#464 - [🫀 From The Heart] - Right Drugs, Wrong Heart - A TTTS Recipient That Fooled Everyone

Hello friends 👋

In this episode of From the Heart, Dr. Nim Goldshtrom and Dr. Adrianne Bischoff dissect a hemodynamics consult that changes shape twice in 48 hours. A 30-week recipient twin from twin-to-twin transfusion syndrome presents with biventricular dysfunction and suprasystemic pulmonary hypertension, starts on epinephrine and milrinone, and stabilizes. Then overnight, everything falls apart: hypotension, rising lactate, falling urine output. Only on repeat echo does the real diagnosis emerge: hypertrophic obstructive cardiomyopathy (HOCM) with dynamic left ventricular outflow tract obstruction, where the "correct" initial therapy becomes dangerous. Nim and Adrianne unpack why milrinone can worsen outflow obstruction, why vasopressin beats dobutamine, and when esmolol helps or harms. It's a masterclass in resisting anchoring bias and treating evolving physiology, not just numbers.

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

Dr. Nim Goldshtrom (00:01): Hello, everyone, and welcome back to From the Heart. My name is Nim Goldshtrom, joined by my wonderful colleague, Dr. Adrianne Bischoff. How are you today?

Dr. Adrianne Bischoff (00:24): I'm great — how are you, Nim? Just got back from PAS (Pediatric Academic Societies) at the time of this recording, so there's always lots of ideas buzzing in my mind.

Dr. Nim Goldshtrom (00:40): I know — what a wonderful conference to get excited about research across the entire spectrum of pediatrics. I couldn't make it this year, but I saw the wonderful pictures on the 'gram. Looked like an amazing experience. So glad so many folks, including our trainees, got to attend, present posters, and meet interesting people — find research collaborations, job opportunities, that kind of thing. It's a great environment.

Dr. Adrianne Bischoff (01:10): Agreed. It was good catching up with people, and also moving away a bit from the very clinical-heavy day-to-day and actually engaging in science, discussion, and networking. That was great.

Dr. Nim Goldshtrom (01:20): It's a great way to see our field evolve, and the opportunities away from the bedside sometimes — that's one of the perks. And the other perk is we get to tell wonderful stories to our audience. We're doing our Interesting Case this week, so stay tuned after the presentation — next week we're trying a new interview-style episode of From the Heart, focusing on unique elements of cardiac physiology in neonatal care. More on that toward the end. But Adrianne, you have the pleasure of hosting this week's case — let's hear it.

Dr. Adrianne Bischoff (01:50): We got good feedback from listeners that they enjoy a more practical approach — getting into Nim's and my mind on how we handle cases. So here's a real clinical case: what would the experts do? Our case is a recipient twin from twin-to-twin transfusion syndrome (TTTS) who initially seems to develop systolic dysfunction and pulmonary hypertension — but, as you'll see, ends up being something quite different.

We have 30-week mono-di twins; this is the recipient. There were antenatal concerns for hydrops. Both babies were born by emergency C-section for non-reassuring fetal status and placental abruption. This baby was intubated at delivery. Apgar scores were 2 and 5. The cord gas wasn't too bad — pH 7.23, base excess −4. The baby received surfactant fairly early. A targeted neonatal echocardiogram (TNE) was done on day one of life. At that time the baby was on a high-frequency jet ventilator with a mean airway pressure (MAP) of 8, and an FiO2 (Fraction of Inspired Oxygen) requirement, after surfactant, of 45%. Blood pressure was 83/33, mean 52. Hemoglobin was 13.2 — not too high, actually. Platelets were 130[,000]. The gas at that time showed a pH of 7.23, CO2 of 49, base excess −7. No arterial line yet, so no PO2, and lactate was 2.9.

