conversely if Qp falls, SaO2 will also fall. If the SaO2 is low, then a higher Qs is necessary to maintain systemic O2 uptake; if Qs falls, then SaO2 also falls. Changes in SaO2 result in opposite effects on pulmonary and systemic oxygen economy. Conversely, since a tradeoff of Qs and Qp will exist for any Qt, increases in SaO2 that are not a result of increased Qt will be offset by a reduction in Qs. Referring to the first three examples in Table 50.1, moderately large changes in Qp/Qs with constant Qt (assuming a hemoglobin of 15 gm/dL, SpvO2 of 100%, and indexed VO2 of 160 mL/m2/min) show a range of SaO2 from 63% to 82% but a narrower range of SvO2 for 44% to 50%. As a result, moderate alterations in Qp/Qs balance will have minimal effect on DO2; more effectively alterable determinants of DO2 include hemoglobin and Qt. Oxygen economy at higher or lower Qp/Qs and varying Qt is illustrated in Table 50.1. In single-ventricle parallel circulation, solution of the Fick equation shows that the SaO2 depends on both systemic and pulmonary flow and saturation: Changes in Qt, over a range of Qp/Qs, have a more profound effect on SvO2. Thus matching of DO2 to changes in VO2 are more effective via interventions in total cardiac output or hemoglobin concentration than by precise manipulation of Qp/Qs balance. An important limitation in circulatory reserve resulting from this complex relationship is that increases in systemic oxygen consumption cannot be buffered by increased extraction (160). This limitation is best clarified by comparison of the oxygen cascade diagram between in-series and parallel circulation (Fig. 50.11). In a patient with normal in-series circulation, at constant cardiac output, increased VO2 will reduce SvO2, but pulmonary P.1015 oxygen uptake will increase to match. In the critically ill patient, tissue oxygen utilization will usually continue until the SvO2 falls to <50%; thus, a doubling of VO2 can be met without an increase in cardiac output. Since normal lungs can fully oxygenate fully desaturated systemic venous blood, the resulting SaO2 is unchanged, DO2 is maintained, and the increased VO2 can be met by increased extraction alone. Similarly, cellular oxygen utilization can be maintained during a reduction in cardiac output and DO2 by increased extraction. In a patient with univentricular parallel circulation, increased oxygen extraction (either because of increased VO2 or decreased DO2) will reduce SvO2 and SaO2. The result is that conditions that increase oxygen extraction will also decrease oxygen delivery through a reduction in SaO2. For any given Qp/Qs, the increased tissue oxygen demand can be met only by increased cardiac output. For any given fall in cardiac output, DO2 and SvO2 will be disproportionately reduced, because SaO2 will also fall. Thus, changes in oxygen supply and demand are interdependent and destabilizing in the patient with parallel univentricular physiology.

Parallel circulation 2

Oxygen flux in series and parallel circulations. In contrast to series circulation, in a parallel circulation, arterial blood derives from a mixture of systemic venous and pulmonary venous return and is divided into systemic and pulmonary flow according to relative resistances. A report of increased stability with the use of inspired carbon dioxide (CO2) (161) led to the wide adoption of manipulation of medical gases to control PVR and Qp/Qs. Theoretic and experimental models showed that inspired CO2 increased PVR, and moderately decreased systemic vascular resistance (SVR), and would increase systemic oxygen delivery (165,166). As part of this approach, the SaO2 was used as a key indicator to detect pulmonary overcirculation, which would result in a higher P.1016 SaO2 as Qp/Qs rose. However, this would be true only if the systemic arteriovenous difference did not increase, which would occur only if the increase in Qp resulted from increased Qt at constant Qs. The primary concern over preventing a runaway spiral of increased Qp/Qs led to the use of low or even subatmospheric fraction of inspired oxygen (fiO2) in further attempts to raise the PVR (167,168).

Parallel Circulation

Parallel Circulation [Print Section] The patient with HLHS faces similar physiologic challenges before, during, and after stage 1 palliation. The superimposition of inefficient parallel circulation, cyanosis, myocardial dysfunction, and autonomic and inflammatory responses to stress and surgery result in high likelihood of critical impairment of P.1014 oxygen delivery with subsequent organ dysfunction or death. Thus, facility with the principles of hemodynamics and oxygen supply/demand economy is a prerequisite for rational perioperative treatment of first-stage palliation patients. Maintenance of adequate organ substrate delivery, oxygen, is necessary to reverse or prevent ischemic injury, which can result in multisystem organ dysfunction, prolonged morbidity, and mortality (110,111,112,113,114,115,116). Interventions targeting early treatment of inadequate whole body or regional oxygen supply/demand relationships (shock) have improved outcome in critical illness; therefore detection of inadequate oxygen delivery is important for preventive or therapeutic interventions (110,111,117,118,119,120,121,122).

Parasternal Long-Axis and Short Axis

Parasternal Long-Axis View The diagnosis of HLHS is often suspected immediately from a parasternal long-axis view with identification of a small, muscle-bound left ventricular chamber that does not extend to the cardiac apex (Fig. 50.4). The endocardial surface of the left ventricle is often echo-bright, indicating areas of endocardial fibroelastosis. The left atrium is usually small but may be dilated in patients with a restrictive atrial septal defect. The ascending aorta can be well visualized from the long-axis view and is frequently small (2 to 3 mm in diameter); the aortic valve may or may not be patent. The mitral valve is often imperforate, but when patent, the leaflets are thickened, with short or even absent papillary muscle chordal attachments. A ventricular septal defect is rare in the presence of aortic atresia, but color Doppler interrogation of the ventricular septum may show ventriculocoronary arterial connections. Although the significance of these abnormal coronary connections in HLHS is unclear, coronary artery sinusoidal connections have had prognostic implications in other forms of congenital heart disease (97,98). Several measurements are available from the parasternal long-axis view, which can be helpful when trying to differentiate critical aortic stenosis from HLHS. A left ventricular cross-sectional area <1.5 cm2 is found in most infants with HLHS, as well as a left ventricular end-diastolic inflow dimension <25 mm (measured from the hingepoint of the posterior mitral leaflet to the apex) and a mitral annulus diameter of ≤6 mm (89,90). Parasternal Short-Axis View The parasternal short-axis view again allows assessment of left ventricular size and function (Fig. 50.5A). The mitral valve papillary muscles are well visualized from this window and should be carefully examined. At the base of the heart, aortic valve size and anatomy can be well visualized. Doppler interrogation of the coronary arteries is often best assessed here. Bidirectional coronary flow is consistent with left ventriculocoronary arterial connections. Last, the main pulmonary artery, pulmonary valve, and branch pulmonary arteries are all well seen from the short-axis view. Scanning more superiorly, the patent ductus arteriosus can be visualized as it sweeps to the descending aorta (Fig. 50.5B).

