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In this discussion,
I'm going to consider an area of major importance in
the following of patients with neuromuscular disease,
the nature recognition and management
of heart involvement.
I'm going to emphasize the cardiomyopathy
of the muscular dystrophy because these are
probably the most frequently encountered.
The first slide presents an overview of the
neuromuscular diseases in which
cardiomyopathy is significant.
Note,
two general points.
First,
cardiomyopathy can occur in virtually all
forms of muscle disease
and most neuromuscular diseases,
whether whether muscular or not
I am focusing on those in which it
is most important note.
Secondly,
that the conditions listed are not listed because
of their individual frequency,
but because cardiac disease is significant in
these conditions.
Thus,
some conditions such as periodic
paralysis,
a rare form of distal myopathy and several other
conditions can occasionally have
cardiomyopathy,
but they are not particularly but it is not particularly
frequent in those disorders.
The first group of conditions
arbitrarily listed as muscle
disease can all present with
cardiac disease and arrhythmias or heart
failure can occur.
I will return to this group in detail.
The Guillain Barre syndrome is not the only
neuropathy in which cardiac disease occurs,
but I felt the only one likely to be followed
primarily by this audience.
Obviously,
other neuropathies,
amyloid alcohol collagen
disease and so forth can have coincident heart
disease.
The spino cerebral generations may not really
belong on a listing of neuromuscular diseases but
are important in terms of the frequency of
cardiomyopathy.
And in fact,
cardiac disease occurs with a higher
frequency in Friedreich's
ataxia than in most of the other conditions that I am
discussing.
So,
I will be coming back to this disease.
This slide shows the familiar faces of a
patient with myotonic dystrophy.
And it is appropriate to lead off the discussion of the
cardiomyopathies of neuromuscular disease with this
disorder because probably in upwards of
90% there is clinically detectable evidence
of cardiac disease in myotonic dystrophy.
Our series is now considerably enlarged from the 33
adults mentioned on this slide and the figures
remain roughly the same.
Namely,
a majority of patients have detectable
conduction abnormalities and conduction abnormalities are the
most prominent abnormality that one sees in these patients.
And the one that's most clinically important.
23 of the 33 patients had first degree heart
block,
five right bundle branch block,
two left bundle branch block,
left anterior hemi block and
even three patients with complete heart block and
myotonic dystrophy has been reported on a number of
occasions as the first detectable
manifestation or the first presenting
manifestation rather of complete heart
block presenting to
hospital.
It should also be pointed out that first degree heart
block can be detected on the cardiogram in
family studies before the
patient has been diagnosed as myotonic dystrophy.
Though in most of the patients,
we have studied other signs of the disease were
present,
multiple premature ventricular contractions are seen somewhat
less frequently and surprisingly,
although this is listed as a cardiomyopathy.
Frank congestive heart failure occurs in a
minority,
usually 10% or less of patients.
This slide illustrates the typical
electrocardiographic findings of the patient with
myotonic dystrophy and shows the
prolonged pr interval
shown there with apr interval of about
0.26 1st degree heart block.
A leftward shifting the axis which probably
represents left anti your hemi block and a
right bundle branch block pattern with a
prolonged Qs
in studies which we've done of myotonic dystrophy
trying to define the nature of the
conduction abnormalities.
We have found that there is evidence of disease,
not just of one facile,
the anti facile or another
facile,
but in all patients in whom bundle branch block is present,
we found evidence of disease by his bundle
electrogram.
So this is a diffuse disease of the conducting
system.
This slide shows a his bundle
electrogram with tacky pacing and
shows that with tacky pacing
shown here,
there is with a pacemaker spike,
a failure to conduct.
Thus,
a evidence of a higher degree of
block,
a waky box type of conduction defect,
which we are able to detect with rapid atrial tay
pacing in patients with myotonic dystrophy.
And we think this may be a way we're not certain at this
point,
it may be a way of picking up higher degrees of conduction
abnormality before the patient gets into
difficulty with this
summarizing.
Then on the next slide,
the electrophysiologic abnormalities,
which we have found trifascicular disease
has been found by the his bundle studies and
these abnormalities appear to occur early in the course
of myotonic dystrophy.
And we think that stress of the conduction
system by rapid pacing through
pacemaker wire may produce higher
degrees of heart block and may in the future
provide some way of detecting those patients who
are going to go on and develop a third
degree heart block.
The next slide is
going to describe a
complication or another abnormality of
the heart,
which we have recognized in a number of patients with
myotonic dystrophy that is the
occurrence of mit valve prolapse.
And this slide shows a pedigree of a
large kindred with myotonic
dystrophy.
Not in the legend,
myotonic dystrophy indicated here,
valve prolapse.
On the other side of the figure,
the proband in this case was actually presented
for evaluation of a heart murmur and
palpitations.
