By Jan Masila
United States
Introduction
Hypoplastic Left Heart Syndrome is one of the most complicated congenital cardiac defects. It can easily be diagnosed at the fetal stage with the use of Echocardiography. Surprisingly, fetuses do well even with the presence of this condition as long as they are confined to the womb. It becomes very fatal after birth when babies have to survive on their own without depending on fetal circulation.
Hypoplasia is underdevelopment or incomplete development of a tissue or organ. It is descriptive of many medical conditions such as chambers of the heart in hypoplastic left heart syndrome. Hypoplastic left heart syndrome is a collection of diverse congenital heart anomalies in which a diminutive left ventricle is incapable of providing adequate systemic perfusion.
Historical Background
Commonly abbreviated HLHS, Hypoplastic left heart syndrome was first reported in 1952 by Lev but was first described by Noonan and Nadas. According to Goldberg and Rychik, it may include abnormalities such as mitral stenosis or atresia, left ventricular hypoplasia, aortic valve stenosis or atresia, and ascending aortic hypoplasia.
Prevalence and Associated Anomalies
Based upon recent literature reports, the prevalence of HLHS in the population ranges from 0.02% to 0.08% or 0.21 and 0.28 per 1000 live births. These figures are currently on the increase because of increasing survival of patients owing to accurate diagnosis and successful management strategies. The syndrome comprises 8 percent of all cases of congenital heart disease. It is one of the top three heart abnormalities to cause problems in the newborn. HLHS occurs slightly more often in boys than in girls.
The prevalence of extra cardiac anomalies or chromosomal syndromes has been described in autopsy series with HLHS. Numerous syndromes have also been reported in association with HLHS including Holt Oram, Jacobsen and Smith-Lemli-Opitz. Turner syndrome is equally included in this category and has notably been well described in association with HLHS. It is imperative that this particular disease be investigated in every female infant with Hypoplastic Left Heart Syndrome.
The association of HLHS with Developmental brain anomalies has been the focus of much research. Details of the type, frequency, and clinical presentation of developmental brain anomalies in 41 infants with the hypoplastic left heart syndrome encountered during a 52-month interval have been published following a joint study by the Divisions of Neurology, Pathology, and Cardiology, the Children's Hospital of Philadelphia, and the Departments of Neurology, Pathology, and Pediatrics, the University of Pennsylvania School of Medicine. Brain anomalies ranging from agenesis of the corpus callosum, holoprosencephaly to micrencephaly have been associated with HLHS. The study indicated that the occurrence of developmental neuropathology was elevated in those infants with hypoplastic left heart syndrome who did not have a recognizable pattern of malformation but who were small for gestational age, microcephalic, or had ocular abnormalities. This study suggested that infants with hypoplastic left heart syndrome undergo careful genetic, ophthalmologic, and neurologic evaluations which should include imaging of their intracranial anatomy, and long-term neurologic follow-up.
Etiology
Due to the phenotypic differences evident in HLHS, the exact cause is unknown. Some of the developmental origins of HLHS which have been hypothesized include fetal aortic stenosis, altered flow into the developing left ventricle owing to aortic or mitral stenosis/ atresia, obstruction of right-to-left flow early in gestation because of abnormalities of the atrial septum and abnormalities of left ventricular myocardium. HLHS is obviously a heritable disorder with a strong genetic association. It is one of many congenital heart defects with a genetic link, either occurring due to a defect in a gene, a chromosome abnormality, or environmental exposure. This may probably explain why heart problems occur more often in certain families. There have been reports of mutations associated with HLHS in genes NKX2-5, connexin 43 and NOTCHI.
Researchers at Cincinnati Children's Hospital Medical Center have shown in a study, a high heritability and likely genetic underpinnings of HLHS and recommend a direction for future research into its cause, development and possible therapeutic strategies.
“Our study demonstrates that HLHS has high heritability, suggesting it is caused almost entirely by genetic effects instead of environmental factors, and that families with a child with HLHS carry a significant recurrence risk of HLHS or related heart defects. This should be considered by physicians when counseling parents to ensure they are aware of potential risks,” said Robert B. Hinton, Jr., M.D., a physician and researcher at Cincinnati Children's and the study's lead author.