Echo 1

Parasternal long-axis view in a patient with hypoplastic left heart syndrome. The left ventricular chamber is small and muscle bound. The endocardial surface of the left ventricle is echo-bright, consistent with endocardial fibroelastosis (arrow). Ao, aorta; LA, left atrium; RV, right ventricle.

Echo Parasternal short

Parasternal short-axis views in a patient with hypoplastic left heart syndrome. In (A) the right ventricle (RV) is enlarged with a smaller, hypertrophied left ventricle (LV). Scanning more superiorly from a parasternal short-axis view (B), the larger main pulmonary artery (MPA) and patent ductus arteriosus (arrow) are seen connecting to the descending aorta. No brachiocephalic vessels are seen arising from the ductal arch, a key finding in differentiating the ductal arch from the true aortic arch. Ao, aorta.

Postoperative Management

Postoperative Management [Print Section] Unbalanced Qp/Qs, reduced total cardiac output, higher oxygen demand and the potential for myocardial ischemia contribute to morbidity and mortality. Oxygen delivery is limited by myocardial edema with attendant diastolic dysfunction and the potential development of tamponade physiology (241,242,243). This physiologic vulnerability peaks in the first 6 to 12 hours postoperatively, and all monitoring appropriate for the operating room should be maintained throughout this period (118,220). Postoperative management should target adequate organ oxygenation including stabilization of oxygen consumption to reduce morbidity and mortality. Strategic improvements in oxygen delivery have paralleled improved survival (244) and neurologic outcomes (245) in our series. SvO2 and NIRS data as primary markers of systemic oxygen delivery are used targeting SvO2 >50%, cerebral rSO2 >50%, and somatic rSO2 >60% to minimize organ dysfunction and the risk of secondary multisystem organ dysfunction (175,246,247). Evidence of anaerobic metabolism with SvO2 approaching 30% has been demonstrated, and management strategies that target a SvO2 of ≥50% have reduced mortality (62,175). Delaying sternal closure until postoperative day 2 to 4 has reduced early hemodynamic compromise and the need for mechanical circulatory support (248). The development of moderate tamponade physiology is expected. Therefore, the procedure should be timed such that inotrope-recruitable stroke volume is available. An increase in inflammatory responses including elevated temperature setpoint is expected after sternal closure, with possible need for additional support. An increase in oxygen consumption of about 30% can be expected with the transition to spontaneous ventilation. Pharmacologic support should be adjusted during this transition as appropriate. Excessive work of breathing owing to altered mechanics will quickly destabilize the circulation.

Pre-Op

Preoperative Preparation [Print Section] Prostaglandin E1 Maintaining ductal patency in a neonate with HLHS is vital in the preoperative management. Although ductal closure is rarely immediate, nearly all infants will have physiologic closure of the ductus arteriosus by the fourth day of life; 20% of infants will demonstrate functional ductal closure during the first day of life, and >80% of infants demonstrate ductal closure during the second day of life. For this reason, prostaglandin E1 (PGE1) therapy should be initiated immediately when HLHS is diagnosed or suspected (180,181,182). The patient's physiologic state often directs initial PGE1 dosing. For patients who present in shock with suspected ductal closure or a restrictive duct, initial dosing will range from 0.05 to 0.1 μg/kg/minute. Once ductal patency is ensured, the infusion rate can be decreased to an effective dose of 0.01 μg/kg/minute (183). Maintaining ductal patency with the lowest effective PGE1 dose minimizes the most common dose-dependent side effects of PGE1: hypotension prompting volume resuscitation and respiratory depression requiring mechanical support (183,184,185). Initiation of intravenous caffeine with a loading dose of 20 mg/kg followed by a maintenance dose of 5 to 10 mg/kg/day has been effective in reducing the need for mechanical ventilation preoperatively. This approach is based on a study in neonates receiving low-dose PGE1 while simultaneously being treated with aminophylline or placebo. Patients who received aminophylline had a decreased incidence of apnea and did not require intubation when compared with the placebo group of whom 35% required intubation (186).

