JUAN: Good morning, everyone. Welcome again to our Heart Failure Tuesday Lecture series. Today, we have Dr. Sabrina Phillips. Dr. Phillips is a board certified adult congenital heart disease specialist, providing care in the Adult Congenital Heart Disease Clinic here at the [INAUDIBLE] campus.

She is an expert in echocardiographic assessment of complex congenital heart disease. Her research interest includes clinical research involving patients with congenital heart disease. And she is also involved in [INAUDIBLE] at the local and national level, with the goal of increasing awareness of the unique challenges in caring for an adult with congenital heart disease. So with no further introduction, Sabrina, take over.

SABRINA PHILLIPS: Thank you for that introduction, Juan. I'm really happy to be here with you guys today. I have to say I was a little anxious coming in because this is a very sophisticated group and audience with vast experience caring for patients with advanced heart failure. But I wanted to share some thoughts on the unique challenges of the patient with congenital heart disease who has heart failure and maybe introduce some potentially different concepts about how I think of my patients who are not thriving or who are not meeting their needs from a cardiac standpoint.

So just to step back, for those of you who may not be well aware of the scope of congenital heart disease, it's actually not a rare patient population. Sometimes, when I start to talk with people and tell them what I do, they're like, well, where do you get any patients from? And the truth is that, unfortunately, this is a common problem because congenital cardiac disease is the most common birth defect. And that occurs in about 1% of all live births, which roughly translates to about 32,000 new cases of congenital heart disease every year in the US.

And we have become, thankfully, very good at caring for this patient population. And so if you're born today, even with the most severe forms of congenital heart disease, you have an 80% chance of survival to your first birthday. And if you survived to your first birthday, there's a 90% chance you're going to be in my clinic and then potentially later in the advanced heart failure therapy clinic. So most one-year-olds will live to adulthood.

There are now more adults in the US with congenital heart disease than children. This is an adult problem. So it's important for adult providers to be aware of this. And it's over one million adults right now who need to seek care in specialized centers.

Just a little historical perspective-- we have made rapid advancements back from the '30s and '40s, when you really-- we didn't think you could operate on the heart. All of the congenital heart defects that were taken care of before the 1950s were things that were outside the heart, so PDA ligation, the BT shunt-- and there's a wonderful movie about the development of that at the Hopkins Center-- and then coarctation repair.

But then you see the '50s we explode into intracardiac repair, starting with VTD then going on quickly to tetralogy of Fallot. And then Mustard and Senning around the same time, two different surgical centers, thought of a way to repair complete transposition using complex atrial baffling. So we call that an atrial switch.

And then they are fairly quiescent. These techniques are being improved and surgeries being improved. But then in the '70s, a French surgeon, Fontan, comes up with a surgery to palliate the patient who has a single ventricle circulation. And we're to spend a lot of time at the end of this lecture talking about that.

And then we don't have much advancement till the '80s, when we see our last two big surgeries come onto the scene, which really revolutionized care for our most complex patients. And that was the treatment of hypoplastic left heart syndrome, which before the '80s was universally, unfortunately, fatal unless you could get a neonatal transplant.

Norwood comes up with a procedure to help those patients. And now we're seeing those patients in adulthood, which is quite gratifying. And then we refine the treatment for complete transposition with the arterial switch-- which I'll talk about briefly coming up-- which allows patients to hopefully do better longer because they're going to have a left ventricle supporting the systemic circulation.

So we're really still in pioneer mode for these patients. You can imagine if you were born in the late '80s, you're just now really becoming an adult. We're starting to see the fruition of this work, as we're learning more and more about how these patients may present with cardiac difficulties.

So patients with congenital heart disease, they are, for the most part, palliated not cured. We've tried to treat their lesion. But when we look at how do they do in terms of exercise and just kind of using the currency of peak VO2-- which I think we're all very comfortable with thinking about that in terms of patients' outlook and abilities-- we see really somewhat sad outcome with patients with congenital heart disease.

These are grouped patients with different kinds of CHD. And if you look at age matched controls-- so these are the young patients-- so they're younger with congenital heart disease, average age 33. And then the heart failure group who came from an advanced heart failure center to be compared, they were average aged 59.

So when you look especially at New York Heart Association Class I, if I have a patient in my clinic, I say you're doing great, you're Class I, look how much lower the achieved peak VO2 unobjective testing is than their age matched controls. That's not true for the patient who has traditional forms of heart failure who is New York Association Class I when we compare to their age matched controls.

