This week we speak with Professor Robert Hamilton of the University of Toronto about a recent case-control study in which his team identified a novel auto-antibody targeting a fetal cardiac protein that proved to have excellent sensitivity and specificity for the identification of fetuses that would develop heart block in fetal life in the offspring of women with maternal connective tissue disorders. How did the team in Toronto choose these particular target proteins? How well did this test perform in predicting heart block in pregnancies where there had been a prior pregnancy affected by block? Does this test possibly mean that fewer fetuses of mothers with connective tissue will need surveillance? Dr. Hamilton shares the details of this fascinating study this week.
https://doi.org/10.1016/s2665-9913(25)00092-x
We also speak with Drs. David Ezon and Kenan Stern about the upcoming 16th Annual Mount Sinai Imaging Symposium - Conversations in Care: Cardiac Conundrums & 3D Echo Workshop which will be taking place at Mount Sinai on 5/31/25. Details are available at the following website:
https://mssm.cloud-cme.com/course/courseoverview?P=5&EID=46043
https://doi.org/10.1016/s2665-9913(25)00092-x
We also speak with Drs. David Ezon and Kenan Stern about the upcoming 16th Annual Mount Sinai Imaging Symposium - Conversations in Care: Cardiac Conundrums & 3D Echo Workshop which will be taking place at Mount Sinai on 5/31/25. Details are available at the following website:
https://mssm.cloud-cme.com/course/courseoverview?P=5&EID=46043
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:16):
Welcome to Pdheart Pediatric Cardiology today. My name is doctor
Robert Pass and I'm the host of this podcast. I
am Professor of Pediatrics at the Icon School of Medicine
at Mount Sinai, where I am the chief of Pediatric Cardiology.
Thank you very much for joining me for this three
hundred and forty third episode of Pdheart. I hope everybody
enjoyed last week's episode, in which we discussed the topic
of food and security and possible long term impact on
(00:39):
cardiovascer health. We spoke with doctor Niela Shah of Northwestern University,
and for those of you interested in this very important topic,
I'd certainly recommend you listen to last week's episode three
hundred and forty two. As I say most weeks, if
you'd like to get in touch with me, my email
is easy to remember. It's pdheart at gmail dot com.
This week we move into a very interesting area of
(01:02):
both electrophysiology, but perhaps more importantly, fetal cardiology. The title
of the work we'll be reviewing is Maternal auto antibodies
to the sodium potassium pump alpha one subunit AT one
A one and Fetal autoimmune congenital heartblock a case control study.
The first author of this work is Stephanie Benjamin and
(01:22):
the senior author is Robert Hamilton. And doctor Hamilton comes
to us from the University of Toronto at Toronto Sick
Kids Hospital. When we're done reviewing this very interesting and
fascinating work, doctor Robert Hamilton has graciously agreed to join
us once again to speak about it. After our conversation
with doctor Hamilton, we're going to briefly speak with doctor
Kennon Stern and doctor David Eazon, who are running the
(01:45):
sixteenth annual Mount Sinai Imaging Symposium, which is going to
be occurring at Mount Sinai, my own institution, on May
thirty first, twenty twenty five. The name of the conference
is Conversations and Care Cardiac Conundrums with the Hands on
on three D Echo Workshop. We'll be speaking with both
course directors shortly after our conversation with doctor Hamilton. Therefore
(02:07):
a lot on our plate, so let's get straight onto
the article and then a conversation with doctor Hamilton, followed
by our conversation with doctor Zison and Stern. This week's
work begins with a number of comments about congenital heart
block reminding us that it was first described back in
the early part of the twentieth century, but it was
not until over seventy five years later in nineteen seventy seven,
(02:28):
that it was understood that maternal connected tissue disease, mostly lupis,
had a higher risk of autoimmune congenital heart block. Further
studies showed that seventy five to eighty three percent of
mothers of children born with heart block tested positive for
SSA row ribonucleoproteins during pregnancy or shortly after birth. However,
(02:50):
though this strong association is clearly there, as most fetal
cardiologists know well, only one to two percent of autoimmune
pregnancies actually result in offspring are affected by complete heart block.
This is a major issue because it means that all
fetuses of mothers with these disorders need extremely careful surveillance
looking for that one to two percent of fetuses that
(03:12):
actually will develop heart block. And I'm sure you recall
prior episodes of the podcast in which we spoke with
doctor Pettinacuneo and Joe Byron about novel approaches to surveillance
of this patient group, which all require extremely frequent follow
up with newer approaches, including home surveillance by the mothers themselves.
If there were a way to hone in on those
(03:33):
fetuses who were actually at higher risk amongst these maternal
autoimmune patients, it might reduce the need for the sort
of gunshot approach whereby we surveil all of these fetuses
in the setting, despite the fact that over ninety eight
percent of them will be fine and not develop heart block.
With this as a background, the author's hypothesize that maternal
auto antibodies to fetal cardiac protein targets are associated with
(03:56):
autoimmune congenital heart block and could potentially serve as predictive biomarkers.
To assess this hypothesis, the group adapted an autoantibody discovery
platform and used a discovery and validation approached for analysis.
This was a case control study using samples from two
sensors in Toronto and Italy to evaluate anti cardiac autoantibodies
(04:18):
in maternal serum samples from at risk pregnant women and
for this work, cases were pregnancies that resulted in fetal
or neonatal congenital heart block, whereas controls were pregnancies that
had offspring with normal conduction. All of the subjects had
either sl chogrins or undifferentiated connected tissue disease or were asymptomatic,
(04:38):
and all women were anti SSA row antibody positive. The
maternal serum specimens in Toronto tested for fetal cardiac proteins
were collected over a ten year period from twenty ten
to twenty twenty. In the author's review, when the specimens
were obtained for women with fetuses that did and did
not develop heart block, a verification cohort of anti SSA
(04:59):
row positive pregnant were obtained over twenty years at the
University of Patawa, and a final validation cohort of anti
SSA row positive maternal serum samples were obtained at the
Hospital for six Children in Toronto from June twenty eighteen
till August twenty twenty three. Now let me be clear
in stating that I am not a scientist and so
(05:19):
I am not going to go into great detail regarding
the methodology used by the teams in Italy and Toronto
led by doctor Hamilton, but the authors go through how
they use their auto antibody discovery platform to identify maternal
auto antibodies that were targeting proteins in young cardiac tissue,
and explained that initially they used fetal proteins from the
middle of the second trimester, but eventually used stem cell
(05:42):
derived ventricular like cardiomyocytes. The authors used two dimensional Western
blots of commercial proteins to validate maternal auto antibodies to
complete hart Block specific targets. The paper goes through in
wonderful detail how the authors identify possible target proteins and
fetal hearts, and then how they tested for antibodies against
these proteins, and also why the authors believed that these
(06:05):
proteins were potentially good targets to study given their gene
and protein expression studies in the developing a V node,
and Fig. Four shows how they quantified imminofluorescence of sodium
and potassium ATPA sub units at one A one and
at one A two in neonatal and adult rabbit av
node and ventricular myacardia, and how AT one A two
(06:28):
was not expressed in the av noodal cells. Again, please
read this paper for those interested, particularly pages three to nine,
in which the authors do a splendid job of explaining
how they chose seven potential targets of maternal auto antibodies,
including vime anx A one, bip, myp C three, AT
(06:49):
one A one, AT two A two, and SO one
A two. They speak of how they identified auto antibodies
to four of these targets before fetal hart block even occurred,
specifically to ANXA one, bip MYPC three eighty one A one.
