2014 Scientific Sessions Presidential Address


– [Voiceover] Ladies and gentleman, please welcome the American
Heart Association’s Chief Executive Officer Nancy Brown. (regal music) – Welcome to Chicago, and the American Heart
Association’s scientific sessions. The world’s preeminent
cardiovascular science meeting. Thank you for joining us. We’re honored that so
many esteemed scientists and clinicians have come together to share ideas, expertise, and passion. The people in this room are pushing the boundaries of science to save lives. Truly mankind’s most noble pursuit. On behalf of the American
Heart Association, I thank you for your efforts. As you know, cardiovascular
diseases and stroke, are the world’s leading causes of death but they can be defeated through science. The scientific journey
requires courage and dedication because the destination
cannot be guaranteed. However it can be envisioned, and that vision is critical to the many patients urgently in need of answers. As well as to the many people who would rather not become patients. Our scientific journey to defeat cardiovascular diseases and stroke brings to mind one of my favorite quotes, written some 200 years
ago by William Blake, “what is now proved,
was once only imagined”. Everything you experience
at scientific sessions reflects our shared commitment to the acceleration and advancement of science, toward the proving of
what once was imagined. Over the next four days, you will have the opportunity
to observe, discuss, and share the very latest developments in cardiovascular and stroke research. In all, nearly 20,000 people are attending scientific sessions from
more than 110 countries. A meeting like this would not be possible without the outstanding work of the American Heart Association’s Committee on Scientific Sessions Program. The committee is led by Chairman Dr. Robert Harrington
of Stanford University, and Vice Chairman Dr. Frank
Sellke of Brown University. Will you please join me
in a round of applause for Drs. Harrington, Sellke, and the entire Committee on
Scientific Sessions Program! (audience applause) And now it’s my honor to
introduce Dr. Elliot Antman who will deliver his presidential address. Dr. Antman is a professor of medicine, an associate dean for clinical
and translational research at Harvard Medical School and senior physician in
cardiovascular medicine at the Brigham and Women’s
Hospital in Boston. His leadership is critical to the American Heart Association’s
efforts to achieve our 2020 strategic impact goal of improving the cardiovascular
health of all Americans by 20% and reducing deaths from
cardiovascular diseases and stroke by 20%. Please welcome Dr. Elliot Antman. (regal music) (audience applause) – Good afternoon, and welcome
to Scientific Sessions. On behalf of all of the
American Heart Association’s clinicians, scientists,
lay volunteers and staff, I extend a warm welcome and
offer my thanks for your efforts to understand, prevent, and
treat cardiovascular diseases. We are inspired by your dedication to saving and improving lives. The burden of these diseases
is something we all share. No matter where you live or work. So let’s make the most
of our opportunities to learn from one another
throughout Scientific Sessions. For these next four days,
Chicago is home to the latest in cardiovascular and stroke research, and Chicago is also home to significant cardiovascular history. 90 years ago Chicago
resident, Dr. James B. Herrick joined Dr. Paul Dudley
White and four other pioneering physicians
at Chicago’s Drake Hotel to create the American Heart Association. They started this life saving organization just four miles away from
where you’re sitting right now. Yet, it was world’s away when you consider what we can offer patients today. We now have tools at our disposal that we could barely imagine
only a few years ago. New diagnostic and therapeutic options are being discovered at a
pace unseen in human history. We have an unprecedented opportunity to harness these advances
to save and improve lives. And that is what I would
like to talk to you about. But first, I would like to
share a quick illustration of just how much our tools have changed. This 28 pound box is
the actual ECG machine Paul Dudley White used in
his office decades ago. It was considered state
of the art back then. With the patient lying supine,
and connected to the device, a paper recording of the ECG could be obtained a single lead at a time. Now let’s compare that to how we gather similar information today. Patients simply place their fingertips on these little metal plates, attached to a smartphone case. And record their own
lead one rhythm strip. And instead of lying down
in the doctor’s office, patients can do this from
anywhere in the world. The remote village in
the Dominican Republic shown in this slide, is
just such an example. Few people here have electricity, but ECG tracings were easily
recorded on smartphones, and transmitted to a research team at a U.S. hospital in just a few seconds. Proving the concept
that remote acquisition of ECG’s is possible. How do we best take advantage of the rapidly changing technologies and the seemingly endless array of big data engulfing us? And translate it into
practical applications for the every day care of our
patients around the world. This is a critical question. Heart disease and stroke remain
the leading causes of death in the world taking more than
17 million lives annually. That figure is expected to
surpass 23 million by 2030. Leading cardiology
organizations around the world have set bold goals to deal with the burden of cardiovascular diseases. We all know we can save and improve lives with evidence based treatments
and a focus on prevention. But we also know that
even our very best efforts at implementing them more
widely will not be sufficient. Yet, the solution is within our grasp which is why we are all here. We have come to Chicago to
discuss how scientific research can most rapidly uncover
and implement new therapies. And I believe, that to
accelerate the pace of discovery we need more than just science as usual. We need disruptive innovation. Disruptive innovation
is a concept introduced by Harvard Business School
Professor Clayton Christiansen. It occurs when a new
development has an unexpected and profound impact on
how we live and work. For example, landlines
gave way to cell phones, which gave birth to the smartphone, which is an all in one tool, like a modern day Swiss Army knife for patients and members of
the healthcare community alike. Now here’s an example
from my own practice. A 67 year old patient, was referred to me for
evaluation of palpatations, that were not diagnoses
despite multiple prior, 12 lead ECG’s using the modern version of a machine like Paul Dudley White’s. Ambulatory monitoring
sessions and exercise tests. I prescribed a heart
rhythm monitoring device like the one on the smartphone
I demonstrated a moment ago. He recorded several
tracings at home and work and then he emailed them to me. They showed recurrent episodes
of atrial fibrillation, and so very quickly and
with the help of technology I could formulate a therapeutic plan. My patient is one of about
33 and a half million people around the world affected
by atrial fibrillation, which increases their
stroke risk five fold, and drastically increases
healthcare costs. The number of patients
with atrial fibrillation is expected to grow dramatically because it occurs with greater
prevalence in elderly people a rapidly growing segment
of our population. For over half a century we have
treated atrial fibrillation with the standard oral
anticoagulant Warfarin. The story behind the
development of Warfarin is actually a wonderful illustration
of disruptive innovation. In February 1933, a farmer in Wisconsin noticed his cows developed
a severe and often fatal bleeding problem after
eating sweet clover hay. Looking for answers, one snowy Saturday, he loaded his truck
with hay from his barn, drove about 240 miles
to Madison, Wisconsin and ended up meeting agricultural
biochemist Paul Link. Researchers in Dr. Link’s lab
were already familiar with coumarin, a naturally
occurring hydrocarbon found on the shaft of sweet clover hay. They discovered that
when the hay became wet a fementation reaction fused
two molecules of coumarin and the resulting compound was
the source of the bleeding. They named it dicoumarol, and advised the farmers not to feed his cows any more wet hay. Because the researchers
recognized the potential benefit of drugs to inhibit
the coagulation system, they synthesized various derivatives, including one that proved to be an even more potent anti-coagulant. They named this derivative
after the lab sponsor. The Wisconsin Alumni Research Foundation, and the original substance coumarin, and that’s how we got the name Warfarin. So an effort to save dairy
cows led to an innovative drug with dramatic implications for patients. The effectiveness of this
therapy in preventing stroke in patients with atrial fibrillation was confirmed decades later. However, as you know, there are difficulties in
administering Warfarin. Food and drug interactions, the need for frequent monitoring and dose adjustments to
optimize anti-coagulation. Investigators have long searched
for potential replacements leading to large phase three trials comparing Warfarin to
novel oral anti-coagulants. Including the direct thrombin
antagonist Dabigatran, and the specific factor 10A inhibitors, Rivaroxaban, Apixaban, and Edoxaban. Each of these compounds
blocks the catalytic center of specific proteins in
the coagulation system and went through a lengthy
development process. This starts with the
initial drug discovery phase follower by the pre-clinical phase, and then a series of clinical trials. A typical development
program takes about 15 years with 10,000 compounds originally screened for one that makes it
to regulatory approval, and this all costs about
a billion U.S. dollars. Clearly this is a system in
need of disruptive innovation. I am very familiar with this process because I’ve been a TIMI’s
study group investigator for three decades. Evaluating multiple
new therapeutic agents. I led the team that
studied Edoxaban’s effect on stroke and systemic embolic events. In the Engage AF TIMI 48 study which Dr. Robert Guiliano presented during scientific sessions last year. We published our findings simultaneously in the New England Journal of Medicine. We studied 21,000 patients
and then pooled our data with the results of the three prior trials of novel oral anti-coagulants. In that analysis of 72,000 patients, we found that the new drugs
are similar to Warfarin at preventing ischemic stroke, of great importance to patients. Their use is also associated with a 50% reduction in hemorrhagic stroke. These new drugs have important implications in clinical practice. On the plus side, there’s no need for
therapeutic drug monitoring or frequent dose adjustment, on the other hand these
medications are quite costly. And approved antidotes
are not yet available although they are being developed. And data on some are being
presented at this meeting. Now let’s think about the two pathways, by which oral anti-coagulants
for atrial fibrillation were introduced into clinical medicine. Warfarin came to us by serendipity. The novel oral
anti-coagulants were developed through a targeted and expensive approach. Obviously we can’t rely on either method to find effective new therapies. We need innovative and new approaches that do not require chance
delivery of tainted hay, or billion dollar projects
that span two decades. How might we improve the
discovery and pre-clinical phase of drug development as
well as the clinical trials by which we assess new treatments. It would be useful to focus drug discovery on a systems medicine approach. Here, one synthesizes a
network of information, from genetic, molecular,
and cellular studies. And constructs a model that predicts an individual patient’s response to treatment streamlining further testing. We may then extend the
observations to sub-groups who have a similar profile, and ultimately pool that information, to develop a picture of how
a population of patients might need a range of
customized treatments. An important discovery by
Professor Yamanaka from Japan, represents another
innovation that takes us closer to individualized therapy. He found that human skin fibroblasts can be reprogrammed to
pluri-potent stem cells, known as IPS cells, which
can then differentiate into specific cell types,
including cardiomyocytes. Today, a skin cell can be
harvested from a patient with a given disease phenotype. The resultant IPS cells
can then differentiate into disease specific cardiomyocytes. Drug screens can be
