Lynne Ramsay: When I was pregnant with Joseph, we expected just to have another normal pregnancy, normal child. And I went to find out if he was a boy or a girl, and instead of finding out that, we also found out that he had a heart problem. That was very shocking after having had healthy boys before.

Anthony Ramsay: We heard — it was just before Christmas, so it was — you know, it was a bad time and, you know, I mean all of us, everyone in the family pulled, you know, together.

Lynne Ramsay: It was very hard on me to be pregnant and to be that sad and scared and also to have my other two children to take care of when I had all that constantly in the back of my mind.

Thomas L. Spray, MD: All of heart surgery is 50 years old, and we've come from a situation of being able to treat nothing to being able to at least deal with most, if not a vast majority of, congenital heart defects in a way that allows children to grow into adulthood.

Jack Rychik, MD: We live in an era where there are very few things that we really can't take care of.

Thomas L. Spray, MD: And children with a heart defect born today, I am sure, are going to have a much better outcome at age 50 than somebody born 30 years ago.

Sarah Tabbutt, MD: It used to be we were just trying to get the babies to survive to discharge, and now we're really focusing on more than that. Now we're focusing on how to give the parents a better child to take home.

Thomas L. Spray, MD: And as things continually improve, and as these children have issues when they get older, I have no doubt we will have ways to treat those issues. So I don't see any reason to be pessimistic about the long-term outlook for these children.

Jack Rychik, MD: The term "single ventricle" relates to a series of abnormalities in which nature has only allowed for the development of one pumping chamber. Normally, there should be two ventricles, one assigned to delivering blood to the lung, one assigned to delivering blood to the body. But there are a very wide spectrum of abnormalities in which there is functionally, or even anatomically, only one pumping chamber.

Peter J. Gruber, MD: This is a really complex group of lesions in general, and from a medical standpoint, they're categorized through a number of complex anatomical names. But practically, you can divide them into sort of three different categories. The first would be those in which it's difficult for blood to get from the heart out to the body. Second would be those in which it's difficult to get blood from the heart to the lungs. And the third in which there's a balance situation in which blood gets both from the heart to the lungs and the heart to the body, and yet you still can't use two ventricles. You can only use one pumping chamber.

Jack Rychik, MD: In order to understand and to comprehend any of the different forms of heart disease that exist, it's very important to make sure we understand what the healthy or the normal heart looks like. The normal heart has two sides, a right side and a left side, and four chambers, the top receiving chambers, or atrium, and the lower chambers, which are thick-walled pumping chambers called ventricles. Red blood cell will come from either the superior vena cava or the inferior vena cava and enter into the right atrium. The blood then flows across the tricuspid valve to the right ventricle. The right ventricle then squeezes and ejects that blood cell into a vessel called the pulmonary artery. The pulmonary artery splits into two vessels, each going to the lungs. As that red blood cell makes its way through the lung, it returns through the pulmonary veins to the left atrium. That blood is now oxygenated. It's picked up oxygen, then goes across the mitral valve into the left ventricle, which does most of the work in terms of delivery of blood flow to the body. That blood cell is now ejected into the aorta to some organ or muscle or skin in the human body. Now, there are some significant differences between the heart in the newborn and the heart in the fetus.

Elizabeth Goldmuntz, MD: The heart actually is — assumes its almost complete anatomy often before a woman would even know she was pregnant.

