Aug 29, 2016
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.