Hello friends 👋
In this inaugural episode of From the Heart, Drs. Nim Goldshtrom and Adrianne Bischoff explore critical neonatal hemodynamics and cardiovascular care developments. Aimed at neonatologists, the series focuses on research, journal clubs, and expert discussions to deepen understanding of neonatal cardiac intensive care. This episode reviews four groundbreaking studies, including advancements in PDA closure techniques, the role of lung MRIs in understanding pulmonary hypertension, and the outcomes of targeted neonatal echocardiography (TNE) programs.
Dr. Goldshtrom presents an analysis of transcatheter versus surgical PDA closures, highlighting the evolving utility of these techniques. Dr. Bischoff dives into lung MRI studies, emphasizing their potential to refine the diagnosis and management of BPD and pulmonary hypertension. Together, they discuss the impact of TNE consultations, showcasing its role in reducing mortality and guiding treatment strategies for critically ill neonates.
The hosts advocate for a balanced approach to hemodynamic assessment, debating centralized expertise versus broad training in point-of-care ultrasound. They emphasize the value of physiology-driven care and the continuous evolution of neonatal cardiovascular medicine. With engaging discussions and actionable insights, From the Heart establishes itself as a vital resource for neonatal professionals.
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The articles covered on today’s episode of the podcast can be found here 👇
Leahy BF, Edwards EM, Ehret DEY, Soll RF, Yeager SB, Flyer JN.Pediatrics. 2024 Aug 1;154(2):e2024065905. doi: 10.1542/peds.2024-065905.PMID: 39005106
Bjorkman KR, Miles KG, Bellew LE, Schneider KA, Magness SM, Higano NS, Ollberding NJ, Hoyos Cordon X, Hirsch RM, Hysinger E, Woods JC, Critser PJ.Am J Respir Crit Care Med. 2024 Aug 1;210(3):318-328. doi: 10.1164/rccm.202310-1733OC.PMID: 38568735
Joye S, Kharrat A, Zhu F, Deshpande P, Baczynski M, Jasani B, Lee S, Mertens LL, McNamara PJ, Shah PS, Weisz DE, Jain A.Arch Dis Child Fetal Neonatal Ed. 2024 Sep 3:fetalneonatal-2024-327347. doi: 10.1136/archdischild-2024-327347. Online ahead of print.PMID: 39227145
Noori S, Ramanathan R, Lakshminrusimha S, Singh Y.Pediatr Res. 2024 May 22. doi: 10.1038/s41390-024-03248-7. Online ahead of print.PMID: 38778230
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The transcript of today's episode can be found below 👇
The Incubator (00:00.28)
Hi there, my name is Dr. Nim Goldshtrom. And I am Dr. Adrianne Radhe Bischoff. And we're here with From the Heart, the brand new incubator segment on everything hemodynamic and cardiovascular related for the neonatologist. Thank you guys for joining. Adrianne, how are you doing this week and today? I am very happy to be participating on this again. So thank you for your initiative, Absolutely. And thank you to Daphna, Ben, and everybody at the Incubator podcast who are giving us this opportunity to share our experience.
on our insights on hemodynamics, neonatal cardiac intensive care, and really everything cardiovascular, which we love and love so much. We've both done extra training in it and we hope some of you do as well. And so here we are going to talk about the novel stuff that we're reading and interested in about and that we're hoping is moving the field in these domains. We're going to do a slightly smaller version than last time. We're going to do four articles that we picked.
But I think these are outstanding articles that give a good overview of what has been happening in the field in the last couple of months. So I'm excited to dive in and see what we will be able to share with the audience and also learn from each other. Yes, absolutely. And we hope and plan to have this be a regular series, much like the other wonderful incubator series focusing on research, neonatology across the world, where here we can focus
both on interesting articles and great speakers and leaders in the field that are pushing the various aspects of hemodynamics and cardiac intensive care in neonates and preterm infants. And hopefully for you to get involved as well, if this is your niche or your home area of interest, there's plenty of space right here, right from all things related to point of care ultrasound, targeted neonatal echocardiography, being involved in the elements of congenital heart disease.
We're going to continue to platform through great speakers and great talks with the support of the incubator. And in that same vein, we've got four great articles today for our journal club that will be available on the website at the end of this podcast, the end of our talk. And so we are going to get started. We've got a wonderful pulpary of things from PDAs to imaging, with a focus on the evolving utility of hemodynamics and point of care ultrasound.
The Incubator (02:24.334)
Awesome. So, Nim, would you like to get us started with the first article? It's obviously a topic that is very dear to my heart and they've out passed me on my previous article and they have a bigger number of babies undergoing PDA closure. So I'll let you get started on the first one. Yeah, and what a novel project. This article is titled Transcatheter and Surgical Ductus Arteriosus Closure in Very Low-Birth Weight Infants from 2018 to 2022, published this year in Pediatrics.
The first author is Brianna Leahy and the senior author is Jonathan Flyer out of University of Vermont, who was once a Columbia Cardiology Fellow. So great to see our formal fellows thriving and succeeding as well. Again, the background here is that the transcatheter occlusion devices, particularly for preterm infants have been available really since 2019. This group had a wonderful novel idea and took the Vermont Oxford Network database to look at outcomes in preterm infants since the availability and deployment of these devices for
ductus arteriosus closure. It queried von data for preterm infants between 400 to 1500 grams with a birth between 22 to 29 weeks gestation for the years between 2018 to 2022, which is, I guess, a five-year span. Inclusion criteria were standard things, excuse me, the exclusion criteria were standard things such as congenital heart disease, those with incomplete data, those who received both a transcatheter and a surgical closure, which we'll talk about a later, which was a very, very small fraction of the data.
and those who had trans catheter occlusion failure. Statistical analysis involved general estimating equations, looking at outcomes of death, length of stay, and a variety of complications and medical support at discharge to home. And using the system, confounders were included if any had a 10 % change in the model. Again, this is a statistical methodology approach when using things like just a general estimating equations.
