Circulation June 23, 2020 Issue

Today’s episode discusses the paper “Randomized Comparison of the
Polymer-Free Biolimus-Coated Biofreedom Stent With the Ultrathin
Strut Biodegradable Polymer Sirolimus-Eluting Orsiro Stent in an
All-Comers Population Treated With Percutaneous Coronary
Intervention: The SORT OUT IX Trial”


 


Dr Carolyn Lam and Dr Greg Hundley also discuss the following:


“Incidence, Microbiology, and Outcomes in Patients Hospitalized
With Infective Endocarditis” by Shah et al.
“Reducing Hypermuscularization of the Transitional Segment
Between Arterioles and Capillaries Protects Against Spontaneous
Intracerebral Hemorrhage” by Joutel et al.
TRANSCRIPT


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: And I'm Greg Hundley, associate editor from the
Pauley Heart Center at VCU Health in Richmond, Virginia.


Well, Carolyn our feature article this week, we're going to dive
into evaluating stent efficacy and looking at biodegradable
stents and polymer free stents, and I can't wait to get to that
feature.


But before we do that, how about we get to other articles in our
journal today? Would you like to start?


Dr Carolyn Lam: You bet, Greg. So this paper describes temporal
changes in the incidence, microbiology and outcomes of infective
endocarditis and the impact of changes in national antibiotic
prophylaxis guidelines on incident infective endocarditis in
Scotland.


Dr Anoop Shah from University Center for Cardiovascular Science
at University of Edinburgh, and colleagues used a Scotland wide
individual level linkage approach to identify all patients
hospitalized with infective endocarditis from 1990 to 2014, and
linked their records in national microbiology, prescribing and
morbidity and mortality datasets.


Dr Greg Hundley: Interesting, Carolyn. So what did they find in
this study?


Dr Carolyn Lam: The crude incidence rate of infective
endocarditis hospitalizations increased from 1990 to 1995 but has
remained relatively static thereafter with both short and
long-term adjusted case fatality rates showing a steady decrease
over the last 25 years. However, the incidence rate has doubled
in the elderly.


Importantly, there was no change in crude incidence following the
2008 change in antibiotic prophylaxis guidelines. The majority of
patients with endocarditis in their cohort did not have positive
blood cultures. However, in those that did have positive
microbiology, staphylococcus and enterococcus conferred the
highest risk for all-cause mortality.


Dr Greg Hundley: Ah, very interesting. More in the world of
endocarditis. Well, Carolyn, my paper is also interesting and it
involves both mouse and human experiments to identify the
etiology of deep intercranial hemorrhagic stroke. Now I'm not
going to quiz you this week because I think you're going to want
to quiz me in anticipation of some of these exciting study
results.


A little bit of background. First of all, the study comes from Dr
Anne Joutel from INSERM and it has been thought that smooth
muscle cell degeneration at the site of arterial wall rupture may
be sufficient to cause hemorrhage. However, deep intracranial
hemorrhages are rare in some aggressive small vessel diseases
that are characterized by significant arterial smooth muscle cell
degeneration.


Therefore, the authors hypothesized that a second cellular defect
may be required for the occurrence of intercranial hemorrhage. So
to address this hypothesis, the author studied a genetic model of
spontaneous deep intercranial hemorrhage in mice, and analyzed
cerebral retinal micro vessels, performing genetic rescue
experiments, vascular reactivity analysis, and computational
modeling.


And in the human experiments, they examined post-mortem brain
tissues from patients that had sporadic deep intercranial
hemorrhage.


Dr Carolyn Lam: Wow, that's a lot of work from mice to men. Well,
let's start with the mice. So what did they find there, Greg?


Dr Greg Hundley: Right, Carolyn. So the authors identified in the
normal cerebral retinal vasculature, a novel segment between
arterials and capillaries herein called the transitional segment,
and that is covered by neural cells distinct from smooth muscle
cells and parasites.


In Col4a1 mutant mice, this transitional segment was hyper
muscularized with a hyperplasia of neural cells expressing more
contractile proteins, whereas the upstream arterial exhibited a
loss of smooth muscle cells.


Moreover, the hyper muscularization of the retinal transitional
zone increased its contractility in tone and raised the
intravascular pressure in the upstream feeding arterial.


Dr Carolyn Lam: Wow, masterful explaining, Greg. Okay. What about
in the humans?


Dr Greg Hundley: Well, the author similarly found that hyper
muscularization of the transitional segment and focal arterial or
smooth muscle cell loss in brain tissues from patients were
observed in those with sporadic deep intercranial hemorrhage.


Dr Carolyn Lam: Okay, so put it together for us, Greg.


