Hypoplastic Left Heart Syndrome is a pathological condition in which the left heart chamber and its structures (mitral valve, aortic arch, ascending aorta, aortic valve, and left ventricle) remain underdeveloped. Hypoplasia is defined as the clinical condition in which the affected organ or part of the body cannot grow well or remains immature. Due to this, the left heart can not pump sufficient blood to the systemic circulation. It most commonly affects newborn infants.
Hypoplastic left heart syndrome was first described by Noonanfontan and Nades in 1958. In this syndrome, the mitral and aortic valves are not developed completely and the infant has patent foramen ovale and atrial septal defect (ASD). His systemic blood supply is mainly derived from a large right ventricle and patent ductus arteriosus (PDA).
In addition, the mortality rate of this syndrome is very high if surgically not addressed. Infants with hypoplastic left heart syndrome die in the first week of life if they remain untreated.
The prevalence of hypoplastic left heart syndrome is about 1-3 cases per 10000 live births in the United States of America. It accounts for 1.4 to 4% of all congenital heart diseases. The mortality rate of this cardiac defect is 23% in the first week of life if it remains untreated. This sex-dependent syndrome is more prevalent (50-70%) in males than females.¹²

Anatomy of Normal Heart

Normally, there are four chambers in the heart that are responsible for the blood supply. First is the right atrium, which carries deoxygenated from the superior and inferior vena cava. When the right atrium contracts, it sends blood to the right ventricle via tricuspid valves. From the right ventricle, the deoxygenated blood is pumped toward the lungs for oxygenation via pulmonary arteries.
Oxygenation of the blood takes place in the lungs. From the lungs, oxygenated blood enters into the left atrium via pulmonary veins. The left atrium contracts and pumps blood toward the left ventricle. The left ventricle is the main pump of the heart that distributes blood all over the body via the aorta.³

How HLHS Occurs?

In hypoplastic left heart syndrome, the left heart is hypoplastic, and the right heart is hypertrophic (increases in size). In this syndrome, the overall structure of the left heart is underdeveloped. Mitral valve stenosis, aortic valve stenosis, a small left ventricle, and a small ascending aorta characterize it. The left atrium may be small or normal in size. There are 3 most common forms of hypoplastic left heart syndrome. These are:

Mitral Valve Atresia & Aortic Valve Atresia :

It is the most severe form of the disease, characterized by a small left ventricle (slitlike) with a hypoplastic ascending aorta and aortic arch. The right ventricle derives the overall systemic supply through the patent ductus arteriosus (PDA), resulting in right ventricle hypertrophy. Compared to other types, the mortality rate is higher in this condition.

Hypoplastic Mitral Valves & Aortic Valve Atresia:

It is a less severe form of hypoplastic left heart syndrome. In this form, the aortic valve has atresia, resulting in a small aortic arch and ascending aorta with patent mitral valves. The left ventricle is not small but hypertrophic to continue contraction against the stenotic aortic valve, and the right ventricle carries the overall systemic blood supply via PDA.

Hypoplasia of the Mitral Valve & Aortic Stenosis:

Unlike aortic atresia, aortic stenosis allows some extent of blood to pass through the aortic valve resulting in hypoplasia of the left ventricle.

Causes of Hypoplastic Left Heart Syndrome

There are multiple factors that cause Hypoplastic left heart syndrome. It is a heterogeneous syndrome that involves multiple genes like NOTCH1 NKX2, ERBB4, GJA1, and MYH6. This syndrome has an association with other genetic abnormalities;

Turner syndrome
Edward syndrome (trisomy 18)
Jacobs syndrome (deletion of the long arm of chromosome 11)
Patau syndrome (trisomy 13)⁴

Symptoms of Hypoplastic Left Heart Syndrome

The clinical presentation of the hypoplastic left heart syndrome depends upon the severity of the disease. The severity of the disease upon the following factors:

Patency of the ductus arteriosus
Pulmonary resistance
Intra Arterial collaterals

Newborn babies who are not diagnosed prenatally present with the following:

infants with NLHS need urgent medical and surgical managemnt — Infants with NLHS need urgent medical and surgical management

Cool and clammy skin (hypothermia)
Increased heart rate (tachycardia)
Breathing difficulty
Cardiogenic shock (a condition when the heart can not pump enough blood)
Difficult to thrive
Weaker pulse
Cyanosis
Hemodynamic instability

Diagnose Hypoplastic Left Heart Syndrome

As it occurs most commonly in infants, a prenatal history, and screening will help your doctor make a diagnosis. Additionally, physical examination, laboratory investigations, and imaging studies also help to diagnose HLHS.

History:

In History, your doctor may ask the parents some related questions to confirm the diagnosis. History includes points:

Name, age
Family and Drug History
Any previous screening during the prenatal period?
History of smoking, alcoholism, and previous illness?
Did you get a fetal echocardiogram at 16 weeks of gestation?

