July 18, 2025 • 31 mins
This week we review a recent important longitudinal follow up study of patients who have undergone palliation for the treatment of HLHS at The Children's Hospital of Philadelphia over the past 35+ years. What are the 'transplant-free' survival numbers at 35 years follow up following newborn palliation? Are there differences between hybrid and traditional "Norwood/Stage I" palliation? What factors explain the group of HLHS patients who do are 'super-Fontan's'? What accounts for the marked variability in outcomes of these complex patients? Dr. J. William Gaynor shares his deep insights both from his large scale paper and long-term experience caring for patients with HLHS.
doi: 10.1016/j.jacc.2025.04.028
doi: 10.1016/j.jacc.2025.04.028
Mark as Played
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 for joining me for this three hundred and
forty ninth episode of Pdheart. I hope everybody enjoyed last
week's episode on the topic of using the melody valve
(00:36):
for palliation of atrioventricular valvular dysfunction in the small child.
For those of you interested in cardiovascular surgery, i'd certainly
recommend you take to listen to last week's episode three
hundred and forty eight with doctor Samantha Gilg of the
University of Nebraska. 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
(00:59):
week we move on to a very interesting topic that
is always of great interest to everyone in this podcast.
The title of the work is long Term Survival and
Patient Reported Outcomes after staged reconstructive surgery for hypoplastic left
heart syndrome. The first author of this work is Jay
William Gaynor and the senior author, Susan Nicholson. Doctor Gaynor,
of course comes to us from the Children's Hospital, Philadelphia.
(01:21):
When we're done reviewing this paper, I'm hopeful that doctor
Gaynor will be able to join us to discuss it. Therefore,
let's get straight onto this very important article and then
a conversation with Professor Gaynor. This week's work is about
long term outcomes in the hypoplastic left heart patient and
so the author's review a bit of the history of
the Norwood operation, which was first described in nineteen eighty three.
(01:43):
The author's review how many improvements in care have occurred
in the over forty years since that first report, including
in fetal diagnosis, preoperative stabilization approaches, operative and anesthetic considerations,
and of course post operative care. And we've covered many
of these advances on the podcast during the last seven
and a half years. However, despite the market improvements and
(02:04):
morbidity and mortality for patients undergoing the Norwood for hypoplastic
left heart syndrome, mortality rates still remain high, and the
authors over the literature showing that though there are many
papers out there characterizing overall single ventrical outcomes long term.
There are surprisingly few that assess outcomes specifically for the
hypoplastic left heart patient and the author's state and I
(02:26):
quote there is a critical gap in our knowledge concerning
survival and adult outcomes for neonates undergoing staged reconstructive surgery
for hypoplastic left heart syndrome and variance. With this as
a background, the authors stated that the primary objectives of
this work were to examine long term survival and patient
specific risk factors on survival, and to secondarily examine functional
(02:49):
and health outcomes, including quality of life and adult patients
who have survived and made it well into adulthood. This
was a single center, very long, longitudinal study that included
all hypoplastic left heart syndrome patients who had a Norwood
or a hybrid between January one of nineteen eighty four
and December thirty first of twenty twenty three at the
Children's Hospital Philadelphia, and the authors review the very complex
(03:12):
ways that data was obtained and collected from the Cardiac
Surgical database as well as the electronic medical record and
paper charts. They also performed checks on the data using
the National Death Index as well as Scientific Registry of
Transplant recipients to confirm that the data was robust and correct.
Adult survivors greater than are equal to eighteen were contacted
and asked to complete quality of life questionnaires. Once again,
(03:36):
the primary outcome was the rate of death or cardiac transplant.
The last contact with secondary outcomes of adult data like
educational attainment, marital status, employment, mental health issues, Fontaine related
complications like pl or a pacemaker, and of course, quality
of life. The authors review that patients had a standard
Norwood or a hybrid based on the decisions of the
(03:58):
surgical conference at Chop but not following a defined protocol.
To investigate changes and outcomes over time, they divided this
long study period from ERA one, which was nineteen eighty
four to eighty eight, and so on and so forth
in four year periods for a total of eight such periods,
with ERA eight being twenty nineteen to twenty twenty four.
(04:18):
The goal of these different era divisions was to see
or allow for analysis of differences and outcomes as surgical
teams changed and practice. Similarly, did the author's review how
they statistically performed this very large database study and also
how the quality of life analysis was performed and for
the granular data on how this was performed. I would,
as usually recommend the listener take a look at the paper,
(04:39):
specifically pages twenty three eighty nine and twenty three ninety
for these details, and on to the results. Let me
begin by stating that this strikes me as a very
important paper, and so I would strongly recommend that all
review this work and read it for themselves and the
link to the paper as usual as in the show notes.
Given that there are a lot of data and it
is challenging to review all of this in a podcast format,
(05:02):
I'll share with you four or five of the most
important findings of this work. First, let's just review the cohort.
There were two thousand and twelve neonates who underwent a
stage reconstructive surgery for hypoplastic left heart syndrome during the
time period, with nineteen hundred and twenty one having the
traditional NORWOULD approach as the initial strategy and ninety one
the hybrid as would be expected. The authors have an
(05:24):
admirable ninety percent completeness of follow up, and so let's
just review some of the important findings. First, overall survival
at thirty five years was thirty four point six percent
with transplantation performed in ninety eight total patients, with the
vast majority being a heart only transplant and a very
small minority having a heart liver five patients or heart
(05:47):
lung one patient. Thus, said in a different way, transplant
free survival was as follows, sixty three percent at one year,
fifty two percent at ten years, forty four percent at
twenty years, and thirty one percent at thirty five years.
And so, just to emphasize, transplant free survival for patient's
(06:07):
undergoing staged reconstruction for hypoplastic left heart syndrome during this
long period at the Children's Hospital Philadelphia was thirty one
percent at thirty five years. Follow Up, Second, the author's
analyzed outcomes by the eight four year eras that we
reviewed a moment ago and showed that in the first
four eras from nineteen eighty four to two thousand and three,
(06:28):
there was consistent sequential improvements in outcomes, but there has
been no subsequent improvement from ERA five to eight, meaning
two thousand and four till the present year twenty twenty three. Third,
what were the factors associated with worse transplant free survival
on a multivariable analysis? These were earlier era, smaller acending
(06:50):
a order at birth, more severe av valve regurgitation at
the initial intervention, younger gestational age, the presence of a
genetic anomaly, and finally, non white race. Fourth, and not surprisingly,
BTT shunt and RV to PA shunt were as shown
in other large series to be equal in regards to survival,
(07:11):
but there was reduced survival for the hybrid procedure compared
to the Norwood when adjusting for patient characteristics. And finally,
what about the health survey data. Well, remember that five
hundred and thirty six adult survivors were sent to survey
and during that process the authors determined that twenty two
patients had died and so ultimately five hundred and thirteen
(07:32):
a live subjects received the survey and seventy percent or
three hundred and sixty two declined participation, meaning that only
thirty percent or two hundred and thirty three subjects agreed
to participate and only two hundred and twenty eight actually did.