The overall conclusion of that echo was suprasystemic pulmonary pressures. The PDA (Patent Ductus Arteriosus) was large — 3.4 mm — bidirectional but predominantly right-to-left. There was also biventricular dysfunction: moderate LV (left ventricular) dysfunction with an ejection fraction of 50%, and moderate-to-severe RV (right ventricular) dysfunction — a TAPSE (Tricuspid Annular Plane Systolic Excursion) of 3.3 and a fractional area change (FAC) of 0.26. Multiparametric assessment suggested the RV was a bit more dysfunctional than the LV; it looked hypertrophic and a little dilated. Calculated cardiac output was decreased on both sides. The PFO (Patent Foramen Ovale)/ASD (Atrial Septal Defect) shunt was bidirectional. The recommendation was to start epinephrine at 0.05 to support the systolic dysfunction of both ventricles, plus milrinone, started at 0.5, given the baby was borderline-to-hypertensive, with a plan to reassess in a couple of hours.

Before we keep going — let's zoom out, Nim. When you hear "twin-to-twin transfusion recipient," what physiology are you primed to look for?

Dr. Nim Goldshtrom (05:51): Generally, I think "big baby, failure" — big, giant, failing babies. Hydrops, failing organ systems, heart failure, but usually of the large/thick type — hypertrophy, not dilated myopathy. And often hypertension. This baby's blood pressures are a bit high, so he fits that bill with some of those early features. But the dysfunction is interesting — I usually think of this population more on the hypertrophy spectrum, so significant biventricular dysfunction like this is a little out of the ordinary. The PH (pulmonary hypertension) makes sense, but now — what's the chicken and what's the egg? It's a little outside the usual, without other overt signs of hydrops — this degree of cardiopulmonary disease at 30 weeks for a recipient twin is interesting, if not unheard-of.

Dr. Adrianne Bischoff (06:35): One question our audience will probably have: why scan this baby at all at that point? He's on 45% oxygen, blood pressure's okay, lactate's a little high but not dramatically. So — do you guys routinely scan all twin-to-twins at your center?

Dr. Nim Goldshtrom (06:55): No — I'll hedge, because we don't see these babies as young or as often; they're not rare, but not as frequent as, say, extreme prematurity. So based on our criteria and this clinical picture — only 45% FiO2, not profoundly hypoxic — nothing here would have screamed "echo this child." We don't have a protocol like you do in Iowa, where the baby sneezes wrong and gets an echo — great if you have the resources. This probably wouldn't have met our threshold. If the exam had shown poor perfusion, low renal NIRS (Near-Infrared Spectroscopy) values, climbing lactate, or persistently low urine output beyond six to twelve hours, that would push us toward more objective evidence of shock. But what you're describing before the echo — we probably wouldn't have blinked, other than maybe early duct management if the diastolics were low and that looked like ductal runoff.

Dr. Adrianne Bischoff (08:20): So to clarify for the audience — this baby was scanned not because of anything clinical, but because we routinely echo all TTTS babies. Recipients are more likely to be sick, so you could argue for screening just the recipient, but as a rule we screen both twins, symptomatic or not, given the risk of volume overload, hypertrophy, dysfunction, pulmonary and systemic hypertension, and related diastolic issues. As for timing — if this baby was born at 3 a.m., do you need the echo overnight? As a rule we scan within the first 24 hours of admission, but it doesn't have to be the middle of the night without clinical concern.

Dr. Nim Goldshtrom (09:30): Good to hear. Two things — one tangential: I've been watching a lot of The Pit, a great show. Aside from the drama, I'm fascinated by how often they ultrasound every trauma patient instantly — eFAST (extended Focused Assessment with Sonography in Trauma): pleural, pericardial, abdomen. If that's the state of the field, kudos — high negative and positive predictive value, fast, targeted, teachable.

Not to veer too far from hemodynamics, but look at this patient: mild lactate, mild-to-moderate mixed acidosis, normo- to hypertensive — yet the echo shows multiple markers of biventricular dysfunction. Without the echo — heart rate in the 160s, on a jet ventilator, 45% FiO2, some RDS (Respiratory Distress Syndrome), no ascites, no big liver, no effusions — this kid could've been a ticking time bomb on epinephrine and milrinone with no monitoring: waiting for function to worsen, for hypotension, for the lactate to climb, for end-organ dysfunction and kidney injury to follow. The value of these tools, and of training people to use them, is huge — it can save a patient from missed inotrope or vasoactive support just because the numbers looked okay on the surface. Nobody would have treated an 83/33 blood pressure in a 24-hour-old preemie on 45% oxygen with pre- and post-ductal saturations in the 80s to low 90s — other than maybe a duct check — and yet there was smoldering, compensated shock that could easily have become uncompensated. These protocols catch what we may have missed in the past.

