Prof. Daniel Lenihan:

Well, thank you everyone. This is Daniel Lenihan. I am a cardio-oncologist at St. Francis Healthcare in Cape Girardeau, Missouri, in the United States. And it’s my great honor and pleasure to be with Raul Cordoba and Iskra Pusic for our VJHemOnc presentation. And we’re going to be talking about cardio-oncology or cardiac safety and hematologic conditions. And Raul, I wonder if you could introduce yourself?

Dr. Raul Cordoba:

Thank you, Dan. Hello to everybody. My name is Raul Cordoba. I am the Associate Chief of Hematology at Fundación Humanidad University Hospital in Madrid, Spain. And I am very interested in cardio-oncology, not only in the classical heart failure induced by anthracyclines, but also in cardio-toxicity of other drugs that we are now seeing in our daily clinical practice. And thank you very much for the invitation.

Prof. Daniel Lenihan:

Thank you so much Raul. And Iskra, please introduce yourself. Iskra and I go way back, so it’s great to see you again.

Dr. Iskra Pusic:

Yes, very nice to see you. I am Iskra Pusic and I’m an adult hematologist and I treat primarily hematological malignancies with a particular interest in transplant and graft-versus-host disease, and then long-term post-transplant complications and survivorship. And I lead a graft-versus-host disease clinic here at Washington University in St. Louis, Missouri, United States. But you can also hear I have an accent, so I’m originally from Croatia.

Prof. Daniel Lenihan:

Fantastic. Thank you all so much and let’s jump right into it. But one of the main motivations to talk about these things is, and you all are certainly aware of the European Society of Cardiology 2022 guidelines for cardio-oncology. Honestly, I believe it’s been one of the most downloaded articles, certainly in ESC history. I don’t know if that’s a fact or not, but I know that the number of downloads of that guideline is really incredible, well into the hundred thousands or more. But nonetheless, I’m still not really sure that any of us really understand all the things that are in there because it is quite long and very definitive.

One of the things that we wanted to talk about today is not only the awareness of the guidelines in general, but understanding the cardiovascular risks and cardiovascular toxicities associated with hematologic malignancies and their treatment. And the real basic point is, how can cardiologists and hematologists provide the best care by having a collaborative practice? I think that’s really the purpose of our conversation today. I would just ask Raul, how do you see that in general, how do you engage with cardio-oncology in Madrid, for example?

Dr. Raul Cordoba:

Thank you for your question. I think that we have to work in very close collaboration with national societies, and I’m going to provide with two examples. The first one is the collaboration with the Spanish Society of Cardiology. They have translated the ESC guidelines into Spanish and it has been uploaded in the web page of the Spanish Society of Cardiology. And at the end, it helps when you are facing a very huge and large file with more than 130 something pages, it can be tough. If it’s translated into your local language, to me, it’s more easy to face that. And that task was done by the Spanish Society of Cardiology and of course it was of help to disseminate the information and all the knowledge all over the country.

And the second link with national societies is with the Spanish Society of Hematology. As we were very interested in covering this topic, the National Society of Hematology organized a workshop in order to translate this information and to collect the information that would apply only to patients with hematological malignancies. And when a hematologist faces the entire document, if we are going to read a lot of things related to solid tumors, we are going to escape reading it. And probably we have to make a summary to sum up the most relevant things that apply to hematology and that’s something that we did in the Spanish Society of Hematology. Probably my advice to other countries or societies is to involve the ESC-ICOS to National Society of both hematology and cardiology in order to disseminate these guidelines.

Prof. Daniel Lenihan:

Yeah, no, I’m sure that’s a critical piece to make sure that people that you work with on a day-to-day basis can actually utilize the information. Iskra, how do you see that? You and I have worked together before, so I can speak about it from my perspective working with you, but how do you see that working with other cardiologists or cardio-oncologists in your practice? How do we get the information that’s in the guidelines into actual use or how do we actually help these to improve patient care? How do you see that?