They also speak of which of these antibodies were identified
(07:10):
earliest in maternal serum during pregnancy, which was eight one
A one, which was seen as early as seven weeks gestation,
followed by the other ones at seventeen weeks, all prior
to the development of heart block. And so, without me
entirely butchering the science of this wonderful and potentially game
changing research, let me just review some of the major findings. First,
(07:33):
mass spectroscopy identified eleven potential cardiac protein targets from maternal autoantibodies,
and as I mentioned, there were seven identified in the
maternal serum samples from affected case pregnancies with heart block. Second,
as I just mentioned, four were identified before the onset
of block, and again these were ANXA one, bip, MYPC three,
(07:55):
and AT one A one, which is a sodium and
potassium atpas alpha isoform, and again this particular autoantibody was
identified the earliest at seven weeks gestation in all affected
pregnancies of moms with and without prior fetal heart block,
with six of the six and discovery cohort twenty two
of twenty two in the verification cohort, and then sixteen
(08:17):
of sixteen in the validation cohort. Importantly, Anti eighty one
A one autoantibodies were absent in all unaffected pregnancies in
pregnant women with no fetal heart block history. However, Anti
eight one A one antibodies were also present in the
maternal serum of four of seven unaffected pregnancies in which
(08:38):
there had been a prior history of a fetus or
child with heart block, meaning that for women with a
past history of heart block in an offspring, this finding
had a specificity of fifty seven percent and a positive
predictive value of twenty eight percent, compared to women who
were complete heart block naive, in which ANTI eighty one
A one positivity had a one hundred percent diagnostic accuracy,
(09:02):
with sensitivity and specificity of one hundred percent, respectively, and
the authors remind how much more effective this is than
just antissa row positivity in identifying patients who will develop
heart block. Again, the authors identified differential expression of AT
one A one in immature versus mature rabbit av noodal
tissue and not AT one A two, and they therefore
(09:24):
explain that this means that immature av nodes express this
protein but not the other at gene and protein levels.
In their discussion the author's state and I quote, this
study identified distinct patterns of maternal autoantibodies targeting fetal cardiac
proteins in pregnancies affected by congenital heart block compared with
unaffected at risk pregnancies. This repertoire of autoantibodies expands through
(09:48):
at gestation in congenital heart block cases, whereas in unaffected controls,
autoantibodies are limited to the fifty two kilode row and
LAW proteins. This differential pattern of protein recognition suggests a
unique autoantibody profile associated with a significantly increased risk of
congenital heart block in effective pregnancies. The authors explain that
(10:10):
many different autoantibodies may affect the development of heart block,
but they re emphasize how this work identified a subset
of these autoantibodies specifically an XA one, bip MYPC three,
and AT one A one, as findings that actually precede
the onset of heart block and could in theory identify
at risk patients while also identifying those not at risk,
(10:32):
a potentially very important clinical observation. The authors review the
potential mechanistic reasons for why an antibody against the AT
one A one sodium and potassium ATPAS might cause heart
block and fetuses, and review how having an autoantibody assay
that can identify patients as early as seven weeks gestation
to have this antibody can have meaningful impact on clinical
(10:54):
fetal cardiology practice. They then address the relevance of these
findings in the anti row law positive woman who had
prior pregnancies with a fetus or child with heart block,
and review how these findings showed that if there was
no anti at one A one antibodies, none had a
fetus with heart block, meaning it seems to have been
very good at identifying those in whom there was no risk.
(11:16):
But anti eight one A one antibodies were occasionally seen
in maternal serum samples of unaffected pregnancies after a prior
affected one and so this autoantibody was not perfect in
prediction in the development of cart block in that subset
of patients who had a prior pregnancy affected by block,
and the authors provide a few possible explanations for this.
(11:36):
They review the limitations of this work, including the non
randomized nature of the discovery cohort and reliance on only
one single maternal serum sample limiting the generalizability of these findings.
They mentioned the absence of avnodal cells in their study,
as well as limited understanding of the functional data of
the identified autoantibodies on heart block and now much more
(11:57):
study regarding mechanism is warranted. We speak about how having
a future study with serial samples would be very useful,
including samples between pregnancies, and so the authors conclude by
stating this case control study has identified and validated maternal
anti eight one one autoantibodies as a highly sensitive and
specific biomarker for the early first tremester detection of autoimmune
(12:21):
congenital heart block in at risk pregnancies of women with
no previous congenital heart block offspring. However, the test was
not accurate in the at risk pregnancies of women with
a history of congenital heart block. These findings support the
potential use of this novel serological marker for the early
assessment of autoimmune congenital heart block to help evaluate the
(12:42):
need for or supplement serial fetolecocardiography in at risk pregnancies.
With further clinical translation, this biomarker could enhance the diagnosis, management,
and development of interventional therapies for at risk pregnant women
and fetuses. While this is certainly a very interesting work that,
if validates, could really change the evaluation and management of
(13:02):
pregnant women with positive connective tissue antibodies, as we've said,
only a very small percentage of these women will actually
go on to have a child or fetus with heart block,
and yet we surveil them all aggressively because of the
significant mortality and morbidity associated with heart block. This work
preliminarily has identified an antibody test that can be performed
(13:23):
early in pregnancy, long before the window in which heartlock
will typically develop in fetuses, and could help us better
understand who should be treated prophylactically, who we need to
be very aggressively surveiling, and who we should stop those
expensive and frequent checks in This would seem the most
important potential benefit of this work, and so in the
interest of time, I think we'll speak with the work
(13:44):
senior author, Professor Hamilton, to get a better understanding of
this work and what is now needed going forward. Joining
us now to discuss this week's work is the work's
senior author, Doctor Robert Hamilton. Professor Hamilton is a pediatric
electrophysiologist and senior Associate Science at the Hospital for Sick
Children and Research Institute in Toronto. He is a senior
(14:05):
electrophysiologist and manages and inherited Arrhythmic clinic, and is well
known both in my field of pediatric ep but also
in our entire universe of congenital heart disease worldwide. Some
may recall that we had Bob on the podcast a
number of years ago speaking with us regarding new biomarkers
he had discovered with his team for both ARVC and
(14:26):
Brugatta syndrome. It is a delight to speak with Bob
again on the podcast about his latest wonderful discovery. Welcome
Professor Hamilton to Pdhart.
Speaker 2 (14:36):
I'm here now with doctor Bob Hamilton. Bob it's a
real pleasure to have you join us this week on PDHART.
Speaker 3 (14:41):
Thanks real good to be here.
Speaker 2 (14:43):
Thank you very much and long overdue, Bob. I'm wondering
if you could give for the non scientist listeners maybe
a brief summary of how you and your investigators identified
these target antibody proteins and what evidence exists that these
proteins are actually important for conduction in the heart.
