Pediatric Hypoplastic Left Heart Syndrome

Updated: Dec 30, 2015
  • Author: Syamasundar Rao Patnana, MD; Chief Editor: Stuart Berger, MD  more...
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Overview

Background

The term hypoplastic left heart syndrome (HLHS), initially proposed by Noonan and Nadas, [1] describes a spectrum of cardiac abnormalities characterized by marked hypoplasia of the left ventricle and ascending aorta. This is the same disorder characterized as hypoplasia of the aortic tract complex by Lev. [2] The aortic and mitral valves are atretic, hypoplastic, or stenotic. A patent foramen ovale or an atrial septal defect is usually present. The ventricular septum is usually intact. A large patent ductus arteriosus supplies blood to the systemic circulation. Systemic arterial desaturation may be present because of complete mixing of pulmonary and systemic venous blood in the right atrium. Coarctation of the aorta is also commonly present. See the images below.

This echocardiographic still frame shows a long-ax This echocardiographic still frame shows a long-axis view of the aortic arch in a patient with hypoplastic left heart syndrome (HLHS). The ascending aorta is markedly hypoplastic, serving only to deliver blood in a retrograde fashion to the coronary arteries. An echo-bright coarctation shelf is seen at the insertion of the ductus arteriosus.
This echocardiographic still frame shows a 4-chamb This echocardiographic still frame shows a 4-chamber view of the heart in a patient with hypoplastic left heart syndrome (HLHS). A large right ventricle (RV) and hypoplastic left ventricle (star) are seen. Right atrium = RA. Left atrium = LA.

Hypoplastic left heart syndrome is a uniformly lethal cardiac abnormality if not surgically addressed. Since the description of surgical palliation by Norwood in the early 1980s [3, 4] and the description of allograft cardiac transplantation by Bailey in the mid 1980s, [5] the interest in this lesion has remarkably increased. Currently, the Norwood surgical approach consists of a series of 3 operations: the Norwood procedure (stage I), the hemi-Fontan or bidirectional Glenn procedure (stage II), and the Fontan procedure (stage III). Orthotopic heart transplantation provides an alternative therapy, with results similar to those of the staged surgical palliation. Currently, the survival rate of infants treated with these surgical approaches is similar to that of infants with other complex forms of congenital heart disease in which a 2-ventricle repair is not possible.

Pathologic anatomy

Hypoplasia of the left heart structures is noted, with enlargement and hypertrophy of the right heart. Similar to other congenital heart defects, hypoplastic left heart syndrome also has a spectrum of severity. [6] In the most severe form, aortic and mitral valve are atretic, with a diminutive ascending aorta and markedly hypoplastic left ventricle. The left atrium is usually smaller than normal, although it may be normal in size or enlarged. It receives all pulmonary veins. Pulmonary vein stenosis is a rare but important abnormality.

The mitral valve may be atretic, hypoplastic or severely stenotic. The atretic mitral valve consists of fibromuscular tissue instead of a membrane. When the valve is stenotic, the entire mitral valve apparatus, including the valve annulus, valve leaflets, papillary muscles, and chordae tendineae, is small and hypoplastic.

The left ventricle is usually a thick-walled, slitlike cavity, especially when mitral atresia is present. When the mitral valve is perforate, the left ventricular cavity is small. Endocardial fibroelastosis is usually present. The aortic valve is either severely stenotic or atretic. The ascending aorta is often severely hypoplastic, measuring 2-3 mm in diameter, serving as a conduit to supply blood to both coronary arteries in a retrograde fashion. However, it may approach normal dimensions. [7, 8]

Coarctation of the aorta may be present in a significant number of patients with hypoplastic left heart syndrome, [3, 9, 10, 11] but interrupted aortic arch is rare. The right heart (ie, right atrium, right ventricle, pulmonary arteries) is markedly enlarged.

A patent foramen ovale is common; herniation of the valve of the septum into the right atrium may be noted. Rarely, the patent foramen ovale is completely closed. A true atrial septal defect is rarely present. Ventricular septal defect is not considered to be an integral part of hypoplastic left heart syndrome, although it may be present in the syndrome of mitral atresia with normal aortic root.

The most common presentation is visceroatrial situs solitus with D-ventricular loop and atrioventricular and ventriculoarterial concordance, as well as levocardia. Rarely, dextrocardia and heterotaxy may be present.