Types
For the purpose of clarity, HLHS can be divided into three main anatomic categories, namely;
mitral and aortic stenosis
mitral stenosis and aortic atresia
mitral and aortic atresia
With respect to anatomy, a review of pathology specimens indicates that 5% of patients with HLHS had left superior vena cave. This can alter surgical technique during palliation. A small left atrium and abnormalities of the atrial septum are common features of HLHS. Inter-atrial communication is crucial for the survival of patients with this condition. An intact atrial septum poses a great risk for poor outcome. The pulmonary venous connections into the left atrium are an important consideration in the description of HLHS and particularly in planning for surgery. Great care must be taken to differentiate anomalous pulmonary drainage from anomalous pulmonary connection.
In hypoplastic left heart syndrome, most of the structures on the left side of the heart are small and underdeveloped. The degree of underdevelopment differs from child to child. The structures affected usually include the following: Mitral valve, Left ventricle, Aortic valve and Aorta. The risk of mortality is increased in patients who fall within the HLHS subcategory of mitral stenosis, aortic atresia, most especially in those patients with coronary connection to the left ventricle. Occurrences of abnormality in the morphology of the tricuspid valve are relatively common in HLHS and may play a big role in short-/long-time survival.
Systemic flow is predominantly through the PDA in the fetus with HLHS and very necessary for survival. The ductal arch therefore develops with a continuous, smooth transition into the descending aorta. Another common feature of HLHS is coarctation of the aorta. In extreme cases of coarctation, coronary perfusion and survival depend on sufficient antegrade flow across the aortic valve. According to Goldberg and Rychik, patients in the category of HLHS marked by mitral stenosis and aortic atresia, may be at risk of fistulous connections, with or without stenosis, from the left ventricle to the coronary arteries. They are at a higher risk for morbidity and mortality than the rest of the patient population with HLHS.
Pathophysiology
Infants with Hypoplastic Left Heart Syndrome can develop life-threatening shock when the ducutus arteriosus begins to close. In most cases, the ductus arteriosus is widely open at the time of birth, supplying the blood flow to the body and babies may not be diagnosed right away. The right ventricle must then do a "double duty" of pumping blood both to the lungs and out to the body via a patent ductus arteriosus (PDA). As the ductus arteriosus closes, the perfusion to the body is seriously diminished and shock rapidly ensues.
Peripheral pulses may be weak, with cool extremities due to poor perfusion. Blood flow to the body will severely diminish resulting in dangerously low blood flow to vital organs and leading to shock. Prostaglandin E1 infusion should be initiated immediately after HLHS is identified in order to maintain the PDA. Hypoplastic Left Heart Syndrome without treatment is fatal, often within the first hours or days of life.
Signs and Symptoms
blue color of the skin, lips and nail beds (cyanosis)
pale skin
sweaty or clammy skin
cool skin
Fast breathing or working hard to breathe
Trouble feeding
Weak pulse
Diagnosis
HLHS is one of the most common cardiac defects picked up on obstetrical screening with ultrasounds and could most readily be diagnosed on fetal echocardiograms . Such early diagnosis of the anomaly allows for prompt intervention for stabilization at the time of birth so that severe shock may be avoided. Alternatively, a child's physician may have heard a heart murmur during a physical examination and then refer the child to a pediatric cardiologist for a diagnosis. Heart murmurs are fairly common and are caused by the turbulence of blood flowing through a narrow region. The pediatric cardiologist will perform a physical examination, listening to the heart and lungs, and make other observations that help in the diagnosis.
Other tests and/or procedures which are employed in the diagnosis of HLHS include; Chest X-ray, Cardiac Catheterization, Cardiac Magnetic Resonance Imaging (MRI) and most especially, Echocardiogram (echo). Due to its non-invasive nature and detailed information, Echo is the principal method of diagnosing Hypoplastic Left Heart Syndrome. It provides detailed information of the anatomy of the various cardiac structures affected in HLHS, as well as important information about the function of the right ventricle, the heart valves, the size of the atrial septal defect (important for blood mixing) and the size of the patent ductus arteriosus. Although Cardiac catheterization is the gold standard, it is rarely used as part of the initial evaluation, with this heart defect due to the high risks in an often unstable newborn.