J. William Gaynor, MD: The heart is actually functioning and pumping blood to the baby throughout most of fetal life.

Jack Rychik, MD: Because the lungs are collapsed in the fetus and it's really the placenta through which much of the oxygenation takes place through the mother, there are various bypass pathways within the fetal heart that direct blood away from the lung. The first is a structure called the foramen ovale. That's communication between the two top chambers of the heart that allows for blood to go from the right atrium to the left atrium. In fact, because there is very little blood that's returning from the lung which would normally go to the left side, the majority of blood that fills the left atrium and left ventricle is coming across the foramen ovale from the right side. Because the lungs are collapsed, there's high pressure, high resistance in the lungs. As blood is ejected out the right ventricle and enters into the main pulmonary artery, very little goes down into the lungs themselves. The majority goes into a structure called the ductus arteriosus, which is the second important communication between the pulmonary artery and the descending aorta. The third structure that's important that connects the umbilical vein to the fetal circulation is a site, a junction, called the ductus venosus. That acts as somewhat of a resister, if you will, in terms of controlling the return of blood from the placenta to the fetal circulation. Birth is a wonderful process and an amazing process, and there's a dramatic change that takes place in what we call the fetal transition, this transition of the circulation from fetal life to neonatal life. As soon as the cord is clamped, the ductus venosus ceases to carry blood to the heart, and it begins to constrict within the first few hours or days of life. The very first thing that happens when a fetus is born is it takes its first breath, the lungs expand, and so the resistance or pressure in the lungs drop, and that promotes blood flow into the lung itself. The ductus arteriosus begins to constrict and is typically fully closed within 24 to 48 hours of life, and blood is now then fully directed into the lung. As the blood returns to the left side of the heart, after traversing the pulmonary circulation and picking up oxygen, the pressure in the left atrium rises just a bit, and the trap door of the foramen ovale, which was open before birth, now begins to close, usually within the first few days of life. So one can imagine that if you are solely dependent on your one ventricle to do the job of delivering blood to the body, once that ductus arteriosus begins to constrict or close, then there's no way for blood to get to the body, and unfortunately these babies — these babies die.

Peter J. Gruber, MD: But if we know a complex lesion is coming up, a child that's suffering from one of these, we can prepare for that ahead of time.

J. William Gaynor, MD: We can avoid having a sudden cardiac arrest at home, or even death, sudden death at home, by knowing that the baby has the heart defect. If necessary, we can arrange to have the baby delivered at CHOP —

Thomas L. Spray, MD: In a much more controlled treatment strategy. So that's a huge advantage in terms of prenatal diagnosis.

Thomas L. Spray, MD: What we want to do after a baby is born is we want to stabilize the child, make sure that there are no other organs involved, because there are other associated anomalies in some children. We want to make sure that there are no genetic issues that we need to address. We want to make sure all the other organ systems are as good as they can be and assess them if we have to. And then once that is done, then it's more a matter of scheduling the surgery.

Jack Rychik, MD: We have identified some risk factors in patients who have single ventricle type of heart disease.

J. William Gaynor, MD: Certain forms of single ventricle may not do as well as others.

Jack Rychik, MD: Since one has to utilize the well-functioning ventricle to do the job of delivering blood flow to the body, if that single ventricle in some way is not functioning well, or if there's leakage of the valve that leads into it, that could be a significant risk factor for reconstruction.

Peter J. Gruber, MD: Many times there are other associated genetic abnormalities that we have to look for carefully, and these sorts of genetic abnormalities would provide incremental or increased risk for the operation itself.

Jack Rychik, MD: If the babies are immature, premature, that can add significant risk.

J. William Gaynor, MD: One of the things that can cause a real problem is when there's blockage to blood flow from the lungs getting back to the heart.

Jack Rychik, MD: An obstruction of blood flow coming out of the lung, that we know can result in poor development of the lungs and can add risk, as well.

J. William Gaynor, MD: For many children with complex heart disease, there's blockage of the blood either going to the body or to the lungs. And there's a blood vessel called the ductus arteriosus which connects those two arteries. Everybody has one, and it usually closes after birth.

Sarah Tabbutt, MD: You can keep that blood vessel open with a medication called prostaglandins. And so, therefore, by giving a baby prostaglandins, you're actually replicating the same physiology that it had in the uterus, when it was very stable, to when it's outside the uterus.

J. William Gaynor, MD: So instead of having a child come in critically ill where there was nothing we could do, we can stabilize these children, do diagnostic procedures, and then have a stable child who goes for surgery.

Thomas L. Spray, MD: The various surgical options for single ventricle depend initially on how much blood flow there is to the lungs, and is there obstruction to the body.

Jack Rychik, MD: The strategy for single ventricle can really be distilled down to a plumbing problem.

Thomas L. Spray, MD: This is not an operation that creates a normal heart.

Jack Rychik, MD: We can't fix the heart.

J. William Gaynor, MD: We cannot make another pumping chamber.

Thomas L. Spray, MD: What we do surgically is rearrange things, close holes, make connections —

J. William Gaynor, MD: So that you can have blood going to the lungs and blood going to the body with only one pumping chamber.

Thomas L. Spray, MD: But that isn't the same as a normal heart.