Speaker 3 (15:02):
Sure, I think this study is quite unique in that
we used a broad, unbiased approach to identify antibodies based
on the potential target proteins that can be found in
immature heart tissue or heart muscle cells. We first assessed
normal fietal hearts, but then we moved quickly to use
(15:23):
stem cell derived cardiomiocytes, which are known to be developmentally immature,
and this avoided the need to obtain fetal heart tissue
and also provided only the cardiomiocyte cell type for analysis
post all the different cell types that are in a
full heart. So really the only constraint on the study
(15:43):
was the antibody targets had to be present in immature hearts,
and we felt that these would be targets of the
antibody since this is what's damaged in autoimmune heart block?
Speaker 2 (15:54):
Yeah. Yeah, Well, you know, Bob, you and your co
investigators identify four antibodies to fetal cardiac proteins that are
associated with the development of heart block. But one, the
sodium potassium pump ata one antibody, was extremely good at
identifying fetuses that were going to go on to have
heart block. And this was also the one that you
(16:16):
identified very early in pregnancy. I wondered how good were
the other three, the ANXA one, the BP, and the
NYPC three at identifying at risk fetuses.
Speaker 3 (16:28):
Yeah, I mean, so we were limited here by the
small number of samples that we had that were drawn
prior to the onset of fetal heart block. Many of
our samples were drawn after heart block had ensued at
eighteen to twenty weeks, so we had limited number of
examples that we could use to predict block block. And
so for these other three protein targets that you mentioned,
(16:50):
they were present in three samples in the early second
trimester prior to the onset of heart block, and they
were absent in all heart block negative patients. Statistically significant,
but based on small numbers of pregnancies where they were
measured prior to heart block. For AT one A one.
We had one additional patient the heart block serum that
(17:12):
was drawn at seven weeks gestation for a total of
four patients where it was predictive for heart block and
absent in the non heart block pregnancies.
Speaker 2 (17:21):
I see, I'm wondering, Bob, if you could speak to
the audience about what is the presumed mechanism for anti
ATA one antibodies to cause heart block? What does the
sodium potassium pump alpha one subunit do in the conduction
system that makes it so important?
Speaker 3 (17:39):
Well, it's important in lots of cells for creating the
membrane rest ingradient. But the question is why why are
these antibodies unique to cause fidel avi noodle damage? And
you know, as the sodium potassium pump is present in
most cells, so the answer may be in the relative
(17:59):
expression of different isoforms of the pump in different tissues
at different times of development. We partially address this by
demonstrating that developmentally immature hearts only expressed the at P
one one gene and the at one A one protein
based on human field cardiac gene expression and based on
(18:21):
some rabbit heart staining studies that we did as part
of this work. Yes, we think the AVY node really
only expresses the alpha one isoform, un thus is particularly
sensitive to its autoantibodies, whereas other tissues that have alpha
two isoform may be rescued by the function of that protein.
Speaker 2 (18:40):
I say, I see interesting, you know, Bob, it was
very interesting to see how perfectly this antibody was at
identifying the development of BLOCK and those women who did
not previously have a pregnancy affected by BLOCK, but how
it sometimes was positive in patients who previously had a
pregnancy affected by BLOCK, but actually that pregnancy in which
(19:02):
you'd obtained the sample did not progress to have feed
us with BLOCK. I'm wondering if you had any thoughts
on why this might be, and would you suggest that
maybe the test is more helpful in the patient group
to rule out the future development of BLOCK, but not
as good at predicting BLOCK in that group of patients
who previously had block.
Speaker 3 (19:21):
Yeah, I mean, this is indeed a challenge. There may
be several issues at play here. First, you know, we
should recognize that this study only assesses maternal factors, specifically
the repertoire of anti cardiac antibody's present in maternal serum
in a single sample and at variable times and snapshots
during the pregnancy. It didn't address fetal factors. So, for instance,
(19:44):
we know that even in twin pregnancies there can be
discordance for heart block outcomes, so there's likely to be
fetal genetic and even epigenetic factors that influence whether heart
block occurs. Secondly, I mean primary responses and secondary immune responses,
such as pregnancies where there's been a prior child with
(20:05):
heart block may have some differences in the timing and
type of immune response. So ideally we would have liked
to have had sequential samples in early pregnancy onward to
address this and further evaluate the predictive potential of these antibodies.
So for this, we're going to need the cooperation of
at risk mothers and collaboration of many of our adult
(20:28):
rheumatology and reproductive medicine colleagues who see these pregnancies early.
Speaker 2 (20:32):
I see, I see really fascinating work. So you know, Bob,
for those in the audience, it's kind of early in
the evening, and Bob is nice enough to speak with
us while he's in the middle of doing all sorts
of other things. So I'm going to wrap this up
with my final question. You know, for the non scientists
such as me and the many lesseners, this paper is
(20:53):
very very exciting. However, I'm wondering, can you share with us,
like what's needed to validate these findings so that we
can prove that these preliminary data that you have, you know, reported,
are reproducible. I mean, how do you validate this sort
of finding? You hinted at it a little bit about
getting serial samples. How long do you think this sort
of validation could take? I was thinking it might be
(21:15):
very long because it's so hard to get these specimens
and if you validated it, is this like the type
of assay that you could imagine one day would potentially
be clinically available. Is this a very difficult test to perform?
Speaker 3 (21:29):
For example, Well, you know we did everything in research blots,
so what are called westerns and two dimensional blots, and
you know, to become a clinical test, it needs to
be switched over to you know, an assay like that
in solution, like an enzyme linked immunosorbent assay or ELIZA
(21:50):
enzyme any kind of enzyme immuno assay, and so we're
working on that, and we're also working with a pharmaceutical
company that's interested in this test as a companion biomarker
to try to identify those pregnancies that are specifically at
rest at risk. And then we would also like to
(22:15):
develop in a lives or a similar assay just to
provide this two you know, labs that are evaluating women
in all jurisdictions to try to you know, just decide
who needs and feed laco, and then if better therapies
come along, to identify the patients and the pregnancies that
(22:39):
might benefit from therapy. There's are a couple other biobanks
of maternal serum already collected from at risk pregnancies, and
I'm aware that one is already performing validation assays in
a very independent fashion, and so I think we'll hear
from that lab relatively soon.
Speaker 2 (22:59):
Wow, that's very exciting. So in other words, another lab,
unrelated to your lab is taking your data and trying
to validate it, as you and I are speaking basically, Yeah,
that's correct, that's terrific. Well, once again, Bob coming to
us with game changing research really extraordinary for those in
(23:19):
the audience. I'm going to put links to the prior
episodes that we had with Bob talking with us about
a novel way of identifying ARVC and also Bragata syndrome. Bob,
I really can't thank you enough for speaking with us
this week on the podcast, and I want to congratulate
you and your Mini co investigators on really remarkable work
and I'm hopeful that it will pan out to be
(23:41):
a really important approach to managing fetuses with heart block.
Thank you so much, Thank you very much for pleasure.