They also included a subgroup analysis just for trans catheter group in the last three years for infants greater than 700 grams, because in 2020 that is when this device became approved for this group. And so in the results, they were able to query 726 of the U.S. funded hospitals and find over 216,000 potentially very low birth weight infants and ultimately, we'd all down to 42,000 eligible participants based on this criteria.
The Incubator (04:47.598)
So out of these, 19.4 % received any PDA treatment. Out of those, 96.3 % received just medical therapy and 88 % required no additional treatment at all. And so that's our first lesson here, right? Medical therapy and time apparently do work, right? For a large fraction of these babies. And let's not lose that message because it's still wonderful study on the utility of device closure. But the reality is time, pharmacological therapy do work for preterm infants, which is great. And it's a great lesson to take away.
right? They then were able to procure data on the remaining patients who received non-pharmacological interventions. 6.4 % received transcatheter device closure and 5.6 % received surgery. So basically less than 0.1 % received both transcatheter device and surgical closure. Out of those, the remaining 3.7 % who did not receive pharmacological therapy, just over 52%.
trans catheter device closure and 47 % had surgery with 1 % having both. And so they ended up with 3,393 who received a trans catheter device closure, just under 3,000 with surgery and the device closure group usage actually increased over the time period of the study from 30 to 71 % in that five year span. The differences between birth weights between the catheter group and surgical group were a bit different, 740 versus 690 grams.
There's also less small for gestational age in that group and lower respiratory support in terms of inhaled nitric, user surfactant and RDS. Those in the transcatheter group were more commonly to have higher birth weights and gestational age as well. And so for the main outcomes in the transcatheter device group, there was a marginally higher survival, 96.1 % versus 93 % and a decreased median length of stay, 128 versus 132 days that were not statistically significant.
Out of any of the reported complications, there was no statistically significant difference, 94.4 versus 95.7 % versus the surgical group. There was no significant difference between medical support at discharge to home and no differences between tracheostomies as well. So while overall survival didn't look statistically different in their adjusted risk models, they did find that there was an improvement in transcatheter device closure.
The Incubator (07:14.734)
with an adjusted risk ratio of 1.03 after adjusting for things like gestational age, small for gestational age, maternal hypertension, transfer status, and then clustering infants by hospital. Beyond survival, there was no difference statistically in length of stay, complications, or home discharge with home support. And then going into their subgroup analysis for that group, just over 700 grams from 2020 to 2022, while there was no difference in survival or support at discharge,
There were improvements in complication rates and length of stay, marginally so, but statistically significant. And so what I take from this study is that transcatheter device is clearly possible. It's clearly being rolled out more into more centers. It doesn't seem to be any less inferior, at least by this report from a large registry.
In terms of superiority on gross outcomes that we can look at it, it looks to be at least as good as surgical ductal closure and it may have features that are showing a slight improvement over surgical closure in getting kids out of the hospital potentially sooner, potentially with less complications. And there are not many large studies like this. As the article notes, another large retrospective review from the pediatric health information system showed that there was actually no change in death or length of stay.
where this more modern study does start to show those improvements potentially, right, in between the groups of transcatheter closure and surgical closure. I mean, I think this is a wonderful representation of where our field is moving in a wonderful descriptive study on how things are changing and what we're seeing. Those changes reflected in the kind of outcomes that we care about. What do you think, Adrianne? Yeah, no, this is really cool. Again, this is not a study that's going to...
answer that long-term question, right? Do we need or do we not need to close the PDA? That's the biggest debacle in neonatology, as we all know. But if you do choose to close it in a definitive way, the Vermont Oxford Network does show us here additional evidence that this procedure seems to be safe or potentially safer when you compare it to traditional surgical ligation. And I think that that's a good message on its own for now.
The Incubator (09:25.292)
Right? Because a lot of people still do believe in definitively closing the duct. There is a clear shift in clinical management strategy. And as we keep doing this more and more, we all want to be reassured that at least we're not causing harm in terms of the procedure. And then we can continue to study in better ways if this is the right thing to do for the patients or not. Yeah, absolutely. It's really fascinating how the general outcomes between the groups look the same, but was interesting, although not surprising,
with this database is that they really couldn't tell us about some of the other things that we would like or want to know that you're probably going to capture in things like a cath or a critical care database rather than the Vermont Oxford Network. Things like how many experienced thromboembolic events, right? How many had vessel clots, for example, and had to be treated? Do you avoid any of this kind of post-PDA ligation syndrome or low cardiac output syndrome?
that they weren't able to capture. And I'm curious for the next studies like, or other, again, registries or data sources, whether we can get some of that data to help expand on these kind of, you know, at least in general, is it impacting the ability to get home, major complications that we can look at, and from other sources of data? Thankfully for me, who really likes this topic and who likes to do research on this topic, there's still a lot of questions to be answered. I can, we, myself and other people who are working on this still have a lot of...
work to do and hopefully contribute to how we take better care of these patients. Yes, and as you mentioned, it doesn't answer the question of who needs to close or when should we do closure and maybe the next paper we talk about will touch on some of those concepts. But I also found it fascinating that in the discussion, they also said that for many centers, it's still actually more expensive because of the current device costs and cardiac catheterization time.
than to do an OR surgical ligation. I had no idea and it's kind of wild to me to think that it would be more expensive to do a less invasive procedure in terms of the costs it incurs for hospitalization. And that's something we don't have enough and perhaps we can try to dig into the literature for one of our next segments, if there are more studies in the realm of neonatal hemodynamics and cardiovascular care on cost effectiveness studies, because I don't see a lot of that in the NICU.
