Pediheart Podcast #330: Can Aortic Arch Dimension Following Coarctation Surgery Predict Late HTN?

Introduction to PD Heart Podcast and Episode Overview

[00:00] Welcome to PD Heart Pediatric Cardiology. Today my name is Dr. Robert Pass.

[00:20] I'm the host of this podcast. I'm Professor of Pediatrics at the Icahn School of Medicine at Mount Sinai. Thank you very much for joining me for this 330th episode of PdHeart. I hope everybody enjoyed last week's episode on the concept of preoperative feeding in infants and whether or not it has an effect on postoperative feeding. We spoke with Dr.

[00:40] a seal to the bar of Children's Mercy Hospital in Kansas City. And for those of you with an interest in this topic, I'd recommend you take a listen to last week's episode. As I say most weeks if you'd like to get in touch with me, my email is easy to remember. It's PDHeart at gmail.com. This week, we move on to the world of cardiovascular surgery. The title of the work will be reviewing

Understanding Coarctation of the Aorta and Hypertension

[01:00] is impact of surgical strategy and post repair transverse aortic arch size on late hypertension after cartation repair during infancy. The first author of this work is Sanam Safi and the senior author Ashwin Prakash and this work comes to us from the Department of Cardiology and Cardiac Surgery at Boston Children's Hospital.

[01:20] as well as the Department of Cardiology at Copenhagen University Hospital in Copenhagen, Denmark. When we're done reviewing this paper, I'm hopeful that one of the authors will speak with us about it. Therefore, let's move straight onto this article and then a conversation with one of its authors. This week's work starts with the fact that we're all quite familiar with, namely that patients

[01:40] have a co-arctation that is successfully repaired have a high rate of hypertension, and they also have higher than usual rates of late stroke and coronary disease. They explain that prior works have shown that some of the factors accounting for the late hypertension after repair in this group is older age at repair, residual isthmic obstruction, and the shape of the aorta itself.

[02:00] They then review how transverse aortic hypoplasia is common in patients with a co-arctation, and they review how surgically it is addressed in a variable manner. The authors then reference their own prior work suggesting that persistent late hypoplasia of the transverse arch in co-arctation patients was associated with an elevated risk of hypertension.

[02:20] The authors aren't sure if this is because the aorta doesn't grow well after repair, or if the late hypoplasia is due to inadequate surgical enlargement. They further state that it is unclear if the severity of transverse aortic arch-hypoplasia at initial treatment, or the manner in which the aorta is surgically addressed, have an impact on the prevalence of late hypertension.

[02:40] The authors explain that the size of the transverse aortic arch after repair is a nice objective marker of the extent to which the transverse aortic arch hypoplasia was addressed surgically, and so they explain that the goal was to determine if there was a relationship between transverse aortic arch hypoplasia seen after repair and the development of hypertension

[03:00] in late follow-up, and as a secondary goal, the authors sought to see if there was an association between late hypertension and other secondary predictors, with one of the more important being the type of surgical incision, thoracotomy versus sternotomy, as well as the type of co-artation repair. This was a single-cent or retrospective study from Boston Children's Hospital over a very

[03:20] long time period from January 1980 to December 2010 and there needed to be repair in the first year of life to be in this study as well as at least 10 years of follow-up after surgery. People who had other complex cardiac disease were removed from the cohort as were patients with more than a 20 millimeter gradient at the isthmus itself.

Surgical Strategies and Their Long-Term Impact

[03:40] presumably since this is a well-established cause of hypertension. And those with other aortic heart cases like mid-thoracic or abdominal heart cases were also excluded. The authors used all available blood pressure recordings taken pre and post repair and at the last follow-up from medical records. And for children less than or equal to 18, hypertension was defined as a

[04:00] or diastolic blood pressure above the 95th percentile, and for adults, a systolic blood pressure over 130 or a diastolic blood pressure over 90. And there needed to be at least two separate outpatient visits with blood pressures that high in order to be considered hypertensive in this work. Echocardiograms are reviewed pre, immediately post,