They are a little worse, but they're not significantly limited. So we realize that our young patients start out a little bit behind the 8-ball. And then as they progress, they look very similar to our other heart failure patients, but they're dropping off their peak VO2 achievement quite significantly compared to their peers.

So just like an acquired heart disease or traditional forms of advanced heart failure, VO2 is important. I get a lot of these cardiopulmonary tests to follow my patients. And it does predict clinical outcome, which is not surprising. We know this is a pretty good marker and a tool.

And we can see that patients who have congenital heart disease have very low peak VO2s-- less than 15-- do very poorly in terms of freedom from hospitalization or death. So it's not the same measurement potentially as what we utilize for other patients, but we know that it matters and lower VO2s are important.

So the adult with congenital heart disease may face sort of unique forms of heart failure or lack of cardiac efficiency, including right ventricular failure, when the right ventricle is in the systemic circulation. So our patients with hypoplastic left heart syndrome-- we talked about the great advance there-- their left is a single ventricle circulation with a right ventricle.

But we do have two-ventricle patients who have a systemic right ventricle, and that's a unique problem. Because, remember, the RV and the LV are not just a right and a left hand glove. They're like a glove and a mitten. They had completely different jobs to do. They were designed to do something different.

The right heart was never meant to pump to increased afterload. It was meant to be this low afterload pump with good volume sensitivity. And so its adaptation to be in systemic circulation leads it, unfortunately, to early failure as you get hypertrophy and dilation to try to keep up with the demands.

Systolic failure of the subpulmonary right ventricle is fairly common in our patients, say, with tetralogy, who are often left with significant valvular heart disease that produces a volume loading on the right ventricle. Thankfully, I think we're recognizing this better, and we're not letting patients get to the failure stage.

But these forms of heart failure I'm not going to spend a lot of time on because I think that they lend themselves to the more traditional approach. We do what we need to do for subpulmonary or systemic ventricular dysfunction utilizing the medical tools at our advantage, including even mechanical support options.

But what I want to draw attention to mostly in this talk is maybe something we don't think about as often, and that's diastolic dysfunction or severe noncompliance of the right ventricle, how that can lead to patients with congenital heart disease to have low cardiac efficiency, poor exercise tolerance, and how difficult that can be to address and to recognize.

Because in the echo lab, nobody's thinking about diastolic dysfunction of the right ventricle. We're talking about E to As in the left heart. And we're looking at all this stuff that nobody's really thinking about, the RV, because we're so used to it being a compliant pump.

And then this may be a little unfair to lump in here, but I think it matters. And so a lot of my patients are failing to thrive or doing poorly, not able to achieve the exercise capacity they want because they can't deliver their needed oxygen content. And several things can cause low oxygen content delivery to the periphery, including inability to just oxygenate your blood. You don't have a good source of pulmonary blood supply.

Maybe you have a good source of pulmonary blood flow, but you are shunting across an intracardiac shunt right to left. So you're mixing your blood, and you're not delivering things well. And you're putting a strain on the subpulmonary ventricle. We'll talk about some cases of that.

Or maybe you have other reasons to not deliver oxygen content, like you're anemic. So we're going to look at some cases I think illustrate the diastolic dysfunction of the right heart and this failure to deliver oxygen content. I think cases are a good way to introduce these concepts.

And then we're going to end today just a little bit more didactic, not case-based because I want to talk about some of the complexities of the single ventricle patient and how they may present to us with heart failure and some things to think about. And I think instead of going off on various case reports, it's better to just talk a little bit more mechanistically.

All right, so right heart failure, just as I said, systemic right ventricle, we're mostly seeing that in the congenital population in congenitally corrected or L transposition of the great arteries. That's patients who maybe have never had any surgery, but this is-- they've got a systemic right ventricle.

But then the complete transpositions with that old atrial switch, we're not seeing that too often because, remember, the arterial switch came into play in the mid '80s. And now we're seeing those patients do better with the left ventricle. Really not much to say here. We don't have any data.

There's like these terrible studies that are 15 weeks long with crossover. And they look at a VO2, and they're like, oh, ACE inhibitors don't help. Well, 15 weeks was not a very long trial. But I just basically utilize traditional guideline-directed heart failure therapies for these patients because we have to do what we have with our toolbox.