Most of these were fontane patients two hundred and three,
with nineteen being heart transplant patients and two biventricular repairs.
(07:54):
The mean age of the respondents was twenty five, and
they were more likely to be male, white, and have
had a fontane. Eighty five percent of those who answered
the survey viewed their health as excellent, and more than
forty percent reported having anxiety. Thirty four percent had completed
high school, and forty two percent had attended college or
technical school, with a bit over fifty percent having full
(08:16):
or part time employment. Most of these patients did not
have fontane associated complications and so perhaps different from the
majority of fontane patients. And when we look at the
quality of life assessment of Norwood patients versus the general
population in Fig. Three of this paper, we see that
in all parameters like perception of physical health, psychological health,
(08:36):
social relationships, and environment, the respondents were as good or
better than the general population in the opinion of those
answering the survey. I would refer all to the central
illustration which is seen on page twenty three ninety five,
which shows the long term survival after reconstructive surgery, showing
that the first four eras had relatively poor survival, but
(08:58):
the more recent four eras are all unch together with
improved survival in comparisons to the earlier era, but without
real differences in the later era in their discussion the
author's state and I. In this large cohort of consecutive
newborn's undergoing staged reconstructive surgery for hypoplastic left heart syndrome,
we found that transplant free survival at thirty five years
(09:19):
of age is approximately thirty percent. Although transplant free survival
significantly increased from the introduction of the Norwood until the
early two thousands, survival has not significantly improved over the
past twenty years, despite improvements in surgical strategy and care
for the newborn with HLHS, most notably the introduction and
wide use of the RV to PA shunt and hybrid procedures.
(09:43):
Consistent with other studies, including the SVR Reconstruction study, we
found no difference in long term transplant free survival for
the RV to PA conduit compared with the modified BTT shunt.
As in other studies, patients selected for an initial hybrid
procedure were a high risk population. After adjustment for patient characteristics,
we found no evidence for improved outcomes for those undergoing
(10:06):
and initial hybrid procedure. Our data do not provide insight
into the mechanism underlying the lack of continued improvement. The
authors speak about the rarity of these data and compare
it to other prior general font Hane papers. They speak
about the good outcome patients who had such a high
quality of life with scores that were very high, and
how this is consistent with more recent literature about so
(10:27):
called superfont Hanne patients who do much better than the average,
and they wonder aloud how there is clearly a selective
group of higher functioning Fontanne patients who have had fewer complications,
with good educational attainment, higher levels of employment, and good
or excellent quality of life. They do emphasize, however, that
these are the outliers and that there are many who
(10:48):
were not as robust. In regards to limitations, the authors
speak of the fact that patients who did not have
a hybrid or Norwood were not included, and so the
outcomes are likely overall better than they really are since
they are not accounting for patients in which comfort care
was chosen. They speak also of the non randomized way
that decisions for Norwood versus hybrid were made and the
(11:09):
bias that this can introduce. They speak about difficulties in
some data collection due to the very long time horizon
of this study and also of the bias in the
quality of life reports, since only a small percentage of
survivors actually was willing to fill out the questionnaire. And
so they conclude in this cohort of greater than two
thousand consecutive infants undergoing stage reconstructive surgery for hypoplastic left
(11:33):
heart syndrome, less than thirty five percent were alive without
a transplant by thirty five years of age. There was
no statistically significant difference in survival rates for Norwood with
modified BTT shunt compared to Norwood with RV TOPA conduit.
In addition, use of the hybrids did not result in
improved outcomes compared to the Norward procedure. However, there is
(11:53):
a group of adult survivors who reported good to excellent
general health and few fontine related complications. This finding suggests
that there is a selected group of patients with excellent survival,
quality of life, and functional outcomes consistent with a high
performing Fontaine phenotype. Well, this is a very interesting work
that can be viewed in a positive or negative light.
(12:15):
On the one hand, it's clear that there has been
market improvement in care with improvements in outcomes in survival.
This is to be applauded. However, on the other hand,
the past one to one and a half decades have
not demonstrated anywhere near as much improvement, with basically no
detectable outcome differences. The question is how can we impact this?
(12:35):
Do we need more dedicated teams devoted exclusively to this
patient group as some centers have started, like Chopped for example,
and what about long term survival and quality of life?
Clearly there's cause for alarm in this patient group where
we have such poor long term survival and even among
survivors lots of morbidity. We clearly are going to need
to rethink our long term management of this patient group
(12:57):
and perhaps look more closely as some investigators are or
at the super fontane patients. There is clearly something different
about that group of patients who do so well. Some
of the differences are likely not modifiable, but some may be,
and we need to continue to aggressively study these so
called better fontane patients to see if there are factors
that we can identify and then perhaps amplify that are
(13:20):
associated with better outcomes. At this point, I think we
should move forward to our conversation with the works first author,
doctor Gaynor, joining us now.
Speaker 2 (13:28):
To discuss this week's work is the Works senior author,
Doctor William Gaynor. Doctor Gaynor is an attempting surgeon in
the Cardiac Center at the Children's Hospital Philadelphia. He holds
the Daniel M. Tabass Endowed Chair in Pediatric Cardiothoracic Surgery
and specializes in heart surgery and infants. He currently serves
as director of the Long Term follow Up Program in
(13:48):
the Cardiac Center at CHOP and as the co Principal
investigator of the Birth Defects Bio Repository. Doctor Gaynor is
a graduate of the Medical University of South Carolina, followed
by residency at Parkland Memorial Hospital in Dallas, Texas and
Duke University Medical Center. He also completed a research fellowship
at Duke University and did cardiac surgical training in congenital
(14:11):
heart disease at the Hospital for Sick Children as well
as Great.
Speaker 1 (14:14):
Ormond Street in London, England.
Speaker 2 (14:16):
It is a pleasure and honor to have him join
us this week on the podcast Welcome Doctor Gaynor to
pet Heart. I'm here now with doctor Bill Gaynor of
the Children's hostle Philadelphia. Doctor Gaynor, thank you so much
for joining us this week on PD Heart.
Speaker 3 (14:27):
Thank you for inviting me.