[04:20] then at the latest follow-up and measurements of the aorta made. And in those who had a CMR, that data was also included. And onto the results. There were 130 patients who made the study criteria and were included for analysis. Table 1 gives a nice summary of the patient characteristics and though not the purpose of this work, I think it's interesting

[04:40] to see that 62% had an end-to-end anastomosis, 30% an extended end-to-end anastomosis, 4% had an arch repair that was described as extensive with a patch, and 5% a subclavian flap. Roughly three quarters were performed via thoracotomy and one quarter by sternotomy, and the median postoperative transverse

[05:00] ARCH Z scores were all roughly 2.0 in the entire group. Of interest, 28 patients or 22% needed a surgical or catheter-based second procedure at a median of 1.9 years following co-arctation surgery. An 18.5% had balloon dilation for residual co-arct, 3% had a stent, and 78.5%

[05:20] 5% needed no intervention. I think these rates of intervention following co-arctation are of use for us in counseling patients, though of course the rates change in different centers and this is a cohort of patients repaired as far back as 1980 to 2010 and so may represent a different sort of cohort than we see today. And so first and importantly,

[05:40] What percentage of patients had hypertension at late follow-up? Well, the answer was 33% or 43 patients at a median age of presentation of hypertension of 16 years. Of this group, 49% were receiving antihypertensive medications. Importantly, patients who have hypertension at late follow-up were similar to those without hypertension.

[06:00] hypertension in respect to the age at initial repair, arm-leg blood pressure differences prior to surgery, type of initial repair, type of surgical incision. Perhaps not surprisingly, those with hypertension were more likely to have had a reintervention. And here's the most important finding for the authors. What was the relationship between hypertension and

[06:20] the post-repair initial transverse aortic arch dimension. Well, in a multivariable model, there was no significant association seen between the Z-score of the transverse aortic arch diameter even after adjusting for age at follow-up. The only factors in a multivariable model that were associated with late hypertension were older age

Key Findings on Hypertension Risk Factors

[06:40] at surgery, male sex, and older age at follow-up. Similarly and importantly, there was no association in a multivariable model between late hypertension and the type of incision. The authors also report on a subanalysis of those who had preoperative transverse aortic arch diameters less than 2.5 zerosprins.

[07:00] scores and showed no association between this and late hypertension. Interestingly, the authors did a subanalysis on the 52 patients who had a CMR and follow-up and using multivariable modeling, the transverse aortic arch diameter Z score by CMR was not associated with the type of surgery or incision also. In their

[07:20] In this discussion the authors review the major findings that parameters of initial surgical repair like postoperative transverse aortic arch diameter Z score type of incision and repair were not associated with prevalence of late hypertension and follow up, but they emphasize what I noticed for you earlier that a third did have hypertension and follow up.

[07:40] and I quote, given that late hypertension has been associated with late transversauretic arch hypoplasia, these results suggest that factors other than surgical strategies such as growth of the transversauretic arch during childhood may have a larger impact on the development of late hypertension. The authors speak of the many factors that have been shown to be associated with hyper

[08:00] hypertension and coarctation patients, such as generalized vascular dysfunction, older agent repair, male sex, and longer duration of follow-up. They reemphasize their prior work showing that smaller transverse arches later in follow-up are associated with hypertension and they wonder if the near universal smallest transverse arch in all

[08:20] co-artation patients means that perhaps we should consider more extensive initial repairs of co-artations. The investigators review the fact that the transverse aortic arch diameter Z-score was not associated with later hypertension and also not affected by surgical repair or surgical incision type and wonder aloud if the eventual size of the transverse aortic

[08:40] is not dictated only by surgery, but by varying rates of aortic growth in childhood, and they bemoan the lack of data on rates of growth of the aorta after repair, contrasting two smaller studies that seem to have different findings regarding growth of the transverse aortic arch with time. In regards to limitations, the authors speak about the retrospectives

