International Position Statement on New Concepts and Advances in Multimodality Cardiac Imaging

Podcast Transcript

Announcer:

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

Allan Klein, MD:

My name is Dr. Allan Klein. I'm the director of the Pericardial Center at the Cleveland Clinic. I'd like to introduce my colleague, Dr. Tom Wang, who works with me in the Pericardial Center. And we're pleased to discuss this latest document entitled Pericardial Diseases: International Physician Statement on New Concepts and Advances in Multimodality Cardiac Imaging. And we're very, very excited about this document because this is a document with 22 experts all around the world that came up with a position statement about pericardial diseases. The only thing out there was back in 2013, which I wrote for the American Society of Echocardiography, and more recently in 2015, European Society of Cardiology has a document. This is the latest in North America concerning pericardial diseases. And I want to ask Tom, how did this document come to fruition?

Tom Kai Ming Wang, MBChB:

Yes. About two years ago, we were invited by the American College of Cardiology Imaging Section, as well as the JACC Cardiovascular Imaging Editorial Board to come up with a state-of-the-art article on pericardial disease, which is a very hot topic due to the increasingly seen clinically advances in multimodality imaging as well as the novel therapeutics of this condition. So therefore, we set out to invite 22 experts around the world and also being endorsed by the ACC Imaging Council and the Society of Cardiac Magnetic Resonance to coming up with this document. It's really a tool to force effort from everyone on board over the last two years to finally get this published earlier this month.

Allan Klein, MD:

So I think this field is making a new renaissance. Pericardial diseases have been around for a long time, but currently with this document it shows how we've come into vogue in terms of diagnosis. Now we have advanced imaging. Multimodality imaging can diagnose pericardial diseases and particular acute and recurrent pericarditis, constrictive pericarditis. And now we have new targeted therapy, so called IL-1 blockers that can treat very precisely the inflammation in pericarditis. So this is a major advance and this document really outlines a paradigm shift in the management and diagnosis of pericardial diseases. Tom, maybe talk about advanced imaging, multimodality imaging in this disease.

Tom Kai Ming Wang, MBChB:

So cardiac imaging is the cornerstone in the evaluation, diagnosis, risk stratification, and also monitoring response to therapies for all types of pericardial diseases. So broadly speaking we are looking at pericardial inflammation, whether it's acute, recurrent or chronic. We're looking at pericardial effusion. We're looking for pericardial constriction as well as pericardial masses in congenital anomalies. So the three main cardiac imaging modalities that are used in pericardial diseases is starting with the first line, echocardiography. Followed by the second line, which is a more comprehensive assessment with cardiac magnetic resonance or CMR. And also with supplementary support from cardiac CT.

Each of these modalities are widely used and have their strengths and limitations. So for example, echocardiography is the first line imaging modality that's traditionally used. It's most accessible, the cheapest, portable. And it's very good at assessing, for example, pericardial effusion, size of effusion, also signs of tamponade and signs of pericardial constriction. On the other hand, cardiac magnetic resonance, the main benefit of CMR is in the tissue characterization. So we can see pericardial edema on the T2 STIR sequence, pericardial inflammation on the late gadolinium enhancement sequence, preferably with fat suppression, and also with a new qualitative grading criteria that we've supplied in this document. So using a combination of those, we can assist the severity, risk stratify and predict how long treatment is anticipated using CMR and also for serial monitoring. And then lastly, CT has some use, for example, in identifying pericardial calcifications as well as preoperative management. So I'll let Dr. Klein talk to us about what are the main management strategies for pericarditis.

Allan Klein, MD:

In 2015, the Europeans came out with a stepwise approach to treating pericarditis, acute and recurrent pericarditis. And traditionally you go the first line with NSAIDs and colchicine. Sometimes you give aspirin instead of the NSAIDs and exercise restrictions. So that's the first line approach and that is given quite often. And then in this older paradigm, the next line would be low-dose prednisone, low-dose steroids. And then the third line would be things like what rheumatologists give, things like azathioprine, IVIG or biologics. And the fourth line would be a pericardectomy.