Severely hypoplastic left ventricle can be present in hearts with double-outlet right ventricle and common atrioventricular canal; in some studies, these variants constitute as many as 25% of hypoplastic left heart syndrome cases. [12]

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Pathophysiology

Prenatal circulation

The oxygenated blood from the placenta is returned to the inferior vena cava and is not shunted preferentially across the patent foramen ovale into the left atrium; instead, it mixes with the superior vena caval blood in the right atrium. The pulmonary veins drain into the left atrium, and the pulmonary venous blood gets shunted across the atrial septum into the right atrium because of mitral valve obstruction. The vena caval and pulmonary venous blood along with the coronary sinus flow enters the right ventricle and the pulmonary artery. [13, 14]

Because of widely patent ductus arteriosus and high pulmonary vascular resistance in the fetus, a small portion of the blood from the right heart enters the lungs. Most of the blood is directed into the aorta via the ductus. Once in the aorta, the blood gets distributed into the brachiocephalic vessels, ascending aorta, and descending aorta. The quantitative distribution into these different vascular beds depends on their relative vascular resistances. The ascending aortic blood flows in a reverse direction and supplies the coronary arteries.

The fetal hypoplastic left heart syndrome circulation differs from the normal fetus in the following manner:

  • Larger quantity of flow across the ductus with a higher PO 2: Whether these factors influence the development of ductal musculature, which may, in turn, influence postnatal ductal closure, is unclear.
  • Lower PO 2 and questionably lower blood flow to the brain: The weight of the brain is generally normal, although no detailed studies on the cellular development of brain have been performed. However, whether the reported association between brain anomalies and hypoplastic left heart syndrome is related to abnormal flow and PO 2 to the brain remains unknown.
  • Higher PO 2 to the lungs: The low PO 2 in the pulmonary artery blood in the normal fetus is believed to be responsible for development of muscular pulmonary arterioles. Higher-than-normal PO 2 in hypoplastic left heart syndrome may lead to lack of normal medial muscular hypertrophy, which may result in rapid decline of pulmonary vascular resistance after birth.
  • Retrograde coronary blood flow via a long channel with lower PO 2: This abnormality is not believed to interfere with supply of normal quantities of oxygen and nutrients to the myocardium. However, whether myocardial reserve is adversely affected is unclear.

Postnatal circulation

The newborn infant with hypoplastic left heart syndrome has a complex cardiovascular physiology. Fully saturated pulmonary venous blood returning to the left atrium cannot flow into the left ventricle because of atresia, hypoplasia, or stenosis of the mitral valve. Therefore, pulmonary venous blood must cross the atrial septum. In most babies, a patent foramen ovale is present and is small and partially obstructive. [15] This blood mixes with desaturated systemic venous blood in the right atrium. The right ventricle then must pump this mixed blood to both the pulmonary and the systemic circulations that are connected in parallel, rather than in series, by the ductus arteriosus. Blood exiting the right ventricle may flow (1) to the lungs via the branch pulmonary arteries or (2) to the body via the ductus arteriosus. The amount of blood that flows into each circulation is based on the resistance in each circuit. [6, 13]

Blood flow is inversely proportional to resistance (Ohm law); that is, when resistance in blood vessels decreases, blood flow through these vessels increases. Following birth, pulmonary vascular resistance decreases, which allows a higher percentage of the fixed right ventricular output to go to the lungs instead of the body. Although increased pulmonary blood flow results in higher oxygen saturation, systemic blood flow is decreased. Perfusion becomes poor, and metabolic acidosis and oliguria may develop. Coronary artery and cerebral perfusion also depend on blood flow through the ductus arteriosus and then retrograde flow via the aortic arch and ascending aorta. Therefore, increased pulmonary blood flow results in decreased flow to the coronary arteries and brain, with a risk of myocardial or cerebral ischemia.

Alternatively, if pulmonary vascular resistance is significantly higher than systemic vascular resistance, systemic blood flow is increased at the expense of pulmonary blood flow. This may result in hypoxemia. A delicate balance between pulmonary and systemic vascular resistances should be maintained to ensure adequate oxygenation and tissue perfusion.

Most patients with hypoplastic left heart syndrome also have coarctation of the aorta. This can be significant enough to interfere with retrograde flow to the proximal aorta.

