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Welcome back. We're going to talk now about inflammatory
diseases of the myocardium.
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This can be a cause of heart failure. It can be acute, it
can be chronic, it can be fatal.
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So it's an important entity to be able to recognize.
Myocarditis, simply stated, is an
inflammatory disease of the myocardium, that's all we're
saying. It's an itis, inflammation
of the myocardium, has multiple different causes. It can be
idiopathic. In most cases,
it is probably an autoimmune myocarditis but we don't know
necessarily what drives
In most cases of myocarditis in the US, in European
population, that's going to
have a viral cause. The most common amongst these include
Coxsackievirus B,
influenza virus, HIV, echovirus and, there's a big question
mark that we'll come back to
the end is whether corona virus can be a cause of
myocarditis. I'll tell you, the answer
right now is no but we'll talk more about that. We can also
have bacterial forms of
myocarditis. One is associated with the Corynebacterium
diphtheriae causing the
diphtheric myocarditis that is really due to the elaboration
of diphtheria toxin. You can
have staphylococcus or streptococcus myocarditis and that
can cause lesions that
you might expect in any other tissue where there is an
infection. We can have Lyme
myocarditis. That's the spirochete that you see there on the
right due to borrelia.
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We can have parasitic infections and in many places in
developing parts of the world,
Trypanosoma cruzi is a major form of myocarditis so called
Chagas disease. You can also
have Toxoplasma gondii which is also a very common form of
myocarditis in the
immunocompromised host. So, there are other forms. In
addition, you can have a fungal
myocarditis, aspergillus and candida are common players in
that world. And you can have
immune-mediated myocarditis; things associated with lupus,
rheumatoid arthritis,
sarcoidosis, other vasculitides and hypersensitivity
myocarditis due to drug administration
and not illicit drugs. Any of a variety of drugs can elicit
a hypereosinophilic or
and not illicit drugs. Any of a variety of drugs can elicit
a hypereosinophilic or
hypersensitivity myocarditis. What are the underlying
etiologies? So there is a genetic
predisposition. There is some increased susceptibility to
myocyte damage or there
can be genetic polymorphisms in immune function that
predispose an individual to
getting inflammation of the heart. There are also a variety
of drugs that we know
quite a bit about that can cause an ongoing myocardial
injury, doxorubicin used for many
chemotherapeutic regimens, cyclophosphamide in the same
general category, cocaine, and other drugs
In terms of the general mechanisms, we talked about
etiologies, we talked about the
mechanism. So there are kind of 3 general flavors. One is
antibody mediated, the other
is cell mediated, and then there is mediator-mediated
dysfunction. For humoral,
we have our vessel here and on the outside of the vessel is
going to be myocardium.
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If we have antibodies that recognize either endothelial cell
antigens or myocardial cell
antigens, they can bind and activate compliment. They can
also then recruit Fc receptor
bariant cells causing endothelial damage and we can also
then get direct myocardial
damage if the antibodies happen to be directed against the
myocardium. But when we get
endothelial damage, we're going to get movement of plasma so
we're going to see
a lot of edema. Edema in the heart is not a good thing. It
means the heart is going to be
boggy and not as tightly contractile. So that's going to be
a problem. And then,
with an injury to the endothelium we're also going to get
thrombus. And that can become
completely occlusive so that we end up with downstream
infarction, things that have
gone gray there. So we can have cell death like regular old
myocardial infarct but at a
microvascular level due to humoral-mediated injury. There is
the cellular component.
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We can have lymphocytes, T-cells, and then the recruited
macrophages that are
recognizing either endothelial and/or myocardial antigens.
And you can see them here
both attacking the endothelial cells as well as the
underlying myocardium. When those
cells attack the myocytes, they can be directly cytotoxic.
When they attack the
endothelial cells, they cause them to die and as a result of
that we get thrombus and
then oh my goodness, now we get ischemic injury on top of
that. So we can have direct
cellular injury causing both myocyte killing, cytotoxicity.
But also microvascular
thrombosis causing ischemic injury. And then finally, all
these inflammatory cells that
are coming in, they are elaborating a variety of cytokines.
Those cytokines may actually
cause a lot of dysfunction and as we'll see in a subsequent
slide, that dysfunction may be
way out of proportion to how many inflammatory cells we
actually see. So, the various
cytokines that are being elaborated include interleukin II,
that causes increased vascular
permeability so we get that boggy heart again. You can have
tumor necrosis factor
that's being made by the macrophages in particular that
causes cellular death and
dysfunction. You can have interferon gamma made
predominantly by the T-cells.
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Interferon gamma acts on inducible nitric oxide synthase,
INOS, of the myocytes and
causes them to become less contractile, it become more
relaxed and they don’t generate
as much contractile force. And then you can have TGF beta,
transforming growth factor
beta, that causes increased fibrosis, it drives the
fibroblasts that are part of the normal
myocardium to make more scars, you end up with a stiff
heart. All of those mediators
combine to make the heart really very dysfunctional and way
out of proportion to any
amount of inflammatory cells that we may see on a biopsy or
even at autopsy.