The Incubator (11:44.268)
I don't, it's not what we care the most, but it is important in the grand scheme of things. So maybe we should dig into that on some future episodes. Yeah, definitely. mean, our center is participating in a multi-center randomized trial of device closure of the patent ductus arteriosus versus surgery to see if we can really better adjust for these outcomes and find a superior therapy. So it would be fascinating because I mean, this touches on the aspect of things like regionalization a little bit.
You can only do surgery at so many centers. You could theoretically do cardiac cath procedures, even bedside, right? In some centers like in Tennessee do. It could technically make accessibility and availability a lot broader for this high-risk population, kind of fail into this need of procedure. More accessibility for more people can kind of come to your center rather than kind of moving these babies all around states or multiple states.
on logistics of how to get those things done. It is fascinating and looking forward to seeing how the research plays out in this. And so onto PDA management, right? And maybe this next study we'll be talking about will help us answer the question of when and who, about the timing of surgery and its impact on ductal arteriosus closure and hemodynamic significance. Take it away, Adrianne. So our next article that we chose to discuss today is
Patent Ductus Arteriosus and Lung Magnetic Resonance Imaging Phenotype in Moderate and Severe Bronchopulmonary Dysplasia Pulmonary Hypertension. The first author used to be a fellow here at the University of Iowa, a cardiology fellow, Kurt Bjorkman, and the senior author is Paul Kritzer, and they are at Cincinnati Children's Hospital. This article was published at the American Journal of Respiratory and Critical Care Medicine in August this year.
And their objective was to assess the association between a hemodynamically significant PDA duration and clinical outcomes, pulmonary hypertension, and phenotypic differences on lung MRI. We joined it on, I think it's super cool. And that's why I wanted to bring this one because I don't know about you guys, Nim, but we are definitely not doing lung MRI around here. I know Cincinnati did a lot of research on this, but I don't know how much they're doing it clinically. And I think it's fascinating because as you all know,
The Incubator (14:06.734)
BPD is a very complex disease and very difficult to quantify. It's the one of the only diseases in NICU that we define on the basis of the therapies that you are using and not on the disease itself. So I think it's really nice that they have a more objective way of quantifying their disease. Yeah, I find it just hard to get brain MRIs, my baby. So we're, far from lung MRIs, maybe one day. I know kudos to Cincinnati. Can you please teach us all how to do this?
So anyway, this was a retrospective cohort study and they included premature babies that had a clinical diagnosis of BPD as per the usual definitions. And all of these babies had undergone lung MRI before 48 weeks of gestational age. These patients had been recruited for another lung MRI study and I guess they just piled up the ones that fit into the criteria for this particular study. And of course, given
the setting that they had, most of their patients had a diagnosis of either grade two or three BPD, which obviously is a limitation when we are interpreting their findings. But either way, I think it's valid nonetheless. And then in terms of ECHO, they had a standardized screening protocol to evaluate for pulmonary hypertension in all babies with BPD at 36 weeks.
Their definition of pulmonary hypertension was based on the eccentricity index, so septal flattening, or an RV systolic pressure of at least 40, or related to the gradient across a VSD or a PDA if there was a reliable Doppler available. And interestingly, they also looked at 36 weeks. If they did have pulmonary hypertension, they try to categorize them in two different phenotypes, which is, don't, it's not something that I think
People think about it a lot, but pulmonary hypertension is not all related to only pulmonary vascular disease, which is the classic one that all neonatologists are thinking, but it could be also related to flow, especially if you have an ASD, obviously a VSD, which is more uncommon, or if you still have a PDA that is open. So they were able to kind of look at that in a bit more detail as well. When it comes to looking at the shunt, because obviously they were looking at duration of shunt,
The Incubator (16:31.118)
their definition for hemodynamic significance had to do with size. So the PDA diameter had to be at least 1.5 millimeters or greater than or equal to half of the diameter of the proximal left pulmonary artery. And then in terms of shunt evaluation itself, they looked at the shunt velocity, the presence of diastolic reversal of flow in the descending aorta or left heart
dilation, specifically left ventricular and diastolic dimension. Anyway, moving on a little bit from that, their primary outcomes were pulmonary hypertension at 36 weeks. And then they also looked at MRI information, which I'm not going to go into the details because I obviously am no expert on this. But basically, they were looking at total lung volume and lung hyperdensity. So things a bit more detailed in terms of the type of lung disease that these babies could have.
And then they looked at the association between PDA exposure and secondary outcomes, including BPD severity and other morbidities such as tracheostomy, death at discharge, and so on and so forth. Ultimately, they ended up with 133 premature infants that had BPD. They were a mean gestational age of 26 weeks and 776 grams at birth. And not surprisingly, based on what they had already told us about their demographics,
almost 50 % of the babies included in this particular study had grade 3 BPD. So these were kind of babies with sick lungs to begin with. If you look at table one on this study, those patients that had a PDA that was hemodynamically significant for more than two months, so more than 60 days, those babies tended to be younger at birth, they tended to be smaller at birth, and not surprisingly, they
had a more frequent need for interventional PDA closure. They also reported that out of all of the babies included, almost 80 % of them had some echocardiographic evidence of pulmonary hypertension on at least one of the echocardiograms during the baby's admission. And those were echocardiograms beyond seven days of life. So we're not talking about transitional pulmonary hypertension, we're probably talking about kind of late or persistent phenotypes.
