Melanie Cole, MS (Host): Welcome to AHN MedTalks, an informative resource for physicians across various specialties as we delve into the latest medical insights and best practices ensuring you stay at the forefront of your field. I'm Melanie Cole. And here today to highlight patient referral for heart transplant is Dr. Manreet Kanwar. She's the Medical Director for Mechanical Circulatory Support and Cardiac Transplantation Program at the Allegheny Health Network.

Dr. Kanwar, thank you so much for being with us today. I'd like you to start by giving us a little bit of an overview of your role at AHN and your expertise in this field.

Manreet Kanwar, MD: Sure. First of all, thank you so much, Melanie, for having me. I think any opportunity we get to increase awareness about, A, the fact that transplants are available for those who have end-stage heart disease, and B, talk a little bit about appropriate referrals, as I would say, from our general cardiology colleagues or our primary care physicians, I think this opportunity just helps increase awareness amongst our medical community.

So, a little bit about myself. I've been at AHN Pittsburgh for about 13 years now. About five years ago, I took on the role as the Medical Director for LVAD, which is the artificial heart or left ventricular assist device, and also the Cardiac Transplantation Program. Now, we've had a heart transplant VAD program for over, I think, a couple decades now. And my role here is to facilitate appropriate referrals, walk patients through the process to see if they're a candidate for one or the other. And then, if they are, then help them through the process until either they receive an LVAD or get listed for heart transplantation and then subsequently follow them through their postop journey as well. So, I take care of the medical side of things.

And, as in many things in heart care management these days, it's a team sport. I think that holds true for heart transplantation more than anything else. So, our team will include, you know, on the pre-transplant side, our medical personnel, social worker, nutritional experts, and then also, folks who help us process patients through insurance processes, et cetera, et cetera; and then, of course, our surgeons, who would perform the transplant itself; and then, a vast team of coordinators who help us, you know, find the appropriate donor, take, you know, decision managements, and then really are the first line of defense to follow these patients for the rest of their life through screening them for rejection, infection, et cetera, et cetera. So, it is a lifelong journey. It does take a lot of patients to run a successful heart transplant program, and that's definitely something we take a lot of pride and joy in here at Allegheny Health Network.

Melanie Cole, MS: Well, thank you for that, Dr. Kanwar. How common is heart transplant? How common is the need? How many are performed generally on a yearly basis? Tell us a little bit about your hospital's history with heart transplants and the scale of what we're talking about.

Manreet Kanwar, MD: Sure. And actually, before we even talk about transplant, I'll take a step back and talk about the scope and scale of heart failure and then advanced heart failure. And by advanced heart failure, we mean those patients who have dealt with heart failure but now are beyond the scope of medical therapy.

So, starting with heart failure, you know, if you look at the U.S. prevalence, it's estimated that by year 2030, we'll have somewhere between eight to nine million people with heart failure. And almost one in four, which is about 25% patients will be at risk for heart failure. Now, most of them, vast majority of them, will be managed with medical therapy, and we have excellent medical therapy in today's age and day. But unfortunately, about 2-3% of them, so that comes out to approximately some 70,000 to 80,000 patients will go on to develop every year advanced or end-stage heart failure.

And in that scenario, we start looking at them for options such as durable LVAD and/or heart transplantation. So in the United States, we perform on an average approximately 4,000 heart transplants a year. This number has slowly, but surely started to inch up a little bit. Worldwide, about 5,500 to 6,000 heart transplants are done, so that gives you an idea that United States performs the most heart transplants in the world.

And specifically to our region and my institution, we perform approximately, I would say, 25 to 30 heart transplants a year. Now, there are multiple centers that perform a higher number, we would be considered medium in terms of size of the transplants we do. Of course, you know, we serve the Pittsburgh region along with our colleagues at University of Pittsburgh, so that's sort of our share of the market, if I may. So, that is the scope and scale of heart transplants done at AHN and then, of course, in reference to the rest of the nation.

Melanie Cole, MS: Now, as we speak about heart transplant referral criteria, and you mentioned heart failure and the truly significant scope that we see of that today, when should a patient be considered? Tell us a little bit about your hospital's pre-transplant criteria and the program, the waitlist experience, speak about that.

