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Advances in Left Ventricular Assist Device Therapy
Maria Costanzo, MD
Midwest Heart Specialists
Naperville, IL
So, my task is to discuss ventricular assist devices and
where we are at with them. Just to put it in perspective,
we know that by the year 2037 we’ll have more than 10
million people in the US with heart failure, and this is
not a surprise because heart failure is highly dependent on
age. As of 2020, we’re going to have 54.6 million people in
the US alone over the age of 65, a number that will
increase by 87 million projected by 2050. On the other
hand, while we made great strides with transplants, we now
have a half-life of 13 years. You can see below that the
number of transplants, both in the US and worldwide has not
changed. In fact, we have been doing about 2,500
transplants in the US each year since 1997 and this is not
changing. Actually it’s further decreasing this year.
Cardiac transplantation has multiple contraindications,
some of which are general, some are more specific, some are
uncertain, but there is a proportion of patients that
because of these contraindications cannot be listed for
heart transplantation.
This is why we turned to ventricular assist devices as what
we call destination therapy. Some people ask destination to
what, but essentially it means for long -term use. In fact,
if you look at the results of the REMATCH trial in terms of
one-year relative benefit, it had a benefit far superior to
that of any other drug used in the study of patients with
advanced heart failure. The other advances that we are
witnessing in heart failure is that we understand more and
more that as heart failure progresses, not only do symptoms
get worse but more and more organs become involved to the
point where patients that are end stage have a truly
systemic illness with a generalized inflammatory milieu and
hypoxic damage of organ and vessels.
So, if you look at the anticipated survival according to
the severity of advanced heart failure, you can see that in
some cases there is a greater than 50% mortality
anticipated. In hospital patients with chronic heart
failure that are inotrope dependent are likely to die in
three to six months. Those that are not inotrope dependent,
12 to 24 months, but you can see that survival is very
short in all of these patients with advanced heart failure.
As far as the devices that we now have available, we
started out with acute support devices that were placed
paracorporeally and then we advanced to pulsatile
electrically driven pumps which now are the equivalent of
this very ancient car because…this is Luigi’s car by the
way. We have devices that are much smaller and provide
continuous flow. Although there are multiple current uses
of assist devices, the reality is that at least 50% of
devices that we are implanting now are a bridge to
decision, ie, will this patient become a transplant
candidate if he loses weight, if he stops smoking, and so
on?
The REMATCH trial as you know was a landmark trial that
showed the superiority of devices over optimal medical
therapy in very advanced patients. I think that it is
interesting that everyone, the majority of people actually
focused on this part of the curve, and not only to the
increased survival but also to the tremendous attrition
occurring even in the device group due to infection, device
malfunctions, need to replace the device, and stroke. Only
more recently have we paid more attention to what happens
in this part of the curve, and that is that the greater
attrition actually occurred very early after device
implantation; 56% of death occurred before hospital
discharge, and even in the device group there was an almost
30% in-hospital mortality after implantation of the device.
So, that suggests that perhaps these patients were too sick
to receive the device in the first place if we exclude the
fact that there were bad surgeons.
We began looking in greater depth at the risk factors that
might predict the poor outcome and cause such a high early
mortality. Through multivariable analysis Katherine Lietz
and Les Miller came up with a risk score that can be
applied and can well stratify patients that are considered
for devices. As you can see here, the major risk factors
really reflect when the disease turns from class IV to endstage class IV when it becomes a systemic illness. Why?
Because nutritional deficiency leads to infection. Abnormal
coagulation is responsible for bleeding, as is liver
dysfunction. Renal insufficiency leads to renal failure,
and right heart failure is really the Achilles heel of all
the left ventricular assist devices in addition to
infection. The goal is to identify patients that are sick
enough to receive a device but that are not sick enough so
that the implantation of the device becomes futile like in
these patients that have the highest risk score. On the
other hand, these patients may have been implanted too
early.
We need to become better at identifying these two groups
with intermediate scores because they may derive the
greatest benefit from the implantation of the device. Based
on the risk score and based on the severity of heart
failure, the large national registry INTERMAX has indeed
created seven conditions, each one of which reflects a
certain risk, being highest in patients that have
cardiogenic shock and lowest in patients that have advanced
class III. Keep this in mind because this is where the next
steps are going to occur. In fact, if you stratify survival
according to the INTERMAX levels, you see that they well
reflect the outcome after device implantation.
The main advance has really been the availability of
continuous-flow devices, which in addition to providing a
similar flow, they also have other advantages including
being silent which is very important to the patients. Even
more important is the fact that because they don’t have a
lot of mechanical parts, the durability is greatly
extended. Now there are more than 500 patients worldwide
who have had for example the HeartMate II device for longer
than five years. Definitely we have made great strides in
terms of durability. Although the most commonly used pumps
now are axial flow pumps, I believe that the next
generation will be centrifugal flow pumps.