Speaker 2 (14:28):
Great pleasure. Congratulations to you and your many co authors
on this very important work. I was wondering as I
was reading at doctor Gaynor, what was the main motivation
for your team to assess these outcomes in the hypoplast
cohort from CHOPP.
Speaker 4 (14:43):
Well, first of all, I do want to emphasize it
as a team. I mean, this is a forty year experience,
and it's there have been countless pete people who have
cared for these kids and are responsible for the outcomes
and help put together the data. I started a job
in nineteen ninety five in Or it was still relatively
knew even a CHOP. I mean doctor Norwood had done
(15:03):
the first and successfully in the early eighties and then
came to CHOP in nineteen eighty four, so it was still,
you know, on the cutting edge of heart surgery. And
obviously CHOP had a very large experience with these and
they are a very complex patient population. And as results
(15:24):
for other types of control heart disease were improving, there
was improvement for kids with HHS invariants, but not to
the same extent, and as we looked at this over
the years, it seemed like some of the outcomes may
have been plateauing.
Speaker 3 (15:40):
Were we getting better? That was one of the motivations.
Speaker 4 (15:44):
And the other was again because of the unique population
of chop we are positioned to look at the outcomes
for thirty to forty year olds. No one else really
has a significant number of patients. So those were the
two motivating factors I see.
Speaker 2 (15:59):
Thank you, very interesting, doctor Gayner. I mean, one of
the more sobering findings of this work is that the
past few decades have not been associated with as substantial
improvements in outcomes in comparison to the earlier eras of
this work, which it sounds from what you just said,
was one of the impressions you had. What do you
think is the main reason that things haven't noticeably improved
(16:22):
in the last ten or so years. Is it the
simple physiology or that, I should say, the complex physiology
of hypoplasticalote heart syndrome. Is it the surgical approach? Why
do you think we seem to be kind of peaking
in our outcomes in this regard?
Speaker 4 (16:37):
Well, I think there's a couple of things. So when
I think the physiology is key. It's so very difficult
physiology in reality. You know, even with newer techniques like
the hybrid, the physiology in the post operative period is
not significantly different from that of a normal would you
avoid bypass, but the physiology is very similar. And we
(16:58):
found that the hybrid is not very different in outcomes
and definitely not better in outcomes.
Speaker 3 (17:05):
Than the NERO would procedure.
Speaker 4 (17:07):
We've seen over time there have been introductions of other
strategies such as the RB top A conduit instead of
the modified Blaylock Tastic Thomas Shunt, and again the data's
coming in in the long run there's really no difference.
Speaker 3 (17:21):
So I think it's the part of it is the
underlying physiology, but I think a big part of it
is our lack of knowledge. I think one of the biggest.
Speaker 4 (17:29):
Problems in conjinal heart surgery today is unexplained.
Speaker 3 (17:34):
Variation and outcomes.
Speaker 4 (17:35):
If you look at all the risk models for mortality
for NERD developmental outcomes, the known risk factors, the factors
that we put into our statistical models, things like genetic syndromes, prematurity,
et cetera, only explain about thirty to thirty five percent
of the observed variation in outcomes.
Speaker 3 (17:54):
That means this variation is being driven.
Speaker 4 (17:57):
By factors that we don't We have an identical and
we don't understand, and if we could identify them, they
might become potential therapeutic targets. One of the key things
that we're really interested in CHOP now is the maternal
fetal environment and you know and pre birth life. We
(18:18):
know that kids will contain heart disease, the pregnancies can
be difficult, there's a higher incidence of maternal complications such
as pre acclamcy and gestational hypertension. We know de bate,
there's a high instance of fetal growth restriction and pre
term birth. All of these can affect the long term outcomes.
We're now beginning to show that there's a high incidence
of placental abnormalities and placental dysfunction, and we're looking at
(18:43):
and targeting and beginning trials of potential fetal interventions. And personally,
I think I think that intervening before birth to improve
fetal growth is going to be one of the real
areas innovation going forward. I mean, if we need to
have babies who are full term with normal organ maturation.
(19:07):
If we're going to achieve the best outcomes that we can,
there are many other things such as social in terminus
of health. We know that families who are not English speaking,
who live in under resource neighborhoods, the results are worse
for those kids. We need to have strategies to help
overcome those if we're.
Speaker 3 (19:26):
Going to get the best outcomes for everything.
Speaker 4 (19:28):
So I think, you know, a lot of what we
do is driven now currently trying to explain this unexplained variation.
If we can begin to understand what is driving that,
then we can understand the mechanisms and we could potentially
develop new therapeutic targets.
Speaker 2 (19:44):
Very interesting, Thank you very much. You know, one of
the things that I found interesting was that quality and
life by this patient group was perceived by the survivors
to be very good on average. And I wondered if
you thought that this was true for the entire group
of hypoplastic single metrical survivors, or do you think perhaps
this was biased as a sample by the relatively small
(20:08):
number of people who actually answered the QOL surveys.
Speaker 3 (20:12):
Well, I think it's I think it's two things.
Speaker 4 (20:15):
One, I think, you know, we should be happy that
we do identify a sizeable group of adult survivors who
have not had Fontaine related complications, who are have jobs,
good education, are married, having family lives, and are happy
with their quality of life. For many years, it was
all gloom and doom, and you know, you get to
be twenty years old, it's over.
Speaker 3 (20:36):
Well, that's clearly not true. But only about half of the.
Speaker 4 (20:42):
Of the survivors that we contact or attempted to contact, responded,
so there probably is some selection bias here. So I think,
to me, the good news is there is a group
who are doing well at twenty five, thirty, thirty five
years old. How they will how that will persist as
they move into the later, you know, the next decade
(21:03):
of life. Don't know that's going to be one of
the next studies, but I think we do need to
understand why is there.
Speaker 5 (21:08):
A group of children are now adults who undergo these
three operations, have a font in physiology, and yet twenty
to thirty years later report very few complications.
Speaker 4 (21:20):
And good quality of life. How are they different? Is
probably not the surgery. It's probably something intrinsic in either
their environment or their genetics or something else. We need
to understand what those factors are, what are driving these
high performing fontanes and try to increase that proportion. But
I agree not it clearly not everyone is thriving. If
(21:42):
you look the survival transplant pre survival is only about
thirty percent. So that's again there's a selection as in
a survivor bias here. But the good news is there
is a group and it's not just one or two
patients who are doing very well and hopefully they can
will continue to do well.
Speaker 2 (22:00):
I wanted to sort of harp on that group of
what we sometimes refer to as super font had patients
who clearly do globally much better. Do you have any
guesses on what makes them so good? And do you
think that there are lessons from this patient cohort that
we could apply to the care of all of our
fonts and patients.
