Pediheart Podcast #328: Outcomes For CHD Children With Ventricular Assist Devices

Introduction to PD Heart Podcast and Episode Overview

[00:00] Welcome to PD Heart, pediatric cardiology today. My name is Dr. Robert Paz.

[00:20] and I'm the host of this podcast. I'm Professor of Pediatrics at the Icahn School of Medicine at Mount Sinai. Thank you for joining me for this 328th episode of PdHeart. I hope everybody enjoyed last week's episode in which we turn back the clock to speak with Dr. Jennifer Cohn about corrected transposition in fetal life. For those of you interested in this important

[00:40] topic, I'd recommend you take a listen to last week's discussion of a Fetal Heart Society project, episode 327. As I say every week, 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 into the world of heart failure and transplantation. The title of the work we'll be reviewing is Out

Background on VADs and Pediatric Heart Failure

[01:00] outcomes for children with congenital heart disease undergoing ventricular assist device implantation, and action registry analysis. The first author of this work is Shanawaz Amdani and the senior author Matthew J. O'Connor, and Dr. Amdani comes to us from the Cleveland Clinic Children's Hospital in Cleveland, Ohio. When we're done reviewing this paper

[01:20] Dr. Amdani has graciously agreed to join us to discuss it. Therefore, let's get straight onto the article and then a conversation with its first author. The authors begin this week's work by commenting on how our successes in the treatment of children with congenital heart disease have resulted in growing numbers of pediatric patients with congenital heart disease who are being evaluated for heart failure-related emergency

[01:40] emergencies and hospitalizations, and how some children in that circumstance will need advanced heart failure therapies including ventricular assist devices and heart transplantation, and they reference PDMAX data that support this statement. They then comment on the technical challenges of putting a VAD in a child with congenital heart disease and mention how there's only one

[02:00] disorder. The authors then explain how the action network or the advanced cardiac therapy is improving outcomes

[02:20] network has resulted in many improvements in the care of children on mechanical support, and so with these improvements, it's important to reassess outcomes for children undergoing ventricular assist devices in the present era. With this as a background, the authors state that the primary aim of this study was to evaluate differences in post-VAD implantation morbidity and mortality

[02:40] for children with congenital heart disease compared to those who do not. The secondary aims were to evaluate differences post-VAD implantation, morbidity, and mortality among biventricular congenital heart disease patients and univentricular congenital heart disease patients, and also to look at preimplantation differences and clinical characteristics between those with and

Study Overview: VAD Outcomes in Congenital vs. Non-Congenital Heart Disease Patients

[03:00] without congenital heart disease, as well as those with and without univentricular congenital heart disease. This was a retrospective study using the Action Network database for subjects enrolled from April 2018 to February 2023, and it included all patients under 19 years of age with congenital heart disease or those who did not have it, who had a VAD placed in

[03:20] that timeframe. As would be expected, tons of data regarding demographic and clinical details were recorded, as well as post-operative clinical course and adverse events. The authors explain how there are data quality members of the action group to ensure that the information recorded is robust and very accurate. And on page four, there is a very nice detailed description

[03:40] of the statistical techniques that are used and for those interested in large dataset analysis, for certain, I'd recommend you take a look at this part of the paper. And on to the results. There were a total of 966 pediatric VAD implants in the time period, of which 36% had congenital heart disease and 64% did not. The mean

[04:00] The median age of the cohort was 4.4 years and the majority, or 56%, were male, and 54% were white. 31% of patients were listed as Intermax 1 and 53% Intermax 2. For those unfamiliar, Intermax 1 represents a significantly more critical advanced heart failure compared to Intermax 2,

[04:20] Patients classified as Intermax I are considered the most severe symptomatic, and they require immediate intensive life-saving interventions, while Intermax II patients still have significant deterioration, but are not as acutely ill and may require high doses of inotropes to maintain stability. Essentially, Intermax I patients are considered the sickest and most likely to require

[04:40] immediate mechanical circulatory support, lack of AD. Figure 1 is a great bar graph showing that from 2018 to now the numbers of congenital heart disease patients has gotten larger and larger steadily, while the non-congenital heart disease patient group has seemed fairly stable. Larger than the congenital heart disease group, but with time the difference in numbers in patients

[05:00] is smaller and smaller. Perhaps not surprisingly, the majority of these patients who did not have congenital heart disease had dilated cardiomyopathy, 81%, and the median follow-up in this work was 2.6 months. And so how did the patients who got VADs and had congenital heart disease compare to those who did not have congenital heart disease?