So let's now go into these other forms-- diastolic right ventricular dysfunction. So the right ventricle we're so used to being compliant. But if you've had a lot of afterload in the right heart, maybe you've had PS or branch PS that provided afterload. Or maybe you have abnormal pulmonary vascular resistance long term. The right heart is going to become noncompliant.

And here are some of the things that I look at in the echo lab. So this is a patient who had a tetralogy of Fallot with a lot of outflow tract obstruction. It was relieved in childhood. Now they actually have severe pulmonary valve regurgitation after their surgical intervention, which is common.

But I want to draw your attention to this Doppler finding. So for those of you who don't read echo, we're looking at blood flow out the pulmonary valve essentially in the RVOT. And this is systole right here. So this is the blood flow that's ejecting while the right heart's contracting in systole.

So we should really see, in a normal pattern, this systolic forward flow. Then if there's some regurgitation in diastole, that's this time period here-- if you guys can see my little hand cursor, I hope, on the screen. This should be all above the baseline, going back into the ventricle.

But look at this interesting pattern. I see what looks like inflow. If you are used to looking at tricuspid or mitral inflow, in diastole it looks like this but flow's going out the pulmonary artery. So what's happening is the RV is so stiff that as the right ventricle tries to fill through the tricuspid valve in diastole, it's increasing the pressure enough that you can just drive flow right across the RV outflow tract.

So this is a very non-compliant right ventricle when you see this. And we see this quite commonly. And what is hard for these patients is all of our mechanisms to say when we should replace a regurgitate pulmonary valve are based on the RV dilating.

Because we're saying, OK, that's when the RV is not handling the volume load. But these patients can maybe not dilate very much because the RV is very noncompliant, very stiff, very fibrotic. So we're not seeing that nice ventricular dilatation, but they're very limited in their exercise capacity, and it's just because of this poor efficiency and poor compliance.

We can also see changes in the hepatic vein flow that lead us to understand the RV is non-compliant. And this is if the patient's in sinus rhythm. You wouldn't see this if they were in atrial fibrillation. But when they have atrial contraction, if they get this big reversal in the hepatic vein, that's telling you that the AR pressure is very high, and we're having some difficulty here.

This is synonymous-- for those of you used to looking at the left heart diastolic parameters-- this would be like a big A wave reversal in the pulmonary vein. So this is very synonymous, and we see this often in our patients who had had severe PS. We see it also in Eisenmenger syndrome. And this is just another marker of inefficiency of that right ventricular circulation.

Well, the problem is what to do about it. Just like left heart diastolic dysfunction, if we had a lusitropic agent, that would be great. But unfortunately, usually this is because of fibrosis, and there's no going back sometimes from this microscarring. We don't have great lusitropic drugs. But we can do-- just like we do in the left heart-- we can prevent volume overload, slow the heart rate so we can improve filling times.

And then I'm quite interested in these last two drugs, at how they work potentially at the cellular level, not just for their diuretic properties. I've, for many years, felt that aldactone clinically has been very helpful in my patients with a very stiff right heart. And so I'm a big believer in this part of our guideline-directed medical therapy, as I'm sure all of you. I think aldactone kind of an unsung hero.

I'm now more and more intrigued with the SGLT2-type drug. I think that class could be very helpful. And in early clinical use for me in my congenital heart disease patients with right ventricular dysfunction, I've had fairly good results. Now of course, that's a little bit of anecdotal medicine right now, but I think we're going to get more and more information so I'm very hopeful that maybe this class of drug is going to give us a new tool in our toolbox for treatment of this complex problem.

Well, let's look at some cases now that sort of encompass these ideas of a stiff right ventricle, poor oxygen delivery, and maybe how we can think about these patients and how to approach them. So this is a patient. I did not see him here at Mayo Clinic. This was when I was at the University of Oklahoma.

He was a 60-year-old man. He came to the ED actually for a fairly minimal complaint. He had a little upper respiratory tract infection. But people freaked out in the ER because he was desaturated. And they were like, oh, my gosh. You've got acute on chronic respiratory failure. You must go to the MICU.

And so here's this guy who walked into the ED with some sniffles, and now he's in the MICU, diagnosed with severe COPD, which he's never been diagnosed with. And his sats were 80. And first they put him on high flow nasal cannula, and it didn't improve his sats. And then they put him on BiPAP, which he was pretty unhappy about as he sat there. And it didn't improve his sat.