In summary, the postnatal circulation in hypoplastic left heart syndrome depends on 3 major factors:

  1. Adequacy of interatrial communication
  2. Patency of the ductus arteriosus
  3. level of pulmonary vascular resistance
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Etiology

The exact cause of hypoplastic left heart syndrome is unknown. Although familial cases with autosomal recessive inheritance have been reported, [6]  hypoplastic left heart syndrome is generally postulated to follow multifactorial mode of inheritance. [16]

Most likely, the primary abnormality occurs during aortic and mitral valve development. During cardiac development, adequate flow of blood through a structure is largely responsible for the growth of that structure. With little or no blood flow because of aortic and mitral valve atresia, growth of the left ventricle does not occur.

Similarly, growth of the ascending aorta does not occur because of lack of left ventricular output. The ascending aorta is perfused in retrograde manner from the ductus arteriosus functioning only as a common coronary artery.

Premature closure or absence of the foramen ovale represents another theoretical cause of hypoplastic left heart syndrome because it eliminates fetal blood flow from the inferior vena cava to the left atrium. [17]  Fetal pulmonary blood flow is not sufficient for normal development of the left atrium, left ventricle, and ascending aorta.

Another postulated cause is misalignment of the atrial septum to the left. [18]

More recent studies suggest that hypoplastic left heart syndrome is genetically heterogeneous and hypoplastic left heart syndrome and bicuspid aortic valve are genetically related. [19, 20]

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Epidemiology

United States statistics

Incidence of hypoplastic left heart syndrome is 0.16-0.36 per 1000 live births. [21] It comprises 1.2-1.5% of all congenital heart defects. [22, 23] Hypoplastic left heart syndrome accounts for 7-9% of all congenital heart disease diagnosed in the first year of life. [12] Before surgical treatment was available, hypoplastic left heart syndrome was responsible for 25% of cardiac deaths in the neonatal period. [12] The rate of occurrence is increased in patients with Turner syndrome, Noonan syndrome, Smith-Lemli-Opitz syndrome, or Holt-Oram syndrome. Certain chromosomal duplications, translocations, and deletions are also associated with hypoplastic left heart syndrome.

The international frequency is similar to that in the United States.

Sex- and age-related demographics

Hypoplastic left heart syndrome is more common in males than in females, with a 55-70% male predominance.

Hypoplastic left heart syndrome typically presents within the first 24-48 hours of life. Presentation occurs as soon as the ductus arteriosus constricts, thereby decreasing systemic blood flow, producing shock, and, without intervention, causing death. Infants with pulmonary venous obstruction (absent or restrictive patent foramen ovale) may present sooner. Very rarely, an infant with persistence of high pulmonary vascular resistance and the ductus arteriosus may present later because of balanced pulmonary and systemic blood flow.

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Prognosis

Overall survival to the time of hospital discharge after the Norwood procedure is nearly 75%. [24]  Success rates are higher in uncomplicated cases and lower in cases in which important preoperative risk factors are present, such as age greater than 1 month, significant preoperative tricuspid insufficiency, pulmonary venous hypertension, associated major chromosomal or noncardiac abnormalities, and prematurity.

Note the following:

  • High Aristotle scores (>20) are associated with high hospital mortality and low survival at follow-up. [25]
  • Low cerebral near-infrared spectroscopy oxygen saturations during the first 48 hours after Norwood procedure are strongly associated with adverse outcomes. [26]
  • Survival after the bidirectional Glenn/hemi-Fontan and Fontan operations is nearly 90-95%.
  • The actuarial survival rate after staged reconstruction is 70% at 5 years.
  • Institutional success rates vary.
  • Neurodevelopmental prognosis is not known; however, abnormalities are reported.
  • Approximately 20% of infants listed for cardiac transplantation die while waiting for a donor heart. After successful transplantation, the survival rate at 5 years is approximately 80%.
  • When the preoperative mortality is considered, the overall survival rate after cardiac transplantation is approximately 70%, or similar to the results for staged reconstruction.

Mortality/morbidity

Hypoplastic left heart syndrome has the greatest mortality rate among all coronary heart conditions. [27]  Without surgery, hypoplastic left heart syndrome is uniformly fatal, [27] usually within the first 2 weeks of life. Survival for a longer period occurs rarely and only with persistence of the ductus arteriosus and balanced systemic and pulmonary circulations.

