Cardiac Sarcoidosis

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.

Christine Jellis, MD, PhD:
Thank you for joining us in the Heart, Vascular and Thoracic Institute of Cleveland Clinic, where today we would like to speak with you about cardiac sarcoidosis. I'm here with members of our team, and together we would like to provide a multidisciplinary approach to cardiac sarcoidosis. We are fortunate that we have all the resources available to us to do this. And for that reason, we see many patients from across the globe who have this somewhat rare, but very interesting condition.

Christine Jellis, MD, PhD:
I'm Christine Jellis. I'm a cardiologist from the Imaging Section. And I'd like to introduce my colleagues, Dr. Manny Ribeiro, director of the Sarcoidosis Center and a pulmonologist, and Dr. Ziad Taimeh, who's an expert in Heart Failure who will be joining me in this discussion.

Christine Jellis, MD, PhD:
So guys, I think one of the things that I enjoy about cardiac sarcoidosis is that we don't completely understand it. Manny, some insights about the etiology of cardiac sarcoidosis and how we approach working these patients up, because I think it's something that we are fortunate to see quite a bit of, but in the general population it's still a relatively rare condition, particularly pertaining to the heart.

Manuel Lessa Ribeiro Neto, MD:
No, absolutely, Chris. This is definitely something that we still don't know, right? What is etiology of sarcoidosis? What causes it? But there's a huge debate in the literature, many great researchers looking for specific antigens. I think even though we have different hypotheses, the one that is the most accepted nowadays is that it is a reaction from our immune system to something that we get exposed in the environment. I think this environmental theory is very well accepted. And of course it's not just the environment, but there's definitely some genetic predisposition as well. There's some study showing that this interaction between in the environment and specific genes or HLA molecules, they lead to sarcoidosis in some patients and to different manifestations, right? There are different interactions that will lead to different manifestations.

Manuel Lessa Ribeiro Neto, MD:
As far as of specific etiologies, again, we still don't know exactly what causes it, but there's some good research looking into infectious agents as potential causes like microbacteria as one potential cause or Cutibacterium acnes, the old Propionibacterium acnes. They just changed the name just to make our lives a little harder. But that's a very common bacteria that is present in our skin, and the Japanese, they do a lot of research looking into that as maybe being the cause of sarcoidosis. Some metals have been implicated, working in molding environments. So all of those things are things that specific researchers identify as potential causes. But the right thing to say nowadays is that I think we still don't know what the cause is, but definitely something from the environment.

Christine Jellis, MD, PhD:
Ziad, when you see patients come into your clinic, what are the red flags that you're looking out for to suspect that someone may have cardiac sarcoidosis? Because I think in the past, there have been cases that haven't necessarily been detected until they've gone for transplantation or had an LVAD implanted and on the explanted heart, or the tissue that's analyzed, they have been found to have sarcoid. So what are some red flags that we can advise people of upfront so we start going through these diagnostic algorithms earlier, hopefully therefore being able to initiate treatment more promptly?

Ziad Taimeh, MD:
Yeah, absolutely. We typically see two scenarios, two major scenarios for these patients. Scenario number one, somebody coming with a heart disease that just does not make sense. There is something that is not right. It doesn't fit under the criteria of coronary artery disease, does not fit the criteria under viral inflammation. There is something that does not really make sense. And in those cases, it's always nice to think about sarcoidosis. For example, ventricular tachycardia of unclear etiology in a young person, I would think cardiac sarcoidosis. Heart block, it's somebody who's 40 years old, I would think about cardiac sarcoidosis. And oftentimes it turns to be the case.

Ziad Taimeh, MD:
The other scenario is when somebody coming with a heart disease, but they have a history of pulmonary sarcoidosis or sarcoidosis of the skin or the joints or the liver in the past, and they are now coming with a heart disease. Oftentimes we found that they have reactivation of the sarcoidosis this time in their hearts. So at the end of the day, we should have a low index of suspicion for considering that as the etiology.

Christine Jellis, MD, PhD:
I think one of the reasons that I am interested in sarcoidosis is that we don't understand it, because it's always nice to be involved at the forefront of research and an area that is still yet to be defined. I think we can see from our current diagnostic criteria that there are some discrepancies there, and so there's definitely room for us to become more aligned in how we can diagnose sarcoidosis.

Manuel Lessa Ribeiro Neto, MD:
Correct.

Christine Jellis, MD, PhD:
Manny, do you mind commenting on some of those criteria, how they've evolved, and how we use them in a practical sense?

