Circulation February 9, 2021 Issue

This week features Two Feature Discussions. In our first
discussion, author Thomas Metkus and Guest Editor Allan Jaffe
discuss the article "Myocardial Injury in Severe COVID-19
Compared to Non-COVID Acute Respiratory Distress Syndrome." Then
in our second discussion, author Naveed Sattar and Guest Editor
Ileana Piña discuss the article "Effect of Empagliflozin on Left
Ventricular Volumes in Patients with Type 2 Diabetes, or
Prediabetes, and Heart Failure with Reduced Ejection Fraction
(SUGAR-DM-HF)."


TRANSCRIPT BELOW


Dr. Carolyn Lam:


Welcome to Circulation on the Run, your weekly podcast, summary
and backstage pass to the journal and its editors. We're your
co-hosts, I'm Dr. Carolyn Lam, Associate Editor from the National
Heart Center and Duke National University of Singapore.


Dr. Greg Hundley:


I'm Dr. Greg Hundley, Associate Editor, Director of the Pauly
Heart Center at VCU Health in Richmond, Virginia.


Dr. Carolyn Lam:


Guess what? Double feature again, this episode with the first
talking about empagliflozin and its effect on left ventricular
volumes in patients with type two diabetes, pre-diabetes, and
HFrEF, and this is the sugar DM heart failure study.


Dr. Greg Hundley:


Carolyn, the second of our double feature Tuesday is a paper that
involves myocardial injury in severe COVID-19 compared to
non-COVID acute ARDS. Well, let's grab a cup of coffee and
Carolyn this week, I'm going to jump into my first paper, which
comes to us from Dr. Are Kalstad from the University of Oslo at
the Oslo University Hospital. Carolyn, this study tested the
hypothesis that the daily addition of 1.8 grams of N-3 PUFA to
standard of care, secondary prophylaxis in elderly patients who
have survived a acute MI would reduce the risk of subsequent
cardiovascular events during two years of follow-up.


Dr. Carolyn Lam:


Interesting, Greg and a clinically important question. So what
did they find?


Dr. Greg Hundley:


Yes, Carolyn. They enrolled 1,027 subjects who were randomized in
this investigator initiated, multi-center randomized clinical
trial of adding that 1.8 grams of n-3 PUFA, 930 milligrams of
EPA, and 660 milligrams of DHA versus placebo, which was a corn
oil supplement, daily to the standard of care in 70 to 82 year
old patients with recent, so within two to eight weeks, acute
myocardial infarction. The authors found that they could not
detect reduction in clinical events in these elderly patients
with the recent acute EMI treated with the 1.8 grams of n-3 PUFAs
daily for two years. So, a negative study, Carolyn.


Dr. Carolyn Lam:


Surely, we'll add to that debate that's just so interesting
surrounding the PUFAs. But let's go onto another paper I want to
tell you about, it provides novel insights into the complex
crosstalk between the cardiac endothelial cells and
cardiomyocytes during cardiac repair after myocardial infarction.
This paper is from Dr. Taleb and colleagues from Park Inserm in
France. Their study suggested a deleterious role for endothelial
indoleamine 2,30-dioxygenase-1, which I'm now going to abbreviate
as IDO, which is an enzyme involved in tryptophan catabolism.
They found that the specific deletion of IDO in endothelial cells
enhanced cardiomyocytes survival and contractility leading to
cardiac function improvement. The IDO dependent effects were
mediated by endothelial cell production of kynurenine. The study
in essence found that therapeutic strategies targeting cardiac
IDO could, in fact, constitute an innovative approach to curb
cardiac dysfunction following MI. This was followed by an
editorial by Drs. Ma and Wang from Thomas Jefferson University.


