American College of Cardiology Concise Clinical Guidance on Pericarditis

Podcast Transcript

Announcer:

Welcome to Cardiac Consult, brought to you by the Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute at Cleveland Clinic. This podcast will explore the latest innovations, medical and surgical treatments, diagnostic testing, research, technology and practice improvements.

Allan Klein, MD:

My name is Dr. Allan Klein. I'm the Director of the Diagnosis and Treatment of Pericardial Diseases at the Cleveland Clinic. I'm past president of the American Society of [Echocardiography] and current president of the National Board of [Echocardiography], and it's my great honor to introduce Dr. Tom Wang.

Tom Kai Ming Wang, MBChB:

Hi, everyone. My name is Dr. Tom Kai Ming Wang. I'm a staff cardiologist here at the Cleveland Clinic, associate director of the Pericardial Disease Center, and assistant professor at the Cleveland Clinic Learner College of Medicine. We're both part of the cardiovascular imaging section of the Heart, Vascular and Thoracic Institute at Cleveland Clinic.

We're going to start talking about this very exciting document that came out and was published in August 2025, which is the 2025 concise clinical guidance document on the diagnosis and management of pericardial disease. This is a very exciting opportunity for us to discuss and share our ideas on the latest updates on pericardial disease, as the first pericardial management document from North America. Also, exciting times given the recent publications in this field from here and Europe.

So, Dr. Klein, do you want to talk more about that?

Allan Klein, MD:

Yes, this is a very exciting time. Pericardial disease is an old disease, but there's a new renaissance in the field. Recently, there have been several key publications. Back in 2024, Tom and I were involved with an international consensus on pericardial disease from 22 experts all around the world, and this led to the ACC document that Tom just mentioned. This is basically a concise version, a practical approach for clinicians on how to diagnose and manage pericardial disease. Finally, more recently, in August of this year, the Europeans came out with a guideline on myocarditis and pericarditis for the first time linking both myocarditis and pericarditis.

So, Tom, let me ask you, how do clinicians use all these documents to manage these patients?

Tom Kai Ming Wang, MBChB:

Up until basically 2024, the last guidelines and documents we had were back in 2015 from the European guidelines on pericarditis, and also the 2013 American Society of Echocardiography document, which Dr. Klein led as well. Up until then the management of patients had relied on documents from about 10 years ago. Over the last 10 years, there's been a rapid evolution in terms of the diagnosis of pericarditis, including multimodality imaging, and also a paradigm shift in the treatment of pericarditis.

In this session, we would like to discuss each of these novel aspects, and also perhaps provide some context into what's the similarities and differences between our document and the ESC (European Society of Cardiology) document.

So, a question for Dr. Klein to start with. What is new or the latest in the clinical diagnosis of pericarditis?

Allan Klein, MD:

Well, the first thing, the ACC concise document comes out with a new definition. In the past, they used 2-4 clinical criteria, but now we have equal weight to imaging such as MRI and inflammatory markers such as TRP.

The classic thing would be patients presenting with pleuritic chest pain, often going to the left shoulder. If you have two or more other criteria, for example, a new or worsening pericardial effusion or very abnormal, inflamed pericardium on an MRI, this would be definite. If you only have the pain plus one criteria, it's possible. If you just have the pain, then this is unlikely. This is a major advance to try to get the right diagnosis. That's a major advance in terms of definition.

Tom, how about multimodality imaging? That's another important aspect for the first time we're using multimodality imaging, especially MRI to guide therapy. How does that work?

Tom Kai Ming Wang, MBChB:

Multimodality imaging plays a central role in both the diagnosis evaluation of patients, in grading severity and risk prognostication, as well as guiding treatment and monitoring and surveillance of therapies.

So, to come back briefly to that novel diagnostic criteria, the reason for this change is to ensure that we optimize sensitivity and specificity of diagnosing pericarditis. The concern with the prior guidelines, relying on factors such as abnormal ECG changes and auscultation with the rub and not using lab markers like inflammatory markers or CMR evidence of pericarditis, we feel was inadequate. For example, things like rub and ECG changes only occurred in a minority of patients. Pericardial effusions only present in about 50% of patients with pericarditis. So, you're really relying on just the chest pain component.

