Novel treatment options for acute hf a multidisciplinary approach (printer friendly)

12/26/13 Novel Treatment Options for Acute HF: A MultidisciplinaryApproach (printer-friendly)
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CME Information
CME Released: 12/23/2013 ; Valid for credit through 12/23/2014
Target Audience
This educational activity is intended for cardiologists, internists, primary care physicians, emergency medicine
physicians, nurse specialists, physician assistants, and pharmacists.
Goal
The goal of this activity is to discuss current and emerging therapies for acute heart failure with an emphasis on a
multidisciplinary approach in order to improve patient outcomes.
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Upon completion of this activity, participants will be able to:
1. Evaluate current and emerging therapeutic opportunities for patients with acute heart failure.
2. Summarize collaborative strategies for multidisciplinary management of acute heart failure that starts in the
emergency department and continues following discharge.
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Author(s)
Mona Fiuzat, PharmD
Assistant Professor of Medicine, Duke University Medical Center, Durham, North Carolina
Disclosure: Mona Fiuzat, PharmD, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Roche
Received grants for clinical research from: Astellas Pharma, Inc.; Gilead Sciences, Inc.; Otsuka Pharmaceutical Co.,
Ltd.; ResMed; Roche
Owns stock, stock options, or bonds from: ARCA Biopharma
Dr Fiuzat does not intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics approved
by the FDA for use in the United States.
Dr Fiuzat does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not
approved by the FDA for use in the United States.
Christopher M. O'Connor, MD
Director, Duke Heart Center; Professor of Medicine, Department of Medicine; Chief, Division of Cardiology and Clinical
Pharmacology, Duke University Medical Center, Durham, North Carolina
Disclosure: Christopher M. O'Connor, MD, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Actelion Pharmaceuticals, Ltd; HeartWare International, Inc.; ResMed; Roche
Received grants for clinical research from: Amgen Inc.; Astellas Pharma, Inc.; GE Healthcare; Gilead Sciences, Inc.;
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.; Otsuka Pharmaceutical Co., Ltd.; Roche
Owns stock, stock options, or bonds from: NeuroTronik; Syncor
Owns patent with: Biscardia, LLC
Dr O’Connor does not intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics
Dr O’Connor does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not
John R. Teerlink, MD

Professor of Medicine, University of California, San Francisco; Director, Heart Failure and Clinical Echocardiography,
San Francisco Veterans Affairs Medical Center, San Francisco, California
Disclosure: John R. Teerlink, MD, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Amgen Inc.; Corthera, Inc.; Cytokinetics; Merck & Co., Inc.; Novartis
Pharmaceuticals Corporation; Trevena, Inc.
Received grants for clinical research from: Amgen Inc.; Corthera, Inc.; Cytokinetics; Merck & Co., Inc.; Novartis
Pharmaceuticals Corporation; Trevena, Inc.
Dr Teerlink does intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics approved
Dr Teerlink does intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved
Robin J. Trupp, PhD, RN, ACNP-BC, CHFN
Clinical Associate, Duke University School of Nursing; Heart Failure Nurse Practitioner, Duke University Hospital
System, Durham, North Carolina
Disclosure: Robin J. Trupp, PhD, RN, ACNP-BC, CHFN, has disclosed no relevant financial relationships.
Dr Trupp does not intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics approved
Dr Trupp does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not
Editor(s)
Joy Marko, MS, APN-C, CCMEP
Scientific Director, Medscape, LLC
Disclosure: Joy Marko, MS, APN-C, CCMEP, has disclosed no relevant financial relationships.
Steering Committee
James L. Januzzi, MD