Speaker 1 (23:48):
Well. Once again, doctor Hamilton has provided us with a
very interesting and novel approach to the question of heart block,
as he suggested in our conversation and in the accompanying
editorial comment, as well as his comment in the discussion
to this work. Validation of the findings of this work
will be critical given the small numbers of patients included
in this study. However, it would seem that if we
(24:10):
could in fact identify most patients at risk for heart
block early in pregnancy with the tests such as the
one described in this work, the opportunity to devise better
and more effective treatments for this problem are substantial. I
do think it's exciting that the test is getting turned
into an Eliza test to make it practically easier to perform,
and I am sure that doctor Hamilton and other investigators
(24:32):
he works with, both in his lab and in other centers,
will work to validate this impressive study and hopefully provide
clinicians caring for women who have fetuses at risk for
heart block, another way of identifying these fetuses before block ensues,
and in so doing potentially enhance the window for therapy
to prevent it, while also sparing many others from the
(24:54):
very challenging enhanced surveillance that is needed at the present time.
I'd once again like to thank doctor Hamil for taking
time from his very busy schedule to speak with us
this week on.
Speaker 4 (25:03):
P D Heart.
Speaker 1 (25:04):
Before we come to the end of this week's podcast,
I wanted to have a brief conversation with the directors
of our upcoming course here at Mount Sinai, which many
have attended year after year. This week, actually tomorrow is
the sixteenth annual Mount Sinai Imaging Symposium.
Speaker 4 (25:20):
Again.
Speaker 1 (25:20):
It's on Saturday May thirty first, twenty twenty five, and
the title of the conference is Conversations in Care Cardiac
Conundrums with a hands on three D Echo Workshop. Our
course director is doctor David Ezon and co course director
doctor Kennon Stern. Both gentlemen are associate professors of pediatrics
here at the Icon School of Medicine at Mount Sinai,
(25:41):
and I've asked them to come speak with us briefly
about this wonderful conference, and I'm hopeful that some of
you may listen today and be inspired to come by
Mount Sinai tomorrow and check out the wonderful presentations that
are planned. Therefore, without further ado, here's my brief conversation
with doctor David Eeson and doctor Kennon Stern.
Speaker 2 (25:59):
I'm here now with doctor David Eason and doctor Kennon Stern,
who are the course directors of this year's sixteenth annual
Mount sun I Image in Conference Conversations and Care Cardiac Conundrums.
David Kenon, Welcome to PDRTS.
Speaker 5 (26:14):
Thank you.
Speaker 2 (26:15):
I'm wondering, David, if you could sort of give us
the broad strokes of what the general focus of this
year's particular conference is on.
Speaker 6 (26:23):
Yeah, so once again we're ditching the powerpoints and it's
really about having an interactive conversation with experts in the field.
Where we bring together multi disciplinary experts, surgeons and divensialists
and imagers together to talk about how we can advise
each other to get.
Speaker 2 (26:38):
That best outcome.
Speaker 6 (26:40):
So what does the surgeon actually need to know, how
does he or she actually think about it? And how
can the imager give the surgeon critical data that they need.
Speaker 2 (26:50):
I think it's really terrific how you have gotten rid
of the PowerPoint makes it harder for the speaker having
been one of them before, but I do think it
really forces people people to speak to one another more.
And that dear listener is an innovation that Davidson had
for this conference, really has enriched it tremendously. Kennon, I'm wondering,
(27:11):
you know, there's a lot of wonderful sessions that's going
to that are gonna happen, and again for those in
the audience, it's going to be tomorrow May thirty first,
But Kenon, is there one or two that you are
particularly excited and looking forward to. Well, I'll tell you.
Speaker 4 (27:25):
About all three of the morning sessions because I'm excited
about that.
Speaker 2 (27:28):
Cool.
Speaker 7 (27:28):
As David said that, the topic is conundrus in care,
so we're really are tackling difficult lesions. You know, anatomically,
physiologically more imaging can.
Speaker 4 (27:40):
Really play a big part and big role in helping
the surgeon or interventionalist. First one is complex micro valve repair.
There's always a crowd pleasers how one structure can be
so complicated, But those of us know can jun heart disease,
know that can be the case with many aspects of cardiology. Sure,
(28:00):
complex double outlet right venture cole repair in terms of
how you performed biometricular pair and complex outflow reconstructions in
these patients. And then the session on congenerally corrected transposition
of the Great arteries, which is always a clinical chnogrum.
Speaker 2 (28:18):
Wow, you guys are not taken on some serious stuff here.
We're no little VSDs or ASDs for this conference this year,
at least, David, I know that as the main course
director for this conference, it would be unfair of you
to ask you what your favorite or most looked forward
to session is, because I'm sure you actually chose all
(28:42):
of them, but with the course directors, But is there
one that you're particularly excited and looking forward to?
Speaker 6 (28:47):
Well, this year we're innovating further and in the afternoon
we're going to be doing an interactive three D workshop
with the idea to make this as participatory as possible.
We're going to have live models. People will get practice
on both the Phillips and the GE platforms throughout the
afternoon doing image acquisition and learning really how to go
(29:10):
about getting the best images, and then a separate session
on post processing with each platform. Then in small group
sessions as well as reviewing really nifty and cases that
use three D. That really made a big difference with
some experts in the field that are very adept at
three D, showing both how they process the images to
(29:31):
make it palatable for the surgeon and how you, as
the clinician can go home and take that with you.
Speaker 2 (29:38):
And the attendees will actually have hands on experience using
this equipment. That's right, that's right, that's exciting. I'm sure
that's going to be very appealing to many. Well, David,
maybe you could share with the audience those of you
who are listening today and are saying, Wow, I don't
have anything going on tomorrow on center right, this sounds
really exciting. How would someone get information to I know?
Speaker 6 (30:01):
Yeah, So first, as you know, you can actually do
same day registration, So if you come to the Mount
Signey Hospital on Madison Avenue in one hundred in Manhattan. You
can come to Annenburgh twelfth floor, the Annenburg Building, twelfth
floor and you can sign up right then and there.
It's ninety dollars for attending physicians and free to everybody else.
(30:22):
We really try to make this as easy as possible
for people to participate. It's about educating the community. And
so you can just come in at the Mount Sainnday
on Saturday morning. It starts at eight am and it
runs throughout the day till four. We've got a delicious
meal cater throughout the day. Please join us.
Speaker 2 (30:40):
Wait, there's no such thing as free lunch. Back to
Stern coming through with his outstanding humor. No wait, I
don't remember agreed to make this free for everybody else
times we need to have a conversation after this meet it. Well, guys,
I really want to thank you for sharing this exciting conference,
and again I would encourage everybody to go online to
(31:01):
learn about the conference that's going to be tomorrow. And
as David said, you can come even day of and
register right in person. And so I want to thank
you both, guys, both for all the hard work that
you and the co course directors do for this every year,
and thank you so much for spending a few moments
with us this week on the podcast. Thank you.
Speaker 1 (31:21):
To conclude this three hundred and forty third episode of
p D Heart Pediatric Cardiology, Today we hear the gavote
from Messines Manon and we hear it sung brilliantly by
the up and coming wonderful Spanish soprano Ruth Niesta, who
is the winner of the prestigious Premios Lyricos Campo Amor
twenty fifteen and the Cordellario Prize as the Best New
(31:43):
Artist of twenty fifteen. And since her debut and opera
at the Tiatro de la Sarzuela in Madrid in twenty twelve,
Miss Iniesta has sung all over Europe in many different roles,
debuting new ones each time. She has a wonderful presence
on social media. Her beautiful Castilian Spanish has helped me
learn and speak Spanish better, reminding me of the wonderful
(32:06):
Spanish teachers I had back at Polly Prep growing up
in Brooklyn, New York. Thank you very much for joining
me for this episode, and thanks once again to doctor Hamilton,
I hope we'll have a good week ahead.