Speaker 4 (22:20):
Well, I don't know about specific lessons and I don't
know about the specific mechanisms, but that's something we're going
to be looking at. We're going to continue to follow
this cohort and try to understand We're going to begin
to work with others to try to develop cohorts. We're
now enrolling, you know, newborns with hyperplastical syndrome is part
(22:40):
of our birth Defects by our repository at shop where
we enroll in.
Speaker 3 (22:46):
Fetal life kids with a variety of birth.
Speaker 4 (22:49):
Defects, including cogeneral heart disease.
Speaker 3 (22:52):
We're doing whole genome sequencing.
Speaker 4 (22:54):
We're tracking things like social terms of health and environmental exposures,
and hopefully by building this new or where we have
much more detailed genetic information, the trajectory of their life,
the neighborhoods they live in, that we can begin to
understand what are some of the fact.
Speaker 3 (23:10):
Here's driving better versus worse survival.
Speaker 4 (23:13):
But that's the next step.
Speaker 2 (23:17):
Yeah, yeah, Well, for those in the audience, doctor Gainer
was nice enough to join us today late in the day,
and so I don't want to take up a whole
lot more of your time. You sort of hinted at this,
and I was wondering. You have a very very large
experience and caring for patients with hypoplastic left heart syndrome
for many decades now, as well as being a researcher
(23:37):
in this area. You talked about how you felt that
fetal intervention and an understanding fetal life of these patients
could be an area for improvements any other areas where
you think there is an opportunity for us to potentially
improve the outcomes and get a better decade coming forward.
Speaker 4 (23:59):
Oh, I think you know, we need to understand who
is likely to do better. I doubt every child will
do the exact same with a Norwood procedure, with a
BT shunt, a neual feizure, with an r V.
Speaker 3 (24:11):
Twop, a conduit initial hybrid procedure.
Speaker 4 (24:15):
I think we need to understand who's going to do
best with a specific operation and try to individualize treatment
that way.
Speaker 3 (24:22):
And one size does not fit all.
Speaker 4 (24:24):
I think we probably need you know, one of the
options has always been transplantation.
Speaker 3 (24:29):
Perhaps we should.
Speaker 4 (24:30):
Move to that earlier for some some patients, but that
leads brings a whole another set of medical issues and
risk for long term survival and the and I think
you know we need to and with with the lack
of donor organs, transplantation is just not going to be
feasible for everyone. Uh, there may be as the devices improved,
(24:53):
there may be some some role for fontan assist devices
and implannabile of add particul subculminary bad if that was
implannable that might improve the opple So I think there's
a lot of things that could be done. Understanding the
genetic differences in the biologic pathways driving these differences in outcome,
working to truly personalized medicine and individual therapies and individual
(25:16):
surgical strategies. Considering as the technology improves, assist devices as destination,
not just as a bridge transplant.
Speaker 3 (25:24):
The devices have to get better, but I think that's
within the palm of possibility.
Speaker 2 (25:31):
Yeah, yeah, all interesting exciting areas and arenas to go
forward for those younger people. We haven't figured it all
out yet. A lot of things to investigate going forward
over the next few decades. Well, doctor Gainer, I can't
thank you enough for coming on and speaking to us again.
You've been a guest once in the past, and very
much appreciate your spending time with us, and again want
(25:53):
to thank you and congratulate you and your many many
co investigators and what was really very important that I
very much enjoyed.
Speaker 4 (26:01):
Well, thank you very much, and again I appreciate the
opportunity to discuss that work.
Speaker 3 (26:05):
Thank you, thank you.
Speaker 2 (26:06):
Well.
Speaker 1 (26:06):
I'm sure you found doctor Gainer's comments to be of
great interest. I won't review all of his many outstanding points,
but I think his general notion of trying to unlock
the factors that might explain the unexplained variability in outcomes
for this patient group to be an important general mental
model when thinking about how we can address them. There
clearly are factors that we do not understand, and to
(26:28):
some degree it is remarkable that using a sort of
one size fits all approach we've achieved the results we have.
But I think that as comments have clearly demonstrated that
there are levels of complexity of these different hypoplastic left
heart syndrome patients that are substantial and still unknown, I
certainly do believe that they will be a day where
we will take a much more personalized approach to the
(26:49):
management of these patients, and I'm hopeful that this sort
of approach will be informed by the sort of research
that doctor Gainer and his colleagues are conducting, as well
as more study of our so called super fontine patients,
looking for those positive factors that we can leverage for
improvement in outcomes in all of our patients. I'd again
like to thank doctor Gainer for taking time from a
(27:10):
very busy schedule to speak with us this week on
pd Heart to conclude this three hundred and forty ninth
episode of pet Heart Pediatric Cardiology. Today we celebrate the
life of the great Welsh tenor Stuart Burroughs, who died
last week at the age of ninety two. Burroughs was
born in South Wales, and he was a boy soprano
before becoming an adult tenor. And he was also a
(27:31):
great rugby player and turned down a professional career in
that field to become a tenor. Burrows sank throughout the world,
starting his career in the UK, appearing at the Royal
Opera House in London for twenty two seasons, and singing
also all over the globe, including twelve years at the
Metropolitan Opera. Though great in many areas of tenor singing,
(27:51):
he was perhaps most known for his work in Mozart,
and sometimes even given the nickname of King of Mozart.
Today we hear why when we hear Burrows in a
live performance of the fiendishly difficult Eelmia tosorro from Mozart's
Don Giovanni. Thank you very much for joining us for
this episode, and thanks so.
Speaker 6 (28:09):
Much to our guest I hope I'll have a good
week ahead.
Speaker 7 (28:24):
Welcome should mother alone.
Speaker 8 (28:41):
A girl.
Speaker 2 (29:00):
R car.
Speaker 6 (29:04):
Pa the case recority.
Speaker 8 (29:08):
In decory in declary.
Speaker 9 (29:16):
Amory goody, sorry you torm.
Speaker 8 (29:29):
So is time on?
Speaker 9 (30:04):
He didn't go to.
Speaker 7 (30:08):
Jacos jo dis deep pase.
Speaker 8 (30:44):
Any post you.
Speaker 2 (31:16):
What's you?
Speaker 7 (31:22):
It's small, distant, Sure you are, said
Speaker 4 (31:32):
Soup for your
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 for joining me for this three hundred and
forty ninth episode of Pdheart. I hope everybody enjoyed last
week's episode on the topic of using the melody valve
(00:36):
for palliation of atrioventricular valvular dysfunction in the small child.