The Incubator (18:56.718)
And then when they looked at the 36 weeks echocardiograms, almost 55 % of the babies with BPD had pulmonary hypertension. The majority of them actually, 63%, were characterized as flow-driven and only 37 % were categorized as pulmonary vascular disease, which I think is pretty cool because if everyone is thinking that these babies only have pulmonary vascular disease type of pulmonary hypertension,
perhaps all of these babies would be on pulmonary vasodilators, which could be making them worse instead of actually better. So I think knowing that distinction is quite striking. It surprised me how big their numbers were. And I thought that that was pretty cool to highlight here on this episode. Looking at their outcomes, interestingly, but not surprising to me, hemodynamically significant duct exposure beyond 60 days.
predicted modestly the development of pulmonary hypertension from the pulmonary vascular disease phenotype. The age of resolution of pulmonary hypertension was not different between those who had short duration of PDA exposure versus long duration of PDA exposure. However, the prevalence of pulmonary vascular disease related pulmonary hypertension beyond 36 weeks was associated with the duct
exposure in a stepwise fashion. So the longer you have a duct, the more likely you are in a stepwise fashion to develop pulmonary vascular disease. And even after you adjust for BPD severity and birth weight, a hemodynamically significant duct exposure beyond 60 days continues to be independently associated with pulmonary vascular disease at 36 weeks of gestational age. I'm not going to delve too much into the MRI, but I will highlight that
Most of the MRIs that they did were at about term corrected, so 40 weeks gestational age. And what they did see was that there was an association between prolonged exposure to a hemodynamically significant duct and severity of lung injury. And that the lung MRI patterns were compatible with a phenotype of small airway disease or air trapping more than with that inflammation fibrosis phenotype. So, so much more that we need to learn about this population and the impact of having
The Incubator (21:23.426)
prolonged shunts have on lung disease and the types of lung disease and even how we treat these types of patients. And then when they looked at those secondary outcomes and exposure to duct beyond 60 days of life was kind of associated but didn't quite reach statistical significance, but increased risk of death or the need for tracheostomy at this charge. So to sum it up.
My take from this, obviously this was a very interesting study, different techniques. I hope Cincinnati will continue to send out data like that or teach us all how to do it so that we can continue to explore how to use Lung MRI and the association between PDA and BPD. But one of my take homes is that I hope also that we continue to have better definitions and better ways for tracking how that
burden of PDA exposure impacts on lung disease. And that should include severity of shunt and also how long the shunt is present. Because we know that this is not a linear process. It's not like you have a shunt and it's the same bad shunt for 60 days. It's probably a remitting relaxing course. And that also probably impacts on how lung disease occurs. know, it is so remarkable and fascinating the pathophysiological crossover that this has to like
moderate and large VSDs. Nobody, for example, would let a large enough VSD sit around for six months at home, almost certainly at that point on diuretics and not repair them by three or four months of age. Because all the research, animals and humans, is going to show you that you are at risk by six months of getting permanent pulmonary vascular remodeling. And so you can't leave these large enough shunts unrepaired before you're going to get from a reactive, over-circulated pulmonary vascular bed
and hypertension to permanent remodeling that may not be amenable to medical therapy. That then you are going to have much higher risk for permanent PH. We talk about, I'll just use one patient group as an example, the trisomies, or let's say getting to a month or a month and a half, and who may not be on diuretics at that point with let's say moderately large VSDs, they're developing pH right in front of your eyes. There's no kid with a large enough shunt.
The Incubator (23:46.078)
or ventricular level shunt, regardless of its location, that is not over-circulated in huffing and puffing, right? It's a huge problem. And this just fits with that same physiology, right? We don't have a great way. mean, you, Adrian, probably have a great way of monitoring ductal flow and patency and size, more on a serial basis, but fitting that in with the clinical picture, why is this preemie still on, you know, forget pressure and CPAP, but also on oxygen?
and that's what looks to be like pulmonary edema and X-ray, and it's responsive to diuretics, which improved the clinical picture. These are all suggestive of a large shunt clinically, right? And the burden that is presenting on the kids. So kudos to this program. And second of all, know, feed and wrap has their method for MRI, right? You know, the primary method of getting these kids into the system, right? Incredible thing. And then additionally, a median of five echoes per baby.
in this cohort. It's pretty fantastic stuff. We can barely get one or two when they're critically ill, different problems getting solved and improved upon at our program. But this makes sense. The other fascinating thing I thought was 60 days as they're cut off. I wonder how much of that is biased based on the population that they were able to study and how their data born out. And when they talk about like,
not too much ASD, but let's say like large VSDs, right? You talk about three to six month window and they're pointing at 60 days, right? It feels like it's in that flavor, right? Of time for changes that are occurring to start becoming more clinically symptomatic and potentially unmedically manageable. So 60 days, I guess, kind of makes sense. I wonder if that's going to get replicated in the literature, whether we'll see more repeated evidence like this in months and years to come, but it's not trivial.
And so some people might say, well, you can't really compare a PDA to a VSD. A VSD is going to have so much more likely so much more shunt than a small vessel, 1.5 millimeters. How can you compare that? But I would argue also that when you're looking at VSD impact on pulmonary vascular disease, most of the data that is out there is on term babies who have had their pulmonary vasculature already developed and who most of them should not have other
The Incubator (26:07.968)
lots of risk factors that our preemies have. The younger the preemie, the less developed their pulmonary vasculature is, the less vessels they have because they never had enough to grow. So the capacitance of those vessels is going to be surpassed sooner and they're going to have pulmonary edema and all the sheer stress plus the inflammation, plus being on the vent, plus the inergen and all the things that come up with being a premature baby. So yes, they are not the same thing, but
the there is a common pathology that is going on through having that increased flow through those tiny vulnerable vessels that these babies have. I mean, correct me if I'm wrong, as I'm not a professional echocardiographer, but some of the criteria and part of the criteria we use for impact of ductile size and flow in hemodynamic significance is beyond just reversal of diastolic flow in descending order or things like left atrial size and atrial size as compared to the left ventricle.