So from our studies with the RHAPSODY trial, which looked at an IL-1 blocker called rilonacept, which is the IL-1 alpha beta trap, IL-1 blocker so called, this showed that it was very useful in treating the recurrent episodes, decreasing the number of recurrences and allowing patients to get off steroids. So in this document and from the RHAPSODY trial, we have shown that instead of giving the steroids, perhaps the second line should be IL-1 blockers. So this is a major paradigm shift.

We look at patients whether they have an inflammatory phenotype, whether they're inflamed. For example, if their CRP is elevated or the sed rate is elevated. Or in particular, as Tom mentioned, the MRI as an imaging biomarker if it shows a lot of swelling around the heart or a lot of inflammation. Then definitely instead of the steroids, go with the IL-1 blocker. If you don't have the inflammatory phenotype, then it's more empiric therapy, maybe low-dose steroids would be the next line.

And if you fail that, then in centers of excellence like Cleveland Clinic, you could consider radical pericardiectomy. So it's a major shift in management with the combination of imaging and now therapeutics. People are coming from all around the country to see us here. This document really lays out different easy to follow algorithms in terms of the treatment of pericardial diseases.

Tom Kai Ming Wang, MBChB:

So the document in particular, some of its strengths is preparing these algorithms both for diagnosis and for management of the variety of pericardial conditions. We also give some recommendations in terms of which imaging modality is recommended, reasonable to consider or not recommended, as well as which treatments first line, second line in terms of all of these conditions. And maybe Dr. Klein would also want to talk a little bit about the multidisciplinary nature of managing this condition as well as the Pericardial Center of Excellence.

Allan Klein, MD:

Tom, that's a very good point. The Pericardial Center of Excellence where a patient can come to such a center and see the cardiologist, perhaps spend one to two days and then see a rheumatologist to make sure there's no autoimmune etiology. Collect samples of blood to analyze inflammatory factors or autoimmune factors. Get involved with research projects. See a surgeon, even have a CAT. So basically one stop shopping and at the end of it all, they come back at the end of the day and they're given a report. So this is that concept. So you need a multidisciplinary approach for this. So this is quite unique. And then we are encouraging this approach.

Patients are coming far and wide with difficult to treat pericarditis. I should mention, in the community, patients often take six months to a year to come here. They've had multiple recurrences, there's a lot of morbidity, a lot of chest pain, and it's often under-treated or misdiagnosed in the community. So they come here and we are very objective about it. We are looking at the lab test, we are looking at their MRI, looking at their echo and coming out with a plan. So once they come here to the center, we do have a follow-up every three to six months they do come back. We follow their inflammatory markers. They may have an MRI once every six months to one year and we follow along. Often they even want to take the picture of their MRI because they're very distressed with this chest pain and they want to see that the inflammation is getting better over time. I should mention this is a long-term disease. This is a chronic disease and often it could take up to three to five years to treat.

Now in terms of testing at a center like this, not all testing is equal. We use a pericardial-specific MRI for this. So often the MRIs in the community may not be as focused on pericardial diseases. These are very complex patients. And what do you think about the COVID era or vaccine era with people coming and they may not have pericarditis? Any comments?

Tom Kai Ming Wang, MBChB:

That's right. So that's a good question. So the first thing to say is that chest pain is a very common reason for presenting to the ER or seeing your primary care doctor. And pericardial diseases is probably the second commonest cardiac cause or heart cause for chest pain. So it's important to tease out what is the cause for chest pain, whether it's from the standard coronary artery disease, whether it's from pericardial disease, another heart cause or even a cause outside the heart. And we are seeing probably about one in five patients coming referred to us with chronic or recurrent pericarditis, which we actually find they do not have pericarditis. So they may have been mistreated or misdiagnosed as something else. But occasionally we can also see the opposite where patients coming here for chest pain of unknown cause and they have not been assessed for pericarditis being the cause. And early treatment, identifying the right patients and targeting them is what's going to lead to better outcomes and hopefully a shorter duration and burden of diseases and complications associated with pericarditis.

Allan Klein, MD:

And I'd like to emphasize the imaging-guided approach, imaging-guided therapy. So for the first time, we can actually, from the first visit when we look at the advanced imaging, particularly MRI, we can assess based on the degree of inflammation and edema, how long it's going to take. Often it could take up to three to five years, how many recurrences the likelihood of going on a biologic, even the possibility of pericardiectomy. So from that first visit, from a good testing and good clinical history, it can tell us how long.

