Cardio-Oncology

Podcast Transcript

Announcer:
Welcome to Cleveland Clinic Cardiac Consult, brought to you by the Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute at Cleveland Clinic.

Steven Nissen, MD:
I'm Dr. Steve Nissen and I'm here with two colleagues to talk about the field of cardio-oncology, something that's become more and more important over the last say decade or so. Perhaps each of you could introduce yourself and we'll dive into this.

Rohit Moudgil, MD:
Perfect. My name is Dr. Moudgil and I'm Assistant Professor here in Cleveland Clinic and I've been here for three years. I was trained in MD Anderson for cardio-oncology and that's the specialty I've practiced here the last three years.

Patrick Collier, MD, PhD:
My name is Patrick Collier. I'm a staff cardiologist and co-director of the cardio-oncology center.

Steven Nissen, MD:
You see a lot of cancer patients and one of the questions I think everybody wants to know is when should a patient with cancer be referred to a cardiologist? What are the real issues that people should identify?

Patrick Collier, MD, PhD:
Well, I think Dr. Nissen, it's very clear there's a very large number of patients with cancer. We really don't have the bandwidth to see every patient and I think our job as cardio-oncologists is try and be strategic and try to identify those patients that do need to be seen. Right now, we're focusing on those with pre-existing cardiovascular disease, those with increased cardiovascular risk factor profiles, those who have symptoms and those that may be facing higher risk treatments.

Steven Nissen, MD:
Yes. Okay. That's a very good summary. So, let's take those one at a time. The patient with risk factors, what does that patient look like and what are the risk factors that you want to be identifying in the cancer patient to know that they need a cardiologist?

Rohit Moudgil, MD:
So interestingly, a lot of the cancer patients tend to have the same risk factor that our cardiac patients have. So for example, obesity, diabetes, hypertension, sedentary lifestyle, if there's a strong family history of any cardiac or cancer diseases. Those kinds of things we definitely are looking for the patients so that we can risk stratify them before they go for cancer therapy.

Patrick Collier, MD, PhD:
And Dr. Nissen, this field is expanding so much that we are now beginning to move even beyond these standard risk factors that we know and now we're beginning to think of about things like inflammation, immunity, genetics, and I think the next horizon will be trying to better characterize these patients in those terms.

Steven Nissen, MD:
So development of maybe new biomarkers, part of the strategy to be able to know who's at risk?

Patrick Collier, MD, PhD:
For sure, and I think that really is a key goal because if we can use biomarkers, it really helps us risk stratify. Our problems right now are a lot of these biomarkers are not necessarily specific and they're very sensitive. So, we have to be cautious not to over interpret what these small changes in biomarkers mean. That being said, they look like they do there, they will have a role, but we need to try and tease it out better.

Steven Nissen, MD:
Yeah. So echocardiography is commonly used as a tool here. Which patients undergoing cancer therapy should have an echocardiogram before the therapy is administered?

Patrick Collier, MD, PhD:
Well, I think this remains a controversial area because even amongst the guidelines, there's variants. And I think it depends on where you are treated and how the practice is. I think, in general, we would say that patients who are higher risk who are facing anthracycline chemotherapy should get a baseline study and follow-up studies to make sure they're not developing toxicity. For those agents with maybe lesser toxicity, such as the HER2-targeted therapies, we've really been very, very cautious in those patients based upon the kind of anecdotal and our historical knowledge of how anthracycline exposure has been for the heart. And we've probably over tested those patients. So I think, again, trying to understand the balance of when and where these patients should be tested is controversial.

Patrick Collier, MD, PhD:
Going forward, we have new techniques that can help us. So for example, artificial intelligence is being applied to echo, opening up the area of echo to those maybe novice users and, in the future, I think we may have other strategies to help apply this technology to our patients.

Steven Nissen, MD:
People like me are always think of this as, "Well, you're going to check the ejection fraction and then you're going to look for patients who have a fallen ejection fraction." But there are newer echo techniques. Maybe you could say something about those techniques because I think you're using them, are you not? Maybe gain additional insight.

Rohit Moudgil, MD:
Absolutely. So the thing is what we have identified with ejection fraction from the studies is that when the ejection fraction falls, about 58% cannot come back to the original number. So we have to identify ways subclinically to identify patients who have a decrease in the function, but the ejection fraction that's not decreased.

Steven Nissen, MD:
It's still okay. So you're going to pick up this disorder before the ejection fraction falls because half of those patients, they're not going to regain that cardiac function. So what do you do?

Rohit Moudgil, MD:
This new technique is called a global longitudinal strain. So what we can do is we can identify these small pixels in the heart muscle itself and we can see how they move against each other. And from that, we can ascertain what the function will be in the future and predict that. And if we can identify these patient early on and start them on cardioprotective medication, we may prevent extra decrease in the function of the heart.

Steven Nissen, MD:
And is this being used routinely? Are you measuring strain in everybody or is it something that's being used selectively?

Patrick Collier, MD, PhD:
Really historically, we've been applying it quite broadly in this patient population. I think recent data would suggest we have to be careful. I'm thinking particularly about the SUCCOUR trial, which suggested that the application of strain may be not as efficacious as we thought and may even result in patients stopping or holding their chemotherapy. So it's not without its problems. I think one of the issues we have is inter-test variability with this parameter. You know, just like ejection fraction, these numbers can vary between tests and these patients that are undergoing chemotherapy go through a lot of changes, not just in hemodynamics, but in their fluid status and there are often a lot of confounding issues.