Associate Professor of Medicine, Harvard Medical School; Roman W. DeSanctis Endowed Clinical Scholar; Director,
Cardiac Intensive Care Unit, Massachusetts General Hospital, Boston, Massachusetts
Disclosure: James L. Januzzi, MD, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Amgen Inc.; Critical Diagnostics; Novartis Pharmaceuticals Corporation;
Roche
Received grants for clinical research from: BG Medicine; Critical Diagnostics; Roche; Thermo Fisher Scientific Inc.
Ileana L. Piña, MD
Professor of Medicine & Epidemiology and Population Health, Albert Einstein College of Medicine; Associate Chief
for Academic Affairs, Montefiore Einstein Center, Bronx, New York
Disclosure: Ileana L. Piña, MD, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: GE Healthcare; Novartis Pharmaceuticals Corporation
Served as a speaker or a member of a speakers bureau for: Otsuka Pharmaceutical Co., Ltd.
John R. Teerlink, MD
As listed above.
Peter S. Pang, MD
Associate Professor, Northwestern University Feinberg School of Medicine; Associate Chief, Department of
Emergency Medicine, Northwestern Memorial Hospital, Chicago, Illinois
Disclosure: Peter S. Pang, MD, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Janssen Pharmaceuticals Products, L.P.; Medtronic, Inc.; Novartis
Pharmaceuticals Corporation; Otsuka Pharmaceutical Co., Ltd.; SpringLeaf Therapeutics; Trevena, Inc.
Received grants for clinical research from: Abbott Laboratories; Alere
William T. Abraham, MD
Professor of Internal Medicine, Physiology, and Cell Biology; Director, Division of Cardiovascular Medicine, Ohio
State University Wexner Medical Center, Columbus, Ohio
Disclosure: William T. Abraham, MD, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Abbott Laboratories; BIOTRONIK; CardioKinetix Inc.; CardioMEMS, Inc.;
CVRx, Inc.; Medtronic, Inc.; Novartis Pharmaceuticals Corporation; St. Jude Medical; Sunshine Heart, Inc.; Zoll
Medical Corporation
CME Reviewer(s)
Nafeez Zawahir, MD
CME Clinical Director, Medscape, LLC
Disclosure: Nafeez Zawahir, MD, has disclosed no relevant financial relationships.
From Medscape Education Cardiology
John R. Teerlink, MD; Christopher O’Connor, MD, FACC, FESC; Mona Fiuzat, PharmD, FACC; Robin J. Trupp, PhD,
Novel Treatment Options for Acute HF: A Multidisciplinary
Approach CME

RN, ACNP-BC
Slide 1.
John R. Teerlink, MD: Hello. I am John Teerlink, Professor of Medicine at University of California San Francisco and
Director of the Heart Failure and Clinical Echocardiography Department at the San Francisco VA Medical Center in
San Francisco, California. I would like to welcome you to this program titled, “Novel Treatment Options for Acute
Heart Failure: A Multidisciplinary Approach”.
This program may include discussion of investigational drugs, biologics, or diagnostics not approved by the FDA for
use in the United States. The goals of this program are to evaluate current and emerging therapeutic opportunities for
patients with acute heart failure and to summarize the collaborative strategies for multidisciplinary management of
acute heart failure that starts in the emergency department and continues through the patient’s care at home.
CME Released: 12/23/2013 ; Valid for credit through 12/23/2014

Slide 2.
Joining me today is Dr Mona Fiuzat, who is an Assistant Professor of Medicine at the Duke University Medical
Center, as well as Dr Christopher O’Connor, Professor of Medicine and Chief of Cardiology, as well as Director of the
Duke Heart Center at Duke University Medical Center, as well as Dr Robin Trupp, who is a Nurse Practitioner in the
Division of Cardiology and Clinical Associate of the School of Nursing at the Duke University Medical Center.
Welcoming them makes me wonder who is actually taking care of patients back at Duke with basically all of you
here with us today. Anyway, welcome.
Christopher O’Connor, MD, FACC, FESC: Thank you, John.
Mona Fiuzat, PharmaD, FACC: Thank you, John.
Robin J. Trupp, PhD, RN, ACNP-BC: Thank you, John.

Slide 3.
Dr Teerlink: We are here to talk about the acute heart failure epidemic. I think all of us recognize that over six million
persons are currently diagnosed with heart failure now and over 670,000 new diagnoses this year. This has resulted in
over 1 million hospitalizations for heart failure, over 3.6 million diagnoses of heart failure in the hospitalized patients,
and an annual cost over 23 billion dollars. It is the most common cause of admission in the elderly in the United
States, and it is clearly a major problem. You all confront these patients. Do you have a sense of who these patients
are and who are you seeing in the clinic? What are the kind of characteristics of these folks that you are seeing and
taking care of? Hunt et.al. Roger VL Jencks

Slide 4.
Dr O’Connor: John, from a heart center standpoint, this is a huge problem, these admissions, these 1 million
admissions. As the Director of the Heart Center, we are very concerned about how can we prevent these admissions,
but more importantly, once they are admitted, how do we get them through the hospital course safely, without
complications, without increasing the length of stay, treated well, so they are not readmitted in 30 days. We are
penalized as a heart center if they are readmitted, and we want the best course for these patients.
Dr Teerlink: Certainly, with the change in these CMS rules now, that is kind of a real pressure on us, and I think one
of the things that you are working at a very specialized heart center. I think one of the things that we have had to
transition a bit from is the view of the heart failure patient at these highly specialized transplant centers to getting an
understanding of who the general patients are with acute heart failure. http://www.cms.gov/
Dr O’Connor: Yes.