Pre-Op Monitoring

Preoperatively, these approaches may be partially effective in limiting pulmonary overcirculation, but only hypercapnia increases systemic oxygen delivery (169). In contrast, a synthetic shunt placed at the time of initial palliation imposes a large fixed resistor into the total pulmonary resistance, which is of similar magnitude to the SVR. This arrangement reduces the efficacy of PVR manipulations on hemodynamics (170,171). Reduction of fiO2 may cause the resulting alveolar oxygen tension to be inadequate to fully oxygenate the pulmonary capillary blood, an effect that may be common at fiO2 <0.3 (172). Thus, reduction in SaO2 by intentionally limiting fiO2 may result solely from pulmonary capillary desaturation rather than reductions in Qp. This will reduce oxygen uptake across the lung, waste pulmonary blood flow, and reduce oxygen available for tissue utilization. Unless SpvO2 is measured or fiO2 is high enough to make pulmonary capillary desaturation unlikely, the calculated Qp/Qs at low fiO2 may be falsely low because of SpvO2 <95%. Because of variability in both SpvO2 and the arteriovenous saturation difference, the SaO2 does not reliably characterize the parallel circulation. The importance of both SVR and PVR in determining Qp/Qs was emphasized in modeling studies (170). In these studies, the Qp/Qs range could be restricted by placement of a resistive shunt, and the importance of shunt size was emphasized. These models also demonstrated that the combination of low total cardiac output and high Qp/Qs severely impaired systemic oxygen delivery. Even in the presence of a resistive shunt in the pulmonary circulation, control of elevated SVR was more effective than increases in PVR to optimize systemic oxygen delivery. Without knowledge of SvO2 or tissue oxygenation, the effect of any intervention on systemic oxygenation remains difficult to assess. Not surprisingly, perioperative management based primarily on optimization of SaO2 is associated with an early mortality of >20%. With this approach, cardiovascular collapse and mortality typically result from an acute hemodynamic event that occurs unexpectedly in an apparently stable postoperative hemodynamic setting (62,173,174). Because sympathetic vasomotor tone and thus SVR increase as systemic flow falls, changes in Qp/Qs can occur rapidly, resulting in deterioration of systemic oxygen delivery in a self-reinforcing cycle. Precisely because of the Qp/Qs tradeoff, these changes are usually not readily apparent with arterial pressure or oxygen saturation monitoring as demonstrated in Figure 50.13. This above analysis provides an explanation for the profound circulatory derangements that are possible despite having SaO2 in the typical target range. These theoretical and actual limitations have led to the development of management strategies aided by SvO2 measurement to more closely assess Qp/Qs, adequacy of oxygen delivery, and whole-body oxygen economy. It is not possible to obtain a true mixed venous blood sample in the patient with HLHS, but approximate measures of the mixed venous oxyhemoglobin saturation can be obtained from blood withdrawn from the SVC. Placement of a catheter in the SVC primarily to allow sampling of quasi-mixed venous blood is more likely to be helpful in guiding perioperative management. Small (4 Fr) oximetric catheters placed in the SVC just prior to weaning from bypass in neonates undergoing Norwood-type repairs allow continuous readout of SVC saturation. Used as an approximation of SvO2, monitoring of SVC saturation allows for timely hemodynamic intervention to avoid anaerobic metabolism, which has an apparent SVO2 threshold near 30% in this population (175). The use of continuous SVO2 has greatly reduced the perioperative occurrence of sudden unexpected circulatory collapse (62,173,176). Recently, near-infrared spectroscopy (NIRS) (INVOS, Somanetics Corporation, Troy, MI) monitoring of tissue oxygen status has been used as an adjunct to perioperative management. NIRS specifically measures the average oxyhemoglobin saturation (rSO2) about 2 to 3 cm below the skin and has been used to monitor oxyhemoglobin saturation in a range of tissue beds (177,178). The probes are most commonly placed on the forehead to monitor cerebral oxygenation, and on the T10-L2 flank region to monitor somatic saturation, as an attempt to capture circulations under intense autoregulatory (cerebral) P.1017 and autonomic (renal or splanchnic somatic) control. Combining NIRS information from two regional circulations in a linear model allows better approximation of SvO2 and thus provides information about both regional and global oxygen economies as a noninvasive SvO2 surrogate (179) (Fig. 50.14). Given the instability of oxygen supply/demand relationships, and the inadequacy of data solely based on arterial blood pressure and SaO2 monitoring, improved outcome requires early detection and treatment of deficiencies in oxygen economy. Measurement of SvO2 permits continuous assessment of adequacy of systemic oxygen delivery in the most vulnerable postoperative period. Low total cardiac output and unbalanced Qp/Qs can be differentiated physiologically, interventions can be rationally based, and patient responses can be quantified and trended. Continuous SvO2 monitoring has been shown to be the single most important factor in improving survival after stage 1 palliation

Presentation

Presentation [Print Section] Today, many cases of HLHS are detected in the second trimester when a screening obstetric ultrasound shows an abnormal four-chamber view. Prenatal recognition of the disease allows for timely parental counseling as well as optimal delivery planning. Delivery at a tertiary care facility is recommended, avoiding transport-related morbidities, and allows the mother to be in close proximity to her baby after birth (84). Most centers continue to advocate a vaginal delivery, although induction of labor may be deemed necessary if the mother lives a significant distance from the tertiary care facility. Following delivery, prostaglandins are initiated to maintain ductal patency, and an echocardiogram is performed to confirm the diagnosis. If severe atrial septal restriction is suspected on the prenatal ultrasound, interventional cardiology and/or cardiothoracic surgery should be immediately available. If the infant has not been prenatally diagnosed with HLHS, timing of presentation is somewhat variable and dependent on the degree of atrial level restriction as well as ductal patency. During late fetal development, pulmonary vascular resistance (PVR) is high and pulmonary blood flow is limited to <10% of ventricular output. At birth, PVR decreases abruptly as a result of mechanical distention of the lung, increased oxygen tension, and increased shear stress. Although the greatest fall in PVR occurs shortly after birth, a clinically important decline in PVR continues within days of birth (85,86,87). Abu-Harb et al. (88) reviewed the time of presentation of obstructive left heart malformations. About one quarter of their infants with HLHS became symptomatic within 24 hours of age. However, most infants had a "normal" neonatal examination, with development of symptoms after 48 hours of age, often after hospital discharge. When the atrial septum is restrictive, the resultant left atrial hypertension leads to pulmonary congestion, resulting in early onset of tachypnea and cyanosis. When the atrial septum is widely patent, neonates with HLHS may initially appear normal, with adequate oxygenation and systemic perfusion. These infants have a more delayed presentation, with symptoms developing as the ductus arteriosus undergoes gradual spontaneous closure. With ductal regression, there is hypoperfusion of the systemic circulation with an associated augmentation of pulmonary blood flow. These infants present at 2 to 3 days of age with feeding difficulties and respiratory distress, with rapid progression to congestive heart failure and shock.

HLHS Doppler

Pulsed Doppler examination from the suprasternal notch in a patient with hypoplastic left heart syndrome. With the sample volume positioned in the transverse arch, retrograde systolic flow (arrows) from the patent ductus arteriosus into the aorta is identified, consistent with ductal-dependent systemic circulation.