performed on those cells to identify the most effective regimen for patients with specific
disease characteristics. Another intriguing innovation is a novel bioengineering platform, referred to as organs on a chip. Here is a slide of a heart on a chip. Neonatal rat cardiomyocytes are layered on a deformable thin elastic film or chip. When the mycocytes contract
they cause the film to bend. The chip is placed in a
microfluid test chamber where drugs can be infused
and electrical currents can be delivered to stimulate the cells. In a proof of concept experiment, a dosed response curve for Isoproterenol affecting twitch stress is shown. You will hear more about
this concept shortly. From Dr. Donald Ingber. This year’s Conner Lecturer who’s presentation will also
explore the use of IPS derived human cardiomyocytes with a
specific disease phenotype. Now let’s consider some new technologies that can enable clinical research. You can do that by simply
looking around this room. How many of you are
wearing devices that track your heart rate, calories burned, or other physiologic parameters? These sensors communicate
with our smartphones, which 75% of us have within
five feet of us all the time. Is it possible to use these technologies to conduct clinical research
across the biologic continuum from ideal health to disease. This powerful and novel research platform could allow us to evaluate therapies in ways that were not available
a few short years ago. In fact, one important study
is already doing just that. The Health eHeart Study, based out of the University of
California at San Francisco. The plan is to enroll one
million people worldwide to create a distributed
cohort that leverages the internet and mobile technology. Of course, data security
measures are in place to protect individual privacy. Participants can link
their wireless sensors to the research database and allow real time acquisition of physiologic measurements. The software interface is being written to link electronic medical records and correlate a subject’s
data with outcome events. The American Heart Association, has a scientific collaboration
with the Health eHeart Study. We are referring participants
from our programs such as Go Red for Women, and in the future we will be
receiving depersonalized data, tracking their progress in Health eHeart in improving their cardiovascular health. We also plan to conduct randomized trials in this new research environment. I invite you to learn more about the power of embedding randomization
in observational studies. At Dr. Lars Wallentin’s Paul Dudley White International
Lecture, Tuesday at 2:00 PM. And my final example,
is a dramatic example. The Cardiovascular Genome Phenome Study. Also known as CVGPS. Was announced last year at Sessions and is changing the landscape
of clinical research. The study began as a collaboration between the American Heart Association and the academic homes of
the Framingham Heart Study and the Jackson Heart Study and it was inspired by our
longstanding relationship with the National Heart,
Lung, and Blood Institute. CVGPS will provide comprehensive genomic and phenomic information, combining data from
these landmark studies. As well as several other
prominent cohort studies. Many areas of investigation
will now be possible. For example, the study
of phenotypic extremes. This will enable us to understand
the biology of individuals affected at a very young
age, those affected severely, or those who are protected from disease. Investigators will examine
genetic and epigenetic determinants of differences in disease incidence, prevalence,
risk, and prognosis. And the response to
treatments across ethnicities. Investigators in CVGPS
will also provide access to a comprehensive state
of the art biorepository and introduce new ehealth approaches to digital data collection. And now it is my pleasure
to introduce to you the very first CVGPS investigators. They are building the future
on the power of the past. And are following in the footsteps of the American Heart Association’s founders in a bold and novel way. Please join me in applause for these investigators and co-investigators. (audience applause) They are the first eight grant awardees in the Cardiovascular
Genome Phenome Study. Thank you. (audience applause) Just imagine what the
future would look like, if we take advantage of the technologies we’ve discussed today and those being developed as we speak. We could envision the emerging
data from clinical medicine and biomedical research being
fed into a knowledge network. That could offer new
insights into disease. These insights should lead
to novel clinical approaches and serve as a resource
for basic research. The disruptive innovation exemplified by this continuously updated
learning system approach, takes us ever closer to the goal of precision medicine for our patients. Big data, like that which
will be produced in CVGPS, is so omnipresent that
it can be overwhelming, but we need to focus on
what it represents and why. We are collecting it. Big data and the technologies
that help us generate it. Our modern day tools for
finding innovative new ways to save and improve
lives for our patients. We must also use our tools and data to inform our future advocacy
and prevention strategies to create a culture of health where ideal cardiovascular
health is the norm. This is a state that should
be enjoyed by everyone. Why has the American Heart
Association invested in CVGPS? And why are our researchers tackling the challenges of big data? Why are we involved in
the Health eHeart Study? And looking deeper into ways
to harness technology and data? In addition to the many other things the organization does to
save and improve lives. It’s simple. We do these things so people
can live longer healthier lives so they can enjoy more of
life’s precious moments. Moments that truly matter. Here in the languages of the attendees at this meeting is the answer. Life, life is why. Thank you, ladies and gentleman. (audience applause) Thank you very much. Now I’d like to introduce
the Chairman of the Board for the American Heart
Association, Bernie Dennis. (regal music) – Elliot thank you. This is where you have to read the script. The Chairman’s Award honors individual excellence
in volunteer service, that significantly advances the Association’s strategic goals. This year’s recipient
is Dr. Jennifer Mieres. Senior Vice President for
Community and Public Health and Chief Diversity and Inclusion Officer, at North Shore Long Island
Jewish Medical Center. Medical Director of the Center
for Learning and Innovation and Professor of Cardiology
and Population Health, at Hofstra North Shore Long Island Jewish School of Medicine. Dr. Mieres has been a passionate volunteer for the American Heart Association. She’s been a force in fostering diversity and equity in medical education, eliminating disparities
in healthcare delivery, and educating women about
the risks of heart disease. Her efforts are exemplified in her academic and professional activities through educational programs
such as the Red Dress campaign, and her frequent media appearances in print, television, and radio. She has served on many
and multiple initiatives of the American heart Association
for more than 15 years. Dr. Mieres has been recognized
with numerous awards, among them the AHA’s Louis B. Russel Memorial Award in 2011. For addressing healthcare disparities and service to minority or
under served communities. Dr. Mieres was honored with the New York State Governor’s
Award for Excellence for her work in heart disease among women. She plays a prominent role in
her community and nationally and her longstanding commitment to the American Heart Association
is truly inspiring. Please join me now in
welcoming Dr. Mieres. (regal music) (audience applause) – Good afternoon, ladies and gentleman. Bernie, thank you so much
for that kind introduction. I am truly honored to accept this year’s Chairman’s Award and even more delighted to be presented with the
award by our current Chairman Bernie Dennis, with
whom I have the pleasure of serving on the Founder’s Board of the American Heart Association. Thank you to the nominating committee, the entire AHA team, my esteemed colleagues of the
Clinical Cardiology Council or of the dedicated volunteers of the American Heart Association, my friends at NYU Langone, and my North Shore LIJ
Health System family. This past September 11th,
I was driving to work and was actually listening to my daughter’s favorite radio station Z 100. Nearing the end of my commute, the new song by the singer and songwriter Alicia Keyes came on. The song titled We Are Here began to play. Her message was simple in it’s delivery. We are here, we are here for all of us, that’s why we are here. The song dovetailed
perfectly with the emotions I was experiencing that day and I knew immediately that
I wanted to share with you the theme of volunteerism. We are here for all of us,
that’s why we are here. To help each other and make
a difference in the world. Receiving the 2014 Chairman’s Award from the American Heart Association
is an incredible honor and represents a huge milestone for me on a journey that began long before I even considered a career in medicine. I grew up in Trinidad surrounded
by a family who supported and encouraged me to work hard
and believe in my abilities to reach for the stars. My parents were truly global thinkers. They considered themselves
citizens of the world. And that perspective
had a fundamental impact on how I viewed myself, my career, and my potential to effect
change in the world. I grew up with the knowledge
that giving back was essential. That to be an observer was not enough and that knowledge was truly power. My decision at age
seven, to become a doctor stemmed from the loss of my
dearly beloved grandfather who died at 67, from heart disease. My choice of cardiology
as a career was influenced and supported by two
amazing female cardiologists Drs. Alice Jacobs and Dr. Judith Hochman who shared their passion for cardiology and continue to be exemplary role models. My work in women’s heart
health was inspired by two outstanding clinical researchers, Drs. Nanette Winger, and Dr. Leslie Shaw, who are wonderful friends,
colleagues and mentors. Being a volunteer for the
American Heart Association went hand in hand with
the mantra of my parents. Being a good doctor was not good enough. I needed to somehow pay it forward and use my skills and my position to help in the drive
for equity and education in the delivery of healthcare. Why we are here is a question
we each must face every day and for every one of us the
answer will be different. We have limitless potential to make a significant
difference in the world and to accomplish real change. For me it’s empowering
women and their communities to be proactive partners in their health. And to that effect, sort of
elicit a fundamental shift away from the focus on heart disease to a holistic approach of
heart health and wellness and that is one of the
reasons that I am here. The statistics have shown
that educating and empowering women and their communities
about heart health has contributed in part to the decrease in cardiovascular mortality,
but ladies and gentleman, there is still so much work to be done. So that being said, I would now like to ask you all today to join me
in expending of volunteerism. Create that expansion by enlisting your colleagues, friends, and family, to pledge at least one hour each month volunteering in some capacity that advances the mission of the
American Heart Association. Deliver a lecture at your
local community center, Organize a team to walk in a race. There are countless ways to get involved and make a difference. With your support,
action, and participation, we can ensure that we meet the American Heart Association’s 2020 goal of improving the cardiovascular health of all Americans by 20% and reducing death from
cardiovascular diseases and stroke. So once again to borrow a line from the Alicia Keyes song,
that is why we are here. Heartfelt thanks to my
family, my husband Haskel, and daughter Zoe who are
in the audience today and thank you to my many amazing mentors, my colleagues and friends. Thanks to Sue Floor, and Michael Wimer, special shoutout because they
encouraged me to get involved, actively involved with the
American Heart Association over 14 years ago. So I share this award with all of you as you’ve been an integral
part of my success. In closing ladies and gentleman, an important saying from
the great Winston Churchill, resonates with the entire theme of this year’s Scientific Session. We make a living by what we get but we make a life but what we give. Ladies and gentleman, thank
you for your attention. (audience applause) – Congratulations Dr.