Jack Rychik, MD: By rerouting the plumbing, we normalize the circulation.

J. William Gaynor, MD: And that procedure that does that is called the Fontan operation.

Jack Rychik, MD: And that operation is common amongst all the single-ventricle patients. What is different between these various categories is what is done in the first few days of life.

Peter J. Gruber, MD: It really boils down to how you're going to get blood flow in an unobstructed fashion without any resistance to either the body or the lungs.

Jack Rychik, MD: In Category 1, where there's obstruction of blood flow to the body, one will have to undergo a Norwood-type operation to allow for unobstructed blood flow to the body.

Thomas L. Spray, MD: And the principles of that operation are to connect everything so that the one good pumping chamber has to pump to the body. So you have to connect the arteries to the lungs and the body in such a way that all of the blood goes out to the body without any obstruction.

Peter J. Gruber, MD: The aorta is usually too small, so we correct that by putting a patch on to enlarge it.

J. William Gaynor, MD: And that's done by connecting the pulmonary artery, which comes from the right ventricle, to the aorta and then usually putting a patch on to finish the connection of those two blood vessels and enlarge the aorta.

Thomas L. Spray, MD: In addition, you have to prevent blood from backing up inside the left side of the heart, so you have to cut out the partition between the two upper chambers of the heart. And then the third principle of the Norwood operation, or the first-stage operation, is to provide some restricted blood flow to the lungs.

Peter J. Gruber, MD: What we call pulmonary blood flow, and we do that by placing a shunt, or a small tube, from one of the systemic arteries, or arteries that goes from the heart to the body, to the pulmonary artery.

Thomas L. Spray, MD: That is enough flow that you can get enough oxygen in the blood stream but not so much flow that you have resistance problems, because that resistance is what prevents you from doing any further surgery.

J. William Gaynor, MD: In other forms of single ventricle, such as tricuspid atresia or pulmonary atresia, you have blockage of blood going to the lungs.

Jack Rychik, MD: If one falls to the category in which there's obstructional blood flow to the lung, then one will need a shunt.

Peter J. Gruber, MD: So if the pulmonary artery is too small or doesn't form or one of the valves that leads to that artery doesn't form, then you need to supply blood flow to the lungs. And we usually do that through the formation of a shunt.

Thomas L. Spray, MD: The idea being to control how much blood goes to the lungs but allow blood to get to the lungs to mix in the heart.

Jack Rychik, MD: In Category 3, if nature has allowed for such, if there's adequate blood flow to the body and to the lung —

J. William Gaynor, MD: You may have a single ventricle with no blockage.

Thomas L. Spray, MD: There are children who have a type of single ventricle where there's unrestricted blood flow to the lungs and no obstruction to the body. In that situation, if you were just to leave that after birth, these children would get more and more flow to the lungs because of the resistance dropping, and then they go into heart failure. As that happens, the body tries to protect itself by creating a high resistance in the lungs. And that, of course, is the worst thing you can have for single ventricle because it prevents you from doing the final operation, the Fontan operation.

Robert E. Shaddy, MD: One thing that we can offer to infants is to put a band around the pulmonary artery which is just a ligature that is placed around the pulmonary artery and then tightened down and allows, then, restriction of blood going to the lungs so that babies get enough blood and have adequate oxygenation but not so much that we flood the lungs or damage the lungs because of excessive pulmonary blood flow.

Jonathan J. Rome, MD: The banding procedure to limit blood flow to the lungs is a surgical procedure. Although people have started developing bands that are adjustable, they're still typically put in by surgery.

Thomas L. Spray, MD: There are some children who have what is basically a perfect balance between the arteries to the lungs and the arteries to the body in such a way that they have no obstruction of flow to the body, but they've controlled how much blood goes to the lungs with some narrowing at some point in the pulmonary artery.

Sarah Tabbutt, MD: And that group of patients can actually have their first heart surgery when they're older, usually around four to six months of age.

Lynne Ramsay: He predicted that Joseph probably would not need that first surgery.

Anthony Ramsay: Because of his makeup, the blood was actually mixing very well, where actually he didn't have to go through the first-stage operation.

Sarah Tabbutt, MD: That group will still require two heart surgeries to get through the pathway of palliation for single ventricle, but they're lucky. They get to miss the neonatal procedure.