Whereas if you add in the inflammatory markers, elevated CRP or CED rate, which is present in 80 to 90% of patients, as well as CMR findings of pericardial late gadolinium enhancement (LGE) and edema, then both of those are present in the vast majority of patients. That really improves the sensitivity and specificity. We've divided that into “definite”, “possible” or “unlikely”.

So, coming back to multimodality imaging for pericarditis specifically, echo remains the first line imaging modality. To assess this at the bedside, you want to look for pericardial thickening, presence of pericardial fusion, presence of constrictive physiology. But remember, echo could be normal in half of these patients and that's where cardiac MRI comes in. On cardiac MRI for looking at pericarditis, it's critical that we do the pericardial late gadolinium enhancement sequence to look for late gadolinium enhancement, preferably using fat-suppressed sequences so we can distinguish pericarditis from its great masquerader of epicardial fat, and also edema sequences, T2-STIR for example, to look for pericardial edema.

From that, we can then introduce two important concepts for CMR evaluation of pericarditis, the first being grading the severity of pericarditis. What we've found is that we've developed this new five-point tier grading criteria from none, trivial, mild, moderate, severe, based on three components of pericardial LGE analysis.

So, that includes, firstly, how circumferential the inflammation or enhancement can be seen on LGE. If it's completely around, it's considered the halo sign. Secondly, how many levels – base, mid or apex – of the short axis do have pericardial enhancement. Thirdly, how thick the pericardial enhancement is. That's the first important novel criteria that is only in this document in the position statement, but not in the ESC criteria for grading severity, and we have several observational studies to show its importance in risk prognostication.

Dr. Klein, do you want to talk a bit about how CMR is helpful for staging pericarditis in terms of from early to late?

Allan Klein, MD:

The first thing is that when we see a patient with pericardial disease, we decide where they are on the spectrum. For example, if you have acute pericarditis, in particular, advanced imaging such as MRI will light up. You'll have this halo sign, the late gadolinium enhancement (LGE), which usually implies neovascularization, inflammation. Then, you'll have edema, swelling in the pericardial space. Then over time, you'll see that the edema disappears, LGE will remain, and then over time the LGE would disappear and eventually we will have calcification.

So, we decide where you are on the spectrum. The MRI basically guides the therapy. If you come in with acute or recurrent pericarditis and everything is very positive, the MRI is very positive, you can predict that this will take perhaps three to five years or longer to heal. It'll be a little bit of a rocky course. It will also guide you in terms of perhaps what therapeutics, and we'll get into therapeutics very shortly. You’re more likely to go on more advanced therapies such as IL-1 blockers. This is very crucial, and we call this imaging-guided therapy.

On the other hand, if it all disappears over time, you're more likely to say it's time to stop the medicines and see how it goes. It's not a final thing that you won't have a recurrence, but at least it'll tell you that you actually healed. Patients actually take a picture on their cell phone of the before and after sequences. When they come in, it's very, very severe. We say this could take several years, and several years later you can see over time that inflammation will disappear. This really revolutionized how we manage patients.

Now, I should mention, and Tom may elaborate, that not every MRI is the same, so you have to do a very pericardial-specific MRI to have an adequate diagnosis.

But Tom, let's get into a little bit about the new therapies, the paradigm shift. What does the ACC document recommend? What's the new thing with therapeutics?

Tom Kai Ming Wang, MBChB:

So, the first-line treatment for acute pericarditis remains the same. It's a combination of colchicine for three months for the first event, six months or more for the second event, with a combination of either high-dose nonsteroidal anti-inflammatories such as ibuprofen, or high-dose aspirin, if there are contraindications to ibuprofen. The main paradigm shift lies in the second-line treatment or in patients who don't respond to first-line treatment. What's the next step?