Manreet Kanwar, MD: Sure. Patients are usually referred to heart failure cardiologists like myself when they are sort of kind of running out of options with medical therapy. So, the single, I would say, main criteria to be considered for advanced options is that the patients are not doing well, despite what we consider standard of care medical therapy. We sometimes do heart transplant for patients who have, let's say, refractory angina or have medical or cardiac conditions that are just not going to respond to medical therapy. These could be congenital conditions, restrictive cardiomyopathies, arrhythmias, valvular diseases that are beyond the scope and scale of medical or even percutaneous interventions.

So generally speaking, we are looking for patients who have limited life expectancy or quality of life, but it is from a cardiovascular reason. Now, generally speaking, the age cutoff for heart transplantation is around 70. Now, there are rare cases where, you know, we may look at somebody a little bit beyond that. But usually, that's the average cutoff. And another limitation we have is that of the weight-height ratio, which is the body mass index. Usually, we are unable to find suitable donors for patients at either extreme of body weight, be it very low or very high. Now, of course, the main things we look into when we say, you know, how long does a patient have to wait, for example, on the waitlist is dependent on how sick they are, what their blood group type is, et cetera.

So, the main indications to answer your question is patients who are suffering from either repeat hospitalizations, poor quality of life, or we think that they're not going to actually make it because of an underlying heart condition would be patients we consider for transplant. And usually, these are patients with reduced rejection fraction, although that's not a must, so to speak.

Now, patients who may meet this criteria but would not be considered eligible for transplantation are those, you know, with very advanced age or also comorbidities that would unfortunately limit them from candidacy. So, for example, the way to look at it is do we think their life expectancy, if we were to do a heart transplantation, will be beyond several years? So, if let's say they have malignancy or cancer, that's going to limit their life expectancy. If they're actively smoking or drinking heavily or using drugs or have other conditions such as a different organ that is involved that would preclude the transplant candidacy, then those would be some of the main things we would look at.

But to anybody who's wondering if they have a patient who they not meet the criteria, I think that burden falls on the transplant center. So if you have a patient that you're wondering, you know, maybe they're a candidate, maybe they're not, before you assume, because beyond transplantation we can offer other options, clinical trials, LVAD, et cetera et cetera. So, I would say if you have a patient and you're not sure if they're good candidates or not, ask your heart failure colleagues. And if they're not, we will let you know. But many a times, we worry that patients are sent to us too late, because people assume that they're not going to be candidates for criteria that may not be unsurmountable.

Melanie Cole, MS: Dr. Kanwar, this is such an interesting topic. And one thing I wonder, as an exercise physiologist, has better awareness for heart disease helped reduce the need for heart transplants? As we think of other organs that are transplanted and lifestyle changes that we hear about and there's so much more awareness, well, heart disease is certainly a big one, and we hear a lot, it certainly seems that people are hearing the message. Do you hear that as well? Has that reduced the need?

Manreet Kanwar, MD: So, I don't think so, Melanie, because again, vast majority of patients with heart disease will not end up needing heart transplant. And when we talk about prevention, we talk about, you know, the role of exercise, nutrition, all these wonderful medical therapy options we have at our disposal now and lifestyle changes, frankly. I think they have a major, major contribution in preventing heart disease. But unfortunately, we are talking about a subsegment of patients with end-stage heart disease, which by the time they progress to that stage. I think these preventative strategies have less and less role to play in impacting the prevalence.

So, if I look at the big scope of things, for sure, I think between lifestyle modification and also medical therapy, the need for advanced options has been impacted, but transplant is again limited to such a relatively smaller patient population that, unfortunately, the need for-- we talked a little bit about the supply-demand ratio earlier, is the number of patients who need advanced therapies keeps on rising and, unfortunately, we're not able to keep up with that scale despite doing more and more transplants every year. But the delta or the increase is so small relative to the prevalence of the disease that I still don't think we are at a point where we say we have enough organs for those who need them.

Melanie Cole, MS: Can you speak a little bit about the role of patients supported with ECMO as a bridge to transplantation versus LVAD? You mentioned LVAD earlier. Can you speak about what your team does for the patients while they wait, managing their situation while they wait for that heart to come through?