Mieres and thank you Bernie. Each year the Association confers the Distinguished Scientists
designation on members who’s innovations have led
to far reaching implications in the field of cardiovascular
and stroke research. Let’s take a look at this video which highlights outstanding
and groundbreaking careers. – [Voiceover] The
American Heart Association and American Stroke Association’s
Distinguished Scientists are a select group who’s
innovations have led to far reaching implications in the field of cardiovascular
and stroke research. This year we honor six forward thinkers and their seminal
contributions to their fields. The 2014 Distinguished
Scientists honorees are Gerald W. Dorn II, MD, FAHA. Dr. Dorn is internationally
recognized for his contributions to defining the molecular
signaling pathways that govern the development of cardiac hypertrophy and programmed cell
death with special focus on G-protein coupled
receptor signaling cascades. The Dorn Laboratory
investigates multiple aspects of genetic reprogramming
and heart failure. With research efforts
in cardiac signaling, non coding RNA’s and most recently mitochondrial mechanisms of heart disease. His recent work is among the
first to define the molecular regulation and dynamic
alterations in mitochondrial homeostasis in health and disease states using a large array of animal
models from fly to mouse. In addition, he led a
series of clinical genetics and functional genomics investigations that revealed for the first
time a genetic signature for common human heart failure. Dr. Dorn’s research spans over 30 years of outstanding accomplishment. Barabara J. Drew, PhD, RN, FAHA. Dr. Drew’s program of research
has influenced standards for accurate electrocardiographic
monitoring of patients at risk for arrythmias,
myocardial ischemia, and QT interval prolongation. Her research represents a
major breakthrough in knowledge development and has resulted
in significant changes in clinical practice with
recognizeable benefit to the public. In a highly collaborative
manner Dr. Drew made major breakthroughs in cell phone
transmitted electrocardiograms for patients who call 911 for chest pain, and an ST segment ischemia
monitoring in patients admitted to coronary intensive care units. Her studies have informed
the development of arrythmia monitoring algorithms
to more accurately detect arrythmias and reduce false alarms that result in clinical alarm fatigue. Dr. Drew founded the ECG
Monitoring Research Laboratory in the School of Nursing at UCSF. Her signature courses are in
clinical electrocardiography which she has taught for
more than three decades to medical students, residents, and graduate nursing students. Her lectures are known
for their relevance to clinical practice and for
her underwater photography. Charles T Esmon, PhD, FAHA. Dr. Esmon’s research
examines the mechanisms that control the blood clotting process and how they contribute to human disease. He and his collaborators
were the first to show that activated protein C could prevent and treat a normally lethal
septic response in animals. With collaborator White Owen, they were the first to
identify thrombomodulin, and subsequent work from
their laboratories led to the isolation and characterization
of thrombomodulin. Dr. Esmon identified,
cloned, and characterized the endothelial cell protein C receptor that serves as a co-factor for thrombomodulin mediated
protein C activation. His laboratory has since
identified histones as major mediators of sepsis and activated protein C
as a critical regulator of the septic response. Dr. Esmon holds 20 patents, several of which have been
licensed and are in development by U.S. companies for diagnosis and treatment of vascular
diseases involving blood clots. Bruce Furie, MD, FAHA. Dr. Furie is a leader in the field of thrombosis and hemostasis
with over 300 publications. His research focuses on an
interdisciplinary approach to the study of blood coagulation, platelet function, and vascular biology. Among his many scientific accomplishments is the major discovery
of P selectin in 1984. This receptor mediates
binding of leukocytes to both platelets and endothelial cells. In 1992 he reported in Nature that P selectin plays a role in thrombosis. More recently Dr. Furie
has developed an in vivo imaging system to visualize clot formation in the blood vessels of mice in real time. This work has provided new insights into the mechanism of clot formation. With improved spatial resolution
of platelet packing regions and the recognition of the
requirement of extracellular thiol isomerases including protein disulphide isomerase
in thrombos formation. William R. Hiatt, MD, FAHA. Dr. Hiatt’s clinical research career has focused on peripheral
artery disease, PAD, and understanding the
mechanisms underlying the disease pathophysiology as a basis for developing new treatments. He has made important contributions to understanding the mechanisms
of intermittent claudication and the exercise impairment
characteristic of PAD. Through a series of
clinical investigations his group along with
collaborators from UCLA characterized mitochondrial dysfunction in the skeletal muscle of PAD patients, altering the existing paradigm of the pathophysiology of PAD. Dr. Hiatt’s team developed
the key functional measures in the field and demonstrated
the positive effects of exercise training
in PAD leading directly to clinical practice guidelines. Since 2003 Dr Hiatt has
provided critical service to FDA Advisory Committees including the Cardiovascular and Renal
Drugs Advisory Committee and currently the Endocrinologic and Metabolic
Drugs Advisory Committee. Over the last two decades
he has played a leading role in clinical trials on PAD and on the regulation of cardiovascular therapeutics by the FDA. Mark A. Hlatky, MD, FAHA. Dr. Hlakty is a cardiologist
with major research interests in clinical trials,
clinical research methods, outcomes research, and comparative
effectiveness research. Dr. Hlatky has participated
in many large multi-center randomized clinical
trials including studies of coronary revascularization, treatment of acute myocardial infarction, hormone therapy to prevent
cardiovascular disease, and management of life threatening
ventricular arrythmias. He pioneered the collection of data on economic and quality of life outcomes as part of randomized trials, which has become a standard
tool in outcomes research. He has also conducted large
outcomes research studies of coronary revascularization,
sudden cardiac death, implantable cardioverter defibrillators, heart failure, and
coronary artery disease. He developed decision models
to assess the effectiveness and cost effectiveness of a wide variety of clinical strategies, including prevention of
sudden cardiac death, use of testing to guide preventive treatment of heart disease, use of genetic testing in
cardiovascular medicine, and management of cardiac risk
during non-cardiac surgery. – Hello, I’m Rose Marie Robertson, Chief Science and Medical Officer of the American Heart Association. Scientists like these,
at the cutting edge of cardiovascular disease and stroke research are the driving force
behind our mission to build healthier lives free of
cardiovascular diseases and stroke. I’d like to personally
congratulate these scientists as they receive the
American Heart Association and American Stroke Association’s
highest scientific award. If you’d like to learn more about the American Heart Association’s
Distinguished Scientists Award, just go to myamericanheart.org (upbeat music) (audience applause) – Now we’d like to pay
tribute to cherished friends of the American Heart
Association who have passed away. Each person we are remembering made a significant contribution to our goal of fighting cardiovascular
diseases and stroke, and the impact of their work will live on. As their names appear, please
pause for a moment of silence. (majestic music) Thank you. The Basic Research Prize
recognizes researchers who make significant contributions to the advancement of cardiovascular science and who head outstanding
research laboratories. This years honor goes to Dr. Andre Terzic, Director of Regenerative Medicine and Professor of Cardiovascular Diseases, Medicine, and Pharmacology
at the Mayo Clinic. Trained as a physician scientist, Dr. Terzic is recognized
nationally and internationally for his contributions to cardiovascular medicine and science. He has pioneered multiple cardioprotective and cardioregenerative modalities. In the more than 450
publications he has authored Dr. Terzic has advanced
diagnostic and therapeutic strategies for heart failure. His work includes discovery
of genes for dilated cardiomyopathy and atrial fibrillation. Dr. Terzic holds diverse patents and his teams work on the
treatment of cardiac diseases led to a biotechnology company launch through initial public offering. Dr. Terzic’s contributions include more than two decades in mentoring. He has trained more than
50 physician scientists, fellows, and students
who have received dozens of prestigious awards and grants. It is now my privelege to
introduce the recipient of this year’s Basic Research