It's important at this point to establish whether the patient has active inflammatory pericarditis, which is why it’s crucial to measure the inflammatory markers to see if their CRP or high-sensitivity CRP is elevated. Also, to check a cardiac MRI to ensure that diagnosis is pericarditis and not something else. As we see in our clinic, 20-30% of patients don't actually have pericarditis after our extensive evaluation. You don't want to start someone on a high-powered treatment that may have side effects if you're not sure if they have pericarditis or not.

But the main paradigm shift is in the second-line treatment. If you're in the inflammatory group, which is 80-90% of these patients, then anti-interleukin-1 agents are the new kids on the block that have been around for the last two or three years. That includes essentially anakinra and rilonacept, which are the main ones available in the United States. Anakinra is available particularly in the inpatient setting as a once-a-day intravenous agent, and rilonacept being the mainstream FDA-approved agent to use in the outpatient setting.

These have been shown in randomized trials from the AIRTRIP for anakinra to the RHAPSODY for rilonacept, which was published in New England Journal of Medicine, led by Dr. Klein. It’s a multi-center international study from a few years ago to show the strong efficacy of these treatments in number one, reducing the risk of recurrence compared to placebo, especially in those who are steroid-dependent or culture-seem-resistant. Secondly, to diminish their patient's pain. Thirdly, to normalize their inflammatory markers all in a very quick fashion within typically one to two weeks.

Of course these are the new therapies that have come out, and steroids or corticosteroids are now sort of reserved for either patients who don't have the inflammatory phenotype because of the lack of clinical trials of anti-IL-1 agents in those patients. These are, for example, the patients with autoimmune pericarditis or normal inflammatory markers, or in patients who for some reason or another cannot get onto an anti-IL-1 agent.

So, Dr. Klein, do you want to discuss some of the tips and tricks when patients are started on anti-IL-1 agents? What should we be looking for? What do you think about duration of therapy? What are the main side effects?

Allan Klein, MD:

Okay, so as Tom mentioned, the new kids on the block are these biologics, IL-1 blockers. As he mentioned, anakinra is actually given sub-Q. It's very short acting. The rilonacept is much longer acting. They block the IL-1 alpha and beta. That's a very important distinguishing factor.

So, if we have somebody that's flaring in the outpatient, let's say with recurrent pericarditis, it's their third attack. They're clutching their chest, they're in distress, they have fever, their CRP is very, very high, and they're failing the standard of care NSAIDs and Colchicine, they'll get admitted quickly. Once we get all our testing, we'll check their labs. In particular, we'll check for any things that will limit their use, for example, if there's TB, HIV or Hepatitis. Then, they'll be given anakinra sub-Q in the hospital and that will take away their pain very quickly. But the rilonacept, which is FDA approved, is much longer-acting. We'll do the paperwork to put them on rilonacept and transition them from the anakinra to rilonacept.

This way we're avoiding steroids. Steroids are the bad actor here because steroids will have a lot of side effects, and it'll take months and months to get them off. They'll have cushingoid features, buffalo hump, osteoporosis, ulcers, cataracts, etc. This way, we're avoiding the steroids.

Now, how long do we treat these patients? Well, just say a severe case, it could be more than two years, but it could be up to three to five years. We gradually, as they go on the rilonacept, the longer acting agent, will wean off their ibuprofen and colchicine. If they're on steroids, we will wean that off as well. Then they'll go on monotherapy. That monotherapy, we don't know how long it will take, but we know it'll be a good two years before we can try to come off that.

Now, how do we get them off these high-power therapies? There's some debate. We just had an article published suggesting that the choice would either be stopping cold turkey or to wean. Our article in Heart showed that perhaps with shared decision-making, perhaps weaning with colchicine may be more beneficial. However, even with that, it has a higher recurrence rate. Anywhere from 50-75%. This becomes a chronic disease, more of a long-term disease, and we're coming up with different strategies on how to get them off.

Maybe Tom can mention some of the exciting work with some new clinical trials in these patients?