Dr. Adrianne Bischoff (12:15): There'll be naysayers who say the opposite — if nothing's clinically wrong, why scan or treat before the baby shows it? I'd counter that this is probably still compensated shock. Not to dwell on the tangent, but for those making that argument — look at the literature comparing multi-modal physical exam and vital signs, across trainees, mid-levels, and experts, to the gold standard of echocardiographic cardiac output. The correlation is still poor. As much as we try, maybe NIRS (Near-Infrared Spectroscopy) data gives us a somewhat better venous surrogate for mixed venous saturation, but we're still not good enough by exam alone. We have to stay humble — the exam is not a perfect surrogate, especially for compensated shock: blood pressure looks normal only because SVR (Systemic Vascular Resistance) is up to compensate for falling function. Eventually that compensation fails and end-organ dysfunction follows.

Let's get back to the first steps of management. We have a baby with biventricular dysfunction and high pulmonary artery pressure who isn't hypotensive, and the team chose epinephrine and milrinone. Full disclosure — I was the consultant, so I'm not throwing anyone under the bus; it was my call. Would you have done the same, and what are the goals of that combination?

Dr. Nim Goldshtrom (13:29): Noble of you to jump in front of the bus. Honestly, probably yes — though this is non-congenital heart disease, so I have to set aside the pre-/post-op population where epi-milrinone is standard (though we're moving toward single-agent epinephrine). It's interesting with biventricular dysfunction, because you're trying to nail down the mechanism — here, a less-than-24-hour-old preterm infant with biventricular dysfunction and features of PH, and the cause could be many things: early-onset sepsis, a global picture, compensated until it isn't.

Milrinone can be great, and if you're normotensive, one could argue: stay on milrinone alone, buy yourself time, and add a beta-adrenergic if that's not enough. I don't think epi-milrinone is a poor combination — you get lusitropy from one, and if you're starting milrinone at a higher dose you may worry about dropping SVR, so epi keeps blood pressure up and adds a beta-adrenergic effect, since milrinone acts downstream of the beta-adrenergic receptor as a phosphodiesterase inhibitor. Especially since most places, like yours I'd guess, don't bolus milrinone in neonates anymore — given the half-life before it takes effect, you don't want the baby to decompensate in the meantime. I can see using both. Monday-morning quarterbacking, milrinone alone might have held if the blood pressure stayed up — but I have no problem with this therapy, since it's a dynamic picture: things change, function improves, you titrate down. As long as you keep reevaluating every few hours and adjusting.

Dr. Adrianne Bischoff (16:09): Agreed. My philosophy: epi acts faster and is more readily available at our bedside — under five minutes to infusing. So when I see severe dysfunction, like this RV, I want a direct inotrope like epinephrine on board. But I also know these babies often have an upregulated renin-angiotensin-aldosterone system from chronic in-utero fluid overload — this baby was already hypertensive with elevated pulmonary pressure. So the thinking was: epi to treat the dysfunction and get the heart moving quickly, milrinone for some afterload reduction. I don't think of milrinone in preterm infants as much of an inotrope or lusitrope, given how immature the myocardial calcium handling is — but it's a good afterload-reduction agent, and through stress-velocity mechanisms it can secondarily improve systolic and diastolic function.

Dr. Nim Goldshtrom (17:23): Makes sense. In the preterm literature it's hard to say what milrinone's true inotropic effect is, but if afterload reduction is one of your goals, you're not reaching for something aggressive like nitroprusside — that wasn't your intent. You're offering some pulmonary and systemic afterload reduction while letting epi keep output and SVR up, so the blood pressure doesn't tank the way it might with milrinone alone.

Dr. Adrianne Bischoff (17:55): Anything else we're missing before I tell you what happened next?

Dr. Nim Goldshtrom (18:10): No, this is a sound strategy. You've got the images, understood the physiology, offered a reasonable plan — now let's fast-forward. What happened?

