Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And today, we're highlighting the impact of heart transplant allocation change on waitlist mortality and post-transplant mortality in patients with left ventricular assist devices or LVAD.

Joining me is Dr. Anjan Tibrewala. He's an Assistant Professor of Cardiology at Northwestern Medicine. Dr. Tibrewala, thank you so much for joining us. I'd like you to start by setting the table for us. And tell us a little bit about the evolution of LVAD itself and its impact on patients that have been using it. Tell us how it kind of came about and then we can get into the rationale behind the revision of the U.S. Heart Transplant Allocation System that happened in October of 2018.

Dr. Anjan Tibrewala: So, LVADs or left ventricular assist devices are an established therapy for patients with advanced heart failure. Those are patients that have failed conventional therapies, medicines, other devices. And so, these are truly patients that are at the extreme stages of the disease that need increased level of support and increased therapies. And so, LVADs are mechanical heart pumps. They truly do the work of the heart for them. It's a surgery where the pump gets implanted to the heart and it's continuously flowing. It's taking blood out of the heart, pumping it to the rest of the body, again, taking over the pumping function of the heart. They've been around for probably close to two decades now. And as with any machine, the LVADs have iterated over time. Each generation has gotten better than the last. And by getting better, what I'm saying is patients are living longer and they're having less complications and better quality of life with each subsequent iteration of the LVAD.

Melanie Cole, MS: Tell us about the revision that happened in 2018 that gave LVAD patients intermediate priority status and that there hadn't been that many studies that examined the impact of this policy change on outcomes among patients with LVAD. So, tell us a little bit about why that happened. Why was that so important?

Dr. Anjan Tibrewala: Historically, LVADs were used as a treatment for advanced heart failure, but they were predominantly used as breached transplants. So, the LVAD would be put in, a patient would get out of heart failure, they would survive for some amount of time. And then, eventually, while on the LVAD, they would then get a heart transplant. And this was actually done at that time, because at that time, the pumps were not that good. The survival is not as good, at least, and it paled very much in comparison to heart transplant. As heart failure has become more prevalent, and advanced heart failure has become more prevalent, and as LVADs have become better, we are realizing that patients can live for a long time on LVADs. The most recent device, the HeartMate III, has a median survival of six to seven years after pump implant. And so, the most recent heart transplant allocation revision was partly designed to prioritize those patients without an LVAD device, because those patients were at higher risk of mortality, whereas patients that already had an LVAD because these were newer generation pumps were expected to have a relatively good survival. And so, because these patients were already supported, the transplant allocation system was designed to prioritize those other patients potentially more in need of a donor organ.

Melanie Cole, MS: So, how did the allocation change affect the waitlist mortality among patients with their LVAD? Were there significant differences in mortality rates before and after this change?

Dr. Anjan Tibrewala: It was interesting because the initial hypothesis, the thing that everybody thought was, well, if LVAD patients are deprioritized on the newest allocation system, we would actually expect waitlist mortality to be higher because these patients are not getting transplanted. They're sitting on the list for longer, and as they're sitting on the list for longer, they're just dying more just because they're not getting a donor organ.

And what we found in this study was actually the opposite. That patients that were listed for heart transplant after the allocation change in 2018 actually lived longer on the wait list. And the reason for that, we found, was because of the pumps themselves. Because the pumps got better with time, there were more patients with newer pumps after the allocation change, and this effect was far greater than any other effect of the allocation change and actually impacted waitlist mortality in a positive way for patients.

Melanie Cole, MS (Host): So, I want you to expand, Dr. Tibrewala, on that because I read the study myself and said that the mortality post allocation change was driven by, as you just said, LVAD technology. What LVAD technology? What's exciting? What's changed that made this so significant?

Dr. Anjan Tibrewala: So, the prior generation of LVADs were what we call axial flow pumps. It worked like an Archimedes' screw. This was called the HeartMate II pump and that's how it pumped blood. And the Achilles heel of that pump was actually pump thrombosis. So, it had these ball bearings and there was these metallic components that came into contact. And over time, you can imagine that some of these pumps , became predisposed to developing clot in the pump itself that prevented the function of the clot, that amongst other complications. And the newest generation of pumps are actually centrifugal flow pumps that are magnetically levitated, do not have the same mechanical components, and the rate of pump thrombosis, or really clot forming in the pump, is significantly lower.

Beyond that, the rate of other complications, such as strokes, infections, bleeding, although they're still present, are somewhat lower than they were. And in this process, we're actually finding that patients are living longer, both as the pumps are getting better, there's less complications, and the patient management has gotten better.

Melanie Cole, MS (Host): So, we've talked about waitlist mortality and this allocation change. Now, let's talk about posttransplant mortality. If we're looking at the main factors that are associated with posttransplant mortality among those patients that had LVAD, did ischemic time, patient acuity play a significant role? Tell us about how that changed from this revision.

