hello and thank you for this opportunity
to share our knowledge and highlight
the importance of recognizing area but potentially
serious cardiovascular complication related to specific targeted
cancer therapy
at this topic is a hopefully of
great interest for the general medical providers
audience air air and especially oncologist and
cardiologist
i believe that shedding some slides will
hopefully you drive at my message a
little bit better
this topic was recently published in a
jack under this section of a case
challenge and at and jack cut your
oncology and the main aim was to
illustrate the importance of recognizing myocardial edema
as a rare but a serious a
manifestation of drug relate
it got pillory league at syndrome
after said the stage i want to
add briefly discuss at the condition of
popular leak syndrome or app called c
of as the most known form of
it is at the idiopathic at c
l as syndrome or on a disease
and this
air condition at that is a usually
an unknown a trigger a a systemic
cytokine to release that can lead to
a and it teal dysfunction with a
couple or a leak and a secondary
loss of protein rich a fluid
into the insisted should have many a
buddy organs and this leads to as
shown here hypertension with acute kidney injury
can lead to a massive but for
edema can lead to pleural effusion and
uncut eugenic pulmonary edema in addition to
a gastrointestinal edema and a
sites
ah the key issue here is that
volume resuscitation at a can watson or
can improve the condition it's all based
on at what stage the the patient
is being managed and the syndrome is
being recognized
at to understand the complexity of management
of this condition it is important to
recognize the two phases of the couple
or leaks into the phase one at
where there is initially as at the
that the initiation of the a capella
really and then that is a face
to which is and
recovery
if it's in management depends on what
face the patient is is act in
early phase at eb
and that is usually a hypertension i
could kidney injury pulmonary edema and the
treatment is is driven by volume resuscitation
add in addition to sometimes need of
pressures to support blood pressure
during the recovery phase a patients at
typically show stable blood pressure with a
recovery from the couple or a leak
and now the fluid is moving back
into the situation
it that is associated with it some
pulmonary edema and systemic edema but the
treatment is completely different and is in
fact use of they are ethic and
and id albumin in order to help
increase the uncle take a brush so
add that are also other as suggested
and like steroids and i the i
g to help
at protect the ended the yelled a
function but he that role is not
a fully proven however they're commonly used
it is also important to point out
that in idiopathic clerk at or clubs
and syndrome there is a component the
proven by kodak imaging and my guardian
biopsy based on case studies and case
reports that is evidence and sometimes if
if the disease is
source is severe that that is myocardial
edema and a interstitial swelling in the
myocardium that is typically a divorce
however this situation of the her cut
edema has never been shown
with other ecology of a leak syndrome
like viral infection or more specifically it
has never been published in in capital
leaks into trump related to a drugs
a month on drugs and this is
known to be the most common of
the cause of baby syndrome and are
a cancer drugs that can eat to
see a desk and eighty percent of
cl as syndrome now reported are generated
or triggered by certain cancer
at hey this is this is the
case that to drive the point at
this is a thirty seven year old
it made with acute a pulmonary edema
that at occurred eight days after receiving
first those therapy with the a a
a drug addict add that was under
study as l one forty
currently up with by ft eight and
called that glaxo first and is used
for a specific kind of into kinda
could be be busy and
is the patient is a had previously
and know best medical significant on what
we did he he had normal baseline
is cg on the day of admission
he has significant reprise issued a diffuser
imprecision of the makes on easy cheap
suggestive of my or ethic process
at his a cadet biomarkers were elevated
and had significantly elevated bnp and more
importantly a a finding that fits the
criteria of drug induced capita read syndrome
which is a abrupt and seaview drop
in serum albumin from four point eight
to three point two
again air as as the as a
sign of this couple or a leak
and a loss of a boom into
the infestation
his baseline echocardiogram before the initiation of
the treatment as showed a normal a
cardiac chambers shown here this is to
chamber if you have that left ventricle
this is fourteen bit of use and
this is that goes for views
at the day next to the admission
after the event a cute wasn't asian
the repeated echocardiogram showed diffuse thickening of
all the codec chambers at at cavities
including the left ventricle and also the
left ventricle with you can tell hear
that is and diffuse
the guinea compare to baseline this was
subsequently at shown in a cardiac care
about i showing increase at juju maps
and easy v volumes and that really
typically at his is reflect the presence
of of edema or or air it's
official
water in them in the god
how did this have how does this
happen in fact at a grad so
first air is known to have been
associated with high incidence more than forty
percent chance of of having these side
effect high incidence of certain degree of
popularly syndrome at not all of them
are seaview there can be mine ah
but ah
also can be catastrophic so it's a
spectrum
and the way it happens is that
at this drug air it is is
made of the arab of a recombinant
protein that at comprise a i l
three a molecule that is used to
aid that diphtheria oxen in the leukemic
cells that is abundancy of i l
three you
he suffers so this drug is a
targeted track it gets attached to the
i three it gets at it and