[05:20] Well, congenital heart disease patients were younger with a median age of 1.2 years compared with 9.4 years in the non-congenital heart disease cohort and were more likely white, 64% versus 48%. And they were generally sicker with a higher percentage being Intermax I patients, 36% versus 29%.

[05:40] They also had a higher bilirubin, lower GFR, and were more likely on mechanical ventilation or dialysis prior to device. ECMO was also used more commonly in the congenital heart disease patients prior to a VAD, 33% versus 21%. Perhaps not surprisingly, given the differences in age, the congenital heart disease patients were

Key Findings: Patient Demographics and Pre-Implantation Differences

[06:00] more likely to have a Berlin heart 45% or a PD MAG or Centromag 33% and less likely to have a heart wear vad or heart mate 3 used in just 11% of congenital heart disease patients. Unaventricular congenital heart disease patients were generally younger by nearly a year 1 versus 1.7 versus

[06:20] their two-ventrical comparison group and were more likely Hispanic, 23.5% versus 12.3%, and were more likely to have a lower GFR and more likely to have a VAD as a bridge to transplant or listed within 24 hours. However, there was no difference in pre-implant intermax level, mechanical ventilation or ECMO use or the type

[06:40] device in comparing the biventricular to univentricular patients. And what about after the VAD? How did the congenital and non-congenital heart patients compare? Well generally, congenital heart disease patients fared worse with more stroke, bleeding, renal dysfunction, and liver dysfunction, as well as more infections, as well as

[07:00] malfunctions and respiratory failure. However, when comparing the single to two ventricle VAD patients after the VAD, there was more bleeding in the single ventricle patients, but rate of stroke, infections, renal or hepatic dysfunction, device malfunctions, or respiratory failure rates were similar in the two congenital heart disease groups. And here's perhaps one of

[07:20] most important questions. How did mortality rates differ between those with and without congenital heart disease and a VAD? Well, in a multivariable adjusted analysis, those who had congenital heart disease had significantly higher post-VAD mortality, comparing to non-congenital heart disease patients, with a hazard ratio of 2.05.

[07:40] Figure 2 is a very nice visual demonstration of the difference in post-VAD survival, comparing those with congenital heart disease and those without, showing a very significant divergence in lines in survival, with survival on the Y axis and time of VAD support on the X axis. The other risk factor for death were use of ECMO before the use of a VAD.

[08:00] with a hazard ratio of 1.99, use of a paracorporeal continuous device with a hazard ratio of 2.09, and an elevated bilirubin and lower GFR. In their discussion, the authors state and I quote, in this analysis of contemporary outcomes for children undergoing VAD implantation, there were several important findings. One, the

[08:20] number of children with congenital heart disease undergoing vat implantation, particularly those with univentricular congenital heart disease, is rising. Two, compared to children with non-congenital heart disease, those with congenital heart disease are undergoing vat implantation at a more advanced heart failure stage, more likely to be intermatics I, and non-mechanical ventilation, dialysis, and

[08:40] ECMO. 3. Compared with children who do not have congenital heart disease, those with congenital heart disease were significantly more likely to experience major adverse events post-VAD implantation. Stroke, bleeding, infection, renal dysfunction, hepatic dysfunction, and respiratory failure. 4. In the current era, children with congenital heart disease compared to those

Post-VAD Outcomes: Complications and Mortality Rates

[09:00] who do not have congenital heart disease are twice as likely to die post-VAD implantation, and five, there were no differences in post-implantation survival for those with univentricular and biventricular congenital heart disease undergoing VAD implantation. The authors then make a few general observations about how the numbers of patients getting VADs in the setting of congenital heart disease

[09:20] disease is rising rapidly, with a near tenfold rise in congenital heart disease vat implants in the most recent era reviewed in this report, and also how two thirds of the congenital heart disease patients getting vats are those who have a single ventricle, highlighting for us the importance of this work and this growing tsunami of challenging single ventricle patients.

