Circulation August 3, 2021 Issue

This week's episode features author Shih-Chuan Chou and
editorialist Alexander Sandhu discuss the article "Impact of
High-Deductible Health Plans on Emergency Department Patients
With Nonspecific Chest Pain and Their Subsequent Care."


Dr. Carolyn Lam:


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


Dr. Greg Hundley:


And I'm Dr. Greg Hundley Associate Editor, Director of the Pauley
Heart center at VCU health in Richmond, Virginia.


Dr. Carolyn Lam:


Greg, I am so excited about today's feature discussion that's
going to be about high deductible health plans and their impact
on emergency department patients with chest pain and their
subsequent care. Now, I can tell you as coming from outside of
US, I learned so much from this discussion so everybody's going
to want to hear it. But before we go there, let's discuss the
other papers in today's issue. Greg, do you have a paper?


Dr. Greg Hundley:


You bet. Thanks Carolyn. So my paper is going to really evaluate
a very interesting question about the role of measuring
lipoproteins and their subfractions in patients, not with
coronary disease, but peripheral arterial disease. And it comes
to us from Dr. Scott Damrauer from the University of Pennsylvania
School of Medicine. So Carolyn lipoprotein related traits have
been consistently identified as risk factors for atherosclerotic
cardiovascular disease, just like we said. Largely based on their
role in progression of coronary artery disease, but the relative
contributions of these lipoproteins to those with peripheral
arterial disease really haven't been as well defined. So these
authors leveraged a large scale genetic association data to
investigate the effects of circulating lipoprotein related traits
on peripheral arterial disease risk.


Dr. Carolyn Lam:


Interesting. So what did they find, Greg?


Dr. Greg Hundley:


Right, Carolyn. So ApoB was prioritized as the major lipoprotein
fraction usually or almost causally responsible for both
peripheral and coronary artery disease risk. Extra small VLDL
particle concentration, we'll call that excess VLDLP was
identified as the most likely subfraction associated with
peripheral arterial disease risk while large LDL particle
concentration was most likely the sub fraction associated with
coronary artery disease risk. And genes associated with excess
VLDLP and large LDL particle concentration included canonical
ApoB pathway components although gene specific effects were quite
variable. And then finally Carolyn, lipoprotein A was associated
with increased risk of peripheral arterial disease, independent
of Apo protein B. So therefore Carolyn, I think the take home
message from this study is that ApoB lowering drug targets and
ApoB containing lipoprotein subfractions had really diverse
associations with atherosclerotic cardiovascular disease and
distinct subfraction associated genes suggested that possible
differences in the role of these lipoproteins really are involved
in the pathogenesis of peripheral arterial as opposed to coronary
arterial disease.


 


Dr. Carolyn Lam:


Wow. Thanks Greg. Hey, it struck me that we haven't had a quiz in
a long time. Okay, but we're not going to do it now. Don't choke
because this one's kind of tough. I don't think I could even
answer it. What is phospholamban?


Dr. Greg Hundley:


Well, let me guess. I remember having this, I think. Let's
just... Carolyn I do not know what phospholamban is.


Dr. Carolyn Lam:


Let me just tell us all. Phospholamban is a critical regulator of
calcium cycling and contractility in the heart. The loss of
arginine at position 14 in phosphate lanvin is associated with
dilated cardiomyopathy and a high prevalence of ventricular
arrhythmias. But how this deletion causes dilated cardiomyopathy
is still poorly understood. And there are no disease specific
therapies. And hence today's paper, which comes from Dr.
Karakikes and colleagues from Stanford university school of
medicine. What they did is they employed human induced
pluripotent stem cells and CRISPR Cas9 gene editing technologies
to create an in vitro model of dilated cardiomyopathy associated
with this phosphate lanvin 14 deletion mutation. Single cell RNA
sequencing revealed the activation of an unfolded protein
response pathway, which was also evident by significant
up-regulation of marker genes in the hearts of patients with the
deletion. Pharmacological and molecular modulation of this
unfolded protein response pathways suggest a compensatory role in
this type of dilated cardiomyopathy. Augmentation of the unfolded
protein response by the small molecule BIP protein inducer X
Millia rated contractile dysfunction.


