Daniel S. Yip, M.D., a cardiologist specializing in advanced heart failure and transplantation at Mayo Clinic in Florida, presents in the Advanced Heart Failure Grand Rounds series on the indications and contraindications for heart transplant.
So um just going to talk a little bit about contraindications, indications to transplant really it's more of a you know what kind of goes through our minds when we um assess somebody, determine whether or not they're a suitable candidate for transplant. And and really that evaluation whether it's official or not official begins when we first meet them. There's a number of different factors that we kind of look at. It's all data driven and there's a reason why we look at what we do and sort of from outcome standpoint. So we're going to go through that and uh please stop me anytime if you have any questions. So you know, when would be a good time to think about, someone may be needing advanced heart failure um treatment or just or transplant evaluation. And what we say is well if you've had a multidisciplinary heart failure care, so it's not just medical therapy but making sure that they're doing the best they can from the lifestyle standpoint exercise and sort of pharmacologic as well. Non pharmacologic strategies to treat heart failure, you know, let's say they got the best you can and that they're sort of optimize and maybe they are limited for whatever reason to optimal doses, but but they're really limited and they've had record hospitalizations and they have a decreased exercise capacity. And I think very importantly that they find that the lifestyles unacceptable, there are going to be individuals who are maybe have recurred heart failure, but they you know, they're okay with them. They don't feel that it's worked while doing the necessary steps and their hoops to jump through to undergo evaluation for a transplant of the trickle assist device implantation. But for those people it probably would not that but for others, you know, whatever their lifestyle, whatever their their norm is, it's just unacceptable. Those are the times that we kind of think about transfer or at least advanced heart failure knowledge. Um So let's start with the case. We've got a 50 year old gentleman referred with to his two years. I said heart failure from non ischemic cardiomyopathy. Currently into our heart association, 3 to 4 symptoms have been hospitalised three times the past six months. His left ventricle ejection fraction has decreased, 15% is left ventricular end diastolic dominators increased 70, mm, cm, 70. He's got at least moderate much regurgitation. He's got renal sufficiency with the credit 1.8. So that's a little low at 1:35. Did a treadmill test but he couldn't get out of stage one of the Bruce protocol uh on exam, he's pretty comfortable. His blood pressure is 100 over 75. His um CBP is certainly elevated. He's got an S. Three, his liver's a little bit large and the extremities got some mild oedema but there's somewhat cool he's taken for a guideline therapy guideline directed medical therapy including um you know an ace inhibitor beta blocker, al gastro block or loop diuretic warfarin for whatever reason as well as the Jackson. So looking at that, you know what would be the reason why you would think about transplant? Because the rejection fraction which was 15 the soda stream side is 1 35 lb side is a little bit big. The L. B. And I stock diameter is seven centimetres. Is it because they're cracking is 1.8 or is it because of their functional capacity? So what would be the main indications for transplant? Why would you think about transplanting this person? So we'll go to that to that a little bit later and let's go to get some sort of background has to help try to understand understand that question. So when someone referred for the dance heart failure care, first thing we do is we look to see if they've been optimized medically surgically. Have they been optimized? And they do have do they have the optimal devices in place? Um How about the non pharmacologic, non medical treatments such as lifestyle changes? You know fluid limitation, sodium limitation, exercise. Has that been optimizing? We've done the best we can with them and then certain people or certain patients are gonna be on a truck dependent. They come to us on on the tropes can't get them off its legitimate um depends your honor tropes and if that's the case then then we really will think about they be considered for transplants to be considered for mechanical assist device or investigational drugs or or perhaps it's just an end of loch discussion. Not just an important part of heart failure care, but if they're not a truck, depending what we're going to figure out what their prognosis is. So carnival me stressed that your car association heart failure out stores. There are all tools to help us assess prognosis in patients with heart failure. It turns out the ejection fraction is not a great prognosis of great predictor of events. Heart failure. Uh, prognosis. Uh, it's an easy thing to look at it. Easy thing to measure. You can measure by left Tripoli. Grand, you can left, you can measure it by a mug. A scan. You can measure with an echo. It's a it's a number. You can hang your hat on, Patients are many times uh good or bad, right or wrong or fixated on their on their ejection fraction. They they have access to the portal and so they're listening, they're