[09:00] single-center design and also the long 10-year follow-up requirement to be in the study, meaning that patients by definition had to be obtained going back a long time, even to the early 1980s, and how this spanning of different surgical eras and techniques is suboptimal for a study. They bemoan also the absence of clear transverse aortic

Role of Transverse Aortic Arch Hypoplasia in Hypertension

[09:20] archdimensions over time on echo due to limitations in imaging and how this disallowed analysis of a growth assessment for this work. And so they conclude. In patients undergoing surgical repair of co-artation of the aorta during infancy, excluding those with residual isthmus narrowing, late hypertension was not associated with

[09:40] immediate post-repair, transverse aortic size, or type of surgical repair. Because late hypertension has been previously associated with late transverse aortic arch hypoplasia, these results suggest that factors other than surgical strategy, such as variable growth of the transverse aortic arch during childhood, may have a greater impact on

[10:00] development of late hypertension. Well, this is an interesting work in that it suggests that the early appearance of the transversiotic arch at discharge from the surgery does not necessarily predict long-term hypertension. The authors own work on this in the past showing that at long term, this measurement of the transversiotic arch was smaller in those patients

[10:20] to have hypertension clearly suggests that this area of the aorta plays a very important role, but why some infants with a smallish one at discharge seem to do fine with adequate growth of this area, while others do not, is not clear, but I do think there is something to the author's suggestion regarding different growth rates. I do think

[10:40] it's hard to hang one's hat too aggressively on this study regarding present-day co-arc patients given the differences in surgical technique and era. Also, it's hard to know how applicable these results are in the so-called real world. Let's just think about this for a moment. Most of these surgeries were performed by people like Altocastinata, Rich

[11:00] Jonas, Pedro Del Nido, Redmond Burke, John Meyer, and Ram Amani, amongst many others. These are amongst the finest surgeons in the history of congenital heart surgery, and so it's certainly difficult to know if the results of these masters would be reproducible or similar today. That said, I think probably we can

[11:20] One guess that what we are seeing in this report is likely the quote unquote best case scenario, and it's sobering to see how one third of the patients need hypertensive therapy at about 10 to 20 years out, and also how about a quarter, a reintervention of some type. And the study does not even use ambulatory blood pressure monitoring

[11:40] which we know can sometimes identify more patients who have unknown hypertension. There's a lot to unpack and so in the interest of time, I think we'll move forward to our conversation with one of the works authors. Joining us now all the way from Denmark to discuss this week's work is its first author, Dr. Sanam Safi-Rasmuson. Dr. Safi-Rasmuson is a graduate of the University of New York.

Growth Patterns of the Aorta and Long-Term Outcomes

[12:00] of Copenhagen for medical school and presently is doing her PhD studies at the Department of Cardiothoracic Surgery at Copenhagen University Hospital with a primary focus on lymphatic disorders and interventions in Fontan patients. Following her PhD, she tells me she will start her residency and then fellowship. Dr. Safi Rasmussen,

[12:20] this research during a one-year research fellowship at Boston Children's Hospital. It is a delight to welcome an up-and-coming superstar to the podcast all the way from Denmark. Welcome Dr. Safi Rasmussen. I'm here now with Dr. Sanam Safi Rasmussen all the way from Denmark. Dr. Safi, thank you so much for joining us this week on PD Heart. Thank you so much for having me.

[12:40] here today. It is truly an honor. Well it's a great pleasure to have you. Always enjoy having up and coming superstars like yourself. So really excited to have you. You know Dr. Safi Rasmussen, prior works by the team in Boston which you worked with on this project showed that the transverse aortic arch dimension at long-term follow-up

[13:00] did actually correlate with the development of hypertension. But your work shows that at least the immediate early post-op transverse aortic arch dementia did not, and that the early post-operative Z-scores of the transverse aortic arch diameter were largely similar when you compare patients who had late hypertension to those who did not.