For those of you interested in cardiovascular surgery, i'd certainly
recommend you take to listen to last week's episode three
hundred and forty eight with doctor Samantha Gilg of the
University of Nebraska. 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
(00:59):
week we move on to a very interesting topic that
is always of great interest to everyone in this podcast.
The title of the work is long Term Survival and
Patient Reported Outcomes after staged reconstructive surgery for hypoplastic left
heart syndrome. The first author of this work is Jay
William Gaynor and the senior author, Susan Nicholson. Doctor Gaynor,
of course comes to us from the Children's Hospital, Philadelphia.
(01:21):
When we're done reviewing this paper, I'm hopeful that doctor
Gaynor will be able to join us to discuss it. Therefore,
let's get straight onto this very important article and then
a conversation with Professor Gaynor. This week's work is about
long term outcomes in the hypoplastic left heart patient and
so the author's review a bit of the history of
the Norwood operation, which was first described in nineteen eighty three.
(01:43):
The author's review how many improvements in care have occurred
in the over forty years since that first report, including
in fetal diagnosis, preoperative stabilization approaches, operative and anesthetic considerations,
and of course post operative care. And we've covered many
of these advances on the podcast during the last seven
and a half years. However, despite the market improvements and
(02:04):
morbidity and mortality for patients undergoing the Norwood for hypoplastic
left heart syndrome, mortality rates still remain high, and the
authors over the literature showing that though there are many
papers out there characterizing overall single ventrical outcomes long term.
There are surprisingly few that assess outcomes specifically for the
hypoplastic left heart patient and the author's state and I
(02:26):
quote there is a critical gap in our knowledge concerning
survival and adult outcomes for neonates undergoing staged reconstructive surgery
for hypoplastic left heart syndrome and variance. With this as
a background, the authors stated that the primary objectives of
this work were to examine long term survival and patient
specific risk factors on survival, and to secondarily examine functional
(02:49):
and health outcomes, including quality of life and adult patients
who have survived and made it well into adulthood. This
was a single center, very long, longitudinal study that included
all hypoplastic left heart syndrome patients who had a Norwood
or a hybrid between January one of nineteen eighty four
and December thirty first of twenty twenty three at the
Children's Hospital Philadelphia, and the authors review the very complex
(03:12):
ways that data was obtained and collected from the Cardiac
Surgical database as well as the electronic medical record and
paper charts. They also performed checks on the data using
the National Death Index as well as Scientific Registry of
Transplant recipients to confirm that the data was robust and correct.
Adult survivors greater than are equal to eighteen were contacted
and asked to complete quality of life questionnaires. Once again,
(03:36):
the primary outcome was the rate of death or cardiac transplant.
The last contact with secondary outcomes of adult data like
educational attainment, marital status, employment, mental health issues, Fontaine related
complications like pl or a pacemaker, and of course, quality
of life. The authors review that patients had a standard
Norwood or a hybrid based on the decisions of the
(03:58):
surgical conference at Chop but not following a defined protocol.
To investigate changes and outcomes over time, they divided this
long study period from ERA one, which was nineteen eighty
four to eighty eight, and so on and so forth
in four year periods for a total of eight such periods,
with ERA eight being twenty nineteen to twenty twenty four.
(04:18):
The goal of these different era divisions was to see
or allow for analysis of differences and outcomes as surgical
teams changed and practice. Similarly, did the author's review how
they statistically performed this very large database study and also
how the quality of life analysis was performed and for
the granular data on how this was performed. I would,
as usually recommend the listener take a look at the paper,
(04:39):
specifically pages twenty three eighty nine and twenty three ninety
for these details, and on to the results. Let me
begin by stating that this strikes me as a very
important paper, and so I would strongly recommend that all
review this work and read it for themselves and the
link to the paper as usual as in the show notes.
Given that there are a lot of data and it
is challenging to review all of this in a podcast format,
(05:02):
I'll share with you four or five of the most
important findings of this work. First, let's just review the cohort.
There were two thousand and twelve neonates who underwent a
stage reconstructive surgery for hypoplastic left heart syndrome during the
time period, with nineteen hundred and twenty one having the
traditional NORWOULD approach as the initial strategy and ninety one
the hybrid as would be expected. The authors have an
(05:24):
admirable ninety percent completeness of follow up, and so let's
just review some of the important findings. First, overall survival
at thirty five years was thirty four point six percent
with transplantation performed in ninety eight total patients, with the
vast majority being a heart only transplant and a very
small minority having a heart liver five patients or heart
(05:47):
lung one patient. Thus, said in a different way, transplant
free survival was as follows, sixty three percent at one year,
fifty two percent at ten years, forty four percent at
twenty years, and thirty one percent at thirty five years.
And so, just to emphasize, transplant free survival for patient's
(06:07):
undergoing staged reconstruction for hypoplastic left heart syndrome during this
long period at the Children's Hospital Philadelphia was thirty one
percent at thirty five years. Follow Up, Second, the author's
analyzed outcomes by the eight four year eras that we
reviewed a moment ago and showed that in the first
four eras from nineteen eighty four to two thousand and three,
(06:28):
there was consistent sequential improvements in outcomes, but there has
been no subsequent improvement from ERA five to eight, meaning
two thousand and four till the present year twenty twenty three. Third,
what were the factors associated with worse transplant free survival
on a multivariable analysis? These were earlier era, smaller acending
(06:50):
a order at birth, more severe av valve regurgitation at
the initial intervention, younger gestational age, the presence of a
genetic anomaly, and finally, non white race. Fourth, and not surprisingly,
BTT shunt and RV to PA shunt were as shown
in other large series to be equal in regards to survival,
(07:11):
but there was reduced survival for the hybrid procedure compared
to the Norwood when adjusting for patient characteristics. And finally,
what about the health survey data. Well, remember that five
hundred and thirty six adult survivors were sent to survey
and during that process the authors determined that twenty two
patients had died and so ultimately five hundred and thirteen
(07:32):
a live subjects received the survey and seventy percent or
three hundred and sixty two declined participation, meaning that only
thirty percent or two hundred and thirty three subjects agreed
to participate and only two hundred and twenty eight actually did.
Most of these were fontane patients two hundred and three,
with nineteen being heart transplant patients and two biventricular repairs.