[09:40] reference the single ventricle reconstructive trial which we've previously highlighted on the podcast over the last seven years, demonstrating nearly 40% of children with single ventricle palliation dying or needing a heart transplant in the six years after initial reconstructive operation. The authors then make one of the most important points of this work, namely that children with congenital

[10:00] heart disease and heart failure are being referred late, which means they are sicker at presentation and they reference a prior work on Fontan's sent for transplantation evaluation, where it was demonstrated that 40% of these patients needed either inotropes, vads, or listing for transplant within only 30 days of referral and they review how this work was similar

[10:20] with the congenital heart disease patients in this work, being more commonly intermax 1 and having many other comorbidities at higher rates than the non-congenital heart disease children in this work. The authors reference the Action Network's recently released guidelines for pediatric cardiologists caring for Fontan patients with advanced heart failure, which was written to try and improve referring

[10:40] at a more optimal time, and I think this is for sure something we'll discuss with Dr. Amdani. The authors speak about improving VAD outcomes in congenital heart disease patients, again touting earlier implantation, and also the Action Network, which is famous for rapidly disseminating best practices among centers to rapidly improve in all the centers providing these therapies.

[11:00] They mentioned the finding that VAD-single and 2V patients did similarly in this work and that this was somewhat different from prior literature on this, and they offer one or two possibilities as to why, but ultimately suggest that more work on this to confirm these observations is needed. In regard to limitations, they point to the registry-based nature of the data

[11:20] The absence of socioeconomic variables like residential zip code, household income, or parental education or income. And so this database largely misses social determinants of health that have been shown in other works, some reviewed in this podcast, to be of importance. The authors also mentioned how non-VAD surgery for those with congenital heart disease is needed.

[11:40] not included in the database. And so in some of the congenital heart disease patients, the referral may not have been laid at all, but instead have been used as a rescue following congenital heart surgery that did not go well. And so they conclude. Children with congenital heart disease, particularly those with unaventricular congenital heart disease, are increasingly undergoing vat implantation.

Late Referral and Its Impact on Congenital Heart Disease Outcomes

[12:00] Children with congenital heart disease are often in more advanced heart failure compared to those with non-congenital heart disease at the time of vat implantation. Subsequently, such children with congenital heart disease are twice as likely to die and significantly more likely to experience major adverse events post-vat implantation compared to those who do not have congenital heart disease.

[12:20] There was no significant difference in post-VAD implantation survival for those with uni or biventricular congenital heart disease. Timely referral of congenital heart disease patients with heart failure for VAD implantation has the potential to improve outcomes for this important cohort of children who are at increased risk for experiencing heart failure. Well, this is a very interesting work demonstrating that

[12:40] numbers of congenital heart disease patients needing vads is growing rapidly, and also that outcomes thus far are substantially inferior to those without congenital heart disease. This is not entirely shocking given what may be later referrals, as well as greater complexity of placing a vad in this complex and heterogeneous patient group. I'm interested

[13:00] to learn more about how the action network thinks that general cardiologists can be encouraged to send their cases earlier to heart failure doctors and what it is that we should be looking for. I also wonder what Dr. Amdani believes will be the factors that will most improve these outcomes into the future. Thus, at this time, I think we should move forward with our conversation with the work's first author.

[13:20] Joining us now to discuss this week's work is the work's first author, Dr. Shannawa Amdani. Dr. Amdani is the medical director of the VAD program, as well as the Fontan Multidisciplinary Program and Cardio-oncology Program at Cleveland Clinic Children's Hospital. Dr. Amdani is a graduate of SMT-NHL Municipal Medical College in Ahmedabad,

[13:40] India, followed by a residency at Lincoln Medical Center in the Bronx, New York. He completed fellowship in cardiology at Children's Hospital of Michigan in Detroit, followed by heart failure and transplantation training at St. Louis Children's Hospital. It is a pleasure to have him join us this week. Welcome Dr. Amdani to PeeDeeHeart. I'm here now with Dr. Amdani of the

[14:00] Cleveland Clinic. Dr. Ambani, thank you very much for joining us this week on the podcast. It's great to be here, Dr. Bass. Real pleasure to have you. You know, very much enjoyed this very important work that you and your colleagues at the Action Network have performed. One of the most important lessons of the work I think is that congenital heart disease patients were likely