So we're looking at volume overloaded situations. I wonder if this potentially is missing the forest for the trees, because we think it's a small vessel. Does it really matter? Most of the things in the body run by resistance, right? It is PVR versus SVR. We talk about flow patterns. And by six weeks of life, PVR has really hit its nadir. And so shots need to be big enough to create this clinical scenario of tachypnea and pulmonary edema, a left-sided overload. I'm wondering if a better picture
right, whether it's MRI or just more serial, he went in and make evaluations can give you that sense of, is it worth keeping this child in this state? You know, clearly it's like a month of PDA is not closing. What do you do? Well, it gives us a better picture. And so as the last study showed, it's clearly a small fraction of our population, right? who end up not responding to medical therapy or time. And so it's this small population within a small population. It's clearly going to need larger studies, more multi-center work.
know, cohorting numbers to get a better answer. Yeah, we can continue to talk about this, but wonderful articles on tools and shifting our focus to more programmatic kind of things, right? Hemodynamic programs, how to deploy these structures in the real world, the successes of these programs. And so moving on to our first of two papers on this topic, we have this great discussion out of this multicenter cohort group. This next article titled,
The Incubator (28:30.144)
Impact of Targeted Neonatal Echocardiography Consultations for Critically Sick Preterm Infants led by a group of leaders in this field, Amish Jain, Patrick McNamara, Luke Martin, and Danny Weiss. Just a wonderful collaboration of people leading this domain. Coming to us from the Archives of Disease in Childhood, the Fetal and Neonatal Edition.
So the rationale here is that these programs, hemodynamics and targeted echo programs have existed for over a decade. This multi collaborative paper run by Canadian hospitals and the University of Iowa looking at preterm infants who are critically ill and exposed to things like rescue medications, inotropes, inhaled nitric oxide are known to be a high risk group for mortality and complications. And those are also the same kind of indications for obtaining targeted echocardiography or hemodynamics. So this group.
looked at this console process during an acute illness, critical illness period for preterm infants versus those who were not receiving or did not get exposed to the console program over a 10 year period of time from two tertiary centers between 2010 and 2019. It included all infants less than 37 weeks of gestational age who were exposed to at least four hours of the exposure groups, meaning an inotrope or inhaled nitric oxide.
that then compared those who received the T and E guided consultation within 24 hours of this event to those who were not exposed to the consultation. And they only looked at the first episode of acute critical illness per subject. They excluded reasonable things such as congenital anomalies, genetic conditions, any congenital heart disease outside of ASD, VSDs and PDAs. The primary outcome included pre-discharged mortality, episode related mortality.
which they defined as death within seven days of the acute care critical illness, new IVH of at least grade three and competing outcomes of death and IVH or death and BPD. They used a novel and interesting statistical methodology, which I highly encourage anyone who's not as familiar with it to do a bit of reading, because it's always good things to kind of pick up and improve on our skill sets. And they used weighted, logistic and quantile regression. And so the weights that they used were a method called inverse
The Incubator (30:50.456)
probability of receiving the treatment estimated by a propensity score method. Propensity score estimates were using a logistic regression model for whether you were likely or not likely to receive the treatment. And so this established method, when you have two potential groups that could be wildly discrepant in their covariates, received TNE, didn't receive TNE, and they're kind of going to normalize it and reduce the mean difference that could be experienced by those two groups.
by creating this propensity score, combined score, to make the differences between them less apparent. And so they show in this paper that you can see in one of their later figures how the standardized means improved significantly when they were able to create this propensity score method to improve on their ultimate regression analysis for the outcome variables of interest. And they used a lot of classic things that you'd want in there that relevant to the treatment, the site, gestational age.
multiple birth, maternal diabetes, low Apgar score, and you can read all about it in the paper, but kudos to them for using these more advanced statistical methodologies to improve on the analysis. In total, they found 873 eligible participants over this 10-year period, 622 of which met criteria, and 297, which is about 48%, that received a targeted neonatal echocardiography consultation. The mean gestational age of this group was around 26.4 weeks, and over this 10-year period,
they know that there was no significant change in mortality overall over this timeframe. And so for the targeted neonatal echo group, that's a baseline, they had a higher severity defined in the study as a higher ventilatory support, more use of bicarbonate supplementation, which I think some who are listening will have very strong feelings about, which is okay. The group also received less prophylactic indomethacin, and that's partly a practice between the site differences of the two centers. There's more therapeutic exposure.
And so they received more inotropes, more pulmonary hypertensive medications specifically. And they also were more represented in combination therapy groups, receiving not one, but multiple inotropes. They were also much more represented in the last EPAC. And so when they divided the 10-year group into three, four-year chunks, there was a much higher representation, close to 60 % of TNE exposed groups in the 2017 to 2019 EPAC. Comparatively, the group that did not receive
The Incubator (33:09.966)
TNE consultations were represented by single therapy, specifically dopamine and dobutamine. And the TNE group in terms of a inotropic use had much broader variety of agents, more epinephrine, no renown, no epinephrine, and actually much more combination agents. So the use of multiple agents at the same time rather than single drug therapies. TNE group also had a higher heart rates at baseline, higher FI2 requirement. They saw a higher rise in blood pressure in the first 24 hours. And they have this nice dot and
whisker graphs at the end of the paper, nicely showing the 24-hour trends of vital signs. And so can see that the TNE group has a much faster rise in blood pressure and sustained in the first 24 hours. Their vasoinotropic scores, VIS, remained high after 10 hours, but then actually were able to come down in the last 12 hours. They note that the TNE group also experienced 82 % of them had a change in management in response to targeted neonatal echocardiography consultations.
And what they were able to show was that over this 10 year period, TNE group was associated with a lower odds of mortality without having an increase in short-term morbidities and an association with earlier and more sustained increases in blood pressures compared to the non-TNE group without causing greater inotropic burden as measured by the VIS, but rather just more inotropic complexity and varied use of drugs.