Physical Examination:

On physical examination, your doctor looks at your child to check for cyanosis, clubbing, pulse, cardiac murmur, oxygen saturation, signs of breathing difficulty, and hypothermia.

Laboratory Studies:

Laboratory investigations are also advised to check hemodynamic instability (unstable blood pressure leading to inadequate blood supply) and rule out other causes. These investigations are:

Complete Blood Count

Your doctor will advise the complete blood count to check the hemoglobin level. In some cases, severe anemia can cause cardiogenic shock. However, patients with hypoplastic left heart syndrome have normal CBC reports.

White Blood Cell Count

White blood cell count rules out the other cause of the disease and ongoing infections in the body.

Serum Electrolytes

Serum electrolytes are advised to check hemodynamic stability. Therefore, infants with HLHS may have electrolyte abnormalities due to poor intake and respiratory insufficiency.

Acid-Base Level

Bicarbonates and carbon are used to assess acid-base status. If the infant has metabolic acidosis, then the carbon dioxide level will be low, but if there is respiratory insufficiency, carbon dioxide levels will be high.

BUN & Creatinine Level

Your doctor will advise BUN/creatinine levels to look at renal status because renal failure can occur due to low perfusion. However, most patients with HLHS have elevated creatinine levels.

Liver Function Tests (LFTs)

Due to low perfusion, hepatocellular damage can also occur. Patients with HLHS show elevated levels of alanine aminotransferase and aspartate aminotransferase.

Genetic Testing

Your doctor may advise karyotyping because multiple genes are involved in causing HLHS.

Lactic Acid Level

Due to low perfusion and hemodynamic instability, lactic acid levels may rise in patients with HLHS. Most infants present with metabolic acidosis that should be immediately corrected.

Arterial Blood Gasses (ABG)

This test is advised to check the respiratory status of the infants. Patients with HLHS show a drop in Po2 level to low perfusion.

a doctor doing echocardiography of child with Hypoplastic Left Heart Syndrome — A doctor doing an echocardiography of a child with HLHS

Electrocardiography

Electrocardiography is a baseline investigation to assess cardiac function. Patients with hypoplastic left heart syndrome show the following abnormalities:

Tachycardia (increased heart rate)
Hypertrophy of the right ventricle
Right acid deviation
Increase in size of the right atrium

Imaging Studies:

Imaging studies used to diagnose the hypoplastic left heart syndrome are:

Chest X-ray

Chest radiography is one of the most important baseline investigations which is easily available to everyone. In the chest radiography of a patient with HLHS, chest X-ray shows cardiomegaly (increased heart size ) and an increased pulmonary vascularity.

Echocardiography

This imaging technique is the investigation of choice in patients with HLHS. Echocardiography provides a two-dimensional heart structure, and the findings are:

The small size of the left ventricle (LV hypoplasia)
Hypoplastic ascending aorta
Right ventricular hypertrophy
Enlargement left atrium

It is essential to rule out other cardiac abnormalities.

Ultrasound (USG) Abdomen

Ultrasound of the abdomen is the best prenatal screening method to assess dysmorphic changes during the developmental phase.⁵

prenatal ultrasonography for Hypoplastic Left Heart Syndrome — prenatal ultrasonography for HLHS

How to treat Hypoplastic Left Heart Syndrome?

Hypoplastic left heart syndrome is a lethal disease that needs urgent medical and surgical interventions. Patients with HLHS need admission to ICU and stabilized before surgery during the first week of life.

Medical Management:

After confirmation of prenatal diagnosis of hypoplastic left heart syndrome with the help of fetal echocardiography, the patient needs urgent medical intervention to stabilize. The aim of medical management is:

Open Patent Ductus Arteriosus

In hypoplastic left heart syndrome, open patent ductus arteriosus carries the overall systemic circulation. So, start infusion of prostaglandin E1 immediately after the birth to ensure the opening of PDA and systemic perfusion. Your doctor will manage the dose of prostaglandin E1 accordingly.

Correction of Metabolic Acidosis

Metabolic acidosis occurs due to hypoperfusion. Immediate correction of metabolic acidosis is necessary to avoid myocardial damage. Infusion of sodium bicarbonate helps to manage acidosis.