Prize, Dr. Andre Terzic. (regal music) – It is an immense honor to accept the 2014 Basic Research Prize. I take this opportunity to
extend my deepest thanks to the American Heart Association, to the Functional Genomics and
Translational Biology Councils, to colleagues that have nominated me. And indeed to the whole
team at the Mayo Clinic that has worked closely with
me over the last two decades. I’m humbled by the award. It reflects a rich history
of science in medicine and an enduring paradigm in the advancing the frontiers of healthcare. As we look into the future, the pandemic of cardiovascular disease will mandate new solution. Indeed, disruptive innovations to address the unmet needs of patients and populations across the globe. The unison of fundamental discovery with clinical translation
and population application will provide a guiding principle for the generations to come. Thank you. (audience applause) – Thank you Dr. Terzic. The Clinical Research Prize
recognizes an individual who is making outstanding contributions to the advancement of
cardiovascular science and who heads a distinguished
clinical research laboratory. The recipient of this year’s
award is Dr. Judith Hochman of the New York University
School of Medicine. She is Director of the school’s Cardiovascular Clinical Research Center and co-Director of it’s Clinical Translational Science Institute. She is also Clinical Chief of
the Division of Cardiology. Dr. Hochman is an internationally
recognized pioneer and investigator in clinical
cardiovascular research. Her work has led to guidelines and practice changing findings in the field of acute coronary syndromes. Dr. Hochman has been the
driving force for multiple NIH sponsored trials examining critical clinically relevant patient
management questions. She organized and spearheaded
the landmark shock trial that studied the optimal
treatment strategy in patients with cardiogenic shock due to acute myocardial infarction. Another achievement was the
oat trial to study whether occluded arteries should be opened in patients who have
recently suffered an MI. Currently, she is the study Chair for yet another NIH sponsored study. The ischemia trial. The largest and most comprehensive, regarding the optimal
management of patients with multi-vessel coronary artery disease. The findings will have a profound impact on how these patients are managed. Dr. Hochman has been an
exceptional investigator and has made an outstanding contribution to the advancement of
cardiovascular science. It is my honor to introduce the recipient of the 2014 Clinical Research Prize. Dr. Judith Hochman. (regal music) – Thank you Elliot, and thank you for all you
have done for the AHA, and for being such a wonderful colleague through so many years. I would also like to thank
the nominating committee and the Council on Clinical Cardiology. I am deeply honored to receive this prize. Isaac Newtown observed, “If I have seen further, it is by standing on
the shoulder of giants”. If I have achieved anything, it is because I have worked hand in hand with hundreds of co-investigators that have played important roles in the challenging trials
we’ve tackled together. Clinical research is truly a team sport. I’m grateful for my
terrific colleagues at NYU, and elsewhere. Early in my career, there were giants who
were wonderful mentors and role models, Eugene Braunwald, Mike Weisfeld, and Bernadine Healy. Before my mentors,
there were other giants, my parents who raised me
with a love of learning. And now I find inspiration
in my sons and grandson. And my many mentees, too numerous to name, who’s successes are a
great source of pride, including Jennifer Meires who just received the Chairman’s Award. Most importantly I want to acknowledge and thank my husband
Richard Fukes is here today, who serves the dual role of remarkable life partner
and trusted colleague. It’s been a privilege to
be among the leadership of many trials that have
proven the efficacy of new acute coronary syndrome therapies but equally important in my
career was my involvement in several trials with
unexpected findings of harm from therapies widely used in practice, with profound implications
for patient care. HERS NWHI trials that demonstrated
harm from hormone therapy and CAST which showed harm
from anti-arrhythmics. Before these trials there were huge biases towards using these therapies that made many physicians question the ethics of randomization, and made enrollment challenging. But the results changed clinical practice. I have Chaired trials like Shaw, with colleagues who’s names
you see on this slide, that proved the efficacy of an
invasive management strategy in oat which failed to show a benefit for an invasive strategy. These disparate results
point to the importance of continuing to evaluate clinical practice critically with randomized trials. Despite widely held pre-existing opinions as to which therapies work. I would like to conclude
my acceptance with a plea especially to the next generation, to continue to test medical dogma with traditional randomized trials despite all the difficulties
in carrying them out, and with newer models for clinical trials that maximize engagement of
practitioners and patients. Thank you. (audience applause) – Thank you Dr. Hochman. The Population Research Prize recognizes an individual
who is making outstanding contributions to the advancement
of cardiovascular science and who heads a major
population research laboratory. This year’s recipient is
Dr. Vasan Ramachandran, Chief of the Section of
Epidemiology and Preventive Medicine in the Department of Medicine at the Boston University School of Medicine. Dr. Ramachandran has an
international reputation for his work in
cardiovascular epidemiology, and is known for his stellar
research productivity. He has published cutting edge research in more than 560 peer reviewed articles in high impact journals. Dr. Ramachandran’s research
has made fundamental contributions to the fields of systemic markers of
cardiovascular disease. Echocardiography and
epidemiology research, heart failure risk
factors in hypertension. He has an original research mind and seizes on opportunities
to translate cutting edge basic science into the
epidemiologic context. All while adhering to the highest ethical principles in his research, and in the treatment
of those he supervises. Considered one of the leading
cardiovascular epidemiologists Dr. Ramachandran is a
revered mentor and teacher. His commitment to mentoring
has been recognized by the NIH which has twice awarded him a
prestigious mentoring grant. While developing a distinguished research reputation in the United States, he has not forgotten his country of origin on health issues in the developing world. He continues to collaborate, mentor, and conduct and publish research in India. Please join me in welcoming
the recipient of this year’s Populaton Research Prize,
Dr. Vasan Ramachandran. (audience applause) (celebratory music) – Dear colleagues, I stand before you humbled and honored. I offer my sincerest gratitude to the American Heart Association
for this recognition. Foremost I salute the three generations of Framingham study participants who have gifted their time, blood, and data altruistically to humanity
for over six decades. A big shout out to my mentors
and mentees and colleagues. You made this possible. Thank you. Upon learning of this award. I paused. And I wondered, boy am I really that old? And the thought had just begun. Inspired, let me share a
dream we still need to create. A Framingham Heart Study Without Walls. With two additional virtual floors. One for budding investigators
worldwide freely access all our data and make new
scientific discoveries. And another floor with
international experts and national scientists who will guide us maintain a state of art 21st century public health laboratory without walls. Wow, on to another dream. 150 years ago, John Snow
stopped the Cholera epidemic by removing the handle of a pump. 50 years ago Bill Kinell
identified the key risk factors for heart disease. Today, we live with a chilling high lifetime risk of these same risk factors. Together we all have to shut off this tap so that a child who’s born in
2020 lives a different future. As we travel to realize these dreams, I’ll end on a personal note, two decades ago my daughter and I stopped by the Heart
Study on a snowy morning. It was my fellowship interview. Wading through knee deep
snow the three year old gave her trinkets a shake and asked
if there was some mistake. Thus began, a life
refining family adventure which continues to date. Today, she’s a medical student passionate about public health. I want to acknowledge my wife
and partner in this journey for her patience,
understanding, support, and love as we walk hand in hand the
miles to go before we sleep. Thank you. (audience applause) – Congratulations Dr. Ramachandran. This next award is the Eugene Braunwald Academic
Mentorship Award. This award honors a special individual who for at least 20 years has successfully mentored promising young academicians. Every year when I come to sessions and I see the presentation of this award, it resonates very deeply with me. Not just because Dr. Braunwald
