Alright, that's the overview.
And if you've got that, then
you've really understood about
80% of what we're going to be talking about.
The next 20% are going to be details that are
important for you to take care of patients,
and also to ace those board examinations.
Let's start with dilated cardiomyopathy.
We are looking at the the the schematic
that we've used many, many times
to show the various chambers of the heart.
We have the right sided heart all in blue.
The inferior and superior
vena cava to the right atrium,
to the tricuspid valve to the right ventricle,
pulmonic valve going out to the lungs,
and then returning, in pink, to the left
atrium, through the pulmonary veins,
across the mitral valve, into the
left ventricle and out the aorta.
In dilated cardiomyopathy, we get
a progressive cardiac dilation
for a variety of causes that we'll talk about.
It's associated not only with that dilation, but
because we are stretching the cardiac myocytes,
we are actually causing a
rearrangement of the gap junctions
that connect between the myocytes so there's
electrical and mechanical dysfunction.
And overall, there's impaired systolic
function, it just doesn't squeeze very well.
It is the most common cardiomyopathy
causing about 90% of cases of
cardiomyopathy not otherwise specified.
Most commonly diagnosed in 20's,
to 50's, somewhere in that ballpark
but in fact, you can have it
much younger as we'll talk about.
You can have much later, as we'll talk about.
It is a lethal disease, one half of patients,
50% will be dead within a couple of years
if not successfully treated, and only 25%, a
quarter will survive longer than five years.
So this is as bad as or worse than many
malignancies in terms of mortality.
Again, it's 50/50 roughly for the
the causes of dilated cardiomyopathy,
we'll cover first the non genetic causes.
So it turns out that infections, in
particular, myocarditis will cause
damage to the cardiac myocytes
and then over a period of time,
you may develop a dilated cardiomyopathy.
You may not even have recognized the
original infection of the heart muscle.
But the consequences that we can see downstream,
will nevertheless, chronically progress.
Toxic exposures, and this can be
a variety of chemotherapy agents.
This can be heavy metals, this can
be alcohol in alcohol use disorders.
So all of those can cause it.
A relatively, unfortunately rare cause non genetic
cause of dilated cardiomyopathy is pregnancy.
So postpartum, or peripartum cardiomyopathy, and
we'll talk a little bit about those mechanisms.
So ischemic heart disease is probably
one of the greater non-genetic causes
and low levels of ischemia, not necessarily even
frank infarction, but low levels of ischemia,
can lead over time to progressive
dysfunction with a dilated heart.
You can have something called
This is the so-called "broken
heart syndrome", due to stress.
And what do we mean by stress?
We mean actually elevated catechols
which cause microvascular spasm.
Microvascular spasm that lasts
for greater than 20 to 30 minutes
will cause microvascular infarct and
then you get an ischemic cardiomyopathy.
So you can have stress
cardiomyopathy, or Takotsubo.
So just having a very rapid heart
rate for prolonged periods of time,
can also cause dilated cardiomyopathy.
And the reason for that is it's
part of high output failure.
It is actually a mechanism by which we can
induce heart failure and experimental animals,
just pace them very quickly.
And it is because over a period of time we've
talked previously, the normal cardiac cycle,
roughly a third of a second is going to be for
systole, and two thirds of a second for diastole.
And if you have 60 beats per minute,
that's kind of the the sequence,
but now if I increase heart rates
significantly - 120, 180 beats per minute,
the systole stays the same,
but the diastole shortens.
Remember, we only perfuse
the heart during diastole.
So chronic tachycardia, chronic
high output will actually drive
a dilated cardiomyopathy due to ischemia.
diseases like hemochromatosis, either
whether it's primary or secondary,
will also cause a dilated cardiomyopathy.
We'l ltalk about mechanisms shortly.
Let's look at the genetic causes.
Most of these are defects in
a variety of proteins involved
in the contractile apparatus of the sarcomeres.
And I will say, as we're getting more and
more sophisticated, smarter and smarter
and looking at more genes, we are
finding increasing genetic causes
of dilated cardiomyopathy, things that
had previously been called idiopathic.
As they said, majority of these seem
to be defects in force generation.
So the way that the actin and myosin
fibers interact with each other
or regulated by troponin and tropomyosin, we
don't get affective sarcomeric contraction.
But some of the genetic causes
involve signal defects that we're not
getting the appropriate movement,
say, of ions within the myocytes
or it may even be defective ATP generation.
Regardless of the cause - genetic or
non-genetic, in dilated cardiomyopathy,
again, we overall have
decreased myocardial contractility.
And the phenotype for all of these regardless
includes dilation of the cardiac chambers,
that's how we get the name dilated cardiomyopathy.
There is myocyte hypertrophy.
So in as we are getting less and less
contractile, the response, the adaptation
of the heart is to say, well, we
we need to have stronger myocytes.
So even as we're getting less contractile
force, the myocytes are undergoing hypertrophy,
so they will be enlarged.
The abnormal volume and pressure
will lead to the myofibroblast,
the fibroblasts within the heart
to lay down increased fibrosis
that's going to also materially
affect the contractility of the heart.
And because we have these
dilated chambers with diminished
movement of blood through them, they're
going to be prone to developing thrombi
which can eventually embolize