So hypertrophic cardiomyopathy
has 100% genetic basis.
We now understand this and the vast
majority are autosomal dominant.
So if mom or dad has it, 50% of
the kids will have it as well.
The main effect of proteins where wetalked
about, 60-70% of the time involves
beta-myosin heavy chain mutations.
But there are also other proteins that
regulate the interaction of actin and myosin.
So myosin binding protein C, troponin T
tropomyosin, and others may be involved.
We get hypercontractility, the
sarcomeres squeeze really well.
They don't relax, they don't release myosin heavy
chain from the accent quite as well as they should,
so we tend to have a very muscular heart that
is hypercontractile but poorly relaxing.
The phenotype is myocyte hypertrophy, we
classically see myocyte or myofiber disarray,
those are the classic buzzwords, and I'll
show you what that looks like in a moment.
That's the classic appearance on histology.
And it's basically an exaggeration of
the normal cardiac myocyte appearance.
So as I've already mentioned
previously, in other talks,
the cardiac myocyte is not a
boxcar, it is not a rectangle.
It's actually a branched cell that interacts in
multiple ways with adjacent cardiac myocytes.
As the individual cells
undergo prominent hypertrophy,
we've just seen exaggeration of that
normal kind of branching architecture,
but then we can recognize it as myofiber disarray.
There will be fibrosis, so in the same
way that the cardiac myocytes are squeezing
and becoming hypertrophic.
They also tug very vigorously on
the associated cardiac fibroblast.
And those fibroblasts when they feel
increased pressure and squeezing like that,
they elaborate more connective tissue
so you will see interstitial fibrosis.
You can have left ventricular outflow tract
obstruction, and that is going to be the HOCM,
H-O-C-M, hypertrophic obstructive
And one of the other manifestations
that we can see on histology
are thickened septal vessels.
A way to think about this is that the
cardiac myocytes are squeezing so vigorously,
the poor blood vessels that are permeating
into the muscle of the myocardium
are trying to keep themselves
open and not be squeezed shut.
So they get a very thickened wall.
I'm not sure that that's the accurate
description of why that happens,
but it does happen, make sense to me.
You end up with poor left ventricular
relaxation, poor filling, diastolic dysfunction.
As a result, you don't fill the ventricle.
And so you get reduced systolic output volume.
And particularly if you have
HOCM where you get that premature
closure of the left ventricular outflow tract,
you will have a markedly reduced systolic output.
So even with a heart that's squeezing really well,
you may not have the same volume of
blood perfusing the peripheral tissues,
so you have reduced peripheral perfusion.
And as a result of reduced myocardial perfusion,
you may actually now worsen the entire process
by also imposing an ischemic component.
Overall, these patients are
going to be very much predisposed
to cardiac arrhythmias and/or heart failure.
The cardiac arrhythmias are happening because
you have markedly enlarged cardiac myocytes
and all the cells are individually larger,
the number of capillaries perfusing those
do not increase.
So you have a relative intracellular ischemia,
with a propensity to have arrythmias.
Signs and symptoms, so we don't typically
see hypertrophic cardiomyopathy,
until individuals go through
their pubertal growth spurt.
And during that time, there are profound
changes in the expression of various genes,
including some of the cardiac sarcomeric
proteins, and that's when we start,
beginning to see the manifestations
of hypertrophic cardiomyopathy.
Importantly and tragically, hypertrophic
cardiomyopathy is a cause of almost
a third of sudden cardiac deaths and
athletes younger than 35 years of age.
And again, this is because they have an
hypertrophied heart that is prone to ischemia,
they then exercise and they may
get a sudden, arrhythmic death
What are the other signs and symptoms?
Well, basically, this is
usually frequently asymptomatic,
particularly the non-obstructive
type, So if you have okay outflow,
and you don't get a syncopal episode
or you don't have arrhythmias,
you may not have much in the way symptomatology.
We typically pick up on kindreds
who are affected by the disease.
When we have an initial individual who develops a
sudden cardiac death or has some sort of episode,
we identify hypertrophic cardiomyopathy, and
because it's autosomal dominant dominant,
we go back and look at all of
the related family members.
And in that case, we can
pick up those individuals.
and we will try to prevent the consequences.
So we will give them
antiarrhythmics, we will give them
drugs that will reduce myocardial contractility.
We'll put in cardiac pacers, so
they don't have a fatal arrhythmia.
So the patients are frequently asymptomatic.
and if they do have symptoms, this is
going to be due to either regurgitant flow,
because we have we have moved the entry
leaf of the mitral valve out of the way
and we have now insufficiency of the mitral valve
with pressure and volume going into the lungs.
So exertional dyspnea.
You can also have diminished forward flow, and so
patients will present with systemic hypotension,
which we manifested as dizziness,
or lightheadedness or frank syncope.
If you have diminished perfusion to the
cardiac muscle cells, we can have angina,
and in fact, can be a cause
of a myocardial infarct.
Patients can present with arrhythmias,
which to them will feel like palpitations,
the heart is just beating out of
their chest or is beating irregularly.
And because of the tight left ventricular outflow,
you can have a very harsh systolic ejection murmur.
So signs and symptoms of