ejection fraction is 25%. And now they had an echo repeated and now it's 30%. So they'll say, Hey, I must be doing much better right away from 25 to 30%. Then you have to sit down and have a discussion with them and say, you know what the uh ejection fraction calculation regarding what methodology used. It's not an exact sign. It's really not an exact science. It's really an eyeball thing. We all know, you know, you move the cursor around, your GF goes from, you know, 25-40 just by moving things around a little bit. And it turns out that there's a lot of people with the gesture fractions between 20 and 35%. There are people who never need a transplant. Their class one, they're playing basketball, they're so active that you can't that you never figured out they have heart disease. And there's other people with ejection fractions, you know, more than 35, And they're very symptomatic heart poor. So it turns out the ejection fraction by itself is not a very good predictor of the vast heart failure. Uh, prognosis and people aren't that smart. So what is, well, actually turns out her association classification is and how much walking you can do in six minutes is a great um, great predictor too. And so you can see the worst your your heart association classes, the worse your prognosis is going to be in the one year. So the four class for patients usually have a 50 to 60% 1 year mortality. Those are the people that we're most concerned about. But hopefully you're getting to them in class to class three because many of these people, you know, if you intervene on them early on, will never get to class form six minute walk is a very powerful tool. If you can do 450 m in six minutes, Your prognosis is good. You're more likely not. To me, you're probably gonna do better without a transplant. Probably do better with just medical therapy um than undergoing either a transplant or building. So 415 m six minutes. That's the sort of the mark that would where make you feel pretty confident that their prognosis is going to be pretty good. But it's just that one time thing. You want to trend that over time and so doing that periodically, you know, year for sure. If they're stable is valuable to what we do in most heart failure programs. Will do is do a card at home a stress test for oxygen oxygen consumption study. Um So basically what you're doing is just a treadmill test, routine treadmill test now turn blood pressure e. K. G. Heart rate but also measures oxygen consumption. Um And it turns out that you're you're a pig. Vo two is more than 14 million per kilogram per minute. Your three year survival is probably about the 95% range. Compared to if it's less than 14 or between 10 and 14. Your your one year survival or three year survival is going to be you know less than 30%. Really it's at the one year less than it's going to be 80% survival in three years. And really the it's the first year that makes the difference. And it's important to note that the one year survival after transplant is gonna be 85 to 90% in in sort of national programs. So so if your vo two max is less than in this case 14 million per kilogram per minute. That is um their prognosis is going to be better than transplant. So regardless of where ejection fraction is, that's what we're really going to look at. But equally important is percent predicted. So if you can imagine someone who's % 20 years old, they're there Expected uh exercise capacity on a treadmill is gonna be much different than someone who is expected, let's say 60 or 70 years old. And so that's where the percent predicted becomes very powerful. And so that um if you're more than 50% predicted, your survival is still in that high 90% range at three years. If you combine the two. So if you have if your vo two max is greater than 14 but your vo two max is less than 14 but it's more than 50% predicted. Your prognosis is about the same as those whose vo two max is 14. So let me just say that again. So these are usually people who are sort of you know 16 years old and maybe above somewhere in there. But they're vo two max is less than 14 but they're percent predicted is greater than 50%. Their prognosis is just as good as other people whose vo two max is great in the 14th which is the old traditional sort of number that transplant centers will look at to see what they're what should they be evaluated for, transparent. So this is a key thing and we'll review that in a second. Um Also what's important, what's the peak blood pressure that was achieved during the stress test. If their peak blood pressure is greater than 1 20 P exercising their Vo two max is less than 14. Their prognosis better than if your vo two max is less than 14. And you are not able to get your systolic blood pressure Greater than 1 20. So these are the folks were the most of the highest risk people who have had a blunted size six. Um not and so there are other parameters have been shown up the V. V. C. 02 slopes of the auction consumption. Total answer total consumption versus divided by the uh go to expire. If their slope is greater than 34 then that is also a poor prognostic sign. So the limitations of the card from the stress test is many times people are vast hardware, particularly if they've not been exercising cannot really reach a true plaque. Vo two plateau because their efficiency of exercise is actually quite poor and their de conditioned and so it's very difficult sometimes to get a true reading on a video to stresses. And so what we do is what we'll do is optimized for medical therapy. In the meantime we get them to exercise either in a formal cardiac rehab program or at least doing that at home. Um And they're not doing the cardio for me stress tests until they had some time to uh to get better condition and optimizing medic. So that is actually awful time to do a credit for the stress test. Um And again just reactivating the things that we look for our peak Vo 2. 