Hypoplastic Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) is a spectrum of congenital malformations with underdevelopment of the left ventricle, mitral and aortic valves (stenosis or atresia) and ascending aorta. The right ventricle supports both the pulmonary and systemic circulations, with systemic flow dependent on the arterial duct. It is fatal in the first weeks of life without treatment.

It occurs in about 1 in 4000 to 1 in 5000 live births and forms 2 to 3% of congenital heart disease. Males are affected more often. It was once responsible for about a quarter of cardiac deaths in the first week.

Associated conditions include Turner syndrome, Jacobsen syndrome, Noonan syndrome and 22q11 deletion, and extracardiac anomalies occur in a minority. Genetic variants (including NOTCH1) are implicated. Sibling recurrence risk is about 2 to 8%.

Adverse factors for outcome are low birth weight (under 2.5 kg), prematurity, restrictive or intact atrial septum, ascending aorta under 2 mm, right ventricular dysfunction, significant tricuspid regurgitation, and genetic syndromes.

Pathophysiology.

In foetal life, reduced flow across the left heart limits left ventricular growth. After birth, pulmonary venous return crosses the atrial septum to the right atrium and ventricle, and the right ventricle ejects into the pulmonary artery, with systemic flow through the duct and retrograde perfusion of the aortic arch and coronary arteries.

When the duct closes, systemic and coronary perfusion fall, causing shock, acidosis and death. A restrictive atrial septum causes pulmonary venous hypertension and severe hypoxaemia.

Pulmonary and systemic flows depend on the balance of resistances. Falling pulmonary vascular resistance after birth draws flow into the lungs at the expense of the body, and causes systemic hypoperfusion, necrotising enterocolitis and renal failure.

Most infants appear well initially, then within the first days of life develop tachypnoea, poor feeding, pallor, grey colour, weak or absent pulses, cool peripheries, hepatomegaly, gallop rhythm, a single second heart sound and cardiogenic shock as the duct closes. Cyanosis is modest because of mixing, and is severe with a restrictive atrial septum. Some are diagnosed antenatally.

• Foetal echocardiography at 18 to 22 weeks gives antenatal diagnosis, and allows delivery at a cardiac centre.
• Postnatal echocardiography: small left ventricle, atretic or stenotic mitral and aortic valves, diminutive ascending aorta with retrograde arch flow, atrial septum (restrictive when flow is to-and-fro or the gradient is over 10 mmHg), right ventricular function, tricuspid regurgitation, coarctation.
• Arterial blood gas and lactate. Pre-ductal and post-ductal saturations. Renal and liver function. Head ultrasound before surgery.
• Genetic testing (microarray and karyotype), and review for extracardiac anomalies.
• Target arterial saturation in the balanced circulation is 75 to 85%.

Differential diagnosis.

• Critical aortic stenosis, interrupted aortic arch and critical coarctation.
• Sepsis, inborn errors of metabolism and primary cardiomyopathy.
• Other duct dependent lesions (pulmonary atresia, transposition).
• Total anomalous pulmonary venous return with obstruction.

Immediate stabilisation (first hours).

• Alprostadil (prostaglandin E1) intravenously to keep the duct open: 0.05 to 0.1 microgram/kg/min to reopen a closing duct, reduced to the lowest effective dose (0.01 to 0.03 microgram/kg/min) once patent. Watch for apnoea (about 10 to 20%, so intubate for transport or doses over 0.05 microgram/kg/min), fever, hypotension, flushing and seizures. Prolonged use causes gastric outlet obstruction and bone changes.
• Avoid supplemental oxygen and hyperventilation, which lower pulmonary vascular resistance and steal flow from the body. Keep saturation at 75 to 85%, PaCO2 at 40 to 50 mmHg and normal pH. Avoid pulmonary vasodilators.
• Treat shock: volume 10 mL/kg if hypovolaemic, correct acidosis, milrinone 0.25 to 0.75 microgram/kg/min (no loading dose when hypotensive; reduce in renal impairment), or dopamine 5 to 10 microgram/kg/min. Maintain haemoglobin 13 to 15 g/dL.
• Restrictive or intact atrial septum: urgent balloon atrial septostomy, or stenting, or surgical septectomy.
• Transfer to a paediatric cardiac surgical centre immediately.

Staged surgical palliation.

• Stage 1 (Norwood procedure, in the first 2 weeks): reconstruct the aortic arch and create unobstructed systemic outflow from the right ventricle, with pulmonary flow from a modified Blalock-Taussig-Thomas shunt or a right ventricle to pulmonary artery conduit. Hospital survival is about 85 to 95% in experienced centres.
• Alternative hybrid approach: ductal stenting with bilateral pulmonary artery bands, in high risk neonates or as a bridge to transplantation.
• Stage 2 (bidirectional Glenn procedure at 3 to 6 months): superior vena cava to pulmonary artery.
• Stage 3 (Fontan completion at 2 to 4 years): inferior vena cava to pulmonary artery.
• Transplantation is an alternative primary strategy, or follows failure of palliation.

Medical therapy.

• Interstage: aspirin 3 to 5 mg/kg orally once daily after shunt placement. Furosemide 1 mg/kg orally every 12 hours as needed. Enalapril 0.05 to 0.1 mg/kg orally daily, increased gradually to a maximum of 0.5 mg/kg daily with potassium and creatinine checks at 1 to 2 weeks, for right ventricular dysfunction or significant tricuspid regurgitation.
• Home surveillance during the interstage period: daily weight, oxygen saturation (target 75 to 90%), feeding and temperature, with a weight gain of 20 to 30 g daily. Early return for saturation under 70%, poor feeding or illness. This reduces interstage mortality to under 10%.
• Ventricular dysfunction: carvedilol 0.05 mg/kg twice daily, doubled every 2 weeks to a maximum of 0.4 to 0.5 mg/kg twice daily when stable.
• After Fontan: aspirin 3 to 5 mg/kg daily, or warfarin to INR 2.0 to 3.0 for high risk circulations (thrombus, arrhythmia, low flow).
• RSV prevention in infants under 2 years: palivizumab 15 mg/kg intramuscularly monthly during the season (up to 5 doses), or nirsevimab as a single intramuscular dose by weight (50 mg under 5 kg, 100 mg for 5 kg or more) where available.
• Endocarditis prophylaxis for dental procedures with prosthetic material: amoxicillin 50 mg/kg (maximum 2 g) orally 30 to 60 minutes before.

Neurodevelopment and growth. Early developmental screening and intervention, feeding support (often nasogastric feeding), and vaccination.

Monitoring. Saturation, weight and feeding at each contact. Echocardiography at each stage and at least every 3 to 6 months in infancy. Cardiac catheterisation before the Glenn and Fontan stages. Ambulatory ECG for arrhythmia. Lifelong follow up of Fontan circulation (liver, kidney, protein losing enteropathy, arrhythmia).

Referral and escalation. Refer every suspected case to a paediatric cardiac centre at once, and deliver the pregnancy at a centre with neonatal cardiac services when diagnosed antenatally. Urgent review for fall in saturation, poor feeding, tachypnoea, vomiting or lethargy.

Special groups.

• Pregnancy: counselling before conception for women with a Fontan circulation. Maternal and foetal complications are higher. Avoid ACE inhibitors during pregnancy.
• Siblings and parents: offer foetal echocardiography in subsequent pregnancies, and genetic counselling.
• Region specific: where prostaglandin infusions and neonatal cardiac surgery are unavailable, outcome is poor, and palliative care for the family should be offered.