The topic of our conference this afternoon
is is a very important one
namely, heart
failure
and its important, as you'll hear from my colleagues,
for a number of reasons. The sheer prevalence of heart failure in our population
says that
you're going to deal with a tremendous numbers of patients having
related problems.
The associated
morbidity and mortality is very significant and
heart failure, one way or another, consumes a very, very significant
fraction of our health care resources.
So it's a problem that you're going to be dealing with
a lot of the time.
I will spend my time
just introducing the general concept which we've had a little
bit in lecture, but will try to embellish that
and illustrate some of the pathologic anatomy associated with heart
failure one way or another.
Then I'll pass the baton to Dr Matthews
who will make clinical reality out of this
and translate all of this into signs and symptom that the patients manifest
and
appropriate strategies
of medical therapy and then we will conclude the afternoon with
Dr Jonathan Haft
and with the participation of a patient of his
and discuss the treatment of advanced heart failure
with mechanical support and cardiac transplantation.
So that's
the agenda for this afternoon.
Now in its
very simple definition, and there are a lot of ways to define it, the very simple
definition of heart failure
involves the inability of the heart
to meet
to really pump sufficient blood to meet the metabolic needs of
the body.
Now this can happen in a in a variety of ways.
It can come to pass, and this isn't as frequent, that the
heart is putting out a normal or even an excessive amount of blood.
It's really pumping it out there, but it's being
driven by
an increased demand in the peripheral tissues that it just can't keep up with.
This sort of thing we see in thyrotoxicosis.
It used to be seen,
we don't see it much any more thankfully, in beriberi - vitamin deficiency
with vasodilatation
all over the place and the heart just couldn't keep up with
that volume
of the
cardiovascular system.
It's seen occasionally with arteriovenous fistulas
that dump a lot of blood directly from arteries into the veins in the heart
The heart just can't keep up. Or severe anemia.
Those sorts of things will result in what we call a high output sort of failure,
but much more
often, we're dealing with
the problem of
not enough blood being ejected
for one reason or another
from the heart to support even normal demands
and this is a combination really of
the loss of systolic umph,
in other words, the contracting heart just can't get it out there
in the way it should and
often this can be accompanied by
diastolic,
i've listed it here as diastolic failure but it's a difficulty in diastolic filling
which can impair the heart action. If the heart muscle can't relax and is ineffective
it's stiff
it won't
accept
the right volume coming into it and that's going to lead
also to failure.
One way or another, these factors can lead to a constellation
of signs and symptoms,
we'll get to that at the end.
It's really related on the one hand to congestion of organs which you know all
about now after
your
lectures in pathology and hypoprofusion of tissues which
we haven't emphasized as much, but it's a
very important point.
Now, when we look at the causes of heart failure and there are many, many of them, far more
than we can talk about,
but
if we look at those situations where there is
some unusual demand
on the heart, and the heart just can't meet it, they
fall into a number
of categories, and I will
illustrate each of these in a moment,
but one very important category is resistance
to flow, in other words,
if something is keeping the flow of blood from going so
the heart has to work harder to push it past that resistance
it will come to the point where the heart could no longer do it and it fails.
Another problem is what we call regurgitant flow, I mean you like to think of the
blood flowing in one direction through the cardiovascular system, but
sometimes it comes to pass where, at a point,
there's
regurgitation, instead of things pulsing forward, they slosh
backward, and that
imposes a strain on the heart as you will see
and thirdly and very importantly there is disease of various sorts, lots of sorts,
targeting the myocardium itself
so that there's no resistance to flow, there's no regurgitant flow
perhaps, but the
heart muscle is sick.
And finally, we won't talk
at all about this, I won't, about conduction abnormalities
which can also lead to decompensation
of the heart.