Dr. Iskra Pusic:

I absolutely agree with what Raul says. I think that it is crucial to raise awareness and include not just societies of cardiology, but hematological societies that can reach a wide brim of oncologists and hematologists who are practicing. And I know we have recently done it here by involving the colleagues from American Society of Transplantation and Cellular Therapy, which is ASTCT, and then American Society of Hematology, ASH. And I know that within both of these societies, there are very active groups of people who are interested in cardio-oncology, who are interested in survivorship. I belong in a survivorship group with ASTCT and also there are groups working on developing practice guidelines.

And I think that with our better techniques in treating cancer, we do two things. We transplant, or even treat for any cancer, more older population and population that is then at risk for other comorbidities. And also we use a wide variety of new drugs, a lot of targeted therapies that have just very complex side effects. And with all that, I think a significantly larger population of patients are going to be at risk to live longer and then be able to develop some of these side effects, but just also a whole variety of new adverse events with these drugs that didn’t exist before. Within all these societies, as I said, there is a very active group of people who are researching that and developing practice guidelines.

Prof. Daniel Lenihan:

Super, very important comments. I think that the other really major point that I would say the guidelines emphasized a significant portion is about risk assessments. If you have a person that has CML or CLL or some hematologic malignancy and you’re contemplating what’s the best therapy to deal with their cancer, there’s that piece. But how do you address cardiovascular issues that may be coexistent at the time that the diagnosis is made? Or as you’re going along with treatment, you suddenly encounter a particular cardiovascular problem where you might’ve been able to identify that at baseline. I just wonder how do you guys approach that? Raul, what do you think about that?

Dr. Raul Cordoba:

I think we hematologists are very pretty much aware of the cardiovascular toxicity of the drugs that we use and prescribe to our patients. But to me, despite this awareness, we have to do better because I think that the patients that we usually refer to the cardiology clinic are those patients who had already had cardiovascular disease and acute myocardial infarction or severe valvulopathy. And we are not used to refer patients at high risk, but without a prior cardiovascular disease. Probably we will have to work based on the guidelines on the identification of these patients at high risk. And I think it’s one of the strategy that we have to work in the national societies of hematology because at the end, the patients are in the hematology clinic, not in the cardiology clinic, and we are the one to refer the patient to the cardiology clinic. Probably we will have to work closely with the regional and national hematology societies in order to identify better those patients at high risk and not only those patients with prior cardiovascular disease.

Prof. Daniel Lenihan:

Iskra, if you have a patient that you’re about to begin either a traditional hematologic treatment or perhaps even a stem cell, how extensive do you do cardiovascular risk assessment and do you feel comfortable doing that yourself or do you get help from your colleagues?

Dr. Iskra Pusic:

First wanted to add, I wanted to say is that the same factors often in many cancers that increase the risk of heart disease such as high cholesterol or hypertension or being overweight or inactive or smoking. All these factors also increase the risk of cancer, and they’re often intertwined. But I think that frequently when somebody is diagnosed with cancers, we tend to put this as a priority and other things tend to go on a back burner. And it depends on what kind of cancer and what kind of treatment we are planning, but ultimately I do think that we need to be more proactive and think ahead, what are we going to do and what can we do to optimize the heart function so that we don’t run into problems later as a consequence of our treatment?

But that will depend somewhat what is the urgency of the treatment we need to do. And some situations might require an urgent start of chemotherapy such as, let’s say, acute leukemia with high white count. While in certain other situations we might have little more leeway to do better optimization upfront. In example of transplant, we have certain procedures such as cardiogram, EKG, chest x-ray, which are quite baselines that we will do. And if all is normal, then we are not going to do additional cardiac evaluation and we will usually stop there. On the other side, if somebody has some pre-existing cardiac conditions or has some other risk factors, we will then reach out to our colleagues from cardio-oncology and try to involve them before we start treatments.

Dr. Raul Cordoba:

Dan, to answer your question, I think we don’t do in a structured way.

Dr. Iskra Pusic:

Correct.

Dr. Raul Cordoba:

We collect information and we make the decision to refer the patient to the cardiologist, but not in a structured way, so probably we will need to work on that. We have to create the awareness of tools that may help us in order to identify these patients at higher risk, for example, the HFA-ICOS tool to identify those patients at high risk. I think we hematologists have to work to do things in a better way. Probably one task of our societies is to disseminate these tools that are there to help us to do our job in a better way. But I would say that in most of the cases we are the hematologists that we check for the risk factors, but not in a structured way.