Speaker 2 (32:17):
O jes.
Speaker 8 (33:00):
H S word.
Speaker 5 (33:20):
Said she you see.
Speaker 8 (33:28):
You susy, you said, looking little lady. She is a
(33:56):
sec see it was like.
Speaker 9 (34:46):
Us. You can't go it sun as to loos of
(35:26):
sass cocks to loss of sex fact shut so.
Speaker 5 (36:31):
Other spun song fist short ass, oh little shot
Speaker 9 (37:02):
Six sas show to also se
Welcome to Pdheart Pediatric Cardiology today. My name is doctor
Robert Pass and I'm the host of this podcast. I
am Professor of Pediatrics at the Icon School of Medicine
at Mount Sinai, where I am the chief of Pediatric Cardiology.
Thank you very much for joining me for this three
hundred and forty third episode of Pdheart. I hope everybody
enjoyed last week's episode, in which we discussed the topic
of food and security and possible long term impact on
(00:39):
cardiovascer health. We spoke with doctor Niela Shah of Northwestern University,
and for those of you interested in this very important topic,
I'd certainly recommend you listen to last week's episode three
hundred and forty two. As I say most weeks, if
you'd like to get in touch with me, my email
is easy to remember. It's pdheart at gmail dot com.
This week we move into a very interesting area of
(01:02):
both electrophysiology, but perhaps more importantly, fetal cardiology. The title
of the work we'll be reviewing is Maternal auto antibodies
to the sodium potassium pump alpha one subunit AT one
A one and Fetal autoimmune congenital heartblock a case control study.
The first author of this work is Stephanie Benjamin and
(01:22):
the senior author is Robert Hamilton. And doctor Hamilton comes
to us from the University of Toronto at Toronto Sick
Kids Hospital. When we're done reviewing this very interesting and
fascinating work, doctor Robert Hamilton has graciously agreed to join
us once again to speak about it. After our conversation
with doctor Hamilton, we're going to briefly speak with doctor
Kennon Stern and doctor David Eazon, who are running the
(01:45):
sixteenth annual Mount Sinai Imaging Symposium, which is going to
be occurring at Mount Sinai, my own institution, on May
thirty first, twenty twenty five. The name of the conference
is Conversations and Care Cardiac Conundrums with the Hands on
on three D Echo Workshop. We'll be speaking with both
course directors shortly after our conversation with doctor Hamilton. Therefore
(02:07):
a lot on our plate, so let's get straight onto
the article and then a conversation with doctor Hamilton, followed
by our conversation with doctor Zison and Stern. This week's
work begins with a number of comments about congenital heart
block reminding us that it was first described back in
the early part of the twentieth century, but it was
not until over seventy five years later in nineteen seventy seven,
(02:28):
that it was understood that maternal connected tissue disease, mostly lupis,
had a higher risk of autoimmune congenital heart block. Further
studies showed that seventy five to eighty three percent of
mothers of children born with heart block tested positive for
SSA row ribonucleoproteins during pregnancy or shortly after birth. However,
(02:50):
though this strong association is clearly there, as most fetal
cardiologists know well, only one to two percent of autoimmune
pregnancies actually result in offspring are affected by complete heart block.
This is a major issue because it means that all
fetuses of mothers with these disorders need extremely careful surveillance
looking for that one to two percent of fetuses that
(03:12):
actually will develop heart block. And I'm sure you recall
prior episodes of the podcast in which we spoke with
doctor Pettinacuneo and Joe Byron about novel approaches to surveillance
of this patient group, which all require extremely frequent follow
up with newer approaches, including home surveillance by the mothers themselves.
If there were a way to hone in on those
(03:33):
fetuses who were actually at higher risk amongst these maternal
autoimmune patients, it might reduce the need for the sort
of gunshot approach whereby we surveil all of these fetuses
in the setting, despite the fact that over ninety eight
percent of them will be fine and not develop heart block.
With this as a background, the author's hypothesize that maternal
auto antibodies to fetal cardiac protein targets are associated with
(03:56):
autoimmune congenital heart block and could potentially serve as predictive biomarkers.
To assess this hypothesis, the group adapted an autoantibody discovery
platform and used a discovery and validation approached for analysis.
This was a case control study using samples from two
sensors in Toronto and Italy to evaluate anti cardiac autoantibodies
(04:18):
in maternal serum samples from at risk pregnant women and
for this work, cases were pregnancies that resulted in fetal
or neonatal congenital heart block, whereas controls were pregnancies that
had offspring with normal conduction. All of the subjects had
either sl chogrins or undifferentiated connected tissue disease or were asymptomatic,
(04:38):
and all women were anti SSA row antibody positive. The
maternal serum specimens in Toronto tested for fetal cardiac proteins
were collected over a ten year period from twenty ten
to twenty twenty. In the author's review, when the specimens
were obtained for women with fetuses that did and did
not develop heart block, a verification cohort of anti SSA
(04:59):
row positive pregnant were obtained over twenty years at the
University of Patawa, and a final validation cohort of anti
SSA row positive maternal serum samples were obtained at the
Hospital for six Children in Toronto from June twenty eighteen
till August twenty twenty three. Now let me be clear
in stating that I am not a scientist and so
(05:19):
I am not going to go into great detail regarding
the methodology used by the teams in Italy and Toronto
led by doctor Hamilton, but the authors go through how
they use their auto antibody discovery platform to identify maternal
auto antibodies that were targeting proteins in young cardiac tissue,
and explained that initially they used fetal proteins from the
middle of the second trimester, but eventually used stem cell
(05:42):
derived ventricular like cardiomyocytes. The authors used two dimensional Western
blots of commercial proteins to validate maternal auto antibodies to
complete hart Block specific targets. The paper goes through in
wonderful detail how the authors identify possible target proteins and
fetal hearts, and then how they tested for antibodies against
these proteins, and also why the authors believed that these
(06:05):
proteins were potentially good targets to study given their gene
and protein expression studies in the developing a V node,
and Fig. Four shows how they quantified imminofluorescence of sodium
and potassium ATPA sub units at one A one and
at one A two in neonatal and adult rabbit av
node and ventricular myacardia, and how AT one A two
(06:28):
was not expressed in the av noodal cells. Again, please
read this paper for those interested, particularly pages three to nine,
in which the authors do a splendid job of explaining
how they chose seven potential targets of maternal auto antibodies,
including vime anx A one, bip, myp C three, AT
(06:49):
one A one, AT two A two, and SO one
A two. They speak of how they identified auto antibodies
to four of these targets before fetal hart block even occurred,
specifically to ANXA one, bip MYPC three eighty one A one.