[13:20] And I'm wondering if you had any thoughts on why this might be and what other factors might be at play. Thank you so much for this question. And yeah, to be honest, we were kind of surprised by this finding as well, as we had expected that a smaller CAA-sized post-op would predict the development of late hypertension, which would again support our

[13:40] previous findings. But as you already mentioned, our results showed no association between early post-op C-scores and late hypertension. And we thought that maybe this suggests that our surgeons are generally very good at doing what they do and they do it very well when repairing the corticosteroid during their surgery, which of course is

[14:00] very good thing. So why do we still see that some patients with smaller aortic arches at long-term follow-up develop hypertension? And here I think we have to keep in mind that we are talking about two very different measurements. One is the late follow-up TIA size and then ours is the early post-op TIA size. And our

[14:20] hypothesis is that it's not the immediate post-op size of the arch that matters the most, but rather how this arch develops over time. And why do I say that? So when we look at the studies from the past two decades, we have seen that patients with corticosteroid disease have increased bacterial stiffness, they have

[14:40] bacterial dysfunction, they have abnormal vascular reactivity and also remodeling, even despite a successful repair. There's a specific study from 2005 that demonstrated that newborns with corticosteroid already had impaired elastic properties of the ascending aorta

Surgical Approach: Thoracotomy vs. Sternotomy

[15:00] both before and after the surgery. And a more recent study from 2023 from our own group in Boston followed patients who had undergone a patch-augmentated arch reconstruction and found that while all segments of the aorta grew over time, this growth was not uniform with parts

[15:20] it growing more than other. So we think that all of these studies that have been conducted so far supports the idea that corticosteroid is not just a localized narrowing, but rather a larger systemic vascular disease, which again means that even if the aortic arch appears perfectly repaired,

[15:40] There is still some underlying vascular dysfunction that predisposes these patients to late hypertension. Yeah, I see. Very interesting and very thorough answer. Thank you very much. Your work did not demonstrate an association between the surgical approach, meaning from the front or the side, and development of late hypertension.

[16:00] Why do you think that's the case? Is this simply a situation where the cardiologist and the surgeon together correctly anticipated who would need a more extensive archery construction, or do you think there might be other factors at play? Thank you for this. And this is a very interesting question, I think, and I don't think that there is only one explanation to this as well.

[16:20] First, I think as you suggested already, it is likely that our cardiologists and surgeons are already doing a very good job selecting the most appropriate surgical approaches for each of these patients by adapting their decisions to the patient's anatomy and also needs of course, and thereby minimizing the impact of the approach itself.

[16:40] We have to bear in mind that our study is a single center study in one of the best pediatric cardiology centers in the world and with a very large number of cases each year. So I think it's safe to say that these clinicians are very very good at doing what they do and they do it quite often as well.

[17:00] what most other centers do, I think. Second, the fact that we have standardized surgical techniques and also post-operative care is another important factor. So if both surgical approaches are performed with very high precision and also followed by consistent post-op management in these highly specialized departments,

[17:20] any differences there might be between these approaches I think would become very very little or at least negligible and then finally I think again it's important to remember that late hypertension is most likely driven by some intrinsic systemic vascular dysfunction rather than just a surgical approach. Yeah, well

[17:40] good points there. Yeah, you don't have the opportunity to hear what I say before this interview, which I've already recorded because we're recording this on the 12th of February, Wednesday. But one of the observations I made is that the outcomes you are reporting are probably the best-case scenario because the surgeons over the period

[18:00] from 1980 to 2010 were amongst the best congenital heart surgeons on the planet and I think today would still be viewed that way. So very interesting points to all of them. I'm wondering what we know about growth of the aortic and coartation following repair. You hinted at it a little bit in the first question. Could you share with us what we know about

[18:20] that now? Yeah, so this is a very big or broad question I would say and I think it would take us more than just one episode to cover all of them. But if I had to start somewhere I would say that we have learned quite a lot about this specific topic, which is very good, but then again we still have a very long way to go. I think the most important