Dr. Greg Hundley:


So Carolyn, tell me what are the clinical implications?


Dr. Carolyn Lam:


Well, these findings suggest a mechanistic link between
proteostasis and the phospholamban 14 deletion induce
pathophysiology that could be exploited to develop a therapeutic
strategy for this kind of cardiomyopathy. The study also
highlights how human induced pluripotent stem cells and
cardiomyocyte modeling could be combined with small molecule
testing as a paradigm for studying genotype, phenotype
associations in heart disease.


Dr. Greg Hundley:


Very nice Carolyn. Well, my next paper comes to us also from the
world of preclinical science. And it's from Dr. Philip Marsden
from the University of Toronto. And Carolyn endothelial nitric
oxide synthase or eNOS is an endothelial cell specific gene
predominantly expressed in medium to large size arteries where
endothelial cells experience athero-protective laminar flow with
high shear stress. Now disturbed flow with lower average shear
stress decreases eNOS transcription, which leads to the
development of atherosclerosis especially at bifurcations and in
the curvatures of arteries. So the prototypical arterial
endothelial cell gene contains two distinct flow responsive SIS
DNA elements in the promoter. The shear stress response element
and the Kruppel-like factor or KLF element. Previous in vitro
studies suggested there're positive regulatory functions on flow
induce transcription of the endothelial genes, including eNOS.
However, the in-vivo function of these SIS DNA elements remains
unknown.


Dr. Carolyn Lam:


Wow. So what did these investigators do, Greg?


Dr. Greg Hundley:


Right. So Carolyn the authors report for the first time that the
shear stress response element and the KLF elements are critical
flow sensors necessary for a transcriptionally permissive hypo
methylated eNOS promoter in endothelial cells under chronic shear
stress in vivo. Moreover endothelial nitric oxide synthase
expression is regulated by flow dependent epigenetic mechanisms,
which offers novel mechanistic insight on eNOS gene regulation in
atherogenesis.


Dr. Carolyn Lam:


Nice. Thanks Greg. Well, let's go through what else is in this
week's issue. In a cardiovascular case series, Dr. Ribeiro
discusses the Platypnea-Orthodeoxia Syndrome, a case of
persistent hypoxemia in an elderly patient. In ECG challenge, Dr.
Challenge shows a case of diffuse St. Segment elevation with
idiopathic malignant ventricular arrhythmias. There's an exchange
of letters between doctors Wang and Sattler regarding the article
cross priming dendritic cells exacerbate immunopathology after
ischemic tissue damage in the heart. And there's an On My Mind
article by Dr. Mullasari Sankardas on of occlusions, inclusions
and exclusions time to reclassify infarctions. So interesting.


Dr. Greg Hundley:


Very nice, Carolyn. So I've got a couple of things in the mail
bag. There is from Professor Kunfu a Research Letter entitled PTP
MT-1 is required for embryonic cardio lipid biosynthesis to
regulate mitochondrial morphogenesis and heart development. And
then finally our own Bridget Kuhn has a cardiology news entitled
vegan diets that are culturally aligned with traditional soul
food gained popularity among black individuals. Well Carolyn, I
can't wait to get to your feature discussion today.


Dr. Carolyn Lam:


Me too. Today's feature paper is about the impact of high
deductible health plans on emergency department patients with
non-specific chest pain and their subsequent care. I'm so pleased
to have with us the first author Dr. Andrew Chou from Brigham and
Women's hospital, as well as the editorialist Dr. Alexander
Sandhu from Stanford university. Welcome gentlemen, please tell
us about your current study.


