Hypoplastic left heart syndrome

Introduction and Etiology

Hypoplastic left heart syndrome (HLHS) represents a spectrum of congenital heart anomalies characterized by severe underdevelopment of the left side of the heart, rendering the left ventricle incapable of supporting the systemic circulation.
HLHS accounts for 2% to 3% of all congenital heart defects, with an estimated incidence of 0.2 to 0.26 per 1000 live births and a male-to-female predominance of 1.5:1.
Anatomical sub-classifications are based on the status of the mitral and aortic valves: mitral atresia with aortic atresia (MA-AA), mitral stenosis with aortic atresia (MS-AA), and mitral stenosis with aortic stenosis (MS-AS).
The etiology is multifactorial, strongly driven by the "no flow–no grow" hypothesis, wherein decreased fetal blood flow through the left heart (e.g., due to severe aortic stenosis) stunts left ventricular development.
Other contributing mechanisms include intrinsic myocardial cell defects and genetic mutations involving genes such as GJA1, NKX2-5, NOTCH1, and MYH6.
HLHS is associated with genetic anomalies in up to 15% of cases, including Turner syndrome, Trisomy 13, 18, and 21, Holt-Oram syndrome, and Jacobsen syndrome.

Survival depends entirely on the morphological right ventricle maintaining both the pulmonary and systemic circulations.
Oxygenated pulmonary venous blood returning to the left atrium must cross the atrial septum via a patent foramen ovale or an atrial septal defect into the right atrium, where it undergoes complete mixing with systemic venous blood.
The right ventricle ejects this mixed blood into the main pulmonary artery; a small portion travels to the lungs, but the vast majority shunts right-to-left across the patent ductus arteriosus to supply the descending aorta.
The ascending aorta and coronary arteries are supplied via retrograde flow from the ductus arteriosus through the transverse aortic arch.
If the atrial septum is intact or highly restrictive, pulmonary venous blood cannot effectively exit the left atrium, leading to profound pulmonary venous hypertension, muscularization of pulmonary vessels, and pulmonary lymphangiectasia (often visualized as "nutmeg lung" on imaging).

Infants with an unrestrictive atrial communication may appear relatively asymptomatic and hemodynamically stable in the first 24 to 48 hours of life.
As the ductus arteriosus naturally begins to constrict, systemic perfusion falls, leading to lethargy, poor feeding, severe respiratory distress, hypotension, and progressive cyanosis.
In neonates presenting with an intact or highly restrictive atrial septum, life-threatening profound cyanosis, severe acidosis, cardiovascular collapse, and pulmonary edema manifest within minutes to hours after birth.

Modality	Specific Findings
Electrocardiogram (ECG)	Initially shows the normal neonatal pattern of right ventricular dominance; subsequently, right ventricular hypertrophy becomes prominent with reduced left ventricular forces, right axis deviation, and tall P waves indicating right atrial enlargement.
Chest Radiograph (CXR)	Heart size is variable initially but rapidly progresses to cardiomegaly; pulmonary vascularity is increased; in patients with a restrictive atrial septum, severe bilateral infiltrates and pulmonary edema are prominent.
Echocardiography	The definitive diagnostic tool demonstrating a hypoplastic or atretic mitral valve, a variably miniaturized or slit-like left ventricle, an atretic or severely hypoplastic aortic root, and enlargement of the right atrium and right ventricle. Echo-bright endocardium suggests endocardial fibroelastosis. Doppler confirms retrograde flow in the transverse aortic arch and left-to-right shunting across the atrial septum.
Cardiac Catheterization	Rarely required for primary diagnosis; however, angiography will define the hypoplastic ascending aorta and right ventricular-dependent coronary circulation. Therapeutically utilized for emergent balloon atrial septostomy or stent placement.

The absolute priority is the immediate initiation of a continuous Prostaglandin E1 (PGE1) infusion to maintain ductal patency and guarantee systemic oxygen delivery.
Supplemental oxygen must be avoided or used with extreme caution, as it is a potent pulmonary vasodilator that will decrease pulmonary vascular resistance, thereby "stealing" blood flow away from the systemic circulation and exacerbating systemic hypoperfusion.
Elective intubation and mechanical ventilation are pursued if clinically indicated for heart failure or shock.
If an intact or severely restrictive atrial septum is identified, emergent catheter-based balloon atrial septostomy or surgical atrial septectomy is required to decompress the left atrium.

Due to the inability to achieve a biventricular repair, management involves a three-stage univentricular palliation pathway leading to a Fontan circulation.
Stage 1 (Neonatal Period): The Norwood procedure involves reconstructing a neoaorta using the pulmonary root and the hypoplastic ascending aorta, performing an atrial septectomy, and establishing controlled pulmonary blood flow via a modified Blalock-Taussig-Thomas shunt or a right ventricle-to-pulmonary artery conduit (Sano modification). An alternative is the Hybrid procedure (stenting the ductus arteriosus combined with bilateral pulmonary artery banding).
Stage 2 (4 to 6 months): The Bidirectional Glenn procedure (superior cavopulmonary anastomosis) connects the superior vena cava directly to the pulmonary arteries, removing a volume load from the single right ventricle.
Stage 3 (2 to 4 years): The Fontan completion routes the inferior vena cava return to the pulmonary arteries, placing the systemic and pulmonary circulations in series and eliminating cyanosis.
Primary orthotopic heart transplantation remains a valid alternative pathway, though limited by donor organ availability.