Circulation August 30, 2016 Issue

 


Carolyn:
Welcome to "Circulation on the Run", your weekly podcast summary
and backstage pass to the journal and its editors. I'm Doctor
Carolyn Lam, Associate Editor from the National Heart Center and
Duke National University of Singapore. In just a moment, we will
be discussing the very topical subject of wearable cardioverter
defibrillators in patients at high risk of sudden cardiac death.
Yes, this is the topic of our feature paper which really builds
on prior US data using these devices and extends it, now, to a
healthcare system outside the United States. First, here's the
summary of this week's journal.


 
 
The first paper describes a novel class of mediators that may
revolutionize the nonsurgical treatment of limb ischemia. This
paper from first author Doctor Jung from University of Louisville
School of Medicine and corresponding author Doctor Spite from
Harvard Institute of Medicine and colleagues looked at
resolvents. Resolvents are a family of lipid mediators
synthesized from Omega-3 polyunsaturated fatty acids that promote
the resolution of inflammation and have been shown to regulate
the transition from inflammation to repair. Now, this is very
relevant to limb ischemia because most other mediators that
promote revascularization also exacerbate inflammation, thus
potentially limiting their therapeutic use in chronic
inflammatory diseases such as diabetes.


 
 
To assess the role of resolvents in revascularization and
resolution of inflammation, the authors using a Murine model of
hindlimb ischemia coupled with Laser Doppler profusion imaging,
micro-computed tomography and targeted mass spectrometry. They
identified that resolvent D2 is produced in the skeletal muscles
of their Murine model of limb ischemia as well as in skeletal
muscle biopsies of patients with peripheral artery disease. They
showed that resolvent D2 increases tissue profusion by promoting
arterial genesis that is collateral artery growth and,
importantly, that it rescues defective revascularization in
diabetic mice. These findings are important because they could
inform the development of novel strategies for the clinical
management of limb ischemia.


 
 
The next paper addresses food fortification with folic acid,
which we all know prevents neural tube defects but may now even
prevent congenital heart defects. This paper is from Doctor [Mule
00:02:53] and colleagues from The Center for Chronic Disease
Prevention, Public Health Agency of Canada who studied
approximately six million Canadian births from 1990 to 2011 and
compared the prevalence rates and temporal trends in congenital
heart disease sub-types before and after 1998 when folic acid
fortification was mandated in Canada. They quantified the effects
of folic acid fortification on the birth prevalence of specific
non-chromosomal congenital heart disease sub-types, after
controlling for concomitant changes in maternal age,
pre-pregnancy diabetes, preterm pre-eclampsia, multiple birth and
pregnancy termination. They found that there was an eleven
percent reduction in non-chromosomal congenital heart defects
following folic acid fortification. Specifically, folic acid
fortification was associated with a twenty-seven percent
reduction in conotruncal defects, a twenty-three percent
reduction in coarctation of the aorta, a fifteen percent
reduction in ventricular septal defects and an eighteen percent
reduction in atrial septal defects. This large ecological study,
therefore, provides evidence of a modest protective effect of
folic acid fortification on congenital heart defects.


 
 
The last study suggests that in patients with ischemic
cardiomyopathy and right ventricular systolic dysfunction, we
should perhaps be taking a look at the mitral valve. This is work
from first author Doctor Seib from the Beth Israel Deaconess
Hospital and Harvard Medical School, corresponding author Doctor
Kwon from the Heart and Vascular Institute of Cleveland Clinic
Foundation and colleagues, who looked at over five hundred and
fifty patients with ischemic cardiomyopathy, all of whom
underwent cardiac MRI. They found that mitral regurgitation, as
measured by effective orifice area, was a significant independent
predictor of right ventricular ejection fraction. They further
found that the relationship between right ventricular ejection
fraction and mortality may be affected by mitral valve surgery in
that a reduction in right ventricular ejection fraction was
associated with increased mortality in non-repaired patients but
not in patients who had undergone mitral valve repair.


 
 
The clinical take-home messages are that right ventricular
function should be carefully assessed in patients with ischemic
cardiomyopathy and if systolic dysfunction is found, patients
should be assessed carefully for significant mitral regurgitation
as well as other known risk factors such as right bundle branch
block, right ventricular scar or a decreased left ventricular
ejection fraction. The study suggests that mitral valve surgery
may mitigate the relationship between right ventricular rejection
fraction and mortality, however further studies are clearly
needed.


 
 
Those were the summaries. Now, for our feature paper discussion.


 
 
I am thrilled to be joined by three guests today to discuss the
feature paper on wearable cardio defibrillators in patients at
high risk of sudden cardiac death. This is a real world
experience all the way from Germany. Joining us today we have two
authors of the paper, the first and corresponding author Doctor
Nadine Visnic as well as author Doctor Ruth Strasser, both from
the University of Dresden and Heart Center Dresden in Germany.
Welcome, ladies.


 
Ruth:
Hello, how are you?


 
Carolyn:
Very good, thank you.


 
 
We have Doctor Mark Link, Associate Editor from UT Southwestern.
Thank you for joining us, Mark.


 
Mark:
You're very welcome.


 
Carolyn:
Mark, let's start with a behind the scenes look. We have data
from the United States describing the wearable cardio
defibrillator. We have ample data on the implantable cardio
defibrillators. What made the editorial board decide that this
particular paper from Germany was so important?


