Hypolastic Left Heart Syndrome - SD

Introduction

Hello, my name is Dr. Shing. I'm an associate professor of pediatrics, Chief of pediatric cardiology, co-director of the Heart Center for Children and director of the Cardiovascular Imaging and Research Laboratories at the St. Christopher's hospital for Children and Drexel University College of Medicine.

The topic of my presentation today is hypoplastic left heart syndrome. I want to use this as an example to illustrate the challenges and opportunities in the management of complex congenital heart disease in the current era.

Objectives

Our objectives for today are, I'll start with the case since this is an imaging session. We'll start with the fetal echocardiogram. Then we'll discuss the natural history of left ventricular outflow tract obstructive lesions, causes of hypoplastic left heart syndrome or HLHS, the diagnosis management strategies, outcomes, and then the summary and technical message.

Case Presentation

Let's start with the case. This is a 27 week old fetus referred to us from our high risk OB unit for possible congenital heart disease and a fetal ultrasound. Therefore, a fetal echocardiogram was performed.

This is a four chamber view of the heart, the spine sternum, so posterior, anterior, left and right. So the right ventricle and right atrium looked slightly enlarged. The left ventricle and left atrium relatively smaller. And the right ventricular systolic function seems to be adequate. The left ventricular systolic function seems to diminish.

Here is a cross-section of the aorta. You can see that the aortic valve is thickened hypodysplastic and appears to not move that well. Here's again, the left ventricle with increased the echogenicity, the aorta, which appears to be slightly increasing in size. Here's the aortic valve, which is again, not moving that well if we add color to this picture.

So here's the color Doppler flow from the right atrium across the tra valve to the right ventricle. The flow is laminar and appears to be normal in appearance. In contrast, here's the left heart. The flow from the left atrium across the mitral valve in to the left ventricle appears to have diminished. There's mild amount of mitral regurgitation, and when you see the flow across the aortic valve from the left ventricle to the aorta, there is a small amount of antegrade flow, turbulent flow into the aorta.

And furthermore, this is the atrial septum. There is a fairly good amount of flow from the left atrium to the right atrium, which is abnormal in a fetal circulation 'cause the flow from across the far mill valley should be from the right to left instead of from left to right. So this is reversed the flow across the four mill valley.

This is aorta arch with the head and neck vessels. Here again, you can tell that the flow across the aorta arch is from decenting aorta back to the in aorta. So this is abnormal. Obviously, this is retrograde flow in the aorta.

What is your diagnosis? So this is a fetus with severe aortic stenosis.

Natural History of Left Ventricular Outflow Tract Obstructive Lesions

Now what about the history, natural history of this disease? This is a study done by Hoberg and colleagues a few years ago to look at the natural history of left ventricular outflow tract obstructive lesions in fetuses.

When you look at the size of the left ventricle in this disease over gestational period, if the left ventricle started normal in size or close to normal in size, and the progression is adequate over the gestational period, the left ventricle will grow into adequate size into a biventricular circulation.

If the left ventricle started as a small ventricle and does not progress adequately during the gestational period, these ventricles will not grow into a normal sized left ventricle. These fetuses will become, will develop into hypoplastic left heart syndrome.

If the left ventricular size is somewhat borderline, obviously some will progress into a inadequate size left ventricular with a two ventricular circulation. Some will develop into hypoplastic left heart syndrome with a single ventricle palliative pathway after birth.

There are additional risk factors to differentiate these two groups to the risk factors. For hypoplastic left heart syndrome include a small natural valve, a small aorta slow in the growth rate of left heart structures, reversed all bi direction flow across the Farm Mill Valley. And finally, retrograde flow is in the a RA arch.

Therefore, in the case that we present it, this is, this fetus is very likely to develop into hypoplastic left heart syndrome.

Causes of Hypoplastic Left Heart Syndrome

What is the cause of hypoplastic left heart syndrome? As you know that so far, there's no genes or genetic causes that has been identified to lead to the development of hypoplastic left heart syndrome.