Dr. Adrianne Bischoff (18:30): We come back that afternoon — same drugs, epi and milrinone. The baby's now on 30% FiO2. With a UAC (Umbilical Arterial Catheter) now in place, blood pressure is 60/41, mean 49. The LV is essentially unchanged — moderate dysfunction, EF 51%. But the RV has recovered: TAPSE and other markers of RV function are now normal for gestational age. The PDA is still bidirectional, predominantly right-to-left, so systemic-level pulmonary pressures persist. The atrial-level shunt is now left-to-right.

So: moderate LV dysfunction persists, but RV function has normalized with improved overall cardiac output. As we've discussed on another case — is this now predominantly precapillary or postcapillary pulmonary hypertension? Given persistent LV dysfunction and a left-to-right atrial shunt, this looks more postcapillary in origin. We recommended continuing epi and milrinone, coming down slightly on milrinone if the baby got hypotensive overnight since blood pressure was no longer as elevated, and reassessing the next day or sooner. Thoughts?

Dr. Nim Goldshtrom (19:36): So far so good — the rationale makes sense. Postcapillary is being outweighed by residual precapillary features, since the RV has improved but the LV hasn't, and there are still signs of pulmonary hypertension — which is tricky, because postcapillary disease is harder to diagnose definitively; it's almost diagnosis by exclusion, watching whether recovery continues over the next several hours or days. Did management change after these findings, or did the team stay the course?

Dr. Adrianne Bischoff (20:15): Then night comes, and things can change — and unfortunately, they did.

Dr. Nim Goldshtrom (20:31): That's why we have ECMO (Extracorporeal Membrane Oxygenation).

Dr. Adrianne Bischoff (20:35): On a thirty-weeker, we didn't have that ability yet.

Dr. Nim Goldshtrom (20:40): Not for this patient — yet. Edge of the field, we're pushing it.

Dr. Adrianne Bischoff (20:45): But yes, the night happens, and things change. Overnight, the baby developed hypotension, rising lactate, and low urine output. The team was understandably thrown — at the time, we had a much smaller hemodynamics team without 24-hour coverage, so we weren't called. They managed empirically, appropriately: given the low urine output and hypotension, they weaned and then stopped the milrinone. Worried the lactate might be from the epi — unlikely, since lactate had been normal all day — they switched epi to dobutamine. Still hypotensive, they tried vasopressin briefly, but stopped it out of concern for the low urine output. We came back the next morning to reassess. By then, the baby was still on 30% oxygen.

Dr. Nim Goldshtrom (21:54): Before you get to the next day's echo — none of those in-the-moment decisions seem unreasonable. Stopping for hypotension, switching beta-adrenergic agents, trialing vasopressin — all reasonable. But the teaching points are fascinating: switching beta-adrenergic agents is fine, but if you're worried about hypotension, is dobutamine really the right choice? It's very cardiac-specific but can also lower SVR — not the perfect drug for that. Not a criticism; people try what's reasonable in the moment.

I always tell trainees: think about mechanism. Low urine output here is probably from hypoperfusion — heading toward uncompensated shock, low output, not delivering. It's genuinely hard to know if vasopressin is the cause, or if you're just seeing early AKI (Acute Kidney Injury) from low cardiac output. My preference would have been to stay on vasopressin, get the blood pressure controlled, and worry about urine output later — these things are usually transient, and you're rescuing the core physiology. We blame vasopressin a lot for low urine output, but that doesn't outweigh the fact that hypotension itself is a low-perfusion state the kidneys won't recover from regardless. There are other options we'll get to — but I'd have stayed on it and only turned it off during normotensive periods. Practice style, but I think hypotension was the real problem, not a consequence of staying on vasopressin.

Dr. Adrianne Bischoff (23:00): This also shows how hard it is to manage without more advanced information — the team might have thought vasopressin wasn't ideal if LV dysfunction was the predominant feature. Hard to say which choice is safest or least evil. To round this out for listeners wondering what's going on: this baby is two days old, on antibiotics for presumed sepsis, and — if this were Iowa — likely already on hydrocortisone, so we're not talking adrenal insufficiency. No tamponade, nothing to suggest anything obscure — it's probably cardiovascular, but genuinely hard to tell without more information.

