Circulation March 17, 2020 Issue

Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly
podcast summary and backstage pass to the journal and its
editors. 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 from the Pauley Heart Center
at VCU Health in Richmond, Virginia.


Dr Carolyn Lam: Greg, this issue features a very important, but
rather somber subject and it talks about suicide attempts among
LVAD recipients and the real-life data from the Assist-ICD study.
Now we have to get to that and it's a very interesting
discussion, but first, let's discuss a couple of papers and I'll
start.


Now, we know that extracorporeal cardiopulmonary resuscitation
using extracorporeal membrane oxygenation or ECMO, for
hemodynamic support has been shown to enhance survival for
patients with refractory VF or VT out of hospital cardiac arrest.
However, what are the effects of prolonged CPR on development of
metabolic derangements and neurologically favorable survival in
these patients?


Well, this was examined by Dr Bartos from University of Minnesota
School of Medicine and colleagues who retrospectively evaluated
survival in 160 consecutive adults with refractory VF/VT out of
hospital cardiac arrest, treated with extracorporeal
cardiopulmonary resuscitation, and compared these with 654 adults
who had received standard CPR in the amiodarone arm of the ALPS
trial.


They found that extracorporeal CPR was associated with improved
neurologically favorable survival compared to standard CPR at all
CPR durations less than 60 minutes. However, CPR duration
remained a critical determinant of survival with a 25% increase
in mortality with every 10 minutes of CPR beyond 30 minutes. The
progressive metabolic derangement which developed during
prolonged CPR was associated with reduced neurologically
favorable survival.


Dr Greg Hundley: This mirrors an article that we had maybe about
a month ago. What are the clinical implications of this
particular study?


Dr Carolyn Lam: Well, healthcare systems utilizing extracorporeal
CPR for out of hospital cardiac arrest should optimize
pre-hospital and in-hospital processes to minimize time to CPR.
Further research is needed to identify strategies to increase CPR
efficiency, improve profusion, and decrease the metabolic demands
such that the progressive metabolic derangement associated with
prolonged CPR can be delayed. This is discussed in an editorial
by Dr Sonneville and Schmidt.


 


Dr Greg Hundley: Very nice, Carolyn. Well, my next article is
from Roxana Mehran from the Icahn School of Medicine at Mount
Sinai. It's really getting at the issue of high-risk implantation
of inter-coronary stents and balancing where is that risk. Is it
from bleeding or a complication from the procedure? In this
study, they had a total of 10,502 patients and they were included
from four registries. 3,507 were identified as having high
bleeding risk. The authors aimed to evaluate the long-term
adverse events in the high bleeding risk patients undergoing PCI
with cobalt chromium, everolimus-eluting stent implantation.


Dr Carolyn Lam: Ah, Greg. Awesome. I'm a fan of Dr Mehran and
looks like I'm going to be a fan of this study. What did they
find?


Dr Greg Hundley: Well, Carolyn, I love just thinking about coated
stents. How about that? Interestingly, those at high bleeding
risk had more comorbidities. They had higher lesion complexity
and a higher risk of four-year mortality. In fact, four times
that of those without those risk factors. The risk of mortality
was increased after coronary thrombotic events and after major
bleeding. Thus, rather than just being evaluated as a subset of
patients in whom the risk of bleeding takes precedence, high
bleeding risk patients must be considered a vulnerable population
in whom both ischemic as well as bleeding events have a
significant impact on their mortality.


Dr Carolyn Lam: Nice, Greg, and you said all of that without
repeating everolimus.


Dr Greg Hundley: Coated, remember, coated stents.


Dr Carolyn Lam: These tongue twisters, but hey, my next paper
provides novel insights into mechanisms underlying diastolic
stiffness in cardiomyocytes and the myocardium. This is from Dr
Prosser from Perelman School of Medicine in Philadelphia and
colleagues, who interrogated the role of the microtubule network
in the diastolic mechanics of human cardiomyocytes and
myocardium. They found that stable detyrosinated microtubules
contributed viscous forces during diastolic stretch that
increased cardiomyocyte stiffness, particularly in patients with
heart failure. Depolymerizing microtubules reduced myocardial
stiffness over the range of strains and strain rates associated
with early rapid filling in tissue from patients with diastolic
dysfunction.


