Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And we have two Northwestern Medicine physicians for you today in a thought leader panel discussion, highlighting the Pericardial Disease Program within the Bluhm Cardiovascular Institute. Joining me is Dr. Paul Cremer, he's the Director of Multimodality Cardiac Imaging and an Associate Professor of Medicine in Cardiology and Radiology; and Dr. Mohamed Al-Kazaz, he's the Section Chief of General Cardiology within the Bluhm Cardiovascular Institute and an Assistant Professor of Medicine in Cardiology. Doctors, thank you so much for joining us today. Dr. Al-Kazaz, I'd like to start with you. Can you please speak about the prevalence of pericardial disease within the population and what you've seen in the trends?

Mohamed Al-Kazaz, MD: Thank you for having us. So, pericardial disease spans a different kind of range of pathologies. For example, acute pericarditis is one of the most common disorders involving the pericardium. We don't have a lot, like epidemiological studies are largely lacking. So, we don't know the exact incidence and prevalence of acute pericarditis.

However, we know when patients, let's say, are hospitalized, 0.1 to 0.2% of those patients reported to have acute pericarditis. And 5% of patients admitted to the emergency department for chest pains in general could have pericarditis in some observational studies. So, it's a very common disorder in several clinical settings, inpatient, outpatient. These first encounters are very important because recognizing it, treating it appropriately, aggressively, with an appropriate transition to outpatient care in specialized places where they can follow them and taper the anti-inflammatories appropriately can decrease the chance of recurrence and provide better quality for those patients.

And the span of pericardial disease has expanded beyond just acute pericarditis. A portion of those patients with acute pericarditis can have myocardial involvement, let's say around 15% or so of those patients. Some of those patients with acute pericarditis can be more sicker. Let's say 1% or 2% can come with what's called cardiac tamponade, which can be a medical emergency. And 15-30% though different, there's some variabilities among studies, patients can have recurrent pericarditis. And from those, let's say, 5% or 6% can have multiple, multiple recurrences. And a much smaller minority can develop into chronic constrictive pericarditis. However, we're learning more and more to differentiate between transient and irreversible constrictive physiologies in the context of either a post drainage, post what's called effusive constrictive physiologies, or even just plain result of inflammatory processes or other etiologies.

So, it's a disease that's getting more attention because we have more treatments medically, surgically, and we're developing centers of excellence to try to tackle those complicated patients, especially with recurrent or incessant pericarditis or constrictive pericarditis, requiring advanced medical or surgical expertise.

Melanie Cole, MS: Thank you so much, Dr. Al-Kazaz. And Dr. Cremer. Tell us about the program. How did it come about? What offerings make the Pericardial Disease Program at Northwestern Medicine Bluhm Cardiovascular Institute so unique?

Paul C. Cremer, MD: Yeah. Thank you, Melanie. And it's great to be with my friend and colleague, Dr. Al-Kazaz, who really covered a lot in those opening comments. Just to highlight a couple of points, acute pericarditis is quite common. So, about 5% of patients presenting to emergency departments with non-ischemic chest pain. And, as Dr. Al-Kazaz highlighted, those patients can have acute complications, like tamponade or myocarditis or can really go on to have more chronic complications such as recurrent pericarditis. And recurrent pericarditis affects about 15-30% of those patients after the first episode, after the episode of acute pericarditis. And I would say in our pericarditis center, that's a big patient population that we focus on, those patients with either single or multiple recurrences of pericarditis, because those patients require comprehensive evaluations; imaging evaluations, often with echocardiography, with cardiac MRI. And based on those evaluations, they may be candidates for additional therapies, therapies that we're not as used to prescribing within cardiology clinics. So, I think in the acute pericarditis setting, we should all be comfortable using NSAIDs and colchicine as first-line therapy. And we know if we do that, we can half risk of having a recurrence. But when people go on to have a first and multiple recurrences, they may require medications beyond NSAIDs and colchicine, such as new medications like the interleukin-1 blockers. So, part of our center is to really identify those high-risk patients that may be good candidates for some of these novel immunomodulatory therapies.