(07:54):
The mean age of the respondents was twenty five, and
they were more likely to be male, white, and have
had a fontane. Eighty five percent of those who answered
the survey viewed their health as excellent, and more than
forty percent reported having anxiety. Thirty four percent had completed
high school, and forty two percent had attended college or
technical school, with a bit over fifty percent having full
(08:16):
or part time employment. Most of these patients did not
have fontane associated complications and so perhaps different from the
majority of fontane patients. And when we look at the
quality of life assessment of Norwood patients versus the general
population in Fig. Three of this paper, we see that
in all parameters like perception of physical health, psychological health,
(08:36):
social relationships, and environment, the respondents were as good or
better than the general population in the opinion of those
answering the survey. I would refer all to the central
illustration which is seen on page twenty three ninety five,
which shows the long term survival after reconstructive surgery, showing
that the first four eras had relatively poor survival, but
(08:58):
the more recent four eras are all unch together with
improved survival in comparisons to the earlier era, but without
real differences in the later era in their discussion the
author's state and I. In this large cohort of consecutive
newborn's undergoing staged reconstructive surgery for hypoplastic left heart syndrome,
we found that transplant free survival at thirty five years
(09:19):
of age is approximately thirty percent. Although transplant free survival
significantly increased from the introduction of the Norwood until the
early two thousands, survival has not significantly improved over the
past twenty years, despite improvements in surgical strategy and care
for the newborn with HLHS, most notably the introduction and
wide use of the RV to PA shunt and hybrid procedures.
(09:43):
Consistent with other studies, including the SVR Reconstruction study, we
found no difference in long term transplant free survival for
the RV to PA conduit compared with the modified BTT shunt.
As in other studies, patients selected for an initial hybrid
procedure were a high risk population. After adjustment for patient characteristics,
we found no evidence for improved outcomes for those undergoing
(10:06):
and initial hybrid procedure. Our data do not provide insight
into the mechanism underlying the lack of continued improvement. The
authors speak about the rarity of these data and compare
it to other prior general font Hane papers. They speak
about the good outcome patients who had such a high
quality of life with scores that were very high, and
how this is consistent with more recent literature about so
(10:27):
called superfont Hanne patients who do much better than the average,
and they wonder aloud how there is clearly a selective
group of higher functioning Fontanne patients who have had fewer complications,
with good educational attainment, higher levels of employment, and good
or excellent quality of life. They do emphasize, however, that
these are the outliers and that there are many who
(10:48):
were not as robust. In regards to limitations, the authors
speak of the fact that patients who did not have
a hybrid or Norwood were not included, and so the
outcomes are likely overall better than they really are since
they are not accounting for patients in which comfort care
was chosen. They speak also of the non randomized way
that decisions for Norwood versus hybrid were made and the
(11:09):
bias that this can introduce. They speak about difficulties in
some data collection due to the very long time horizon
of this study and also of the bias in the
quality of life reports, since only a small percentage of
survivors actually was willing to fill out the questionnaire. And
so they conclude in this cohort of greater than two
thousand consecutive infants undergoing stage reconstructive surgery for hypoplastic left
(11:33):
heart syndrome, less than thirty five percent were alive without
a transplant by thirty five years of age. There was
no statistically significant difference in survival rates for Norwood with
modified BTT shunt compared to Norwood with RV TOPA conduit.
In addition, use of the hybrids did not result in
improved outcomes compared to the Norward procedure. However, there is
(11:53):
a group of adult survivors who reported good to excellent
general health and few fontine related complications. This finding suggests
that there is a selected group of patients with excellent survival,
quality of life, and functional outcomes consistent with a high
performing Fontaine phenotype. Well, this is a very interesting work
that can be viewed in a positive or negative light.
(12:15):
On the one hand, it's clear that there has been
market improvement in care with improvements in outcomes in survival.
This is to be applauded. However, on the other hand,
the past one to one and a half decades have
not demonstrated anywhere near as much improvement, with basically no
detectable outcome differences. The question is how can we impact this?
(12:35):
Do we need more dedicated teams devoted exclusively to this
patient group as some centers have started, like Chopped for example,
and what about long term survival and quality of life?
Clearly there's cause for alarm in this patient group where
we have such poor long term survival and even among
survivors lots of morbidity. We clearly are going to need
to rethink our long term management of this patient group
(12:57):
and perhaps look more closely as some investigators are or
at the super fontane patients. There is clearly something different
about that group of patients who do so well. Some
of the differences are likely not modifiable, but some may be,
and we need to continue to aggressively study these so
called better fontane patients to see if there are factors
that we can identify and then perhaps amplify that are
(13:20):
associated with better outcomes. At this point, I think we
should move forward to our conversation with the works first author,
doctor Gaynor, joining us now.
Speaker 2 (13:28):
To discuss this week's work is the Works senior author,
Doctor William Gaynor. Doctor Gaynor is an attempting surgeon in
the Cardiac Center at the Children's Hospital Philadelphia. He holds
the Daniel M. Tabass Endowed Chair in Pediatric Cardiothoracic Surgery
and specializes in heart surgery and infants. He currently serves
as director of the Long Term follow Up Program in
(13:48):
the Cardiac Center at CHOP and as the co Principal
investigator of the Birth Defects Bio Repository. Doctor Gaynor is
a graduate of the Medical University of South Carolina, followed
by residency at Parkland Memorial Hospital in Dallas, Texas and
Duke University Medical Center. He also completed a research fellowship
at Duke University and did cardiac surgical training in congenital
(14:11):
heart disease at the Hospital for Sick Children as well
as Great.
Speaker 1 (14:14):
Ormond Street in London, England.
Speaker 2 (14:16):
It is a pleasure and honor to have him join
us this week on the podcast Welcome Doctor Gaynor to
pet Heart. I'm here now with doctor Bill Gaynor of
the Children's hostle Philadelphia. Doctor Gaynor, thank you so much
for joining us this week on PD Heart.
Speaker 3 (14:27):
Thank you for inviting me.
Speaker 2 (14:28):
Great pleasure. Congratulations to you and your many co authors
on this very important work. I was wondering as I
was reading at doctor Gaynor, what was the main motivation
for your team to assess these outcomes in the hypoplast
cohort from CHOPP.
Speaker 4 (14:43):
Well, first of all, I do want to emphasize it
as a team. I mean, this is a forty year experience,
and it's there have been countless pete people who have
cared for these kids and are responsible for the outcomes
and help put together the data. I started a job
in nineteen ninety five in Or it was still relatively
knew even a CHOP. I mean doctor Norwood had done
(15:03):
the first and successfully in the early eighties and then
came to CHOP in nineteen eighty four, so it was still,
you know, on the cutting edge of heart surgery. And
obviously CHOP had a very large experience with these and
they are a very complex patient population. And as results
(15:24):
for other types of control heart disease were improving, there
was improvement for kids with HHS invariants, but not to
the same extent, and as we looked at this over
the years, it seemed like some of the outcomes may
have been plateauing.
