Chagas Disease: Diagnosis, Treatment, and Prevention

On episode 39 of Inside the Studio, Dr. Alexander Postalian, an interventional cardiologist at The Texas Heart Institute Center for Cardiovascular Care, sits down with Grand Rounds guest Dr. Carlos Morillo to discuss Chagas disease, syncope, and autonomic dysfunction. 

They discuss:

• Chagas Disease:
  • The prevalence and impact of Chagas disease, particularly in Latin American communities, and its growing presence in the United States.
  • The complexities of diagnosis, treatment, and prevention strategies.
  • The latest research and clinical trials, including the groundbreaking BENEFIT trial led by Dr. Morillo.
• Syncope and Autonomic Dysfunction:
  • The challenges of diagnosing and treating syncope, especially in milder cases.
  • The latest advancements in understanding and managing syncope, including medications, devices, and emerging therapies like cardio neuroablation.

Watch Dr. Morillo's Grand Rounds: https://tv.texasheart.org/inside-the-studio/videos/chagas-disease-diagnosis-treatment-and-prevention-with-dr-carlos-morillo

Register for upcoming live talks at https://www.texasheart.org/grandrounds

Watch On Demand Videos on Texas Heart TV

Visit Our Website: texasheart.org

Transcript

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All right.

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I'm Dr. Alexander Post Stallion,

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a cardiologist here at THI, Texas Heart Institute.

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Welcome to another episode of Inside the Studio,

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and I'm here with, uh, Dr.

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Carlos Morillo, who visits us from Calgary.

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Thank you for coming. Uh,

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you gave a really amazing grand rounds today.

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Uh, he's an expert in Chagas disease,

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has led several clinical trials that are,

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have been extremely important for, uh, the disease, as well

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as a lot of research in the area of syncope

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and autonomic dysfunction.

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Again, welcome. Uh, thank you for coming.

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Well, thank you for having me here.

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Well, Chagas was a big part of my childhood,

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I would say when I was growing up.

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Um, El Chio, which is the kissing bug, was like the,

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the boogeyman, you know, I remember from primary school,

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first grade, second grade, hearing about El Chio.

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You know, be careful with the ceilings

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that have hay in it if the walls have a lot of holes.

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And I grew up sort of learning about Chagas

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and I was exposed to it in med school.

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I'm originally from Venezuela.

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I'm assuming the experience might have been somewhat similar

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to you if you're coming from Columbia,

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but can you remind us what Chagas is

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and how it's treated and why it's important?

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Yeah. Well, Chagas disease is, uh, it's a disease

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that is transmitted by a bug that transmits a parasite.

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And this parasite is very avid for the heart tissue

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and it produces damage

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of the heart tissue, the conduction system.

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So your pacemaker of the heart produces arrhythmias

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and it's actually very devastating

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with a very high mortality and morbidity.

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And it's just estimated that it affects about seven

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to 10 million people across Latin America.

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But because of migration patterns, well, you know, a lot

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of people from Latin America have moved to the states

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and out of, to Europe.

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So the United States is one of the countries

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that has about 400,000 people that have been infected

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with Chagas and that are living around here.

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Now, the thing with Chagas is that, you know,

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you get the infection early on and only about 20

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or 30% are going to have the heart disease,

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but we don't know which 20 or 30% are gonna get the disease.

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So some of the research that I've done has been trying

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to focus on identifying these people early on

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so we can treat them and prevent the progression of disease.

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And again, even in Texas, there's been some what we call,

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so it means that people that have got Chagas here,

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because actually there's some mosquitoes in Southwestern,

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uh, Texas that can transmit the disease.

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Uh, a lot of dogs actually have, uh, t cruisey,

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which is the parasite that transmits disease.

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So it's an important disease from that perspective,

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because if not identified on

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and treated on time, it will end up developing this

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bad cardiomyopathy.

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It's obviously very important in the developing world.

