#446 - Is Bedside Transcatheter PDA Closure Ready for Your NICU?

Hello friends 👋

What if closing a PDA could be done at the bedside in under 10 minutes, without transporting a fragile preterm infant to the cath lab? Dr. Shyam Sathanandam, Chief of Cardiovascular Medicine at Nicklaus Children's Heart Institute, joins us to discuss the evolution of transcatheter PDA closure in extremely preterm infants. We cover how bedside procedures protect the most vulnerable neonates, which infants are most likely to benefit from closure, the learning curve and complication profile, and Dr. Sathanandam's vision of eventually training neonatologists to perform this procedure themselves.

Dr. Shyam Sathanandam has consulting and compensation relationships with Abbott Laboratories and Medtronic, both relevant to topics discussed in this episode.

Link to episode on youtube: https://youtu.be/z4D1xBbDmv4

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Short Bio: Dr. Shyam K. Sathanandam is a globally recognized pediatric interventional cardiologist serving as Chief of Cardiovascular Medicine and Co-Director of the Nicklaus Children's Heart Institute. He earned his medical degree from Stanley Medical College in Chennai, India, and completed advanced training in pediatric interventional cardiology at the University of Pennsylvania/Children's Hospital of Philadelphia. His clinical focus includes interventional cardiology for neonates and infants, particularly closure of ASDs, VSDs, and PDAs in extremely premature and low-weight infants. Dr. Sathanandam has served as principal investigator on numerous clinical trials resulting in FDA approval of life-saving devices for newborns. He pioneered bedside transcatheter PDA closure in extremely premature infants and founded the International PDA Symposium in 2018, the first global conference dedicated to PDA management in preterm newborns. He is board certified in general pediatrics and pediatric cardiology and is a fellow of the American College of Cardiology.

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The transcript of today's episode can be found below 👇

Daphna Yasova Barbeau MD (00:02.036) Hi everybody, we are back in the studio for a really interesting interview this afternoon. I'm here with Dr. Shyam Sathanandam, a globally recognized pediatric interventional cardiologist who serves as chief of cardiovascular medicine and co-director of the Nicklaus Children's Heart Institute here in Miami. Before I go into the rest of your bio, thank you so much for being with me today.

Dr. Shyam (00:33.198) Thank you so much for having me. I am thrilled and excited to participate today.

Daphna Yasova Barbeau MD (00:39.434) Well, for people who are not familiar with your work, your clinical interests focus on interventional cardiology for neonates and infants, particularly closure of ASD, VSD, and the PDA in extremely preterm and low birth weight infants, as well as percutaneous pulmonary valve replacements in children and adults. If that wasn't enough, you're a leader in pediatric cardiology research serving as PI on numerous clinical trials. Several of these have resulted in FDA approval of new devices for newborns and infants, as well as pioneering groundbreaking procedures. We'll talk in a little bit about bedside transcatheter PDA closure in extremely preterm infants in the NICU, as well as pulmonary flow reduction in neonates with complex congenital heart disease and stent therapies for infants. In addition, you're also at the forefront of interventional cardiac MRI, lymphatic imaging and interventions, as well as the integration of virtual and augmented reality in cardiac interventional procedures. We've got a lot to talk about today in a very short amount of time. I also wanted to mention, we were so grateful to hear your talk at our Delphi conference this year. It was entitled "Innovation in Neonatal Cardiac Interventions." Before we get into hearing about the interventions, tell me a little bit about your path in medicine and how you became committed to caring for infants with cardiac disease, but not just caring for them, really taking the next step and innovating in terms of procedures, tools, and equipment, which I think is a step that a lot of physicians never get the opportunity to do.

Dr. Shyam (02:22.38) Thank you. My career path actually started in India, where I'm originally from. I was actually an orthopedic surgeon in India. When I came to the States and started doing my training in pediatrics, I was scared of neonates. My first rotation was in the neonatal ICU, and I was worried I was going to break some poor baby's bones because that's what I did as an orthopedic surgeon. I was breaking bones and putting them together. So I was very nervous and obviously very timid. But my interest grew in cardiology, and I knew from the beginning I wanted to do interventional cardiology. Just being a surgeon, I was also an artist. I had a career as an artist before I became a physician. My focus was on microsurgeries; I was thinking of doing hand surgeries at some point. When it came to interventions, obviously my focus became more directed towards the smallest of human beings, the neonates. When I first got into interventional cardiology, I wanted to do procedures on these tiny babies, except we didn't have devices made for them. There was a huge unmet need in this field. For example, with PDAs, as you mentioned, when I was training, the only definitive closure was an operation, which required a thoracotomy. When I saw how this procedure was done, and as a surgeon, I knew exactly how to do it, I just felt it was too invasive for these tiny human beings. I believed there had to be a less invasive way to close PDAs. So that's the genesis of my interest and developing an expertise in interventions in neonates. I must say, even though I've never trained as a neonatologist, I've spent so much time in the NICU that I feel I'm half a neonatologist, because these babies have taught me so much. Over the years, I've learned so much just being in their presence, learning how they grow and develop, the special needs they have, and what it takes to get them not just to survive. Most of us know how to help these babies survive. It's more about their long-term outcomes: how they do in school, and how they perform as productive citizens. My interest grew because I felt there was a big unmet need in this field. We can talk about all the innovations we've come up with over the years, which hopefully will be a stepping stone for future physicians to build better devices and better therapies for these patients.