Dr. Greg Hundley:


Very nice, Carolyn. Great studies again from the world of basic
science. Well, my next paper comes to us from Professor Gerasimos
Filippatos from the University of Athens Hospital. Carolyn, this
was a sub-study of the FIDELO-DKD trial that evaluated the effect
of the nonsteroidal selective mineralocorticoid receptor
antagonists finerenone on kidney and cardiovascular outcomes in
patients with chronic kidney disease and type two diabetes with
optimized renin angiotensin system blockade. Compared with
placebo, finerenone reduced the composite kidney and
cardiovascular outcomes. Here the authors report the effect of
the finerenone on individual cardiovascular outcomes and in
patients with and without a history of atherosclerotic
cardiovascular disease.


Dr. Carolyn Lam:


This is a much anticipated paper. Very excited for you to
describe the findings, Greg.


Dr. Greg Hundley:


Thanks, Carolyn. Among patients with chronic kidney disease and
type two diabetes, finerenone reduced the incidents of the
composite cardiovascular outcome, that included time to
cardiovascular death, myocardial infarction stroke, or
hospitalization for heart failure. Additionally, there was no
evidence of differences in treatment effect based on pre-existing
cardiovascular disease status.


Dr. Carolyn Lam:


Emerging therapies. Isn't that awesome? Well, some other papers
in this issue, there's a White Paper (Frontiers) about the
therapy in patients with atrial fibrillation treated with oral
anticoagulation undergoing PCI, a North American perspective,
2021 update by Dr. Angiolillo. There's a Research Letter on the
gradient of risk and associations with cardiovascular efficacy of
ertugliflozin by measures of kidney function, and these are
observations from VERTIS-CV trial by Dr. Cherney. There's also a
sub-study analysis from Explorer HCM, and that is entitled
“Mavacamten Favorably Impacts Cardiac Structure in Obstructive
Hypertrophic Cardiomyopathy.” This is by Dr. Saberi. There's
another Research Letter on COVID-19 myocardial pathology
evaluation in athletes with by CMR and that's by Dr. Clark.


Dr. Greg Hundley:


Very nice, Carolyn. I have an exchange of letters from Dr.
Alkhalil and Kuzemczak, as well as Dr. Navarese regarding the
article, “Comparative Efficacy and Safety of Oral P2Y12
Inhibitors in Acute Coronary Syndrome: A Network Meta-Analysis of
52,816 Patients From 12 Randomized Trials.” Next, there's another
exchange of letters from Dr. Kastrati and Ferracane regarding the
article, “Comparative Efficacy and Safety of the Same Oral P2Y12
Inhibitors in Acute Coronary Syndromes.” Dr. Karabinos has a nice
ECG challenge. It's a bizarre down sloping ST segment elevation
challenge. Finally, Carolyn, there's a Perspective piece from Dr.
Okorodudu entitled, “Exposure to Cardiology as a Strategy to
Increase Black Men Involvement in Medicine.” Well, Carolyn, how
about we get on to those two feature discussions?


Dr. Carolyn Lam:


Oh, yes. Exciting. Let's go.


Dr. Greg Hundley:


Well, listeners, we are here for our first feature discussion
today on this February 9th. We have with us Dr. Tom Metkus from
Johns Hopkins and Dr. Allan Jaffe from Rochester. Tom, can you
tell us what was the background that really framed this study and
what hypothesis did you want to address?


Dr. Thomas Metkus:


This study really arose out of a time and a place in the COVID
pandemic. If you can all turn your clocks back to late last
spring, we were all enmeshed in the clinical care of many
patients with COVID here in the United States, depending on your
geography, and also reading an increasing number of reports from
other centers that had been enmeshed in the pandemic for some
time about myocardial injury, elevated troponin, different
aspects of cardiac disease in patients with COVID-19. My
background is as a cardiac intensivist, dual boarded in
cardiology and critical care, and so this was of particular
interest to me, specifically so in that my clinical practice at
the time was in a COVID ICU. I spent much of the day every day
taking care of these patients, so conceptualizing what myocardial
injury meant, what's the pathogenesis, and what does it mean, was
an open-ended question at the time. There are certainly many
reasons to think that COVID-19 is particularly cardiotoxic.
There's obviously the pro-thrombogenic nature of the illness.
There's the inflammatory nature of the illness.