Prof. Daniel Lenihan:

Yeah. Let’s take a couple of examples of just not only what’s in the guideline, but how does this affect the practicality of treatment? For example, if you have a patient with CLL that you want to treat with whatever you think is the best initial therapy, if you knew that they had, say for example, a history of bleeding or a history of high blood pressure that was difficult to control, would that influence your choice in terms of what drug you would use?

Dr. Raul Cordoba:

Yeah, definitely. We check for all the possible adverse events that the new targeted therapies may use in our patients in order to reach out the final treatment decision. If we are thinking about a BTK inhibitor to treat the CLL, for sure, now we are following the guidelines with regards of electrocardiogram and an echocardiogram. And if we find any abnormality, we refer the patient to the cardiologist in order to have the clear out of the patient to be treated safely with a BTK inhibitor. And of course, we take into consideration all this information before checking the final decision of the treatment strategy.

Dr. Iskra Pusic:

I can also give you another example since you mentioned CLL, another chronic leukemia, CML. We just recently had a patient who was a relatively young person, in their 40s, who was diagnosed at the same time with CML, with the white count way over 100,000, and also with quite severe aortic stenosis. And we have communicated a lot and just between our team from oncology and our cardio-oncologist here to discuss what to do and what should take a priority, starting the treatment for CML or doing valve replacement. And in the end, the decision was to lower the count with hydroxyurea and then proceeded with fixing the heart first. But then after that this person will require anticoagulation with Coumadin. And then the discussion was, what would be the best TKI to use in that situation? Because some TKIs, as we know, have cardiac risk factors, some can make you more prone for bleeding. This was very complex decision which required just input from different sides.

Prof. Daniel Lenihan:

Yeah, no, I think that is a great example and needless to say, I think that one’s pretty challenging. There’s a lot of considerations one way or the other. Do you initiate treatment for the hematologic condition or is the aortic valve disease so critical that you need to address that first? Wow, you really have to personalize that one. And I suppose that’s a good way of how do you build a team to address these issues? Obviously in your straight-up, straightforward patient that maybe just has a diagnosis of CML and it’s not an acute problem, it’s a chronically developing problem, and there’s no urgent need to address the problem from a cardiac point of view, you would probably just initiate your CML therapy and go on and see how it goes. Whereas if the cardiac issues are so severe that they have to be addressed, then how do you build a team approach to these types of questions? Raul, how do you encourage those connections a priority with your patients?

Dr. Raul Cordoba:

I think that one of the success of these multidisciplinary teams is the tumor boards or any regular committees with regular meetings. In many, many centers, I’m not sure in all of them, but at least in the large academic centers we have tumor boards. We are used to meet in a regular basis, in my site every week, with all the healthcare professionals that are involved in patients with specific cancer subtypes. In my case, I am a hematologist that treat patients with lymphoid malignancy, so we have a lymphoma and CLL tumor board, and we are used to meet every week to discuss every single patient.

I think it was a very good step, at least in my site, and it can be an advice for other sites to reach out the cardiologists and to invite them either to join to our lymphoma tumor board or to create a new tumor board just focused in cardio-oncology. And at the end, it’s a question of agreement with the cardiologists if they want to join to the more broad tumor board or to a specific one. And in our case, if there is a patient with a very complex situation, we invite the cardiologists to the tumor board only if a patient is going to be discussed with a cardiac abnormality. But we are now just starting a cardio-oncology tumor board just to discuss and to learn from each other. Because at the end, cardiologists must learn from us, from the hematologist and the other way around. And to me, the only way to learn is to mix in a meeting and to discuss and to learn from single cases.

Prof. Daniel Lenihan:

Well, I totally agree with that. And at St. Francis, they have a weekly tumor board, and I participate in that. And to me, it’s essential. I learn a ton just from listening to you guys discuss what your options are, but then also where imaging is shown or complex problems are discussed, you can provide a cardio-oncology opinion right then, and that would influence how the care goes in those patients. I think that’s a critical step. I agree, totally. Iskra, I know-

Dr. Iskra Pusic:

Another thing I wanted to add to that is that I agree with everything you said, however I also think, and my experience here at WashU has been that often these cases happen, and today you have situations that you need to resolve. And that our team here, our cardio-oncologists, have always been very receptive and I can call them and I will receive the email probably within an hour, and they’re going to go and see the patient and help me in decision making. This two-way communications that can sometimes really needs to happen quickly is really important.

