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>> Our next speaker is Dr. Shelby Kutty.
Dr. Kutty is the Director of Pediatric
and Congenital Cardiology at Johns Hopkins.
His research interests include myocardial function,
theranostic, ultrasound,
and cardiovascular analytic intelligence.
>> Thanks Melissa for the introduction.
I'd like to thank [inaudible] for the invitation to speak today.
These are my disclosures.
Failure of the myocardium is
such a common problem with heart disease of all causes,
so accurate assessment is fundamental to clinical management.
The task would seem straightforward, image the heart,
observe the motion of the myocardium,
make precise measurements,
and compare to normal.
Unfortunately, the methods so far all have
their weaknesses, particularly low dependency.
Lately, attention has been given to
incorporating afterload directly with
strain trying to calculate or
at least approximate myocardial work.
Let's discuss whether this approach would
be a useful complement to strain.
Could this be the proverbial better mouse trap
enabling us to capture the essence of myocardial function?
Before we get too deep into our discussion,
let's deal with some fundamentals.
What is work, scientifically speaking?
Then they say we are measuring myocardial work,
is that actually true?
Physicists will tell us that work is force times displacement,
but what is force?
Isaac Newton figured that for us centuries ago,
it's mass times acceleration,
and that might be calculated for an apple of
non mass falling with known acceleration of gravity.
But how do we figure myocardial force?
That doesn't simply jump off an echocardiogram for us,
but we can use pressure as a surrogate.
We won't be invasive to put in
a pressure transducer into the ventricle,
instead we can use the cuff blood pressure and call it good.
The pressure against which
the myocardium is working serves as force,
and strain serves as displacement,
and the product is myocardial work.
With a caveat that we are not actually measuring
work but estimating and hoping for the best.
Now let's go into some details about methodology.
Pressure and strain varies with time through
the cardiac cycle and one can be plotted against the other,
and a pressure strain loop emerges for
the cardiac cycle beginning as the mitral valve
opens and as the ventricle
fills and proceeding through isovolumic contraction,
ventricular rejection, and finally isovolumic relaxation.
Myocardial work is the area inscribed by the slope,
the pressure times strain loop.
Pressure strain loops can be created from echo measures of strain
from three apical views and
then a cuff blood pressure down at the same time.
The timing of opening and closing of the aortic and mitral valves
are needed to transform this data and plot the loop.
We need to introduce one more physics concept here, power.
Power plotted here on the vertical axis is the rate of doing work.
If you graph power against time in one cardiac cycle,
the area under the curve is
the myocardial work index
corresponding to the area of the pressure strain loop.
In addition to power above the baseline,
you can see that there are times during which
the power goes below the baseline,
but it's all power and implies the work being
done and helps us distinguish
three additional myocardial work indices.
Constructive work is the work performed during
segmental shortening and reverse during isovolumic relaxation.
This is shown by this green images.
Then we have wasted work,
which is work performed during
segmental elongation and reverse
during isovolumic relaxation shown in pink.
Finally, work efficiency is calculated as fraction of
constructive work divided by constructive plus wasted.
The software output of converting the images and
pressure into the myocardial work rendering looks like this.
Normal values for myocardial work parameters
including work index,
constructive work, wasted work,
and work efficiency have been derived.
There is data from 1,800 adults and reference values have
been published for the pediatric age group based
on a smaller number of 183 subjects,
and correlations shown with age, body,
surface area, heart rate, and blood pressure.
Now, let's turn attention to how myocardial work
has been applied in patients with heart disease.
Starting with hypertension,
we expect that myocardial work which takes afterload into
the calculation goes up and
afterload is high and of course, it does.
It's well established that global work index and
constructive work are elevated in hypertension in adults,
and even more elevated than hypertension
is associated with type 2 diabetes.
Xander Jacquemyn and Rita Long from our center confirmed
these clinical associations in
a population of hypertensive children.