Dr. Thomas Metkus:


Yet, we also found that clinically, there was certainly many
patients with COVID-19 who acted like they had myocardial injury
from ARDS and pneumonia and we had investigated this in some
prior studies prior to the pandemic. Really, the aim of the study
was to clarify to the extent that we could and contribute to the
growing body of knowledge about what is the prevalence and
prognostic significance of myocardial injury in COVID-19. We felt
that we had a unique lens on this because we also had a cohort of
patients with generic ARDS who had cardiac biomarkers assessed,
gave us a nice opportunity to do that.


Dr. Thomas Metkus:


Our hypothesis, that was really based on our clinical gestalt at
the time from being in the ICU every day with COVID-19 patients,
was that there are assuredly COVID-19 patients who have unique
features of myocardial injury, myocarditis or malignant
arrhythmias, or requiring mechanical support. But perhaps more,
or at least a majority have myocardial injury that looks and acts
an awful lot like it would in a sepsis patient, in an ARDS
patient. We hypothesized that myocardial injury in COVID-19 would
be more similar than different to the generic ARDS population. As
such, we drew a population of patients with COVID-19 from our
health system here across several hospitals, and did a bit of a
comparison with our historical cohort of ARDS patients.


Dr. Greg Hundley:


Great description, Tom. Tell us a little more about that study
population. You said there was going to be a comparison. What
were some of the outcomes that you wanted to evaluate?


Dr. Thomas Metkus:


Right. This question alludes to an important point as we try to
delve and do inference around the COVID literature in general,
which is to say the pandemic is heterogeneous across geography
and across time. In looking at this study, or indeed any study,
and understanding of the study population where these ambulatory
patients or intubated patients or patients on the ward, for
example, as well as any comparison group are these sepsis
patients, pneumonia patients, influenza patients, it's just
imperative to do inference and to place the study in context.
This study, we sought to look at only intubated patients, and
that was partially driven by clinical interest, partially driven
by the ability then to provide a comparison to our ARDS cohort.
So, intubated patients with COVID-19.


Dr. Thomas Metkus:


The comparison group is from a study of acute respiratory
distress syndrome patients. Primary lung injury patients that
were drawn in turn from NHLBI sponsored areas, network clinical
trials. That was a study that was a secondary analysis that we
did where we checked troponin levels in everybody. A true cross
sectional assessment. That's important in that there's a
selection bias, isn't there, when you just look at patients who
had troponin drawn in the context of clinical care? So, I think
for this study in particular, it's important to note that the
comparison group of ARDS patients was truly cross-sectional and
that it was a population defined who had biomarkers assessed in
the entirety; whereas our COVID-19 population was intubated
patients who had troponin checked at the point of clinical care.


Dr. Thomas Metkus:


Now, to address some of the potential biases that are inherent in
that assessment of exposure, we purposefully looked at only
patients who had troponin assessed within 24 hours of intubation,
really to sync up time zero in a sense. It's also important to
note the time course of the pandemic. These patients were all in
the late spring and very early summer. This was really before
steroids, before the recovery trial, before steroids became
standard of care. And really, health systems wonder a fair bit of
duress at that time and indeed, as many of the listeners will
know, the outcomes for hospitalized patients have improved since
then for many reasons. But it's only to point out that this study
was a place in geography and a place in time, and there are
certainly implications about that that I'm sure we'll focus on
subsequently.


Dr. Greg Hundley:


How many subjects did you enroll and what were your study
results?


