#456 - [Journal Club] - 🫀 From The Heart - Do These Newborns Have Diastolic Dysfunction, or Just Different Physiology?

In this prospective study, Adrianne and Nim dig into an area with almost no normative pediatric data: right ventricular diastolic function. Comparing 57 infants with RV pressure overload after intervention for pulmonic stenosis or tetralogy of Fallot to 134 healthy controls, the authors found a consistent pattern, reduced beat-to-beat variability, a higher atrial contribution to filling, and an E/A ratio inversion that was nearly universal in the CHD group versus about half of controls. It's one of the first real attempts to define what a right-sided diastolic pattern actually looks like in this population. But without a comparison against cardiac catheterization, the hosts agree the findings are hypothesis-generating at best, a starting point for a multi-parametric approach, not a reason to skip an invasive workup.

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Echocardiographic Markers of Right Ventricle Diastolic Dysfunction in Neonates and Infants with Congenital Heart Disease. Cantinotti M, Capponi G, Scalese M, Palladino E, Giordano R, Franchi E, Viacava C, Corana G, Marchese P, Pizzuto A, Assanta N, Santoro G. J Clin Med. 2025 Dec 23;15(1):98. doi: 10.3390/jcm15010098. PMID: 41517351 Free PMC article.

Transcript

Adrianne Rahde Bischoff (00:00.000) And the next paper is "Echocardiographic Markers of RV Diastolic Dysfunction in Neonates and Infants with Congenital Heart Disease." First author is Massimiliano Cantinotti. And it was published in the Journal of Clinical Medicine, now in 2026. I will say, even though Nim said, "well, this is your domain, TnECHO (Targeted Neonatal Echocardiography)" — this is not TnECHO, because this is in congenital heart disease, which is not my population, but I'm still interested — it's a disease we talk about all the time in a theoretical standpoint, but we haven't really done a lot of studies in the normal-heart population on diastolic function.

Nim Goldshtrom (01:10.234) That's okay. I was hoping we'd join forces again on this paper, because RV failure can be such a big problem for us. So using your expertise, understanding how to think about this paper, I'm curious to hear your thoughts — please.

Adrianne Rahde Bischoff (01:22.234) So they decided to look at RV diastolic function, which is obviously very complex to assess in any baby, because the RV has its unique geometry. There's respiratory variability, which impacts the right side much more than the left side. There are obviously developmental changes that happen as the PVR (pulmonary vascular resistance) is changing, and the physiologic inversion you'd expect of the E/A ratio — the early-to-atrial-filling ratio of the right ventricle. And what we know from adult Doppler data is that it obviously doesn't translate to infants — pediatric normative data is pretty limited in our population. So what the authors of this paper wanted to do was understand what the tricuspid inflow patterns look like in infants who have RV pressure overload after interventions for pulmonic stenosis or tetralogy of Fallot. So they enrolled 57 babies prospectively, and did uniform post-intervention timing, at 12 to 48 hours after either surgery or catheter-based therapies. They compared those to 134 matched healthy controls — roughly twice as many — to try to validate a normative dataset. And the primary focus was the tricuspid E and A wave with the E/A ratio and the E-wave deceleration time, which is something that we obtain images for, but haven't explored, at least locally, in the targeted neonatal echo world.

Nim Goldshtrom (03:19.234) Do you do anything else for diastolic dysfunction, just out of curiosity?