Daphna Yasova Barbeau MD (05:19.409) I love that. I'm going to go back and highlight something you said about being an artist first. I didn't know that about you. I wonder how your passion for art has enhanced your work as a physician, and do you still get the opportunity to do any art outside of the suite?

Dr. Shyam (05:37.294) Right now, my career is too busy to focus on art, but I do think it has enriched me because as an artist, you are creative. The innovative mindset comes from the creativity that art taught me from childhood. I used to do sketching, portraits, landscapes, and carving. It creates a very imaginative and creative mind, and I do think our field requires us to think outside the box, be creative, and be innovative, but also be thoughtful. We cannot just experiment on these babies. We have to be very thoughtful and work in a very scientific manner to develop therapies tailored to a certain group of individuals.

Daphna Yasova Barbeau MD (06:39.847) As you well know, we're in a time in neonatology where PDA closure is still a very hot topic. In the last handful of years, a lot of units are moving away from PDA closure altogether, even though we recognize that exposure to the PDA certainly worsens outcomes. We haven't quite found the solution to whether closing the PDA improves outcomes. What do you think transcatheter closure brings to the table that medical or surgical closure doesn't?

Dr. Shyam (07:20.002) Let me answer this question in three different ways. One, the reason we do not know whether PDA closure is beneficial or not is because we've never done these clinical trials based on a definitive closure technique. Most of these clinical trials are done with pharmacotherapy, which is at most 50% to 60% successful in extremely premature babies. In my field, if I say I can only close 50% of the PDAs, nobody is going to accept that as a successful procedure. The procedure should be 100% successful. We never answered the question of whether PDAs need to be closed because clinical trials haven't included definitive closure therapies. Surgery was the only definitive closure technique, and none of these randomized trials included it. That is number one. The second point is I do think some PDAs need to be closed, but not all of them. Spontaneous closure is still pretty high in these babies, so we don't have to close all PDAs. It is important to identify which patients benefit from closure. The third important point is I wanted to come up with a definitive closure therapy that is so safe that even if you close all PDAs—including some that may have spontaneously closed—the adverse event rate is extremely low, so the intent to treat will go up. Those are the three principles by which I operate. The transcatheter closure is a very safe procedure. During the initial IDE trial, we found that the serious adverse event rate was very minimal. Any adverse event rate was 5%, which is relatively low for a very first clinical study. As people get skilled at this, that rate should come down even further. In my experience of over 500 transcatheter PDA closures in babies less than two kilograms, the adverse event rate I quote is about 1%. The therapy is evolving. We've been working with industry to come up with a bedside PDA closure kit, which is super quick. Actually, I did a procedure this morning with this new bedside kit. My entire procedure time was seven minutes. This patient is five weeks old and had received three courses of medical therapy, and it took seven minutes to close this duct. Why expose this patient, who is still on a high-frequency ventilator, to a large volume left-to-right shunt for five weeks when you could close it successfully in seven minutes without any adverse events? Medications still have side effects. The idea of developing this therapy was to make the procedure super safe, 100% effective, and hopefully have zero adverse events. Then you can offer a therapy that may be utilized by a neonatologist. Honestly, I would like for neonatologists to actually do this procedure because when you have to trust a different subspecialist to do a procedure, it's never going to take off. I really wish I could teach all neonatologists how to do this at the bedside.

Daphna Yasova Barbeau MD (11:07.919) I didn't realize that was your vision.

Dr. Shyam (11:10.306) That is my ultimate goal: to arm the neonatologist with the skills to do this procedure at the bedside. If I teach you and give you the skills to close it in less than 10 minutes, you will not choose medicine as your primary therapy. You'll probably choose to do the procedure yourself, get it done in 10 minutes, and forget about the PDA. You have so many other things to focus on with these tiny babies.