Dr Greg Hundley: Now, how are we going to take this to patients?
Are there any translational insights?


Dr Carolyn Lam: Microtubule deep polymerization using colchicine.
Colchicine, the stuff we use for gout, this reduced myocardial
viscoelasticity with an effect that decreased with increasing
strain. Post-hoc subgroup analysis revealed that myocardium from
patients with heart failure reduced ejection fraction were more
fibrotic and elastic than myocardium from patients with heart
failure preserved ejection fraction, which were relatively more
viscous. Now, colchicine reduced viscoelasticity in both HFpEF
and HFrEF myocardium, but may confer greater benefit in
conditions with limited myocardial fibrosis including HFpEF.
How's that for translational?


Dr Greg Hundley: Oh, very nice, Carolyn. My next paper comes from
Dr Lior Zangi from Mount Sinai School of Medicine. Carolyn, in
this study, the authors performed transcriptomics sphingolipid
and protein analyses to evaluate sphingolipid metabolism and
signaling after myocardial infarction. They investigated the
effect of altering sphingolipid metabolism through a loss of
chemical inhibitors or gain modified MRNA and modified RNA of
acid ceramidase function post hypoxia or MI.


Dr Carolyn Lam: Whoa, so what did they find?


Dr Greg Hundley: Well, Carolyn, translationally, the authors
found that transiently altering sphingolipid metabolism through
acid ceramidase over expression is sufficient and necessary to
induce cardio-protection after myocardial infarction. Carolyn,
these results highlight a new therapeutic potential of acid
ceramidase modified messenger RNA in ischemic heart disease. The
basic science is just phenomenal in our journal.


Dr Carolyn Lam: It is, and I loved the way you explained that
one, Greg, thanks. Now, there's lots of stuff also in the
journal. There's an On My Mind by Dr Ray entitled "LDL
Cholesterol Lowering Strategies and Population Health: Time to
move to accumulative exposure model." We also have a research
letter by Dr Chen describing a novel mouse knock-in strategy
utilizing a biotin ligase-based system called biotin
identification 2, to identify the cardiac diet proteome in vivo.
Well, very interesting stuff, especially in terms of this
particular novel strategy.


Dr Greg Hundley: You know, Carolyn, this week the mailbox is just
full, so I've got a research letter emphasizing trends in
anti-arrhythmic drug use among US patients between 2004 and 2016
and it's from Dr David Frankel from the Hospital of the
University of Pennsylvania.


I've also got a letter to the editor regarding the association
between the use of primary prevention implantable cardio
defibrillators in mortality in patients with heart failure, a
prospective propensity matched analysis from the Swedish Heart
Failure Registry, and the corresponding author is Professor
Laszlo Littman from atrium health at the Carolinas Medical Center
in Charlotte, North Carolina. There is also a response to this
letter from Dr Gianluigi Savarese from Karolinska Institute.


Then finally I have a new another EKG challenge, Carolyn, from Dr
Miguel Arias. It's a case of new onset, recurrent syncope
triggered by fever. Can you get it right from just looking at the
EKG?


Well, Carolyn, should we head on to our feature discussion, which
this week has a very somber tone?


Dr Carolyn Lam: Let's go.


Left ventricular assist devices or LVADs are really becoming
established therapy for end stage heart failure. Now, we who
manage such patients realize there are numerous complications and
have seen patients who suffer things like anxiety and depression.
Interestingly, until today, there was very little data regarding
the suicide risk in this population.


I am so pleased to welcome the authors of a very unique and
important research letter and they are Vincent Galand as well as
Erwan Flécher, both from Ren University Hospital in France, and
of course Mark Drazner, our associate editor from UT
Southwestern. Vincent, could you start us off by telling us what
made you do this important study and what did you find?