As you might imagine, there is a relationship between the
pump rate and the pulsatility. If you support the patient
with a very low rate, for example 8,000 RPM, you’ll have
complete pulsatility. As you increase the RPMs, the
pulsatility declines and almost disappears. The constant
struggle is to find the ideal RPMs for that individual
patient. If you think that the echocardiographic criteria
for the synchrony are imprecise, this is even funnier
because basically what we do is determine the speed at
which the aortic valve opens with each beat. Then we
increase the speed until the aortic valve opens only
intermittently, and then the speed at which the aortic
valve doesn’t open at all, and then we place the patient in
between the slowest and maximal speed.
There have been now two large randomized trials, large for
this particular population. One was the HeartMate II as a
bridge to transplant, and this confirmed the hemodynamic
benefits of the pump in terms of cardiac index and which
pressure. Obviously with these patients as bridge to
transplant it is very difficult to evaluate the long-term
outcomes because there are competing outcomes such as the
occurrence of heart transplantation, but clearly much, much
better than what we saw with the pulsatile pump with a sixmonth survival of over 75% and a 12-month survival of
nearly 70%. You can see that the enemies remain
approximately the same with sepsis and the ischemic stroke
being the most common causes of death, but you can see that
the percentage according to implants is much, much lower
than we saw with pulsatile devices. Also it is important to
remember—and I don’t have time to stop on the se—but there
are different adverse events that occur in these patients
depending upon whether they are early or late after their
implant. There was a very substantial improvement in New
York Heart Association functional class. In fact, the
majority of patients returned to class I or II. There was a
consistent improvement and significant improvement in sixminute walk as well as quality of life based on the Kansas
City quality of life cardiomyopathy questionnaire. So, I
think this is the study that propelled continuous-flow
devices into the arena of bridge to transplant.
There was another study that was presented last year
regarding the HeartMate II as destination therapy, which
was compared head-to-head with the pulsatile version of the
HeartMate pump. You can see very briefly that basically the
continuous-flow pump won at every level over the pulsatile
pump, and we now consider pulsatile pump as really
obsolete. There was a dramatic decline in primary composite
endpoint. As you can see, the hazard ratios fav ored the
continuous-flow device also in terms of death alone,
reoperation, and disabling stroke. These are the survival
curves again showing a dramatic improvement in survival
with the continuous-flow device, and that this improvement
was sustained over time whereas you can see that in the
pulsatile arm, there was an ongoing attrition after two
years.
As I mentioned earlier, right heart failure remains an
Achilles heel and I will not belabor the point, but there
are multiple risk scores that have been developed to
evaluate whether right ventricular dysfunction is
prohibitive or not, but there are many issues that we are
still dealing with despite the progress in the pumps. One
is the so-called suck down phenomenon where the patient may
be dehydrated and the RPMs are too high and actually the
part of the left ventricle gets sucked into the inflow
cannula causing hypotension and shock. The other issue is
that if you keep the patient at excessively high RPMs and
you don’t allow intermittent opening of the aortic valve,
you may have situations like this where the leaflets of the
aortic valve fuse, and there is then insufficient flow due
to newly developed aortic stenosis. The biggest nemesis
that I see in our patients with axial flow pumps is that
they developed an acquired von Willebrand disease and they
are highly susceptible to bleeding, especially GI bleedings
that can be very dramatic and of acute onset and
progression.
Another thing that is very different is the tolerability of
arrhythmias. I used to show pictures of our patients with
pulsatile pumps that were bicycling while they were in fast
VT, and there was absolutely no hemodynamic consequence in
those patients. This is very different with the axial flow
pump because this type of arrhythmia can decrease flow
dramatically and is tolerated for short periods of time.
There are standard algorithms that have been developed to
treat arrhythmias. One of the causes that are specific to
these patients is that the arrhythmias can be triggered by
malposition of the inflow cannula, and this is one of the
situations that if recurrent requires surgical
repositioning of the inflow cannula. So, it’s something to
really pay attention to.
The other hopeful approach is to use devices that are much
less invasive and provide partial support such as the
Synergy Micro-Pump which provides between two and three
liters per minute of blood flow. You can see it is the size
of a double-A battery with the cannula inserted into the
right subclavian artery and the outflow cannula in the
right atrium. I think this could be well suited for those
patients that have exceeded the tolerability of oral
medications and yet are not sick enough to have devices
that provide greater support.
What remains true though is that whereas coronary deaths
are continuing to decrease, deaths related to heart failure
continue to increase. Both end-stage heart diseases create
multiple complications, but unfortunately there remains
collateral damage with mechanical circulatory support. The
main problems include surgical trauma, the shock that I
described due to hemorrhage, general anesthesia, mechanical
ventilation, and we have to remember that these patients
have an indwelling catheter at all times as if they
developed an infection, the only way to cure the infection
is really removal of the device. I think that where we are
moving towards and actually where the NIH is moving towards
is the application of these devices to patients that are
less sick such as late stage C, early stage D chronic heart
failure, patients that may be salvageable because they have
not reached the systemic stage of their illness. The NIH
actually launched an RFP. I don’t know yet the results, but
there were four proposals. This program called the REVIVE
IT Program is intended to evaluate an y continuous-flow
device in patients that we now consider class III B and I
think that’s where the field is moving toward. Thank you
very much for your attention.