Now, I'd like
to illustrate some of these very quickly, don't get lost in the details,
just
let it flow over you, you're going to get these details later on
in the year
later on in your careers, but just for a little orientation,
I'll give you an example first of resistance to flow,
there is a good hallmark for
it, I can't show you hypertension obviously
but think of
the situation when a patient has established significant hypertension,
it means that 24/7
every minute, every beat of the heart
that poor left ventricle is having to force against an increased resistance to flow,
that's what hypertension
is all about. The result
one of the results you see here is is this rather massive
myocardial hypertrophy which i'm sure you all recognize,
so that's one
kind of resistance to flow. Here's another one, this takes a
little explaining, it's an unusual plane of section of the heart,
but what attracts your attention right away is that the left ventricle
is immensely hypertrophied, very thick
and very heavy, and the reason
for it is not terribly well shown here
but here is the aortic outflow, this is the aorta here, and this would be the aortic valve
which you can't get a good view of, but
a common lesion is stenosis of the aortic valve,
and obviously, in that situation, it's very analogous to hypertension, every time
the ventricle contracts, it's got to push that blood
through a stenotic valve
and it's a lot of work.
I'll show you one of these valves from above, this is an interesting one,
this is a pretty typical example of aortic stenosis,
you're standing in the ascending aorta, looking back
towards the left ventricle, and
you're aware from your gross anatomy that this should be a three cusp valve
and you're seeing a couple of things here,
first of all this is only two cusps
and that was a congenital problem
and it's a fairly frequent one in our population, there are probably a
couple of so-called
bicuspid valves in this room
and
whatever the case
the aortic valve is very susceptible to calcification
and stiffening with age, and if you
plot it against the aging population, we see an increasing
incidence of stenotic
aortic valves even if they're not
bicuspid, if they're congenitally bicuspid like this they get wrecked
very frequently
earlier on so that
instead of maybe in the seventies or eighties, it might be in the
fifties and sixties that the patient would suffer from such stenosis.
But you can see
that every time
the ventricle is trying to push blood through that orifice, and it's really like brick
it doesn't move.
It's going to be a
tremendous load on the left ventricle.
here's another valve stenosis for you, we don't see this as much anymore,
it's a result usually of old rheumatic fever in childhood, but the mitral valve
here is reduced to a fish mouth, it's all puckered up
and scarred, and frequently calcified,
and the valve leaflets
can't move at all,
so that the blood coming out of the lungs into the
into the left atrium trying to get through
into the left ventricle, you're looking down towards the left ventricle,
it's got to pass by that stenotic slit.
The result is damming back,
very obviously you know about passive congestion, you can see this immensely dilated
left atrium
and you can imagine
what was happening in the lungs
behind that sort of obstruction.
Now as far as
regurgitant flow, hold on with me
and i'll try to explain it, here is another mitral valve, we've chopped off the
the atrium and you're looking right at the
mitral valve, and
think about what you saw in gross anatomy, the mitral valve leaflets usually come together
like that and keep the blood, during systole,
keep the blood from flowing back into the atrium so all the blood goes out
the aorta like it should.
Here,
and this happens for a variety of reasons, but here this leaflet of the valve
is sort of pooched up and
and with every ventricular systole, blood is able to force its way back
into the atrium, which means
the poor old left ventricle is pumping some of that blood more than once
in other words it's putting part of it out the aorta, part of it back up the atrium,
and that comes
sloshing down for the next
beat of the heart
and it consists,
it induces a volume overload on the valve
and
on the ventricle
and it may fail.
Now when you get to the realm of myocardial abnormality per se, in other words disease of the myocardium
there are lots
and lots of examples, and the most frequent one and most important one is myocardial ischemic disease
in other words, the result of coronary artery disease, atherosclerosis
and its complications, and what happens when the myocardium
becomes ischemic.
Clearly many patients who have a myocardial infarct, an acute heart attack
will go into
acute failure if enough of the myocardium is involved right then and there in the
emergency room.
But chronically it can become a big problem even when the
situation heals. Here, for example,
a slice of a heart, this is left ventricle over here,
and this individual sustained a myocardial infarct, I don't know how long ago,
it could be years ago,
months ago, and you see a lot of scar
throughout the ventricular wall, a little bit back there, a little bit in the septum,
but a tremendous scar here
and when this involves enough of the ventricular myocardium, it puts a strain
on what's left of viable myocardium, because this
obviously doesn't contract.