Manreet Kanwar, MD: Sure, Melanie. When we list somebody for transplant, we list them based on their severity of illness. So, the list goes from one to seven. One is the sickest of them all, and seven is actually almost inactive. So, I would say effectively speaking, it's one to six. Now, a patient who is one, two, or three is sick enough to be in the hospital, whereas the patient who is four, five, or six is at home, but eventually needs a transplant.

So, how it works, loosely translated, is status one, limited to very few patients, the sickest of them all, we feel that they have days, maybe weeks, left to live. These are typically patients supported via ECMO or other mechanical circulatory support devices where we know that we cannot even get them out of the ICU. We can't even get them off of the machine that they are currently supported on, and these are the patients who will have the least amount of waiting time, because the organs are prioritized for them.

Now, the status two is somebody who may be not as sick, maybe they don't have days, but maybe weeks, but not months left to live. They are also typically in the hospital, in the ICU, but not what we call sort of crash and burn where they're on ECMO, but they may be on, let's say, a balloon bump or an Impella or other therapies that keeps them in the hospital, most likely ICU, but they're stable on that therapy.

And then comes status three, which is they're still in the hospital, but they're not in the ICU, they're not on a machine and yet, they're not well enough to go home. Everybody else, four, five, six is at home. So here, we start saying they have months, maybe a couple of years. But at some point, they're definitely going to need transplant. And these are patients we follow very frequently. And if they get sicker, we escalate their status based on predefined criteria that are dictated by UNOS so that, again, we all follow the same method, whether the patient's at Allegheny or another hospital. It's not subjective opinions. It's very, very objective data that we have to follow.

If a patient's on ECMO based on their blood group type, body size, and other comorbidities, they would have a waiting time of days, sometimes maybe a couple of weeks if they have a bigger person or extreme of BMI and have a blood group O, which is a very, very common blood group type and is a universal donor. Whereas if a patient's on durable LVAD, they are usually status four and at home because they're not sick. You know, a VAD can buy you five, six, seven years of life. So, we try to follow the policy of net prolongation of life, as I call it. So if they're doing great on a VAD, I'm in no rush to transplant them. We want to maximize their time on VAD before we proceed with transplant with them.

Now, if they have an issue or complication with LVAD, they're not doing well on an LVAD, then we would want to transplant them sooner. So, we follow these criteria as does every other center, so that it is based on some key justifications as why we are upgrading them or downgrading them on the waiting list, so to speak.

Melanie Cole, MS: Dr. Kanwar, what's involved in post-transplant care? As we speak about, you've mentioned the multidisciplinary care, the transplant coordinators and support staff. Tell us a little bit about after the transplant, some do's and don'ts, including major medical issues to look for.

Manreet Kanwar, MD: The way I approach all my patients. And when we talk about transplant is I always tell them, as much as I would like to say it's a sunrise in the horizon and, you know, they live happily ever after, the truth of the matter is it's a lifelong journey that they start and there is a compromise. Of course, you know, considering the alternative, the compromise is something that is not unfavorable. So, an average life expectancy post-transplant in this age and day is somewhere around 13 years, give or take a few months. Now, this is the average, of course. We have patients who've been out 30 years and there'll be patients who sometimes don't make it very far based on a lot of circumstances.

So, the first year, Melanie, is the key sort of milestone for us, because this is when they're at highest risk for rejection, especially if they're very young and they have a very robust immune system and some other, you know, medical criteria as well. So, we always tell people that the first year is sort of the key where we see them multiple times. They undergo extensive testing, screening for rejection, echocardiogram, blood work, et cetera et cetera. After the first year, their risk of rejection goes down considerably.

So, the first year, you know, we always worry about rejection and infection. Those are sort of the two key things we look for. After the first year, life calms down a little bit. We stop worrying about them as much, but the risk of infection still stays. And then, it goes down as the farther out they are from transplant, the less and less immune strict we have to be with immunosuppression. Now, of course, they have to be on immunosuppression for the rest of their lives, but we reduce them. Initially, we start them as triple therapy, then it goes down to double therapy, and then the levels of that goes down. So, the first couple of years, it's always an interplay between the risk of rejection and infection. After that, there is usually a bit of a honeymoon period where the risk is down considerably and the other issues have not crept up.