Tom Kai Ming Wang, MBChB:

A critical part of advancing the science and the literature is being involved in clinical trials. There are several that we are involved with at the moment, three to four. Some of the trials involve how we stop or wean rilonacept. As Dr. Klein mentioned, the recurrence rate from the long-term RHAPSODY trial suggests at least two-thirds to three-quarters of patients may experience recurrence of pericarditis after stopping rilonacept. Options include stopping cold turkey, weaning or even weaning with adding colchicine on. Those latter methods appear to be helpful.

One of the trials that we've been working on is the MAVERICK trial, and that includes the CardiolRx medication for which the phase two trial was presented at AHA (American Heart Association) last year. That shows that there is some benefit in helping dampen inflammation and reducing recurrence in patients with recurrent pericarditis.

So, in the MAVERICK trial, we are trying to enroll patients who've been on rilonacept at least a year, and they can be randomized to stop rilonacept by starting the CardiolRx drug, which is an oral solution that patients take every day, versus the placebo arm to see whether that reduces the recurrence rates.

There are also clinical trials actively ongoing regarding treating active flares of pericarditis. There's one trial with the oral medication called the Ventyx trial, where we're randomizing patients who've not been on biologics before, but who have recurrent pericarditis and have ongoing active flares despite first-line therapies, NSAIDs and colchicine to see if this medication can help improve their symptoms and ultimately help reduce recurrence down the line.

And then thirdly, the third trial is also involving the drug company that manufactures rilonacept, which is Connexa, and the new drug is the KPL drug, which also is looking at an injection medication, hoping to be able to do that every two to four weeks as opposed to a week for rilonacept, and to see whether that can also help treat these recurrent pericarditis patients that are failing first-line therapy and help to see whether that can improve their care. Managing these patients is very critical.

Now, Dr. Klein, do you want to have a bit of comment about surgery and pericardiectomy surgery, which still has a role in the treatment of both pericarditis and constrictive pericarditis?

Allan Klein, MD:

Tom, very good summary. We're blessed at Cleveland Clinic to be a pericardial disease center of excellence, perhaps one of the few in the nation or the world. Patients can come for one to two days and see Dr. Wang, myself and my colleagues, or the nurse practitioner, perhaps see subspecialties, including surgery, rheumatology. We get the analysis of their blood for inflammation, get involved with research that we heard about clinical trials, get a cath if you want to measure pressures and to see a cardiac surgeon.

We offer surgery. We have excellent surgeons that actually do what we call radical pericardiectomy, where they remove 98% or more of the pericardium in the front, leaving the phrenic nerves intact, the pedicle, and also lifting up the heart and removing the pericardium posteriorly. This is called radical pericardiectomy, and this could be used for two circumstances.

One could be constrictive pericarditis, where you have a thickened lining around the heart, compressing the heart, causing heart failure. Or the other one, if you're failing those IL-1 blockers or steroids, they'll remove the lining for pain. Not for heart failure, but for pain. We offer that, and the typical scenario would be somebody that's been involved with this, let's say a 40-year-old active person that's very limited. Their quality of life is very poor. They're trying to wean some of the medicines, it seems to come back, and they'll be referred for surgery. Surgery in great centers like Cleveland Clinic, they have a high volume. This is another option. The results are very good for these patients. It is a sternotomy, but it does help the patients dramatically, and it helps them get off the medicines.

Not every center has that pericardial disease center of excellence. We offer here at Cleveland Clinic proper diagnosis with advanced imaging, we offer newer therapeutics or clinical trials, and we offer radical pericardiectomy. Really, one-stop shopping.

Tom, maybe you can mention a little bit about auto-inflammatory versus autoimmune. Some of our patients have conditions like lupus, and these treat a little bit differently. What would be the approach to some of these autoimmune patients?

Tom Kai Ming Wang, MBChB:

So that's an excellent question, Dr. Klein. Just to briefly recap on what Dr. Klein said as well, the pericardial disease center of excellence, as well as surgery, those are all emphasized in the document in terms of what defines a pericardial disease center, the referral process, the indication, the scheduling, triaging, having this constant referral stream. And then, the four main things we have to manage, firstly, multidisciplinary collaboration, second, education of patients, thirdly, the research component, clinical trial involvement, and fourth, the long-term follow-up and close follow-up of these patients.