They also speak of which of these antibodies were identified
(07:10):
earliest in maternal serum during pregnancy, which was eight one
A one, which was seen as early as seven weeks gestation,
followed by the other ones at seventeen weeks, all prior
to the development of heart block. And so, without me
entirely butchering the science of this wonderful and potentially game
changing research, let me just review some of the major findings. First,
(07:33):
mass spectroscopy identified eleven potential cardiac protein targets from maternal autoantibodies,
and as I mentioned, there were seven identified in the
maternal serum samples from affected case pregnancies with heart block. Second,
as I just mentioned, four were identified before the onset
of block, and again these were ANXA one, bip, MYPC three,
(07:55):
and AT one A one, which is a sodium and
potassium atpas alpha isoform, and again this particular autoantibody was
identified the earliest at seven weeks gestation in all affected
pregnancies of moms with and without prior fetal heart block,
with six of the six and discovery cohort twenty two
of twenty two in the verification cohort, and then sixteen
(08:17):
of sixteen in the validation cohort. Importantly, Anti eighty one
A one autoantibodies were absent in all unaffected pregnancies in
pregnant women with no fetal heart block history. However, Anti
eight one A one antibodies were also present in the
maternal serum of four of seven unaffected pregnancies in which
(08:38):
there had been a prior history of a fetus or
child with heart block, meaning that for women with a
past history of heart block in an offspring, this finding
had a specificity of fifty seven percent and a positive
predictive value of twenty eight percent, compared to women who
were complete heart block naive, in which ANTI eighty one
A one positivity had a one hundred percent diagnostic accuracy,
(09:02):
with sensitivity and specificity of one hundred percent, respectively, and
the authors remind how much more effective this is than
just antissa row positivity in identifying patients who will develop
heart block. Again, the authors identified differential expression of AT
one A one in immature versus mature rabbit av noodal
tissue and not AT one A two, and they therefore
(09:24):
explain that this means that immature av nodes express this
protein but not the other at gene and protein levels.
In their discussion the author's state and I quote, this
study identified distinct patterns of maternal autoantibodies targeting fetal cardiac
proteins in pregnancies affected by congenital heart block compared with
unaffected at risk pregnancies. This repertoire of autoantibodies expands through
(09:48):
at gestation in congenital heart block cases, whereas in unaffected controls,
autoantibodies are limited to the fifty two kilode row and
LAW proteins. This differential pattern of protein recognition suggests a
unique autoantibody profile associated with a significantly increased risk of
congenital heart block in effective pregnancies. The authors explain that
(10:10):
many different autoantibodies may affect the development of heart block,
but they re emphasize how this work identified a subset
of these autoantibodies specifically an XA one, bip MYPC three,
and AT one A one, as findings that actually precede
the onset of heart block and could in theory identify
at risk patients while also identifying those not at risk,
(10:32):
a potentially very important clinical observation. The authors review the
potential mechanistic reasons for why an antibody against the AT
one A one sodium and potassium ATPAS might cause heart
block and fetuses, and review how having an autoantibody assay
that can identify patients as early as seven weeks gestation
to have this antibody can have meaningful impact on clinical
(10:54):
fetal cardiology practice. They then address the relevance of these
findings in the anti row law positive woman who had
prior pregnancies with a fetus or child with heart block,
and review how these findings showed that if there was
no anti at one A one antibodies, none had a
fetus with heart block, meaning it seems to have been
very good at identifying those in whom there was no risk.
(11:16):
But anti eight one A one antibodies were occasionally seen
in maternal serum samples of unaffected pregnancies after a prior
affected one and so this autoantibody was not perfect in
prediction in the development of cart block in that subset
of patients who had a prior pregnancy affected by block,
and the authors provide a few possible explanations for this.
(11:36):
They review the limitations of this work, including the non
randomized nature of the discovery cohort and reliance on only
one single maternal serum sample limiting the generalizability of these findings.
They mentioned the absence of avnodal cells in their study,
as well as limited understanding of the functional data of
the identified autoantibodies on heart block and now much more
(11:57):
study regarding mechanism is warranted. We speak about how having
a future study with serial samples would be very useful,
including samples between pregnancies, and so the authors conclude by
stating this case control study has identified and validated maternal
anti eight one one autoantibodies as a highly sensitive and
specific biomarker for the early first tremester detection of autoimmune
(12:21):
congenital heart block in at risk pregnancies of women with
no previous congenital heart block offspring. However, the test was
not accurate in the at risk pregnancies of women with
a history of congenital heart block. These findings support the
potential use of this novel serological marker for the early
assessment of autoimmune congenital heart block to help evaluate the
(12:42):
need for or supplement serial fetolecocardiography in at risk pregnancies.
With further clinical translation, this biomarker could enhance the diagnosis, management,
and development of interventional therapies for at risk pregnant women
and fetuses. While this is certainly a very interesting work that,
if validates, could really change the evaluation and management of
(13:02):
pregnant women with positive connective tissue antibodies, as we've said,
only a very small percentage of these women will actually
go on to have a child or fetus with heart block,
and yet we surveil them all aggressively because of the
significant mortality and morbidity associated with heart block. This work
preliminarily has identified an antibody test that can be performed
(13:23):
early in pregnancy, long before the window in which heartlock
will typically develop in fetuses, and could help us better
understand who should be treated prophylactically, who we need to
be very aggressively surveiling, and who we should stop those
expensive and frequent checks in This would seem the most
important potential benefit of this work, and so in the
interest of time, I think we'll speak with the work
(13:44):
senior author, Professor Hamilton, to get a better understanding of
this work and what is now needed going forward. Joining
us now to discuss this week's work is the work's
senior author, Doctor Robert Hamilton. Professor Hamilton is a pediatric
electrophysiologist and senior Associate Science at the Hospital for Sick
Children and Research Institute in Toronto. He is a senior
(14:05):
electrophysiologist and manages and inherited Arrhythmic clinic, and is well
known both in my field of pediatric ep but also
in our entire universe of congenital heart disease worldwide. Some
may recall that we had Bob on the podcast a
number of years ago speaking with us regarding new biomarkers
he had discovered with his team for both ARVC and
(14:26):
Brugatta syndrome. It is a delight to speak with Bob
again on the podcast about his latest wonderful discovery. Welcome
Professor Hamilton to Pdhart.
Speaker 2 (14:36):
I'm here now with doctor Bob Hamilton. Bob it's a
real pleasure to have you join us this week on PDHART.
Speaker 3 (14:41):
Thanks real good to be here.
Speaker 2 (14:43):
Thank you very much and long overdue, Bob. I'm wondering
if you could give for the non scientist listeners maybe
a brief summary of how you and your investigators identified
these target antibody proteins and what evidence exists that these
proteins are actually important for conduction in the heart.
Speaker 3 (15:02):
Sure, I think this study is quite unique in that
we used a broad, unbiased approach to identify antibodies based
on the potential target proteins that can be found in
immature heart tissue or heart muscle cells. We first assessed
normal fietal hearts, but then we moved quickly to use
(15:23):
stem cell derived cardiomiocytes, which are known to be developmentally immature,
and this avoided the need to obtain fetal heart tissue
and also provided only the cardiomiocyte cell type for analysis
post all the different cell types that are in a
full heart. So really the only constraint on the study
(15:43):
was the antibody targets had to be present in immature hearts,
and we felt that these would be targets of the
antibody since this is what's damaged in autoimmune heart block?
Speaker 2 (15:54):
Yeah. Yeah, Well, you know, Bob, you and your co
investigators identify four antibodies to fetal cardiac proteins that are
associated with the development of heart block. But one, the
sodium potassium pump ata one antibody, was extremely good at
identifying fetuses that were going to go on to have
heart block. And this was also the one that you
(16:16):
identified very early in pregnancy. I wondered how good were
the other three, the ANXA one, the BP, and the
NYPC three at identifying at risk fetuses.