Melanie Cole, MS: Dr. Al-Kazaz, clinicians are often faced with several diagnostic questions relating to the various pericardial syndromes, as you've said. Is there criteria for diagnosis that's been established and does the diagnosis and management of pericardial disease remain challenging, because, as you said, the vast spectrum of manifestations and the lack of clinical data on which to base your guidelines by?

Mohamed Al-Kazaz, MD: I do think that there's a lot of established criteria for many of the conditions, but it does require clinical judgment to make sure we had the right diagnosis for the patient to get the appropriate treatment. So, for example, there are criterias for pericarditis where they're having pleuritic chest pain, EKG changes or precardial effusion in imaging or, on exam, you can hear a rub, supplemented by inflammatory markers, or advanced imaging. And we're lucky to have Dr. Cremer with us here, who has expertise in multimodality imaging using CT, MR, particularly CMR, cardiac MRI to help us understand the process better, whether from myocardial involvement all the way to the vascularity, and the new vascularization of the pericardium with late gadolinium enhancement, indicative most commonly of acute inflammation. So, we have made strides in the diagnostic criteria clinically and from imaging standpoint.

However, this becomes even more relevant in those subset that Dr. Cremer mentioned who are more complicated, not the plain acute pericarditis that resolves by itself or with anti-inflammatory therapies like NSAIDs or colchicine. Those recurrent pericarditis are a target for these advanced pericarditis centers and pericardial disease centers. Those patients who might have transient constrictive physiology, identifying those patients using echocardiography for hemodynamic studies and supplemented with cardiac MRI in majority of those cases can help understand, one, the diagnosis from pericarditis, constriction standpoint, effusion, the physiology of the effusion, and the reversibility potentially of it, and can help us prognosticate as well the response of these patients to anti-inflammatories, and with some data from work from Dr. Cremer, which he has been influential in many of these studies in the pericardial disease realm, that we can help maybe understand the natural history of those patients, how they respond to therapy. We have more work to be done to fine tune it more and understand and re-stratify further, especially as we have advances in therapies. But thankfully, we have made strides in diagnostics from clinical and imaging standpoint, and that's why we're building centers that are not just for doctors to see them. It takes a village, a heart team. We need imagers, we need clinical cardiologists. And obviously, our cardiac surgery department involvement when needed. So, it takes a village and having expertise in imaging, having expertise in clinical judgment and exposure to those patients can make the case easier to diagnose them and treat them appropriately. And we're lucky to have people like Dr. Cremer who has expertise across the spectrum, from research all the way to clinical imaging and advance care in those patients.

Paul C. Cremer, MD: Dr. Al-Kazaz, you know, that was fantastic. I think an important point to emphasize is the disease duration in recurrent pericarditis. As we said, most patients with the acute pericarditis will resolve and fortunately not have any further complications. But when patients go on to have recurrent pericarditis, the median disease duration is about three years. So, it's something that we can treat them through and improve the quality of life and decrease the risk of further recurrences. But it usually requires several years, sometimes more. A lot of our diagnostic evaluations, in terms of checking the inflammatory markers, understanding in depth the history of the patient's pericarditis history, and using the imaging like the echo and the MRI. Yes, they help us diagnostically, but they also help us prognostically to really inform, "Okay, how long do I think this patient is going to need to be treated?" And if it is someone that I'm going to be treating for several years, what are the best treatment options for that patient? So, that's a big part of what we do in the Pericardial Center as well.

Mohamed Al-Kazaz, MD: And Dr. Cremer is absolutely right, because those patients, when they come to us, they have seen multiple providers, they have been struggling with this for some time. Part of it is missed, part of it is undertreated, or part of it is they just have a bad disease that's having multiple recurrences. And they're a very well-informed group of patients, and I love interacting with them. They want to know, not just what's the next step today, because they have been struggling with this for some time. They want to know, to the best of our knowledge, based on objective data, what's the possible duration of therapy? What are the options down the road? And that's where a pericardial program like ours can offer to those patient, trying to answer and treat them, because they have went through a lot and they are very well informed. So, they ask very, very good questions about their disease process.