And so they called us up to consult on him. And when he talked with me, he had a scar on his chest. So you're like, hey, what's that all about? And he said, well, I had severe pulmonary valves stenosis. And at age 30, I saw a surgeon, and he said we should just take out the pulmonary valve to relieve your outflow tract obstruction.

So they did that, and he didn't feel a lot better. He said he had been pretty active. So he just decided to not come back to medical care. He's like I went through this big surgery, and you took up my pulmonary valve, and I feel about the same. So he's been trucking along for another 30 years but now in the setting of a previous severe outflow tract obstruction and now obligate severe PR.

So here's what his transesophageal echo looks like. I apologize for the quality of this, but I think it gets the point across. So you can see here that the right heart is huge. Right heart's dilated. The tricuspid annulus is dilated.

And the tricuspid valve, they're not touching each other. So we know there's going to be severe tricuspid regurgitation before we even put on the color. The systolic function's pretty well preserved of this ventricle. And so often, again, that's all we think about. Systolic function is good.

Look at this picture. The right atrium is big. And look at the right atrial-- or the atrial septum. It's going continuously to the left. So I know my right atrial pressure is almost always higher than my left atrial pressure. Now normally, they're about equal with the left atrium pointing out, of course. Not the case here. This thing's not moving much.

And not a surprise, that TR is directed right at the atrial septum. It's severe TR. It's coming back there. And here is a stretched PFO, and all the shunt is right to left. There was severe PR. I didn't show that because it's obligate it was there.

So I read both the transthoracic and the transesophageal echo. I said, well, there's wide open PR-- not unexpected-- severe TR with annular dilatation, and a stretched PFO. And he's hypoxic, or desaturated more appropriately to say, because he's got a right-to-left shunt.

And I said, well, we just need to call our cardiac surgeon, and we should think about a pulmonary valve replacement and tricuspid valve repair or replacement and closure of the PFO. And the MICU staff thought I had lost my mind. They're like, well, this guy has a right-to-left shunt. He's got Eisenmenger syndrome. He clearly has bad pulmonary vascular disease.

And I said, no, I suspect he actually doesn't have bad pulmonary vascular disease at all. And looking at several echo parameters and having a lot of gray hair, I knew I was going to be right about this. So I was going for C, and most everybody else was going for A or D in the MICU that day, just worried about this idea of how can you shunt right to left.

Well, here was his cath data. His PA systolic pressure was 23. PVR was very low, 0.9 Wood units. This guy did not have pulmonary vascular disease. So you say, well, how can you shunt right to left? Well, remember, you can have a right-to-left shunt in the absence of elevated PA pressure, especially at the atrial level because the atrial level shunting is a diastolic phenomenon. RA pressure and LA pressure are essentially related to diastolic parameters of the ventricle.

So of course, if you get pulmonary hypertension, you're going to increase pulmonary diastolic pressure, RV diastolic pressure, and RA pressure eventually. So yeah, if I've got pulmonary hypertension, I'm going to shunt potentially right to left. But I can do that without systolic hypertension and just having diastolic noncompliance in specific settings.

So think of it like this-- if you're more of a graphic person. So when we think of what does the tracing of basically pressure look like in the RV and the RA over the course of the cardiac cycle? This would be pretty normal. We have these low RA pressures. We have the A wave. We can have a little wave out here. But most of the time, we're just following right along diastolic pressure of the RV, of course. It has nothing to do with the systolic pressure.

And so in this case with severe TR, if we keep the systolic pressure of the RV the same, but I make the tricuspid valve regurgitant, look what I do to the RA pressure tracing. As we get to the end of systole, I have an increase in RA pressure. And all it takes is a little bit of difference between the RA and the LA to shunt. So in this case, you could shunt right to left and have no evidence of RV or PA systolic hypertension.

What if I have a case like this poor guy? He's shunting almost all the time. And that's because he had severe RV diastolic dysfunction. He had 30 years of severe outflow tract obstruction. This RV had tried to compensate for that.

And now, it was a non-compliant RV, but then we volume-loaded it in diastole from two sources. We gave it its inflow, which it meant to deal with, but now PR was also loading it. So we increased that diastolic pressure of the RV, so we increased the RA pressure without changing the systolic pressure. And then we gave him severe TR, further increasing that.

So this is the case where we were at. And this is a unique case of someone who was not doing well because they couldn't deliver oxygen content that they needed because of shunting, and they had RV noncompliance.