Speaker 3 (16:28):
Yeah, I mean, so we were limited here by the
small number of samples that we had that were drawn
prior to the onset of fetal heart block. Many of
our samples were drawn after heart block had ensued at
eighteen to twenty weeks, so we had limited number of
examples that we could use to predict block block. And
so for these other three protein targets that you mentioned,
(16:50):
they were present in three samples in the early second
trimester prior to the onset of heart block, and they
were absent in all heart block negative patients. Statistically significant,
but based on small numbers of pregnancies where they were
measured prior to heart block. For AT one A one.
We had one additional patient the heart block serum that
(17:12):
was drawn at seven weeks gestation for a total of
four patients where it was predictive for heart block and
absent in the non heart block pregnancies.
Speaker 2 (17:21):
I see, I'm wondering, Bob, if you could speak to
the audience about what is the presumed mechanism for anti
ATA one antibodies to cause heart block? What does the
sodium potassium pump alpha one subunit do in the conduction
system that makes it so important?
Speaker 3 (17:39):
Well, it's important in lots of cells for creating the
membrane rest ingradient. But the question is why why are
these antibodies unique to cause fidel avi noodle damage? And
you know, as the sodium potassium pump is present in
most cells, so the answer may be in the relative
(17:59):
expression of different isoforms of the pump in different tissues
at different times of development. We partially address this by
demonstrating that developmentally immature hearts only expressed the at P
one one gene and the at one A one protein
based on human field cardiac gene expression and based on
(18:21):
some rabbit heart staining studies that we did as part
of this work. Yes, we think the AVY node really
only expresses the alpha one isoform, un thus is particularly
sensitive to its autoantibodies, whereas other tissues that have alpha
two isoform may be rescued by the function of that protein.
Speaker 2 (18:40):
I say, I see interesting, you know, Bob, it was
very interesting to see how perfectly this antibody was at
identifying the development of BLOCK and those women who did
not previously have a pregnancy affected by BLOCK, but how
it sometimes was positive in patients who previously had a
pregnancy affected by BLOCK, but actually that pregnancy in which
(19:02):
you'd obtained the sample did not progress to have feed
us with BLOCK. I'm wondering if you had any thoughts
on why this might be, and would you suggest that
maybe the test is more helpful in the patient group
to rule out the future development of BLOCK, but not
as good at predicting BLOCK in that group of patients
who previously had block.
Speaker 3 (19:21):
Yeah, I mean, this is indeed a challenge. There may
be several issues at play here. First, you know, we
should recognize that this study only assesses maternal factors, specifically
the repertoire of anti cardiac antibody's present in maternal serum
in a single sample and at variable times and snapshots
during the pregnancy. It didn't address fetal factors. So, for instance,
(19:44):
we know that even in twin pregnancies there can be
discordance for heart block outcomes, so there's likely to be
fetal genetic and even epigenetic factors that influence whether heart
block occurs. Secondly, I mean primary responses and secondary immune responses,
such as pregnancies where there's been a prior child with
(20:05):
heart block may have some differences in the timing and
type of immune response. So ideally we would have liked
to have had sequential samples in early pregnancy onward to
address this and further evaluate the predictive potential of these antibodies.
So for this, we're going to need the cooperation of
at risk mothers and collaboration of many of our adult
(20:28):
rheumatology and reproductive medicine colleagues who see these pregnancies early.
Speaker 2 (20:32):
I see, I see really fascinating work. So you know, Bob,
for those in the audience, it's kind of early in
the evening, and Bob is nice enough to speak with
us while he's in the middle of doing all sorts
of other things. So I'm going to wrap this up
with my final question. You know, for the non scientists
such as me and the many lesseners, this paper is
(20:53):
very very exciting. However, I'm wondering, can you share with us,
like what's needed to validate these findings so that we
can prove that these preliminary data that you have, you know, reported,
are reproducible. I mean, how do you validate this sort
of finding? You hinted at it a little bit about
getting serial samples. How long do you think this sort
of validation could take? I was thinking it might be
(21:15):
very long because it's so hard to get these specimens
and if you validated it, is this like the type
of assay that you could imagine one day would potentially
be clinically available. Is this a very difficult test to perform?
Speaker 3 (21:29):
For example, Well, you know we did everything in research blots,
so what are called westerns and two dimensional blots, and
you know, to become a clinical test, it needs to
be switched over to you know, an assay like that
in solution, like an enzyme linked immunosorbent assay or ELIZA
(21:50):
enzyme any kind of enzyme immuno assay, and so we're
working on that, and we're also working with a pharmaceutical
company that's interested in this test as a companion biomarker
to try to identify those pregnancies that are specifically at
rest at risk. And then we would also like to
(22:15):
develop in a lives or a similar assay just to
provide this two you know, labs that are evaluating women
in all jurisdictions to try to you know, just decide
who needs and feed laco, and then if better therapies
come along, to identify the patients and the pregnancies that
(22:39):
might benefit from therapy. There's are a couple other biobanks
of maternal serum already collected from at risk pregnancies, and
I'm aware that one is already performing validation assays in
a very independent fashion, and so I think we'll hear
from that lab relatively soon.
Speaker 2 (22:59):
Wow, that's very exciting. So in other words, another lab,
unrelated to your lab is taking your data and trying
to validate it, as you and I are speaking basically, Yeah,
that's correct, that's terrific. Well, once again, Bob coming to
us with game changing research really extraordinary for those in
(23:19):
the audience. I'm going to put links to the prior
episodes that we had with Bob talking with us about
a novel way of identifying ARVC and also Bragata syndrome. Bob,
I really can't thank you enough for speaking with us
this week on the podcast, and I want to congratulate
you and your Mini co investigators on really remarkable work
and I'm hopeful that it will pan out to be
(23:41):
a really important approach to managing fetuses with heart block.
Thank you so much, Thank you very much for pleasure.
Speaker 1 (23:48):
Well. Once again, doctor Hamilton has provided us with a
very interesting and novel approach to the question of heart block,
as he suggested in our conversation and in the accompanying
editorial comment, as well as his comment in the discussion
to this work. Validation of the findings of this work
will be critical given the small numbers of patients included
in this study. However, it would seem that if we
(24:10):
could in fact identify most patients at risk for heart
block early in pregnancy with the tests such as the
one described in this work, the opportunity to devise better
and more effective treatments for this problem are substantial. I
do think it's exciting that the test is getting turned
into an Eliza test to make it practically easier to perform,
and I am sure that doctor Hamilton and other investigators
(24:32):
he works with, both in his lab and in other centers,
will work to validate this impressive study and hopefully provide
clinicians caring for women who have fetuses at risk for
heart block, another way of identifying these fetuses before block ensues,
and in so doing potentially enhance the window for therapy
to prevent it, while also sparing many others from the
(24:54):
very challenging enhanced surveillance that is needed at the present time.
I'd once again like to thank doctor Hamil for taking
time from his very busy schedule to speak with us
this week on.
Speaker 4 (25:03):
P D Heart.
