Hypoplastic Left Heart Syndrome

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15 Hypoplastic Left Heart Syndrome

Rima S. Bader, James C. Huhta

I. CASE

A 22-year-old African American woman, gravida 2, para 1+0, was referred by the obstetrician at 26 weeks’ gestation for ventricular disproportion (right ventricle [RV] larger than left ventricle [LV] for gestation). The mother has a bicuspid aortic valve.

A. Fetal echocardiography findings

1. The fetal echo reveals situs solitus of the atria, levocardia, left aortic arch, and increased cardiothoracic ratio (0.45).

2. The LV is severely hypoplastic, with atretic mitral and aortic valves.

3. There is evidence of increased echogenicity at the ventricular walls and papillary muscles of the mitral valve. The LV shows endocardial fibroelastosis with decreased function. The RV is dilated, with large tricuspid and pulmonary valves that were not dysplastic and had no significant regurgitation.

4. The transverse and distal aortic arch are of normal size and by color and pulsed Doppler there was flow reversal into the distal arch. Usually, the distal arch is the largest aspect of the arch in a patient with hypoplastic left heart syndrome (HLHS), presumably because it receives the greatest amount of flow.

5. The RV Tei index (myocardial performance index) is normal (0.4).

6. There are no signs of hydrops fetalis.

7. The interatrial septum is intact (no flow across the atrial septum) (Fig. 15-1). The left atrium (LA) is mildly enlarged, with bowing of the interatrial septum toward the right atrium (RA).

8. The pulmonary veins in the LA are decompressed through a vertical vein, which is obstructed at the site of the left pulmonary artery and left bronchus (mean gradient, 6-7 mm Hg). The pulmonary venous flow is abnormal, with a significant a wave reversal in systole and no forward flow in early ventricular diastole, suggesting severely elevated LA pressure.

9. The pulsatility index is increased in the proximal pulmonary artery, suggesting elevated fetal pulmonary vascular resistance (PVR).

Fig. 15-1 Intact atrial septum on a four-chamber view of the fetal heart. Note the thickened and intact atrial septum (vertical arrow) and the dilated pulmonary veins (horizontal arrows). RA, right atrium; RV, right ventricle.

B. Cardiovascular profile score

1. The cardiovascular profile score is 9/10.

2. One point was deducted for cardiomegaly.

C. Associated syndromes and extracardiac anomalies

D. Fetal management and counseling

1. Amniocentesis was performed before referral and showed normal fetal karyotype and negative fluorescent in situ hybridization (FISH) analysis for 22q11 microdeletion.

2. Fetal intervention.

a. Rationale and consent.

(1) The patient was informed of the poor prognosis for the fetus. A few days after the diagnosis she gave written informed consent for an attempt at in utero interatrial laser septostomy (IALS) at 26 weeks’ gestation.

(2) The aim was to increase the chances of survival in the immediate neonatal period and in the long term.

(1) Under ultrasound guidance and local anesthesia and using a percutaneous approach, an 18-gauge needle was inserted into the RA.

(2) A 600 contact Nd:YAG (neodymium:yttrium-aluminum-garnet) laser fiber was passed through the lumen of the needle and placed against the atrial septum.

(3) The septum was opened with short bursts of 5 to 10 watts of energy.

(4) Color Doppler confirmed flow of blood from the LA to the RA.

(5) A hemopericardium of 6 mL was drained with a 22-gauge needle without complications.

c. Follow-up included serial antenatal studies at weekly intervals initially and then every 2 to 4 weeks.

(1) The size, mean gradient, and direction of flow across the foramen ovale were monitored after the successful laser septostomy (normal right to left).

(2) The size, gradient, and pattern of flow were monitored in the pulmonary veins. An α wave reversal in systole suggests elevated LA pressure (Fig. 15-2). Prenatal pulmonary vein flow patterns, looking at the magnitude of a wave reversal in HLHS, and presence or absence of forward flow in ventricular systole can identify the fetus at risk of severe LA hypertension at birth.

(a) Patients with type A or B flow (in which there is forward flow during ventricular systole and early ventricular diastole, with some a wave reversal) can be clinically stable at birth.