14 or a vo two max of Greater than 50%. Um Also great literature percent good prognosis but their Vo two max is less than 14 Or less than 50% predicted order of the E. V. C. 02 is greater than 34. 35. That's a poor prognostic side. And that's what we would think about. Perhaps thinking about transplant or advanced heart failure care. Now the Vo two max of 14 million per kilogram for a minute is was done at a time where people have not been really using beta blockers very much. And as you know people are in beta blocker their hardware response exercise is going to be a little bit decreased and as a result there auction consumption may be a little bit less. And so there is some um guidelines that would suggest if you're on a beta blocker. Um their prognosis the poor prognosis really may not start until your vo two max is less than 14. Um So if you're on a beta blocker the number may be a little bit different um in some studies. So going back to the question, what's the primary indication for transplanting this man would be es una sodium LV side. Real functional functional capacity uh turns out it's functional capacity. Remember dissipation, could not get out of stage one of Bruce protocol. So as exercise capacity is quite limited. Now what you don't know is this this is even is this a maximal study or sub maximal study. But presumably those are the things that make us most concerned. I will stay in the story. Other things that make me really concerned is um The fact that he was hospitalized three times in six months. That's a big concern. I think someone who gets re hospitalized, someone who we have to perhaps not tolerant of guideline directed therapies. You had to decrease their beta blockers to decrease their ace or army or A. R. B. Because the blood pressure. Those are people at high risk those who functional capacity, decrease those who had returned hospitalizations. Those are the people that we're most concerned about. And I would want to see those folks soon around questions so far. So these are the conditions, there's a whole slew of conditions that affect morbidity and mortality after transplant. And they go through our minds like you know, irreversible renal dysfunction. You're through the hepatic disease, severe obesity, diabetes within organ damage. And then all of these sort of sort of play in our lives where we are thinking about that would uh decreased survival generally when you're getting beyond more than 10 years. It's not the heart of the graph that limits your survival. It's usually something else. So even up to 15 years. So the sweet spot really is a 50 to sixties. And but where I think doing better with folks in their sixties. Yeah. Um so back to the patient. So he gets um right heart catheterization and blood pressure is 100 over 75. With the me to 85. Um the RS 10 appears um 65/24 to 35. The west pressure is not too bad is 15. Credit output is 3.6. Um and the ambassador resistance is um for 40. Um if you do, the wood units is about 5.5 minutes. So he's got pretty high pressure. That's for sure. SpR is up as well too. Um And so looking at the questions which one of the following is true for the vast resistance is not reversible because the transport rate is too high. We'll go through those definitions. Second intravenous feroz bhai will lower PVR blood pressure is too low to assess the PVR with natural pressed high blood pressure is only 100 systolic miller known is going to decrease appointed resistance resistance primarily by increasing card gap. So in order to answer these questions you have we have to go through some definitions because yes, if a vegetable for me, hypertension is one of the significant risk factors that affects morbidity and mortality after transplant. So it turns out that if during the pre transplant phase, if your pony are is to stop pressure is Less than 50. Your prognosis is a little better after transplant than if it's greater than 50. But uh and so let's kind of talk about the different calculations. So transported radiant. Our TPG is simply the main corner pressure minus selective pressure. So and that's really looking at what's the pressure gradient across the plenty vasculature. Right? The pulmonary pressure is on the pre side, pre load side of the lungs, so to speak. The wedge pressure is, so to speak. That after load of the pony basketry step. Yeah. So what's the difference? The difference in pressure there? Um totally vascular resistance is simply the same thing. The meeting, police pressure, much pressure divided the cardiac output or transported grading. Divided by the cardiac output. Just if you don't if you understand what these are, you can pretty much answer the questions uh that the approached earlier. So remember I told you earlier if you're just about the only pressure is um greater than 50 your prognosis is slightly better than if it's less than 50. But if you look at the transport rating right? So that