is a legend in cardiology, who’s published more than
1,000 original articles, conducted important research,
edited a key textbook, and mentored so many of
my respected colleagues. This award always hits home for me, because I am among those
fortunate enough to be one of his mentees during
the early phases of my career and remain so even to this day. I would like to thank
Dr. Braunwald for all that he has done for me and for
all of you in this audience. By inviting him to join
me in the presentation of the Academic Mentorship Award. Ladies and gentleman please welcome my mentor and friend,
Dr. Eugene Braunwald. (audience applause) (celebratory music) – Thank you Elliot. It’s a real pleasure and
an honor to join you today for the presentation of this award. The greatest gift that
can come to a mentor is to learn from his former mentees, and there is no one that has
taught me more than you have. This year’s award goes to a hero of mine, Dr. Jeremiah Stamler, Professor Emeritus at Northwestern University. Dr. Stamler is one of the founding fathers of cardiovascular
epidemiology and prevention. Over the 50 plus years he has directed, we’ve mentored and guided the
careers of thousands of people through hands on mentoring,
scientific acumen, and leadership by example. Indirectly, he has had an impact through the founding and leadership, of the famous 10 days international
seminar and Tehel Corps. Which has trained thousands of leading clinicians and scientists. Dr. Stamler helped to mold the
careers of numerous mentees who hold prominent
positions in the fields of epidemiology and prevention
around the world. The trainees who learned
under his leadership are too numerous to count. Dr. Stamler is quite simply
a giant in his field. This year he celebrates his 95th birthday here in his hometown of Chicago as we celebrate his unparalleled
mentoring accomplishments, and contributions to the
American Heart Association. It is therefore my pleasure
and my very special honor to present the 2014
Academic Mentorship Award to Dr. Jeremiah Stamler. (audience applause) (regal music) – Ladies and gentleman,
colleagues and friends, it’s a pleasure to be here. Thanks to the American Heart
Association for this award. I am of course deeply appreciative. It’s especially gratifying
for me to receive it directly from Dr. Eugene
Braunwald himself. A colleague of great distinction
of my own generation. Dr. Braunwald and I are both
honorary professors in Italy. He at the University of Solerno, I at the University of Naples. My career as an
investigator began in 1948, with a research fellowship. My mentor was Dr. Louis Nelson Katz, Director of Cardiovascular
Research Institute, Michael Reeves Hospital
right near here in Chicago. 1948 was the year that
the cardiologist leading the American Heart Association, Louis Katz and Paul Dudley White, proudly among them as you already heard, worked hard and long to transform AHA from a professional organization, to a voluntary health agency. It was my privilege at
intervals to sit at the feet of Louis Katz, Paul Dudley White,
Howard Sprague and others as they pursued this task. I was impressed by the
programmatic thrust. Professional education,
public service, research, I recall the detailed discussions on the importance of
training young professionals and the elaborate efforts for
training that were undertaken. The funding of one and
two year fellowships, the five year established
investigatorships, et cetera. I personally benefited as an AHA five year established investigator. Over the decades since
1948 AHA has consistently supported training
thereby playing a key role in creating troops
essential for the effort to prevent and control the
cardiovascular disease epidemic. Importantly that support
has included sponsoring and under riding annual U.S. 10 day seminars on CVD
epidemiology and prevention. A unique training effort
involving 25 or more younger investigators and other physicians and other health scientists every year. AHA’s contribution to mentorship have not only been national. The World Cardiology
Congress in New Delhi in 1966 forceful AHA initiative
led to the creation of several international councils. And so Keyes and I were
drafted to organize the Council on Epidemiology
and Prevention. One major consequence was the annual 10 day international teaching seminar on CVD epidemiology and prevention, launched in 1968, ongoing since. The late Rose Stamler and I
participated as core faculty for 24 years along with
the late Dick Remmington and the late Jeffrey Rose. Darwin Labarthe continues
to play a key role in both the national and
international 10 day seminars. The experience of the
international seminars served me well in my
mentorship efforts at our Northwestern University
Department of Preventive Medicine. So to the AHA much thanks
for all of the above for all that AHA has
done to foster training, all that AHA has contributed
to my career development, and for this mentorship award. Thank you. (audience applause) (regal music) – Thank you Dr. Stamler. The Research Achievement
Award recognizes a lifetime of distinguished scientific advancement in cardiovascular
research and or teaching. It is my pleasure to
recognize Dr. Shaun Coughlin, Director of the Cardiovascular
Research Institute, and Distinguished Professor
in Cardiovascular Biology and Medicine at the
University of California, at San Francisco. Dr. Coughlin is a world
leader in platelet biology, and has been Director of the Cardiovascular Research
Institute since 1997. Among his scores of published
original research papers is his most famous work on the cloning of the thrombin receptor. This work identified a new family of protease activated receptors. Dr. Coughlin translated his
basic science discoveries involving the par family of receptors into a proposal that led
to a new anti platelet drug that promises to reduce death
from cardiovascular disease. The par one inhibitor called Vorapaxar was recommended for FDA
approval on January 15th, 2014. For his discoveries,
his seminal publications in the highest tier journals, and his proposal that resulted
in a promising new drug, Dr. Coughlin is most
deserving of this award. It is now my distinct honor to
introduce the 2014 recipient of the Research Achievement
Award, Dr. Shaun Coughlin. (regal music) – Thank you very much, Dr. Antman, and thanks to the American
Heart Association. We all stand on each other’s
shoulders in this business and my laboratory is no exception. I’m delighted to accept the
American heart Association’s Research Achievement Award in recognition of the achievements of many individuals in my laboratory and outside of it. And as a celebration of our field. I’ll use my two minutes to draw
two lessons from this story. First for leaders who
influence funding policies, this story provides a nice example of how single investigator initiated
AHA and NIH funded research aimed at understanding of
basic biological mechanism can lead to a new medicine. When I entered this field
platelets were known to contribute to the thrombi that cause myocardial infarction and stroke, and thrombin was known to be a potent activator of platelets ex vivo. But whether thrombin
induced platelet activation was an important contributor
to cardiovascular events was unknown. Answering this question required first answering a more basic question. How does a protease like thrombin talk directly to a cell like a platelet to trigger a biological response. Dicovery and characterization
of protease activated receptor one or par one
provided an elegant answer. Par one is in essence a peptide receptor that carries it’s own ligand, which stays silent until
cleavage by thrombin unmasks it such that it combines the receptor and trigger receptor activation. Subsequent work confirmed
that par one and the related receptor par four mediate
platelet activation by thrombin and pointed to par one antagonism as a possible approach to
anti-thrombotic therapy. Recent clinical trials
of the par one antagonist for Apaxar indeed provide evidence that par one dependent platelet activation contributes to thrombosis
and hemostasis in humans. With Vorapax are now approved
for secondary prevention of cardiovascular events
in selected patients. Understanding the roles
of pars beyond platelets, remains an exciting area of research. Second lesson for the young people here, is I can’t imagine a more
interesting or rewarding career, than cardiovascular research. I’m been privileged to work
on fascinating problems. I experience the joy of new understanding, and thanks to many in
academia and industry, see discovery benefit the patients. Not to mention the pleasure
of watching one’s trainees go on to make their own contributions. The opportunities to understand biology and alter disease available today dwarf those of 20 years ago. And there’s plenty of great
work for those interested in covering the language of biology and those in translating what we learn. So if you’re able, jump in with both feet. Thank you again for this recognition. (audience applause) – Thank you Dr. Coughlin. Each year the Lewis A.