And honestly, I didn't think this study could get done at this point. T &E, for those of us who read about it and utilize it and want to utilize it in our programs, I thought it was just so mainstream in these programs and hospitals that you couldn't have this kind of comparison group to a non-exposed group. And so this is just incredible to see what we were all hoping to see, right? Which is utilizing it, gets you better outcomes and mortality, doesn't make the burden of care at least based on the
handful of morbidities that they documented and studied here. Worse, showed you that you can target in titrate-deafened physiologies with a broader range of drugs without necessarily increasing the burden of care. I have to imagine as someone who does this for a living, Adrian, you must feel very rewarded by this kind of data. It's kind of speaking for itself where you guys had hoped to kind of evolve and blossom and see how for these high-risk populations,
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when offering something so much more quantifiable, right, and objective in helping the intensivists manage these acute critical illness periods? Yeah, I think obviously this is a kind of a segue to what Reagan Giesinger had done here at the University of Iowa showing the impact of hemodynamic screening in the preterm babies. However, that study obviously was too epoch, so two different time points. And you can't 100 % just say that it was the introduction of doing ECHOES and
having that information. It also comes with new faculty that have a different type of expertise, a different mindset. So I do think that it's interesting that this one compares kind of at the same time that because these faculty are already there, right? And they're just not using that information for whatever reason, right? It could be the middle of the night, it could be lack of resources. There's no downside to it.
But I do love that it proves to a different population and shows the benefits of using targeted assessments and more physiology-based care, which we know makes a big difference when you work with it, but it's hard to prove.
very, very good job. I know that it took them a lot of effort. I know a lot of the people in that paper and I know how much effort they put into collecting the data and doing very sophisticated analysis to try to prove the point. And I loved seeing the results. Obviously, I think this is a sentinel paper for our group. And I hope that we can keep
doing that more and more for the skeptics out there. Because once you've seen it, you know that it gets, you can only do better. There's no right or wrong on what people were doing before, but there is an undeniable value into having a group of people that is experienced, that focus exclusively on this day to day, right? When you are
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being able to focus on cardiovascular care and not have to think about the TPN and the all the antibiotics and everything else, you are able to provide information that could be really relevant on how to take care of critically unwell patients, which is what this paper did. a real testament to these programs and to this service, to what you're saying.
You know, it's not a criticism to things past and hopefully that also be a message or a criticism to current practices. You know, you're not, you're just not flying blind is the goal here. You are getting more data. You're getting things that are become objective, not just subjective and think novel about the practice that you can have with better tools. Right. There, there are just so many drugs available nowadays. And again, I'm trying to be cautious because we are talking about a fragile population.
thousand fifteen hundred grammars and we're using very impressive drugs right in epinephrine, norepinephrine, dobutamine and yes you know we don't really have all the studies to know the complete impact on the brain on the kidneys on long-term outcomes and kind of like driving you know pressure up and the risk for what it may have but again here's another study and you don't get IVH grade 3 you didn't create more brain bleeds you know in in the parenchymal space
at least by what we can assume from these studies. We need longer term studies. We need to know about ischemic hypoxic injury, white matter changes, neurodevelopment, for better or worse, doing things to rescue them, but maybe in rescuing them theoretically, before they get to worse shape, before they're sicker, you kind of get them to survive, but who knows if these outcomes will pan out? we surviving, safer? Maybe you could be rescued, their critical illness right at the right time without letting the sequelae of acidosis and hypoxia ischemia settle in.
that really has to be born out with more data, but everything you just described really is exactly what we do in a neonatal cardiac ICU and any cardiac ICU, right? You see the physiology all the time. And with experience, you understand that tetralogy with map cause can look terrible and a truncus arteriosus with severe truncal regurgitation needs a very different management strategy and will still be terrible. And both will have airway complications as well.
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And I can just focus on the physiology. I get a specialist in nutrition to help me maximize TPN that I don't have to think about it. You need specialized care and specialized data to really maximize the potential and to bring in these extra tools and specialty training to really get to the edge of care for these patients. Yeah, and it just also highlights the fact that the bedside tools that we have without including
echo expertise, they're flawed, right? If you have to change your management 80 % of the time, yes, part of it could be the biases of what drugs these type of clinicians like to use, but it also highlights that sometimes we're not right, right? A baby who's in 100 % of oxygen may not have pulmonary hypertension that is related to pulmonary vascular disease that needs nitric. They might be in 100 % because they have a torrential duct.
that is causing them to be flooded. And sometimes that differentiation is really hard with the traditional tools that we have, which is X-ray, idle sign data. And at the same point where this is a new technology that is helping with more information, we might find out that a couple of years from now with AI and all the physiological data monitoring, we will find out that we were doing something wrong.
that perhaps all my thresholds for left ventricular output or ejection fraction were completely bogus and that I should actually be paying attention to something related to the blood pressure waves or a combination of a score in vital signs or whatever it is, right? So it's the same principle. We just have to keep evolving and I think it's time to embrace this and we are showing that
This does improve what we can do to the preemies and it's the best that is available as of now. Absolutely. But as someone who I'm sure can assess to it's not easy, both embracing and rolling these programs out as we segue to our next and final article on how do we make this happen for others in other programs and for our trainees. Take it away, Adrian.
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So the last article we wanted to discuss today is hemodynamic assessment by neonatologist using echocardiography, primary provider versus consultation model. The first author is Shahab Nouri, but there's other very important authors in this paper that was published on, I cannot find it. This is pediatric research and I'm trying to find the date. This was earlier this year. Let's just bring it up like that.