Dr. Thomas Metkus:


Our COVID-19 patient population here in the Johns Hopkins
Hospital included 243 patients. All of them were intubated with
COVID-19, so severe disease. Of those, we reported that just over
half had clinical troponin levels greater than the upper limit of
normal. We assessed the main clinical factors associated with
elevated troponin in that patient population, which are largely
similar to other reports and they include chronic kidney disease,
lactate levels of the marker of malperfusion, ferritin fibrinogen
levels as markers of systemic inflammation. We showed as have
others that there's a graded increase in mortality with
increasing amounts of myocardial injury. Then, probably what I
would found the most interesting component of the study is that
when we did covariate adjustment for features of critical
illness, renal failure, lactate, how severe your hypoxemia was,
vasopressor use, age, and sex. Age, sex, and multi-organ
dysfunction in a sense.


Dr. Thomas Metkus:


The association of troponin with mortality attenuated quite
significantly. That's similar to what we found in a general ARDS
population and consistent with a paradigm of myocardial injury in
the non-cardiac critically ill. I think the final finding that we
would emphasize is that after you adjust for those mediating
factors, the incidence of myocardial injury in COVID-19 was at
least comparable to that in the general area's population. It
gives an idea to place myocardial injury in context, in my view,
as a function of critical illness in most COVID-19 patients.
Surely, not all. There are patients with unique syndromes, but in
many or most.


Dr. Greg Hundley:


Well, Alan, let's turn to you. Help us put these results that Tom
has described for us really in the context of what we're learning
about the heart and in patients with COVID-19.


Dr. Allan Jaffe:


Well, let me start by saying that as a cardiologist, too, at the
Mayo Clinic in Rochester, Minnesota, we've studied previously
patients with acute respiratory failure. In point of fact,
although most of you are not quite as old and may not remember,
when we first started seeing ARDS patients, many of the same
issues that are here today for COVID, came up. For example, and
people may not remember this, we actually did a randomized trial
of anti-platelet therapy in patients with ARDS because we were
convinced that thrombosis was ubiquitous and was a frequent
contributor to the illness that we saw. So that if one thinks
about it in another sense and says, "If you'll correct for modern
day technology that gives us some additional insights, how
different really is COVID ARDS from standard ARDS." I think what
this paper has substantiated is that there are lots and lots of
similarities that exist. I think that's important because it
keeps us from chasing around and looking for some additional
issues for us to try and take care of or treat additionally.


Dr. Allan Jaffe:


That said, I think the way to conceptualize it is some of the
troponin elevations are because patients who have chronic heart
disease get COVID and they may have those elevations right at
admission. There's an acute component having to do with critical
illness that is nicely described in this manuscript. Then, there
are those unique clinical features, whether you think it's
myocarditis, I'm not sure how common myocarditis, type 2 MI,
ischemia, a variety of things, and maybe a new type of
myocarditis that we're finding with some very peculiar cells that
we see in interstitium with or without increases in troponin. But
I think it puts it into the bucket of saying, treat these
patients conventionally and look for the other complications. I
think that's a terribly important message that I was attracted to
when I read this paper. So, thank you, Tom.


Dr. Greg Hundley:


Very good. Well, Tom, what do you see as the next study really to
be performed in this space? I'll ask you first and then come back
and gather some of Allan's thoughts.


Dr. Thomas Metkus:


Absolutely. I love that framing about kind of COVID in the heart,
which is to say that there are some things that are direct
pathogenic related to COVID and there are some things that are
secondary, and then there are some things related to patients
with underlying heart disease coming to care. I think the next
set of studies that can help us disentangle this are related to
that paradigm in that more multimodal phenotyping, biomarker
phenotyping, but also echo phenotyping and MRI phenotyping, we're
starting to see those come down the pike to say, here's the
biomarker evidence of myocardial injury, but what does that mean,
functionally? What does that mean from an imaging perspective?
The second important facet for the next series of studies will be
the long-term follow-up. We know from the general critical care
literature, that there is indeed a powerful and important entity
of the post critical illness syndrome, and in COVID that's come
to be called long COVID or the long hauling. We've known that
even patients with general critical illness get that and to the
extent that the heart plays a role in that, it implies one needs
to follow these patients prospectively.