Dr. Andrew Chou:


Yeah, so I think the reason we did this study was really
obviously aware of the context, but also me working as an
emergency decision. So anybody in the ED will now that, there's
all kinds of versions of chest discomfort that comes through the
ED and they always are worried about heart attack. And we do this
testing kind of day in day out, it gets kind of inundated. So a
lot of people have put thought into what we should do in the
emergency room. We should get ECG, we should care cardiac enzymes
when we're worried about it. But what really quite remains
uncertain is really what to do afterwards. We get this patient,
we test them, we didn't really find heart attacks, but there's a
lot of uncertainty about what to do after. Do we do stress test,
do we hospitalize them to get the stress test or other testing.


Dr. Andrew Chou:


As a result, there's a lot of variation in care. And I think
partly because of that, they're kind of the shared decision
making came out of that. As a part of the solution was to involve
patient via, Hey, here are your risks. Let's talk about whether
or not this would make sense for you to stay, get testing among
other decisions. But what's always interesting to me is that even
though we have this push towards having patients have kind of
needing to make these decisions because of money, we don't really
talk about costs and even their sort of sense of pride about, oh,
we don't want to talk about costs. We just want to be the best
medical treatment for you, but cost is such a reality for the
patients. So, that's kind of the motivation behind getting this
study done. So the way we wanted to test it was to set it up as
closely as possible to run my trial but knowing that it's not
really possible in the real world to do something like that.


Dr. Andrew Chou:


So we had to be pretty selective about who we include as a study
population. So the first thing we did was we took essentially a
large national insurer and their claims database. We look at only
the people who enrolled in insurance products through their
employer. So employers in the US can choose what type of plan
they want to offer patients. And we only chose employers that
offer only one type of insurance at a time within each year of a
plan. So what we did is we chose people who had essentially two
years of enrollment. And in the first year, they all have to have
loaded up full plans.


Dr. Andrew Chou:


Meaning deductibles are less than $500. It's still a lot of
money, but it's less compared to... The second year either they
still have low deductible plan or the experimental group is going
to be a group of people who employer only offer high deductible
plan, which we define as having deductible greater than $1,000.
So that sort of set up a control and experimental group with a
similar baseline and then a different followup period of a year.
And then we also did additional matching by employer
characteristics and their own, the member characteristics to kind
of make them as close as possible in terms of compabilities, age,
as well as employer size, which we find to be a really big
factor. Because large employers tend to have lower deductibles
because they can risk care a lot better among their employees
where a small employers like companies with five, 10 employees
tend to have high deductible plans. So we use that population to
compare essentially what happens after a certain company switch
to kind of calculate the effect of the high deductible plan.


Dr. Carolyn Lam:


Great. Very novel design. But could you please tell us your
results?


Dr. Andrew Chou:


Yeah, so we found is that once the employees from the companies
that switch, there were less ED visits that ended up with a
diagnosis of chest pain. This is important to bring in also the
nuance here, which is that these are ED visits that effectively
are not have been seen and test it. And they don't have a severe
diagnosis like a heart attack or other significant cardiac issues
that were found at least during the initial ED stay. And that
decreased, which sort of makes the question whether or not these
decreased visits or either where they just another chest visit
without really other diagnoses or are they visits that actually
have diagnosis. The other thing we found was also that there's a
decrease in admissions from these ED visits actually. And
majority of it, even though when we did our study, we actually
were looking at admissions through the 30 days after these ED
visits.


Dr. Andrew Chou:


But we found that the majority of difference is actually the
admissions directly from these initial ED visits with time is
just horrible. Two more things we found was that the amount of
testing that was done after the ED visits, or not really
consistently decreased because of high deductible, some tests
really didn't have a difference and some more invasive and
expensive tests did have some differences. But if you account for
the decrease in the chest pain ED visits, then they're not really
that notable. But the last finding, which perhaps is the most
interesting of which is that there seems to be an increase in
heart attack diagnosis and admissions after these visits for
chest pain and our statistics for the entire study population
actually wasn't significant. But we decided to look at the
subgroup patients from poor communities who presumably have lower
income and found that the same findings in this group was
actually statistically consistent and so we felt comfortable
reporting that. So I think that was probably the most interesting
finding from our study.