Respiratory support

Respiratory Support and Inspired Gases In the preoperative patient without anatomic limitation to pulmonary blood flow, mechanical ventilation and medical gas manipulation of pulmonary arteriolar resistance are sometimes necessary and beneficial. Controlled positive-pressure ventilation with care taken to avoid hyperventilation can limit pulmonary blood flow. Additionally, the use of positive end-expiratory pressure (PEEP) allows delivery of lung volumes that exceed functional residual capacity and subsequently results in compression of pulmonary vasculature with a resultant increase in PVR. Medical gas management can be used to increase PVR and reduce Qp/Qs. Inspired CO2 as a means to limit pulmonary blood flow and treat instability first became apparent in the early 1990s (161). Subsequent animal models have confirmed the effectiveness of inspired CO2 on lowering the pH and raising PVR while successfully increasing systemic flow (165,166,187). Animal models have similarly demonstrated the effectiveness of subatmospheric fiO2 in increasing PVR (166,187). Clinical experience supports the use of hypoxia as a means to attenuate an elevated Qp/Qs (167,188). Hypoxic gas mixtures are achieved through blending nitrogen and oxygen to achieve inspired subatmospheric fiO2 of 0.14 to 0.20. The use of inspired gases in humans has been best studied in an acute model by Tabbutt et al. (169). Preoperative neonates with HLHS who were anesthetized and under neuromuscular blockade were ventilated with a hypoxic gas mixture (fiO2 of 0.17) and with supplemental CO2 (fiCO2 of 0.03). Although both strategies were successful in acutely reducing SaO2 and Qp/Qs, only hypercarbia improved systemic oxygen delivery (169). Furthermore, whereas hypercarbia improved cerebral oxygenation, hypoxia provided no benefit to cerebral saturation (189). In general, supplemental oxygen, a potent pulmonary vasodilator, is avoided in the preoperative management of HLHS, although patients with respiratory distress syndrome, pneumonia, atelectesis or other primary lung pathology might benefit from the use of supplemental oxygen for severe hypoxia. Patients with restrictive atrial communication also necessitate supplemental oxygen administration. For these patients, controlled ventilation is instituted with supplemental oxygen. In patients who have severely restrictive or absent atrial septal defect, supplemental oxygen and other medical therapies are ineffective in treating the severe cyanosis, prompting emergency intervention with balloon atrial septostomy, surgical septectomy, or immediate stage 1 palliation.

Stage I

Stage 1 palliation of hypoplastic left heart syndrome. A: Stage 1 palliation (Norwood procedure) using a modified Blalock-Thomas-Taussig (BT) shunt for provision of pulmonary blood flow. The shunt originates from the innominate artery and inserts into the central pulmonary artery. B: Stage 1 palliation using a right ventricle (RV)-to-pulmonary artery (PA) conduit (Sano modification) for provision of pulmonary blood flow. A larger 5 or 6 mm graft is placed between the right ventricle and the central pulmonary artery. C: Stage 1 palliation using a hybrid approach. Pulmonary blood flow is restricted with branch pulmonary artery bands, and the ductal patency is maintained by placement of a stent. A stent is placed to create a nonrestrictive atrial septal defect.

Surgical palliation

Stage 1 palliation using either a modified Blalock-Thomas-Taussig shunt or right ventricle-to-pulmonary artery conduit (Sano modification) is accomplished using cardiopulmonary bypass, deep hypothermia, and altered perfusion—either circulatory arrest or regional perfusion. A connection is created between the smaller ascending aorta and the pulmonary root for provision of coronary blood flow. Restructuring of the heart's outflow via the pulmonary root is accomplished along with relief of coarctation and arch hypoplasia. Variations in surgical techniques include resection of ductal tissue or coarctectomy as opposed to patching of the region of ductal insertion. The aim of stage 1 palliation is to create a stable anatomy that permits growth and maturation of the pulmonary vasculature so that it can accommodate subsequent single-ventricle palliation. It is important that successful surgical strategies have a low incidence of recurrent or residual lesions because these are a source of interstage mortality and can limit suitability for single-ventricle palliation. Development of a restrictive atrial septal defect rarely complicates the interstage course (194). The observation that smaller ascending aortic size and presence of aortic atresia are risk factors for mortality is an indication that coronary insufficiency is a cause of death following stage 1 palliation, and strategies that target creation of a large ascending aorta-to-pulmonary root anastomosis are likely to result in improved outcome (195,196,197,198). Arch reconstruction strategies that include coarctectomy appear to have a lower incidence of late arch obstruction (59,195). A modification of the systemic-to-pulmonary artery shunt developed by Blalock, Thomas, and Taussig has historically been the source of pulmonary blood flow following stage 1 palliation. Typically, this shunt originates from the innominate artery or the aorta. Both the diameter and length of this shunt are relevant to determining its flow-resistive characteristics (170). The resulting anatomy ideally provides enough resistance to pulmonary blood flow to avoid destabilization from excessive pulmonary blood flow in the postoperative period. Physiologic limitations result from the inherent Qp/Qs mismatch of the parallel circulation and diastolic aortic runoff to the pulmonary circulation with risk of aortocoronary flow impairment (199,200). Additionally, competition between cerebral and pulmonary circulations for blood flow is possible if the shunt originates from the innominate artery (177). Furthermore, the systemic-to-pulmonary artery shunt is susceptible to occlusion owing to thrombosis or thromboembolism (194,201). A significant modification of the established Norwood procedure is the recent use of a right ventricle-to-pulmonary artery conduit, (Sano modification), which provides pulmonary blood flow in parallel with systemic blood flow directly from the right ventricle during ventricular ejection (202). The major theoretical advantage of this arrangement is the avoidance of aortopulmonary runoff, which results in higher coronary and systemic perfusion pressures and may potentially lessen the incidence of ventricular ischemia. Early hemodynamic reports documented higher diastolic perfusion pressures (203,204,205). However, the need for ventriculotomy and its long-term effects remains a cause for concern. Although one might predict less potential for elevation of SVR to impact Qp/Qs with this anatomy (206), early mortality has not been eliminated (207). Studies comparing the two techniques among contemporary patient groups have identified no advantage of one technique over the other (205,208). Branch pulmonary artery banding has been reported as a successful approach to reduce excessive pulmonary blood flow and permit a sufficient decrease in PVR to allow later stage 1 repair or to reduce mortality while awaiting a donor heart (209). Use of this approach has also been reported in the rare neonate who cannot be stabilized by medical interventions because of excessive pulmonary blood flow (210). Recently, a hybrid approach using surgical branch pulmonary artery banding combined with transcatheter ductal stenting and intervention designed to create a nonrestrictive atrial septal communication has been reported by some groups (190,191,192). The result is anatomy that achieves the goals of stage 1 palliation without the need of cardiopulmonary bypass and deep hypothermia. The second-stage procedure, combined aortic P.1020 arch reconstruction and primary cavopulmonary connection, which was attempted unsuccessfully 40 years ago, has now been successful (191,211). Success with this approach has required aggressive multimodal treatment of elevated PVR (191). Branch pulmonary artery banding either alone or in combination with ductal stenting may also prove useful for the patient at increased risk for cardiopulmonary bypass-related complication such as neonates with intracranial hemorrhage.