Dr. Thomas Metkus:


I think the other implication of this work for the next set of
studies is that there are many biases that can be brought to bear
when reviewing the pandemic literature and assuredly an editorial
team sees the entire spectrum of them, but they would include, as
I alluded to, careful selection of patients assuring meaningful
classifications of exposure at a uniform time assuring adequate
comparison groups. That's really going to be the key to doing
good inference. Then, the final thing I'll add is that the next
set of studies should and will integrate clinical research and
clinical epidemiology with causal inference principles with using
what we're learning from the basic science community, to have
conceptual models about how has COVID affecting the heart at the
cellular level, et cetera, et cetera, et cetera. In a sense, that
community of researchers that you see coming together in this
pandemic is why doing this work is very rewarding and I think
meaningful. I think those are all features of the next set of
studies that should include indeed epidemiologic analysis,
randomized trials, and basic science analysis.


Dr. Greg Hundley:


Allan, do you have anything to add?


Dr. Allan Jaffe:


Well, I want to endorse the idea that one of the problems in this
field is that patients present at different times with different
clinical syndromes, because some of them have been at home, some
of them have been hospitalized, some of them are recognized de
novo late. One of the things that's necessary as a consistent
repetitive approach so that we get consistent data, not only on
each COVID patient sequentially, but also on the control group
that is important. The other point I'll emphasize that Tom
mentioned is that individuals who have elevated troponins who are
critically ill with ARDS and most likely with COVID as well, have
some sort of underlying cardiovascular disease. Often once those
patients leave the hospital there, the troponin is out of sight
and out of mind. COVID is reminding us by showing us the panoply
of additional clinical syndromes that exist post-hospitalization.
That as with ARDS, I would argue, that's a mistake. These
patients need to have follow-up with cardiology to investigate
what that underlying cardiovascular component is.


Dr. Greg Hundley:


Great. Well listeners, we want to thank Dr. Tom Metkus from Johns
Hopkins om Johns Hopkins and Dr. Allan Jaffe from the Mayo Clinic
in Rochester, Minnesota for bringing us this study regarding
intubated patients with COVID-19, indicating that the myocardial
injury shares many similarities to that experienced by patients
with ARDS. Now listeners, we will turn to our second feature
discussion on this February 9th.


Dr. Greg Hundley:


Well, listeners, welcome to our second feature discussion today.
We have with us, Dr. Naveed Sattar from Glasgow, Scotland, and
our guest editor, Dr. Ileana Pina from Detroit Medical Center.
Welcome to you both. Naveed, we'll start with you. Could you
describe some of the background that helped you formulate this
study and what hypothesis did you want to address?


Dr. Naveed Sattar:


Yeah, thanks Greg. When I was watching the empirical outcomes
study, I almost fell off my seat when I saw the results in heart
failure, hospitalization. I actually, I sent a text to John
McMurray who wasn't actually at the meeting and I sit next door
to John McMurray who's obviously preeminent heart failure. I
worked also with many of the fantastic heart failure colleagues,
Mark Pietri, Cardic Joon and colleagues. At that time I felt,
well, actually it wouldn't it be lovely, I was aware of MRI
studies they've done on other drugs in heart failure and I
thought, well, if this drug effects improves heart failure, well
potentially, although we didn't have it amply reduced at the time
or have heart failure, they've come subsequently. Perhaps it
changes, lead to cardiac remodeling.


Dr. Naveed Sattar:


So we've designed the randomized placebo control trial of
empirical fluorescent versus placebo and 105 patients who had
heart failure with ejection fraction below 40%. We wanted big 4th
ventricles as Professor McBuddy would tell me, we have lots of
debates about these things to really give us adequate power
follow-up for at least 36 weeks to see if we can see improvements
in left ventricular installment volume or global longitudinal
strain, which were our primary outcomes.


Dr. Greg Hundley:


Very nice. Great overview of the study design. Who did you
enroll? I know patients with an ejection fraction less than 40%,
but equal numbers of men and women, was this ischemic heart
disease?