December, very end of December, I think January of this year. Thank you, Nim. I cannot seem to find that information right in front of me. there you go. Accepted April, 2024. So there you go. So this is a little bit different from the other publications that we went through because obviously this is not data driven. It's not a retrospective study on patients. This is more of a narrative from these authors highlighting both the macro and the micro levels on how
we can impact not only the individual units and their patients, but also how do we implement this technology and how can we balance how long it takes to train people and who should be doing, should we have one specific group of people like we have here at the University of Iowa that has undergone extensive training and does a consultation model. So we're a separate group, we're not on service, we just come see the patients that people ask us to see.
and we provide a recommendation, or should we be working more towards having most or many, at least, neonatologists trained in this technique so that whenever people are on service, irrespective of having a long training and so on and so forth, if they should be able to get the probe and do some assessment and then take care of these patients themselves. And there's obviously pros and cons.
to both ways of doing this. The IOA, which is what I did, takes a long time to train people. It's going to be a while until we're able to put consultation people in most of the big units. And even if you are able to put one neonatologist in each unit, obviously that one neonatologist cannot be available 24-7 for every sick baby that comes. On the flip side, you try to train...
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everybody or most people, you're probably not going to achieve the same high level of expertise that is necessary. Is that good enough for a lot of the situations? Possibly, but is that what's the best thing we should be doing for our patients? So I thought that it was very valuable to go through the pros and cons of what this article discussed, and I would love to hear your thoughts, on this topic.
This paper is great and they really give a roadmap about the hemodynamic assessment and how to consider rolling it out. And just to nuance this a little bit more, we're talking primarily here about targeted neonatal echocardiography and hemodynamic consultation, right? And we should just mention that this is really separate from the concept of neonatal POCUS, right? Point of Care Ultrasound, which are, you know, one could argue a little bit more limited in scope.
but broader in range, right? You can do multiple different organ beds, heart, lungs, abdomen, line placement. You can look for effusions, right? All these kinds of things. I wonder then in that landscape, right, is POCUS, this point of care ultrasound, a skillset that can be ramped up kind of like, you know, we teach residents and fellows, IVs and central lines and intubations. And POCUS may be way to get this concept, right, just like emergency medicine has of
point of care ultrasound, the tools in place using low-fi machines for the purposes of a point of care assessment, right? It's not the same time-intensive cost incentive thing for centers to do or for people to get into like hemodynamics, which is really an advanced skillset. And so for those interested, really need to do a lot more time in terms of training and exposure to be comfortable with TNE.
Not that you don't in POCUS, but doing rapid assessments in ultrasound techniques for a very myriad handful of things like line placement, line assessments, which I do all the time now, despite the tongue in cheek, neo-heart commercials. I just don't do lines anymore without the ultrasound machine, right? And I get called in for the difficult ones along with some of my other expert ultrasound colleagues. We confirm lines with ultrasound at the bedside.
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And this paper is talking about the vital and more focused role of targeted echo, right? In the hands of more providers at the bedside where you don't need a consult from a cardiologist, let's say, and then they're also not doing the sort of measurements that you're doing to get the same utility and seeing, for example, the paper we just talked about, right? The two center 10 year outcomes and seeing how great it can be. I don't know what the right answer and where you should push programs, right?
The people that we're talking about now does a great job, right? By saying that Canon should roll this out earlier, right? Residency and fellowship and, you know, get them baseline training and ultrasound there and get their skills up towards independence in the rest of their training cycles. Through SIMS, through virtual learning, through exposure, right? Usually with low-fi systems, you need 10 or five procedures to kind of gain independence in your practice.
And yet that's not the kind of standard for TNE, nor it should be to gain mastery and experience. So in major programs, you know, that could be really interesting, right? This is not going to get to the level of ACGME to, you know, force all programs into this kind of training. There's just not enough advisors, not enough technicians, and I don't know the right answer. But I would think that point of care ultrasound could be an entry for all of us into this field to make it more universal, particularly at major resource intensive centers.
and isn't that a reachable goal, right? Could that be the next iteration that then helps TNE broaden its applicability into other programs? I don't know what the answer is. I obviously have my biases because this is what I did, right? This is what I did and it's hard for me to, step away from the, not only the risks of doing the kind of the abbreviated version or the not intensive.
version, I do recognize that it's hard to there's a need and there's a there's this hunger for units to have people and they just want to do it now. We don't want to wait five, 10 years until we're able to have trained people to come to our units. But that's how it was everywhere. If you look at Canada, Canada 10 years ago, they didn't have one person on each unit and now they did. And obviously,
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Like I said earlier, one person in each unit may not be enough, but that builds up over time. And I think we just have to caution the balance between being very hungry and wanting to do things fast and not bypassing very important steps and losing on quality that our patients do also deserve. So at the very least, let me just say this. I think it highlights
irrespective of the imaging aspect, that everyone that goes into neonatology needs more training and a higher focus on physiology-based care. Because if we achieve that, even if you don't have the capability of doing echocardiograms, if you leave from a place of very pragmatic, protocolized, symptom-based therapies and start thinking more and more about physiology, which has been lost,
for many years now, I think that on its own is very likely to improve how we are treating our patients, even if people are not able to do echocardiograms themselves, even if people are not able to do this consultation versus primary care model. So I would focus on that while we are training people and trying to get this more broad into the units so that those babies that have complex physiology or those babies that
could be potentially harmed if they get an assessment that is incomplete or not accurately delineated so that those patients are also protected. Is that a good place to kind of end? It doesn't add the imaging part, but at least it adds more knowledge. Yes, you brought up probably the most important concept. Things like tools are great, understanding fundamental concept of physiology is pivotal.
That's our whole job in fellowship is to train the future generation of physicians and neonatologists who are going out into the world how to think and how to apply their craft. If you had all the skills and the tools and the resources available, it's great. You need to know how to use it. A hammer is not a tool for everything and an echo is not a tool for everything as well. Just like you mentioned with a great example, 100 % FIo2 requirement can be a myriad of things, both cardiac, pulmonary, or their interactions.