Prof. Daniel Lenihan:

Oh, for sure. I was just going to say that I know that there are probably 10 different tumor boards at WashU and they probably meet every week or something like that. There’s a large volume, so I don’t know if you could attend all of those tumor boards. I think you do have to have a very personal connection. And I would just encourage all the cardio-oncology people out there that you need to respond and you need to respond quickly. And if a patient is undergoing evaluation for treatment of their cancer and there’s big decisions being made, you can’t push that consult off for three or four weeks, the whole story is over by then. You need to address it right away and be an important step in whatever decision is made. Obviously, Iskra, it sounds like you have those connections, so that’s really important to do. What comments would you make besides having, say, cardio-oncology attend the tumor boards? What other tools do you think have been useful in your practices in terms of building a team? How do you engage people actively beyond the tumor board? How does that happen?

Dr. Raul Cordoba:

What we have done in Spain is to set regional multidisciplinary joint meetings and timing with that to invite not only hematologists but also cardiologists. We are not used to attend the same meetings, so we need to organize these joint meetings and to discuss topics that are relevant to both of them, probably with two perspectives. And these regional meetings are working really well, at least in Spain. And I think it’s one of the, I would say, success in order to implement these cardio-oncology clinics all over the country. These joint meetings, for sure, are very, very relevant to create and to generate this awareness.

Prof. Daniel Lenihan:

Super. Iskra, aside from knowing the cell phone of your colleagues, what things that you’ve done that have enhanced your connections? I’m just curious.

Dr. Iskra Pusic:

I have participated in your activities in cardio-oncology and really get to know some of the cardio-oncologists across the country and across the ocean who are involved in treating patients with cancer. And I went to several of cardio-oncology meetings and that has been really invaluable in opening my horizons and just making me aware further of challenges that we face and how to overcome them. I agree that this is-

Prof. Daniel Lenihan:

I totally agree with what both of you are saying. I think the theme for me honestly is we go to… I’m sure you would say a similar thing, if I go to a cardiology meeting, it’s all things cardiology and they go in great depth about different treatments that you might do. But when I go to an oncology meeting, even if it’s a relatively short meeting or even if I participate in the tumor board, it seems like I learned so much and my perspective is broadened so dramatically just from a few minutes. And just engaging in another world is what you’re doing there, and I think by you participating in cardio-oncology meetings, you’re really broadening your view.

And I think it’s certainly the same for us on the cardiology side if we’re considering how this cancer treatment is going to affect the whole body and in particular the heart and blood vessels and how can we manage that? And honestly, from my perspective, it’s usually, what can we do to help this situation out? Because the patient’s already presented with huge challenges and they’re asked to do just a dramatic number of visits and treatments and doctor appointments, etc, etc. You don’t want to add additional cardiology things to it, so how you can manage these things at the outset could be very helpful in the overall patient experience. But so what strategies do you think have actually worked to prevent some of the toxicities? Raul, what things do you guys do to try to anticipate what’s going to happen and hopefully prevent it?

Dr. Raul Cordoba:

Now we are implementing the monitoring of cardiac biomarkers, for example. We don’t have to wait until the symptomatic heart failure, for example, and in our site, for example, if the patient has an increase in the levels of NT-proBNP, it’s one of the reasons to refer the patients early to the cardiologist, despite the patient was not at high risk in baseline, but we know that the risk is continuous. And it’s one of the strategies that we have implemented in our center.

And the other strategy could be, we are working on that, is a patient navigator. In some centers they are very lucky to have a nurse. We have a research nurse for cardio-oncology because we are participating in several studies in cardio-onc, but not in the daily clinical practice. Probably this patient navigator would be of help in order to identify early patients with mild symptoms and probably to arrange all appointments in order to reduce the treatment burden to patients. Probably I would say that these two initiative would be interesting to be explored.