realized and arab it's internalized at into
that sell were a that a catalytic
a domain of the diphtheria at
at is responsible for that at the
site a toxic effect of the leukemia
sets it is believed
that by the same mechanism at the
end a t leo cells have i
have three receptors and by the same
because i'm very certain degree of and
to chill dysfunction and at loss of
the at it
i'll sell adhesions at that would lead
computer leaks in with edema lot of
i'd be to the interest issue with
the kennedy hyper i'll be convenient and
secondary i put a hypertension
this is a commonly observed the drug
again with the spectrum of clinical presentation
add to the point that there's already
well established a suggested algorithm to manage
these patients they should be usually initial
treatment is done as impatient and patients
are monitored closely with and wounded check
flick with and boom in check out
the ladies if the drug they also
receive at
speak with a bodyweight shake and any
evidence of at a albumin loss or
out with the ensure depleted with their
explore and even if you should add
that is really not a not the
a single process to do this it
it's these are general a guiding parameters
and some patients need nothing but
some need more aggressive treatment if they
show at more severe reaction and this
aggressive treatment include a ads use of
a steroids use of i'd be a
the album in frequently in order to
maintain adequate on kotick the pressure
so the the summit of the tree
but is aggressively use steroids and albumin
and this is what this patient received
typically in two to four days is
the syndrome abates and a patient's respond
to these treatments if if started at
early enough
and this is what happened in fact
patients did well and he got the
shot and is bazelon echocardiogram is against
on here to put in normal during
the event he had significant was sickening
subsequent echo three months ago it as
sorry as three months later showed complete
a resolution of is a wolf thickening
and it's back
to a similar air and is similar
to his baseline echocardiogram findings so this
full thickening of the ventricles completely resolved
and there's one thing to explain that
which is at which is my current
edema
similarly the kartik m r i parameters
this one is at the baseline showing
increase to two maps and lv mass
index which reflects a a increase air
interstitial edema ah after a three month
it was repeated ad showed a clip
normalization of teach to and lt mass
index
so at the this this study is
again a at was meant to raise
awareness and educate provider regarding the importance
of recognizing myocardial edema as the rare
but a serious manifestation of drug related
capital week simple and
fact that took the our knowledge is
is the first ag case of reported
kotick edema associated with syndrome even though
mitigation related and are at well reported
the make a real edema is a
known complication of idiopathic cls this is
the first case we reported it's also
a it
reflect the importance of pattern recognition by
kodak imaging like echocardiography or r i
and also the importance of early initiation
of corrective measures including at full understanding
of a fluid at a fluid management
in addition to the importance of reestablishing
on kotick pressure with
air with
id albumin
now add that that the question that
was at an abrupt brought up is
that are frequently brought up in back
there are two questions at number one
is at how often is the blurry
early syndrome observed in patients on such
drug at this is a drug that
has been an shown to
cause a couple weeks into and about
forty five percent of the time that's
why patients initial treatment is in peace
now at the majority the majority experience
mild reaction a it's simple like edema
that is managed with some ivy and
be in and day recess and they
do well however as we've seen several
cases of at specially those who have
underlying structure heart disease at that they
can
and it easily the compensate into they
are studied heart failure and we've had
previous cases not as obvious as this
one with my current edema but we
were able to prove that they're and
watch pressure and it left ventricle and
diastolic pressure by in invasive of got
categorization significantly go up after such as
at
the second question is what are the
clinical and management differences between at the
drug related capillary since the a bit
at a leak syndrome and the more
known drug related cytokine to release syndrome
typically seen these days with cut the
cell therapy in air air
in in and can guess what patients
this is a very important a question
because at that is definitely certain degree
of overlap but being able to differentiate
between these two has a major clinical
implications with am cocky cell and certain
other immunotherapy is
at that aside to cut really syndrome
also shows spectrum of clinical findings from
fever usually fever is is a is
a common and finding an air as
they can go into at shock air
with air base with a leopard effect
manifests as as a key card yeah
hypertension
and and but that the observation of
a competitive league and profound edema his
neck is nuts usually seen that mediators
are different even though these are site
again mediated also but mainly it's dominant
by l g n f l find
a i l one and i and
six that's why
why
an antibody targeted at a certain treatment
targeting a blockade of a i l
l six at our are the main
treatment with to see these map and
this and this has not been tested
or or a
where does is not expected to have
any effect with the gop pillory leak
syndrome because and mean or at or
a decide to keep and inside two
kinds involved in this and make a
list is it out a little bit
different so it's important for the shade
these two because the treatment is is
slightly different at just be aggressive with
a cup
peter leaks and drunk at early enough
was high and repeated albumin infusions and
aggressive day leases went blah pretty stable
is the week ago
and with this i finish