Melanie Cole, MS: Dr. Al-Kazaz, expand a little on what you were just speaking, about some of the therapies, how patients are well-educated and up-to-date on these things, because they've been researching and seeing different providers, as you said. What's exciting at the Bluhm Cardiovascular Institute as far as therapies for pericardial disease?

Mohamed Al-Kazaz, MD: Yeah. Thank you for that. I think Dr. Cremer alluded to it, and Dr. Cremer has been influential in the foundational work for it, in the RHAPSODY trial, among other substudies, as well in the pericardial disease realm overall. And one of the major advances we have is more evidence to support the use of IL-1 inhibitors such as rilonacept or Anakinra for those patients with recurrent pericarditis to avoid the long-term use o steroids or other agent which we know cause many side effects, and those patients are aware of the side effects. And they have really dramatic response to it. We're still trying to understand those medications better and study them and research them in terms of, long-term use, alternative pathways, because as Dr. Cremer pointed out to, this is not a one month, two weeks kind of situation. This is a couple of years of treatment. So, we're still trying to understand and study this further, but the advancements in the immunomodulator therapies with less side effects and great response, you know, from the RHAPSODY trial, and this is a great, great advancement that we can offer here and follow them and make sure that they have the appropriate response.

And secondly, pericardiectomy as a surgery, we have Dr. Johnston at the Cardiac Surgery Department who is probably the best surgeon to do this surgery on an international and national level. We can offer it in patient with refractory pericarditis despite optimal medical therapy or intolerant to it, in addition obviously to the constrictive pericarditis patient with irreversibility.

I want to give the mic to Dr. Cremer to comment a little bit given his involvement the prior work on IL inhibitors and what he thinks down the road in the field of medical therapy for pericardial disease.

Paul C. Cremer, MD: Sure. Thank you, Dr. Al-Kazaz. Yeah, I think broadly, who are the patients that benefit from these novel therapies? As we've been talking about, it's the patients with recurrent pericarditis, who have disease that is either resistant to colchicine. So, they need therapy beyond colchicine, which has been the mainstay of our approach in treating pericarditis or patients who are dependent upon corticosteroids, so the patients who can't get off prednisone. So, it's really those two patient populations where we need better therapies and blocking the IL-1 pathway has been very efficacious in treating acute episodes and preventing recurrences. And that's been shown in clinical trials. So, that has really been a game-changer for us in the treatment of pericarditis.

As Dr. Al-Kazaz was saying, you know, often you need to treat these patients for a longer period of time. You need to follow them closely in your clinical practices. And then, for patients who really have refractory, recurrent pericarditis, despite medical therapy, you need to have the surgical expertise to remove the pericardium, which is also a highly efficacious way to relieve the pain of recurrent pericarditis.

It's a great time to be in the field of pericarditis in a way, because we have a lot that we can offer these patients that we didn't have before. And I think related to that, in the future, we will see, I hope, other therapies that involve the same pathway. And what is this pathway we're talking about? Well, generally, we're talking about an inappropriate innate immune response and inappropriate activation of the inflammasome. So, future therapeutics that inhibit the inflammasome that block interleukin-1. I really think there's a bright future for those kinds of treatments in recurrent pericarditis, and we'll be involved in those studies, as they develop. And we're currently involved in some of the registries that are looking at the use and the efficacy of IL-1 pathway inhibitors in recurrent pericarditis.

Melanie Cole, MS: This is such an interesting discussion. Thank you both. I'd like to give you each a chance for a final thought here. So, Dr. Cremer, I'd like you to speak a little bit more, expand on that multidisciplinary approach because it's so important, and your vision for the program. How will this care model improve the way patients receive care down the line? Anything that you would like to bring out as far as clinical trials and their role in the program? Give us your summary.