However, from clinical observations and serial fetal echocardiographic studies, we know that if there's altered flow into the left ventricle, for example, if you have decreased flow across the four valley or decreased flow across the mitral valve in the form of mitral stenosis or mitral atresia, or decreased flow across the aortic valve, such as aortic stenosis in our case or aortic sia, the flow into the left heart will be diminished. Therefore, hypoplastic left heart syndrome may develop.

Importance of Hypoplastic Left Heart Syndrome

Why is hypoplastic left heart syndrome important? Well, in the current era, congenital heart surgery has been extremely successful. It has been a safe and effective therapy for most, if not all, type of congenital heart disease.

Here's example, a simple congenital heart defect, ventricular septal defect. Over a thousand cases, the discharge mortality is only 0.6% complex. Congenital heart disease tetrology flow over 500 cases. The mortality is 1.9%. Fairly complex heart disease, transposition of the great arteries. Over 300 cases, they discharge mortality 4% reasonably safe.

What about hypoplastic left heart syndrome? We know that there are three stages of palliation. Stage one Norwood procedure, stage two glim procedure and stage three fontine operation. For stage one Norwood procedure, over 700 cases discharge a mortality over 21%. Stage two glin procedure discharge mortality, 2% stage three font 10, procedure discharge mortality, 4.4%.

So if you add all these three stages up, the total mortality for palliation of hypoplastic left heart syndrome is approaching 30%. So hypoplastic left heart syndrome is one of the final challenges in the treatment of congenital heart disease.

Diagnosis

How do we make the diagnoses? We know that clinical information is extremely important. History and physical examinations are very important in the diagnosis of this disease. ECGs and chest waves are helpful.

Since this is an imaging session, we know that 2D and DOPA echocardiography are diagnostic of this disease.

This is an image of a patient with hypoplastic left heart syndrome. The left ventricle is small and muscle band and does not form the apex of the heart. The left atrium is also small. In contrast, the right atrium and right ventricle are enlarged.

This is an image of the aortic arch in the same patient. So the aortic arch is very small for the A aorta. The transverse arch and decent aorta are not as small due to the retrograde flow from the ductus osis.

This is a color Doppler flow image. There is a small amount of flow from the left atrium to the right atrium. So this is a child with hypoplastic left heart syndrome with a restrictive atrial septum.

Management Strategies

Medical Therapy

What are the current medical therapy for this disease? Initial therapy include prostate gland to keep the PDA open to peruse the systemic circulation, respiratory support and gas manipulations to maintain PVR and very judicious use of oxygen atropic support if needed.

Surgical Approaches

Surgical approaches are currently successful for this disease. There are three surgical options for the first stage of palliation, Also known as the Norwood procedure.

The first option is to reconstruct the aary arch, open up the atrial septum, and to do a modified blade lact toxic shunt. Second approach to do a right ventricle to pulmonary artery shot and a third approach is also available to do a stenting of the ductus cytosis to ban the PA pulmonary artery bilaterally and to open up to stent the atrial septum.

Stage one procedure is generally performed in the neonatal period, stage two in about six month and stage three, the front 10 procedure in about three years.

Over time, survival has significantly improved. We know that in the eighties when normal procedure was first performed, survival is only about 30% Over time. In the late nineties, about 40%, mid nineties, about 50% survival. Late nineties, over 60%. Currently in most of the current series in the literature, survival has reached about 80%.

Outcomes and Research Improvements

Pediatric Heart Network Studies

How do we improve from now? Because these diseases are somewhat rare. National Institute of Health and National Heart Lung Blood Institute have funded pediatric heart network to conduct multi-institutional studies for this relatively rare disease.

One of the questions to study is whether medical therapy is safe and efficacious for this disease. The hypothesis is that if Enalapril improves growth of ventricular function in infants with single ventricle, including hypoplastic left heart syndrome, a multicenter, randomized double blend study using NPR versus placebo was conducted.