 
Mark:
There are a number of aspects that we looked at for this paper.
This is exciting new technology that is beginning to impact the
daily lives of all the physicians in the states, the wearable
defibrillator. This is a very nice prospective study from Germany
that looked at a very large group of patients with this wearable
defibrillator, gave us real world experience and it also fits in
with the circulation mission of becoming a world wide cardiac
journal, not just United States journal. We were very interested
in the topic. We're very interested in the international
collaboration and we're very excited to publish this paper.


 
Carolyn:
I love that. Practicing in a non US system, as well, I found this
particularly special about this paper.


 
 
Nadiene, we're all wondering, could you describe the patient
population, just so we know the kind of patients that your
results are applicable to.


 
Nadine:
The patients included in the register were regular patients we
meet in clinic in every day life. No specific selection was made.
For legal reason, of course, to analyze the data, they signed
informed consent for the register. From April 2010 through
October 2013, in total six thousand forty-three patients were
using the wearable cardioverter defibrillator in Germany. All of
these patients were registered into the life vest network, the
registry to record demographic such as gender and age. Also, the
cardiovascular indications and defibrillation treatments and
daily wear time. The German population consisted of seventy-eight
male and twenty-two female patients with median age of
fifty-seven years.


 
Carolyn:
Great. What were the indications for the wearable defibrillators?


 
Nadine:
Most of the patients had to reduce the ejection faction by below
thirty-five percent or even had experienced ventricular
tachycardia as an indication. The largest group we had in our
analysis was thirty-seven percent where those with newly
diagnosed dilatative cardiomyopathy and ischemic cardiomyopathy
accounted for twenty-seven of patients, especially forty days
after myocardial infarction or after a high risk PCI or cabbage.
Also, in total, we had twelve percent of patients that had an ICD
explantation mostly due to infection situation. What is very
special on that paper is that ten percent of all our patients had
myocardidas as a diagnosis and was reason to use the WCD.


 
Carolyn:
Wow. That does sound very representative of the real world
patients that we would put wearable defibrillators on, as well.


 
 
Ruth, could you tell us, what were the main results? Were there
any differences by sub-groups?


 
Ruth:
Perhaps, we should first go on the compliance because this is
very important to the daily wear time. This was more than
twenty-two hours in ninety-four percent of the patients. Many
patients who complained about the inconvenience but understanding
that this life vest is a potentially life saving and only
temporary treatment strategy made it acceptable to ninety-eight
percent of the patients. As to the [inaudible 10:52] there is a
difference, the younger patients, patients younger than
forty-eight years of age or younger, they wear the life vest
longer, sixty-six days. While the older patients, older than
sixty-eight patients, this was statistically significant, wore it
only forty-nine days. This difference was not used to compliance,
because you do the description based on the cardiac diagnosis.


 
 
We also observed that the longer the cumulative wear of the life
vest was, the longer day hours the patient had the life vest on.
They were somewhat accustomed to it. One thing which is very,
very important is, that in more than twenty-five percent of the
patients, we could save the implantation of a permanent ICD due
to the recovery of the ejection fraction. This was especially
important for those patients who had the life vest, for example
after myocardidas or after myocardial infarction, which is a very
large population.


 
 
Also, which is important is that [full 12:06] shock treatment for
reasons other then VT occurred only in point four percent, of
less than one percent. Whereas those patients were successfully
treated, this was one point six percent. They were treated in
response to VT and VF. This means the incidence rate was eight
point four per hundred patient years. This was even higher in
those patients who had the life vest for the explantation. The
life vest is very effective. It's a very effective strategy for
general patient population with above indications. It can save
the implantation, as I said already, in more than twenty-five
percent in the population in Dresden itself. We could observe
even a reduction of the need of implantation of permanent ICD
more than thirty-five percent due to the recovery of the
ejection. This is a very important treatment, especially for
those patients who have an acute illness.


 
 
The German cohort is the first large cohort outside the US
healthcare system. It confirms the overall value of the life vest
and treatment pathways in Germany. Also, the cohorts analysis
uncovered over two hundred forty-two sustained but
self-terminated episodes of VT among seventy life vest patients,
so that you have safely not treated because they were still
conscious and could still press the response button. We found out
that some of the self terminated VT episodes were even longer
than eight minutes in duration time. All in all, we could see
that the life vest is a device which is safe and which can
prohibit shocks, as well.


 
Carolyn:
Thanks, Nadine. [Ruth 14:12]


 
 
Mark, though, for the readers, I'm sure we need to put in
perspective, as well, because there are still patients where
perhaps an implantable cardio defibrillator is still more
important. Could you share some thoughts about that?


 
Mark:
Yeah. I think this is a very interesting, important study, for a
number of regards.


 
 
One, is that there was a very high rate of compliance with using
the life vest. To leave it on for twenty-three hours a day, for a
mean of sixty days, is really quite impressive patient
compliance. The data showed that it did recognize and treat VF in
a small percentage, but in a important percentage, of people.
This data does need to be put in perspective and the randomized
trial is currently ongoing. The vest trial, which will randomize
people, probably similar population to what the German study did,
and look at the life vest performs in that population.


 
 
We look forward to further data from the vest trial and from
other trials, that are looking at what the place of the wearable
defibrillator will be in the future.


 
Carolyn:
Thank you, Mark and that's perfect take home message for all us
out there.


 
 
Thank you, once again, Nadine, Ruth, Mark. It has been wonderful
chatting with you.


 
 
To all of you out there, you've been listening to Circulation on
the Run.


 
 
Thank you for joining us.