The rates are highest in the
African American population
accounting for just a little under 50% of
cases but it can occur in any ethnic group.
Typically occurs in the maternal population
that's a little bit older, so 30 to 40 years old,
but it can occur in teens and 20 year olds.
It occurs late in gestation and we'll talk a
bit about the the pathogenesis in a minute,
or can occur up to several weeks
following delivery of the child.
Half of these patients fortunately, while they
will develop a transient peripartum cardiomyopathy,
a dilated cardiomyopathy
will spontaneously recover.
So that's the good news.
What is causing this?
So there is hypertension associated
with many cases of pregnancy,
although this is not the only cause.
Volume overload in fact, there are
significant swings in volume overall,
in trying to maintain adequate perfusion
of the developing fetus.
And so that volume overload in the setting of
hypertension may feed into the pathophysiology.
If you have multiple pregnancies, or you have
twins or triplets, that increases the overall risk
by mechanisms that may be related to what's
going on in the placenta, as we'll talk about.
There are nutritional deficiencies.
So mothers who do not get adequate antenatal
care, do not get adequate vitamin supplementation
may end up with a functional beriberi,
for example, inadequate thiamine,
which can cause a dilated cardiomyopathy.
For tocolysis, meaning that we are giving
drugs to diminish the uterine contraction
so we're trying to maintain a
pregnancy so the baby can go to term.
Use of those agents may actually
cause a dilated cardiomyopathy
because of the effect on the
vasculature of the heart.
You can also have metabolic derangement.
So metabolic gestational diabetes
may also feed into this pathway.
And then the immunologic
responses have been implicated,
although there's not a good literature
on that, but immune responses
potentially related to recognition of foreign
HLA from dad's contribution to the fetus
may drive some of this response.
The current thinking is that there is the
major driver for peripartum cardiomyopathy is
probably due to proteins that are being
elaborated from the developing placenta.
So and also from a best part of the
prolactin secretion so we know that prolactin
from the posterior pituitary, those
cleavage products have a propensity
to drive a dilated cardiomyopathy
in some animal models.
The placenta also makes antagonist to
vascular endothelial growth factor.
So up to a certain point, the
placenta is very angiogenic,
but as we get nearer and
nearer and nearer to delivery,
the placenta does not want
to have more angiogenesis.
In fact, it wants to stop it so that at
delivery, and as we deliver the placenta,
the mother doesn't bleed to death.
So there are placental derived antagonists
that inhibit vascular endothelial growth factor
particularly late in pregnancy.
Both of these prolactin cleavage
products, and the antagonists,
will drive an anti-angiogenic effect overall.
And the vasculature within the
heart is constantly remodeling
if we bathe that in anti-angiogenic factors that
can lead to impaired angiogenesis in that tissue
leading to ischemic injury.
As they say, these two pathways are thought to be
the most likely causes for peripartum cardiomyopathy.
But whether the others are contributory
and many cases, some cases they will be,
overall we have diminished myocardial
contractility and a dilated cardiomyopathy.
Arrhythmogenic cardiomyopathy again previously called
arrhythmogenic right ventricular cardiomyopathy
is one that will be another
cause of dilated cardiomyopathy.
It is a genetic disease of the heart muscle
characterized by fibrofatty replacement,
classically the right ventricle, but
we can also get fibrofatty replacement
involving parts of the left ventricle.
What's going on here?
The major presentation is right sided heart
failure because the dominant involvement
involves the right ventricle.
And as we are changing the relationship
of cardiac myocytes, one to another,
we develop significant severe rhythm disturbances
hence the name arrhythmogenic cardiomyopathy.
The main proteins that seem to be involved
are those that regulate cell-cell connections.
So we are looking at a variety
of proteins that connect
one cardiac myocyte to another cardiac
myocyte at the level of the intercalated disc.
And there are desmocolins, desmogleins
at the top, there's a membrane,
And then there are these proteins
that bridge into the cardiac myocyte
that are responsible for maintaining these
interactions again at the intercalated disc,
and the one in the green box, plakoglobin is
probably the most important known mutation
that causes a arrythmogenic cardiomyopathy.
What does it look like?
So the right ventricular wall is markedly thin.
All that yellow, that's fat that used
to be kind of that brown tan color,
and now it's been replaced with fat.
Pretty remarkable, because there's just
a little tiny sliver of cardiomyocytes
that are still within the right ventricular wall.
That fibrofatty infiltration, there's
some fibrous connective tissue
really kind of pervades along the entire
right ventricular wall, and as they say,
can also involve the interventricular septum,
as you see down at the bottom of the picture.
It can also involve focally, the
left ventricular wall as well.
On histology, this looks pretty much
like what we thought based on the gross,
most of the myocytes have been replaced.
So kind of the maroon colored cells,
those are going to be the myocytes.
That entire thickness should be myocytes.
And in fact, it's not, it's been replaced
by fibrosis, which is the blue strands,
and also by adipose tissue.
So the cardiac myocytes are dying, because
they've lost connection one to another.
And as they vigorously contract, they
tend to pull apart, that's our thinking.
And when they do that, they undergo apoptosis.
And then the myocytes or the myocardium,
replaces that with scar and fat.
So the mutations that we do know about
involve those desmosomal junctional proteins
at the intercalated disc,
and particularly plakoglobin.
There are also some mutations that
are known that interact the desmosomes
in the intermediate filaments inside the cell.
So connecting that bridging between the
cardiac myocytes to the rest of the cell.
Desmosomal detachment, particularly during
strenuous exercise is kind of the thinking
leads to apoptosis.
As the cells are dying, we are also
getting some degree of inflammation.
That combination of apoptosis and inflammation
is going to be clearly myocardial cell death,
and then we will get dilation of the ventricles and
leading to ventricular arrhythmia and dysfunction.
That dilation of the ventricle and loss
of myocytes is the dysfunction part.
The arrhythmias is because we've
lost connection cell to cell to cell,
and that's how we get a normal conduction
wave from throughout the ventricle.