Dr Vincent Galand: As you know, in the entire population where a
lot of tests have thromboses or infection or ventricular
arrhythmias, but there is a lack of data about the clarity of
life for the secret distress or suicide in this population. I
think it's very important to have information about the
population.


At the beginning is the Assist-ICD study is a study focused on
arrhythmias in this population, but we recorded data about
suicide in this population. What the objective of this study was
to analyze the incidents of suicide in this population and to see
if there is some predictor of suicides in this population.


Dr Carolyn Lam: What did you find?


Dr Vincent Galand: We find that in centers without LVAD nurse
coordinator, the incidents of suicide, was higher. It was not
significant, but it was a very big trend. Additionally, we found
that patient implanted in destination therapy was a bigger risk
of suicide compared to patient granted bridge transportation or
bridge to recovery. I think there is two factors of suicide. The
first one is a lack of LVAD nurse coordinator and the second one
is the implementation and destination therapy.


Dr Carolyn Lam: Yeah, and the really cool thing is that that
first factor is something that I suppose can be addressed in
future efforts. Mark, could I just ask you to put these findings
and this research that are into context for circulation to
publish quite a specialty, if you may, topic, why is this so
important?


 


Dr Mark Drazner: DT vans are really a rapidly emerging therapy
for patients with advanced heart failure, with almost exponential
growth. As these profound technologies are emerging on the scene,
it's important, first, to consider all the ramifications for our
patients. I think anyone could imagine having an LVAD implant and
how that might have profound influence on your life in totality
and the impact on the psychological aspects.


While there's been previous studies, there seems to be much
avoidance in us really fully understanding the total impact.
There have been previous case reports of suicide, but not
anything to this magnitude where a systematic series with an
estimate of the frequency of as high as 2%, which may not sound
high, but, compared to the general population, is increased. We
view this as an important look at a critical topic. It's the
beginning, there needs to be, as you said, it's a research writer
on a case series, but it's a cautionary tale and really is
pointing the way for us to proceed with further investigation as
potentially important complication related to that. That's
essentially why the editorial board found this interesting.


Dr Carolyn Lam: Indeed. Could you just remind us how big this
study was? Because this is really big for an LVAD study.


Dr Erwan Flécher: We collected data from 19 university centers in
France over 10 years period and we collected a lot of that
especially in the fields of arrhythmia. As Vincent said, we
thought it was interesting to take the entire picture, so we
collected data about quality of life and how do they live and if
they had a lot of risk of suicide, if not, and that's how we
succeeded to lead this study.


In France, what is important also for you to know is that we do
implant a different population of patients than in the US. We do
implants in bad patients, in very, very sick patients. Most of
them are currently in cardiogenic shock or already under
temporary support, ECMO support, IMPELLA support, so it may
impact also our results.


That's an interesting point to say and the overall thing is that
our paper demonstrated, I think, that we need to take care of
these patients not only about the device, not only about the
anticoagulation, but also, I mean again, the entire picture. The
social part, the quality of life, the way they do live is very
important. Probably they should be proposed for psychological
follow-up also, or any kind of support for the family. This is
important in order to decrease the risk of suicide, in my
opinion.


Dr Carolyn Lam: I liked those take-home messages that are very
practical, and you kind of read my mind about that question of
generalizability. Mark, did you have any reflection on that? The
generalizability to the US population?


 


Dr Mark Drazner: Yeah, that's an important point. I was struck in
the paper that 80% of the patients who committed suicide were
followed at centers without LVAD coordinators. That number seems
high compared to what we're used to seeing. It would be
intriguing how widespread that is, where patients who are getting
implanted don't have access to a VAD coordinator in your country.


Dr Erwan Flécher: Well, that's an important point also. It is
different in France. I mean, we just created...That coordinator
did not exist a few years ago in France and I know you are used
to work with VAD coordinator in the US, in the UK, even in
Netherlands and Germany, but in France it was not like that and
all patients were only followed by cardiologist or cardiac
surgeons and a few centers started few years ago, five, eight
years ago to have a VAD coordinator nurse program. We do believe
it is very, very important. That's also plea for a better
organization of care in our country.