Slide 5.
Dr Teerlink: In general, these are patients who are in their mid-70s, half of these patients are women, and they have
multiple multiple comorbidities with an increasing incidence of diabetes in these patients. In your center, where would
you say the mean blood pressure is for your kind of transplant patients coming into the hospital would be? Adams,
Cleland, Fonarow
Dr O’Connor: John, you make a good point. Everybody thinks, well they used to think that advanced heart failure in
these transplant centers was for patients who had these low blood pressures, but as you point out, the most
common type of heart failure has an elevated blood pressure, is congested, and has lots of comorbidities, is elderly,
and it is a real different challenge than we used to think about.
Dr Teerlink: Right. Right. Which makes it sort of an exciting, new area because we have not had the chance to
actually look at it as a specific disease entity. What we are also seeing, I think, is that we are dividing these patients
up into three main groups. You have the patients who have known heart failure, who are coming in with a worsening of
their chronic heart failure episodes. This represents most of the patients or so. The rest of the patients are split
between the patients who are coming in with new-onset heart failure, and then these very advanced heart failure
patients, who places at advanced cardiac centers you specialize in taking care of those types of patients.
As you point out, you talked about the issue with readmission is an issue. Robin, from your experience with these
patients, I mean, clearly they are very sick patients. Do you have a sense of what their kind of post-discharge event
rate is in terms of mortality?

Slide 6.
Dr Trupp: Why I think nationally, we know that it is about 15%, but it is even higher in those that have advanced
heart failure, so it is a big challenge because as you are admitted already, they have a lot of comorbidities and the
whole transition of care form inpatient to outpatient is a huge endeavor that we really never appreciated until now.
Cotter, G.
Dr Teerlink: Right. I think one of the things that has always been interesting to me to discover is if you had a choice,
and this would be a strange choice to be given, of being admitted to the hospital with an acute myocardial infarction,
or an acute heart failure episode that your mortality and chance of being rehospitalized for heart failure are actually
higher if you are admitted with an acute heart failure episode.

Slide 7.
This kind of circles around where we are with, I think, the current goals of heart failure therapy, and Chris, you did a
great job of summarizing them. I think we want to first make people feel better, help them get rapid improvement in
their symptoms, and clinical stabilization, but also try to find ways to improve those longer term outcomes. We
currently are trying to meet those goals and - - Mona, currently, we have current therapies. Can you tell us a bit about
how those therapies are established, and do they help with these kind of current goals?

Slide 8.
Dr Fuizat: Sure. I think that really the cornerstone for acute heart failure right now is the diuretics. We know that here
is a strong story. We know that they work very well when the patients are in the hospital, but really, this therapy has
not changed much in the last, really 15, 20 years from where we started. Really just he symptomatic relief and we do
not have long-term outcome benefits that we can really tie to those types of therapies.

Slide 9.
We also know that from data from registries has shown us that patients are still leaving the hospital congested.
About half of the patients are still having some congestion. About a third of the patients are still having some
significant congestion, and I think that is really leading us back to this high readmission rate. I think with the
challenges, especially in the US, of having shorter hospital stays, we are getting those patients out without really fully
being able to treat them, and so here we are with the 30-day readmission rates post-event rates. (ADHERE)
Dr Trupp: I was just going to add, I think one of the challenges is that with diuretics, the impact on the kidney is so
pronounced that once they start to see a shift in renal function, we kind of back off on the diuretics, which is one
reason they go home probably not fully unloaded, or with normal volume states.
Dr Teerlink: Yes, I think that is something I definitely want to get to a little later, to the pathophysiology of this
congestion and other issues. We have the diuretic therapies. What about other agents that we have to potentially
help patients who are admitted with acute heart failure?
Dr Fiuzat: Right. Again, vasodilators, really not been shown to have long-term benefits, some symptomatic relief in
some patients, not all patients, inotropes, perhaps even dangerous in some patients. We are really left with an unmet
need for treating these patients in the hospital when they come in, and sending them back out where they are going
to end up back in the hospital, so this is really where the needs are, I think, in the pharmacotherapy.
Dr Teerlink: We have these sort of unmet needs. We have a patient population that is growing. Do we have an
understanding of what is the underlying pathophysiology of these acute heart failure patients? Chris, what do you
think?