And on evaluation was found by
echocardiography and other studies to
have microvalve prolapse.
So we studied other members of the family and found that a large
proportion of the members of the family with myotonic
dystrophy also had mitral valve prolapse.
In subsequent studies,
we have determined that a substantial proportion
probably 10 to 20% of patients with
myotonic dystrophy have
electrocardiographic excuse me have
echocardiographic evidence for
mit valve prolapse.
This slide showing the echocardiogram which was
obtained a very characteristic systolic
sag seen here is the
finding felt to be
characteristic of my valve prolapse that can be
diagnosed by echocardiogram.
Most of the patients in whom echocardiography
showed mit valve prolapse also had a murmur and a
click to support the diagnosis.
This leads us then to briefly consider on this slide.
Some of the things which have been observed by in the
cardiology literature in patients with mit valve
prolapse and things that I feel
may be important to look for in the
patient with myotonic dystrophy who has my valve
prolapse,
arrhythmias can occur and
although it can occur in a fairly
high proportion of healthy females,
a number of our patients were male.
And we feel that this finding
of mit valve prolapse may predict
patients who are going to develop trouble with arrhythmias
and other manifestations of
the mit valve prolapse syndrome in the
myotonic dystrophy population.
Another point deserves consideration in the discussion of
myotonic dystrophy and that is having pointed out to you
the frequency with which cardiac conductions are
encountered.
What is the effect of the treatment of myatonia
upon the
conduction abnormalities of these patients?
Since myatonia is characteristically treated with quiNINE
or Pronestyl procaine amide does
this have a deleterious effect upon their cardiac
conduction.
The next slide shows a study which we did of a
group of patients,
some 13 patients with myatonia studying the effects
of quiNINE procaine amide
and diphenylhydantoin on
their cardiac conduction.
And you could see that there was an increase in the pr
interval in the majority of
patients treated with procaine amide,
a substantial proportion of those treated with quiNINE
and a much smaller proportion of those treated with
Dilantin.
And I think for this reason,
we feel that Dilantin may be theoretically at least
preferable in terms of the treatment of
patients with myotonic dystrophy.
If their myatonia is to be treated because it
actually decreased conduction
in terms of its effect conduction time,
in terms of its effect on the pr interval.
So that Dilantin in the patient with
abnormality of cardiac conduction and myotonic
dystrophy may be the preferred agent.
Turning.
Now from my atomic dystrophy,
I want to consider the cardiac
abnormalities of the patients with Duen dystrophy
illustrated in this little fellow on the next
slide,
a typical case of Duchenne dystrophy with
the large calves,
the proximal atrophy and the increased lower doses.
This slide summarizes the studies
which we have done in patients followed clinically with Duen
dystrophy.
Very important points to be made concerning Duchenne
dystrophy is the relative rarity
of clinical cardiac
disease in terms of the patient's symptoms
and the need to treat the patient with Duchenne muscular
Dystrophy
Thus,
congestive heart failure has been seen in only
one of 43 of our patients,
including seven patients who were followed through their terminal
illness,
palpitations seen in only two out of
43.
On the other hand,
as shown in the next group,
electrocardiographic abnormalities are very
frequent and the clinically detectable and
electrocardiographically detectable sinus
tachycardia seen in a majority of
patients ventricular premature beats,
infrequent,
but a very distinctive cardiographic
finding
the abnormal R to S ratio that
I'll be showing you in a moment on a cardiogram of a patient with Duen
dystrophy found in the
majority of patients with duen dystrophy.
Also by echocardiography,
we have found an increased incidence of
valve prolapse in patients with duen dystrophy.
Though these patients tend not to have murmurs and
clicks and it is not certain at this point that this
may not represent either an artifact of the recording
or an abnormality of the papy
muscles as opposed to the valve leaflets
themselves.
This illustrates the
characteristic electrocardiographic
picture of Duchenne dystrophy.
Note the tall are
to
ratio in V one and there are normals that it must be
corrected for in terms of the age of the patient.
This one clearly being abnormal for this child
age 10,
the increased R to S ratio and
deep q waves in the lateral precordium.
Also note the RSR prime.
Actually,
you can see almost an
RR prime double prime and sometimes you
can see three or four RR prime,
double prime and even triple prime
patterns in the right
precordial leads this pattern.
Then being in a child who
is presenting the appropriate age for
dystrophy almost pathetic
of the condition.
Several points concerning this cardiogram.
One is that it has been seen actually in about
10% of carriers of Duchenne
dystrophy who have no other evidence of
cardiac disease.
And it is certain that patients with
definite Duchenne dystrophy that is a
mother who was a carrier and
had an inflicted brother and one of two or three
Children with Duchenne dystrophy
child.
From this pedigree,
which we have does not have
the classic cardiogram.