Dr Mark Drazner: Yeah, that's a thinking point. I didn't realize
that that was not widespread practice and relatively new
implementation. It'll be interesting to see if the rates
subsequently fall with that change in practice. Can I ask, let me
follow up in terms of your previous comment. It sounds like a lot
of these patients were acute presentations and I wonder also
whether they may not have had the full time to grasp exactly what
they were getting into, for example. I think we've all been
there.


Someone went into cardiogenic shock, ends up crashing and burning
and has to go for a durable VAD. A very different complex in
someone who has consolidation has been followed in the center for
a while, has a chance to come to understand what all that really
is. You think that is a major factor in this experience?


Dr Vincent Galand: We think that patients who are granted in case
of emergency; it's a bigger risk of surgical distress afterwards
the implantation. In fact, that they cannot many information
before the implantation, information about the worth life after
the LVAD implantation. Of course if they don't the information,
they can't be prepared for life after surgery. I think it's a
bigger risk, yeah.


Dr Erwan Flécher: That's why maybe in your country or maybe
elsewhere, I don't know, maybe the findings would have been
different. That's, that's an option we should consider, also. In
France, as we told you, we do implants. Most of our patients are
implanted in emergency. They're already in ICU. Most of them are
already under mechanical ventilation, so they just wake up and
they learned that they have been implanted. Not all of them, but
most of them, the vast majority of them, so of course they are
not so well prepared and that may have an impact on the
follow-up. We try to talk to the family; we try to talk to the
general practitioner.


Dr Mark Drazner: Of the 10 patients, it's very interesting that
patients are being implanted and not knowing they're being
implanted in and say waking up with an LVAD. I don't know if you
have the granular detail, but do you know, of these 10 patients,
how many of them were in that situation?


Dr Vincent Galand: The patients were implanted in cardiogenic
shock, so I think it's four patients, but six patients were
implanted without cardiogenic shock. They received this kind of
information before the LVAD implantation, so it's not a big part
of the population, but it's some patients.


Dr Mark Drazner: Could you, just for our readers, it's a little
goory, I will admit, but in terms of how these patients attempted
or actually committed suicide, just to explain in terms of, it
was oftentimes related to a mechanism through the LVAD. If you
could just summarize that and how they tried to commit suicide or
commit suicide.


Dr Vincent Galand: That was the case. The suicide was with drive
line disconnection or drive line section. In two patients, it was
drug suicides, but in most of the patients the drive line is the
main way for suicide.


Dr Mark Drazner: It's interesting that the mechanism that these
patients tried to commit suicide was directly through the LVAD.


Dr Erwan Flécher: Of course it's the easiest way to terminate
their life and they just cut off it. Just don't plug the battery
and they are alone and that was the main way to practice their
suicide.


Dr Mark Drazner: I know we don't have the initial report, we
probably don't have all those, but in terms of you postulating in
the paper why patients might get to the state where they would
try or commit suicide with the LVAD. If you just want to throw
out some of your hypotheses so that our listeners can hear those
as well.


Dr Erwan Flécher: I've got in mind two or three points in order
to improve our results. First of all, we should implant maybe
earlier patients in France in order to have a better way to
prepare and to invest the VAD implantation.


The second point would be to have a better organization of care
and I think we should develop that VAD nurse coordinators program
like in many countries. We still have some but not in all the
hospitals implanting that.


The third point would be also to get the better LVADs. I mean,
probably the drive line in sections, batteries, the controller,
this of course it's much better than it was 10 years ago. There
is no noise. It's less big than it was, but still, I think if we
can improve the device itself, I think we may observe maybe the
decrease in the risk of a system in society, especially the drive
line, if there is no drive line, the quality of life should be
better. We may suggest that the risk of suicide would decrease.


Dr Carolyn Lam: A very somber topic, but those last take home
messages, leaving hope for improvement, were really important.
Thank you everyone for sharing with us today, and thank you,
audience, for joining us today.


 


Dr Greg Hundley: This program is copyright, the American Heart
Association 2020.