Stage 2

Stage 2: Superior Cavopulmonary Connection [Print Section] Superior cavopulmonary anastomosis prior to completion Fontan improves ultimate survival and is associated with low operative and late mortality (198,251). In this operation, CPB is usually employed to allow anastomosis of the SVC to the proximal ipsilateral pulmonary artery and takedown of prior shunts placed to provide pulmonary blood flow (Fig. 50.21). Progression to the cavopulmonary anastomosis reduces both wall stress and atrioventricular valve insufficiency through elimination of the volume load on the single systemic ventricle. It creates a more efficient in-series circulation and increases diastolic pressure with improved coronary artery perfusion (105,109,199). The delayed timing of stage 2 palliation to 6 months of age has been supported by previous reports that early cavopulmonary anastomosis has been associated with severe hypoxemia, prolonged pleural drainage, pulmonary artery thrombosis, poor pulmonary artery growth, early development of pulmonary arteriovenous malformations, and excess mortality (252,253,254,255). However, it seems logical that by simply shortening the period of risk linked to the inefficient parallel circulation after stage 1 palliation, interstage survival will be enhanced. In a series of home-monitored patients, those who breached home-monitoring criteria proceeded to stage 2 palliation at a significantly younger age of 3.6 ± 1 months compared with 5.6 ± 2.1 months for those receiving conventional management (p <0.01) (60). Despite the younger age at stage 2 palliation of the monitored patients, weights between groups were similar: 5.3 ± 0.9 vs. 5.7 ± 1.3 kg (p = ns). The success of early cavopulmonary anastomosis in these patients deemed at greatest risk for interstage mortality has modified our overall practice in that stage 2 palliation is electively performed at 4 months of age or earlier if necessary. he implications of early cavopulmonary anastomosis have been further reviewed by Jaquiss et al. (255,256). Patients who underwent cavopulmonary anastomosis at <4 months of age (mean 3.1 ± 1.4 months) were compared with their older counterparts (mean 5.5 ± 1.5 months). All patients survived with an actuarial survival of 96% at 1 year in both groups. The younger group, however, required prolonged mechanical ventilation, had a greater duration of pleural drainage, and had a longer hospital stay. Younger patients also had lower oxygen saturations postoperatively compared with the older group, but by hospital discharge, groups had similar oxygen saturations (255). Follow-up data on this cohort demonstrated no difference in late complications, preoperative hemodynamics at the time of Fontan palliation, or status of the patient after completion Fontan (256). After the stage 2 operation, patients experienced improved activity and physiologic reserve, which lasted several years. However, increasing cyanosis following stage 2 palliation is predictable and is due to several factors including increased lower-body growth and oxygen consumption with concomitant increase in desaturated inferior vena caval blood return. Patients will also develop venovenous collaterals from the high-pressure superior vena cava to veins ultimately draining to the inferior vena cava or atrium. Furthermore, patients are at risk for the development of arteriovenous malformations that result in intrapulmonary shunting of blood from pulmonary artery to pulmonary vein without gas exchange. These are postulated to be the result of a lack of so-called hepatic factor, which prevents the shunt formation (257). Pulmonary arteriovenous malformations can be reversed by the completion Fontan operation, presumably by restoring hepatic factor to the pulmonary circulation.

Staged Palliation

Staged Palliation [Print Section] With inadequate anatomic substrate for a two-ventricle repair, surgical approaches must address the high PVR in the neonate as well as the subsequent reduction in PVR that allows for an eventual more stable and economical in-series circulation. Recognition of such physiologic necessities drove the development of numerous surgical approaches (99,100). Permutations of a staged surgical pathway that was successfully championed by Norwood et al. (101,102) are now widely used. The staged approach ultimately leads the patient on a pathway to a single-ventricle in-series circulation culminating in a Fontan operation with the final result similar to patients with tricuspid atresia and hypoplastic right heart syndrome (103). Most commonly, stage 1 palliation consists of reconstruction of the aortic arch into the right ventricular outflow, separation of branch pulmonary arteries from the right ventricle, and creation of a restrictive source of pulmonary blood flow from a systemic artery or directly from the single ventricle (102,104). Stage 2 palliation unloads the single ventricle by replacing the systemic-to-pulmonary shunt with a superior cavopulmonary anastomosis (105). The staged pathway is completed by modifications of a Fontan connection from the inferior vena cava (IVC) to the pulmonary arteries (102,106). Most mortality associated with the staged surgical approach occurs during and after stage 1 palliation, with recent cumulative early and interstage mortality in the 5% to 30% range (62,107,108). Improved outcome has been associated with early diagnosis, preoperative stabilization, early repair, systematic management approaches, and increased monitoring both in-hospital and at home (60,62,109).

Echo subcostal coronal

Subcostal coronal view in a patient with hypoplastic left heart syndrome. The left atrium (LA) is small with leftward deviation of septum primum and anomalous attachment of the septum to the posterosuperior left atrial wall (arrow). RA, right atrium.Pulmonary venous anatomy and drainage should also be interrogated from the subcostal window. It is important to identify connections of the pulmonary veins (anatomic attachment) as well as pulmonary venous drainage (the end point of pulmonary venous flow). The pulmonary veins may connect normally to the left atrium, but especially in cases of an intact atrial septum, there may be a levoatrial cardinal vein that originates directly from the left atrium and drains either all pulmonary veins (total) or some (partial) to a variable location. It is important to remember that this anomalous venous structure can be stenotic, so the presence of the "decompressing" vein does not guarantee normal left atrial pressure (52). On the other hand, some or all of the pulmonary veins may not connect normally to the left atrium, but connect to a confluence behind the left atrium with anomalous drainage to a variable location. It is estimated that anomalous pulmonary venous anatomy and/or drainage occurs in about 5% to 10% of patients with HLHS.