Dr. Nim Goldshtrom (25:10): I bet. So what did more information tell you?

Dr. Adrianne Bischoff (25:20): We come in — still on 30% oxygen, so no respiratory worsening. Blood pressure is now 49/16, mean 27 — predominantly diastolic hypotension. This echo: the LV now looks quite hypertrophic, with a normal ejection fraction of 65%. The RV is also more hypertrophic and dilated, but with normal systolic function. Outputs are normal-to-adequate for age. Pulmonary pressures are estimated at half-to-two-thirds systemic. The septum is a little flat, but the PDA is now almost entirely left-to-right, and the PFO/ASD shunt remains left-to-right.

So the predominant physiology now is significant biventricular hypertrophy with preserved systolic function and markers of diastolic dysfunction — for example, a mitral E/A ratio of 0.65, a slightly prolonged IVRT (Isovolumic Relaxation Time), and an elevated E/e'. For those using targeted neonatal echocardiography, these all point to diastolic dysfunction. The overall picture is consistent with left ventricular outflow tract (LVOT) obstruction. So — what happened? Did the physiology actually change, or did we just start seeing it clearly?

Dr. Nim Goldshtrom (27:30): This doesn't happen overnight — it was probably lurking all along. As a TTTS recipient, he likely already had hypertrophied muscle. The transitional physiology — maybe some late precapillary PH early on, RDS and lung disease layered on top — just wasn't well tolerated. You rescued him with inotropes, lusitropes, time, and recovery — until, once things improved systolically, you unmasked the residual lesion: significant hypertrophic diastolic dysfunction driving obstructive, rather than low-output, physiology.

Dr. Adrianne Bischoff (27:50): Comparing that first echo to the next day — the hypertrophy was clearly already there, but on day one the heart was well-filled and adequately preloaded, so it wasn't as visually prominent. The next day, presumably because milrinone and the falling blood pressure reduced afterload — which this kind of heart actually depends on — with less preload, the hypertrophy and its predisposition to LVOT obstruction became far more obvious.

Dr. Nim Goldshtrom (28:35): And the left-to-right shunting couldn't compensate for that lost "preload" via the diastolic steal — there just wasn't enough cardiac preload however you looked at it. It exposed itself, because the management we discussed 15 minutes ago is exactly wrong for hypertrophic hearts — a very different approach, which I'm sure we'll get into.

Dr. Adrianne Bischoff (29:00): Fascinating case. Let's talk about why that management is inappropriate here. To be explicit for listeners: we're describing hypertrophic cardiomyopathy (HCM) physiology with dynamic left ventricular outflow tract obstruction. Starting with milrinone — why is it a potential bad actor in this HOCM (Hypertrophic Obstructive Cardiomyopathy)-like physiology?

Dr. Nim Goldshtrom (29:15): I'll cover the HOCM piece, and you take milrinone. You have a thick, muscular heart that squeezes fine but relaxes poorly — the general physiology of hypertrophic hearts — and that thickness also obstructs outflow.

Not a perfect analogy, but think of a left-sided Tetralogy of Fallot (TOF) with pulmonary stenosis (PS) — functional obstruction to flow. For a tet spell, the answer is: calm the baby, fill the heart with volume, raise SVR for the right-sided problem. Similar principle here — you want a heart full of blood. The difference on the left side: for a tet, you can flood the baby with volume to boost right-heart pressures quickly. For a left-sided obstructive, hypertrophied heart, you can't rapidly infuse volume — it has to fill through the pulmonary veins, and doing that too fast floods the lungs and causes flash pulmonary edema. So these hearts want preload, but you can't "resuscitate" them the way you would a tet — rapid volume, sedation, high SVR, knees to chest, intubation — some of that applies, but it's far more perilous on the left side.

The principle holds: you want the heart full, so lowering afterload doesn't help preload — and you want the heart rate slower, not faster, for more filling time, avoiding tachycardia at all costs. So — why isn't milrinone the right choice?

Dr. Adrianne Bischoff (31:00): Because if you think of milrinone as predominantly a vasodilator, it lowers afterload and can worsen the obstruction. Left-sided hypertrophic hearts need high afterload — this baby's high blood pressure at birth was, in effect, doing that job, keeping more blood in the ventricle at end-ejection so the heart isn't emptied completely each beat. Drop the afterload, and you lose some of that preload reserve with each heartbeat, compromising filling.