Cardiomyopathies, a target of
interest for investigation of myocardial work,
indeed global work efficiency,
work index, and constructive work,
all the three key parameters predict myocardial fibrosis on MRI,
and constructive work may provide
superior predictions compared to global longitudinal strain.
These indices also predict all cause mortality and the need for
transplant in adults with
advanced heart disease and heart failure.
In a large pediatric cities from our center,
Zhan and Jef Van Den Eynde showed myocardial work indices to
deteriorate in advance of [inaudible]
and global strain in anthracycline-induced cardiomyopathy.
It stands to reason that wasted work may
be a hallmark of ventricular dyssynchrony.
Patients with left bundle branch block
have higher amounts of wasted work,
and the degree of ventricular septal wasted work
independently predicts successful re-synchronization therapy.
Coming to valve disease,
there are important associations
between myocardial work indices and
long-term mortality in adults with aortic stenosis.
In separate studies,
these indices correlated well with severity of
aortic regurgitation and the severity of mitral regurgitation.
There has been some explanation of
potential value of right ventricular myocardial work.
In a small series of
heart failure with reduced LV ejection fraction,
RV work indices,
constructive work and work efficiency were depressed,
and RV reconstructive work correlated
with invasively measured stroke volume.
RV work also had significant association with PBR
and with all cause mortality in pulmonary hypertension.
For all the clinical promise,
there are potentially troublesome limitations.
First, myocardial work estimates [inaudible] train,
and all the limitations of defamation imaging that comes with it.
JLS occurs in a single dimension,
so not linearly proportional to
the three-dimensional absolute LV volume change.
Increases in end-diastolic volume do
not translate directly into an increase in strain.
Secondly, while stress
represents an internal work for a given systolic pressure,
the wall stress is higher for ventricles with larger radius,
and maintaining the wall stress
represents the internal work of the ventricle,
and this is not included in
the external myocardial work we measure
from the area of the pressure strain curve.
Finally, using pressure as a surrogate
for force results in unit problems.
Myocardial work is expressed as millimeters of
mercury along with a unitless percentage a strain,
but the classic unit of work as you know is the joule.
Another limitation is that for some conditions in which
myocardial work might be of great clinical relevance are
those in which the measured systolic blood pressure
is not the same as the LV systolic pressure.
Adjustments need to be made for
any pressure gradient that might be
present between the LV in the arm,
for example, in aortic valve
stenosis or hypertrophic cardiomyopathy.
In aortic valve there is gradient at
valve level and below the valve in hypertrophic cardiomyopathy.
Adding cuff pressure to
doppler-derived mean systolic outflow gradient is
potentially useful to address this
but may introduce its own errors.
The amount of published research on
myocardial work is already large,
yet our understanding of how to use
it clinically is still very preliminary.
The links between myocardial work
and outcomes need to be validated
prospectively on multi-institutional cohorts
and various clinical settings.
Diagnostic criteria will be refined in the process and
more meaningful comparisons with
conventional measures of ventricular function will emerge.
It's possible that imaginative investigators will derive
even better methods of assessing
function using the principles of myocardial work,
perhaps accounting for variable ventricular geometry and with
better ways for assessing and
adjusting for ventricular outflow gradients.
Finally, there is a great opportunity to explore
applications in congenital heart disease.
Returning to our original question,
when it comes to capturing the elusive essence of
integral function is myocardial work
a useful compliment to strain?
Is it really a better mousetrap?
Myocardial work has its strengths and weaknesses.
As we look at the data so far,
some things we continue to ask,
does it distinguish between severe disease and mild disease,
does it predict adverse outcomes,
and does it do it all better than existing methods?
Can it guide clinical management?
Finally, is it reproducible,
scalable, and applicable
across a broad spectrum of clinical settings?
I think myocardial work may ultimately find
an important place in care of certain cardiac conditions,
but for now it seems wisest to reserve judgment on
what value it will eventually have. Thank you.
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