Speaker 1 (25:04):
Before we come to the end of this week's podcast,
I wanted to have a brief conversation with the directors
of our upcoming course here at Mount Sinai, which many
have attended year after year. This week, actually tomorrow is
the sixteenth annual Mount Sinai Imaging Symposium.
Speaker 4 (25:20):
Again.
Speaker 1 (25:20):
It's on Saturday May thirty first, twenty twenty five, and
the title of the conference is Conversations in Care Cardiac
Conundrums with a hands on three D Echo Workshop. Our
course director is doctor David Ezon and co course director
doctor Kennon Stern. Both gentlemen are associate professors of pediatrics
here at the Icon School of Medicine at Mount Sinai,
(25:41):
and I've asked them to come speak with us briefly
about this wonderful conference, and I'm hopeful that some of
you may listen today and be inspired to come by
Mount Sinai tomorrow and check out the wonderful presentations that
are planned. Therefore, without further ado, here's my brief conversation
with doctor David Eeson and doctor Kennon Stern.
Speaker 2 (25:59):
I'm here now with doctor David Eason and doctor Kennon Stern,
who are the course directors of this year's sixteenth annual
Mount sun I Image in Conference Conversations and Care Cardiac Conundrums.
David Kenon, Welcome to PDRTS.
Speaker 5 (26:14):
Thank you.
Speaker 2 (26:15):
I'm wondering, David, if you could sort of give us
the broad strokes of what the general focus of this
year's particular conference is on.
Speaker 6 (26:23):
Yeah, so once again we're ditching the powerpoints and it's
really about having an interactive conversation with experts in the field.
Where we bring together multi disciplinary experts, surgeons and divensialists
and imagers together to talk about how we can advise
each other to get.
Speaker 2 (26:38):
That best outcome.
Speaker 6 (26:40):
So what does the surgeon actually need to know, how
does he or she actually think about it? And how
can the imager give the surgeon critical data that they need.
Speaker 2 (26:50):
I think it's really terrific how you have gotten rid
of the PowerPoint makes it harder for the speaker having
been one of them before, but I do think it
really forces people people to speak to one another more.
And that dear listener is an innovation that Davidson had
for this conference, really has enriched it tremendously. Kennon, I'm wondering,
(27:11):
you know, there's a lot of wonderful sessions that's going
to that are gonna happen, and again for those in
the audience, it's going to be tomorrow May thirty first,
But Kenon, is there one or two that you are
particularly excited and looking forward to. Well, I'll tell you.
Speaker 4 (27:25):
About all three of the morning sessions because I'm excited
about that.
Speaker 2 (27:28):
Cool.
Speaker 7 (27:28):
As David said that, the topic is conundrus in care,
so we're really are tackling difficult lesions. You know, anatomically,
physiologically more imaging can.
Speaker 4 (27:40):
Really play a big part and big role in helping
the surgeon or interventionalist. First one is complex micro valve repair.
There's always a crowd pleasers how one structure can be
so complicated, But those of us know can jun heart disease,
know that can be the case with many aspects of cardiology. Sure,
(28:00):
complex double outlet right venture cole repair in terms of
how you performed biometricular pair and complex outflow reconstructions in
these patients. And then the session on congenerally corrected transposition
of the Great arteries, which is always a clinical chnogrum.
Speaker 2 (28:18):
Wow, you guys are not taken on some serious stuff here.
We're no little VSDs or ASDs for this conference this year,
at least, David, I know that as the main course
director for this conference, it would be unfair of you
to ask you what your favorite or most looked forward
to session is, because I'm sure you actually chose all
(28:42):
of them, but with the course directors, But is there
one that you're particularly excited and looking forward to?
Speaker 6 (28:47):
Well, this year we're innovating further and in the afternoon
we're going to be doing an interactive three D workshop
with the idea to make this as participatory as possible.
We're going to have live models. People will get practice
on both the Phillips and the GE platforms throughout the
afternoon doing image acquisition and learning really how to go
(29:10):
about getting the best images, and then a separate session
on post processing with each platform. Then in small group
sessions as well as reviewing really nifty and cases that
use three D. That really made a big difference with
some experts in the field that are very adept at
three D, showing both how they process the images to
(29:31):
make it palatable for the surgeon and how you, as
the clinician can go home and take that with you.
Speaker 2 (29:38):
And the attendees will actually have hands on experience using
this equipment. That's right, that's right, that's exciting. I'm sure
that's going to be very appealing to many. Well, David,
maybe you could share with the audience those of you
who are listening today and are saying, Wow, I don't
have anything going on tomorrow on center right, this sounds
really exciting. How would someone get information to I know?
Speaker 6 (30:01):
Yeah, So first, as you know, you can actually do
same day registration, So if you come to the Mount
Signey Hospital on Madison Avenue in one hundred in Manhattan. You
can come to Annenburgh twelfth floor, the Annenburg Building, twelfth
floor and you can sign up right then and there.
It's ninety dollars for attending physicians and free to everybody else.
(30:22):
We really try to make this as easy as possible
for people to participate. It's about educating the community. And
so you can just come in at the Mount Sainnday
on Saturday morning. It starts at eight am and it
runs throughout the day till four. We've got a delicious
meal cater throughout the day. Please join us.
Speaker 2 (30:40):
Wait, there's no such thing as free lunch. Back to
Stern coming through with his outstanding humor. No wait, I
don't remember agreed to make this free for everybody else
times we need to have a conversation after this meet it. Well, guys,
I really want to thank you for sharing this exciting conference,
and again I would encourage everybody to go online to
(31:01):
learn about the conference that's going to be tomorrow. And
as David said, you can come even day of and
register right in person. And so I want to thank
you both, guys, both for all the hard work that
you and the co course directors do for this every year,
and thank you so much for spending a few moments
with us this week on the podcast. Thank you.
Speaker 1 (31:21):
To conclude this three hundred and forty third episode of
p D Heart Pediatric Cardiology, Today we hear the gavote
from Messines Manon and we hear it sung brilliantly by
the up and coming wonderful Spanish soprano Ruth Niesta, who
is the winner of the prestigious Premios Lyricos Campo Amor
twenty fifteen and the Cordellario Prize as the Best New
(31:43):
Artist of twenty fifteen. And since her debut and opera
at the Tiatro de la Sarzuela in Madrid in twenty twelve,
Miss Iniesta has sung all over Europe in many different roles,
debuting new ones each time. She has a wonderful presence
on social media. Her beautiful Castilian Spanish has helped me
learn and speak Spanish better, reminding me of the wonderful
(32:06):
Spanish teachers I had back at Polly Prep growing up
in Brooklyn, New York. Thank you very much for joining
me for this episode, and thanks once again to doctor Hamilton,
I hope we'll have a good week ahead.
Speaker 2 (32:17):
O jes.
Speaker 8 (33:00):
H S word.
Speaker 5 (33:20):
Said she you see.
Speaker 8 (33:28):
You susy, you said, looking little lady. She is a
(33:56):
sec see it was like.
Speaker 9 (34:46):
Us. You can't go it sun as to loos of
(35:26):
sass cocks to loss of sex fact shut so.
Speaker 5 (36:31):
Other spun song fist short ass, oh little shot
Speaker 9 (37:02):
Six sas show to also se
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