(b) Patients with a type C pattern (forward flow only in ventricular systole with no flow in early ventricular diastole and significant a wave reversal) are critically ill as newborns, with clinical evidence of severe LA hypertension.

(3) Development of regurgitation of the tricuspid or pulmonary valves or RV systolic or diastolic dysfunction could result in the evolution of cardiovascular compromise and hydrops fetalis. Pulmonary regurgitation with a normal valve is usually an ominous sign indicating ventricular dysfunction with poor fetal outcome.

(4) Size and function of the LV was monitored. Size of the transverse aortic arch was compared to the ductus size. The direction of flow in the aortic arch was monitored (reversal of flow—pulmonary to aortic—confirms the presence of aortic atresia). Progression of endocardial fibroelastosis was monitored. All of this should not matter where there is mitral and aortic atresia rather than isolated aortic stenosis.

(5) The maternal hyperoxygenation test was performed after 30 weeks’ gestation.

(a) This test can allow improved functional assessment of the reactivity of the pulmonary vascular bed in the fetus.

(b) In the case of fetal pulmonary hypoplasia, experts agree that a superior method is that of the hyperoxygenation test to assess the fetal lung and the pulmonary vascular reactivity.

(c) This observation does not yet change the outcome, but it gives an idea about the pulmonary vascular reactivity.

Fig. 15-2 Pulsed Doppler in the pulmonary vein (PV) at 23 weeks’ gestation shows no diastolic flow and a biphasic pattern suggesting significant obstruction.

E. Delivery

If the fetus remains well compensated and the lesion is isolated, delivery can be at term in a tertiary care center.

F. Neonatal management

1. Therapeutic options.

a. Compassionate care with either no treatment from delivery or withdrawal of treatment once the diagnosis has been confirmed.

b. Medical treatment.

(1) Treatment with prostaglandin E₁ (PGE₁) infusion.

(2) Optional emergent or urgent cardiac catheterization for further atrial septoplasty.

(3) Possible stent placement to decompress the LA if there is severe LA hypertension. Stent implantation in the ductus arteriosus may be performed while waiting for a donor heart or as a palliative alternative to Norwood stage 1 with bilateral pulmonary artery banding.

c. Staged palliative surgery (Norwood procedure).

d. Cardiac transplantation, particularly in patients with cardiac pathology that can complicate single ventricle palliation, such as significant RV dysfunction or severe tricuspid valve regurgitation.

2. Medical treatment.

a. PGE₁ infusion to keep the ductus open to provide a pathway to the systemic circulation and improve the body perfusion.

b. Administration of oxygen is normally not advisable in neonates with HLHS because this can cause a decrease in the PVR with increased pulmonary blood flow that further steals from the systemic circulation. However, in a neonate with severe restriction of the atrial septum and LA hypertension, oxygen administration can contribute to an improvement in the systemic oxygen levels.

c. Blood gas revealing severe metabolic acidosis and slightly decreased Po₂, a characteristic finding of HLHS, could be due to poor cardiac output. However, babies with severe LA hypertension due to atrial level restriction are both severely cyanotic (Pao₂ < 25-30 mm Hg) and metabolically acidotic. In this setting, therapeutic balloon atrial septostomy can help decompress the LA.

d. The hematocrit should be maintained above 45% to increase the oxygen-carrying capacity.

e. Usually, volume and inotropic support (such as milrinone 0.5 μg/kg/min infusion) may be indicated to improve ventricular function.

3. Surgical treatment.

a. Single ventricle palliation.

(1) Norwood stage 1 can be performed at the first 1 to 2 weeks of life, which carries a surgical mortality of 5% to 15% in the majority of larger pediatric heart centers in North America.

(2) For optimal surgical outcome, the newborn should be allowed to recover from the insults of birth before surgery is undertaken, except when there is an element of obstruction to the pulmonary venous return (total pulmonary venous drainage or restriction at the foramen ovale).

(3) The ultimate goal is to deliver the infant to the operating room in good condition to expect a good surgical outcome.

(4) This operation consists of:

(a) Dividing the main pulmonary artery and closing the distal stump.