means pay pressure minus wedge pressure. The bigger the difference the worst of prognosis. So if you're mean ph minus the wedge pressure is In this case less than 12 in this study. Less than 12 13. Your prognosis is pretty good post transplant as opposed to if you have a large family gradient or there's a big difference between the main courtyard pressure and the pressure. Some people would use the difference between the diastolic pressure minus the blood pressure. It's it's analogous. You can do it that way too. Um So it doesn't make a difference. Yeah, it makes a difference. So when you're and you can say this is 10 year mortality. So even going out 10 years, there's this significance. There's there is significance of what the transport grading is. Pre transplant, if that's 10 year mortality. Um Beyond so really, again, probably after 13 14, 15 millimeters of mercury transporting gradient difference. That's when you start seeing the excess mortality. Um So let's let's go to our patients. So baseline, we're told you the Oreos 10 the way it was 15 The P pressure's 60/24 to meet a 35. So that means 35 -15. Right gives you a transparent Grady at 20. So the cardiac was 3.6. So called Advanced Resistance is simply 20 divided by 3.6 is 5.6. That's pretty high. Spr 1600 or almost 17. So let's use not your press side. So with not your press side you're writing for pressure drops your your public capital vice pressure actually went up. Talk a little bit about that may be why that's the case. The P. A. Pressure went down so the ps systolic went to 40. The diastolic is about the same. 20 for the pony ari pressure me dropped to 30 Transpoint radio announced 10. Right? So 30 minus 2010 Credit card is 4.5 best resistance of about 2.2. So it's a better point of resistance. And your crank up that went up. So all you've done is unloaded the patient right? You improve their after loads. So you have presumably better flo you're unloading the right ventricle so you have better right ventricular contract ill. Itty. Um And that's probably you probably have better feeling the left ventricle. And that's why you're wedge pressure wanted. You're actually now able to fill the left ventricle a little bit better. So you have better flow across the pony vasculature that has resulted in a lower right age for pressure, better transported gradient. Um And better clandestine existence. Yeah. So how about if you use not Miller known. So if you use Miller now it's a little you're pulling pressure, you're you're already pressure. Didn't really change that much. Pulling pressures really didn't change that much. A little bit lower, transported great. It's a little bit lower from 20 to 17, but your cardiac output is much better, went from 3.6 to 5.3. Um and as a result, your point vast resistance went from 5.6 to 3.2. So in nowhere no example is you haven't really done that much to the polio, precious. It really happened. But all you've really done is increased cardiac output. And because point vascular resistance is really just a math calculation, you have improved. Um your point about resistance because you improve the card number to the podcast. Resistance is simply the transport rated Mastercard divided by the card account. So it's a math problem. Right? So you can improve the point that's existence simply by increasing card. Um And so if you continue on, so we'll get back to that point in a second. So is that a big deal is doing this? A big deal is going to natural press sign, dropping the transporting grain and dropping the point bastard system. Is that a big deal or not? It turns out that it is. And so again, this is old data, but we still use it. And so they're basically, what happened was it took everybody who was being evaluated for transplant and you figure out what their transport, what they're pulling down through resistance was. And so if their group is your they have I'm sorry. Um, group. They were people who had high point vast resistance. And even with not your press side, you cannot reduce their ploy vast resistance to less than 2.5. It just stayed high regardless of what you did were regardless of does not propose side. The second group is you are able to reduce the podcast resistance to less than 2.5. But you you did it at the expense of hypertension. You drop the systolic blood pressure less than 80. That was the only way you can get your polio vast resistance less than 2.5. Third group is they were reduced. The podiatry resistance was high baseline. You were able to give them that your press side To reduce your point gas resistance or less than 2.5. But you're able to keep the systolic blood pressure greater than 80. And and then the last group or a group with normal point pressures at baseline. So if you look at the data, People with normal ploy investor existed at Baseline. So the PBR is less than 2.5 or people who had an elevated for a vast resistance. Um, but were you were able to get their point vast resistance less than 2.5 without developing hypertension? Their prognosis um after transplant was quite good. People who you were not able to reduce your podcast resistance to less than 2.5 Or you're able to reduce it to less than 2.5 but at expense of blood pressure, those people had quite high three-month mortality. So during the evaluation phase where we're looking at patients, these two groups, so people with high pressures that we cannot clinical or fixed point