Prof. Daniel Lenihan:

That’s a great point. Iskra, what strategies have you found to be useful from more of a early detection or prevention type of approach?

Dr. Iskra Pusic:

I agree with what Raul said and we implement the similar strategies. I think just the most important thing is to be aware of that and to send these patients early on to be evaluated, particularly if they have risk factors of some arrhythmia or high blood pressure, diabetes, high cholesterol, to be aware that these are the people who are at risk for developing additional toxicities and be proactive in getting them evaluated.

Prof. Daniel Lenihan:

Yeah, I think since both of you are obviously hematologic experts, probably the biggest challenge in the whole cardio-oncology world is the broad view of anticoagulation. Whether that be aspirin, Plavix, Coumadin, as you mentioned earlier, which hopefully we continue to use less of that. But all the DOACs have all these drugs and some of which are really great for prevention of thrombus, but obviously lead to bleeding complications, so this is the most challenging space in my view. Because every person is a little bit different and you can’t just say, oh, I’m going to use Lovenox every time. No, it doesn’t work out that way. Each person has their own different situations, so you can’t make a blanket statement. How do you see that? That may be too big of a question, but how do you manage the whole anticoagulation strategies in your practices?

Dr. Iskra Pusic:

Well, to a certain extent, we all manage it, we all know basics and we all manage it. However, we do have since we are divided a little bit, oncology and hematology, even though I see I’m board certified, but I mostly see hematological malignancies. But we have several colleagues who are specialized particularly in coagulation issues and thrombophilia. And if that is a challenging case that is more complicated, we will involve them and ask them for an opinion how to tackle that.

Prof. Daniel Lenihan:

Raul, what strategies have you found useful in this whole space? And if you could summarize it in one sentence so that I remember it, then that would be great? But that may be asking too much.

Dr. Raul Cordoba:

To summarize in one sentence, hematologists must be trained in the whole spectrum of hematology, not only in hematological malignancies but also in benign hematology. I think it’s more easy for European trained hematologists because we are trained in both sides of hematology. And for example, to me, I am not afraid of facing an anti-coagulation in a patient with a lymphoid malignancy because I was trained on that, despite I have also colleagues that are only focused in coagulation. And I start treating my patients with a anticoagulant or antiplatelet therapy by myself. And only when I am having issues with that, I request assistance of the help of my colleagues. But I think it’s more easy in Europe than in the States. It’s my view.

Prof. Daniel Lenihan:

Yeah, no, that’s interesting. All I can remember is when I was a medicine resident in my third year and I did my Hem/Onc rotation and at the end of my Hem/Onc rotation I thought, oh great, this will be the last time I have to think about the coagulation cascade. Then of course mind was blown when I realized that all of the new drugs have some other target on the coagulation cascade and I’m never going to figure it out. These complexities, they come up every day probably in almost every single patient, so this is not something we’re going to get away from.

Dr. Raul Cordoba:

Yeah, I have to say that the coagulation cascade doesn’t exist any longer. Now we have another model to explain the coagulation, which is the cellular model, and the coagulation cascade is still being taught at medical schools, but it doesn’t work in that way. If you have forgotten it, don’t worry about that.

Prof. Daniel Lenihan:

Yeah, that’s good. But I obviously haven’t learned this new paradigm that you’re talking about, but, no, you can’t get away from it, every aspect of medicine is going to be influenced by coagulation and bleeding. It’s a big deal. And I know that we have lots of collaboration on those decisions.

But one other concept that’s been talked about recently is a concept of permissive cardiotoxicity. I think you could summarize that statement as, we understand that some cancer treatment may have manifestations in the cardiovascular system, but the priority is dealing with a cancer that needs treatment. How do you guys calculate those things? Iskra, you actually brought up a really great example where the cancer was an acute problem, although the cardiovascular issue was quite prominent and then you had to come up with some modified approach to how you do it. Do you have any general way in which you address these things?