[14:20] referred later in their heart failure course than patients who do not have congenital heart disease despite being much younger. And I'm wondering what you believe are the most important reasons that congenital heart disease cases are generally referred for advanced therapies like VADs or transplant later than other pediatric patients

[14:40] patients who have heart failure like, for example, a dilated cardiomyopathy patient? Yeah, I mean, that's a really important question. I think that there are several factors that contribute to the later referral of congenital heart disease patients. And, you know, the first being the clinical complexity and the surgical history. As we know, congenital patients specifically

Interview with Dr. Shannawaz Amdani: Understanding Referral Challenges

[15:00] those with uni-ventricular circulation have undergone multiple palliative surgeries, including stage palliations such as the Fontan procedure. And this creates a more intricate hemodynamic and anatomic substrate that often leads to therapeutic hesitation regarding advanced heart failure therapies. The second thing I'll say is that there is delayed recognition

[15:20] We put out an AHA statement that specifically addresses that it is more insidious and a little bit more difficult to determine progression of heart failure in those with congenital heart disease because of adaptive physiologic baselines. So to give you a complete example, the ARIAB has been reported to be

[15:40] lower oxygen saturation and chronic exposure to systemic venous hypertension and low cardiac output, they may mask the severity of the progression. The third is really the perceived high or high surgical risk. Congenital patients have more challenging anatomic considerations for bad implant and or transplant which may lead to reluctance in early

[16:00] referral by their primary cardiologists or surgical teams. The fourth is the limited bat options. Unfortunately, the available bats, particularly the durable continuous flow bats that have become ubiquitous in the adult world, are not well suited for complex congenital anatomy. Making referral pathways less defined compared to the

[16:20] those for non-congenital patients and the final aspect is the institutional and provider variability. As we know some centers have limited experience in managing congenital patients on a VAD or on their journey to a transplant and this may lead to differences in referral patterns and thresholds for escalation of care. So there are numerous factors here. I see. Well that was

[16:40] great, very clear. Thank you very much, Dr. Amzani. I'm going to go out of order the question since you just referenced the action network's guidelines for addressing the timing of referral for Fontan patients who have heart failure, who in order to be evaluated by heart failure and transplant doctors.

[17:00] You hinted a little bit at this already, Dr. Abdani, but I'm wondering if you could share with us some of the more important principles that you and your colleagues from Action have suggested in that document that we as more general cardiologists could learn to better inform our referral practices. Yeah, sure. So the Action Learning

[17:20] has really been at the forefront of managing advanced heart failure in pediatric patients both in general and non-in general. And so one of the things that we did was to put out a comprehensive guideline that emphasizes earlier and proactive referral of FonTAI patients and so it has a couple of, I'll give you some broad themes.

[17:40] themes are important themes from that paper. The first was early recognition of fontan failure and this guideline really stresses the importance of identifying early signs of fontan failure including PLE, blasic bronchitis and organ dysfunction and something as subtle as declining exercise tolerance. The second aspect is routine surveillance

Action Network Guidelines: Improving Fontan and Congenital Heart Failure Management

[18:00] and multidisciplinary care is key. So, structured surveillance strategy that incorporates biomarker analysis, CPAT testing, liberal imaging, hemodynamic assessments is recommended to identify patients who may otherwise look good and as we saw in the paper that we published in JAP, they often end up in the

[18:20] advanced heart failure therapy realm when their inner max 1 which is essentially critical cardiogenic shock so we want to avoid that. The third aspect is understanding the optimal window for back consideration. So rather than bathing until a Fontan patient is in severe decompensation or in an extremis, the guidelines suggest that patients with worsening Fontan physiology

[18:40] pathology that is documented by worsening ascites, worsening end organ dysfunction, or something even less ominous such as recurrent flu infusions or admissions for just albumin replacement should be considered for bad evaluation before severe end organ dysfunction ensues. And the final aspect is early reporter for transplant evaluation.