hypertension, we cannot drop their pony artery pressure. Um Or drop the point just resistance. Or we were only able to do that at the expense of their systolic blood pressure. Those are the people that we're looking at, Look if they're if they're transplant candidate, we need to ensure that we can treat the polling hypertension adequately. Those are people that would put Uh a durable l bad a ventricular assist device to co two fully unload their left ventricle or maybe use a blue pump or impeller or something like that to see if we can drop the port of investor resistance, drop their transport ingredients at least acutely. These are people who really if they do have priests severe point hypertension. These are the folks that we tell them we're going to try to see what we can do to reduce your primary pressures. But if we're not successful you're not gonna be able to transplant. See So a lot of discussion there. But basically the data bears out that if you're if you're able to at the time of transplant, if you're pulling vast resistance is less than three. Your survival post transplant is significantly better than if you're greater than three. And most of that mortality is early on because of acute right failure, right heart failure. People that we transplant with very high pressures. There, right interval will fail and there three and six month mortality is quite high. So most of the mortality is very early post transplant. If your transplant, somebody with severe hypertension, the new right vegetables just fails. Yeah. Um, so how much money hypertension is too much? You know, that's a moving target. Um, uh, we're really concerned when deployed bastards instances more than 4-6 would units Transport rate is greater than 15. You know, stock point pressure is consistently in the 60s and regard regardless of of unloading with medical management with story of natural press side. Um, or even long term miller known they really can't get their point pressure is lower. Those are the people that were really most concerned. Um, and so when do we do right heart catheterizations? We pretty much do right heart catheterizations on everybody during their transplant evaluation phase. Um if you had demonstrated elevated homemade pressures and you're listed for transplant, we're usually going to repeat the right hard cap every 3-6 months. Or if there's a change of symptom metrology, Anyone with the pulmonary artery systolic pressure greater than 50. Um at baseline or transported greater and greater than 15 or PVR greater than three. We're gonna give them basil dill laters to try to see sodium natural press side. In particular to see if we can't uh to see if there is opportunity to basil dilating to normalize or at least get the public pressures towards normal. And if not, then we need to think about the triple cyst devising plantation or something else to see if they can be fully unloaded. What happens to the coming pressures two. So going back to the questions so holy mass resistance is not reversal because of transport rate is too high. And hopefully I've demonstrated that there is no transport rated that's too high. That you can't really try to see if you can drop the vast resistance intravenous for us. And I will lower the poor bastards instance remember forecasters since it is the transported gradient which is the main ph minus the wedge divided their critic output. Intravenous feroz bhai usually won't decrease the point mass resistance. It will decrease pre load but it really doesn't affect pointcast resistance very much. So it will drop your right atrial pressure but maybe not necessarily the rest of the bachelor church blood pressure is to lotus at the point of resistance. Again, I think the example of blood pressure is one oh five. Again um if your blood pressure I would say it's above 90 systolic then, especially if you do the calculation the baseline point. That's resistance of your baseline systemic vascular resistance is quite high. Then there's an opportunity to lose now cross the intersection, lower polling pressures. And then this is the math question nowhere. No, will lower the poor bastard existence by increasing cardiac output. That's true. Remember, because going back to the formula podcast, resistance me ph my cell was divided by car to complement. So if your cardiac output goes up because of math reported as resistance work. So the answer is no where no lower support and resistance by the increase in credit card just now. So what are the indications? So we kind of talked about, you know, people with refractory um symptoms despite optimal medical therapy that includes it's not only heart, their symptoms with people intractable angina and tracking of ventricular arrhythmias that are not amenable to revascularization um or or and uh huh ablation. If you're talking about ventricular arrhythmias Um if your vo two max is less than $14 per kilogram per minute or less than 50% predicted, that's an indication. You know, just because your ejection fraction is low, just because your your heart association classes three or four doesn't always mean that you need them. You really need to do something functional study determined whether or not they would benefit from survival standpoint from a transform transfer. There are some sort of contra indications um you know, certainly people with malignancy, people with any systemic illness with a life expenses see less than two years