Patients can sustain a lot of myocardial infarcts,
here's serial sections of the same heart, and you can see at least a couple of infarcts
that involve
a tremendous
fraction of the
left ventricle
and again when
that happens, the rest of
this can't keep up with it, and the left
ventricle fails.
Here is a heart that was
was removed from a patient who was still alive
happy and well as far as i know
This is an explant to the heart, in other words, taken out of the time of transplantation
and this was also
ischemic disease, and this
individual had scraped through
with this much of the heart converted into
what amounted to a fibrous sack, totally
non-contractile
and you can see there's even a clot in there because it wasn't moving
and that had
produced failure of the remaining myocardium.
So that's a
good sample of
ischemic
disease leading to chronic failure of the left ventricle.
Now, beyond
ischemic disease there are a whole lot of them, don't worry about the details
I'll show you this as an example of an inflammatory process targeted at
the myocardium. We see this
with certain viral infections, certain protozoan infections,
with bacterial
infections, but you can get inflammation of the myocardium
and you can almost literally hear
these cells chewing at the myocytes
and obviously
obviously that can produce failure.
We see that not infrequently,
then the heart can be involved in a variety of systemic diseases, in other words
you can have something going on affecting many tissues in
the body, but that something may affect the heart and produce
failure. Here's an example
now I don't know
if I want to dart in the auditorium completely to show you this
did you discuss hemochromatosis in genetics? Yes? Not a complete blank.
It's an ineffective storage disease because the body absorbs too much iron
from the gut,
and the iron
gets stored in a variety of issues and one of the tissues it gets stored in
is the heart,
and you recognize instantly that this is myocardium
and as you stare at it a little bit, you'll pick out some nice golden brown pigment
there and there and there, you see a little more over there, and little bit down there and over there.
and one of the pigments
you'd think of in the heart, someone asked me a question about this last week,
it would be lipofuscin (wear and tear pigment)
but another pigment you got to think about is iron, and this is stored iron
in this myocardium. Here is
that blue
Prussian blue iron stain, tremendous iron
load, iron is bad for you
if it gets deposited in certain tissues. This can produce myocardial failure.
This was from a relatively young man who presented with
very advanced heart failure
because of his unrecognized
hemochromatosis.
One other that you will hear about
probably next year
is amyloidosis. Amyloid
is an abnormal protein that could get deposited in a number of tissues
for a number of reasons, which I won't go into.
But all of this
sort of translucent, gray stuff surrounding the
myocytes, you're looking at a cross-sectional view of myocardium,
and you can see that each myocyte is enveloped in this
casing
of amyloid.
And this is
a marvelous example of something that renders the heart rigid
and unable to
expand diastolically, and it can be
a cause of heart failure.
Finally,
this is not a complete list, I'm just showing
the examples, there are
a number of genetic diseases of the heart muscle itself, where from
the get go, because of
abnormal genetic endowment
the heart is
made wrong. Here's an example
of something we call hypertrophic cardiomyopathy.
Cardiomyopathy means heart muscle disease.
This particular heart was immensely hypertrophic, you can see that left ventricle
it's really tremendous with no
valve disease, no hypertension to explain that,
but look at the
goofy muscle, you know
what myocardium is supposed to look like, and the histology people never show you
the kind of
disarray and criss-crossing of fibers like that.
This is the result of the genetic abnormality of this myocardium.
All right, these are just a few examples of the things that can go wrong
and most frequently,
if I had to pick from this whole list, I'd say hypertension and
ischemic disease
are the big actors at least in our population.