Slide 10.
Dr O’Connor: It is multifactorial, as you can imagine. We have not really been very good at totally characterizing
these patients. That is maybe part of the challenge of why the therapies, we try to apply them to everyone, and we
have not seen the benefit, but we know they come in congested, we know that there is myocardial injury, we know
there is intense activation of the renin-angiotensin system, inflammatory markers. We know there is significant
endothelial dysfunction. All these things are happening in this state, so we need therapies that can attack at multiple
levels.
We know that there is a hemodynamic compromise of renal function, and that can play a big role. We know there is
congestion of the liver and congestion of the gastrointestinal tract that can play a role in adversely affecting the
outcome of these patients. A lot of organs are involved, and a lot of pathways that are activated when the patient
comes in decompensated.
Dr Teerlink: Certainly, one of the challenges that Mona referred to is the issues of diuretics, and Robin mentioned
also how we back off on diuretics when the patient’s creatinine goes up, we back off on diuretics. We stop their ACE
inhibitors. You are describing a neurohormonal storm in acute heart failure.
Dr O’Connor: That is right. Yes.
Dr Teerlink: We are yet withdrawing these therapies in many patients. I think one of the things that we are learning
from the trials that all of us have been involved in is that this congested state, if anything, requires more active
decongestion. Rather than backing off, many times, we actually need to intensify therapies, but it requires an
understanding of hat underlying pathophysiology.

Slide 11.
Dr O’Connor: Well in the fluid, we are learning. We have seen recent paper come to jacc heart failure, where the fluid
is, perhaps more interstitial than it is intravascular, and so pulling the fluid out is much more complicated than just
being able to use loop diuretics. I think when we have renal compromise, you start going up on the dose of the
diuretics, you start to get more renal compromise, you cannot pull the fluid off. These patients leave, physicians get
frustrated, and then they leave partially congested, and then when the com back in the hospital, they are even sicker
in that readmission. That is where you get that high mortality.
Dr Teerlink: Each of these episodes during these congested states, are there other adverse sequelae to these other
organs? I mean, do you think there is suggestion of end organ damage in these episodes?

Slide 12.
Dr O’Connor: I think there is, as you and I know, we have published on this, this troponin, I think is really very
important whether that is due to myocardial stretch or myocyte loss from other mechanisms. I think there is an
association with perhaps mortality or morbidity down the road with troponin release. A marker of something bad going
on, and we certainly, as you know, the regulatory industry, very concerned about the development of inotropes and
even using troponin as a potential safety marker.
Dr Teerlink: Exactly. Exactly. We are kind of in this situation where we have a big problem. We are learning more
about the pathophysiology, and I think that has opened some real options for defining these areas of unmet need. If I
may, I guess I will take a little prerogative and outline kind of three areas that I am seeing as real unmet needs.
First, I think we need agents that improve that volume removal while maintaining or improving renal function. Chris,
you were one of the co-PIs for one of the most important trials in this arena. Can you tell us a little bit about rolofylline
and how that worked out?

Slide 13.
Dr O’Connor: Sure. Yes. We had high hopes. We had high hopes for many of the drugs that we worked with.
rolofylline was one of them and it was a drug that looked like it helped renal function. Looked like there was also
benefit indirectly on decongestion. It looked like there was also benefit indirectly on decongestion. When we did the
large trial, we really did not see either of those benefits and a big disappointment. (O’connor)
As you know, ultrafiltration as a device therapy we thought would be very effect acute decompensated heart failure.
We did not see any improved outcomes in that study we did in the network.
Dr Teerlink: The ROSE-AHF study. (Chen)
Dr O’Connor: Yes. The ROSE-AHF study. Low-dose nesiritide, dopamine, not showing any benefits in this space,
so a) there is opportunity, b) we have had a lot of failures.
Dr Teerlink: Yes. There remains an unmet need.
Dr O’Connor: Yes.
Dr Teerlink: Then the second area that I think we have seen is drugs that improve cardiac performance without these
adverse effects, so Mona, you did a nice job outlining some of these adverse effects including hypotension,
arrhythmias, and death. A number of agents have come down the pipe along those lines, stresscopin, and the
nitroxyl donors, both of which were in early phase development kind of gone back for pharmacologic reformulation.