Manuel Lessa Ribeiro Neto, MD:
Absolutely. So Chris, we've been doing this multidisciplinary care for a few years, right? Our group, the pulmonary group and the cardiology group, a few years ago decided that the first thing that we needed to do to take better care of our patients was to start a registry of patients with cardiac sarcoidosis. So we did that. We have this registry ongoing. We all participate on that. And the first question that we tried to answer was, what is the best way to make the diagnosis in those patients? And nowadays there are three most widely accepted criteria to make the diagnosis of cardiac sarcoidosis, three independent societies, two here from the US. One is the Heart Rhythm Society. The other one, it's actually a world institution. It's the WASOG, World Association for Sarcoidosis and other Granulomatous Disorders. Those are the two criteria that we use most of the time here in the US, and then we have the Japanese Ministry of Health criteria that was recently updated, but three main criteria that we can use.

Manuel Lessa Ribeiro Neto, MD:
And then what we decided to do as a group in that registry was let's just apply those criteria to our patients, the patients that we think have cardiac sarcoidosis, and see how they fit. The two main conclusions from that study was number one, about 40% of the time patients that we think have cardiac sarcoidosis don't fit into any of those published, accepted criteria. But we still see those patients. We still need to take care of those patients. That was one finding of that study. The other important finding is in the other group of patients where we could apply those criteria, there was some discrepancies between WASOG and the HRS as compared to the Japanese criteria. So even the known criteria wouldn't always agree when we apply it to our patients.

Manuel Lessa Ribeiro Neto, MD:
I think the most important message from that paper is this multidisciplinary discussion is very important, because we will not be able to make an accurate diagnosis of cardiac sarcoidosis in every patient just by using those criteria. So a multidisciplinary discussion is extremely important.

Manuel Lessa Ribeiro Neto, MD:
And then the last thing I would say is nowadays there's a lot of debate and talks about isolated cardiac sarcoidosis, when cardiac sarcoidosis is only in the heart. The Japanese folks just published the first criteria specifically for isolated cardiac sarcoidosis. We are just now applying that criteria to our registry to see how things will perform there. But again, I think the message is the same, especially in those isolated cardiac sarcoidosis cases. This multidisciplinary discussion is extremely important, and that's how we like to practice here.

Christine Jellis, MD, PhD:
Absolutely. And I think in that scenario where we're relying primarily on imaging, sometimes we don't necessarily have tissue diagnosis for those patients where we suspect they have isolated cardiac disease, and I'll have Ziad comment on the yield of endomyocardial biopsy. But as an imager, we're often putting together the Echo findings, the MRI findings, and then the PET results to, within a certain degree of certainty, come up with a hypothesis that this is cardiac sarcoidosis. So I think what we are learning as we do that, there are specific patterns. There are patterns in where the enhancement is, where the inflammation is that makes us more certain that this is sarcoidosis.

Christine Jellis, MD, PhD:
But there are also patients where you go back into their history a little bit more and you find out that perhaps they've got a family history of sudden cardiac death, or something else that makes you think that there may be well another etiology underlying this. We have to be very careful that we don't misdiagnose these people. So I think genetics counseling we are increasingly doing on patients, particularly those who are young, who are being diagnosed as isolated cardiac sarcoidosis based on non-tissue findings.

Christine Jellis, MD, PhD:
Ziad, do you mind commenting on that? Because I think that is something that increasingly we are wanting to make sure is included within the armament of what we do.

Ziad Taimeh, MD:
Absolutely. Now, it's very important to acknowledge that the clinical history of that particular case needs to match with the imaging like alluded to. Cardiac MRI, cardiac PET, echoes. And it really should match with tissue diagnosis, should match with genetic testing, and it should match with response to treatment. If there are any misalignment in any of those, then we have to reengage with our colleagues and ask ourselves this question: Is it truly cardiac sarcoidosis?

Ziad Taimeh, MD:
Now, once the clinical history matches the actual imaging ... And it's very important not to just depend on one particular aspect of that. We have to build the entire story, then where the tissue diagnosis comes in. We typically like to find out if there are any tissue areas that we can sample that are easy to reach, such as a lymph node, mediastinum lymph nodes, and in certain cases we have to go for a heart biopsy. The myocardial biopsies from the right side that are random have a very low yield of less than 10% because of the patchy nature of the disease. But more sophisticated methods that we have been using, including voltage guidance ... In other words, accessing the left ventricle in collaboration with our electrophysiologist and try to do mapping, see where there's abnormal voltage in fractionation signal, imposing that on the MRI findings and the PET findings, try to take samples from the areas that actually are diseased. This has increased our yield from less than 10% with a random biopsy to more than 70% yield as published in the literature.