Subcostal sagittal view

Subcostal sagittal view in a patient with hypoplastic left heart syndrome. The atrial septum is aneurysmal (arrows), bowing into the right atrium. Color Doppler imaging identifies the superiorly positioned atrial shunt with the jet directed into the superior vena cava (SVC). Aliasing of the color Doppler flow signal across the atrial septum is consistent with a restrictive defect and can result in left atrial hypertension. LA, left atrium. Atrial septal anatomy is best imaged from the subcostal views. Large atrial septal aneurysms billowing into the right atrium are common (Fig. 50.7). Unusual attachments of septum primum can sometimes be seen, specifically anomalous attachment to the posterosuperior left atrial wall (Fig. 50.8). This anomalous attachment has been implicated in the pathogenesis of HLHS (38). If the atrial defect is small and restrictive, peak and mean Doppler gradients across the atrial septum should be obtained to estimate the degree of left atrial hypertension.

Summary

Summary [Print Section] The ventricle is a remarkably preserved structure throughout vertebrate evolution and is the workhorse of the circulation. The fundamental problem of an inadequate power supply remains the primary problem for those caring for the newborn with HLHS and persists throughout life. Although the early and intermediate outcomes in terms of survival have improved over the last decade, considerable challenges remain including options for the failing circulation, optimizing long-term neurodevelopmental outcome, and justifying allocation of increasingly scarce health care resources to a complex group of patients. Ongoing research provides hope for the future. Short-term goals include identification of the causes of HLHS to decrease the incidence, improvements in fetal intervention to improve the outcome for those born with HLHS, and improved medical, mechanical, and transplant strategies for treatment of the failing circulation to improve survival and quality of life of affected individuals.

Suprasternal long

Suprasternal long-axis view from a patient with hypoplastic left heart syndrome and aortic atresia. The ascending aorta (arrows) is markedly hypoplastic, measuring 2 mm, with a fair-sized transverse arch connecting to the descending thoracic aorta (DAo). Brachiocephalic vessels are seen arising from the transverse aorta, identifying this structure as the true aortic arch. Suprasternal Notch Views The suprasternal notch provides an important window for evaluating aortic arch anatomy (Fig. 50.9). Although the ascending aorta can be imaged from many views, the transverse arch and descending thoracic aorta are best seen from the suprasternal notch view. Coarctation of the aorta is common in patients with hypoplastic left heart syndrome, and interruption of the aortic arch has also been reported. Doppler interrogation of the transverse arch should show retrograde systolic flow from the ductus; this finding indicates ductal-dependent systemic circulation and supports left ventricular inadequacy for biventricular repair (Fig. 50.10). The suprasternal notch views also provide images of the proximal pulmonary arteries and the ductus arteriosus. In the patient with a later presentation, the ductus may be restrictive; Doppler interrogation of the pressure gradient from pulmonary artery to aorta should be quantified and follow-up studies performed when prostaglandin therapy is initiated. Pulmonary venous connection and drainage should be reassessed from this window. A persistent left SVC or levoatrial cardinal vein can be well imaged to the left of the descending aorta from the suprasternal notch view.

Varying Qp:Qs

TABLE 50.1 EFFECT OF VARYING Qp/Qs AND Qt ON ARTERIOVENOUS SATURATIONS IN PARALLEL CIRCULATION Qp/Qs SvO2 (%) Spv-aO2 (%) Qp Sa-vO2 (%) Qs Qt SaO2 (%) 1.0 50 25 3.2 25 3.2 6.4 75 2.0 44 18 4.3 38 2.1 6.4 82 0.5 44 37 2.1 19 4.3 6.4 63 1.0 67 17 4.8 16 4.8 9.6 83 2.0 63 12 6.4 25 3.2 9.6 88 0.5 63 25 3.2 12 6.4 9.6 75 1.0 33 33 2.4 34 2.4 4.8 67 2.0 25 25 3.2 50 1.6 4.8 75 0.5 25 50 1.6 25 3.2 4.8 50 Assumptions: hemoglobin 15 g/dL, oxygen consumption 160 mL/m2, pulmonary venous saturation of 100%.

...

TABLE 50.2 CIRCULATORY MANAGEMENT BASED ON SvO2 INTERPRETATION SaO2 SvO2 Qp/Qs Suggested Intervention 80 60 1.0 None; slowly wean support 80 40 2.0 Sedation/analgesia, warmth, vasodilator 70 50 0.67 Resolve atelectasis, raise SVR 70 40 1.0 Raise cardiac output, raise hemoglobin, reduce VO2 75 25 2.0 Raise cardiac output, lower SVR 60 40 0.5 Resolve atelectasis, raise SVR, consider iNO, consider shunt augmentation 87 70 1.5 Wean support 87 40 3.6 Sedation/analgesia, vasodilation, consider shunt restriction SaO2, oxygen saturation; SvO2, systemic venous saturation; Qp/Qs, pulmonary-to-systemic flow ratio; SVR, systemic vascular resistance; VO2, oxygen consumption; iNO, nitric oxide.