Now on the other hand, as Tom mentioned, there are people, you don't find anything there. And also the misdiagnosis in terms of the clinical criteria for pericarditis, let me just go over that very briefly, is pain when you take a deep breath. Now a lot of people have different reasons for that, so that's sometimes tough to say. A pericardial effusion, new or worsening pericardial effusion. That's fluid around the heart. People mix up the fat around the heart with the effusion. So that could be a misdiagnosis. The EKG often looks like a heart attack. ST elevation, PR depression. But a young person may have what you call physiologic ST elevation. So that could be a misdiagnosis.

And finally, listening to a pericardial rub, like a rubbing sound is very, very difficult to hear. Now objectively, you look at the blood test, the CRP, and then you have the MRI. So we're trying to be a little more objective because the clinical criteria are a little bit soft. So sometimes it's a tough diagnosis to make.

In terms of causes that we see, I should mention the most common cause would be viral or idiopathic. Idiopathic, we don't know exactly the cause, but we assume a virus. It could be a flu virus, it could be COVID, it could be the vaccine. But viral would be the most common. If you live in developing countries, it could be tuberculosis. But a leading cause now is post cardiac injury syndrome and maybe Tom, you can comment, what do we mean by post cardiac injury? What type of things cause that?

Tom Kai Ming Wang, MBChB:

So this is definitely a rising cause for pericarditis in a significant minority. And it basically can stem from any type of cardiac procedure a patient has, especially cardiac surgery. But also electrophysiology procedures like pacemakers and device ablations, coronary stent procedures and so on. So any procedure that can either go through the pericardium or interfere with the pericardium can lead to pericarditis. So this has become increasingly common as we do more and more cases and to treat these patients earlier is very important so that they have a good recovery. The other main causes of pericarditis that we are looking into firstly is autoimmune-types pericarditis. Conditions like rheumatoid arthritis, SLE and so on. And of course there are the other infectious causes as well as metabolic causes and malignancy related causes.

Allan Klein, MD:

The other thing I'd like to mention is about precision guided therapy with IL-1 blockers. So in the community or what's available in the US would be an FDA approved drug. As I mentioned, rilonacept, which we did the RHAPSODY trial. So that's available. It was approved in 2021 and we were one of the leaders, I was the PI for that trial. There is another drug that's a little bit off label called anakinra that's available. These are called IL-1 blockers that show tremendous benefit in treating the acute recurrence, decreasing the number of recurrences and perhaps getting off prednisone in these patients. So this has made a major advance.

Let me start with the anakinra. That's an IL-1 alpha beta blocker, and it's a very short acting type drug. It's a given once a day subcu, and it's given daily. And you take it for at least a year and then you gradually taper, then rilonacept. It's given once a week after a loading dose, and you give that for more than a year. Now we’re working on how patients need to take the drug and at this point we're learning how to come off that drug and deciding whether to stop it or taper it. So that's ongoing research. So this is what we call precision-targeted therapy. Now we think of pericarditis as a very personalized disease. So there's personalized treatment with the imaging and targeted therapy.

Tom Kai Ming Wang, MBChB:

So the key parts with these IL-1 blockers, just to emphasize the advantages is that compared to prednisone, which is the traditional treatment, they are far fewer side effects. So the main things to watch out for are injection site reactions and a slightly higher increase of infection. So it's important that before you start patients on these medications, you should screen for whether they've had any prior important chronic infections such as hepatitis, HIV and TB. But really these are injections that are administered subcutaneously and they can avoid a lot of the concerns in the chronic side effects that prednisone used to have.

And the main issue of course, as Dr. Klein has discussed, is that we're working on is how long do patients need to be on these medications and how should they should be weaned off as they should be considered just like other chronic inflammatory disease, which could be long term. So these are all important things to consider and is all summarized nicely in this document, which has been published earlier this month. There's associated algorithms. We talked about there's online videos showing illustrative cases of these on the website and you can review that. It's been a privilege for me as the vice chair. And Dr. Klein is the chair of the steering committee for this document. Thank you for your attention.

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