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Um, but you were saying basically that people here in the US

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and Canada need to start paying attention to it

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because there's a potential of rise in the future, perhaps?

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Well, I don't know about rise in the future,

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but there's a dormant population

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that migrated from Latin America that lives here in addition

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to maybe people, mothers that were infected

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and have had kids that have been born in the United States

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that were never tested for a serology for Chaga,

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that depending on where they come, you know,

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some countries like Bolivia, some parts of Columbia,

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Venezuela have a very high incidence

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and prevalence of positive serology,

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which is like the marker of having the disease.

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So what I'm saying is that it's important

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to pay attention to the disease.

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Uh, there's no crisis

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or a pandemic, anything, nothing like that.

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But it is a disease that usually we don't make the diagnosis

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because we don't think about it.

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Mm-hmm. And if we make the diagnosis early on,

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it can prevent the progression of the cardiomyopathy.

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Got it. Um, chaga has the acute phase, like you mentioned

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during your presentation, sort of like a flu-like syndrome.

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Then there can be a quiescent phase,

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and then some patients will go on to develop

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concerning heart disease from the parasite and some may not.

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Um, you were talking about ways to, how to predict

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who will develop disease, who won't.

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Now, as far as trying to prevent that progression,

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we know we can treat for the parasite,

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but also patients could receive medicines

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to prevent the progression of heart disease independent

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of the parasite like you would do with, from someone

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that has heart failure for other reasons.

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Which one do you think is the key factor?

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Is it controlling the parasitic load

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by perhaps not only treating it once,

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but repeating treatment at various periods in case there's

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repeat exposure depending on where you live,

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or a residual parasite burden

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or more focusing on the metabolic inflammatory milieu

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by using traditional heart failure,

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perhaps anti-inflammatory medications?

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Is it one the other or both?

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Yeah, that's a great question.

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And I think the answer is simple.

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I think it's both because, uh,

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check is a very complex disease

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and it affects very different mechanisms.

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Now, the parasite, when it's embedded in the tissue

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of the heart, it's a very low concentration of the parasite,

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but that low concentration is enough

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to trigger all this inflammatory autoimmune response.

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So you have to control both the parasite

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and that immune response

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that will trigger the alteration in, in the heart

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and leading to heart disease.

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So some preliminary data suggests that treating this

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with drugs that we've been using for early heart failure

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and using se anti-inflammatory drugs, you know, colchicine,

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things like that, that have been tried in other areas like,

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you know, know, uh, myocardial infarction

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and things like that may eventually be an important step

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towards preventing the progression of the disease.

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I thought it was really interesting when, uh,

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Dr. Rogers asked about the parasitic load.

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You, you, you responded, if you have a low parasitic load,

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that might be worse than having a high parasitic load

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because of the chronic exposure to the inflammation that

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that low parasitic load might cause.

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I thought that was really an interesting concept,

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but how about trying to bring in the load to zero

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with repeated treatments for the parasite?

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Yeah, I think that's one of the aims

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that we think we wanna do because it's interesting

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because this low parasitic, uh, concentration

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and load, what it triggers is a kind of a

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modulated immune response.

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Not enough to get rid of the parasite,

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but enough to damage the heart.

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Mm-hmm. If you go the other way around,

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then the response is different.

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So I think that, yeah, if we had the ways

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and means to eliminate completely the parasite,

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and again, the sooner the better.

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If you treat kids with a positive serology,

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you're gonna pretty much eliminate all the parasite.

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But as you get older, it's harder to eliminate the parasite.

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And then new strategies with combinations

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of medications should be needed.

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Unfortunately, this is a neglected disease

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and there hasn't been a lot

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of development in new antiparasitic drugs.

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We still use bissol and OX that were developed 70 years ago

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and we haven't had anything new in that area.

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So this is a call for trying to get new developments

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and some companies are trying to look into that.