Second mechanism: aortic root pressure falls, and in hypertrophy you need higher diastolic pressure to maintain coronary perfusion — which milrinone also undermines, potentially causing systolic dysfunction on top of the diastolic problem (which is the less common issue; these hearts usually squeeze fine, they just relax poorly). At the time of this echo the baby didn't yet have systolic dysfunction, but milrinone could have contributed to it downstream.

Dr. Nim Goldshtrom (32:50): Fascinatingly complex. For anyone who wants to visualize it — look up a pressure-volume loop for HOCM, with and without preserved function. The end-systolic pressure-volume line shifts toward the x-axis as function drops. In HOCM, the end-diastolic pressure curve is already elevated from high diastolic pressure. When afterload (the elastance line) also drops, you're crushing the box representing potential cardiac output — and risking a coronary ischemic event. Visually, it shows why afterload reduction, even with preserved systolic function, can be as dangerous as hypotension itself.

Dr. Adrianne Bischoff (33:54): So the second half of the equation — you said my whole initial management was the opposite of correct for HOCM. What's the other side? It's okay, I can say bad things about myself.

Dr. Nim Goldshtrom (34:15): No — at the time, you were dealing with compensated shock clearly heading toward uncompensated shock, regardless of the underlying pathology, which could've been HOCM — but you still had biventricular dysfunction and pulmonary hypertension. You had to get the heart squeezing again; it's hard to argue, with mild-to-moderate acidosis, a rising lactate, and moderate-to-severe biventricular dysfunction — even in a normotensive baby — that the answer is to lower the heart rate and hold the blood pressure where it was. Maybe, but you didn't know that yet. The blood pressure had room to tolerate some milrinone. That's why you scan and rescan — the physiology evolves. Now the patient is showing you what they need after recovering part of the cardiovascular picture: the opposite — lower heart rate, more volume, more filling time, better ejection and systemic output.

Dr. Adrianne Bischoff (35:00): Which brings me to the inotrope — initially epi, then dobutamine overnight — but neither is warranted now, since systolic function of both ventricles has normalized. We want to avoid them because we want to avoid chronotropy — we need to bring the heart rate down for filling time, and we don't want tachycardia increasing oxygen demand on top of this biventricular hypertrophy.

Dr. Nim Goldshtrom (36:00): Right — slow the heart rate, keep blood pressure normal, bring in alpha agents and beta blockers. Sounds like an out-of-the-box strategy, but it's completely appropriate for these hearts. We see kids with structurally normal hearts and heart failure — various cardiomyopathies — where you just have to slow the heart rate, especially in hypertrophic physiology, because tachycardia leaves no filling time and no good ejection fraction.

Dr. Adrianne Bischoff (36:30): So we shifted strategy: stop the inotropes, and choose vasopressin — despite the overnight concern about low urine output — as the main way to increase afterload, improve filling, and improve coronary perfusion pressure, all of which this heart needs regardless of the urine-output concern.

We wanted vasopressin because it's a vasoconstrictor — raises SVR, no chronotropic effect, improves coronary perfusion. Is that a drug you'd reach for in this scenario? I know it's not your usual population, but what are your thoughts?

Dr. Nim Goldshtrom (37:10): Depending on the stability we're talking about — yes, it's our first-line drug for almost everything. I get the concern about renal effects, but it doesn't cause anuria, it causes oliguria — and the physiology you're rescuing is usually transient. Vasopressin is never permanent.

Even in our cardiac population — structurally abnormal hearts post-surgery, severe low cardiac output syndrome — vasopressin is great, as the top of our algorithm for refractory cardiogenic shock: epi, milrinone, steroids, volume, sedation, then vasopressin. It's first-line — works at low doses with a great effect. Not that phenylephrine doesn't work, but I worry about its side-effect profile, and there's not much great data, though we use it in tets constantly, and it can be bolused. If we needed to rescue this baby from profound hypotension, we've given bolus phenylephrine and then started a drip, since it's in our crash cart. But yes — vasopressin is our first infusion choice, even in preemies, whenever we need something specifically for blood pressure via alpha effect.