Daphna Yasova Barbeau MD (11:37.501) Very exciting. Your second point brought me to my next question: what clinical signs and features is your team looking at to determine which infants are most likely to benefit from the intervention?

Dr. Shyam (11:59.052) That is the million-dollar question: how do we identify which patients benefit from this? I wish I could answer that easily. Without giving too much away—since I haven't published some of these findings yet—we are looking at it slightly differently. There are several groups, including the group in Iowa, looking at echo-based scoring systems to identify hemodynamically significant ducts. Or you have someone like Afif EL-Khuffash from Ireland using echo and clinical data to predict which ducts may be at the highest risk and targeting those patients based on scoring systems. We are looking at it differently, and I will eventually publish what we found regarding which babies need to be targeted. One of the issues with using echo is that while it is good, it still relies on reflected sound waves. Since I do cardiac catheterization for a living and actually place catheters into babies, we are able to calculate flows. Ultimately, the shunt volume is what matters, and we can calculate it. Having done so many of these procedures in tiny babies, we've been calculating shunt volumes to predict which babies actually have high-volume shunts. More to come on that subject, but I do think identifying which babies will benefit is the most important question.

Daphna Yasova Barbeau MD (13:42.006) We've talked about transcatheter closure, but you're really highlighting this opportunity to do bedside transcatheter closure, where you bring your team to the NICU so the baby doesn't have to go anywhere. We obviously recognize those benefits—those babies don't tolerate transport or the loss of heat and humidity. Talk a little bit about how that shift protects patients or has improved outcomes compared to a routine transcatheter procedure.

Dr. Shyam (14:20.866) When I first started out as an interventional cardiologist, we did procedures in the cardiac cath lab. We were transporting these babies from the NICU to the cath lab, taking them out of their incubators, disconnecting the ventilator, and connecting them to a different ventilator. So we derecruited the lungs. It was a process that I don't think is safe for babies. I worked in a children's hospital where no baby was born in the hospital; every baby was transported from somewhere else. For me, transporting from the NICU to the cath lab was not a big deal because these babies were coming from a different hospital anyway. But there are only a few children's hospitals that can perform these procedures. There are many NICUs around the country, but maybe only a hundred centers have the capability of doing transcatheter PDA closures. So how do we reach all babies? Most get transferred to a tertiary care center. Why don't we go to the NICUs where these babies are born instead of transporting them? That was one of my goals. Second, the more I've done this procedure, the more I believe the patients who benefit the most are the very young ones. For those born at less than 26 weeks, the first 10 days are crucial. The spontaneous closure rate is still high in the first 10 days, but if it does not close by day 10 and you're still needing a lot of mechanical ventilator support, those babies benefit the most. We like to do the closures in the second week of life so they can come off the ventilator faster. If they've already been on a ventilator for four or five weeks, we don't see the benefit as much. You don't start medical therapy at six weeks of life, whereas historically most transcatheter patients were referred at six weeks because they were more mature for transport. If you're not going to transport the baby, you can do these procedures much sooner. We go to the baby's bedside, the baby stays in the incubator, we maintain temperature and humidity, and the baby stays connected to the ventilator. It's almost like placing an umbilical line. We just establish intravenous access, and our catheters are designed to go to the duct. Once the catheter reaches the duct, we advance the plug, implant it under ultrasound or echo guidance to verify its position, detach the device from the cable, and remove the catheter. It is a very quick procedure, and the trauma to the child is the same as placing any intravenous line. There's no reason to disconnect the baby from a ventilator or take them out of the incubator. We don't need fluoroscopy or angiograms traditionally required in the cath lab. I think accessibility to the therapy improves if we offer it at the bedside. Eventually, if it's done at the bedside by the NICU team, I think this will be the primary form of PDA closure.

Daphna Yasova Barbeau MD (18:26.984) You haven't shared it here, but in a previous talk, you highlighted your commitment to the utility of this procedure. You're not just saying, "Bring the patient to me, and I'll do it." You have been going out into community hospitals across the world to teach this procedure and show people how to do it at the bedside. Tell me a little bit about that experience.