Whatever the cause, as the heart is
overburdened,
there are certain compensatory mechanisms that kick in
for a while, in other words, enable the heart to keep up
with the abnormal strain,
and some of these you know about, you've heard about I'm sure about the Frank Starling
mechanism,
where the myocyte is stretched by increased filling pressure, it's stretched
and contracts then
with greater vigor,
in other words, it can put out more UMPH
if it starts from a slight stretch. The trouble with that mechanism is that it fails.
In other words, for a while
it's adaptive, you get more and more UMPH for each
contraction and then it peters out
for a variety of reasons.
A second compensation is hypertrophy,
and you know about this, we talked about it last summer I guess.
It's a situation where the same number
of muscle cells are there
but more sarcomeres are added
and the muscle cells enlarge the whole
tissue grossly
enlarges and there's more UMPH.
I mean it's very definitely
a compensatory mechanism.
A third compensation
mechanism I've listed
is activation of neuro-humoral systems and we're not going to go into that
in much detail, just enough detail
so you know that
they are there.
Now here's hypertrophy!
Normal size myocytes you see over here
and each one is on the average just a little bit thicker
than the normal
That's because of addition of sarcomeres, not much change in the number of cells
and you can imagine these cells having more UMPH like a weight lifter,
imagine that, like a weight lifters arm
This is maybe what we see
grossly, there's an increase in the muscle, increase in the weight of the heart,
and sometimes
we see concentric hypertrophy, meaning
the chamber is not enlarged, it may even be a little smaller, gross thickening of the walls
and its
concentric.
We see that usually with pressure overload.
With a volume overload, we may see
what looks like no hypertrophy
at all except that's a lot more muscle
than there is normal, it's just that it's dilated.
That also happens in very advanced failure
from any cause, you see this sort of eccentric picture.
When it comes to the neuro-humoral mechanisms, I'm just going to race through these now,
there is
first of all
all of these things tend to be triggered by pressure and
stretch receptors that are scattered through the heart
the aorta, the carotids,
and the kidney even there is such sensing.
When the cardiac output begins to drop, these receptors say UH OH
and they trigger a number of things, one of the things they trigger is
a central nervous system,
i'm sorry, the sympathetic nervous system
with release of norepinephrine
and this can produce
a contractile boost for the heart
this can produce an increased heart rate
these things will help meet an abnormal load
and also this will produce vasoconstriction peripherally.
This is designed,
this evolved this way presumably to
to make sure that blood gets shunted to essential organs
so there's peripheral vasoconstriction
which increase, well we'll talk about what the bad things it does.
Vasopressin is released
from the hypothalamus, that's also a vasoconstrictor,
and we talked in class previously about
the renin-angiotension-aldosterone system.
The kidney senses the decreased flow that's coming to it, secretes renin which
acts on angiotensinogen which is circulating protein
forms angiotensin I
and then there's angiotensin converting enzyme which takes angiotensin II
that in turn
stimulates the production
in the adrenals of aldosterone.
The importance of all of this is first of all angiotensin II
is also a vasoconstrictor
and
between angiotensin II and aldosterone, there is
sodium retention, salt retention, sodium retention and water retention
and that has
some important consequences.
I just listed, I don't have time to go into it, the natriuretic peptides
secreted by the heart which tend to counteract the renin-angiotensin-aldosterone
system to some extent.
Unfortunately, all of these
mechanisms
are limited in how much help they can provide and there's a downside
to a lot of them.
Now
problems with hypertrophy, it just gets bigger and
bigger and bigger muscle,
it doesn't work out that way because the capillary network in the muscle
does not increase in parallel and you
end up with perfusion problems so there's a limit to how much hypertrophy
the tissue can stand.
Same is true for the ratio between mitochondria and
and contractile protein, so to speak, the mitochondria-to-meat ratio
does not keep up to what it should be so the energy is a problem.