Conner Memorial Lecture is presented by a distinguished
scholar, researcher, or national leader in the health field. The lecture honors the
memory of Dr. Conner, one of the founders of the
American Heart Association and it’s first president in 1924. We are privileged today to
have as our Conner lecturer Dr. Donald Elliot Ingber. The Judah Falkman Professor
of Vascular Biology at the Children’s Hospital Boston and Professor of Bioengineering at the Harvard School of Engineering
and Applied Sciences. Dr. Ingber received his MD
and PhD from Yale University. He is the founding director
of the WYSS Institute for Biologically inspired
Engineering at Harvard University. Dr. Ingber’s most recent innovation is organs on a chip technology. The technology builds tiny
complex three dimensional models of living human organs as a way to replace animal based methods for testing drugs and establishing human disease models. Dr. Ingber has authored more than 375 publications and 85 patents. He has numerous honors
including the Holst Medal, The Pritzker Award from the
Biomedical Engineering Society, the Rous-Wipple Award from the American Society for
Investigative Pathology. The lifetime achievement award from the Society of In Vitro Biology. And the Department of Defense
Breast Cancer Innovator Award. He serves on the Board of Directors of the National Space Biomedical
Research Institute and is a member of both the American Institute for Medical
and Biological Engineering, and the Institute of Medicine
of the National Academies. Today he is presenting
biologically inspired engineering from human organs on chips to
nano therapeutic clot busters. Please join me in welcoming
Dr. Donald Ingber. (regal music) – Thank you Elliot, and
thank you all so much for this wonderful honor. What I liked to do is pick up on the theme of disruptive innovation
that Elliot introduced and tell you a little bit
about what we’ve been doing at the WYSS Institute which as
you can see from our logo has been in the process of self assembling over the last five years or so. We’re actually going up. We’re now up to about 375 full time staff so we’re no longer a little start up. I think most of you know that
medicine has been transformed over the last 50 years by
applying engineering principles to solve medical problems
and that gave us stints and artificial hearts and
pacemakers and so forth. But what we feel is that we’ve
actually uncovered enough about how nature builds,
controls, and manufactures that we’re at a point where
we could actually leverage biological principles to develop
new engineering innovations and this is what we call
biologically inspired engineering. Now we were kickstarted with the largest single gift in Harvard’s history of 125 million dollars. So we had a chance to tackle big problems and the biggest one I could
see as you heard from Elliot is that the drug
development model is broken. You can talk to heads of pharma companies and you’ll often hear the big
challenge is to fail quickly and cheaply which is to me not really a vision for the future. And why is it broken? Well it can cost over two million dollars to test a single drug. Cells cultured in dishes don’t function anything like in our bodies. Animal studies are expensive
and take a long time. It’s ethically a big issue
especially in Europe already where enumerable animal lives are lost, and then more often than not the results don’t predict what happens in the clinic and as a result the number of medicines that have been approved
per dollar invested has just consistently decreased,
as you see in that graph, over the past 50 or 60 years. So many groups set out to come
up with better lab models. We at the WYSS Institute
started a whole platform to focus on this which I call
biomimetic microsystems in my head, and the idea
is to engineer microchips containing living human cells
that reconstitute organ level functions, not cell, not tissue,
but organ level functions for drug screening, diagnostic, and therapeutic applications,
to replace animal testing. Now why microchips? Well microchip manufacturing
offers control over features at the same size scale that
living cells and tissues live at and this is something that I’ve
worked with George Whitesize starting 20 years ago on, both in terms of controlling
cell adhesion and function but also in controlling fluid flow through creating microfluidics which were basically
microvascular networks that allow you to control
flow at that scale. So we made a major breakthrough in 2010, that we call a Human
Breathing Lung-on-a-Chip. And the idea was to model
the major functional unit of the lung, the airsac or the
alveoli capillary interface. And what I’m going to show you
here is that at the top right these are made out of
optically clear silicon rubber. They’re about the size of
a computer memory stick but as you’ll see in this video if you cut that in half you’ll see that it has three channels. The middle one’s about a
millimeter in diameter. The middle one has a horizontal
membrane that’s porous, made of the same silicon rubber palmer coated with extra cellular matrix. We then take human
alveoli epithelial cells and culture them at the top. Human pulmonary capillary
endothelial cells when we culture them on the bottom. We just recreated the
alveoli capillary interface The trick is that we apply suction through those side channels and because it’s flexible
it rhythmically extends and relaxes and undergoes
the same breathing motions that the alveolis cells
experience when all of us are breathing in and out right now. We then can flow air over the
top to create an air liquid interface and we can flow
medium or even blood if you like through the bottom to
mimic the bloodstream and the vascular channel. Now if this works, then we
would expect that we can model a complex organ level
responses, for example, inflammation, or infection. So if we were to have bacteria for example and no air space the
cells would get inflamed and the endothelial
cells would be activated express adhesion receptors like icams, select and immune cells should stick, roll and then diopedese
through where they would then engulf the bacteria
on the other side. What I’m now going to show
you is high resolution real time imaging. Those are human white blood cells. Fresh cells, I know they’re fresh because we took them out of my post doc. We labeled them and you don’t see the epithelial or endothelial cells. Under control conditions
it’s a quiescent endothelium, they just flow by. But if you put bacteria or
cytokines on the opposite sides they get activated and
the immune cells stick. And now we can go to
high resolution imaging, just like in a culture dish, and you can just see one cell come in. These pentagons are holes in the membrane. There’s one white blood cell about here it finds a space
between two endothelial cells. It goes through finds the hole, wiggles it’s rear end through that hole, in the matrix in the membrane, and then it comes out on the other side as you can see now by phase. And now I’m going to show
you the white blood cells in red and the bacteria
in GFP labeled green, and you will see that the white
cells engulf those bacteria. You’ve just watched the entire
human inflammatory response in realtime in high resolution
in this little rubber chip. That is an organ on a chip. Now we then tested more complex responses. We used nanoparticulates, that
mimic airborne particulates and smog that could exacerbate
asthma or arrythmias, and we could measure injury by measuring reactive oxygen species
with microfluorimetry, and very interestingly
is that what we found is that you had either breathing alone or these particles alone,
there was no response. But if you had physiological breathing on these nanoparticles
you saw ROS production and as you can see at the rate you get an inflammatory response as well. Furthermore we can measure
bioavailability and absorption so if we gave the
nanoparticles to the airspace what you see is that we got
an eight to ten fold increase in particles that went
across two cell layers and into the vascular
system and were absorbed. There was no change in
fluorescent Dextran Albumin. This seems to be a specific response but only in the presence
of breathing motions. Without breathing very little got across. Now this is not mimicking physiology, this is a prediction. So we actually developed an ex vivo ventilation profusion model on the mouse and we found exactly the same thing. And so this was why there was
a full article in Science. Now we shared this to a lot
of pharmaceutical companies and they were impressed but what they said was what we really need are disease models so we developed a model of pulmonary
edema fluid on the lungs and we used interleukin two which is an FDA approved cancer drug, but it’s major dose limiting side effect is pulmonary vascular permeability. We introduced it at the same dose, IV, through the vascular channel, and as you see in the top right, when you look from above, and there’s air in the channel, you can barely see the cells. But when we give this drug
in the vascular channel we see a miniscus filling the air channel that over three to four days
completely fills it with fluid and that is the same exact
time course with the same dose that produces pulmonary edema in humans. We could quantitate this
by using fluorescent inulin like kidney physiologists do and you could see at the top right that again you can see the shift of fluid with breathing motions but
without breathing motion it was very little effect. So once again we went back
in viva and we confirmed that this is physiologically
relevant also. I will say a quick side note, when we submitted this paper
to Science Translation Medicine one reviewer said this
should not be published. It’s oversimplified, there
were no immune cells. The other reviewer said this is amazing, you don’t need immune
cells for pulmonary edema induced by interleukin
two and luckily it got in. And so you could actually learn things because these are synthetic
systems that you build up. If you don’t get a response you add back more cells more complexity. Now I’ve worked for 30
years in Mechanobiology and one of the fastest
mechanotransduction mechanisms we found is through an ion
channel called TRIP V4. And because we saw
mechanics was so important and I knew Glaxo Smith Kline
was working on inhibitors we collaborated and they
gave us an inhibitor and we tested it and
we completely prevented pulmonary edema in this human in vitro model of vascular permeability. In parallel they took this drug, tested it in dogs and rabbits with cardiogenic pulmonary edema
and found the same thing. We actually published back to back papers in Science Translation Medicine. So this one model, has
demonstrated the proof of principle for drug efficacy, drug toxicity,
and human disease modeling in using organs on chips. But we didn’t stop there, Kit Parker who’s going to be
speaking oN Tuesday afternoon. As you’ve heard, has developed
a Beating Heart-on-a-Chip. Which you can measure
the contractile stress by measuring how these little
flexible cantilevers bend with living cells on it, and at the bottom right, and he’s hopefully going
to tell you about this, he used human IPS cells cardiac myocytes from human IPS cells and was able to model Barthe Syndrome and see the compromised functionality both by taking cells from patients and actually using CRISPR
based genome editing to make a model of it. And he actually got new
insight into the disease. That’s his story, I’ll
let him talk about it. We’ve begun to link the Heart-on-a-Chip to the Lung-on-a-Chip, and just real preliminary result, we can actually share for
example giving Doxorubicin to the lung through the air space. We could see a dose dependent inhibition of the contractility in the heart and this was done with
Kit’s initial system right across the epithelium
to the vascular channel to his heart but now
he’s put an endothelium in his system so he can go
endothelium to endothelium. We didn’t stop there, we’ve recently, and this is unpublished, we developed what we call
a Small Airway-On-A-Chip because pharmaceutical companies were interested in asthma and COPD. We took the same chip, we
made the height of the channel a millimeter to mimic radius
of a two millimeter bronchial. We took primary human
bronchial or epithelial cells in vivo as shown at the bottom right. They normally grow as a pseudo stratified ciliated epithelium. We put the cells, culture them, give them a narrow liquid interface and we get a pseudo stratified epithelium and there’s endos on the bottom. More importantly if you stain