(b) Establishing a right sided Gore-Tex shunt (usually a 3.5-4 mm tube) to provide pulmonary blood flow or, more recently, an RV–to–pulmonary artery conduit (Sano procedure).

(c) Excising the atrial septum for adequate decompression of the LA and pulmonary venous return.

(d) Connecting the diminutive ascending aorta to the main pulmonary artery.

(e) Reconstructing the aortic arch between the proximal main pulmonary artery and the hypoplastic ascending aorta, often using homograft material.

(f) Reconstructing the distal arch to the descending aorta, often using homograft material.

(5) At 3 to 6 months of age, performing a bidirectional Glenn operation (anastomosis of the SVC to the right pulmonary artery). This procedure carries a surgical mortality of less than 5%. Before this procedure, cardiac catheterization is necessary to assess the pulmonary artery anatomy and resistance, the ventricular function, and the ascending aorta and reconstructed arch anatomy.

b. Corrective surgery.

(1) At 2 to 5 years, the child undergoes a modified Fontan procedure (or total cavopulmonary anastomosis) in which the inferior vena cava (IVC) return is rerouted to the pulmonary arteries, often through an extracardiac conduit or with a baffle in the RA.

(2) Before this procedure, another cardiac catheterization is performed to be certain that the anatomy and hemodynamics of the patient are adequate for a Fontan procedure.

(3) Significant ventricular dysfunction or AV valve regurgitation, for instance, would not be tolerated by this circulation. The Fontan circulation requires:

(a) Low PVR.

(b) No anatomic obstruction from the systemic veins to the pulmonary vascular bed and through the pulmonary veins.

(c) Low ventricular filling pressures.

(4) Contraindications to the Fontan procedure include:

(a) Small or stenotic pulmonary arteries.

(b) Nonconfluent pulmonary arteries.

(c) Elevated PVR (>5 U • m²).

G. Follow-up

1. Short-term and medium-term follow up.

(1) Between the first and second stage, the infant is followed quite closely due to the more tenuous nature of the Norwood circulation.

(2) Between the second and third stage, the intervals of follow-up are often increased, assuming the patient is doing clinically well.

(3) After the Fontan procedure, the patient may be seen only on a yearly basis by the pediatric cardiologist.

b. Medications.

(1) Following the initial stage of the Norwood procedure, infants often require multiple medications to:

(a) Improve right heart function.

(b) Reduce the amount of pulmonary blood flow.

(c) Provide anticoagulation (diuretic and aspirin or stronger medication) given the risk of shunt thrombosis.

(2) Such patients should be checked for obstruction of the:

(a) Foramen ovale.

(b) Aortic arch.

(c) Aortopulmonary shunt.

(3) The number of medications is often reduced to one or two if the infant is clinically well after the bidirectional Glenn procedure and initially after the Fontan procedure.

2. Long-term follow-up (after Fontan operation).

a. Medical therapy:

(1) Afterload-reducing agents (angiotensin-converting enzyme [ACE] inhibitors in particular).

(2) Anticoagulation (including warfarin therapy). The target international normalized ratio [INR] is 1.5-2.

(3) Antiarrhythmia medications (possibly necessary).

(4) Subacute bacterial endocarditis (SBE) prophylaxis (necessary for life).

(5) Low-salt diet (preferred).

b. These patients should be excluded from competitive sports.

c. Patients should be checked for:

(1) Systemic hypertension, particularly proximal to the arch repair, which indicates residual arch obstruction or development of an aneurysm of the aorta near the site of repair.

(2) Prolonged hepatomegaly.

(3) Protein-losing enteropathy.

(5) Stenosis at the anastomosis site.

(6) Venous thrombosis.

H. Risk of recurrence

1. Without a familial component, the risk of recurrence may be as high as 2%.

2. In the current case, the recurrence risk for left-sided heart lesions can be as high as 50% (autosomal dominant inheritance) if both the baby and parents have a normal karyotype and no other abnormalities are detected on physical examination or detailed fetal ultrasound (to rule out conditions such as VACTERL association [vertebral anomalies, anal atresia, cardiac anomalies, tracheoesophageal fistula or esophageal atresia, renal or urinary anomalies, limb defect] and Holt–Oram syndrome).