Monitoring and Managing Hypertension in Coarctation Patients

[18:40] thing that we have learned so far is that we cannot think about quarantation as an isolated and localized mechanical narrowing as we have been taught so far, at least I have. But instead we must see it and also treat it as a larger systemic vascular disorder that is not just magically fixed after a surgical

[19:00] repair. So we have to monitor these patients much longer than what we anticipated in the beginning. And I think one of the biggest takeaways from recent research is that the aortic growth is highly variable as we have already touched upon. And I think this means that even when the initial repair looks perfect, there are some long-term changes

[19:20] in atrial stiffness and compliance that still predisposes these patients to complications like, for instance, hypertension. And other key factors also that vascular dysfunction persists even in well-repaired patients. A study from 2012 by the group of Martins et al. showed that the

[19:40] a major influence on long-term outcomes, meaning that how the arch is shaped post-repair can actually affect blood flow and also blood pressure over time. And a more recent study from a group in Hong Kong from 2015 also demonstrated that the arterial ventricular interactions they actually

[20:00] remain abnormal in cortation patients years after the surgery, which again may contribute to these long-term cardiovascular strain complications. So even though surgical techniques have improved tremendously and we have become much better at treating these patients, we are still dealing with the long-term consequences of corticosteroid

[20:20] as a systemic disease. And that's why I think life-log monitoring is so crucial in these patients. So I think for future research we need to focus on predicting which patients are at highest risk for late hypertension and also vascular complications based on their genetics and their

[20:40] vascular and imaging markers, as well as developing new interventions to improve vascular compliance and also long-term outcomes if we want to have a genuine chance at fighting these late complications in these patients. Well, thank you, Dr. Sonfi, for summarizing probably the work of 50 different doctors. In one question, very much

[21:00] appreciate it. Of course many in the audience are very well aware that much of the literature on this comes from your senior author and my very dear friend Ashwin Prakash. So kudos to Ashwin and of course to you. Well we're going to finish up. This question, as most in the audience know, I will give the speakers on our podcast the questions in advance.

[21:20] But I feel like you've really answered this question already for us. But since I have you here, I'll take advantage of you and ask you to answer it again. But in your discussion, Dr. Safi Rasmussen, you mentioned the prior work of the team showing that smaller transverse aortic arch size at follow-up is associated with a higher prevalence of hypertension.

[21:40] late term. And I'm wondering if you think that surgeons maybe should be more aggressive in addressing co-ortation from the front in a more extensive approach based on this, or do you think that the fact that the immediate transverse arch diameter Z-scores were basically the same after surgery in patients who were hypertensive or not hypertensive?

[22:00] means that the repair decisions regarding front versus side and extensive versus limited are actually largely correct and there are just so many other factors or differences in these patients, many of which you've already spoken to us about, who do and don't develop hypertension and smaller transverse arches. Yeah, so in short, I would say no to your first quenching.

Interview with Dr. Sanam Safi Rasmussen

[22:20] question and yes to your second. But then again this is not a simply yes and no question and I think it's really important to balance the theoretical benefits of a more extensive repair against potential surgical risks as well. The fact that we have shown in our study that early post-op TAAC scores they were similar in our two groups.

[22:40] I think that suggests that what we are doing right now regarding the surgical approach is generally a prokaryote. But then again, we see that some patients later on end up developing hypertension, the ones with small NCAA. So something happens during the growth of the aorta, which we have already touched upon, which was not there

[23:00] from the beginning. And that I think is the important thing to remember that despite this we still see that some patients with smaller TAA at late follow-up they end up with hypertension. So something happens during the growth of the aorta which leads to these late complications which are not there from the beginning as our study showed and which is a

[23:20] very important thing to remember. And we have already touched upon how the aortic growth is variable and also dependent on several factors etc. I think another important thing to remember is also that the more aggressive arch reconstructions are also more associated with higher rates of complications including bleeding and

[23:40] prolonged recovery, neurological injuries, and so on. And since our paper shows that the care strategies have similar short-term results, I don't know if adding the risks of a more aggressive approach would be justified for most of these patients. So to answer your question,

[24:00] Is a more aggressive repair the answer? I would say probably not in all cases at least and instead I think a better strategy would be to closely monitor high-risk patients and also intervene early if signs of progressive archivalplasia or vascular dysfunction appear. All very good points.