Dr. Shyam (19:04.641) I feel the impact I've created has actually been greater outside the United States. We take things for granted here. We have good transport teams who can transport extremely premature babies safely. If you go to other countries, they don't have that resource. For example, I went to Malaysia three or four years ago. They wanted to learn how to do premature PDA closures, and I didn't want to teach them how to do it in the cath lab. I wanted to teach them how to do it at the bedside with just echo guidance. I showed them once. I came back a year later to Malaysia, and they had done about a hundred PDA closures at the bedside using just echo guidance. They travel from hospital to hospital with a team of two physicians, techs, and nurses carrying a little suitcase to perform the procedure. In that country, there's no way they could transport all these babies to one facility. There's another center in Germany with two physicians who travel to around 19 neonatal ICUs to do this with echo guidance. The United States is interesting because our transport teams are better, so the necessity hasn't risen as much. Additionally, there's the complexity of insurance, physician malpractice, credentialing, and contracting between hospitals. You can't just go and provide service in a different hospital without contracts in place. Once you decide how you want to set your program up, you approach it with a service mindset. It's actually not "good for business" for the hospital, because transferring a patient in brings more revenue than sending a physician out. It's about doing the right thing for the babies. It is a much more challenging task in the United States, but with the right support and mindset, it can be done.

Daphna Yasova Barbeau MD (22:37.318) I love that. You mentioned that there are still some adverse events. What are the most common adverse events?

Dr. Shyam (22:56.312) Thankfully, most of the adverse events I had happened very early in my experience when this procedure was still in its infancy and the equipment was not as sophisticated. This therapy has evolved rapidly because the industry has invested a lot of resources. Before we had the current equipment, we worried about injury to a blood vessel or the heart itself, which can result in life-threatening internal hemorrhage. Second is device embolization. Luckily, device embolization doesn't seem to happen in the smallest babies; it happens more frequently in larger children because in extremely low birth weight infants, these devices just don't have enough room to move. What we do see is the device shifting slightly anteriorly, causing obstruction to flow into the left pulmonary artery, or slightly distally, causing obstruction to flow in the descending aorta, almost creating a coarctation of the aorta. Having reviewed complications from different centers, most happen due to two things: either the device is oversized, so it milks one way or the other when the duct closes around it, or the device is not positioned completely intraductal. It cannot hang out on either end of the duct. As people go through a learning curve, these complications should be minimized. The other complication we see is tricuspid valve injuries. Because we have to cross the tricuspid valve, it's easy to get tangled within the septal leaflet's chordal apparatus and avulse it. We realized this complication mainly happened during catheter exchanges. Now, with the new bedside kit, we don't have to do a catheter exchange; the catheter used to cross is the one the device goes through. I think that complication should go away. We have made a lot of changes to make the procedure safe, and the incidence of complications should continue to go down.

Daphna Yasova Barbeau MD (26:21.256) You mentioned doing this in hundreds of babies less than two kilos. What does the lower limit look like? What are the smallest babies this can be done in?

Dr. Shyam (26:34.894) After doing so many procedures, I feel like size is just a number. What I look for more is tissue maturity. The smallest baby I've done was about 400 grams. It's not really the weight of the baby; it's the tissue maturity, because sometimes babies have a lot of edema, making the tissue very friable. The youngest patient I've ever done was a 23-weeker on day of life five. That baby initially made me nervous because opening the incubator caused so much humidity loss. But the procedure went very smoothly. That made me realize it can be done very safely in almost every patient. I'm not advocating that every day-of-life-five baby needs a PDA closure—that was a special circumstance. But it can be done safely regardless of size.

Daphna Yasova Barbeau MD (28:03.226) Is there a gestational age where tissue integrity and maturity make things less complicated?

Dr. Shyam (28:11.63) I wish I could answer that easily because in the last 300-plus patients, I haven't had a complication. But I do think tissue maturity is optimal for the current generation of catheters around 25 weeks corrected gestational age. For example, a 23-weeker who is two weeks old is 25 weeks corrected. At that time, the current catheters are very safe. I think in the future, catheters may get even softer, almost like spaghetti, and these babies will tolerate procedures even better.

Daphna Yasova Barbeau MD (29:06.072) This work obviously takes a lot of collaboration between nurses, neonatologists, and cardiologists. For NICUs interested in doing things at the bedside, what infrastructure and culture changes are necessary for success?

Dr. Shyam (29:27.298) This is truly a team effort. The neonatologists know the babies more than the proceduralist. The bedside nurses and respiratory therapists know even better how the baby reacts to small changes in ventilation or the environment, and the parents know their child best. It is important to understand everything about the patient before a procedure. I spend a lot of time talking to the neonatologist, the bedside nurse, the family, and the respiratory therapist. In my earlier days, I would spend half a day just sitting in the patient's room to understand how they behave to subtle changes in noise or environment. You have to trust everybody in your team during the procedure. Post-procedure, everyone needs to understand what signs to look for. It's good to set up protocols that work for your specific institution. Whether you're working in an open NICU or tiny spaces, you have to decide what works best locally. I'm happy to share our workflow, but it comes down to local needs. You need a champion invested in leading the effort, and longitudinal follow-up is super crucial for any new therapy.