Dr. Iskra Pusic:

I wouldn’t say so. I think when we have certain guidelines they are certainly helpful, but often the cases are different and you have to evaluate case by case, and there are going to be situations where you are going to have to start your cancer treatment upfront in somebody with massive leukemia or lymphomas, it needs immediate attention. And then after you cool that off, you are going to start dealing in parallel with cardiac issues, but you might not have a luxury, I would say, to optimize the heart before you start treatment for cancer.

Prof. Daniel Lenihan:

No, that’s certainly the case, especially when you have, in theory, a correctable cardiac issue, say valve disease or critical coronary artery stenosis that you could deal with stenting procedure or something along that line. You could meaningfully change the cardiac condition to put them in a new spot and then really focus on the cancer treatment going forward. I think the most important part about this whole concept is making sure that you have good communication among the experts to come up with the best decision. But yeah, you’re right, every single one of them is going to be personalized to the immediate needs. Raul, do you have any insights as to how you go about making those decisions in Madrid, or what do you guys do?

Dr. Raul Cordoba:

I must say that I was a bit confused when I first read the concept of permissive cardiotoxicity, but Iskra has addressed it very well. We hematologists are sometimes in the need to make up an urgent treatment decision so we are always putting everything in a balance, risk, benefits. And actually, we hematologists are taking risk every day, all the time when we are making treatment decisions. And I think we are used to share this risk with patients and sometimes we cannot wait to make the consultation with the cardiologist and we take the risk after of course explaining to the patient the risk that we are going to take, but we are used to taking the risk.

And of course if we have an urgent clinical situation that needs an urgent treatment, we are going to take the risk and then despite we may worsen the cardiovascular condition and then we are going to take care of this dysfunction but later on, because we have to treat the hematological condition first, I think. What do you think Iskra, I think we are pretty much sure about taking these urgent treatment decisions and to take risks.

Dr. Iskra Pusic:

Yeah.

Prof. Daniel Lenihan:

Yeah, no, I think when you see a patient with an acute leukemia with a platelet count of 20 and you’re wondering what you need to do, you know you need to do something and you’ll get started. Well, this has been really fascinating. You guys have been tremendous and I so appreciate your insights.

I think that we are trying to understand how the ESC cardio-oncology guidelines could be utilized in practice. And it’s one of those things that it’s such a definitive and lengthy document that you can’t absorb it all at once, you have to take bits and pieces. But I would encourage our listeners to look at those guidelines and understand where they could be helpful in your practice. And even if it’s only one figure or table that comes from the guideline, but hopefully that would be of use in the management of patients.

But thank you both so much. This has been really great and I don’t know if you guys have any further comments or what you think is what is our biggest challenge going forward in terms of getting these types of guidelines to be better utilized? Raul, I don’t know if you want to close us out on that comment.

Dr. Raul Cordoba:

I have already said that I think one of the challenges is to spread these guidelines in the hematological and the cardiologist community. And one good strategy is to organize joint meetings, small meetings in order to give voice to all participants. And at the end, if you attend a meeting with your cardiologist or a cardiologist with his or her hematologist, I think it’s a good strategy to start building a multi-disciplinary team.

Prof. Daniel Lenihan:

Super. And Iskra, what do you think our best step forward would be in terms of getting these types of guidelines to be utilized better?

Dr. Iskra Pusic:

I think that making a community of hematologists, oncologists aware of existence of this guidance, so posting them and making them available through some of the websites that we use such as ASH website or American Society of Transplantation and Cellular Therapy. And I know that we have involved both of these organizations in our conversations before and they were active participants in a recent summit. I think that’s the key, to have these organizations that can reach the larger population of oncologists aware. And I agree with having smaller meetings, but I think we are also often oversaturated with meetings and I think that having this being present at some of the larger meetings. For example, I was just recently at this meeting, this biggest transplant meeting and there was presence of survivorship after transplant with long-term follow-up and long-term, late post-transplant complications. I think it’s important to have a presence of these issues also in part of large meetings that will be attended by a lot of people.

Prof. Daniel Lenihan:

Super. Well, thank you both so much. This has been really great and we look forward to future conversations. Thank you.

Dr. Iskra Pusic:

Absolutely.

Raul Cordoba: Honoraria: Janssen, AbbVie, BeiGene, Astra Zeneca, Lilly, Roche, Gilead.