Slide 14.
A program that we have been involved with very actively is the Omecamtiv Mecarbil program. It is a selective cardiac
myosin activator. It avoids the intracellular increases in calcium, cyclic AMP, which is directly related to those
adverse effects that you outlined for us. We recently reported the Atomic AHS study. It is a 600-patient study in a
kind of complicated ascending cohort dose design, but I think the main message from that was it seemed like the
highest dose from that group. Cleland JGF
DNA proved dyspnea provided trends to reducing worsening heart failure. It seemed to be well tolerated, however, vis
à vis that earlier discussion, there were these very small troponin leaks that were detected, but really unclear
clinically significance this time. We are proceeding with that in terms of the oral program, the COSMIC-HF trial. That
is an area that remains an unmet need, but I think there may be a glimmer of hope there.
Finally, the third area is these vasodilators with demonstrated clinical benefits that health care providers will actually
use. Mona, what are some of the problems with the currently available vasodilators in terms of their use?
Dr Fuizat: Yes. I think one of the advantages that some of these newer therapies do offer is the fact that they do not
have to be titrated up. Really, you just start the medication and you can continue it through the hospitalization
without a lot of monitoring, without a lot of concern over some of the adverse effects that might happen, the
hypotension of course is a problem. We are not seeing that perhaps with some of the newer agents, so I think those
really offer an advantage.
Dr Teerlink: Thank you. One of the questions will be, is that because we are getting smarter in how we design our
trials?
Dr O’Connor: No.
Dr Teerlink: Is it because the agents are really that much better, and we will have to see?

Dr O’Connor: I think it is probably both. I think it is both.
Slide 15.
Dr Teerlink: I think it is probably a combination of both. We have at least three really interesting agents in this
arena. We have the TRV027, and the BLAST-AHF study that is coming up, and TRV027 is in Phase II, it is an
angiotensin type 1 receptor-biased ligand agonist, and this is the only drug that I am aware of recently that has been
endorsed with a Nobel Prize in Chemistry. A colleague from Duke, Dr Lefkowitz, shared the Nobel Prize for this
discovery of this mechanism. Drs Felker and Dr Pang are going to be the co-PIs for the Phase II international dose
finding study with this really interesting new approach in patients for acute heart failure. Additionally, Chris, you are
also co-PI on a very interesting new program with ularitide. Can you tell us a little bit about that quickly?
Dr O’Connor: Yes. This true AHF study, ularitide is an important study. I think it is a study looking at this agent that
pharmacologically vasodilator has very favorable effects on the renin angiotensin activation, renal hemodynamics. It is
what we think is one of those kind of safe vasodilators. We are conducting a clinical outcomes study looking at in
hospital assessment of worsening heart failure and assessment of the patient in the short-term, but also mortality.
This is a study that is planned at the onset of 2,000 patients, but could be sized up to a larger sample size. Really
looking at the acute decompensated heart failure patient, and getting treatment in early. That is something we have
not emphasized. I know you will, but we think one of the lessons we learned from ASCEND is probably early is going
to be very important in getting good outcomes.

Slide 16.
Dr Teerlink: I think it is an excellent point and carrying on in that, so we now have a completed Phase III study in the
acute heart failure arena with serelaxin, and serelaxin is a recombinant form of the hormone of pregnancy, relaxin.
Relaxin is currently in everybody sitting here right now. It is, in pregnancy, believed to contribute to the adaptations,
both cardiovascularly and renally, to the stresses of pregnancy.
We had preliminary studies that also suggested this is an agent that improves signs and symptoms of heart failure.
Clinical outcomes, and had this tantalizing suggestion of an improvement in mortality based on very small numbers,
but also this kind of global improvement in different types of organ protection.
We performed the RELAX-AHF study. 1,161 patients admitted for heart failure, who came in with normal to elevated
blood pressure, so we are targeting a specific patient population having mild to moderate renal impairment, and were
randomized to 48 hours of the placebo versus serelaxin. What we saw in this was we saw improved symptom relief
as measured by this visual analog scale over a five-day period, with a 19% treatment effect. Very highly significant P-
value, meeting the primary endpoint, showing that it was a positive trial.

Slide 17.
Did not show any improvement in the short-term dyspnea benefit, but in addition, along with this improvement in
dyspnea, we also saw significantly greater improvements in the signs and symptoms of heart failure, the worsening
heart failure episodes itself in hospital, the length of ICU and CCU stays were improved, as well as the overall length
of hospitalization, but there was no impact on the 60-day rehospitalizaion rate. In the context of all these kind of
improvements in clinical signs and symptoms, we showed a 37% reduction in the cardiovascular and all-cause
mortality, associated with improvement in those biomarkers. Teerlink
Getting back to that issue about end-organ protection, and showing that maybe there is some relationship between
calming this initial hormonal storm and providing longer term benefits. We are testing this hypothesis again in
RELAX-AHF2, and this is going to be a 6,000 patient study. We are going on and carrying on with this concept.
It looks like we have some interesting things coming down the pike, but all of these therapies do not do anybody any
good if we do not find a good way to take care of the patients in hospital, so Robin, this is something that you have
done extensive research on and really helped. It is why you are doing the great work you are at Duke right now.
Dr Trupp: Thank you.
Dr Teerlink: Can you tell us a bit about how we can approach multidisciplinary care in acute heart failure?