Jack Rychik, MD: So therefore, there are either two or three surgeries that are necessary, depending upon the category that you fall into.

Lynne Ramsay: We left the hospital after he was born, after about three days, normal time. And we had about eight months at home, normal, which was wonderful, and then needed to have his surgery.

J. William Gaynor, MD: Eventually, we're going to go to the Fontan operation. And in the Fontan operation, what we do is we connect the blood flow coming back from the body directly to the lungs. You can do it in one operation, but we've learned that babies do much better if we split it up and do it in two operations.

Thomas L. Spray, MD: When you have this single ventricle malformation, all the blood that goes to the lungs comes back to the heart, goes out to the body, and a portion to the lungs again. And the amount that is going to the lungs is an extra amount of blood that the heart has to pump. So eventually, we want to get to a situation where we're separating the circulations again. The second-stage operation takes away that extra volume that the heart has to pump, and it does that by getting rid of the shunt, or getting rid of the blood flow to the lungs directly from the heart, and connecting the veins from the upper part of the body directly to the arteries to the lungs.

Peter J. Gruber, MD: You have to wait until the lungs essentially mature enough that you can provide a different source of pulmonary blood flow.

Thomas L. Spray, MD: This is called either a Bi-directional Glenn shunt or a Hemi-Fontan operation, half of the Fontan operation.

Susan C. Nicolson, MD: It's very, very important that the family feels comfortable with you, as an individual, taking their child from them and that the child recognizes that nothing bad is going to happen to them, that they can do this without being awake for any painful experience.

J. William Gaynor, MD: They'll go to the operating room. The anesthesiologist will put them to sleep. We'll then clean, prepare everything in their chest and abdomen sterilely so that we can do the operation without infection. It's performed through an incision in the front, over the breast bone. And we put them on the heart-lung machine and cool them down to take care of their brain and other organs while we do the repair.

Peter J. Gruber, MD: We're bypassing the heart and the lungs so that the operative field, the area where we're working, is clean and we can see what's going on. The heart's generally not beating, although occasionally it is, but at least it's decompressed. There isn't blood flowing through it.

J. William Gaynor, MD: We'll then do the operation, warm them up, bring them off the heart-lung machine. We'll make sure that the heart is working OK, that the blood pressure is OK, that there's enough oxygen in the blood, that there's no bleeding. And then usually we leave a couple little tubes inside the heart to let us measure pressures in the heart and give drugs. These come out through the skin. There's also usually two little blue pacing wires which let us change the heart rhythm. We then leave a drainage tube. Once everything is stable, the baby will come back up to the Intensive Care Unit.

Thomas L. Spray, MD: Once we get to that second operation, the heart is in a much better condition, and usually the risk of that surgery is extremely low. And the risk after that surgery becomes quite low, also, of any sudden event. So I always breathe a sigh of relief when we get to that second operation, or that second-stage procedure, because it's a much better physiologic situation for the heart.

Thomas L. Spray, MD: The third-stage operation is a variant of the Fontan operation.

Peter J. Gruber, MD: And that generally takes place somewhere after two years, but the child's physiology really tells us the best time to do that.

J. William Gaynor, MD: There are two types of Fontan operations. One is called the Lateral Tunnel Fontan, in which a baffle is placed inside the heart to redirect the blood flow from the lower part of the body to the lungs. The other is called the Extra Cardiac Fontan, where we actually use a tube that brings the blood outside the heart, up to the pulmonary arteries.

Thomas L. Spray, MD: But the Fontan operation is based on connecting the veins from the body directly to the arteries to the lungs.

Peter J. Gruber, MD: Normally, the inferior vena cava, which drains the bottom of the body, attaches to the heart at the inferior or bottom portion. And what we do is to literally divide this from the heart. We sew up the portion of the heart where the inferior vena cava entered, and then we sew a tube end-to-end to the remnants of the inferior vena cava. We take this tube and loop it around the side of the heart and sew it into a hole we make into the pulmonary artery. So we essentially bypass the entire heart.

Thomas L. Spray, MD: It's a more efficient connection because the tube is a very specific size, and the blood going through there is not turbulent. Turbulence loses power, and power loss is a problem if you don't have anything pushing blood through the lungs. It cannot work unless there's low resistance in the lungs. And the key is you have to have a good pumping chamber on the other side which essentially sort of sucks blood through the lungs.