Dr. Anjan Tibrewala: Specifically, in LVAD patients, what we found was that patients that received a heart transplant after the allocation change actually had increased posttransplant mortality relative to those patients that were transplanted before the allocation change. And as you indicated, this seemed to be largely driven by both ischemic time and patient acuity. And so, the ischemic time was significantly higher in those patients that received a transplant after the allocation change. It was about three and a half hours compared to three hours prior to the allocation change. That 30 minutes might not seem like a big amount of time, but in the world of heart transplant, 30 minutes can actually make a big difference.

 Patient acuity also is associated with it. That I think makes sense to us because the sicker somebody is going into transplant, the sicker we may expect them coming out of transplant. And so that's what we found as it pertains to post-transplant mortality.

Melanie Cole, MS (Host): Give us a little lesson here, Doctor, about the relationship between ischemic time and post-transplant mortality. How does that longer ischemic time contribute to that higher mortality rates you were discussing?

Dr. Anjan Tibrewala: So the way that these organs are transported, these organs are procured from a donor, they're put in some type of storage, and then they're implanted into a new body. And as you can imagine, that in between time is not a natural environment for a heart to be in. And so, the longer that time is, the more bad things that can happen to the heart.

 The mechanisms of this are fully not understood, but what's thought to be is that more ischemic time leads to more cellular damage. So, the myocytes or the heart muscles themselves are getting damaged. There's also some effects on the vasculature, some effects on the conduction system, and some increased inflammation with longer ischemic time. Again, we don't fully understand the mechanisms, but those are some of the proposed mechanisms as to why longer ischemic time leads to more adverse outcomes related to some of those mechanisms.

Melanie Cole, MS (Host): What about the patient's status at the time of the transplant itself? How did that affect mortality post-transplant and the implications of this finding? Tell us about that.

Dr. Anjan Tibrewala: So, the patient status is a surrogate for how sick they are. The status 1 patient is sicker than a status 2, 3 or 4 patient. The lower the number, the sicker the patient. And what we found was that those patients that were sicker, that had lower status, had increased risk of post-transplant mortality.

Some of that was largely driven by devices that they might have needed to support them prior to the transplant, in addition to the LVAD. Some of this might have been due to having had other LVAD-related complications that actually justified the lower status, such as stroke, bleeding, infection, and some of this might represent other organs being affected, which again, supported the higher acuity of that patient. And a heart transplant really only impacts the heart. And some of those other factors still play a role in affecting the patient's outcomes after that transplant.

Melanie Cole, MS (Host): Are there any other factors or variables you want to mention that are found to be significantly associated with that waitlist or post-transplant mortality?

Dr. Anjan Tibrewala: The only other thing I want to mention, which was really interesting, and I think will have implications for the future, is that right now the heart transplant allocation system divides LVAD patients into four different statuses, as we mentioned, 1,2,3, and 4, with 1 having theoretically higher waitlist mortality than those that are status 4, in theory, status 1 should get a transplant sooner than status 4, because they're at higher risk of waitlist mortality.

And what our study found was that the current allocation system does not discriminate amongst the statuses for LVAD patients. In other words, the expected mortality between the status 1, 2, 3, and 4 were not statistically significant in our study. And I think really the true finding, the big finding from there, is that we need better ways to differentiate LVAD patients in their risk of waitlist mortality so that we can allocate the donor organs to those LVAD patients most in need.

Melanie Cole, MS (Host): So, this is something that we can look forward to. It's exciting in your field. And based on the findings of this study, tell us the key implications as we wrap up for clinical practice. Future research in the field of heart transplantation. Take us from bench to bedside with this.

Dr. Anjan Tibrewala: So, I think the biggest takeaway potentially at a population health level is the heart transplant allocation system is an iterative process. The schematic or the scheme changes every so often. And the second one scheme is published and utilized. We're collecting data and we're trying to figure out how to make that better, how to revise it.

And that process is ongoing. It's been six years since the last revision, and I think studies such as this one help inform how the next allocation scheme is going to be implemented. And I think that's important because it allows us to optimize outcomes for all patients with advanced heart failures. Who should get a transplant? Who should get an LVAD? Who should stay on their LVAD? Which LVAD patient should get a transplant? It allows us to really optimize patient outcomes. It allows us to best allocate those donor organs to the patients that are most in need. I think that's really the biggest takeaway from this. I think there's some other nuances about how we as clinicians may manage LVAD patients while they're listed for heart transplants and maybe even they get their transplant. But the biggest finding, I think, is informative for future iterations of the heart transplant allocation scheme.

Melanie Cole, MS (Host): It certainly is. And thank you so much, Doctor, for joining us and sharing this study and your incredible expertise. That was so interesting. Thank you for joining us. And to refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/cardiology to get connected with one of our providers.

That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. Until next time, thank you so much for joining us.