Slide 18.
Dr Trupp: I think these new therapies give us the chance to redesign both the care of acute heart failure, but how
that care is delivered in the inpatient setting. Our guidelines recommend outpatient multidisciplinary teams, but the
guidelines say little about inpatient care and the use of multidisciplinary teams or even interdisciplinary. I actually
prefer that term because I think it is more about the disciplines working together with each other.
I think it is quite exciting and I guess we need to think about forming these teams, who would be on the teams, and
more importantly, everyone can form the team, and the hospitals, we have teams, we have stroke teams, we have
code teams, we have rapid response teams, they all know their roles, they all work together, but how do you suggest
or think it would be good to get these different disciplines together to begin to look at acute heart failure. I think that
this will have an impact on the patient as they transition to the outpatient. Those are just some ideas.
Dr Teerlink: Who do you think are the providers that we - - who do we need to invite to the discussion, I guess is the
question?
Dr Trupp: Obviously, medicine and nursing, but I think pharmacy is a huge player that is typically under-recognized,
dietary plays a role as well, social services is a big one, case management, some places cardiac rehab. I think really
the sky is the limit. It gives us a chance, as long as these people play a role in assisting and facilitating inpatient and
transitioning to outpatient care.
Dr Fiuzat: It think too, it is important to recognize the emergency room as part of this because we are talking about
really early care as soon as the patient hits the door starting their heart failure therapies. I think that they really
should be incorporated more as part of our teams for heart failure care.
Dr Trupp: It think we need to recognize that because that is the portal of entry for most patients, so we need to work
with them so even maybe consulting in the ED when patients appear, to see who should be admitted and who should
not be.

Dr O’Connor: Exactly.
Dr Trupp: It should be a joint decision and not one person.
Dr Teerlink: This sort of goes to what Chris was saying earlier, that one of the things we have learned is there is a
reason it is called acute heart failure. Right? I mean, we have all these teams set up for myocardial infarctions where
time is myocardium. Do you think we have gotten to the stage now where we can actually consider time is
myocardium in acute heart failure as well?
Dr O’Connor: I think that is exciting. I mean, if these new agents really do what we think they might do, and we can
show by early intervention you reduce troponin release, you reduce injury, you reduce mortality, I mean, that is so
exciting. We have been waiting for this for 30 years.
Dr Teerlink: Shh. We are not supposed to talk about that.
Dr O’Connor: Only 20 for you. Ten for my colleagues over here.
Dr Trupp: Thank you, so much.
Dr Teerlink: It is clear that we need to bring into the conversation the emergency room. This is really a very broad
consensus. What do you think are the factors that contribute to developing that kind of good team and that good
teamwork?
Dr Trupp: I think it is everyone coming together and understanding the purpose. You can put people together, but
that does not form a team, so whoever is on the team has to have a common goal and believe in it. Creativity should
be valued because, obviously, what we have been doing is not working, given our readmission rates. Getting them to
feel valued. There has to be trust and mutual respect. It is no longer hierarchical. It is even playing grounds for
everyone.
Dr O’Connor: No. that does not work.
Dr Trupp: To me, it is just really exciting to think that we are going to have something new to offer as well as a new
way to deliver it.
Dr Teerlink: This does offer, as you point out, and exciting opportunity to kind of start again, and to reaffirm that this
is a very important target that really requires an approach across multiple disciplines, what more interdisciplinary
approaches.
Dr Trupp: Correct.
Dr O’Connor: What I think is interesting about that point, Robin, is that it is bringing together the health systems,
the third party payers, the government because we are getting all on the same page now. We all realize that we can
do better, and there is now incentive from all of these leadership positions to encourage these teams to be built.
Dr Teerlink: Not to get political here, but are you saying 30-day readmission rate may actually have some beneficial
effects in terms of instigating this?
Dr O’Connor: Instigating some. Instigating some good behavior.
Dr Trupp: We have to find some good benefits from it [crosstalk].
Dr Teerlink: How have you implemented this in your hospital? Do you have any pointers for people who are saying, I
believe, but how do I do it?