Now, once you hit the five, six, seven years post-transplant mark, we start seeing other problems. The top two issues we face are risk of cancers, because these are patients that have been whose immune system is chronically suppressed. Skin cancer is the most common type of cancer we face in this patient population. And the second is risk of developing issues with the graft itself, such as coronary allograft vasculopathy, which means new blockages in the transplanted heart; kidney problems, because the immunosuppression we give them often affects the kidney functions, so on and so forth. So, those are sort of the five things we worry about: rejection, infection, kidney disease, cancers, and then eventually coronary allograft vasculopathy, or CAV, but that's later on down the years. We are always on hyperalert for these patients because, unfortunately, they go through unphysiological processes, and we have to always look to make sure that, you know, they're not having issues. So, for example, all these patients undergo annual cancer screening, which is age-appropriate, based on them, you know, a skin exam once a year. And also, we try to encourage vaccinations, et cetera, so we can prevent any issues the best we can rather than treat them after they've happened.

Melanie Cole, MS: Dr. Kanwar, I'd like you to tell us about the future of heart transplantation. How do you envision the future evolving over the next decade or so? Is it determined by issues such as the ongoing shortage of donor organs that's fueled a search for alternative therapies? heart transplant, xenotransplant. I mean, there's so many available options being looked at today. It's really an exciting time. What do you see happening in the next 10 years? What would you like to see happen? And I'd like you to give the key takeaways to other providers today.

Manreet Kanwar, MD: Sure. I'll answer the question of what I think will happen, followed by what I wish would happen, and then the key takeaways in that order. So, I think, and I'm sure everybody has read about those in the news, you know, a couple of xenotransplants, you know, heart transplants that were performed by University of Maryland in the last two years, and then also xenokidney transplants that are currently happening. So, I think that that is certainly going to help us expand the donor pool beyond our current limitations of what we have.

Now, do I think that xenotransplant being commercially available and accessible to all is around the corner? I don't think so. I think it'll take years of further investigations before they are easily available and accessible. So, I think maybe by the end of the decade, for sure, but they're not regularly available.

Now, I think the other biggest thing that is happening in our field is our ability to transport human donor organs further and further using technologies and techniques that allow us to preserve the donor organ. So, traditionally, we have to bring in the heart from the donor to the recipient and sew it in, suture it in, and resume perfusion all within four hours. But thanks to some wonderful advancements in recent technologies, that time is being stretched beyond the four-hour window without compromising the graft function. So, I think that's going to help a lot in not allowing us to waste any donor organ, because we can't physically bring it in fast enough.

So, I think those are the two things that are going to start changing the phase of transplant in the next decade or so. But what I wish would happen, I think, and maybe not in the next few years, but certainly I think the future of all heart therapies is going to be heavily affected by gene therapies down the line. But we are talking about not getting to a point where you're going to need heart transplant rather than them necessarily impacting how we do transplant. So, I think between medical therapy, gene therapies, and then, increasing donor availability, we'll hopefully get to a better ratio of the supply and demand, so to speak.

But the key take-home In today's day and age is if you have a patient with heart conditions that is limiting their quality of life, they're in and out of the hospital, they're not doing well, they're not responding to medical therapy, please do refer them to your heart failure colleagues, whether you think they may or may not be candidates for transplantation, or at least reach out over any means of communication, if the patient can't make it to an in-person evaluation, because there are all these other options available above and beyond heart transplantation, durable LVAD, clinical trials.

So, that would be sort of my key take-home point is any patient that you feel is heading in that direction, I think early referral is key. Because, unfortunately, we continue to receive patients in fulminant cardiogenic shock, a very extreme state that there is very little we can offer them this far down the line. So, early referral. If you're not sure, ask. I think that would be my key take-home message.

Melanie Cole, MS: Thank you so much, Dr. Kanwar. This has been a fascinating conversation. And to learn more or refer a patient, please call 844-MD-REFER, or you can visit ahn.org. Thank you so much for listening to this edition of AHN MedTalks with the Allegheny Health Network. Please always remember to subscribe, rate, and review AHN MedTalks on Apple Podcasts, Spotify, iHeart, and Pandora. I'm Melanie Cole. Thanks so much for joining us today.