Then very importantly
we're learning that there is altered gene expression
and alteration in the
proteins that are produced, and these may involve
contractile proteins,
segmentation
contraction coupling them, they may involve energy utilization,
but some abnormal proteins are made
there's an increase in apoptosis
in a hypertrophic myocardium
and, under the influence
of all of this is actually driven by the various hormonal
things that i've mentioned
and with something
we call remodeling occurs, there's a change in geometry of the ventricle
which can have implications of tugs on the chordae tendinae of the mitral valve
the wrong valve, you can get mitral regurgitation,
it's a disadvantageous thing
often associated with a lot of fibrosis, that blue-green tissue racing through the myocardium
is a fibrosis in the remodeled ventricle
which causes problems of its own as you can imagine, I don't have to go into any detail
So that's a problem
and there's a problem
with neurohumoral activation,
vasoconstriction increases the
afterload that this poor old failing heart has to pump against.
It sounds like
a nice mechanism, but it
bites the heart
Various of these humoral substances are
cardiotoxic
chronically
in other words, they are responsible for the increase in apoptosis
they drive the remodeling and it's a bad thing for the heart
in the long run,
and we know about the
implications of sodium and water retention and how that
overloads the heart.
All of these things
contribute to the downward spiral
and I've simplified a very complex business, but
there are many
consequences for the peripheral tissues and that's what we're
really talking about when we talk about heart failure, what's going on
in the peripheral tissues.
These consequences we can talk about in a number of ways, we talk
about sometimes forward failure and backward failure.
Forward failure being the idea that
the failing heart does not perfuse the tissues well enough, and
backward failure you're familiar
with the idea of passive congestion and we talked about that in class
so you have a good image of that.
We speak of left heart failure and right heart failure,
most processes that cause
heart failure start out on the left
but it's a closed plumbing system
so as the left heart fails, the right heart is going to fail.
The commonest
cause of right heart failure then is left heart failure.
There are some of the examples where the right heart fails primarily and it has to do
with things happening in the lungs,
they're relatively less common and you'll hear more about them some other time,
but the backward consequences of left and right heart failure are very
familiar to you already, we know that when the left heart fails you get
pulmonary congestion and edema,
when the right heart fails, you get
elevation of hydrostatic
pressure in a variety of tissues
with associated
congestive changes in organs and accumulation of edema
fluid and this
is when we start to speak of congestive heart failure.
We're throwing that adjective very frequently
What we're not emphasizing, and I'll just conclude by mentioning this,
are the forward changes
associated with left heart failure, in other words, when the left
heart fails, things begin to
happen because tissues in a variety of places simply aren't being perfused.
And you're familiar already with
the activation of the
renin-angiotensin-aldosterone system
from forward failure to
supply enough blood to the kidney,
I would point out that as the perfusion drops more and more,
the kidney can really shut down as far as its excretory function and nitrogenous
waste can pile up.
Sometimes they speak,
people speak, of a cardio-renal syndrome because of this.
Well many other
tissues suffer from this lack of perfusion in the same way.
We've shown you for instance the liver,
and the liver gets caught in a one-two punch,
there's resistance to outflow from the liver
the fact is that the poor old failing left ventricle isn't delivering enough blood
to this, the central
lobular area,
and it undergoes a sort of hemorrhagic
necrosis which you remember that, you never forget
that kind of a picture.
Now something, a little wrinkle that I'll point out here,
is that the aldosterone
levels in patients in failure are way way up there
and part of it
obviously is because it's been triggered by the production of angiotensin II
and so forth, but the liver
when it's in that kind of a state,
does not catabolize aldosterone the way it should,
and the patient may end up with a twenty fold increase in aldosterone level partly because
of synthesis and partly because of
"non tearing down"
by the liver
One more example, the gut
may suffer in very advanced cardiac
failure, patches of mucosa
in the bowel may undergo
necrosis because they're furthest from the blood supply
and we speak of ischemic colitis, a bit of a misnomer as it is an inflammatory condition,
but actually that sort of thing
can be a problem.
Other organs and in fact even the central nervous system in very advanced failure
we see problems
with CNS function.
Well I turn the baton over
to Dr. Matthews
you just keep some of these images in mind and she will flesh them out,
as they say, with the clinical realities
and with some of the
therapeutic strategies
that make sense I hope.