Dr Fiuzat: Well, I think you are seeing three member of the team here, but I think, really, incorporating someone to
represent each of the disciplines and coming together. Doing research together, working together on patient care, and
extending that to the outpatient care as well, I think, has really worked for us.
Dr Trupp: Yes. I think we have to get rid of silos. I know that is an old euphemism, but it is important. You cannot
have home care doing this, and primary care doing. We all have to begin to talk together because what we have in
common is the patient, and I think Chris’s comment is about systematic system wide approaches are very important.
It can no longer just be my facility, it has to be the patient’s community that is looking at them from that perspective
so we have to look beyond our walls to those providers out in the community.
Dr Teerlink: I will say that I have had the pleasure of working with Mona back in San Francisco. I will point out that I
think another very important aspect is just as you were for us, you really end to have some single strong advocate
who will push this through because as much as people are kind of giving lip service to being for this, it really takes an
individual to kind of spur on the process and gather the people together and coordinate the systems.
One of the things that we have been recommending at the VA health network has been having these specific
champions, and this is also H2H, the Hospital-to-Home initiative, where they are trying to find champions at the
individual hospital who will really lead this process forward.
Dr Trupp: You can have a champion, but it has to be the right champion, who believes in what you are doing, who
has the teamwork skills, the leadership communication, et cetera. Not everyone that is willing or wants to do it
should be the selected individual.
Dr Teerlink: Great. Great. This has been a great conversation and I guess I would like to go through and give
everybody a chance to maybe give their last point and summarize, if you will, something that you think is important or
takeaway message. Robin, let us start with you, and anything - - specific summary you would like to share.
Dr Trupp: Just I think it is an exciting time, and yes, no one likes the 30 day readmission penalties, but if some
good comes out of a necessary evil, which may be a political undertone, but it is what it is. I think that it is going to
be good.
Dr Teerlink: This is supposed to be controversial in discussing.
Dr Trupp: Thank you.
Dr Teerlink: Chris, what would you say?
Dr O’Connor: It is an exciting time because of the therapies, and the opportunities to have therapies that actually
work in acute decompensated heart failure. I think the community of healthcare providers are so excited about these
recent developments.
Dr Teerlink: Mona?
Dr Fiuzat: It is hard to add much to what my colleagues have said, but I agree. I think as a pharmacist it is very
exciting to have new therapeutic opportunities in the hospital and really make sure the patients are getting well
treated before they are leaving and making sure they are not going to be coming back, and of course, reducing side
effects as always. A really exciting thing to have in the armamentarium.
Dr Teerlink: Very good. I think you have used one of the required words for all discussions. We have used the word
armamentarium. I think I will add to that and use the other word that you have to use in these kinds of discussions
and say, this can perhaps represent a paradigm shift. We do actually now have an opportunity to look at acute heart
failure from a new and interesting ways, both in terms of understanding its pathophysiology better, having understood
where we have been in terms of current therapies, and how to bring people together to use these old therapies and

perhaps the new therapies to help our patients with acute heart failure.
Slide 19.
I really thank all of you for a really fantastic discussion. I would like to thank you for participating in this activity. You
may now take the CME post-test by clicking on the Earn CME Credit link. Please also take a moment to complete
the program evaluation that follows. Thank you very much.
This transcript has been edited for style and clarity.
Abbreviations
AE = adverse effect
AHF = acute heart failure
ASCEND HF = A Study Testing the Effectiveness of Nesiritide in Patients With Acute Decompensated Heart Failure
ATOMIC-AHF = Study to Evaluate the Safety and Efficacy of IV Infusion Treatment With Omecamtiv Mecarbil in
Subjects With Left Ventricular Systolic Dysfunction Hospitalized for Acute Heart Failure
BLAST-AHF = A Study to Explore the Efficacy of TRV027 in Patients Hospitalized for Acute Decompensated Heart
Failure
CMS = Centers for Medicare & Medicaid Services
IPPS = inpatient prospective payment system
PROTECT = Placebo-Controlled Randomized Study of the Selective A(1) Adenosine Receptor Antagonist Rolofylline
fr Patients Hospitalized With Acute Heart Failure and Volume Overload to Assess Treatment Effect on Congestion
And Renal Function
RELAX-AHF = Efficacy and Safety of Relaxin for the Treatment of Acute Heart Failure