So there are other cause of patients who have cyanosis or low oxygen systemic saturations without elevation of PA pressures. And so the other case would be like the Epstein patients, who have ASDs with increased RA pressure for their TRs. The care could be directed right at the defect. But you could have a tricuspid prosthesis and RA pressure that was elevated in shunt.

And then we have patients who might be shunting extracardiac that I do think about-- maybe not so appropriate for this discussion-- but patients who have a classic Glenn, they can get pulmonary ABMs and shunt right to left. This is similar to hepatopulmonary syndrome. And then patients who obstruct their SVC, they can pop off collaterals from the SVC to the pulmonary vein, which gives them an obligate right-to-left shunt.

So let's look at case 2, another problem of someone failing to thrive or having heart failure with a right heart problem and low oxygen content delivery. So this is a lady who had a patent ductus arteriosus-- big connection between the pulmonary artery and the aorta that caused pulmonary vascular disease. She does have pulmonary vascular disease-- pulmonary hypertension.

She was diagnosed at age 19. And that can happen. These PDAs can kind of slip through the cracks, and they don't show up till the patient maybe gets a little blue or has some issues. And her parents were given a terrible outlook. They were told she would probably only live a few more years. But then they said, in this patriarchal time, don't tell her. Just let her kind of live her life. So she was unaware of the diagnosis, and she went ahead and finished college and got married was doing well.

And because she shunts right to left, she was increasing her red cell count to deliver oxygen content, but she had been undergoing phlebotomy for 30 years because someone was worried that she was hyperviscous. She had one episode of hemoptysis. And she'd had some SVT and was treated with verapamil.

She came to Mayo Rochester for referral for transplant when she had had recurrent upper respiratory and lower respiratory tract infections. She was very short of breath. And it was improving. And when we asked her what was happening, she said, well, I noticed I feel really bad after I get phlebotomy. So I started taking iron on my own. And then I feel better until somebody phlebotomizes me again.

So her hemoglobin was 18.2. Hematocrit was 57. MCV was low at 71.6. So when I present this case often, most people say, well, go ahead and list for transplant. This is terrible. She's 54 with pulmonary hypertension. But really what we should do is stop phlebotomizing in her first.

Now she might, at some point, need transplant listing. But we could actually improve her heart failure and her ability to exercise by giving her better oxygen content delivery to the periphery. And so she doesn't need to have phlebotomy. In fact, that's a bad thing to do.

So when you have a cardiac right-to-left shunt, including those patients with Eisenmenger syndrome, which is PVR elevation and shunting through either adaptive VSD or an ASD, your tissues are hypoxic when you start to mix that. So the body's pretty smart. If it has tissue hypoxia, it turns up the thermostat. It tells the kidney, hey, make some more red cells because you're the delivery train for oxygen, and I need more oxygen.

I don't care what the sat is. I just care how much oxygen you're giving me. So the red cells-- the kidney tells the bone marrow, hey, rev up production, and red cell mass increases, and the tissue oxygenation improves. And this is a perfect feedback loop if we don't mess with it.

So for the most part, my patients with Eisenmenger syndrome, I know what their hemoglobin is. It never changes. If I don't mess with them, or if they're not having blood loss from another source, they'll find their stable state, and they'll be good. And so this is a new equilibrium that we should let happen.

And what's bad about phlebotomy, people say, well, they could be hyperviscous. It's not good to have a hemoglobin that high. But the truth is this is a little bit different state. And if you have low oxygen-carrying capacity with iron deficiency, patients aren't going to feel well.

And if the red cells start to get small-- remember, her MCV with 71-- these red cells are going to be more fragile as they go through the circulation. They're going to fragment earlier than a normal healthy-- normal-sized red cell. And this fragmented, destroyed red cells, that's what increases blood viscosity. That increases the risk of stroke.

And so in our population here, we published this from the Mayo Rochester data. The number one cause of stroke in our Eisenmenger patients was phlebotomy because it was causing low MCV, and the treatment is iron therapy. So it's really distinct from what you've heard about.

And so this is with her permission. This is now actually almost 15 years ago. So she's still going strong. I have a picture of her dancing at her son's wedding. She's not been transplanted, but we did put her on some pulmonary vasodilator therapy, which is working well for her. We let her find her equilibrium, which was about 21 for her hemoglobin.