or so. Uh People with irreversible riedel or hepatic disease would be a communication to heart alone. Although consideration could be made for a combination of hard, dedicated transplanted heart and liver transplant. Those are gonna be people who are more physically fit because it's a bigger surgery. People with severe COPD a relative contraindications really from a culinary standpoint or they're going to be a pulmonary cripple after, you know, do a heart transplant, but there remain on the bed because they have bad lung disease. Those are sort of things to keep in mind and really other sort of systemic diseases that would decrease survival. Um, uh, and worsening outcomes. I think those are sort of relative communications, active smoking, um, active substance abuse. Those are contraindications also. Uh, somebody who does not have an adequate caregiver plan, who has limited psycho social games are certainly not a good candidate for transplant. And, and so it's more than just the medical thing that's also how much support do they have. Um, are they able to um, manager a complex medical regiment? Those are all indications, contraindications or things that we sort of look at determining whether or not someone could sort of handle and manage transfer. Mhm. As far as age goes, we sort of talked about, you know, I would say anyone under the age of 70 should be considered. If you're above 70, it could be uh individualized. We've had really great success in transplanting. Some selective patients above the age of 70. More and more programs are using age 70 as a cut off to using ventricular assist device implantation for destination therapy. So many, many programs will use age as a reason to put destination L. Bad somebody rather than transplanting them, Optimal. Body mass index is less than 35. Although uh less than 30. Although there although being my greater than 35 carries excess mortality. And so from the heart transplant world being my, less than 35 is is considered uh sort of acceptable but optimal certainly is being my listener. Oh, so during our evaluation it's pretty much a history and physical looking to see if there are any contraindications that would um influence survival or outcomes after transplant. We looked at even the compatibility or a. B. O. See if they've developed tissue antibodies in the past. Really look to see if there's any other signs of organ injury, kidney, liver uh, vasculature, crowded arteries, um any signs of malignancy, malignancy, screening, psychosocial evaluation, all those things our go into part of the evaluation process. And so in simple terms when I talk to patients for the first time and they come to us determine, you know, do you need a transplant? Yes or no. I tell them it's too simple but very involved questions. The first question is, do you really need a transplant? Yes or no. And so part of that is, you know, have they been optimized medically? Have they been um are there any surgical alternatives? Are they accounted for mitral valve repair? Um uh If that's what's necessary, Do they need high risk revascularization? Um Do they need perhaps better controlled arrhythmias? Um uh Have they been um uh optimized from cycles from lifestyle standpoint? They limited their fluid intake or they're exercising, you know, things like that. So, you know, staying. Are they have you done everything you can to put yourself in the best situation to succeed? And then when you do that, do you still need a transplant? Yes or no? Based on what we've talked about vo, two max, exercise capacity, recurrent, possible. Ization, things like that. So that first simple but very involved question. You know, do you really need a transplant? Yes or no or or l that or other advanced hard labor camp. And the second question is also simple but very involved. Is are there any things that will interfere with your ability to be successful after a transplant results? Is there anything that that would interfere with your ability to successful? So for example, it's as simple as you don't have a caregiver plan. You don't you can't you cannot manage a complex medical regimen. Or you know, do you have a malignancy or do you have any other um uh condition that would limit your survival? Or is your B. M. I. 40? And we know that the amount of 40 carries excess mortality transfer. So those things, so those are things that we look at from the very initial evaluation the very first time we see them is do you really need a transplant? Can we optimize your medical therapy? And then why we're doing that? Is there anything that I see during the initial screening that would make me concerned? Are you actively smoking? Uh Is your is your are you morbidly obese? Um do you have a malignancy? These are things that from the first time that we see them we're sort of going through our minds to say is there something that we need to do to uh to get those things in order? Because sometimes some of these things take time like slogan secession. They take some time wait last night saying take some time. So what you don't want to do is you optimize the medically do their vo two max and say oh we should evaluate for transplant. Oh you know what, we should have told you a month or two ago that you need to start losing weight. Or we should have told you a month or two ago, you just smoke. So those are things are all happening simultaneously, and we try to do that in a multidisciplinary fashion.