3. Affected children born to healthy parents have been reported, and the possibility of an autosomal recessive mode of inheritance should be considered. In these cases, the recurrence risk can be as high as 25%.

4. There is no way to distinguish between cases with HLHS with multifactorial and autosomal recessive mode of inheritance.

5. Families with left-sided heart lesions associated with NOTCH1 gene mutation and autosomal dominant inheritance with incomplete penetrance and intrafamilial variability of the clinical manifestations have been reported and should be considered in the investigation of such families, including the one in this case.

I. Outcome of this case

1. The baby was delivered at term weighing 2.3 kg. Apgar scores were poor: 4 at 1 minute and 7 at 5 minutes.

2. Pulse oximeter reading was 87% in room air, but the baby had no metabolic acidosis.

3. PGE₁ infusion was started at 0.05 μg /kg per minute.

4. There was a small atrial opening after birth (much smaller than following intervention), but there was evidence of severe pulmonary congestion. The baby was ventilated and treated for pulmonary hypertension with inhaled nitric oxide.

5. He had Norwood stage 1 at day 1 of life with ligation of the vertical vein, thus allowing oxygenated blood to channel to the LA.

6. The PVR was normal at catheterization at 3 months after the Norwood, but the baby had persistent pulmonary dysfunction and remained ventilator dependant at 6 months of age.

7. According to the parents’ wish, supportive care was withdrawn at 6 months of age.

8. No autopsy was performed. Death was related to chronic pulmonary parenchymal disease that was not relieved by atrial opening.

II. YOUR HANDY REFERENCE

A. Prevalence

1. Noonan and Nadas (1958) proposed the term hypoplastic left heart syndrome to describe an obstructive lesion on the left side of the heart associated with hypoplasia of the LV and RV hypertrophy.

2. The incidence of HLHS in infants with congenital heart disease varies from 4.8% to 9% in different series. The prevalence is between 0.1 and 0.27 per 1000 live births. It is considered to be the most common cause of cardiac death during the first week of life.

3. Aortic atresia as part of HLHS is one of the commonest forms of cardiac abnormality encountered in utero.

4. In Allan and Sharland’s (1992) study, HLHS accounted for 17% of the abnormalities of their fetal series.

5. Aortic atresia is most commonly associated with an underdeveloped LV. Such anomaly should be easily detectable by examination of the four-chamber view. Sometimes the rarer forms, which can be associated with a normally developed LV, are missed unless the outflow tracts are properly examined.

B. Outcome

1. Surgical palliation of HLHS is via one of two routes: conventional surgery or primary cardiac transplantation.

a. Chromosomal anomalies increase the surgical risk.

b. Surgery is contraindicated in babies with a neurologic malformation.

2. Norwood procedure.

a. The Norwood procedure (three stages) is the surgical palliation for HLHS. It has been used for about 25 years (with modifications).

b. The outcome of the Norwood procedure has improved with increasing experience with the technique. At the home of the classic operation, the outcome has improved from a 3-year survival of 28% for those operated on between 1984 and 1988 to 66% between 1995 and 1998.

c. The current estimated mortality following the first stage of the Norwood procedure is about 25% and for the second and third stage is less than 10%.

3. Recent comparisons of conventional surgery to primary cardiac transplantation show that identical results can be achieved with either strategy depending on the center’s experience.

a. Of four centers performing a large number of procedures each year, two used reconstructive techniques and two performed primary cardiac transplantation.

b. In both groups, 1-year and 3-year survival was 77% and 61%, respectively.

C. Associated syndromes and extracardiac anomalies

1. HLHS is associated with chromosomal anomalies in up to 10% of cases, particularly Turner’s syndrome (XO), trisomies 13 and 18, and, rarely, microdeletion of chromosome 22q11.

2. Extracardiac malformations after birth are not commonly seen with normal chromosomes.

D. Clues to fetal sonographic diagnosis

Fig. 15-3 Color Doppler of a fetus at 24 weeks’ gestation with hypoplastic left heart syndrome and a left ventricle (LV)–to–coronary artery fistula (F) (arrow). There is mild restriction of the foramen ovale between the left atrium (LA) and the right atrium (RA). RV, right ventricle. See also color version of figure in color insert.