So that although it's characteristic of the
disease,
it is not always present even in
patients who clearly have Duchenne
dystrophy.
The next slide shows the pathology of heart
muscle in Duen dystrophy and
illustrates the severe replacement fibrosis,
which one can see in the heart.
Now,
there's a very important point to recognize concerning the
distribution of the
heart pathology and Duen dystrophy.
And I will be contrasting this to another form
of neuromuscular disease.
In a few moments note that
on this slide,
there is severe
cardiac muscle replacement
with severe fibrosis,
noted on this Trichrome stain loss of
muscle fibers and replacement with connective tissue.
This section is taken from the postero basal
portion of the myocardium.
The next slide from
the anterior
wall shows in this section a
remarkably normal
myocardium with no replacement fibrosis
and it should be pointed out then that this
pathology is confined to the
posterobasal portion of the myocardium.
It is not seen in the right ventricle,
not seen in the septum,
not seen in the anterior portion of the left ventricle and
confined to the posterobasal portion
in studies which were done initially by
Perloff and in several hearts which we have studied
subsequently,
a similar picture has been found.
This means then that the myocardial disease is
not at least by the path
pathological studies which have been done a
diffused process,
a generalized process as is the skeletal myopathy but is
rather remarkably confined to
the posterobasal portion of the heart.
It seems likely that this
distribution accounts for
the electrocardiographic changes which are
seen since in poster myocardial
infarction,
one sees a pattern with the tall R DS
in the V one lead such as I showed you on the Duchenne
cardiogram post true poster
myocardial infarction will have this with
the in these patients.
There is a distribution similar to the fibrosis scene
in the autopsy studies
of Duane dystrophy.
The next slide summarizes some work which we have done
on echocardiographic studies with Reeves and Nonda at
Rochester showing that there are detectable
electrocardiographic abnormalities.
But remarkably,
although there were differences noted in
left ventricular dimension,
shortening post to your wall excursion and the mit valve
prolapse which I mentioned
post to your wall thickness did not seem to be
abnormal in the echo studies which were done.
And so one cannot pick up this finding which is present
pathologically or a post mortem by the
echocardiographic studies,
which we have done.
Although there may be some dispute of this
about this in the literature,
this slide shows again the sagging of the mitral
valve,
which we have seen in a number of patients suggesting a
prolapse of the posterior
leaflet of the mitral valve.
Now,
I've mentioned already the remarkable
localization of the
pathology of the in the heart in
Duen dystrophy.
And it's interesting here just to contrast the
findings of skeletal muscle,
which I've abstracted from Dubowitz and Book and Brooke,
in which 100% of the
skeletal muscle biopsies show
fibrosis.
Basophilic fibers are frequent.
Necrosis is frequent,
fatos of fibers is frequent and the
distribution is generalized
in heart muscle fibrosis is seen
but is remarkably confined to the left ventricle
free wall,
particularly the posterior portion and
in the sections which we have looked at.
And that's many,
many sections from several hearts.
Basophilic fibers,
necrotic fibers and fibers undergoing fatos
have not been seen.
And in studies which we did a post mortem skeletal
muscle,
we saw continuing evidence of necrosis and
basophilic fibers even at the time of
examination of post mortem muscle.
So that there is a distinction to be made between the
cardiomyopathy in terms of its histological
characteristics.
Now,
what is the ideology of the heart disease?
I don't know as listed on the
next slide is it secondary to the clinical
state?
Well,
similar findings are not seen in the disease controls with
spinal muscular abnormality.
It was originally suggested that there might be a vascular
abnormality,
but this appears not to be specific for this condition.
And in fact,
the vessels at least macroscopically
and microscopically in our studies are normal.
Seems unlikely to me that it's related to neural
damage.
The question might be raised.
Is it related to a membrane abnormality?
There's very little evidence for this.
It is interesting to mention in passing that a
recent experimental model of
Mendel Ohio state
has shown in a model in which skeletal myopathy
occurs with the administration of aramine
that a distribution of cardiac lesions
is seen,
which is identical to that scene in the patient
with duen dystrophy.
Why this occurs is not yet clear
summarizing.
Then on the next slide,
the status of the heart in Duen
dystrophy note that clinical heart
disease is rare,
congestive heart failure is rare and only
terminally does it occur?
Distinctive cardiograph,
electrocardiographic changes occur and are useful in
diagnosis.
Echocardiac echocardiographic
studies do demonstrate impaired
contractility and in some patients mit valve
prolapse,
cardiac pathology is confined to the left
ventricle.
As I have pointed out the basis for the
cardiomyopathy remains unknown.
Thus,
in this the most severe form of
muscular dystrophy,
it is probably important to follow the heart from the
point of view of the rare patient who may develop
congestive heart failure.
But it is the pulmonary manifestations in these
patients that far outweigh cardiac complications
as their life threatening problem.