Peter J. Gruber, MD: Now, the one modification is that we put a small hole in the side of the heart and in the side of this graft and sew it together with what's called a fenestration.

Thomas L. Spray, MD: And the reason we do that is that it's been shown that having that little hole, while it does allow some blue blood to mix with the red blood, it also decreases the risk of developing fluid around the lungs after surgery, something called a plural effusion. Effusions used to be the biggest problem after the Fontan operation. Children would have the surgery and do quite well, but they would develop a lot of fluid that collected around the lung, and they'd often have to have a tube in the chest for weeks or even months to drain that fluid. Nowadays, with the use of this fenestration, that is a very uncommon event, whereas it used to be routine.

Lynne Ramsay: Joseph is a pip. He's very friendly. He says hello to everybody he sees. He's just very vivacious and very smart. We can't believe how much he picks up, and he's just a joy.

Victoria L. Vetter, MD: The follow-up for children with single-ventricle physiology involves comprehensive evaluation of their heart muscle function, the surgical connections that were made as part of their staged operations, the cardiac pressures, the pressures in their lungs, as well as their heart rhythm. This comprehensive general health assessment is very important to assess their long-term cardiac well being and life expectancy.

Robert E. Shaddy, MD: From a heart standpoint, most of these children are very good at adapting to their limitations. And so if they're on the playground, playing with other children, they will play with them and get around with them and limit themselves as they need to.

Sarah Tabbutt, MD: We've really pushed the field in, you know, making this a heart disease that is not only not fatal but is actually very survivable with good outcomes. And shouldered on that is the transition to trying to optimize neurodevelopmental outcomes.

Robert E. Shaddy, MD: We're finding out that there are neurologic abnormalities that many of these children have and will have as they grow older, some of them with school — learning difficulties, some of them with ADHD issues, and some of them even more complex than this. So it's not just limited to their heart. It's the neurologic abnormalities that are beginning to show up that in some children are very minor, and others are more significant.

Thomas L. Spray, MD: One thing that we have seen is the rhythm problems, and they may need to have additional surgery to convert their older style Fontan operation to a newer style. Some have required pacemakers. Some, if their heart function has deteriorated over time, have required a heart transplant. What I tell families is that there are more adults now than there are children living with congenital heart disease which, frankly, is a testimony to the fact we've been pretty successful at dealing with these conditions.

Robert E. Shaddy, MD: Our mission is to help children with heart disease and to help their families get through this difficult problem, to do whatever we can to make their lives better.

Anthony Ramsay: After the first surgery, you know, you always talk about blue babies and all this other stuff. And he came home, and he was, you know, pink. He's warm. He's running around. He's the only one out of the three of them that broke his arm. He climbs on everything, you know. You think he would really be tired. He's not. You know, he runs around like crazy.

Lynne Ramsay: We're so lucky. We're so blessed and lucky that he was born where he was and when he was and that he has these people taking care of him. We wouldn't want to be anywhere else but here.

Anthony Ramsay: It gives us a lot of hope, you know, that he'll live long into the future. And that's very comforting.

Elizabeth Goldmuntz, MD: What moves me is to work with the families and to work with the children and to give them the best possible care that we can provide. That's first and foremost.

Susan C. Nicolson, MD: And to see them grow and to see them integrated into the family and to see them interface with their parents and their siblings just as you would any other routine and normal child.

Thomas L. Spray, MD: To be able to take the heart of a child and fix it so that the physiology is better and the child has a chance at a long life, that's very gratifying.

J. William Gaynor, MD: There's nothing better than seeing the kids come back when they're four or five years old.

Susan C. Nicolson, MD: And really see that they're just like any other kid.

J. William Gaynor, MD: A child who had had hypoplastic left heart syndrome, who — I walked into the Intensive Care Unit one day, he was six years old, and he was there with a broken leg. I said, "What are you doing here?" Well, he was out mountain boarding with his cousins. I'm really sorry he broke his leg, but I'm really happy that here's a child who, 20 years ago, would have been dead, and he's alive to be out mountain boarding with his cousins. And that's why to do it.

Jack Rychik, MD: Through the Fetal Heart Program, we're now able to offer hope and promise for the future for these children to go on to lead happy and healthy lives, and that's what this is all about.