Christine Jellis, MD, PhD:
So once we become certain, or with high probability that the diagnosis is cardiac sarcoidosis. Let's talk about treatment, because I think that is also something that varies depending on the center, the location, the geographical spread across the world. And that is something that I think we really believe that these patients, once we make that diagnosis, should be treated.

Christine Jellis, MD, PhD:
Unlike, Manny you may comment on pulmonary sarcoid where we don't necessarily always step in and treat. But because of the potential for arrhythmia and for subsequent development of fibrosis within the heart, we do tend to treat these patients where we are certain of that diagnosis. And then there is always a debate about, what should we treat them with? What are the optimal doses and the duration of therapy, and how often should we be imaging these patients along that journey?

Christine Jellis, MD, PhD:
I've thrown a lot of points at you there, guys. But in the last few minutes, do you mind giving me your thoughts on those? Because I think we have really solidified the way that we do this based on our experience over the last few years, and I think that's something that's worth sharing.

Manuel Lessa Ribeiro Neto, MD:
Yeah. No, a couple of the important points there, Chris. So whenever we make the decision to treat patients with cardiac sarcoidosis, which I completely agree, I think it's most of the patients that we have here. The first line is still steroids. There is some discussion about IV versus oral or what is the optimal dose, but I think it's safe to say that first line should be steroids.

Manuel Lessa Ribeiro Neto, MD:
Here in our center, if the patient is not having like a severe presentation with a VT storm or complete heart block, we usually start with oral prednisone 30 milligrams daily, and I think this is a good starting dose for our patients with cardiac sarcoidosis. This is based on a retrospective study from Japan that showed that given more than 30 milligrams was not associated with improved outcomes, so we go based on that. But again, no randomized control trials yet to guide us there. Hopefully, pretty soon we'll start seeing some of those, but we use oral steroids to begin with. If patients are presenting with a more severe manifestation like a VT storm or a complete heart block, there in the hospital we'll do a pulse dose of Solu-Medrol one gram per day for three days, but steroid is that first line.

Manuel Lessa Ribeiro Neto, MD:
The second point is we here like to start a steroid sparing agent, like a methotrexate or a leflunomide early on. Again, this is based on retrospective data showing that if we do that from the beginning, we achieve better outcomes. The Canadians are actually organizing now a multicenter trial comparing those strategies, steroids monotherapy versus the combined therapy. Hopefully, pretty soon will have that result, but we here like to combine those steroid sparing agents early on.

Manuel Lessa Ribeiro Neto, MD:
The duration of treatment. So once we make that decision and we prescribe those medications to patients, we tell them that it's at least two year years of therapy, especially when we have a very confident diagnosis. This is based on at least one Italian study that showed that if we stop immunosuppression before that in sarcoidosis, the rate of relapse is significant. It's probably even higher for cardiac sarcoidosis, because that study from Italy took a look at patients with pulmonary disease. So because of that high rate of relapse, we tell patients at least two years.

Manuel Lessa Ribeiro Neto, MD:
But I got to tell you that ... We shared some of those patients. More recently, I've been treating patients for even longer. As long as they are not having side effects to the medications, they are doing well three, four, five years. I think the longer we treat patients with cardiac sarcoidosis, the lower the chance of relapse.

Ziad Taimeh, MD:
I echo that. I mean, generally speaking for inflammatory cardiomyopathies, the approach has been followed in the medical community. It either step up or ramp up or step down. Step up, meaning you start one immunosuppressant agent and you see the response three to six months. If there is no response, you add another agent. But unfortunately, we're losing time, three to six months, where we could have cooled down the inflammation, prevented scarring.

Ziad Taimeh, MD:
Here at the Clinic, we'd use a step down approach, meaning that on the front end we start dual agents to save time and be able to save that fibrosis at the back end and prevent really the recurrence. And at the same time, like we discussed, some cases we have still a little bit of doubt. Is that cardiac sarcoidosis or not? But we treat anyways based on the risk-benefit ratio. If we have a good response to the immunosuppression, that does support that diagnosis. But if we don't see any improvement, then we have been actually weaning off the immunosuppression completely and assessing for progress after that.

Christine Jellis, MD, PhD:
Thanks, guys, for your insights. At this stage, I'd also like to acknowledge the other members of our team who've been phenomenal. We work closely with the folks in nuclear cardiology and EP who are integral to our meetings, and I hope that you have all enjoyed some of the insights that we've learned working together as a multidisciplinary team over the last few years. And hopefully, we can bring you some of our updates as we get more information from that registry over time, but thank you for joining us today.

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