Adrianne Rahde Bischoff (03:20.234) Yes. Theoretically, you could look at tissue Doppler or strain imaging — strain rate, specifically — but we just don't know what to make of it yet. We're still in a fairly simplistic world of looking at the direction of the atrial-level shunt and things like that, and guessing. We don't routinely assess this, mostly because we don't even know what normal is. So it's hard to say what would be abnormal, and even if you find something abnormal, what do you do about it? Anyway, what they found was that these babies with congenital heart disease and RV pressure overload had a consistent pattern where they had, first of all, markedly reduced beat-to-beat variability, which is interesting. And anecdotally, I've noticed this in neonates — the well, spontaneously breathing babies have more variability, which is part of why we're kind of skeptical about measuring this, because you'd have to average out many, many beats, while babies who are vented and muscle-relaxed and so on tend to have less beat-to-beat variability. They have a higher A velocity — meaning the atrial kick contributes more to right ventricular filling — and therefore a lower E/A ratio, and the inversion of the E/A ratio was essentially universal in this population, as opposed to about 50% of the controls. And there was minimal correlation between any of these findings and systolic indices, suggesting these diastolic abnormalities seem to be an independent phenomenon. So I thought it was good that it was prospective, with a very clearly defined population, a pretty large sample size actually, with a control dataset. They emphasized beat-to-beat variability, which I think is very important when looking at right-sided, especially inflow, markers. They had pretty good reproducibility, with good inter-rater correlation coefficients. But the main question — first of all, this was obviously a pretty narrow disease spectrum, which matters when you're trying to validate something —but you can't generalize this to pulmonary hypertension, cardiomyopathies, and other complex heart diseases. And also, the assessment at 12 to 48 hours is a pretty broad, and very dynamic, hemodynamic period. So some of these findings could reflect transient physiologic adaptation rather than truly intrinsic diastolic function, from my standpoint. And then, obviously, they didn't look at more advanced techniques like tissue Doppler, atrial strain, or ventricular strain, which could potentially enhance the understanding of true RV diastolic function. So those are my main thoughts — ask me your questions now.

Nim Goldshtrom (05:54.040) So many. The questions I have come from this specific population. Every once in a while you get a kid — not necessarily the tetralogy of Fallot and pulmonic stenosis patients, but like truncus arteriosus, for example, or others who are supposed to be two-ventricle — and you get an RV that's failing. And you want to call it systolic failure, but honestly, a lot of the time it's diastolic failure, and there's just no good way, other than a cath, to figure it out, so you just say, "well, it's probably that." So methodologically, it sounds like all the techniques and measurements they used were standard for what you'd do. Does this finding at all — the lower E/A ratio they found, and the more limited variability — change how you think about this disease, and would it change your practice at all seeing these kinds of findings? Okay, right, it's in the middle. But does it change anything for you? Like, if you measure this, would you be calling these kids, or labeling them, more as at risk? These are populations — tetralogy of Fallot and pulmonic stenosis — where we'd expect these findings, and then they should get better once you fix the disease, do the balloon septostomy, or the pulmonary valve for pulmonic stenosis, or the tetralogy of Fallot repair. I'm curious — if I had a kid with these persistent findings who's at risk for RV failure, can I count on this being enough evidence that I don't need a cath and another invasive procedure on this kid? Is this good enough data? And that's my first question — is this good enough, or does it move us closer to better data for this kind of thing?

Adrianne Rahde Bischoff (07:38.234) I think it's probably not good enough. I think it's all speculative and hypothesis-generating at this point. To really be clear whether this is reliable enough, you'd have to correlate it with cath — you'd need an echo-versus-cath study.

Nim Goldshtrom (07:49.234) That was my next question, which I was wondering — why didn't they do that for this study? I'm not criticizing them, but wouldn't that be the next logical step? You do an echo, either during cath — although that's different, because then they're sedated, paralyzed, and intubated — or right before that, you do the echo in the cath lab, then sedate and paralyze them, get the RVEDP (right ventricular end-diastolic pressure), and try to correlate the pre-anesthetic echo with the cath data. That would be a nice logical step, because otherwise