As Dr. Klein said about the surgery component, it's absolutely crucial for referral to a tertiary center because most hospitals in the country may do one or two or even no pericardial disease surgeries a year. It's a much more complex surgery than the average heart valve or CABG surgery. It really needs to be done at somewhere like Cleveland Clinic where we do 50-100 cases a year, one to two a week, so that we can optimize the clinical outcomes to be lower than half the rates of operative mortality than other centers.

But coming back to the question about autoimmune versus autoinflammatory. As we know, autoimmune diseases are a very common cause, a minority, but common cause of pericarditis, probably making up about 10% of these patients.

So, in the autoimmune or non-inflammatory setting, patients, for example, with rheumatoid arthritis, lupus, inflammatory bowel disease and so on, in the treatment algorithm from the document, we still have corticosteroids in the second line after NSAIDs and colchicine, because many of the underlying conditions are also treated with prednisone. The other issue is that many of these patients are already on a biologic to treat their underlying condition, whether it's rheumatoid arthritis or lupus, and therefore it can be challenging to try and start patients on anti-IL-1 agents, because they'll be on two biologics with overlapping concerns, for example, for immunocompromised state and infections, and things like that.

Nevertheless, we have trialed in small cohorts, studies which we are working on to publish that anti-IL-1 agents are still very effective for treating some of these patients. That really requires a shared decision-making between the caring cardiologist with the rheumatologist and others that are involved to see if that's the best agent, or combination of agents, or we should focus on just the autoimmune conditions.

So, I guess the next part to talk about is the other parts of the document. There are also separate sections on pericardial effusions, cardiac tamponade, constrictive pericarditis and oncologic conditions. Dr. Klein, do you want to lead us off? Let's talk about effusion and tamponade.

Allan Klein, MD:

Yeah, so the document covers that aspect, especially multimodality use, for example echo, to look at effusions, tamponade and constriction. Often, we may go to, for example, MRI, to confirm the constrictive pericarditis and look at inflammation. The CT would be very good to look at calcium around the heart. These techniques help diagnose when to do a pericardiocentesis, when to do a pericardial window, when to do a pericardiectomy. The document also covers pericardial masses, for example tumors or pericardial cysts as well. It does provide very good algorithms, simple to use. In our consensus document, which is over 50 pages, people may not necessarily read the whole document, but the concise document, you can go to a table or a figure, and have the algorithm for how to manage these patients. For example, with constrictive pericarditis, you have to decide whether this is an inflammatory, transient, constrictive pericarditis, a lot of inflammation, or you'll give anti-inflammatories. As opposed to there's heavy calcium burden around the heart, there's no more inflammation, it's all thickened, it's fibrose, and you go to pericardiectomy. What echo-doppler criteria will help us distinguish is this pure constriction or is this restrictive cardiomyopathy such as amyloid, or in between what we call mixed constriction restriction. It has different algorithms based on echo-doppler, EA ratios, tissue-doppler findings, SVC flow, hepatic vein flow. Very important algorithms in this document.

So I think this is very, very exciting. But this document differs a little bit from the Europeans’. Now, the Europeans came out end of August in Madrid. They have, especially for recurrent pericarditis, they have a little bit of a different algorithm. Maybe you can just comment on the differences between the American side and on the other side of the pond, the European side?

Tom Kai Ming Wang, MBChB:

Thanks Dr. Klein, and of course Dr. Klein's also a co-author on the European guidelines. He's got a foot on two boats. But let's talk about the European guidelines. The European guidelines for the clinical diagnosis of pericarditis are actually very similar to the American document in terms of the novel criteria, having the unlikely, possible and definitive diagnosis of pericarditis. We are very aligned there in terms of the diagnosis of pericarditis. The main difference lies in the management of the second line management of pericarditis.