Dr. Carolyn Lam:


Right. Thanks Andrew. Alex, I have to bring you in here. I really
love the editorial love that you said to go or not to go as the
title. But could you put these findings in context, please?


Dr. Alexander Sandhu:


Yes. Happy to and thank you for having me. I think studies like
this study by Andrew and colleagues are incredibly important as
we make health policy decisions that have large impacts on
clinical decision-making for both patients and clinicians. It's
important that we study them to understand how they impact
patient decision-making clinical outcomes and costs, because
obviously that can have important ramifications for future design
at the end detecting unintended consequences. I think this study
adds to a large body of work done by Andrew and his colleagues,
really helping us to understand the implications of high
deductible health plans on patient decision-making and subsequent
outcomes. This is an incredibly important topic because of the
proliferation of high deductible health plans over time and then
potentially since the advent of the Affordable Care Act with
fixed premiums leading to more and more cost sharing for
patients. And it's really critical that we understand how that
cost sharing impacts patients.


Dr. Alexander Sandhu:


And I think that chest pain is a wonderful test because chest
pain can be something very serious. It's almost universal that
when patients have acute onset chest pain, that a clinician asks
them to go to the emergency department for further evaluation.
However, we also have a large body of evidence that suggests that
the large majority of chest pain episodes are not serious and
don't end up needing additional treatment. So it's an area that I
think both you could imagine decreased utilization once you
applied cost sharing to patients. But what were you very much
worried about the unintended consequences of people not going to
the emergency department, if it's a serious condition. I think
this was a well-designed quasi experimental analysis to look at
the lower risk, but majority of episodes of chest pain where
they're non-specific and not resulting in acute coronary syndrome
and to try to demonstrate it that the high deductible health
plans do lead to reductions in those episodes.


Dr. Alexander Sandhu:


I think as Andrew said, one of the most fascinating findings was
this increase in acute MI's it was consistently significant
amongst the low-income patients, but was not related to patients
that were discharged because of potentially the effects of the
high deductible and then came back in with acute MI's but were
actually acute MI's during the initial admission. I was wondering
if Andrew could maybe both explain that nuance a little bit more,
which you get into the discussion of that paper, and then also
walk us through maybe some thoughts that you and your study team
had for causes for that potential finding.


Dr. Andrew Chou:


Yeah, absolutely. Thanks for raising that. So I think going into
it initially, our hypothesis was really that, but when we first
saw it, our initial thought was that, oh, maybe perhaps after
they're discharged, they're supposed to get testing and patients
or then follow up with their doctors. So they have increased poor
outcomes. And so after that thought, that's when we did the kind
of subgroup analysis looking at just patients who were discharged
versus those who were admitted when they were diagnosed with
chest pain at their initial ED visits. And exactly what we found
is that the difference is really among people who were admitted
initially, which is surprising to us. So I think what that
signals to us is that our initial thought was not correct in the
sense that this is not really a result of lack of followup or
didn't intend to the testing that they were scheduled or didn't
go see their doctor afterwards. But really like patients who are
showing up in the ED already are more prone to perhaps having a
heart attack.


Dr. Andrew Chou:


And so it really points to which is what you mentioned at your
program, which we totally agree as well, that more upstream
factors is affecting this. Could it be that they don't tend to
take their medications as they should, or they didn't go to their
doctors for checkups as they should, or they could have had
earlier identification of heart problems if they have more
perhaps milder symptoms beforehand until before the ED visits
that could have presented certain things. So, that's hard to say.
I do think that there is a... One of my mentors in this paper,
Dr. Wareham, who has done a ton of work in the space of high
deductible plan with kind of chronic disease management, they
have definitely shown a lot of differences when patients have
higher cost sharing. They'd certainly defer a lot of carriers,
especially in diabetics have more complications and it might be a
similar scenario here that which would make the most sense and
fits the best with our findings here.