A total of 230 infants were randomized into one of the two arms. Hypoplastic left heart syndrome was present in 63% of this population. Fall up was about 14 month. As you can tell that there is no statistical difference between the two groups in weight, height, ventricular mass, mass volume ratio, ejection fraction, and heart failure class, as well as BNP levels.

The only difference is the Head Start conference. It is somewhat smaller in the NL Pro treatment group. Therefore, the conclusion of this multicenter trial is en NPR does not improve somatic growth, ventricular function and heart failure severity, but it is associated with smaller head size.

The second question that was pursued by multicenter studies organized by pediatric Heart Network is that stage one normal procedure, which one is better outta the three options from 2005 to 2008, a total of 900, over 900 newborn infants were screened. Over 600 were eligible. And finally, over 500 were randomized into two arms, a modified BT Shun group and a RV to PA shunt group.

The primary endpoint demonstrated that transplant free survival is favorable to the RV two P Shun group. Survival is 74% versus 64 per percent for the modified BT Shun Group. At 12 months, however, the RV two pH hun group had more complications with 240 interventions versus 180 interventions in the modified BT Shun Group.

Furthermore, at two years, there's survival benefit of the RV two P shot group disappeared with 68% survival versus six to 4% survival in a modified BD shot group.

This is a very important study, and we should also congratulate our surgical colleagues from, for conducting their very first randomized clinical trial in pediatric heart surgery. And this study was published in New England Journal of Medicine in May of this year.

Fetal Intervention

The next question is, we know that left heart obstructive lesions such as aortic stenosis can't lead to hypoplastic left heart syndrome. And then if we can intervene successfully to open up the aortic valve, whether this will lead to the prevention of hypoplastic left heart syndrome.

This study was conducted by Tosky and colleagues a few years ago. What this study did is that they puncture the abdominal wall of the mother using a needle and go through the chest wall of the fetus into the heart, Put a wire across the aortic valve, and using a balloon catheter to dilate the aortic valve.

This is their result. A total of 70 procedures were performed. Over 50 of the procedures were successful. 18 failures of all the successful procedures. 17 or about a third achieved above ventricular circulation less than 30 fetuses still had a hypoplastic left heart with a single ventricle circulation.

On the contrast, the 18 fetuses with no success in this procedure almost all developed into hypoplastic left heart syndrome. It is apparent from this study that fetal intervention to dilate the aortic valve is feasible. And in a subset of group of patients, these can help to prevent hypoplastic left heart syndrome from happening. And for these FET disease, there is hope that they can achieve a biventricular circulation.

However, how to select this group, this subset of patients is an area of active research.

Late Outcomes and Morbidities

We all know that there are late mortality and morbidities for these kids with hypoplastic left heart syndrome. They include atrial arrhythmias, protein luting neuropathy, so PLE, liver dysfunction, progressive ventricular dysfunction, congestive heart failure or stroke.

Therefore, these children were palliated but not cured. Furthermore, they have decreased the exercise capacity in this children with hypoplastic left heart syndrome. The maximum VO two were diminished as a group relative to normal group.

In addition, their new role, developmental outcome and lifestyle are somewhat compromised as a group with decreased the iq, including verbal IQ performance and others.

Summary

So to summarize, there are many challenges and opportunities for the management of hypoplastic left heart syndrome. We don't know the etiology of this disease, therefore we don't have any preventive strategies for it.

We do know the natural history of this disease and how disturbed the flow can lead to hypoplastic left heart syndrome. Surgical intervention is available and effective. However, with somewhat relatively high mortality, morbidity.

There are areas of active research including how to optimally manage these children medically surgically, how to prevent complications and how to improve quality of life and growth and development.

These children were treated palliated, but certainly not cured. And finally, how to use the limited resources to take care of these children with hypoplastic left heart syndrome and other children with congenital heart disease is another challenge and hopefully another opportunity for all of us.

Thank you very much.