ROSE-AHF = Renal Optimization Strategies Evaluation in Acute Heart Failure
SBP = systolic blood pressure
TRUE-AHF = Efficacy and Safety of Ularitide for the Treatment of Acute Decompensated Heart Failure
USD = US dollars
References
1. Hunt SA, Abraham WT, Chin MH, et al.; American College of Cardiology Foundation; American Heart
Association. 2009 Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and
Management of Heart Failure in Adults A Report of the American College of Cardiology Foundation/American
Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International
Society for Heart and Lung Transplantation. J Am Coll Cardiol. 2009;53:e1-e90. Abstract
2. Roger VL, Go AS, Lloyd-Jones DM; on behalf of the American Heart Association Statistics Committee and
Stroke Statistics Subcommittee. Heart disease and stroke statistics -- 2011 update: a report from the
American Heart Association. Circulation. 2011;123:e18-e209. Abstract
3. Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare fee-for-service
program. N Engl J Med. 2009; 360:1418-1428. Abstract
4. Centers for Medicare & Medicaid Services. Readmissions Reduction Program.
http://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/AcuteInpatientPPS/Readmissions-
Reduction-Program.html. Accessed December 17, 2014.
5. Adams KF Jr, Fonarow GC, Emerman CL, et al; ADHERE Scientific Advisory Committee and Investigators.
Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design,
and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National
Registry (ADHERE). Am Heart J. 2005;149:209-216. Abstract
6. Cleland JG, Swedberg K, Follath F, et al. The EuroHeart Failure survey programme: a survey on the quality of
care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis. Eur Heart J.
2003;24:442-463. Abstract
7. Cotter G, Milo O, Davison B. The pathophysiology of AHF: new insights from recent studies of novel diuretics
and vascular modulating therapies. World J Cardiovasc Dis. 2013;3:133-145.
8. Nieminen M, Bohm M, Cowie MR, et al . Executive summary of the guidelines on the diagnosis and treatment
of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology. Eur Heart
J. 2005;26:384-416. Abstract
9. Gammage M. Treatment of acute pulmonary edema: diuresis or vasodilatation? Lancet. 1998;351:382-383.
Abstract
10. O'Connor CM, Fiuzat M. Impact of serial troponin release on outcomes in patients with acute heart failure:
analysis from the PROTECT pilot study. Circ Heart Fail. 2011;4:724-732. Abstract
11. Chen HH, AbouEzzeddine OF, Anstrom KJ, et al; for the Heart Failure Clinical Research Network. Circ Heart
Fail. 2013;6:1087-1094. Abstract
12. Cleland JGF, Teerlink JR, Senior R, et al. The effects of the cardiac myosin activator, omecamtiv mecarbil, on
cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2
trial. Lancet. 2011;378:676-683. Abstract
13. Marti C, Cole R, Kalogeropoulos A, Georgiopoulou, Butler J. Medical therapy for acute decompensated heart
failure: what recent clinical trials have taught us about diuretics and vasodilators. Curr Heart Fail Rep.
2012;9:1-7. Abstract
14. National Institutes of Health. Efficacy and safety of relaxin for the treatment of acute heart failure (RELAX-AHF)
. http://clinicaltrials.gov/ct2/show/NCT00520806?term=RELAX-AHF&rank=1. Accessed December 17, 2013.
15. National Institutes of Health. Efficacy and safety of ularitide for the treatment of acute decompensated heart
failure (TRUE-AHF). http://clinicaltrials.gov/ct2/show/NCT01661634?term=true-ahf&rank=1. Accessed

December 17, 2013.
16. National Institutes of Health. Study to evaluate the safety and efficacy of IV infusion treatment with omecamtiv
mecarbil in subjects with left ventricular systolic dysfunction hospitalized for acute heart failure (ATOMIC-
AHF). http://clinicaltrials.gov/ct2/show/NCT01300013?term=atomic+ahf&rank=1 . Accessed December 17,
2013.
17. National Institutes of Health. A study to explore the efficacy of TRV027 in patients hospitalized for acute
decompensated heart failure (BLAST-AHF). http://clinicaltrials.gov/ct2/show/NCT01966601?term=blast-
ahf&rank=1 . Accessed December 12, 2013.
18. Teerlink JR, Cotter G, Davison BA, et al; RELAXin in Acute Heart Failure (RELAX-AHF) Investigators.
Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomized,
placebo-controlled trial. Lancet. 2013;381:29-39. Abstract
Disclaimer
The educational activity presented above may involve simulated case-based scenarios. The patients depicted in these
scenarios are fictitious and no association with any actual patient is intended or should be inferred.
The material presented here does not necessarily reflect the views of Medscape, LLC, or companies that support
educational programming on medscape.org. These materials may discuss therapeutic products that have not been
approved by the US Food and Drug Administration and off-label uses of approved products. A qualified healthcare
professional should be consulted before using any therapeutic product discussed. Readers should verify all
information and data before treating patients or employing any therapies described in this educational activity.
Medscape Education © 2013 Medscape, LLC

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