Treatment
Neonates diagnosed with HLHS will be most likely admitted to the intensive care unit (ICU) or special care nursery once symptoms are noted. They may initially be placed on oxygen, or a ventilator to assist them with breathing. Management strategies can be divided into the initial stabilization period and the operative / post-operative period.
In situations where diagnosis took place before delivery, stabilization measures are started immediately so the newborn does not become unstable. In post natal diagnosis of HLHS, stabilization begins even while diagnostic tests are going on. Immediate infusion of prostaglandin to prevent the patent ductus arteriosus from closing is imperative. This will maintain the pathway for blood to reach the body from the right ventricle.
Because infants in HLHS are most likely to have low oxygen saturations, the tendency will be to administer supplemental oxygen. This should be avoided since it tends to promote more blood flow to the lungs which may steal blood flow from the body and place excessive demands on the already stressed single right ventricle.
The primary treatment options available to children with Hypoplastic Left Heart Syndrome include cardiac transplantation. With all its advantages, this treatment is limited by the scarcity of newborn organs available for transplantation as well as the life-long need for anti-rejection therapy. Even as outcomes for transplantation continue to improve along with decreasing incidence of rejection in patients transplanted as newborns, the average life span of the transplanted heart is still currently limited to less than 15 years.
"Staged reconstruction" is the most commonly pursued treatment for Hypoplastic Left Heart Syndrome. It is a palliative procedure in which three series of operations are performed to reconfigure the cardiovascular system to be as efficient as possible despite the lack of an adequate left ventricle. Due to continued improvement in outcome following reconstructive surgery, many cardiology centers have reserved transplantation exclusively for high-risk infants such as those with tricuspid dysplasia and severe regurgitation or marked Right Ventricular dysfunction.
Norwood operation is the first operation in the staged approach which is typically performed in the first week of life. The desired outcome is that the right ventricle becomes the systemic or main ventricle pumping to the body. From part of the pulmonary artery and the original, underdeveloped aorta a "new" or "neo" aorta is reconstructed to provide blood flow to the body. Finally, a small tube graft is placed either from an artery to the lung vessels (modified Blalock-Taussig shunt) or from the right ventricle to the lung vessels (Sano modification) to provide blood flow to the lungs. This operation is one of the most challenging heart surgeries in pediatrics hence, extensive reconstruction of the aorta that must be done. This is then followed by the bi-directional Glenn procedure and the Fontan operation, typically done at 3 to 6 months of age and 2 or 3 years respectively.
Mortality rate for neonatal Norwood reconstruction is relatively high and some investigators have moved toward the development of strategies that avoid a major surgical operation in the neonatal period. This is called the hybrid approach and it involves both a cardiac catheter-driven procedure and surgical technique. It achieves the same physiologic goals that are similar to the Norwood first-stage reconstruction while avoiding performing a challenging neonatal operation.
Prognosis/Follow-up
With current methods, the survival through the Glenn and Fontan operations exceeds 90 percent. Almost all children with hypoplastic left heart syndrome will continue to need some cardiac medications to optimize the function of their heart. They will need follow-up care throughout their life. Regular periodic follow-up visits with their cardiologist to evaluate their cardiac function and detect late complications is not just required but highly recommended.
Summary
2D-echocardiography and Doppler ultrasound are the diagnostic tools of choice in patients with HLHS. The use of Magnetic Resonance Imaging is complementary to Echocardiography and both provide unique information on cardiovascular anatomy, ventricular function and blood flow. A multidisciplinary team approach is important for successful outcome in the management of HLHS. Pediatric cardiac surgeons, neonatologists, social workers and other crucial medical personnel must be involved. Joining support groups and speaking to families with children living with HLHS should be part of the management strategy.