She did overshoot. And this can happen when you're starting to give back iron stores. But we keep our MCV and our iron stores there to normal, and she feels great. And she's actually able to canoe here a little bit. So this was a case where we treated heart failure by making sure you have oxygen content delivery to the periphery.

So our patients who are cyanotic with congenital heart disease do not need routine phlebotomy. Our Eisenmenger patients actually do quite well without heart/lung transplantation if we manage them well. There are a few that need to go to transplant, but thankfully, not that many. And pulmonary vasodilator therapy is a helpful adjunct.

You do perform phlebotomy for long bone pain, headache or altered mentation if you know that they're not dehydrated or already iron deficient. And occasionally, people will recommend this preoperatively to improve hemostasis. I actually don't do that. I think it just gets confusing [INAUDIBLE]. And I think sometimes we overshoot. But if you are going to do a phlebotomy, make sure you give the patient volume stores back with crystalloid so they don't get dehydrated.

So case 3, we have of another weird and wonderful form of right heart failure with poor oxygen content delivery. So this is a 40-year-old man with trisomy 21. He had a membranous VSD. And he had been followed actually quite regularly by pediatric cardiology at Mayo Clinic. And so I had the advantage of a paper chart. For those of you that have rotated up there, you know you can get that little paper chart packet that has every piece of information ever seen about the patient.

And so I had all of his data. And he had been followed and thought that this was sort of a small to medium VSD that didn't need repair. There was no concern that this child and now young man had pulmonary vascular disease or Eisenmenger syndrome.

But he was actually very active, worked full time at kind of a packing factory. And as he'd stand on his feet all day, he was getting more and more lower extremity edema. And he was having increasing fatigue and not-- he used to love going to work, and now he was having trouble completing the work because he was so tired.

And so he's seen by family med, and they send him back to me. They didn't really have any other concerns that they addressed to me. There was no other complaints recognized. Room air sat was pretty good, 95, wasn't completely normal. No evidence on exam that he had high hemoglobin. His conjunctival were not injected, which I tend to see if the hemoglobin is running really high.

He did have mildly elevated JVP. He had a fairly loud murmur, a very loud P2. His lungs were clear, and he was not clubbed or cyanosed on exam.

But this was his echocardiogram. So this is a parasternal view. I want to draw your attention right here. This is part of the membranous septum. But you'll also notice the right heart looks quite large. And we see here that he is shunting across the septum. It looks like a pretty good shunt. He has secondary TR as well. This can get a little confusing in this area.

But this is really the money shot to give us some concern. The ventricular septum is flattened in systole and diastole. This is a pressure-loaded right ventricle. The right ventricle is dilated, and the wall is hypertrophied. So this is an RV that is under pressure.

So I read this as a large VSD with significant right heart enlargement, and some systolic dysfunction, moderate TR. And this is how I estimated the pressures based on TR and PR. 95 over 33 is what I thought the PA pressures were going to be. I thought the LV systolic function was preserved.

So when we went to the cath lab, I thought we should really sort out what's going on. This data was a little concerning when he had been seen at 18 and was doing well. So he did have a VSD, not much of a shunt because the pressures are equal between the systemic and the pulmonary ventricle. So Qp:Qs is almost 1.

PA pressures were high, 86 over 46, as we anticipated. But he was pretty reactive in the pulmonary vascular bed. We gave him 100% oxygen, and he started shunting quite a bit from left to right. Qp:Qs was almost relevant at 1.46 to 1.

And when we gave him nitric oxide, he really increased his shunt. But look at his vascular resistance-- really high numbers, numbers we don't want to see. Now these are indexed to body surface area because we did this in that congenital lab.

So you could kind of divide these by 2 for numbers that you're not indexing. Still, incredibly high-- 18.8, 9.9, and it drops to 8.2 with nitric oxide. So he's reactive but high vascular resistance.

So is this just Eisenmenger syndrome? Did we miss the boat, and I need to treat this right heart failure that he's having with his fatigue and lower extremity edema? Well, I wasn't sure. None of these things excluded this as Eisenmenger, but this was sort of a weird presentation.

Most patients with a VSD, especially with trisomy 21, are going to get pulmonary vascular disease before their fifth birthday. He was 18 at his last visit, and he was fine. He wasn't significantly desaturated, but that doesn't mean anything necessarily. But it just brought my attention that something's going on during the day. He's not always shunting right to left. And his bed was very reactive.

So I sent him to polysomnography. And he has severe non-positional sleep apnea with marked nocturnal hypoxemia. But this was corrected with CPAP alone, so this was not needing supplemental oxygen.