Adrianne Rahde Bischoff (08:21.234) you'd have to argue that the echo should be done at the same physiologic status as the cath, because the ambient conditions could be different — once anesthetized, you might drop PVR, you might change SVR. So it should be at the same time. We actually have a study that's been very hard to recruit for in the neonatal population — Dr. Audrey Hébert is the PI, she's from Quebec, and she's looking at babies with chronic pulmonary hypertension, usually BPD (bronchopulmonary dysplasia)-related, who do go for diagnostic cath. We take the echo machine at the same time and obtain some of our measurements, to try to validate or at least correlate what we see non-invasively with the cath markers. Which I think is relevant, because it's not uncommon to have a kid you're sure has pulmonary hypertension, and then they come back from the cath lab and it's normal, or mild, or not that big a deal, and you're like —

Nim Goldshtrom (09:08.076) Yeah, correct — subsystemic RV pressures, like...

Adrianne Rahde Bischoff (09:15.234) Yeah, but when they're awake and thrashing around, which is how they actually live, they do show some of that. So I think it's important to do that study, and I hope we'll get some more answers. But this is the trend — this is what should be done for any validation of echo markers, is to validate against the gold standard. So this is a start. I think it's hypothesis-generating — I wouldn't stake my reputation on it that you need to change management. You just might think about it a bit more critically. But it's a single parameter, and you know I preach — we preach — a multi-parametric approach. This is only one of them. So I think it's just a start.

Nim Goldshtrom (10:02.234) But diastolic dysfunction — there are so few variables — you end up sounding like every one of my cardiologists: "I don't know what to do with this. Maybe. I guess it's probably diastolic dysfunction, but none of the variables we have are good enough to assess it."

Adrianne Rahde Bischoff (10:15.234) But more than that, it's how do you handle it? How do you treat it?

Nim Goldshtrom (10:19.234) Well, so here's the thing I have no idea about — we just end up putting them on pulmonary vasodilator therapy for forever, basically. But for me, at least at this stage of care — let's say it's congenital heart disease, and you worry the child isn't making clinical progress, and that's the physiology — obviously we live in an age where you're going to get the cath at some point in most of these centers. But because cath is such a big deal for a lot of these kids in the neonatal period — because if you're going to get one, you're going to get many more. Forget even the single ventricles — but once you start down that road, it's a never-ending road, and the thrombus and clot risk from repeatedly instrumenting those vessels eventually leaves you with limited access if you're doing them too repeatedly. We always want to wait. But if you really have an RV that's failing, in most centers or in most places, you're going to go down the route of: is this the heart for us? How else do we better optimize? Are we ever going to get off respiratory support if part of the reason is intracardiac shunting? And then the idea is: do we have less invasive data that can help us move the needle — not just to adjust therapy, but to adjust expectations and the trajectory, and say, well, "we're stuck on oxygen and pressure support for RV failure" — that doesn't make sense, you shouldn't be on pressure modes for respiratory support, but sometimes you are. And to start opening the conversation of: well, you may not be leaving the hospital sooner, which we might know, but then how do we better support you sooner — when do we get the heart failure and transplant teams involved? And it always ends up being the cath, which is the standard of care, and we don't want to suggest otherwise. I was hoping we'd start to find better, earlier, non-invasive techniques that could help us get that data sooner rather than later. But it seems we're still a little far away. Maybe the other modalities you suggested, like speckle tracking, tissue Doppler, could be the future — but we need better studies, like you said, matching them to gold standards. Fascinating stuff. I always love these talks. These are always great articles that inspire more questions, and sometimes help us understand the landscape of our field.

Adrianne Rahde Bischoff (12:13.234) I always learn a lot from you, Nim, so thank you for this partnership.

Nim Goldshtrom (12:18.234) Yeah, it's great — we hope our audience enjoys it too, and this next iteration of "From the Heart." We'll see what we come up with next time. As Adrian said, we have a lot of new formats coming down the pike — interesting cases, more journal clubs, some guest speakers over the next few months. We hope you guys stay tuned with us and our whole Incubator family. So thank you all for having us, and we'll see you next time.

Adrianne Rahde Bischoff (12:38.552) Thank you, everyone.