Dr. Adrianne Bischoff (38:50): And on the vasopressin/urine-output concern — if it does cause some oliguria and fluid retention, that's not necessarily bad in this acute physiology. A reminder: lower urine output from vasopressin, when it happens, isn't AKI — it won't damage the kidneys, it just causes fluid retention, which might even be beneficial here.

I also wanted to ask about phenylephrine — our cardiology colleagues sometimes ask about it as a pure alpha agent when we co-manage these babies. We feel there's limited neonatal data and no personal experience with it — theoretically it could make sense, but it's not something we routinely reach for.

Dr. Nim Goldshtrom (39:40): Yeah, as a drip, for sure — even in cardiac babies, not routine in our NICU. Phenylephrine is nice because it can be bolused for an immediate effect. Our general preference, cardiac and non-cardiac units alike, is vasopressin first. If you're seeing significant side effects — say, severe hyponatremia, dilutional or not — then phenylephrine, if you're not comfortable, or a nice high-dose norepinephrine could be an alternative; several studies in distributive shock use norepinephrine alone with preserved cardiac function. Not perfect, since it still has both alpha and some beta effect, but it's a reasonably well-studied option in neonates outside of phenylephrine infusion.

Dr. Adrianne Bischoff (41:00): One last mainstay for these babies — beta blockers, obviously appealing to drop the heart rate. The recurring question when managing these babies acutely: what if there's also significant acute pulmonary hypertension? Here it was predominantly postcapillary from LV hypertrophy, but occasionally you get a HOCM baby with precapillary PH too — could starting esmolol worsen that? We tend to avoid beta blockers in that early phase here at Iowa, managing instead with vasopressin, sedation, and dexmedetomidine, to avoid a beta blocker while PVR (Pulmonary Vascular Resistance) might still be elevated with low pulmonary blood flow. Curious what you all do.

Dr. Nim Goldshtrom (42:00): I was going to say the same — this is a perfect setup for Precedex (dexmedetomidine), given the competing physiologies. Precapillary PH in a preterm infant, especially in the first couple of days, often has a mechanism that's transient and improves with time, therapy, relaxation, and staying at FRC (Functional Residual Capacity). If it's about buying time and lowering demand and crisis risk, it's a solid drug. Not much data in neonates, and even less in preemies, but the side-effect profile is nice — keeps them calm without heavy opioid dependence, and at higher doses it lowers heart rate, helping the LVOT/hypertrophic picture too. Could be a great bridge for a couple of days until the PH picture, echo, and bedside numbers improve, then you convert to a beta blocker.

Dr. Adrianne Bischoff (43:10): Not this case, but worth a note for listeners: in babies with high FiO2 requirements where you suspect pulmonary hypertension — often present, with a bidirectional or right-to-left PDA — what can you use at the bedside without access to targeted neonatal echo, to distinguish precapillary from postcapillary disease? One clue: which ventricle is more dysfunctional. If the LV is worse, question whether a selective pulmonary vasodilator is right — giving nitric oxide to a dysfunctional, high-pressure LV can make things worse if it's postcapillary in origin.

Another clue from any echo report: direction of the atrial-level shunt. A baby on 80% oxygen with a right-to-left PDA but a left-to-right PFO doesn't fit precapillary pulmonary hypertension — giving nitric oxide there risks pulmonary hemorrhage and worsening. Useful bedside clues for the likely physiology.

Dr. Nim Goldshtrom (44:20): This is why targeted neonatal echo is such a valuable tool. It's not a huge volume of babies — not every center, even high-level ones, sees this often — but these are the kids whose whole trajectory can change with better information. Great to see the potential for capturing these rarer, complex cases that would otherwise be made harder by lacking guidance through an evolving physiology.

Dr. Adrianne Bischoff (45:00): So, briefly — what happened to this baby: he was transitioned to vasopressin and eventually esmolol. Filling improved, blood pressure improved, urine output improved. He had persistent hypertrophy on echo, but stabilized hemodynamically.

Dr. Nim Goldshtrom (45:35): Really cool.