So I started him on CPAP therapy. He was a very compliant young man and was able to do that. I did start Revatio. And I brought him back for re-evaluation 30 days later.

His LV dimension had increased by 10 millimeters. That tells me that he's shunting a lot left to right at the ventricular level. The LV is now volume loaded. And his RV pressure was unchanged though. But maybe he's got a higher Qp:Qs, and PVR is lower. And I've got the same pulmonary pressure.

So I recathed him, and his pulmonary vascular resistance had fallen to about 5 with this therapy. So we sent him for surgical closure after a lot of discussion. And we did have nitric oxide support in the OR, but he did not need that.

He did fantastic. And this is him three months post-op. He is on Revatio on this and on CPAP. But look at the left ventricle. It looks so much better. The RV does not look pressure loaded here. And his RV systolic pressure was 36. He had mild right heart enlargement. No residual VSD and good LV function.

So this was really a case where the patient did have a VSD and that did impact some of his presentation, but this was not Eisenmenger syndrome. So he had right heart failure from untreated severe sleep apnea plus a VSD. And we were able to sort of treat this right heart failure.

And so bring this to attention to remind us that our patients are not just one thing. They can have a VSD and something else. And we have other tools to treat them, such as looking for sleep apnea and things that impact right ventricular function.

Final case in this series, a 25-year-old woman, pulmonary atresia VSD. So this is the cousin of tetralogy, the extreme end. There's no outflow from the ventricle to the PAs, but you do have a big VSD. So you've got to get a source of pulmonary blood flow. There's no connection essentially from the heart to the pulmonary vascular bed.

So she got a central aorta to PA shunt to give her some blood flow. And then she went to the more classic BT shunt, so subclavian artery to PA shunt. And then a modified-- which just means we used the cortex tube there-- at age six. So nobody's tried to treat the underlying condition. We're just giving her sources of pulmonary blood flow using the systemic circulation.

She unfortunately-- nothing since age six, and she's presenting with increasing cyanosis. And she's NYHA Class III. And she really is pretty limited in what she can do.

Well, here's the reason. We're giving her no pulmonary blood flow. So she had these shunts, but the right was severely stenotic, and the left was completely occluded. Because she's really getting blood flow to her pulmonary bed just through some collateral formation. So that's not a very good way to run the circulation.

Her pulmonary arteries were attached to each other. They were confluent. The right and left came together, which is good. Sometimes in pulmonary atresia VSD, there's these tiny little branch PAs. They're not connected to each other. They're really hard to find and deal with.

But hers were there, but they were little. She's an adult, and her RPA was 4 millimeters and her LP was 6 millimeters. Well, they've had no blood flow either. She had a lot of collaterals. That's how she was living with the blood flow.

So this is a patient who's got heart failure because we're not providing any source of pulmonary blood flow that's stable to her. So what can we do about this? Does she need a transplant, or should we do something else?

Well, at cath, it's hard to look at pulmonary resistance when there's not good sources of flow. It's really hard to calculate this and sort it out. Her RPA was 27 over 16. I'm not sure what to make of that, but it's there. She had a VSD.

Remember, these patients are not blue because they're shunting through the VSD. The shunt is obligated and because you have to mix in the ventricle. She's blue because you have to mix, and she's giving her pulmonary circulation from connections from her aorta. Not surprising systemic RV pressure. And then her sat was 75% in the thermal artery.

This is what her PAs look like-- tiny little things with some obstruction. So we thought about giving her a new shunt, doing a staged repair where we tried to give her some blood flow from the heart to the PAs to let them grow a little bit and then maybe consider VSD closure at a later date if it looked feasible.

We could send her to transplant, but we decided to go for a stage repair because her vascular bed in the lungs looked fairly good. And so we thought at least we're going to give her a better source of pulmonary blood flow. So in March of 2012, we gave her a 16-millimeter-- pretty small-- Contegra graft from the RV to the PA. Now we're giving her pulsatile flow, and we're going to hope that those PAs grow.

The VSD is open. We didn't do anything to that. And then we tried the rehab three months later her pulmonary bed by doing some stinting in the more distal RPA and LPA. She did really, really good. And we decided she would tolerate VSD closure. So we did that, reconstructed the RV to PA connection with a more adult-sized outflow, and did some more stinting into the pulmonary bed.