[24:20] You know, I'm going to express my naivete on this. I don't know if I've read this literature, but it would be interesting if Boston were to publish their decision making regarding going from the front or the side and how those decisions are made. This seems to me like something that might actually be a good project for an AI.

[24:40] approach to figure out so that everybody can have the same level of intelligence as the group in Boston, which presently is based on clinical excellence and hunches and some studies. But I think that seems like something where we could level the playing field so that everybody in the entire world could make a similar high-quality decision.

[25:00] as the team in Boston, so that at least our patients are walking out of the OR everywhere with the same size transverse aortic arch and then we'll follow up. You know, one of the other things I noticed or wondered about, Dr. Safi, is, you know, your work showed that about a third of all the patients ended up with hypertension at long-term follow-up, and that was not even with ambulatory blood pressure.

[25:20] pressure monitoring, which we know will uncover a small percentage of patients who do develop, who have hypertension that we don't know. So I think that the, you know, a third is probably the tip of the iceberg in terms of how much hypertension these patients have. And so for that reason, I think the importance of this work really cannot be overstated.

[25:40] And so I want to just thank you very much for making time right in the middle of your day in Denmark here. It's nice and early, so it's not interfering with anything in my day, but Dr. Safi was kind enough to give us time right smack-dab in the middle of her afternoon. So I want to thank you very, very much for giving us time and giving us so many thoughtful answers to these questions.

[26:00] infections. And I want to congratulate you and all of your co-investigators, both in Boston led by Dr. Prakash as well as your team in Copenhagen. Congratulations. Thank you so much. It has been a pleasure. Great pleasure here too. Well, once more we have an outstanding guest. But how rare to hear such a young person who's not even in cardiology training or even

Final Thoughts, Future Research, and Podcast Conclusion

[26:20] who is so knowledgeable about this topic. I think Dr. Safi really gave us many insights into the developing aortas of patients with co-arctation and what makes them different from other patients who don't have co-arctation. And she really made for us clear that there is definitely an element of biology in the development of late hypertension.

[26:40] tension that may have little to do with the surgery. I do think that the surgery is clearly critically important, but this work by removing those who have known postoperative issues related to the surgery again makes the point that there are many factors both known and unknown that enter into the development of late hypertension. Clearly more

[27:00] Our study on this topic is needed and just as clearly, we all need to be very vigilant in assessing our patients with co-artation for hypertension. And let me put a plug out there for ambulatory blood pressure monitoring in these patients, which is recommended by most of our societies and which is definitely underutilized in this patient population.

[27:20] The effects of long-term hypertension are real, and I do believe it is all of our responsibility to be sure that this very common postoperative complication is identified and managed for the long-term health of our co-artation patients. I am sure that you all share my delight at the excellent answers of our guests this week, and I am certain that Dr. Safi Rasmussen

[27:40] We'll have a very significant career with many discoveries and I can't wait to see them happen in the near future. Once again I'd like to thank her for taking time from her very busy schedule as a PhD student to speak with us this week on Pdheart. To conclude this 330th episode of Pdheart pediatric cardiology today we hear the wonderful little song

[28:00] by Rachmaninoff entitled Zidice Korosu, which is translated How Fair is the Spot? And we hear it sung by the Swedish tenor Nikolaj Geda, who had a very long career singing all over the globe and also recording a vast amount of repertoire because of his wonderful voice and terrific language skills. Singing like a native

[28:20] speaker in so many different languages. Today's performance in Russian is often considered one of the very best of the song in all of recorded history so far. Thank you very much for joining me for this week's podcast. I hope you all have a good week ahead.

[28:40] Still,

[29:00] is not a secret. It is a secret that is not a secret. It is a secret that is not a secret.

[29:20] I am not alone.

[29:40] So

[30:00] you