them for cilia and mucous, and this is across a
millimeter of channel, you get incredible beautiful
ciliated epithelium which if you look at
electromicroscopic level looks like the human brochial in vivo, and more importantly they actually beat, and if you give them fluorescent particles you could visualize
mucous ciliary clearance and this is in real time. It’s moving the same real time movement as I’m clearing my throat here. That’s happening on this chip. And just this is a comparison, I won’t go into it because of time but this cilia beating
frequency and structure and velocity and percents
of cells are basically identical on chip and in the human. Now we started to model diseases and we began with making
viral infection using poly IC and what you can see here is on chip, I won’t go into details but you get multiple cyctokines that are
known to be induced in humans that induce monocyte recruitment and we could flow the cells through and they’re recruited
through the endothelium and on to the chip. Recently we’ve obtained
cells from human patients with COPD and we put them
on the chip made normal and diseased, bronchials on the chip, and you see at the left, it’s well known that COPD patients in vivo have decreased expression of
TLR-3 and TLR-4 receptors. We retain that on the chip. It’s also known that they
had increased exacerbations by viral and bacterial infection and as shown here this is
LPS endotoxin and poly IC to mimic virus and compared to normal we get a significantly
increased exacerbation on chip. So we really think these can
be modeled with high fidelity, used to model with high fidelity,
human disease processes. Another organ we’ve published a Peristaltic Human Gut-on-a-Chip. We took the same Lung-On-a-Chip, we made it wider, higher, we gave it peristaltic like deformations trickling like flow. We plated them with human
intestinal epithelial cells Caco 2 cells that the
pharmaceutical industry uses they normally culture them on transwool, as a flat monolayer, they’re
poorly differentiated. We put them in one day as shown
at the bottom there on the monolayer but three days later
we get an intestinal villi across the entire width of the chip. This is in vitro across a millimeter. Now the villis has a very
particular architecture. It’s well known, has a proliferative crip where the stem cells are, they then divide, move
up, differentiate into the four lineages of the intestine. If we label for growth for
two hours there in the crips, they then migrate up and differentiate into all four lineages of small intestine. If you look at trans
epithelial resistance, this is a trans wall, this is our chip. This is pericilial or
permeability, this is our chip. This is cell differentiation. This is P450 which is very
important for the pharmaceutical industry in vivo but you
never see it in vitro in these intestinal
cells, that’s in vitro, this is in our chip, and
this is mucous production which you don’t see in vitro. Across, with gene micro
arrays across 22,000 genes In red at the top left,
are quadruplicate in a static trans wall culture. They’re red, meaning they’re
basically all the same. You just give them trickling flow they’re totally different cells. You give them flow plus peristalsis they’re totally different cells again. I tell my students there are no bad cells just like there are no bad kids. They get into a bad group of friends, or a bad micro environment,
you bring them home you may be able to get it back to normal. Now because we have flow
and mucous and barrier and differentiation,
we can grow microbiome, whch to me is the major
paradigm shift in medicine and nobody could culture these. So these are human gut cells with human derived lactobacillis
commensal bacterium, and what you can see here is that if you do a trans wall
you put bacteria on it, it’s contamination, you
lose a barrier in 24 hours. You put these on our chip, you get better barrier function which is why people take probiotics for intestinal function. We’ve now, here you see
eight different probiotic bacteria living in the crips. They’re wiggling if you look carefully and they stay in the crips. In contrast with pathogenic
enteroinvasive bacteria they overgrow completely and we actually now are modeling inflammatory bowel disease
by adding immune cells. We have about 10 or 15 different organs that we’re developing but because we have a
vascular channel in these a few years ago I
suggested the ideas that we could create a Human Body-on-Chips. If you imagine, you could
have an aerosol based drug go through the lung, get absorbed, be metabolized by the liver, peed out by the kidney, see if you have heart talks and see if bones metabolism
or oral drug the same way and we were very lucky to
get one of two major grants from DARPA to do just this. This is a grant I’m
working on with Kit Parker and John Wikswo from Vanderbilt and CFDRC and the idea was to build
basically a CD player a multi CD player, where
each CD could hold a chip and you could just plug in
heart, liver, lung, kidney or five hearts or whatever
order, generate data, and then with computational modeling do PKPD from human cells to try to mimic what happens in vivo. We’ve had this for a
little over two years. I should say we’ve
partnered with Sony DADC. They make CD’s. They don’t see a big
future in it with iTunes, and so they’re getting
into biology very quickly. And so we’ve made a lot of progress starting two years ago in the summer. This is every student had
tubes coming out of the chips. There was one pump per chip, maybe two chips per whole incubator. Tubes going out to vacuum control. We now have everything
integrated into a chip. No tubes, it’s all in there. We actually have a
simpler system since then and last November we
developed our first prototype of this what we call
the Interrogator device which now could do, and that could do 12 different organs, and now we’re up to 36, and it has high resolution
three color fluorescent imaging and we hit milestones where we could keep 10 different organs alive for a week. We’ve now done two weeks. We could show physiological coupling between two different sets of two organs and based on that for full disclosure we just started a company called Emulate of which I’m on the
scientific advisory board and hold equity, so I
should say all the data was done before that so you can trust me. Now the reason this is
disruptive innovation is because I think right now
the way we develop drugs, is we take 15 years and
half a billion dollars, we design a huge clinical trial like you heard 20,000 patients. We usually fail and then
we do statistical number crunching to find the
genetic sub population that maybe responded
and if you’re lucky you designed a small trial
and you get it approved. With this sort of approach
you could literally develop IPS cells from
genetic sub populations put them on chips, develop
drugs in focus programs for a subpopulation, have your
clinical trial sub population and hopefully accelerate this, and I think this can really
change the way things are done. So before I end I just want to give you two other examples of
disruptive innovation. My platform is just one of six and others called
programmable nanomaterials and the idea is to create
smart medical nanotechnologies to go from implantable medical devices to injectable medical devices and I have targeted cardiovascular medicine in drug delivery. Now as you know the major
causes of death in man are heart attack, stroke,
pulmonary embolism, athereosclerosis, and
they all share the cause of vascular occlusion,
often due to a clot, and so as they create clot
busting drugs like TPA, but only 4% to 5% of patients are eligible because of bleeding, hemorrhage, side effects, often into the brain. So he said what if we could get this drug just to the clot and nowhere else? And we thought well how would you do that? And we said well platelets do that, that’s why the platelets get activated when you have a narrowing of the vessel and you get a clot to
form in the first place. What we came up with we
called platelet mimetics and the idea is we took FDA
approved PLGA nanoparticles at 180 nanometers in diameter. We used spray drying to form little clumps as you see here, that are
the size of platelets. And you can think of them
like a wet ball of sand. If I shape wet sand, it’s round. If I sheer it in my hands,
they fall to grains. This is tuned to fall to
grains at only abnormally high levels of shear stress above about 109 centimeters per square. So the idea would be that if you inject it into the vessel, it would
travel around like a platelet, but whenever wherever
you had an occlusion, high shear stress would activate them, they would deploy into small nanoparticles that would have less drag force. If they were coated with
TPA, they’d bind fibrin and then they would degrade
it and keep degrading it if a bit flew off it would travel with it and keep degrading it. And we actually developed a model in vitro in microfluidics with preformed clot and you actually see these
clots degrade in vitro just like I said. So we went and we
developed an in vivo model and we developed a model of
pulmonary embolism in the mouse. We formed a clot, injected it,
occluded the pulmonary artery and 100% of the mice died in 45 minutes. We then were able to save
80% of the animal’s lives with a single injection
of this nanotherapeutic but the important point is we used one hundredth the dose of TPA. That is basically almost
a homeopathic dose. It doesn’t do anything
to systemic bleeding. So you can begin to envision
a future where you can inject this in an ambulance and
you could still do cardiac catheterization because you
wouldn’t have systemic bleeding and we’re trying to advance this towards, we’ve already moved it
to larger animal models, and had some exciting results. And to end, one other
example is inspiration from the non-medical world that the Institute
doesn’t just do medicine, we do industrial applications
and environmental applications because I always felt there
may be things out there we’ve never heard of that can have value. Joanna Isenbeeg was
trying to develop ways to prevent ice sticking from airplane wings and she developed a non
stick surface coating called SLIPS, slippery liquid-infused
porous surfaces. She was inspired by the
pitcher plant in Africa as shown here, which in the dry season insects can crawl all over, but when it becomes
wet, they just slide in. It’s like a black hole. If you look carefully,
just falling to the center, and they get eaten like a venus fly trap and that’s because it’s
like slip sliding on water. She then used nanotechnology
to create artificial surfaces and put a silicon oil
or perfluorocarbon oil on the top to mimic this and now you have this is crude oil one of the stickiest things in the world and it does not stick
at all to the surface. And you can injure it, and because it flows back
in it’s self healing. Now I was challenged on a project to develop a way to make
surfaces non adhesive for blood. To actually have a surface
that’s completely anti-coagulant, and I thought what if we could use this, but we wanted to use FDA
approved medical devices that already have GMP manufacturing and we couldn’t structure the surface. We wanted to do it on a smooth surface. We recently accomplished
this by developing what we call a tethered
liquid perfluorocarbon method where we take perfluorocarbon
that we covalently link and we add a thin layer
of liquid perfluorocarbon to create the liquid surface
so you have sort of a oil liquid, oil water,
oil blood, interface, and what happens is if you
put blood on this surface as shown here, this is acrolate. That’s fresh human blood
without heperin on the left that clots, that’s the
coded surface on the right. At the bottom we took a clinical AV shunt, arteriorvenous shunt
coated it with this method, put it in a pig for eight hours, and had absolutely no clotting whereas the other uncoated ones clotted. And this was the cover of
Nature Biotech last month. I just tell you this. These are just a glimmer
of what we’re doing at the WYSS Institute. But the answer to disruptive
innovation is people and it’s getting people together from many different disciplines
each of which is passionate about solving a big problem, but they know they can’t do it alone and if you bring them together
amazing things happen, and with that I invite you to our website. We won the Webbie a couple of years ago which is the academy
award of the internet. We beat out NASA space
propulsion lab and WIRED magazine and I hope you come. I