Fig. 15-4 Fetal hypoplastic left heart syndrome at 33 weeks’ gestation with a hypoplastic ascending aorta (AAo) measuring 3 mm in diameter. LV, left ventricle; RV, right ventricle.

E. Progression in utero

1. Most commonly, aortic atresia is associated with an underdeveloped LV, but it can start with a normal-size LV, progressing to a severely hypoplastic ventricle with gestation.

2. The degree of endocardial fibroelastosis can progress depending on LV outflow tract (LVOT) obstruction.

F. Immediate postnatal management

1. Management of patients without a prenatal diagnosis of HLHS.

(1) The neonate is critically ill with mild cyanosis, tachycardia, and tachypnea and has poor peripheral pulses.

(2) The electrocardiogram (ECG) shows RV hypertrophy.

(3) Echocardiography findings are diagnostic.

(4) Acidosis can result in death (such babies die while pink), usually in the first week of life, if the lesion is not treated.

b. Once a patent ductus arteriosus is confirmed, prostaglandins (Box 15-1) are initiated, and maneuvers should be used to minimize systemic vascular resistance and maximize PVR.

c. Observation and monitoring.

(1) We should rely not just on systemic saturations but also on the clinical picture.

(2) Observe the baby for tachypnea or apnea.

(3) Follow lactates, blood gases for evidence of acidosis, and urine output for renal perfusion and systemic perfusion clinically. (The baby should be warm and well perfused, capillary refill should be good, etc.)

d. If the baby is clearly demonstrating problems with either excessive pulmonary blood flow—signs of overcirculation (arterial blood gas showing raised PaO₂)—or inadequate systemic perfusion or both, the following measures can be attempted:

(1) Reducing the fraction of inspired oxygen (FIO₂) to less than room air (19%) by using inspired nitrogen will lower alveolar oxygen to 85% by increasing PVR.

(2) If this fails, one can try various ventilation strategies to assist in reducing the degree of pulmonary blood flow, including manipulation of the PCO₂. Allow PCO₂ to increase (although not to the point at which the lungs are not sufficiently ventilated!).

(3) Paralysis might be required if sedation does not reduce the respiratory drive.

(4) Afterload reduction such as with milrinone can lower the systemic resistance and assist with myocardial function, thus supporting the systemic output.

e. Surgical treatment has been addressed in the management of the case.

(1) Aortic atresia may be associated with other cardiac lesions, including VSD, AVSD, TGA, corrected TGA, and Ebstein’s anomaly of the tricuspid valve.

(2) Each lesion is treated according to the protocol for management of aortic atresia in infancy. Additional lesions add to the late surgical mortality.

G. New hybrid strategy for palliative management of HLHS

a. Despite undeniable recent improvement in survival rates, the Norwood stage 1 operation remains a high-risk endeavor characterized by:

(1) A very invasive neonatal procedure that requires prolonged cardiopulmonary bypass with occasional deep hypothermic circulatory arrest.

(2) Multiple blood transfusions.

(3) Prolonged intensive care recovery.

(4) Delayed sternal closure.

b. When compared with infants undergoing Norwood stage 1, neonates have been shown to have reduced immune defenses, reduced diastolic function, and greater propensity for capillary-leak syndrome.

c. Neurological development of the survivors in relation to prolonged neonatal cardiopulmonary bypass and/or hospitalization in the setting of cyanosis and low cardiac output remains an issue.

d. Therefore, a less invasive method of stage 1 palliation should be beneficial. This is the hybrid strategy for HLHS.

a. Branch pulmonary artery banding is one of the earliest methods of stabilization and remains popular today in specific situations.

(1) Encouraged by initial success of ductal stenting, some groups in Europe began using the strategy of percutaneous ductal stenting followed by surgical band placement for initial palliation of HLHS.

(2) In a hybrid suite, the neonate undergoes sternotomy with bilateral PA banding and stent placement in the ductus. The atrial septum can also be opened at the same setting if it is restrictive.

b. Hybrid palliation controls pulmonary blood flow, provides reliable systemic cardiac output through the patent ductus arteriosus, and creates unobstructed flow from the left atrium, all performed without cardiopulmonary bypass.

c. Initial results are encouraging, but long-term outcome remains to be seen. A randomized trial comparing various options (Norwood or Sano versus hybrid) should tell us the best strategy for these neonates.