Following the Norwood procedure (stage I), overall success (survival to hospital discharge) is approximately 75%. Success rates are higher (85%) in patients with low preoperative risk and lower (45%) in patients with important risk factors. The risk factors for poor result are multiple and vary from study to study and include prematurity and major noncardiac malformations. Other identified risk factors include surgery in older infants (>1 mo), significant tricuspid regurgitation, and pulmonary venous hypertension. High Aristotle scores are also associated with poor prognosis.

A study of data from the Society of Thoracic Surgeons Congenital Heart Surgery Database assessed the mortality rates and postoperative complications after the Norwood procedure in 2,557 patients. The overall mortality rate was noted as 22%, with 75% having at least 1 complication. Increases in mortality rate correlated with increases in the number of complications, with renal and cardiovascular complications carrying the greatest risk of mortality. Factors associated with complications included weight less than 2.5 kg, single right versus single left ventricle, preoperative shock, genetic abnormality, and preoperative mechanical ventilatory or circulatory support. [28]

Some centers have reported stage I survival rates in excess of 90%. This appears to be related, in part, to institutional surgical volume. The overall success following the bidirectional Glenn or hemi-Fontan procedure (stage II) approaches 95%. Success after completing the Fontan procedure (stage III) approaches 90%. Orthotopic heart transplantation results in early and long-term success similar to that of staged reconstruction. Among low-risk patients who undergo staged reconstruction or transplantation, actuarial survival at 5 years is approximately 70%.

Substantial morbidity is associated with multiple cardiac catheterizations, cardiac interventions, and cardiac surgery in patients undergoing Norwood palliation. Similarly the need for multiple cardiac biopsies and hospitalizations related to immunologic management and infections exist in patients who had cardiac transplantation.

Most studies report neurodevelopmental disabilities in a significant number of patients who survive either staged surgical reconstruction or cardiac transplantation.

Complications

Preoperative complications include acidosis, congestive heart failure (CHF), renal failure, liver failure, necrotizing enterocolitis, sepsis, and death.

Postoperative complications include acidosis, CHF, renal failure, liver failure, necrotizing enterocolitis, sepsis, pericardial or pleural effusion, phrenic or recurrent laryngeal nerve damage, stroke, coarctation of the aorta, and death. Early graft rejection and opportunist infection may occur after cardiac transplantation.

Major complications following the Norwood procedure include aortic arch obstruction at the site of surgical anastomosis and progressive cyanosis caused by limited blood flow through the shunt. An inadequate atrial communication contributes to progressive cyanosis. A study of data from the Society of Thoracic Surgeons Congenital Heart Surgery Database assessed the mortality rates and postoperative complications after the Norwood procedure in 2,557 patients. Factors associated with complications included weight less than 2.5 kg, single right versus single left ventricle, preoperative shock, genetic abnormality, and preoperative mechanical ventilatory or circulatory support. [28]

Major complications following the bidirectional Glenn/hemi-Fontan procedure include transient superior vena cava syndrome and persistent pleural or pericardial effusion. The development of systemic venous to pulmonary venous collateral vessels is possible.

Major complications following the Fontan procedure include persistent pleural or pericardial effusion. Neurodevelopmental abnormalities are reported and may be inherent in some patients with hypoplastic left heart syndrome.

Arrhythmias, obstructed venous pathways, and protein-losing enteropathy are some of the other complications observed following the Fontan operation.

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Patient Education

General

At the outset, appropriately warn the parents and other caregivers that hypoplastic left heart syndrome is a complex heart defect that requires multiple hospitalizations, surgeries, catheter interventions and long-term follow-up.

Medication

Educate parents regarding the doses and side effects of their child's cardiac medications.

Discuss interactions with other medications with the family and the infant's general pediatrician.

Feeding

Many infants require nasogastric or G-tube tube feeding after discharge from the hospital. Parents must become comfortable with placement of the nasogastric feeding tube and/or care for the G-tube, as the case may be.

Frequently, increased-calorie formula is required for adequate growth. Provide the formula recipe or a source for purchasing it to the caregiver.

Follow-up care

Stress the importance of follow-up care. If necessary, provide cab or bus vouchers to ensure compliance.

If noncompliance becomes a critical issue, physicians are required to report to the appropriate family services agency.

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