Dr. Carolyn Lam:


So that's a great question Alex and great insight Andrew. I think
at this point, I need to ask you both. So what overall do you
think is the clinical implication or there'd be any practical
next step that you think should follow from this? Maybe I'll let
Andrew start and then Alex finish?


Dr. Andrew Chou:


Sure. Thank you. I think there's kind of... I think two aspects
to this one is really broader policy changes. I think if
anything, it's quite uncertain whether or not the reduction in ED
visits for chest pain is something detrimental. It's unsure
whether or not the reduce admission is detrimental. But what is
certain is that especially in lower income population certainly
feels the higher out-of-pocket costs a lot more. And if there is
an unintended consequence, it will certainly be magnified in this
population. And in fact, I think a couple of past studies who
having compared really high income versus low income population
has found that really, high income patients tend to do okay and
they're able to pick and choose appropriately of type of care
they need. Whereas low-income patients tend to have really
unanticipated changes. So, really trying to minimize the impact
for low-income patients is going to be important policy
direction.


Dr. Andrew Chou:


And there are a number of ways of doing it. I think there
certainly is an increasing trend for companies to fund the health
savings account, which is actually a tax deferred almost like
investment accounts or certain fund to help them offset some of
their healthcare out-of-pocket costs. But the other aspect of it,
which I think is all a bit harder to push for is really for
employers and insurance to just keeping their account patient's
income when they're kind of pushing forward products for a high
deductible plan. So low-income patients should just not have
quite as big of a deductible as the high income earners do. But a
different aspect it's really clinically for clinicians. It's
tough because I think insurance put this forward because they
want to influence patient decisions before they even see the
clinician. But after they decide to come visit clinician, I think
the clinician should be aware of the financial reality for the
patient when making these decisions.


Dr. Andrew Chou:


But it's really hard for me to think about whether or not this is
going to be a good thing for the patient or not. And one of the
biggest concerns for really my colleagues in the department is
really whether or not if we are really talking poor patients out
of certain care by reviewing their financial reality with them
and by through that are we essentially discriminating against
other patients. So that's really a big unknown. I think that's
definitely an area that we should definitely heavily invest in
research because we're just pushing forward with price discussion
for care to encourage price discussion at the clinic here without
really knowing what's going to happen.


Dr. Carolyn Lam:


Yeah. Wow. Alex?


Dr. Alexander Sandhu:


Yeah, I definitely agree with Andrew. I think if we want to make
decisions based on cost and we want patients to make those
decisions and we as clinicians, obviously should be helping them.
We need more transparency around costs, current deductible
status, and that has to be available at the point of care so it
actually can be integrated in decision-making. But I think that's
likely not enough. I mean, even for clinicians, it's hard to
determine how clinically necessary it is to get emergency
evaluation before you see the patient when you get a phone call.
So I think, if it's hard for clinicians with all of our years of
experience, it's hard to understand how we can really expect that
from our patients.


Dr. Alexander Sandhu:


I wholly agree with Andrew that I think a critical step is it's
going to be important to reduce the risk of cost sharing for
low-income patients with a number of potential interventions to
do that, which I think are the real policy implications here. And
then more generally, I think we should make sure that deductibles
aren't discouraging utilization of high value cost effective
intervention. There are currently safeguards in the Affordable
Care Act about that. But I think we need to think about those
closely and probably expand that so we don't see high deductible
health plans leading to lower stat rates or worse diabetes
prevention.


Dr. Carolyn Lam:


Wow. Words of wisdom. I just cannot thank you both enough for
publishing such a beautiful paper, important findings, as well as
just a very lovely editorial in Circulation. Thank you. Learned a
lot. I'm sure the audience did too. Please remember you're
listening to Circulation on the Run. Please tune in again next
week with Greg and I.


Dr. Greg Hundley:


This program is copyright of the American heart association,
2021. The opinions expressed by speakers in this podcast are
their own and not necessarily those of the editors or of the
American heart association. For more visit ahajournals.org.