H. Pathophysiology

1. During fetal life, the PVR is higher than systemic vascular resistance (SVR), and the dominant RV maintains normal blood flow to the upper and lower body as well as to the placenta.

2. The size of the LV is influenced by the morphology of the mitral valve and the presence or absence of a ventricular septal defect. In cases of aortic atresia combined with mitral atresia, the LV cavity is small (Fig. 15-5).

3. If the mitral valve is patent, thus allowing blood inflow, then the LV is usually larger, although still hypoplastic. In such cases, the LV myocardium might show varying degrees of endocardial fibroelastosis.

4. Severe obstruction to the egress of blood from the LV in the presence of an intact ventricular septum is a prerequisite for the presence of endocardial fibroelastosis.

5. Occasionally, the LV cavity can be of normal size with aortic atresia (in 2%-7%). The majority of such cases were associated with a VSD.

6. After birth there normally is a fall in the PVR, with the SVR being higher than the PVR. In addition, the ductus arteriosus typically closes within the first couple of days postnatally.

7. In HLHS, if the lesion is not recognized, there is a progressive increase in pulmonary blood flow that can virtually steal from the systemic circulation (low effective cardiac output).

8. Oxygen content is increased, with large p/s (ratio of pulmonary flow to systemic flow). When saturations approach 90%, the systemic blood flow is reduced, causing inadequate tissue perfusion. This can result in severe hypoperfusion, metabolic acidosis, and shock.

9. In patients with too much pulmonary blood flow, particularly with progressive metabolic acidosis, inotropic support (particularly at doses that cause alpha receptor effect) should be minimized because it can increase the pulmonary blood flow by increasing the SVR. Afterload-reducing agents such as milrinone may be helpful.

10. The volume-overloaded single ventricle also suffers from myocardial dysfunction and AV valve regurgitation

Fig. 15-5 Hypoplastic left heart syndrome with mitral and aortic atresia. RV, right ventricle.

(Modified from Mullins CE, Mayer DC: Congenital Heart Disease: A Diagrammatic Atlas. New York, Liss, 1988.)

I. Risk of recurrence

1. In general, risk of recurrence of some form of left-sided heart lesions ranges from 8% to 16%.

2. Specifically for HLHS, the risk of recurrence may be as high as 2%.

3. In practice, a recessive mode of inheritance should be considered in families with two affected children or in cases of parental consanguinity.

III. TAKE-HOME MESSAGE

A. Diagnosis

1. Management of HLHS starts prenatally with in utero diagnosis.

2. The foramen ovale is usually patent and shows left-to-right shunt (reverse of normal). A clue to the presence of restrictive atrial septum and significant left atrial hypertension can be the abnormal pulmonary venous pulsed Doppler flow.

3. In HLHS, the interatrial septum is usually fibrotic and thick.

B. Treatment

1. Stage 1 Norwood preoperative care should include resuscitation with prostaglandin to maintain ductal patency and careful management of ventilation, avoiding overventilation and accepting a high normal carbon dioxide level.

2. Optimally, a neonate with HLHS should be left unventilated, trying to preserve the physiologic pulmonary and systemic balance and avoiding overventilation or overcirculation.

3. With increasing experience of the technique, the 3-year survival of the Norwood procedure has improved from 28% to 66%.

4. Comparing conventional surgery to primary cardiac transplantation, recent results show that identical results can be achieved with either strategy so long as the center has an adequate throughput.

5. Further developments in the technology of fetal intervention in the very small heart could alter the otherwise poor prognosis of this subgroup of HLHS.

C. Prognosis

1. Morbidity and mortality are significantly better with prenatal diagnosis: 100% survival as opposed to 66% for those diagnosed postnatally (P = 0.009).

2. Limited data are available about long-term survival of the staged Norwood procedure.

3. Critical aortic stenosis can progress to the HLHS by term due to failure of growth of the LV and the development of complete aortic atresia.

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