Dr Greg Hundley: Right. So the results suggest that hyper
muscularization of this transitional segment is involved in the
incurrence of intracranial hemorrhage in these studied mice, and
this hyper muscularization in this zone raises the intravascular
pressure in the upstream feeding arterial and promotes its
rupture at the site of smooth muscle cell loss.


The human data corroborate these findings indicating that these
two mutually reinforcing vascular defects may represent a general
mechanism of deep intercranial hemorrhage. Really interesting
results.


Dr Carolyn Lam: Not just interesting, but very, very nicely
summarized. Thanks Greg.


Well, other very interesting papers in today's issue include a
research letter by Dr Tiantian Li et al, entitled Associations
Between Short Term Exposure to Fine Particulate Matter and
Cardiovascular Disease Hospital Admissions After Index Myocardial
Infarction. A case crossover study from Beijing, China.


There's also a white paper from Dr Milton Packer on the role of
deranged energy deprivation signaling in the pathogenesis of
cardiac and renal disease in states of perceived nutrient over
abundance. This beautiful white paper presents a mechanistic
framework that may explain the findings of large scale randomized
trials of SGLT-2 inhibitors and the close association of
ketogenesis and erythrocytosis with the cardio protective and
renal protective benefits of these drugs. Interesting.


There's also a series of papers on COVID-19, including an online
white paper by Dr Franz Messerli on COVID-19 and
renin-angiotensin blockers, current evidence and recommendations.


A perspective paper by Dr Michael Givertz on the challenges in
heart transplantation in the era of COVID-19. Another online
paper by Dr Harsimran Singh entitled New York City innocence
lost, cardiology in the COVID-19 pandemic.


Dr Greg Hundley: Wow, Carolyn, this issue is just truly full of a
lot of articles in addition to our original research.


So I have an exchange of letters to the editor between Richard
Sutton and Dr Ben Levine regarding Dr Levine's previously
published tilt table manuscript.


Next, Dr James Byrd from the University of Michigan offers a
perspective on pausing clinical research during the COVID-19
pandemic.


Dr Comilla Sasson from the American Heart Association heads a
very large group of authors to provide a very nice piece on
guidance for life support during the COVID-19 pandemic.


Next, Professor Guilo Stefanini from Humanitas University has a
research letter regarding ST elevation myocardial infarction in
patients with COVID-19, both the clinical and the angiographic
outcomes.


And then finally, another ECG challenge from Dr Adrian Baranchuk
entitled an ominous ECG sign in critical care.


Well, Carolyn, what a great issue, and let's get on to that
feature discussion to learn a little bit more about bio
resorbable intercoronary stents.


Dr Carolyn Lam: Great. Let's go, Greg.


Dr Greg Hundley: Well, listeners, We're here for our feature
discussion. And today we have Professor Lisette Jensen from
Denmark and Dr Dharam Kumbhani from Dallas, Texas, one of our own
associate editors.


Lisette, could you tell us a little bit about the background for
your study of intercoronary stenting and what was the hypothesis
that you wanted to address?


Prof Lisette Jensen: The overall background or aim for this
program is that we want to have a quality control of what we put
into the patients, what stent we put in, and also we wanted to do
as much research as possible, and we want to do it if it's
possible on a low budget.


For the present study, the Sort Out IX, before we did the study,
we knew that the Bio Freedom stent was doing very well with a
short time of dual antiplatelet therapy in patients with high
bleeding risk. At the same time, we knew that the Orsiro stent
was doing very well in all common populations, we used it in Sort
out VII also.


We wanted to see how the Bio Freedom stent, the one you could use
with a short time of dual antiplatelet therapy, how it was
compared to a gold standard stent. In this study, we did not
shorten the treatment time with dual antiplatelet therapy, but we
followed the guidelines with six months for patients with stable
angina, and 12 months for patients with acute coronary syndrome.


Dr Greg Hundley: Can you just remind our listeners, what's the
difference between the Bio Freedom stent and then Orsiro stent?


Prof Lisette Jensen: There's several differences. The strut
thickness of the two stents differs. The Orsiro stent is an
ultra-thin stent strut and the Bio Freedom stent is 120 microns.
Also, the Bio Freedom stent is free of a polymer, compared to the
Orsiro stent where the polymer is biodegradable and is degraded
in one to two years.


And also the drug is sirolimus in the Orsiro stent and it is
released within three months compared to the Bio Freedom stent
where most of the drug biolimus is released within one month.


Dr Greg Hundley: So the Bio Freedom is a stainless-steel drug
coated stent, and the Orsiro stent is a biodegradable stent. So
can you tell us what was the study design, and then the study
population?