Patrick Collier, MD, PhD:
So understanding differences between testing has historically been challenging. We've relied on early repeat studies if we identify changes and sometimes we need to go to a higher level and, for example, use cardiac MRI. And I think, again, going forward, MRI looks very exciting in its application to patients.

Steven Nissen, MD:
And what is the MRI parameter that you're measuring?

Patrick Collier, MD, PhD:
So I think, again, we do have gold standard ejection fraction with MRI. And I think at the end of the day that's been our go-to parameter with all its limitations. But MRI can go further now with tissue characterization for example and more sophisticated sequences are being developed all the time. I think the horizon looks very exciting in that regard.

Steven Nissen, MD:
But you're not really using those clinically? Those new tissue-

Patrick Collier, MD, PhD:
I would say not clinically, but it looks like soon.

Steven Nissen, MD:
So it's a research tool that is coming close to being accurate enough to use clinically. Now, for people from my era, we understand that these anthracycline drugs are commonly associated and dose-dependent reduction in cardiac function. Are there other specific chemotherapeutic agents where you're going to worry about heart function and where a cardio-oncology consultation might make sense?

Rohit Moudgil, MD:
So right now there's an upsurge of this particular group of medication called immune checkpoint inhibitors. And basically currently about 50% of the clinical trials in cancer are using immune checkpoint inhibitors. And we identify more and more what these things are doing to the heart. So for example, we know it can accelerate your coronary artery disease. We know it can cause inflammation of the heart. We know it can cause electrical problems in the heart also. So as these medications are becoming more prevalent and given to more and more patients, we are actually seeing upsurge of a lot of these cardiac issues that we haven't seen.

Steven Nissen, MD:
And how do you know that the patient is developing these abnormalities? I mean, what are the things you can do to figure out that the checkpoint inhibitor is causing the problems and they need a consultation, and is there a treatment for it?

Patrick Collier, MD, PhD:
Again, its an emerging field and we're learning as we go. I mean, I think as cardiologists, we're certainly learning from the oncologists tremendously. I mean, some of these targeted therapies are identifying new pathways to diseases we thought we knew how they worked, but this is a new biology and it's just so exciting to work in this field for that reason. But getting back to your point, how do you identify whether the treatment is the issue here. Traditionally, when immune checkpoint inhibitors cause trouble, they cause serious trouble. So it's not common, thankfully, but when it does happen, it's very serious. So for example, the myocarditis that Dr. Moudgil mentioned tends to be a very electrically unstable myocarditis that tends to present either with-

Steven Nissen, MD:
Ventricular tachycardia?

Patrick Collier, MD, PhD:
Absolutely.

Steven Nissen, MD:
And so your patient has received a checkpoint inhibitor. Now they've had evidence of myocarditis. What do you do?

Rohit Moudgil, MD:
So right now, the way things are working out is that if they have myocarditis and there is actually a problem with the heart itself, we have to stop the immune checkpoint inhibitor because we have seen patients who continue on immune checkpoint inhibitor can actually accelerate that cardiac problem quite viciously. So we tend to stop it and we try to treat the patients with the cardiac protective medication so that they can benefit from that. And then we try to liaison with our oncology colleagues to see if there's other therapies that is beneficial for the patient while not affecting on their heart.

Steven Nissen, MD:
If you stop the checkpoint inhibitor, does the problem resolve and how long does it take?

Patrick Collier, MD, PhD:
You know, typically not. Thankfully, again, we're talking about a rare situation and these are sometimes very critically sick patients, but traditionally, it's been almost like a rejection type phenomenon we see in the cardio-transplant population. So steroids would be the mainstay of treatment, but now, more targeted T-lymphocyte therapies have been applied.

Steven Nissen, MD:
Yeah. So this is really a very technically challenging area to manage all of this. I know the checkpoint inhibitors have been a game changer for many of the cancers and thankfully the cardiac effects are not seen commonly, but when they are, you're going to have to obviously be engaged and treat the problems. What about drugs like sacubitril/valsartan? Are you using agents like that for heart failure in these patients?

Patrick Collier, MD, PhD:
I think this is a great point that you're raising. What about the application of all these new heart failure therapies that have been so wonderful over the last number of years? The application of this therapy to cancer patients has historically been slow and that's because cancer patients have been excluded from our heart trials. And same way, our heart patients have been excluded from our cancer trials. And I think from our perspective, with a growing number of physicians interested in cardio-oncology, we have to advocate that these patients be included in these trials so we can learn more. There's no reason why these therapies shouldn't be effective in chemotherapy-related cardiomyopathy, but I think the application of them has been slow.

Steven Nissen, MD:
Yeah. I mean, there's been obviously recent data with SGLT2 inhibitors in both HFrEF and HFpEF, so we need to know more, I assume, to use these drugs wisely in the oncology patients.

Rohit Moudgil, MD:
Absolutely. And the thing is then because they are such a rare event in such small institutions all across the world, we are not seeing too many evidence in terms of how these drugs are affecting these cancer patients.

Steven Nissen, MD:
Well, thank you both. It's terrific that you're kind of leading the way towards better understanding. I understand that you have a lot of things you need to figure out in the treatment of heart disease in the cancer patients, but hopefully you'll get there.

Patrick Collier, MD, PhD:
Thank you.

Rohit Moudgil, MD:
Thank you.

Steven Nissen, MD:
Thank you.

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