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Shunting in one direction, low cardiac output, low preload, not just pulmonary disease. Such a broad range of reasons before you deploy services, diagnostics and treatments. It is crucially important. And at the end of the day, having more advanced skills is great and there's no perfect system. What I like to harp back on are, you know, wonderful quotes and expression and to quote the former Alabama coach of Nick Saban, who says all the time, to be great.
takes what it takes. There's no shortcutting. For example, in your hemodynamics training programs for your fellowships for a year, right? You get them to come in and do something like 50 million echoes, right? And then being facetious, it's clearly no exaggeration, but they do several hundred in an entire year. In my CICU year at Boston, it's the same model as it is for hemodynamics, right? And the cardiac ICU trains individuals in their one year fellowships the same. You go to programs that have a large enough volume of patients.
You see something like another 500 to a thousand post-ops and that's all you do for a year. You very quickly learn the skill sets and you round out what else you're missing. Cath, electrophysiology, other ICU time, right? Cause to take care of these like high risk, high end kids, takes what it takes. And you need to hear exposure and experience from a lot of other practicing attendings. And I do harp on this a lot, you know, for those who are interested, it will just take more training. That's okay. It takes a while to be good at something and nobody gets it.
good right away and you won't get those skills right away either, but that's all right. That's why you go into workplaces with teams and mentors who support you through this. Our cardiology folks and critical care folks and double boarded folks do this all the time. Cardiologists who want to specialize do an extra year in echocardiography, cardiac catheterization, electrophysiology. There is also now becoming landing spots for neonatologists with these additional skill sets.
We already have places that are burgeoning neuro NICU centers, right? And pulmonology, neonatology cohorts for their BPD populations. Places are training you and places want to train you because places are interested in broadening what neonatology can offer to our growing population. All right. Our program here at Columbia is now burgeoning our hemodynamics program. And I hope that more neonatologists will continue to not just see this as an important tool, but want to get involved and get trained. Right. It just takes time.
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One of the additional wonderful things I got to do in Boston is learn ultrasound and point of care ultrasound, right? It was just convenient and ended up working out. It took what it took, which was time and placing a lot of lines and doing a lot of exams under the supervision of people around me, but it works. I hope those, these kinds of papers that we talk about can further encourage those interested to pursue this and reach out to us and find the avenues because whether you're worried about whether they can use it or you can have it as a job, there are people.
who are there like myself and like Adrian and other leaders in the field who understand and can make that happen for you and with you and find you places to work at your highest skill sets. You just need to be interested, find these programs that do exist to get them and you to the level, cause it'll just take time. That's all it takes. Our other colleagues and other participants do it. It takes a year sometimes for depending on the skill sets you want, it takes two.
one day hopefully gets more integrated directly with primary training, residency and fellowship, you get the skill set, but this is the evolution. And like you said, it improves care and it is paving the next generation of work. But I will argue though that even if you don't want to take that additional year and you don't want to be over specialized, you don't want to become a human dynamic specialist or you don't want to necessarily become NIMM who takes care of all these very complex post-ops, but there are ways.
there are educational opportunities out there and there are ways to learn the tools so that your skillset at least is better than the average person coming out of neonatology fellowship. So learn about physiology, watch, you know, neonatal research collaborative center has a lot of talks and there's just other ways of learning about physiology, learning about these patients and remaining interested in this.
And just as an example, some people might say, well, it's easy for you, Adrian, to say, well, you don't necessarily need an echo right away when you are able to just pick up the probe whenever you want because you have that skill. But I try to be critical of that myself. So when I'm on call here at the University of Iowa with one of the fellows and I have a baby that perhaps if it was, you know, 10 a.m., I would have done an echo. I try to critically think, do I actually need this information? Is it going to change or can I try to teach
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my trainee and try to manage this patient by looking at everything else and by trying empiric therapies before I jump into let's do precision management right away. So I do try to find some opportunities so that my trainees that are not going to go into hemodynamics fellowship and that are just going to go out into the world for them to practice the concepts, for them to practice the physiology based and all the thinking that goes into it.
because I think that that's relevant to in the current era where I know that not everyone's going to have imaging available and especially this type of finessed imaging available. And I want them to learn those to have those, you know, abilities as well. So I think that that's important and more people should be doing that to train their fellows or residents or whatever. Yes, it's certainly a great privilege for us. And in my domain,
Neonatal cardiac intensive care, it's the same concept. You have a hypoplastic left heart baby, it's a week after the Norwood procedure and is blue. There is a myriad of reasons, you know, why they're cyanotic, right? And it will not really be figured out by an echo immediately, right? Whether it's low cardiac output, anemia, hypoventilation, myriad of things. It's not always lung or hearts, not always pulmonary veins. So many reasons there could be for why that baby is blue. And an echo might show you
or slightly poor function, which could also be potentially picked up on a murmur and some physical exam. And you're going to treat based on this clinical pictures. The tools are only helpful as an ancillary part of the diagnostic process, which is still very much dependent on good clinical training judgment and putting the pieces together. The echo doesn't solve the problem. You're going to treat on this giant multi-modality picture.
There's so many things you can do and it's about the physiology, not just the tools. Those core lessons can continue to get taught to the future generation of neonatologists as they most importantly should. You know, this has been great and fun. What a great set of articles. Thank you, Adrian, for curating this week for our second of hopefully a long and fruitful From the Heart series. And we're thankful for the entire incubator community and family for giving us this.
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opportunity and platform to talk and continue to talk about everything hemodynamics and cardiovascular. If anyone has ideas or things that you guys want us to discuss, you are welcome to email us or Ben and Daphna and we can take a look and see if it's applicable for this segment and we can maybe discuss in future episodes. It's been great as always, Adrianne. I hope you have a great rest of your week and to everyone out there. Thank you for joining us. Thank you, everybody.
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