Prof Lisette Jensen: It was a randomized trial and we enrolled
3,151 patients. They were randomized one to one, two to two stent
groups, and we followed the patients. The primary endpoint was
after one year, and this is what we're going to publish now in
the journal, and we plan to do up to five years follow-up in the
patients.


Dr Greg Hundley: And what outcomes were you looking for?


Prof Lisette Jensen: The primary endpoint was MACE, and that was
a composite endpoint of cardiac deaths, target lesion
revascularization, and myocardial infarction, not clearly related
to any other segment that the index listed.


Dr Greg Hundley: So 3,151 patients, so a very large study. Can
you tell us a little bit about your study outcomes?


Prof Lisette Jensen: The outcome was the primary end point after
one year was, we saw MACE rate in the Bio Freedom treated
patients was 5.0% compared to 3.7% in the Orsiro group. And the
study was designed as a non-inferiority study, so with these
numbers, Bio Freedom stent did not meet the criteria for
non-inferiority.


 


Dr Greg Hundley: And were there any particular patient
populations or subgroups where you saw differences in performance
from one stent versus the other?


Prof Lisette Jensen: We looked into several predefined subgroups,
which are also in the paper as figure three where we did a force
plot, and in all the pre-specified subgroups, including
indication for PCI, acute coronary syndrome or stable angina,
young patients, old patients, diabetic, non-diabetic, gender, we
did not see any significant difference.


Dr Greg Hundley: Well, Dharam, I'd like to switch over to you a
little bit. Can you help us put this study in perspective to the
other world's literature related to intercoronary stenting?


Dr Dharam Kumbhani: You know, one of the biggest advantages of
the way they enroll patients is they tend to be a lot more
inclusive than many of the other trials that are done. So
typically isn't all common population.


So, now and again, I think it was an important trial because as
she just outlined, it compares the Bio Freedom stent, which is a
polymer free stent to a biodegradable stent. And this was really
the first comparison of this Bio Freedom stent with a more
contemporary stent that is used in clinical practice.


There have been a couple of other trials like the industry three
and industry two trial which have compared it with bare metal
stents. We know that this stent has a better performance than
that, but when you compare it with, especially the thin struts or
Orsiro, the latest in this class of DES, it is the thinnest
strut, one of the thinnest strut stents that is in the market.
The strut thickness, we know it really correlates quite well in
stent restenosis.


I think this really helps move the field forward in terms of
having data available for this comparison, and it suggests that
perhaps in this kind of pragmatic design, that this Bio Freedom
stent did not necessarily in the timeframe that they studied,
meet the criteria for non-inferiority compared with the Orsiro
stent.


So I think there's still valuable insight. The stent is not yet
approved in the US. None of the Bio Freedom stents are available
in the US. This is CE Mark, but not available in the US.


So I think this does add to the overall body of literature for
this group of stents.


Dr Greg Hundley: I would like to ask you both, perhaps one at a
time. Lisette, you first. What do you see is the next research
study that needs to be performed in this field? Lisette.


Prof Lisette Jensen: Can I just give one more comment to what
Dharam mentioned with the restenosis, because that was actually
what we saw in the Sort Out IX. We had a higher rate of the
target lesion revascularization rate in the Bio Freedom stent
group, so the efficacy was less.


It could be because of the bigger stent struts, pushing us in a
direction where we should use stents with thinner stent struts.
And also we saw that the safety did not differ as we saw the
equal number of stent thrombosis within one year.


I think what we should do next is maybe we should continue to
work on the thin stent struts, and then also for the patients,
the bleeding matters a lot. So it should be better to reduce the
bleeding time to develop devices where we can reduce the
treatment time for dual antiplatelet therapy.


Dr Greg Hundley: Very good. Dharam, your thoughts?


Dr Dharam Kumbhani: I would definitely agree. I think one of the
most appealing aspects of this group of stents, because they
don't have polymer, the ability to shorten the duration of
antiplatelet therapy. And over the last couple of years, we've
seen an incredible change in how we think about dual antiplatelet
therapy and a number of trials have really challenged that dogma.


So I really think that a stent like this, I think it will be very
interesting to study this in patients who are either high
bleeding risk. This does perform better than bare metal stents,
we know that. So conceivably we can get away with a much shorter
duration of dual antiplatelet therapy, or just a lower duration
of dual antiplatelet therapy in general.


So I would think that that would be one of the next areas of
research in a randomized fashion for this group of stents.


Dr Greg Hundley: Well, listeners, we've had a wonderful
conversation here with Professor Lisette Jensen from Denmark and
Dr Dharam Kumbhani from Dallas, Texas, related to some new
evolutionary thoughts in intercoronary stenting.


For all our listeners out there on behalf of Carolyn and myself,
we wish you a great week and look forward to speaking with you
next week.


This program is copyright of the American Heart Association 2020.