think you’ll enjoy it. Thank you so much for this honor. (audience applause) – Thank you Dr. Ingber for
that inspirational lecture. Now I’d like to introduce
Dr. Robert Harrington. Chairman of our Committee on
Scientific Sessions Program. He’s the Chairman of the
Department of Medicine and the Arthur L. Bloomfield
Professor of Medicine, at the Stanford University
School of Medicine in Palo Alto, California. Please welcome Dr. Harrington. (regal music) – Good afternoon, on
behalf of the Committee on Scientific Sessions Program, and the American Heart Association, I want to welcome you to
Scientific Sessions 2014. We have a terrific program planned for you in this great city of Chicago, and maybe some of that snow
will keep all of you indoors to enjoy the offerings
over the next few days. First, truly to put together a meeting like Scientific Sessions takes a village. I want to thank our large
and very diverse Committee on Scientific Sessions
Programming for all the hard work that went into planning this meeting. I want to particularly
acknowledge the vice chair of the committee Frank Sellke and
the president Elliot Antman. I’d also like to ask us
to pause for a moment and remember a friend and
colleague to many of us, Ken Bloch who passed away
far too early this past Fall. Ken was an enthusiastic
passionate committed AHA volunteer and one of his most recent
roles for the Heart Association he served as the Vice
Chair of the Committee on Scientific Sessions Programming. Ken was passionate about science. He was passionate about
early career investigators, and he will be very missed. Following last year’s
successful Scientific Sessions in Dallas, we reached out to the community and to many of you and asked you what do you want to see at
your Scientific Sessions? As Clyde Yancy has said, you asked, we listened, and we delivered. We really think that you’re
going to enjoy this meeting and now I’m going to spend a few minutes walking you through what you can expect over the course of the next few days. This really is the
world’s greatest showcase of cardiovascular science in medicine. The best science is presented
here at Scientific Sessions, and this year’s Scientific
Sessions in Chicago is no exception. We have more than 5,000 presentations including 4,000 abstracts
of original science. There’s more than 1,000 invited faculty, and this is one of the only meetings that you will see science
across the continuum from basic discovery, to translation, to clinical research and
ultimately to population health. We have more than 200 exhibitors
in our technology hall and late breaking clinical
trials remains a cornerstone of the excitement of the meeting. Let me give you an overview of
what the meeting looks like. We have almost 900 sessions, of which 560 are original
research sessions. In those original research sessions, we’ve structured most
of the original science as poster presentations this year, and we’ll come back to that in a moment as I explain the thinking of
the committee in doing this. We have four late breaking
clinical trial sessions, five clinical trial
special reports sessions, and all of this totals almost 600 original research sessions. There are over 300 invited
sessions, plenary sessions, special sessions and a
number of other sessions that again, I’ll get to and
discuss with you in some detail. We know that a meeting like Scientific Sessions can be daunting. While it’s great to have
every type of science being presented, navigating that meeting across the continuum from basic to population health science
can be a challenge. The programming committee
has organized this for you in an attempt to help you
navigate the meeting more readily. There are 26 tracks going across those four pillars of science, and this involves all the major cardiovascular specialties as well as multiple domains of science. Always the late breaking clinical
trial sessions prove to be one of the more newsworthy
aspects of Scientific Sessions and this year is certainly no exception. We have an outstanding group of trials, of presenting trialists, commentators, moderators, and panelists
to try to give you not just the presentation but an indepth look at some of the questions that emerge from the data. We hope you’ll join us
right after this sesson for the first late breaking
clinical trial session at 3:45 on the risk and benefits of dual anti-platelet therapy,
where a number of trials including the dual anti-platelet therapy study will be presented. We’ll kick off tomorrow’s
late breaking clinical trials with lipid lowering and the
prevention of coronary disease included in this session
will be the primary results from the Improve It study. On Tuesday we have a fabulous
late breaking trial session devoted to the treatment
of structural heart disease and I want to call out
specifically that two of the trials in this session are NHLBI
supported clinical trials. One through the Pediatric Heart Network and one through the
Cardiothoracic Surgical Network. In this era of constrained funding, the ability of the NHLBI
to do clinical trials in populations that are
frequently under represented is deeply appreciated by the
cardiovascular community. The final session on
Wednesday will look at Ischemic heart disease, drugs,
devices, and systems of care. So we hope you join us for all of the late breaking trial sessions
over the next few days. On Wednesday we’ll be
piloting a new entity at Scientific Sessions and this is the next best thing in cardiovascular science. We’ve asked representatives
of our 16 science councils to present to you in
rapid five minute fashion, what they think will be the next big thing in their area of science
or clinical medicine. There are special lectures
being offered this week. Bob Lefkowitz will present
the Nobel Laureate lecture and it should be noted that
Dr. Lefkowitz was an AHA funded investigator earlier in his career. Rob Califf also from Duke will present the Distinguished Scientist lecture. You’ve heard from Elliot, that Lars Wallentin
from Upsala will present the Paul Dudley White
International lecture, and there will be a special presentation on a patient’s perspective of living with cardiovascular
disease for several decades and this will be a
lecture and presentation by former Vice President Dick Chaney. We’ve heard from attendees
that while they appreciate the scope and the broadness of sessions they want more intimacy,
they want to be engaged with their colleagues around
a specific area of science. We listened to this and
with the help of our electrophysiology colleagues
have planned a one day meeting in a meeting on arrythmias in the Arrhythmia Research Summit. We hope that you’ll join us for this as we look at arrhythmias
again across the spectrum from basic science to population health. Another meeting within the meeting, is the ever popular Global Congress. This year led my Mikel
Kosoba and Chris O’Donnell, The Global Congress is
concentrating on big data. This meeting opened this morning with a standing room only audience in SC. It’ll be in there over the
next several days, S-101-C. And you’ll see the topics
covered like outcomes research, mobile health, basic science with a specific emphasis on genomics, and utilizing the EMR for research in learning healthcare systems. Very popular and started a few years ago, appropriately enough
when Scientific Sessions were in Los Angeles, Case Theaters provide an opportunity
to learn at the movies. These are presentations of taped cases, that have been taped and edited to facilitate your education
around a clinical case. We’ve expanded it this
year to include not just coronary cases, but
structural heart disease, vascular surgery, cardiothoracic surgery, electrophysiology and the
management of heart failure. These are moderated
sessions with expert panels to walk through the cases. Don’t miss these. Opportunities abound for
networking at sessions. We have a number of named lecturers, a lot of researchers, clinicians, nurses attending the meeting
and the number of 17,000 has now been updated to
almost 20,000 attendees at this meeting here in Chicago. We are truly a global meeting
at Scientific Sessions. Almost 30% of our
faculty is international. Approximately half of our original science comes from outside the United States and in celebration of
that and in collaboration with 17 other professional organizations, the AHA will host 17 joint sessions on a variety of scientific
topics over the next few days. The Scientific Programming Committee has really realized that
what you want in science is a discussion with colleagues and so as I said, almost
90% of the abstracts are going to be presented in poster form and we have a number of
enhancements to try to interest you engage you and get you
talking to colleagues and presenters about their
science in the poster hall. One example is the e-abstract sessions at mini theaters in the poster hall. You’ll also find networking
lounges throughout. We have poster professors, senior faculty, who will visit every single poster and lead a discussion with that poster presenter about their science. We’re specifically interested
in senior investigators talking and discussing about science with early career attendees. Come by the basic science poster reception in celebration of the
best of basic science and late breaking basic
science tomorrow evening in the poster hall from 4:00 to 6:00 and throughout the convention center you can use kiosks to visit e-posters and even post a question for the presenter to discuss with you what you think are the key question about their science. Be sure to visit other
places for networking. The FAHA lounge, the member circle, the early career engagement lounge, and please stop by AHA HeartQuarters located in the Science
and Technology Hall. We have Science Subcommittees
Collaboration Station. If you’re interested
in science from the AHA stop by and learn about the
different science subcommittees. Maybe you’ll sign up, volunteer, to work in one of those
science subcommittees with AHA. We have new technology to help you understand and follow
the meeting this year. The mobile meeting guide,
please go to the app store and download under AHA events
the mobile meeting guide. It’s fantastic and will allow
you easily to make your way through and navigate your
attendance at the meeting. We have a new offering this year. All sessions are being livestreamed so don’t worry if you can’t make it to the other end of the lecture hall. Listen to it, by live streaming. If one of your fellows is presenting you can listen to them even if
you’re in a remote location. And in several of the rooms this year we have a new application called Conference Note application. Again, in the app store, conference note, use the code HEART14. You can use it in this
room, the special room, the global congress room or
the nursing symposia room. All slides will be available to you and not just available to you but you can take notes
on them on your iPad and you can take that home with you and share that information
with your colleagues. Tomorrow afternoon, in a
collaboration with entreprenuers technologists, AHA volunteers, and Heart Association leadership, there will be a competition
in the Science Exhibit Hall with the AHA’s Heart Tech Competition. Stop by tomorrow afternoon for this and look at innovative start up companies competing with one another in this space. Don’t miss tomorrow, wear red,
for the Go Women campaign. Sign up for the second
annual Walking Challenge. As a community we walked
10 million steps last year. See if we can top that this year. Wear your sneakers on Tuesday Wear them with your business suit. Allows you to get through the
conference hall a bit more readily and celebrates physical
activity and heart health. We have truly early career
attendees at sessions. Local high school students being sponsored by the midwest affiliate of
the American Heart Association. Please greet them, talk to them, if you see them walking
through the convention center. And finally I thanked at
the beginning the CSSP group for their contribution but
truly nothing takes place at this meeting without the
work of very dedicated staff. So please join me in thanking them and enjoy your meeting. (audience applause) – Great job, Dr. Harrington. Thank you, before we close
I would like to thank all of our members and guests
for being with us today and to recognize our speakers and awardees for their outstanding accomplishments. That concludes our opening session. Thank you all for coming. (audience applause)

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