In their treatment algorithm, the first line treatments are the same combination of colchicine plus either a high dose NSAIDs or aspirin. If you respond to that, you complete your course. But the second line treatment in the European guidelines, currently they still have cortical steroids as the second line option, and they've reserved anti-IL-1 agents as the third line option after trialing steroids and failing steroids. That's the main difference compared to the American documents, which we have the anti-IL-1 agents as a second line agent and steroids only for, for example, people with autoimmune or non-inflammatory phenotype.

I think a few reasons for that. Firstly, the anti-IL-1 agent isn't widely available in most European countries. Rilonacept’s only FDA-approved and available in the U.S. In Europe they don't have access to rilonacept, and only a few places have access to anakinra. In part, the European society serves guidance for 20-30 countries, and they need to make sure everyone's accessible.

Secondly, some of the main writers in the group have much more experience with using prednisone, and found success in that. Although we've not seen that as well, because we find that prednisone, firstly, has far more side effects than anti-IL-1 agents. Secondly, there's a high risk of recurrence and more persistence into chronic disease, and therefore we've moved away from that.

So that's the main difference. But the use of multimodality imaging is the same. They have now strongly emphasized using cardiac MRI, more so than the prior guidelines, as well as complementary roles of CT. CT for example, for assessing differential diagnosis of chest pain for people coming with pericarditis. You want to make sure they don't have coronary disease, aortic dissections, pulmonary embolism, other long pathologies and so on, as well as for pre-procedural planning for pericardiectomy and to look for pericardial calcifications.

The third part that's quite different between the two is the European guidelines are a much more extensive document including both myocarditis and pericarditis. You can look into myocarditis as well. It's got the standard level 1, 2A, 2B, 3, as well as ABC levels of evidence recommendations, whereas our document is more as a consensus document that talks about what's recommended, what should be reasonable, and what should not be performed, both from imaging and treatment.

But the ACC document, I feel, actually has more algorithms for imaging and how to use imaging, which modality to use in which setting, and how do they complement each other for both pericarditis, effusion, and constriction. Both documents also talk about the pericardial disease center as well. That's sort of in a nutshell, the main differences between the ESC document and the American guidance documents.

Clinicians should obviously tailor which document to their patient. In the U.S., I would expect because of the availability of the drugs that we've discussed, that the ACC document should be the main one used in the U.S. But obviously, international audience can pick and choose which one is more appropriate for them.

Allan Klein, MD:

I think in 2025, the patient who's often searching for a good provider, they're going to the ER often and they're sent home without a diagnosis, or there's under diagnosis, which will lead to recurrent pericarditis. Sometimes there's over-diagnosis or misdiagnosis. They're put on these medicines inappropriately. So, I think clinicians who have options to look at these documents, look at the tables, and know when to refer to a tertiary pericarditis center of excellence like Cleveland Clinic.

So, the bottom line is that we want patients’ outcomes to improve. I think what we have in 2025, we have a good diagnosis with the new criteria, multi-modality imaging. We have new therapeutics, we have the centers of excellence to help provide better outcomes for these patients in 2025.

Tom Kai Ming Wang, MBChB:

And also, we also really want to thank and acknowledge all the members of the writing committee. Chairing this, thanks to the American College of Cardiology for the opportunity. Dr. Klein is the vice chair. Then, the other members of the writing committee. There's a total of 11 people, mostly from the U.S. but there are international [writers] from Italy and from Canada who've contributed, as well as the solutions committee for reviewing a document. To make this a clinically user-friendly document, it's a short document, relatively, only 3,000 to 4,000 words filled with tables and algorithms to refer, how to image, how to manage each of these patients.

We’re really grateful to be able to do this and to share our experience with the community to optimize and hopefully homogenize how pericardial diseases are managed so that every patient can be managed in the best possible fashion to improve their outcomes.

Allan Klein, MD:

Also we encourage the ACC and the American Heart Association to have a formal guideline like the Europeans with different levels as opposed to a consensus. We're working on that, trying to convince them to come up with a new guideline. This is a very exciting time for pericarditis to be involved with this field.

Tom Kai Ming Wang, MBChB:

Absolutely, yes.

Allan Klein, MD:

Thank you so much.

Tom Kai Ming Wang, MBChB:

Thank you very much for attention.

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