Dr. Adrianne Bischoff (45:40): But ultimately, unfortunately, his course was complicated by a gastric perforation and some neurological injury, and around the two-week mark, care was redirected to comfort care.

Dr. Nim Goldshtrom (45:55): That's tough. They always look more robust than the donor twin, but they're not as robust as they seem. They look like the big, healthy one — but the big one is often the sicker one.

Dr. Adrianne Bischoff (46:10): Right — big babies is what they are. Unfortunate outcome, but what a fascinating progression of complex physiologies. I'm not sure most centers could untangle this without more directed imaging evidence — this is exactly what it's there for.

Key takeaways from today's case: One — a twin-to-twin transfusion recipient is not the same as simple pulmonary hypertension or systolic dysfunction. Two — milrinone is not benign; it can destabilize preload-dependent or obstructive physiologies. Three — phenotypes can evolve or reveal themselves over time; there's real value in longitudinal information, and you shouldn't assume the initial diagnosis is the permanent one. Four — in HOCM, the pillars of management are: increase afterload, decrease heart rate, and avoid inodilators or vasodilators. Five — treat the physiology, not just the numbers or the lactate alone. This baby's hemodynamics were never static — they evolved, and it humbled me. That's why we keep scanning.

Dr. Nim Goldshtrom (47:40): Absolutely. And if your center doesn't have scanning capability — you're right, many don't; even our own program is still developing — these lessons still apply, imaging or not. You may have cardiology colleagues who aren't easily accessible but can come scan and give you information when asked. I can't emphasize enough what Adrianne said: phenotypes evolve, so always challenge your assumptions. If treatment for "dysfunction" isn't working, ask whether it's still dysfunction — maybe it's tamponade now, maybe the duct has become hemodynamically significant, maybe PH has resolved. Consider other explanations when the physiology stops responding the way it used to.

Staying static while the physiology is dynamic is what delays treatment. Not every place has constant imaging access, but most have people available — and if you can articulate a clear, evidence-based argument ("it looked like this, now it looks like this, here's the data, there's no response, I need more information"), most professionals will come help, if you can explain why what worked before isn't working now — giving the child the best chance as things change.

Dr. Adrianne Bischoff (48:50): Thank you, Nim — great discussion. I was humbled, and learned a lot about how hypertrophy can fool the eye depending on the heart's loading conditions. I can't show it in this format, but if you saw the four-chamber echo view from day one versus day two, you probably wouldn't believe it was the same baby — just different loading conditions.

Dr. Nim Goldshtrom (49:15): Probably not. We see kids with structurally normal hearts come in for heart-failure evaluations, and you look at the septum and think, "that's mostly septum — where's the cavity?" Clinically they look fine, look fine — then something happens, a diaper change, some crying, and their renal NIRS plummets into the 20s, and the baby looks slightly pale and dusky. If you got a gas out of worry, you'd see a lactate of 3, with no reserve because they became tachycardic — not enough preload. An acute low-output state, until they calm down and the heart rate comes back down. It's a tricky, subtly dangerous physiology — not benign, and it can take weeks or months of therapy to help these babies.

Dr. Adrianne Bischoff (50:00): Want to tell listeners what's coming up next?

Dr. Nim Goldshtrom (50:10): We're trying some new things for you. Glad these case discussions have been helpful — we're continuing journal club, and next week is another installment of From the Heart: From the Expert. We'll have a colleague and researcher joining us — I'll keep the details for next time — on the standard of care and benefits of breast milk and human milk exposure in neonates with congenital heart disease: how it may impact fetal, neonatal, and maternal outcomes, and help babies recover through hospitalization. Our guest, a contributor to a recent multicenter study through PCICS (Pediatric Cardiac Intensive Care Society), will discuss her work and upcoming publications on human milk exposure in the pre- and post-operative neonatal population, and how it could support advocacy for more human milk use in this group.

Dr. Adrianne Bischoff (51:20): I'm excited too — I get to just sit and ask questions this time.

Dr. Nim Goldshtrom (51:30): Should be great. This was fun as always — see you next time, Adrianne, and our audience.

Dr. Adrianne Bischoff (51:45): Thanks, Nim. Bye.