[19:00] Given that many foreign patients develop complications such as hyperbolic vascular resistance or sensitization from their prior operations and exposure to blood products, early engagement with transplant centers and transplant teams ensures a smoother transition through listening and eventual transplantation. I see. And for those in the audience, you

[19:20] should be aware that Dr. Amdani not only is an expert in heart failure and transplant but also directs the Fontan clinic at the Cleveland Clinic. So I think they found the right man for that job to really make that transition and surveillance of those patients optimal, I'm sure. And I'm sure you encounter failing Fontan patients.

[19:40] patients with some regularity. Well, I was wondering, Dr. Amdani, why you think that patients with congenital heart disease in general have such worse outcomes. Is it all just late referral? Is it that a lot of them are being referred as rescue from a surgery that went bad?

[20:00] And so are in just lousy shape from that? Or do you believe there are other factors that explain the majority of the very substantial enhanced morbidity and mortality that you described in your paper? Yeah, and I think, you know, while late referrals certainly plays a significant role, it is one piece of a multifaceted challenge and the other key contribute

[20:20] inhibitors here are one, greater preoperative acuity. Our study highlighted that congenital patients are four-marker, far more likely to be intermax one at the time of bad implant, the quine mechanical ventilation, dialysis and ECMA. This severely ill preoperative state predisposes them to worse post implant outcomes. As we

[20:40] demonstrated in our paper, it's not only about survival. They have an increased risk for almost all major adverse events after they have a bad implant. This includes stroke, infection, bleeding, and organ dysfunction compared to those non-congenital patients. And many of these complications stem not only from their high preoperative acuity, but from their prior surgical alterations.

[21:00] the chronic exposure as I mentioned before to venous hypertension and the higher incidence really of the thromboembolic and the hemorrhagic complications that those have with congenital heart disease. The third is you know they have chronic endorphin dysfunction that is often not as is often subtle and may manifest itself

[21:20] in a more direct way after they have a bad implant and that certainly plays a role into all the postoperative complications that we see. The last two comments I'll make is one is the ventricular morphology and pump limitation. So many congenital patients particularly those with uni ventricular physiology required as we do in our center and I'm sure if you

[21:40] and other major congenital centers, acquire non-standard cannulation strategies and have sub-optimal ventricular mechanics that affects honestly in the long-term pump efficiency and increases the thromboembolic complications that we see. And then nationally, over the last few years, unfortunately since the COVID pandemic, we are seeing a really

Future of VADs: Innovations and Challenges in Pediatric Heart Failure Treatment

[22:00] very long, weightless time that these patients in general have to go through. And these violets were never designed for durability in the long term. And then they're getting blood transfusions, they're getting more sensitized. And we really need optimal size-matched, anatomic-compatible donors, which are scarce

[22:20] unfortunately in the current era. So there are multiple reasons why they are more predisposed than inclined to have worse post-implant outcomes. Interesting. I never really thought about the fact that these devices are not intended to be as long used. They're not like destination therapy as some of the continuous devices are in the adult world. So I guess that's a

[22:40] very important point. Thank you. Well, for those in the audience, I got Dr. Amdani right in the middle of his very busy day at the Cleveland Clinic. And so I'm going to take advantage of the fact that we have him and ask him one or two questions now that have nothing really to do with his paper, but sort of peripherally because we have an expert here in heart failure and transplant and device support.

[23:00] and I was wondering as a highly experienced heart failure and transplant expert, what factors or innovations going forward do you think will more positively impact the outcomes of congenital heart patients who need a VAD so that the outcomes start to approach the generally excellent ones that you have demonstrated in those who don't have congenital heart

[23:20] disease and even more, I'm going to just take advantage of the fact that we have you here. How far are we from a durable total artificial heart in kids or even xenotransplantation? So we don't have to think about these vats anymore, just pop in a new JARVIC-29 and ready to go for the next 70 years.

[23:40] This is such a critical aspect of our jobs and certainly keeps me up at nine as I know many others in the field around the country and around the world but I'll say a couple things here. I think there are several key advancements that could improve outcomes for this really vulnerable cohort of congenital patients who are experiencing advanced heart failure. The first is you know we need patients

[24:00] specific bad cannulation and flow strategies. And I know that there's a lot of ongoing work optimizing cannulation strategies specifically for those with univentricular hearts and improving flow dynamics in smaller patients that will be critical I think in reducing thromboembolic and hemodynamic complications that we see. The second aspect is really

[24:20] We've been forgotten in the pediatric realm. Most of the bads have been designed for the belts and why we've gotten really good at successfully putting them in kids using novel techniques. I think what we need is miniaturization and design that is specific for pediatric patients and more specific for congenital heart disease patients.