Speaker 3 (15:40):
Were we getting better? That was one of the motivations.
Speaker 4 (15:44):
And the other was again because of the unique population
of chop we are positioned to look at the outcomes
for thirty to forty year olds. No one else really
has a significant number of patients. So those were the
two motivating factors I see.
Speaker 2 (15:59):
Thank you, very interesting, doctor Gayner. I mean, one of
the more sobering findings of this work is that the
past few decades have not been associated with as substantial
improvements in outcomes in comparison to the earlier eras of
this work, which it sounds from what you just said,
was one of the impressions you had. What do you
think is the main reason that things haven't noticeably improved
(16:22):
in the last ten or so years. Is it the
simple physiology or that, I should say, the complex physiology
of hypoplasticalote heart syndrome. Is it the surgical approach? Why
do you think we seem to be kind of peaking
in our outcomes in this regard?
Speaker 4 (16:37):
Well, I think there's a couple of things. So when
I think the physiology is key. It's so very difficult
physiology in reality. You know, even with newer techniques like
the hybrid, the physiology in the post operative period is
not significantly different from that of a normal would you
avoid bypass, but the physiology is very similar. And we
(16:58):
found that the hybrid is not very different in outcomes
and definitely not better in outcomes.
Speaker 3 (17:05):
Than the NERO would procedure.
Speaker 4 (17:07):
We've seen over time there have been introductions of other
strategies such as the RB top A conduit instead of
the modified Blaylock Tastic Thomas Shunt, and again the data's
coming in in the long run there's really no difference.
Speaker 3 (17:21):
So I think it's the part of it is the
underlying physiology, but I think a big part of it
is our lack of knowledge. I think one of the biggest.
Speaker 4 (17:29):
Problems in conjinal heart surgery today is unexplained.
Speaker 3 (17:34):
Variation and outcomes.
Speaker 4 (17:35):
If you look at all the risk models for mortality
for NERD developmental outcomes, the known risk factors, the factors
that we put into our statistical models, things like genetic syndromes, prematurity,
et cetera, only explain about thirty to thirty five percent
of the observed variation in outcomes.
Speaker 3 (17:54):
That means this variation is being driven.
Speaker 4 (17:57):
By factors that we don't We have an identical and
we don't understand, and if we could identify them, they
might become potential therapeutic targets. One of the key things
that we're really interested in CHOP now is the maternal
fetal environment and you know and pre birth life. We
(18:18):
know that kids will contain heart disease, the pregnancies can
be difficult, there's a higher incidence of maternal complications such
as pre acclamcy and gestational hypertension. We know de bate,
there's a high instance of fetal growth restriction and pre
term birth. All of these can affect the long term outcomes.
We're now beginning to show that there's a high incidence
of placental abnormalities and placental dysfunction, and we're looking at
(18:43):
and targeting and beginning trials of potential fetal interventions. And personally,
I think I think that intervening before birth to improve
fetal growth is going to be one of the real
areas innovation going forward. I mean, if we need to
have babies who are full term with normal organ maturation.
(19:07):
If we're going to achieve the best outcomes that we can,
there are many other things such as social in terminus
of health. We know that families who are not English speaking,
who live in under resource neighborhoods, the results are worse
for those kids. We need to have strategies to help
overcome those if we're.
Speaker 3 (19:26):
Going to get the best outcomes for everything.
Speaker 4 (19:28):
So I think, you know, a lot of what we
do is driven now currently trying to explain this unexplained variation.
If we can begin to understand what is driving that,
then we can understand the mechanisms and we could potentially
develop new therapeutic targets.
Speaker 2 (19:44):
Very interesting, Thank you very much. You know, one of
the things that I found interesting was that quality and
life by this patient group was perceived by the survivors
to be very good on average. And I wondered if
you thought that this was true for the entire group
of hypoplastic single metrical survivors, or do you think perhaps
this was biased as a sample by the relatively small
(20:08):
number of people who actually answered the QOL surveys.
Speaker 3 (20:12):
Well, I think it's I think it's two things.
Speaker 4 (20:15):
One, I think, you know, we should be happy that
we do identify a sizeable group of adult survivors who
have not had Fontaine related complications, who are have jobs,
good education, are married, having family lives, and are happy
with their quality of life. For many years, it was
all gloom and doom, and you know, you get to
be twenty years old, it's over.
Speaker 3 (20:36):
Well, that's clearly not true. But only about half of the.
Speaker 4 (20:42):
Of the survivors that we contact or attempted to contact, responded,
so there probably is some selection bias here. So I think,
to me, the good news is there is a group
who are doing well at twenty five, thirty, thirty five
years old. How they will how that will persist as
they move into the later, you know, the next decade
(21:03):
of life. Don't know that's going to be one of
the next studies, but I think we do need to
understand why is there.
Speaker 5 (21:08):
A group of children are now adults who undergo these
three operations, have a font in physiology, and yet twenty
to thirty years later report very few complications.
Speaker 4 (21:20):
And good quality of life. How are they different? Is
probably not the surgery. It's probably something intrinsic in either
their environment or their genetics or something else. We need
to understand what those factors are, what are driving these
high performing fontanes and try to increase that proportion. But
I agree not it clearly not everyone is thriving. If
(21:42):
you look the survival transplant pre survival is only about
thirty percent. So that's again there's a selection as in
a survivor bias here. But the good news is there
is a group and it's not just one or two
patients who are doing very well and hopefully they can
will continue to do well.
Speaker 2 (22:00):
I wanted to sort of harp on that group of
what we sometimes refer to as super font had patients
who clearly do globally much better. Do you have any
guesses on what makes them so good? And do you
think that there are lessons from this patient cohort that
we could apply to the care of all of our
fonts and patients.
Speaker 4 (22:20):
Well, I don't know about specific lessons and I don't
know about the specific mechanisms, but that's something we're going
to be looking at. We're going to continue to follow
this cohort and try to understand We're going to begin
to work with others to try to develop cohorts. We're
now enrolling, you know, newborns with hyperplastical syndrome is part
(22:40):
of our birth Defects by our repository at shop where
we enroll in.
Speaker 3 (22:46):
Fetal life kids with a variety of birth.
Speaker 4 (22:49):
Defects, including cogeneral heart disease.
Speaker 3 (22:52):
We're doing whole genome sequencing.
Speaker 4 (22:54):
We're tracking things like social terms of health and environmental exposures,
and hopefully by building this new or where we have
much more detailed genetic information, the trajectory of their life,
the neighborhoods they live in, that we can begin to
understand what are some of the fact.