Dr. Naveed Sattar:


I think the majority of patients were male about two-thirds
average age, 68, pretty much like the empirical reduced to that
by half population. About 80% here had type two diabetes, about
20% had pre-diabetes. The other characteristics, the majority had
class 2, NYHA Class IV heart failure, minority Class III. About a
third were already on arnes. Also, the background theoretically
was fantastically well.


Dr. Naveed Sattar:


The other critical thing we really did, we excluded people with
atrial fibrillation because that really affects the quality of
the MRI. Our group and it's a brilliant journey to be, I'm not a
heart failure expert, but working with all these colleagues, they
have brilliant experience in this. They know the mistakes to
avoid, and one of them is, do not include people with atrial
fibrillation because your MRIs will just not be readily
interpretable. Also, it needs to be big enough. It needs to have
big enough volumes to begin with to be able to see a change. It
needs to be long enough to potentially see the remodeling. All
that experience of John, Mark and Pandeep were put together in a
really tight protocol. When the results came, I almost, again,
fell off my seat because well, it worked. I guess, you're going
to ask me about the results and what we find.


Dr. Greg Hundley:


Absolutely. Tell us about those results. We're waiting to hear.


Dr. Naveed Sattar:


Two primary outcomes were really what we saw was a reduction in
the left ventricular and systolic volume index and by six mils
per meter squared, and the diastolic volume index by 8.2 mils per
meter squared. We didn't see a change in global longitudinal
strain. We did not see changes in KCCQ or six minute walk test,
but actually the reality is we now know the size of this chart is
underpowered to see changes in six minute walk tests or KCCQ, in
lieu of another trial that has some changes in that, but we
didn't see them and I think our study was done ... I can tell
you, Greg, the amount of work that went in this study, the
quality control that people should look at the supplement when it
comes out, the degree of attention to imaging protocols and
quality control was, I think in my experience, unparalleled.


Dr. Naveed Sattar:


The team really pulled out all the stops to get this, but so the
reductions in the volumes, that's probably the key thing. We
think that this may reflect the reverse cardiac remodeling and
that we think then fits in what you see with other drugs that
benefit patients with heart failure. Because the bigger the
volumes, the more people tend to die with heart failure or get
readmitted. If you shrink the ventricles, that probably their
contractility improves. What the actual mechanism is, I don't
know, but I'm sure Ileana probably come in there in terms of
discussing potential pathways. The final thing I should say is
just for the internal validity or external validity, NT-proBNP
did come down, suggesting less left ventricle wall stress.
Schematic also went up. All the things that we've seen in the big
trials was there so I think we've done a really strong, robust
trial.


Dr. Greg Hundley:


Thank you, Naveed. Well, Ileana, as a guest editor, what
attracted you to this paper? Then, how do you put the results
from this study in the context with some of the other
publications related to SGLT 2 inhibition in patients with heart
failure?


Dr. Ileana Piña:


I think all of you know, that we, the heart failure community is
pretty excited about these drugs and what they're doing. I also
nearly fell off my chair when I saw the first EMPA-REG and I saw
those curves splitting. Then, I further did that when the DAPA
data came out and you see these curves split up almost
immediately. What was attractive about this paper is that we
really don't know how this happens. We think we do, but we really
don't. We don't think necessarily that it's the glucose
excretion, because that maybe happens in diabetics, but not
necessarily in the non-diabetics. Yet the drugs seem to work in
both. But remodeling is such a fascinating concept. I personally
happen to love the concept of reverse remodeling. It's something
that we in the heart failure community really believes that if we
can reversely remodel the ventricle, then outcomes will get
better.