[24:40] The development of these smaller continuous flow devices is going to be key and is a major area of need for us. And I'd say the third point here is that I think we should be going to eventually get really good at hybrid support strategies so that at mode of air transition, as we define in our paper, there are a lot of general patients end up on

[25:00] So how do you bridge these critically-end cardiac shock patients with congenital heart disease from ECMO to a durable support while optimizing their end-alarm function is going to be key. And I think the ECMO and PELA strategy specifically for the older pediatric patients is now being tested and I could see that being transitioned into the

[25:20] into the congenital population. I think specific to VADs, I'd say biologic modifications are needed to improve the hemocompatibility related adverse events to reduce the thrombotic risk, to reduce inflammation post-VAD that could improve the outcomes. And I'd say

[25:40] Specific to artificial hearts, the total artificial heart is not really optimized for pediatric and general patients, but I know that the new iterations, the Bible Core total artificial heart is showing some promise overall in the adult world. But if you had asked me now, I would say certainly pediatric uses.

Conclusion and Final Thoughts

[26:00] is a few years if not a decade away. As far as xenotransplantation as we've seen in the last year's recent advancements in genetically engineered parts have demonstrated some early feasibility but rejection durability remain major concerns. You know xenotransplant started with Leonard Bailey did

[26:20] transplant 40 years ago. And yeah, and it's interesting that we are still sort of in the infancy stages, but clinical application is still, I would say, several years if not decades away, but currently it would be a dream of mine. I know many of my colleagues are on it. I see. Yeah. Well, that was wonderful. I'm very

[26:40] Dear friends with Guvel Farooqi, who's been working on imaging approaches to optimize vat placement in congenital patients. But despite her brilliance and the effort she's doing, I think you're right that the devices themselves were sort of trying to put a size 7

[27:00] foot in a size 4 shoe or something along those lines. Well Dr. Amdani, I can't thank you enough. I want to thank you so much for joining us this week on the podcast and I want to congratulate you and all the many many centers and co-authors on this very important project. I would encourage everybody to go read the paper. It's a lot of important

[27:20] points made. Thank you so much. Thank you so much, Dr. Paz, for having me. It's an honor and I just wanted to give a shout out to the Action Learning Network for really leading the way here. Thank you. Thank you so much. Well, as I'm apt to say, when the guest is good, there's often not much to add. Dr. Amdani offered a number of reasons. He thinks that congenital heart disease patients do worse with vads.

[27:40] And I think that when thinking about all of these many factors, one could make the argument that the outcomes reported here are remarkable, but clearly have a way to go in reaching the outstanding results that we expect in the present era for patients who do not have congenital heart disease. I found his comments about timing of congenital heart referrals to be of great interest and was also

[28:00] interested to hear his thoughts on how we can improve vads in the future to be better suited to our congenital heart patients. I am most appreciative to him for taking time out of his very busy schedule right in the middle of his day to speak with us this week on the podcast. To conclude this 328th episode of PD Heart Pediatric Cardiology today, we hear the wonderful Lyrico Spin

[28:20] Bulgarian soprano Reina Kabbavanska. Miss Kabbavanska was born in Burgus, Bulgaria and she started in Sofia and made her professional opera debut at the Bulgarian National Opera in 1957. Shortly thereafter she began performing in Italy where she had many gigantic successes and where she was known

[28:40] for her wonderful voice married to her authentic acting skills. Ms. Kavavanska sang at the funeral of her costar Luciano Pavarotti in 2007 and she works today still as a professor in Siena, Italy as well as at the new Bulgarian University in Sofia in Bulgaria. Today we hear her in one of the roles

[29:00] for which she was quite famous, singing Tosca's Visitiarte from Act II of Puccini's masterpiece. Thank you so much for joining me for this 328th episode, and thanks once again to our guest Dr. Amdani. I hope all have a good week ahead.