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You led the, the benefit trial, which was a, you know,

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pivotal trial in determining the effect of medication

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to treat, uh, Chagas disease

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and determine if it helps program prevent progression.

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How do you get involved in, uh,

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such a large multinational undertaking?

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Uh, just gimme the story of how this all kind of came about.

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Yeah. Well the story is kind of funny

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'cause I had, uh, moved

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to McMaster University, which is in Canada.

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This is a university

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that has always led big clinical trials,

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and it's where evidence-based medicine was born.

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And the chief of cardiology that recruited me is Ali Uf,

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who's led some of the largest clinical trials in cardiology.

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So we were at a meeting in Brazil, uh, drinking

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Nias, you know, there.

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And then, uh, there was this discussion, well,

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we should do something about shags disease.

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And that's where, you know, we came up with a concept

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of the benefit trial, but that was just a concept.

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Then we had to get the funding mm-hmm.

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And get to the trial started,

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and we had to recruit almost 50 centers in Brazil,

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Argentina, Columbia, Bolivia, and El Salvador.

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So that was a huge undertaking.

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It took me 10 years to do the trial,

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but uh, it was, you know,

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it's been the largest trial ever conducted in Chagas disease

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with almost 3000 patients that were randomized.

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Sonias were the genesis of Thiss is the answer,

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The thing that benefited thousands of people.

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Yeah. Okay. I like, I like it. I like it.

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Uh, knowing what you know now,

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what would be the next clinical trial

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that you'd say would be ideal to conduct in Chagas disease?

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Yeah, I think that one of the things

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that we learned in the benefit trial is that the parasite

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and treatment behave very differently depending on the

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region of Latin America that you target.

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And this is related with the parasite load

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and also with the strain of the parasite, uh, chaga,

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which is T cruzi has five different strains

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and they have a very different progression of disease

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and they respond very differently to treatment.

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So I think, and the other thing is that, you know,

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we just gave a set treatment

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for about 90 days and that was it.

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But these are chronic embedded, uh, parasitic infections

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that you probably need repeated low dose therapy throughout

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maybe a lifespan or the,

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Brings it out to zero.

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Exactly. So I think that, you know,

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the next trial is a combination of that

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with using other modulators of immune

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and inflammatory response to try

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to prevent the progression of disease.

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So perhaps assessing both sides and viral load

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and inflammatory response.

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Yeah, I think a combination is the answer,

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See what happens.

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Um, you also mentioned briefly, uh,

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and perhaps I didn't get this right,

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but that men seem to have

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more severe imaging characteristics, uh,

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lady galin enhancement, uh,

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when they have chaga cardiomyopathy

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when compared with women.

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Is there a hypothesis as to why that's the case?

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Is it viral, um, para parasitic load?

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Is it lifestyle, lifestyle thing,

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or any exposure to a different hormonal milieu?

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I mean, what do you think? Yeah,

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That's a good question. I don't think

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we know the answer.

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This comes from a small study that I showed there, there,

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but you know, it's always been used as a marker

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of risk being male.

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And this has been repeatedly shown throughout many series

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that were observational

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and even in benefit, we saw a signal on that.

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And basically the, the theory is that

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because males have a higher degree of

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alterations in fibrosis

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and in, uh, myocardial contractility,

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they may develop more rapidly the disease,

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but we don't know if it's really triggered

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by hormonal response or what.

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Lifestyle is pretty much the same.

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So we don't really know the cause,

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but we do know that there's a difference between

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the distribution

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and the amount of fibrosis between men and women.

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Interesting. Um, I wanna switch gears a little bit

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to your other areas.

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Areas of expertise, which are many, but I know syncope

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and autonomic dysfunction is, is one of them.

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Uh, we deal with autonomic dysfunction a lot in the

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office every day.

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Um, I see a lot of patients come in with what seems

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to be very clear, vasovagal syncope, uh, recurrent,

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some more severe than others.