Speaker 3 (23:10):
Here's driving better versus worse survival.
Speaker 4 (23:13):
But that's the next step.
Speaker 2 (23:17):
Yeah, yeah, Well, for those in the audience, doctor Gainer
was nice enough to join us today late in the day,
and so I don't want to take up a whole
lot more of your time. You sort of hinted at this,
and I was wondering. You have a very very large
experience and caring for patients with hypoplastic left heart syndrome
for many decades now, as well as being a researcher
(23:37):
in this area. You talked about how you felt that
fetal intervention and an understanding fetal life of these patients
could be an area for improvements any other areas where
you think there is an opportunity for us to potentially
improve the outcomes and get a better decade coming forward.
Speaker 4 (23:59):
Oh, I think you know, we need to understand who
is likely to do better. I doubt every child will
do the exact same with a Norwood procedure, with a
BT shunt, a neual feizure, with an r V.
Speaker 3 (24:11):
Twop, a conduit initial hybrid procedure.
Speaker 4 (24:15):
I think we need to understand who's going to do
best with a specific operation and try to individualize treatment
that way.
Speaker 3 (24:22):
And one size does not fit all.
Speaker 4 (24:24):
I think we probably need you know, one of the
options has always been transplantation.
Speaker 3 (24:29):
Perhaps we should.
Speaker 4 (24:30):
Move to that earlier for some some patients, but that
leads brings a whole another set of medical issues and
risk for long term survival and the and I think
you know we need to and with with the lack
of donor organs, transplantation is just not going to be
feasible for everyone. Uh, there may be as the devices improved,
(24:53):
there may be some some role for fontan assist devices
and implannabile of add particul subculminary bad if that was
implannable that might improve the opple So I think there's
a lot of things that could be done. Understanding the
genetic differences in the biologic pathways driving these differences in outcome,
working to truly personalized medicine and individual therapies and individual
(25:16):
surgical strategies. Considering as the technology improves, assist devices as destination,
not just as a bridge transplant.
Speaker 3 (25:24):
The devices have to get better, but I think that's
within the palm of possibility.
Speaker 2 (25:31):
Yeah, yeah, all interesting exciting areas and arenas to go
forward for those younger people. We haven't figured it all
out yet. A lot of things to investigate going forward
over the next few decades. Well, doctor Gainer, I can't
thank you enough for coming on and speaking to us again.
You've been a guest once in the past, and very
much appreciate your spending time with us, and again want
(25:53):
to thank you and congratulate you and your many many
co investigators and what was really very important that I
very much enjoyed.
Speaker 4 (26:01):
Well, thank you very much, and again I appreciate the
opportunity to discuss that work.
Speaker 3 (26:05):
Thank you, thank you.
Speaker 2 (26:06):
Well.
Speaker 1 (26:06):
I'm sure you found doctor Gainer's comments to be of
great interest. I won't review all of his many outstanding points,
but I think his general notion of trying to unlock
the factors that might explain the unexplained variability in outcomes
for this patient group to be an important general mental
model when thinking about how we can address them. There
clearly are factors that we do not understand, and to
(26:28):
some degree it is remarkable that using a sort of
one size fits all approach we've achieved the results we have.
But I think that as comments have clearly demonstrated that
there are levels of complexity of these different hypoplastic left
heart syndrome patients that are substantial and still unknown, I
certainly do believe that they will be a day where
we will take a much more personalized approach to the
(26:49):
management of these patients, and I'm hopeful that this sort
of approach will be informed by the sort of research
that doctor Gainer and his colleagues are conducting, as well
as more study of our so called super fontine patients,
looking for those positive factors that we can leverage for
improvement in outcomes in all of our patients. I'd again
like to thank doctor Gainer for taking time from a
(27:10):
very busy schedule to speak with us this week on
pd Heart to conclude this three hundred and forty ninth
episode of pet Heart Pediatric Cardiology. Today we celebrate the
life of the great Welsh tenor Stuart Burroughs, who died
last week at the age of ninety two. Burroughs was
born in South Wales, and he was a boy soprano
before becoming an adult tenor. And he was also a
(27:31):
great rugby player and turned down a professional career in
that field to become a tenor. Burrows sank throughout the world,
starting his career in the UK, appearing at the Royal
Opera House in London for twenty two seasons, and singing
also all over the globe, including twelve years at the
Metropolitan Opera. Though great in many areas of tenor singing,
(27:51):
he was perhaps most known for his work in Mozart,
and sometimes even given the nickname of King of Mozart.
Today we hear why when we hear Burrows in a
live performance of the fiendishly difficult Eelmia tosorro from Mozart's
Don Giovanni. Thank you very much for joining us for
this episode, and thanks so.
Speaker 6 (28:09):
Much to our guest I hope I'll have a good
week ahead.
Speaker 7 (28:24):
Welcome should mother alone.
Speaker 8 (28:41):
A girl.
Speaker 2 (29:00):
R car.
Speaker 6 (29:04):
Pa the case recority.
Speaker 8 (29:08):
In decory in declary.
Speaker 9 (29:16):
Amory goody, sorry you torm.
Speaker 8 (29:29):
So is time on?
Speaker 9 (30:04):
He didn't go to.
Speaker 7 (30:08):
Jacos jo dis deep pase.
Speaker 8 (30:44):
Any post you.
Speaker 2 (31:16):
What's you?
Speaker 7 (31:22):
It's small, distant, Sure you are, said
Speaker 4 (31:32):
Soup for your
Popular Podcasts
Stuff You Should Know
If you've ever wanted to know about champagne, satanism, the Stonewall Uprising, chaos theory, LSD, El Nino, true crime and Rosa Parks, then look no further. Josh and Chuck have you covered.
Dateline NBC
Current and classic episodes, featuring compelling true-crime mysteries, powerful documentaries and in-depth investigations. Follow now to get the latest episodes of Dateline NBC completely free, or subscribe to Dateline Premium for ad-free listening and exclusive bonus content: DatelinePremium.com
CrimeLess: Hillbilly Heist
It’s 1996 in rural North Carolina, and an oddball crew makes history when they pull off America’s third largest cash heist. But it’s all downhill from there. Join host Johnny Knoxville as he unspools a wild and woolly tale about a group of regular ‘ol folks who risked it all for a chance at a better life. CrimeLess: Hillbilly Heist answers the question: what would you do with 17.3 million dollars? The answer includes diamond rings, mansions, velvet Elvis paintings, plus a run for the border, murder-for-hire-plots, and FBI busts.