And so this is what her connection looked like after. So she's got a pretty good sized connection from the RV to decent sized PAs. And she did really well with this. She had normal RV size, tiny residual VSD, no conduit gradient. She was not desaturated.

Not surprisingly, the RV systolic pressure is a little high. And we've got a conduit to go through. Plus, those pulmonary arteries are not normal sized, but she's doing pretty well. EF was 59%. She was now NYHA Class I.

And this was 2013. I was privileged to help her and her husband deliver their first child that she successfully carried to term in 2016. So this was a really nice treatment of right heart failure by providing a better source of pulmonary blood flow. So even with very complex anatomy, sometimes you can benefit from a staged approach to help the right heart cope and to improve pulmonary blood flow.

OK, just have a few minutes left here. We're going to talk about the Fontan circulation. No cases-- again, I just wanted to be a little more didactic. And maybe at a later date, we can do some case series if you're interested.

But remember that Fontan is not a specific operation but a type of surgically-created physiology that we're describing when we use that word. And what we're describing is that we're directing caval blood flow-- SVC and IVC flow directly to the pulmonary bed. We're not using any type of ventricle to pump the blood.

So basically, it looks like this. We're just pouring IVC and SVC flow into a funnel. And it's going to passively come into the pulmonary vascular bed and then go across to-- I say the left atrium, but the pulmonary venous atrium would be the best way to comment on that.

So why would we do that? Well, sometimes we have anatomy that's not going to allow the patient to have two ventricles to support the circulation. And of course, we have to have a ventricle support the systemic circulation. So we'll try to redirect flow for that.

It's better than our patients say, like we just saw in the example, she had these systemic-to-pulmonary shunts, which you could do. You could provide a source of pulmonary blood flow with out of ventricle-- let your one ventricle support both the systemic circulation and the pulmonary circulation. But then you obligately mix, and you're very blue.

And so if we could separate it like this, you wouldn't be blue. And the ventricle would not have to have the volume load or the support of both circulations. It would now just support the systemic circulation.

So this is the classic anatomy that Fontan described using his operation [INAUDIBLE] but we use it for many other anatomies. But you can see in this case, we really would not have good development of a morphologic right ventricle. So we can't have a pump to both circulations.

There's lots of variations. I'm not going to spend a lot of time, but you may hear or see me write in a report all these different variations. But the right atrial appendage to PA connection is the one I worry about the most. Thankfully, we don't do that too much anymore. But this left this big right atrium in the circuit, which can cause clot formation and other concerns.

The SVC to PA can be connected various ways. And if you hear me say a "classic Glenn," that means that the PAs are not confluent anymore, that the SVC usually is just going to the right pulmonary artery, and the main pulmonary artery goes to the LPA. This is what we see most often is a bidirectional gland, which means that the SVC is connected to the RPA, but the RPA is confluent to the left.

So that's what this connection looks like here, the RA to PA connection. But this is a better connection, which we'll see more often now in our patients, a nice streamlined flow tube to direct flow from the IVC to the PAs. And then sometimes, we'll have this extracardiac, where we're not even doing-- it's bringing it completely outside the heart. But you can still make a connection, what we call a fenestration, to the right atrium in this circumstance.

So fenestrated Fontans are a way to give basically pop-off flow. It gives you preload to the ventricle at the expense of a right-to-left left shunt, which will make you cyanotic. So why is that? Why is it always right to left?

Well, this is the flow. So flow through the pulmonary bed is systemic venous pressure, or CVP, minus your pulmonary venous pressure, or left atrial pressure, divided by your pulmonary vascular resistance. So I can't have flow across the bed of my systemic venous pressure is not always higher than my left atrial, or pulmonary venous pressure. That's why the shunt is right to left.

So I'm just going to skip ahead here in the interest of time to talk about some of the things we see in a failing Fontan. So we are going to be paying special attention to intrathoracic pressure. When you breathe, that matters to the Fontan circuit. And volume changes have a lot of effect on cardiac output. So if you can dry someone out make their CVP low, you're going to drop their pulmonary blood flow, and they're going to not do as well.

So to have a successful Fontan, the ideal patient is going to have preserved ventricular systolic function and diastolic function. We've got to have everything efficient in the circuit. The PVR has got to be really low. The valves have to work well. We don't want to have, say, mitral regurgitation that would impact left atrial pressure adversely or impact ventricular performance adversely. That's going to hurt our circulation.