Fetal diagnosis

The Developing Fetus: Echocardiography and Intervention [Print Section] Prior to the advent of fetal echocardiography, the embryologic cause of HLHS was not entirely clear. However, with advances in fetal cardiac imaging, it became evident that many forms of congenital heart disease evolve throughout gestation. In 1989, Allan (31) observed the in utero evolution of HLHS in a fetus initially diagnosed with critical aortic stenosis. A similar case report was published by Danford (32) in 1992. Since that time, several fetal cardiac centers have reported retrospective collaborative data that suggest that serial measurements of left heart growth and assessment of flow direction across the foramen ovale and distal aortic arch may identify fetuses at risk for severe left heart hypoplasia at term (32,33,34,35). It is now postulated that many cases of HLHS are dynamic and progressive throughout gestation, resulting from altered left ventricular outflow (aortic stenosis) or altered left ventricular inflow (mitral valve stenosis/foramen ovale restriction/alterations of atrial septal anatomy) (36,37,38). The field of prenatal cardiac intervention is just beginning, but early recent successes with balloon dilation of the aortic valve suggest that the development and incidence of HLHS at term can be altered (39). Fetal Echocardiography [Print Section] Recent advances in two-dimensional and Doppler echocardi-ography have made it feasible to diagnose all forms of congenital heart disease in the fetus. HLHS is one of the most common structural lesions diagnosed prenatally, as a screening obstetric ultrasound will preferentially identify lesions that dramatically alter the four-chamber view (40,41,42) (Fig. 50.1). The prenatal diagnosis of HLHS is easily made when a small, muscle-bound left ventricular chamber is identified. The challenge for the fetal echocardiographer today is to recognize the potential for the evolution of HLHS, especially since some of these patients may be candidates for prenatal intervention. Another challenge is to diagnose the severely restrictive or intact atrial septum in this patient group prior to birth, as these patients have a particularly dismal outcome and may also benefit from prenatal intervention.

Stage 3 palliation

The completion Fontan operation can be accomplished in two ways. A: The lateral tunnel Fontan involves creating an intra-atrial baffle that connects the inferior vena cava to the pulmonary arteries. B: The extracardiac Fontan uses a tube graft to connect the inferior vena cava to the central pulmonary artery. In both cases all caval return with the exception of the coronary sinus is directed to the pulmonary arteries, simulating as closely as possible the normal circulatory pattern. To improve hemodynamics, especially in the early postoperative period, a fenestration is often placed between the baffle or conduit and the pulmonary venous atrium. This decreases central venous pressure and increases preload to the single ventricle, albeit at the cost of some systemic desaturation.

Fetal Echo

The fetal left ventricle is predominantly filled with oxygenated blood that returns from the placenta and traverses the foramen ovale (43). If blood flow across the foramen ovale is diminished or reversed, the combined cardiac output is redistributed to the right ventricle and pulmonary artery, resulting in enlargement of the right heart structures and creating less impetus for normal growth of left heart structures, possibly evolving into HLHS. Perhaps the most well-recognized mechanism for decreased flow or reversal of flow through the foramen ovale in utero is the presence of severe aortic valve disease (31,32,33,34,35). With significant aortic valve stenosis, alterations in left ventricular compliance may occur, either secondary to the development of left ventricular hypertrophy or secondary to the development of left ventricular dilation and dysfunction. Endocardial fibroelastosis, a poorly understood phenomenon where the endocardial lining of the left ventricle becomes fibrotic, may also be present. As the disease state progresses, with subsequent elevation in left atrial pressure, flow across the foramen ovale becomes bidirectional and eventually left to right, the result of which may be the cessation of left ventricular growth (44). In a classic study by Hornberger et al. (34), the prenatal and postnatal echocardiograms of 21 fetuses with left heart obstructive lesions were reviewed to identify possible prenatal indicators of postnatal disease severity. Prenatal indices that correlated with HLHS at birth included a smaller mitral valve and ascending aorta in the midtrimester, as well as a decreased rate of growth for all left heart structures. Other prenatal features included reversal of flow across the foramen ovale and retrograde ductal supply of the distal aortic arch. In P.1007 a more recent study, Makikallio et al. (45) reviewed the natural history of aortic stenosis in 43 fetuses initially referred prior to 30 weeks gestation. At the time of the initial examination, the LV:RV length ratio was >0.8:1, and aortic stenosis was the dominant lesion. The presence of moderate left ventricular dysfunction, retrograde transverse aortic arch flow, left-to-right atrial-level shunting, and a monophasic mitral inflow on the initial prenatal echocardiogram were found to be risk factors for the development of HLHS. Again, in this study there was decreased rate of growth of all left heart structures in those patients who developed HLHS. Based on these two series, it is now clear that the fetus with aortic stenosis is at risk for the development of HLHS. Serial echocardiographic follow-up is indicated in these fetuses, paying particular attention to growth of left heart structures and patterns of blood flow across the foramen ovale and transverse aortic arch. Importantly, it now seems feasible to reliably select fetuses for prenatal intervention, using both anatomic and physiologic markers. Although the operative survival for infants born with HLHS has improved significantly over time, the subgroup of patients with a highly restrictive or intact atrial septum continues to experience a higher mortality (46,47). These infants can be profoundly cyanotic at the time of delivery and are often unresponsive to medical intervention. Even with prompt resuscitation and adequate decompression of the atrial septum, there is ongoing morbidity and mortality, likely related to secondary anatomic changes in the lung. Some investigators have reported "arterialization" of the pulmonary veins and lymphatic dilation in this setting; others have postulated that there is associated pulmonary artery hypoplasia. The ability to diagnose a restrictive atrial septal defect prior to birth would allow for more accurate prenatal counseling and planning immediate postnatal intervention. Theoretically, prenatal catheter intervention in this subgroup of patients may alter the secondary anatomic changes in the lung, possibly improving long-term outcome. For all of these reasons, routine evaluation of the atrial septum should be performed in all fetuses with HLHS. Direct assessment of foramen ovale size has not correlated well with the degree of left atrial hypertension at the time of birth, likely a reflection of the inability to clearly visualize the defect, which often lies more superiorly and posteriorly in the left atrium (48). Doppler interrogation of the pulmonary veins is technically much simpler, and the pattern of pulmonary venous flow in HLHS has correlated well with left atrial hemodynamics (48,49). The normal fetal pulmonary vein flow pattern consists of forward flow in systole and diastole, with cessation of flow or a small reversal wave with atrial systole. In a study by Taketazu et al. (48), a pattern of pulmonary vein flow with brief forward and reverse flow with minimal early ventricular diastolic flow was associated with the need for immediate respiratory support and emergent atrial decompression. Two of the three patients with this abnormal flow pattern died after neonatal heart transplantation, and the postmortem lung tissue analysis was notable for dilated lymphatic vessels, pulmonary vein arterialization, and abnormal pulmonary artery musculature.