Daphna Yasova Barbeau MD (32:00.745) I think a lot of physicians don't understand how new devices are developed. I'd like to hear about your journey with that before we get into the devices themselves.

Dr. Shyam (32:42.958) The process is super complex. My initial interest was to develop a stent for newborns that can be dilated to an adult vessel size, for example, for newborn coarctation of the aorta. Instead of an operation, could we just stent it? The problem was a small-diameter stent couldn't be dilated as the child grew. So my invention was a stent design that could be dilated with the patient. I faced many roadblocks. You have to have a deep understanding of material sciences, alloys, biochemistry, and the oxidizing or galvanizing properties of metals. Once you have a computer design, you need a manufacturer to build a prototype. Obviously, you must work with patent lawyers to protect your idea. Then comes the tedious effort of animal testing. You need funding through NIH, SBIR grants, or venture capitalists. The easier pathway is to partner with industry because they have R&D and resources. You may not make much money licensing your patent, but it gets done. Currently, we do have an FDA-approved stent for newborn babies that can dilate to an adult size. I was involved in the prototype, animal testing, and clinical trials. My other big contribution is a device called a pulmonary flow regulator, restrictor, or reducer (PFR). The concept has been around, but nobody had a solution for newborns with congenital heart disease and excessive pulmonary blood flow, like VSDs or complex single ventricles. If we can restrict pulmonary blood flow, we can balance the circulation, prevent heart failure, and allow the baby to grow and mature before having heart surgery. For example, Hypoplastic Left Heart Syndrome requires one of the biggest open-heart surgeries in the first week of life, involving bypass and arresting circulation. If we can maintain fetal circulation by restricting flow to the lungs and keeping the duct open, we delay the need for massive surgery until they are older. The impact will be huge outside the US, where newborn congenital heart surgery results aren't as good. You'll hear a lot about pulmonary flow restrictors in the future.

Daphna Yasova Barbeau MD (38:24.677) Incredible. What does the future of neonatal interventional cardiology look like?

Dr. Shyam (38:43.84) I don't know what the future holds entirely. Ultimately, our biggest goal for congenital heart disease is to give the patient a normal heart—either by treating the fetus, identifying genes, or preventing expression to stop the disease from happening in the first place. Another goal would be heart transplantation without rejection using the patient's own myocytes, replacing the heart once for a lifetime. While those are futuristic, in our lifetime, I think surgical interventions could be replaced by percutaneous ones. For example, ECMO cannulation is currently done by surgeons cutting down vessels; we can do this percutaneously. We just need to build the expertise. I also think more devices will come to treat congenital heart diseases percutaneously instead of open-heart surgery, minimizing trauma during the critical first 28 days while the brain and organs are maturing.

Daphna Yasova Barbeau MD (40:50.107) For people who say, "I think I've thought of an invention that would help my patients," what are the first steps?

Dr. Shyam (41:21.838) It's very important to have a curious mind. You cannot just admit that what we are doing is always correct. Question everything. Don't just accept that something is "evidence-based"—it's hard to collect evidence in our field. That's the only way new ideas come. To put it into practice, you have to be very persistent and have absolute conviction that your idea is better than what exists. You have to work through a difficult pathway to make it a reality to improve patients' lives. Stay curious, have conviction, be persistent, and tune out the excessive noise and distractions.

Daphna Yasova Barbeau MD (42:49.977) My last question is, how do we engage families in this process? How does consent work for things that are still partially experimental?

Dr. Shyam (43:15.918) It is difficult to consent families for a clinical trial or experimental procedure, but you'll be surprised how many are willing to participate. When we approach families, we explain the current therapy, the evidence for it, and why there is a need for a new therapy. To convince them to allow a new procedure on their child is difficult, but if the risk is minimal, they are often willing to try. You have to earn their trust because they are signing consent for you to invade their child's body. Trust is important, and you have to be genuine. You must first believe that what you're doing is the right thing for the child. If you're sincere about it, most families are open to this.

Daphna Yasova Barbeau MD (44:53.253) I appreciate that. Dr. Shyam Sathanandam, thank you so much, not just for being with us today and teaching us about what's new in interventional cardiology, but for continuing to push the limits and make lives better for the babies we care for.

Dr. Shyam (45:15.512) Thank you so much for having me. It's been a pleasure.