Paul C. Cremer, MD: Great. Yeah, thank you. Recurrent pericarditis and constrictive pericarditis, which we've touched on a little bit, but not in depth, but as Dr. Al-Kazaz has been saying, constriction is where the heart is encased usually by a thickened pericardium, which results in profound diastolic heart failure. So, it's really those two conditions, the recurrent pericarditis and the constrictive pericarditis, where you need a multidisciplinary team to really sort out what's going on. And that team involves the clinician, most importantly. And that involves Cardiology, and involves Cardiac Surgery. It often involves Rheumatology, that's the clinical team. It involves multimodality imaging. We've touched upon echocardiography, and echo is really our mainstay to look at the hemodynamic consequences of the pericardial disease; and cardiac MRI, which is our primary modality to look at inflammation of the pericardium.

And then also, as we've touched upon, it involves surgery for pericardiectomy, either due to recurrent pericarditis, so pain-related or pericardiectomy for constrictive pericarditis. So, that's who makes up the pericarditis team, in addition of course to our nursing staff and our pharmacist. And you really need that expertise across all of these groups for people who are doing this every day. And for the patient experience, you know, you want the patient to be able to come and have all their evaluations on one day, and really to be able to give them an answer at the end of that day. And so, that's what we've done. You come, you can have the blood work done, the echocardiogram, the cardiac MRI. You can meet with one of our pericardial cardiologists, and with the cardiac surgeon if that's necessary, so that a plan is really in place.

As you mentioned, Melanie, we really want to incorporate the most innovative therapies we have available into that plan when it's indicated. So, that may be a patient where we would decide to start an interleukin-1 blocker and we say, "Hey, you know, we have this registry ongoing. We're really trying to follow the natural history of recurrent pericarditis, because as Dr. Al-Kazaz has touched upon, we don't know a lot about that. What does this look like in five to 10 years time? Would you be interested in being part of that registry?" Or, "We have this new therapy to try and prevent recurrences, try and minimize the use of other medications. Would you like to be involved in that clinical trial?" So, we want all of that sort of centered in one place, and that's really what we've been able to accomplish. And it really is the best option for the patients, because not a lot of people focus on pericardial disease. It really is a small community of pericardiologists, if you will. We all know each other, we all talk to each other, and try and provide the best care for these patients. But it's not something that most cardiologists or most providers are really doing at a high volume on a regular basis. And that's really what we want to provide for our patients.

Melanie Cole, MS: What a comprehensive approach. And Dr. Al-Kazaz, last word to you. I mean, pretty much Dr. Cremer just answered it, but why is the Bluhm Cardiovascular Institute a destination for patients with pericardial disease? And anything else that you would like referring physicians to know about this program?

Mohamed Al-Kazaz, MD: No, I think Dr. Cremer has summarized it very well and comprehensively. What I would say is recognize the disease process, especially for those more complicated with recurrent pericarditis or concern for constriction or unclear diagnostically what's going on from pericardial disease and refer them. Refer them as early as you can. And as Dr. Cremer alluded to, we have a systemic program where we can see people and get them all the testing needed the same day. We see people from across the country thankful to have expertise at the national level and we're involved at different initiatives from different societies and part of different registries.

And as Dr. Cremer says, we're not only focused on building a strong clinical program, we're trying to understand and contribute to the disease process to help future patients. So, what I would say to the community about the program we have at the Bluhm Cardiovascular Institute is it's a state of the art program with the expertise needed to have a true heart team involved in pericardial disease. And the key we need from our community, from our doctors at different levels, you know, is to refer early, especially for those complicated patients, because their course can be long and to get the accurate diagnostic information and steer the patient the right way from a therapeutic standpoint. We have a lot to offer and we're very excited about the future.

Melanie Cole, MS: Thank you both so much for joining us today, telling us about the program and pericardial disease and sharing your incredible expertise. Thank you again. To refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/cardiovascular. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. Please always remember to subscribe, rate, and review Better Edge on Apple podcasts, Spotify, iHeart, and Pandora. I'm Melanie Cole. Thanks so much for joining us today.