Management of Pulmonary Vascular Resistance

The severity of hypoplastic left heart syndrome depends upon the latency of the PDA and pulmonary vascular resistance. In newborn babies, pulmonary vascular resistance is slightly lower than systemic vascular resistance. Moreover, a fall in pulmonary resistance results in increased blood flow to the lungs and decreased blood flow to systemic circulation. Due to the increased blood supply to the lungs, alveolar oxygen saturation is maximum. Therefore, oxygen support is not necessary in patients with HLHS unless severe hypoxemia is not present.
Higher paCO2 levels of 45-50 mmHg help to increase pulmonary resistance. The patient can achieve a higher PaCO2 by the following:

Intubation
Ventilation
Sedation
Addition of Co2 via endotracheal tube

Close monitoring is necessary to avoid serious complications.⁶

Surgical Management:

Surgery is the best option to treat hypoplastic left heart syndrome. There are about three palliative surgical procedures according to the stage of this syndrome. The aim of this procedure is to separate the pulmonary and systemic circulation. The first stage is preferable during the first week of life; the second stage is at 4-6 months, and the third stage is at 2 years of age.

Norwood Procedure (Stage 1):

In 1979, This procedure was described by Norwood et Al. and has become the standard procedure for HLHS.
In this procedure, a modified Blalock-Taussig shunt separates the right ventricle and pulmonary circulation. This procedure includes :

Removal of the atrial septum to allow unrestricted blood flow from the left ventricle to the right vertical
Ligation of patent ductus arteriosus to separate systemic and pulmonary circulation
Formation of an anastomosis between the ascending aorta and pulmonary artery
Blalock-Taussig shunt is a place to maintain pulmonary circulation

Sano Modification:

The disadvantage of this procedure is the diastolic diversion of the blood that causes myocardial ischemia. An alternative procedure called “Sano modification” is performed to avoid this disadvantage.
This procedure forms a tubular connection between the right ventricle and the pulmonary artery. This procedure also has some disadvantages, like aneurysm formation and ventricular arrhythmias.

Hybrid Procedure:

Another procedure called the hybrid procedure is performed in patients for whom the Norwood procedure is contraindicated. This procedure involves the transcatheter and surgical approach to achieve the physiology of the stage 1 procedure. This procedure has significantly reduced the mortality rate in infants.
The oxygen saturation after the stage 1 procedure is in the range of 70-80% due to the mixing of oxygenated blood from the left ventricle with deoxygenated blood from the right ventricle.

Stage 2 Surgery for HLHS:

Stage two surgical procedures are :

Bidirectional Glenn Procedure

Surgeons perform this procedure after 6 months of stage 1 procedure. Before surgery, he will do cardiac catheterization to ensure the patient’s fitness for surgery. In the bidirectional Glenn procedure, surgeons remove the Blalock-Taussig shunt and form an anastomosis between the superior vena cava and pulmonary artery.

Hemi-Fontan Procedure

In this procedure, the surgeon ligates the Blalock-Taussig shunt and closes the junction of the superior vena cava-right atrium with the help of a patch. He will remove it at stage 3.

Fontan Procedure (Stage 3):

Doctors recommend a stage 3 procedure of palliative surgery after two years of the stage 1 procedure. Cardiac catheterization is necessary before this surgery because pulmonary arterial pressure affects the Fontan procedure. Additionally, the aim of this procedure is to drift the blood from the lower body directly into the lungs by making a lateral tunnel between the inferior vena cava and the right pulmonary artery.

Heart Transplant:

A heart transplant is a complicated surgical procedure that involves harvesting the donor’s heart into the recipient. Most of the infants die waiting for a donor for heart transplantation. However, after heart transplantation, regular follow-up, medication, and screening are compulsory to check whether the heart is functioning well or not.

Dietary Modification:

A perfect diet before and after surgery is also essential. Nasogastric feeding with high-calorie breast milk or formula milk is required for patients who can take food orally. However, oral intake is established with time. However, Iron supplementation is necessary to avoid anemia.⁷

Prognosis:

According to a research report, it was noted that 60/100 children with hypoplastic left heart syndrome survived to 4-5 years of age, and 1% of the patients who underwent the Fontan procedure died every year. ⅓ of the infants die in the first week of life before starting the stage 1 procedure.
The mortality is higher in patients with single-functioning right ventricles. According to the report of the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS CHSD), the mortality rate of palliative surgical procedures in 2019 was:

Stage 1 procedure: 15% mortality rate
Hemi Fontan and bidirectional Glenn procedure: 1.8% mortality rate
Fontan procedure: 1%

Recently, the Aristotle score (1-25) was created to check the mortality of the ongoing procedure. The score is collected pre-operatively. The greater the Aristotle score is, the greater the mortality is.⁸

Conclusion

To conclude, hypoplastic left heart syndrome is a congenital disease in which the left heart fails to develop. This is a fatal condition with a higher mortality rate if it remains untreated. Medical and surgical management of HLHS is necessary. If a newborn has cyanosis (blue discoloration of the skin), difficulty breathing, and a weak pulse, immediately consult your doctor for evaluation.

Refrences

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Hypoplastic Left Heart Syndrome: Causes, Symptoms & Care

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