Least affected subgroup of HLHS

The least affected subgroup of HLHS is aortic stenosis with a patent mitral valve. This form is thought to develop later during fetal development when the left ventricle is more completely formed. This form blends smoothly into the spectrum of critical aortic stenosis. Decision-making in patients with left ventricular outflow obstruction can be challenging. In the patient deemed to have a left ventricle that is non-apex forming with a prohibitively hypoplastic mitral valve, stage 1 palliation is generally chosen with a prognosis that may be favorable because the left ventricle is able to contribute to cardiac output.

Spectrum of disease

The spectrum of hypoplastic left heart syndrome (HLHS). A: Aortic atresia with mitral atresia is the most extreme form of HLHS. The left ventricle (LV) is diminutive. The ascending aorta and arch are extremely hypoplastic, and flow is retrograde. Systemic output is ductal dependent. B: Aortic atresia with a patent mitral valve. As in aortic atresia with mitral atresia, the ascending aorta and arch are hypoplastic and all systemic output is ductal dependent. There is inflow without outflow. As a result, the left ventricle is hypertensive with hypertrophy and endocardial fibroelastosis. The left ventricular mass can be greater than normal and result in distortion of the inflow of the right ventricle, resulting in tricuspid valve insufficiency. C: Aortic valve stenosis with a patent mitral valve. The left ventricle is hypoplastic, but antegrade flow through the aortic valve persists. The degree of ascending aortic and arch hypoplasia is less than that observed with aortic atresia. This end of the spectrum of hypoplastic left heart syndrome blends smoothly into critical aortic stenosis, and decision making concerning suitability for two-ventricle repair can be challenging.

HLHS Spectrum

There are corresponding changes in the right side of the heart when there is left ventricular cavity hypoplasia. All right-sided cardiac structures are larger than normal including the right atrium, tricuspid valve, pulmonary artery, and pulmonary valve. The right ventricle is both enlarged and hypertrophied (8,9,55,57,61,65,66,67). The anatomy of the interventricular septum may be affected. The apex of the right ventricle and apex of the hypoplastic left ventricle remain in proximity and may be identified externally by the junction of the anterior descending coronary artery and the posterior descending coronary artery. The apical junction of the right and left ventricle will not correspond to the apex of the ventricular mass, because the right ventricle is folded around the hypoplastic left ventricle (68). This may impact tricuspid valve anatomy and function of the right ventricle (69,70). Abnormalities of the tricuspid valve have been identified in ≤35% of patients with HLHS. In aortic atresia and a patent mitral valve, the left ventricle has inflow but not outflow; the result is significant hypertrophy of a left ventricle that is larger than that with aortic and mitral atresia and in fact may have greater than normal mass (71). The larger ventricular mass may create distortion of the basilar inflow portion of the right ventricle. The septal surface of the right ventricle may appear to have deep apical sinuses or recesses, the result of the apex of the right ventricle folding around the hypoplastic but hypertrophied left ventricle. The subvalvar apparatus of the tricuspid valve may be more distorted than that found in aortic atresia with mitral atresia. The finding of tricuspid valve dysplasia is more common among patients with a patent mitral valve, occurring in 50% in this subgroup (70,72). In addition to alterations of tricuspid valve function owing to left ventricular mass effect, other abnormalities of the tricuspid valve including identification of a bileaflet right atrioventricular valve are seen in 12% patients whereas some degree of dysplasia of the tricuspid valve can be found in a third of patients. Volume overload of the single right ventricle and resultant annular dilation may further contribute to the development of tricuspid insufficiency. An additional cause of tricuspid insufficiency may be right ventricular subendocardial ischemia occurring in the neonatal period either at the time of presentation or following stage 1 palliation. Evidence for this includes the observation of a bright appearance of the papillary muscles by echocardiography consistent with ischemia and elongated cords in association with the development of tricuspid insufficiency. Patients with aortic atresia and a patent mitral valve may be at increased mortality risk. Endocardial fibroelastosis is frequently present and is thought to be the result of subendocardial ischemia as a consequence of suprasystemic left ventricular pressure (68,71,73). Within this subgroup, the potential for tricuspid valve insufficiency is increased and arrhythmias associated with endocardial fibroelastosis may both contribute to an increased mortality risk (74) (Fig. 50.3).

Vasoactive

Vasoactive Medications The need for preoperative inotropic support is variable and directed by presentation and echocardiographic features. Patients who present in cardiogenic shock most commonly benefit from inotropic support as do patients with significantly reduced right ventricular function. Inotropic agents have been shown to reduce or have no effect on Qp/Qs in an animal model (166). However, caution should be taken to avoid a dose escalation that results in an undesired increase in SVR that subsequently raises Qp/Qs. For those patients in whom Qp/Qs is elevated and systemic perfusion is compromised, inodilator therapy with milrinone, a phosphodiesterase inhibitor might be warranted. Milrinone, however, also has been shown to reduce PVR and again carries the undesired risk of increasing Qp/Qs. Furthermore, milrinone could result in significant hypotension in patients already at risk for decreased perfusion secondary to aortopulmonary runoff.

HLHS: Spectrum 2

view from the diaphragmatic surface of a heart with aortic valve atresia and a patent mitral valve (MV). The left ventricular (LV) cavity is hypoplastic, but the left ventricle is hypertrophied. Septal anatomy is distorted, and the triangle marks the apex of the interventricular septum. The hypertrophied but hypoplastic left ventricle can distort the basilar septum and result in tricuspid valve insufficiency. B: The septal surface of a heart with aortic atresia and a patent mitral valve. The triangle indicates the apex of the left ventricle and the stars indicate the boundaries of the interventricular septum (S). The deep apical sinuses are the result of the remaining right ventricle wrapping around the hypoplastic but hypertrophied left ventricle. C: A view from the diaphragmatic surface of a heart with aortic and mitral atresia. The left ventricle can be identified but is extremely hypoplastic. There is less potential for distortion of the anatomy of the interventricular septum and the subvalvar apparatus of the tricuspid valve. E, endocardium; LA, left atrium; PV, pulmonary valve; RA, right atrium; RV, right ventricle; TV, tricuspid valve. Reprinted from Anderson RH, Pozzi M, and Hutchinson S. Hypoplastic Left Heart Syndrome. 2005. With kind permission of Springer Science and Business Media.