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And this can be really frustrating, uh, for patients

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because we can tell them, Hey, you know,

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what I think you had is benign.

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We did a lot of tests. Things look okay,

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but they keep having the problem

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and there's always a conversation to be had there to try to

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reassure them about the diagnosis

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or discussing what potential next steps could be done

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to prevent syncopal events.

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I'm talking about mild cases, not frank lifestyle, limiting

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severe pots in this adenoma.

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What would you tell a patient that comes to your office?

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I mean, I wanna learn from you, uh, with those complaints

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and how do you sort of manage that conversation?

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Yeah, that's a great question.

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So out of Calgary, we've, uh,

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in Canada basically we've run all the post trials,

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the prevention of syncope trials,

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which actually we're right now on the post 10.

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So we've done 10 trials trying different

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medications maneuvers and things

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Like Timmy, you know. Yeah.

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Like, so the things

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that we've learned are, are, are several.

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Now we know who are the people

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that are gonna have more recurrence of syncope.

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So people that have three episodes in a year are the ones

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that are gonna have recurrence syncope.

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Women are usually also much more

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frequently affected than men.

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It usually starts at around 14 years of age

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and then it has another peak around 60.

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But you know, people that are having that, you know,

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usually we start with easy maneuvers, like, you know,

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increase your water intake, salt intake that doesn't work.

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You know, counter pressure maneuvers, you know,

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stocks that help with that.

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But the thing is that sometimes we need medications

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and there's two trials that we've conducted

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that were randomized placebo controlled trials.

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One with fluorine and the other one with midodrine.

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The most effective drug is midodrine.

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That is an alpha agonist and it works quite well.

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And usually with a low dose people

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are maintained quite well.

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The other thing that we've learned in the last five years is

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what we call the low blood pressure phenotype.

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So these are people that usually they tell you, no,

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you know, my mother had the low blood pressure and my aunt

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and you know, they say, what is this?

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And when you go and te

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and check these people, they usually have blood pressures

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around 195 systolic

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and they have frequent dips in blood pressure throughout the

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day that you can detect by a 24 hour

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ambulatory blood pressure monitor.

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Now, we've likely discovered that if we treat those people,

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they're the best responders to treatment like midodrine.

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And those are the people that do well.

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There's a very small subgroup

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of people usually over 50 years of age

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that have these asystole.

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In other words, long pauses that don't respond to anything.

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And pacing from a couple of trials that we did

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with some special pacing algorithm works quite well.

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And now more recently,

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there's something called cardio neuroablation.

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Mm-hmm. Now the heart is very complex, uh, little organ

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that also has a very intrinsic

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autonomic nervous system of its own.

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And we've seen that in some patients

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that have these recurrent falling all the time

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and nothing works, that if you go

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and target these little ganglia that are around the heart

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and you cauterize them, you may have a really good response.

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And now we're doing another trial in which we wanna compare

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this technique to a sham procedure.

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Mm-hmm. Because before when we did the pacemaker trials,

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we saw that there was a huge placebo effect.

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So bottom line is that we do have several treatments

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for people that have this mild

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to moderate vasovagal syncope.

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It's easy to to treat.

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The other thing that usually treats it is that

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as you get older, you get less of these episodes. So

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Just just wait, wait around a little bit.

350
00:15:34.795 --> 00:15:36.325
Yeah, exactly. Well, doctor,

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I wanna take too much of your time.

352
00:15:37.445 --> 00:15:39.205
Thank you for coming again. It's a pleasure having you.

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I have one question for you, which we will be off,

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we'll discuss offline, which is EZ Venezuela.

355
00:15:44.095 --> 00:15:46.925
We'll colo we'll talk about that later. We'll,

356
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The eternal debate, and I won't get into that.

357
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Yeah, we'll talk about the

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repa later. Thank you for coming.

359
00:15:51.365 --> 00:15:53.045
Okay. Well thank you very much for having me here.