 


Dr. Ileana Piña:


We really link them. Your proBNPs were elevated but not huge.
This wasn't a very sick debilitated population. This was
primarily Class II. Pretty well-medicated in background, you
didn't necessarily give the doses clearly, but pretty well with
percentages of RAS inhibition and everything else. Now you see
that the volumes are coming down and you say, "Wow, is that
what's it doing?" If it happens that quickly, because remember,
we've got to explain why the curves of heart failure,
hospitalizations split up almost immediately. You did show in
your time of follow-up that these changes occurred during that
follow-up. I am actually not at all surprised that you didn't see
anything in the KCCQ because we know that first of all, the
patients weren't that sick to start with so it's hard to see
improvement when you don't have a lot of sickness and a six-
minute walk. This group, for a six-minute walk, is going to have
a very wide standard deviation. A six-minute walk doesn't really
distinguish the people who are doing well. To me, it's more for
the sicker.


Dr. Ileana Piña:


The fact that neither of these things change doesn't bother me at
all. But I think that the next step before Greg asked me, is
what's the outcome. In other words, can you tie that reverse
remodeling directly to an outcome, be it mortality, which is
getting argued out there, whether all the drugs are the same? Or
just even the heart failure hospitalization, which I think is a
very important outcome in this population. You did it well, you
did it carefully, you can tell the data's very clean. You did do
a little bit better with the women, so I can't scold you for that
as I usually do, because you've had about 30 some percent women,
which is very similar to what the big EMPEROR trial has had. I'm
always fighting to get more women in the trial.


Dr. Ileana Piña:


At some point you may want to examine the reverse remodeling by
gender, by sex, actually and see, even though you have a small
number, you have 105 patients, you may not have enough data. But
I think in the future, because we do believe that women remodel
differently and reversely remodeled differently. That would be
very interesting to see if there's any differences.


Dr. Greg Hundley:


Thank you, Ileana. Naveed, do you have anything to add? Ileana's
really laid out on a nice course to follow forward. Do you have
anything to add to her comments?


Dr. Naveed Sattar:


No, I completely agree with all of them. I think the key thing is
nice that this came out straight after EMEPEROR-reduced and a
year after that, for heart failure with the team that, John and
colleagues were led out. I was involved in the EMPEROR-reduced so
that the mechanism helps. I think clinicians buy into this
concept. It does what they think drugs do to improve heart
failure outcomes. I think that helps and it might help
prescribing, get people the confidence that these drugs do work
in a mechanism that works.


Dr. Naveed Sattar:


The only thing that I think we would love to have done is if
doing the MRIs even sooner, how quickly do these actual volumes
change? We think it's reverse remodeling, but maybe we need
another trial doing MRIs at one month, three months just to see
how quickly these volumes do actually change. Because I still
think that's a bit of doubt. But having said all that, I've loved
this journey working with my fantastic Hatfield colleagues, a
brilliant team in Glasgow. We're now thinking about the next
trial. Let's see where we get to in terms of algorithms and
trials, but the diabetes, heart failure, kidney disease
fraternity coming together is fantastic. I'd loved being part of
that journey. So great.


Dr. Ileana Piña:


There's another interesting observation in your data was a
hematocrit. It's really tiny, but the signal is there, which to
me has also been fascinating. We see a lot of anemia in this
population. A benefit in the hematocrit, I think, is really
important. The fact that you did this with MRI, I don't think
this is a good echo study, to do this with echo. I think you need
the reliability and the precision of an MRI.


 


Dr. Naveed Sattar:


Yeah, I agree. We have other data coming up, Ileana, in terms of
renal blood flow, because you've mentioned that as well at the
same time, which we haven't yet analyzed. There's a lot more data
which needs a good Biobank and pick some of these mechanisms. So,
yeah, fantastic.


Dr. Greg Hundley:


Well listeners, this has been an excellent discussion and we want
to thank Dr. Naveed Sattar from Glasgow and our guest editor, Dr.
Ileana Pina from Detroit Medical Center, bringing us these
results regarding the administration of empagliflozin and
favorable changes in left ventricular volumes in patients with
heart failure and a reduced ejection fraction.


Dr. Greg Hundley:


Well, on behalf of Carolyn and myself, we want to wish you a
great week and we will catch you next week on the run. This
program is copyright of the American Heart Association, 2021.