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QUARTERLY | FALL 2016AT THE FOREFRONT OF CARDIOVASCULAR MEDICINE

Welcoming New Faculty! Cardiovascular Faculty Recruitment:Koen Nieman, MD, PhD, was recently recruited by the Stanford

Cardiovascular Medicine, Department of Radiology and the Cardio-vascular Institute, as a new faculty member. He is a pioneer in CT coronary angiography, publishing over 90 research articles on car-diac imaging. Prior to joining Stanford he was the Medical Director of the Intensive Care Unit at Erasmus Medical Center Rotterdam. He recently published a multi-center randomized trial (BEACON) study measuring the performance of cardiac CT in the emergency ward entitled, ‘Coronary CT Angiography for Suspected ACS in the Era of High-Sensitivity Troponins: Randomized Multicenter Study,’ in the Journal American College Cardiology (2016 Jan 5;67(1):16-26).

• Two full-time academic advanced heart failure and transplant cardiologists in the Medical Center Line. Click for details.

• One full-time faculty member with an interest in biobanking and the use of biobanked sam-ples in population research in the University Tenure Line, Medical Center Line, or Non-Ten-ure Line (Research). Click for details.

T32 ImagingPostdoctoral Fellowship

We are seeking highly qualified MD, PhD, or MD/

PhD graduates. Applicants must be either a U.S.

citizen or permanent resident to apply. Intended

start date: January 1, 2017.

Application Deadline is Dec. 1, 2016.

For information and to apply:http://tinyurl.com/zz6pkaq

Koen Nieman, MD, PhD

The Division of Stanford Vascular Surgery is pleased to announce the recruitment of Clinical Assistant Professor Jennifer Avise, MD.  Dr. Avise specializes in open and percutaneous treatment of peripheral vascular disease including management of claudication and limb salvage techniques, vascular trauma, dialysis access, treatment of venous disease, aortic disease including aneurysm and dissection, and management of carotid artery disease.

Jennifer Avise, MD

2017 Stanford Drug Discovery Symposium

Art by Ryoko Hamaguchi

April 24, 2017 Stanford University

Register:http://tinyurl.com/cvidd2017

Invited Speakers Include:

Thomas Sudhof, PhD (2013 Nobel Laureate)

James Bradner, MD (President Novartis Institutes

for Biomedical Research)

Eric Olson, PhD(Professor, University of

Texas, Southwestern)

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The Cardiovascular Institute hosted its “Stanford-Karolinska Cardiovascular Research and Medicine Symposium” in Paul Berg Hall in the Li Ka Shing Center on Oct. 20, 2016. Attendance was 262 guests. The meeting featured keynote guest speaker Michael Levitt, PhD, Robert W. and Vivian K. Cahill Professor in Cancer Research in Stanford School of Medicine and Professor (and 2013 Nobel Laureate).

Special guests from the Karolinska Institute in Stockhom, Sweden, were: Ralph Knöll, PhD; Lars Magdefessel, MD, PhD; and Ulf Hedin, MD. Other speakers included, Stefan Jovinge, MD, PhD; Daniel Bernstein, MD; Latha Palaniappan, MD, MS; Roland L. Dalman, MD; Erik D.Ingelsson, MD, PhD; Themistocles, L. Assimes, MD, PhD; Kenneth Mahaffey, MD; Manisha Desai, PhD; Roham T. Zamanian, MD, FCCP; Koen Nieman, MD, PhD; Alison Marsden, MD; and William Hiesinger, MD. Moderators were: Robert A. Harrington, MD; Y. Joseph Woo, MD; Michael Snyder, PhD; Philip S. Tsao, PhD; Mark Mercola, MD; and Nicholas Leeper, MD.

Christopher Kowalewski

Evaluating New Imaging Software for Focal Impulse and Rotor Mapping in Atrial Fibrilla-tion Ablation Procedures

Sanjiv Narayan, MD, Lab

Vedant Pargaonkar, MD

The Diagnostic Value of Abnormal Heart Rate Recovery during Exercise Stress Testing in Predicting the Presence of Endothelial and Microvascular Dysfunction

Jennifer Tremmel, MD, Lab

2016 Stanford-Karolinska Cardiovascular Symposium

Clinical Research Poster Award Winners

Amber Smith, PhD, T32 postdoc from the lab of Calvin Kuo, MD, PhD, explains her research to Michal Roof, PhD

(Left) Keynote speaker, Michael Levitt, PhD, (2013 Nobel Laureate in Chemistry). (Center) Ralph Knöll, PhD, from the Karolinska Institute and AstraZeneca. (Right) Stefan Jovinge, MD, PhD from Spectrum Health Hospitals.

The Stanford-Karolinska Symposium had 262 attendees over the full-day event.

Milos Pjanic, PhD

TCF21 Interacts With Aryl-hydrocarbon Receptor to Modify Coronary Smooth Mus-cle Cell Response

Thomas Quertermous, MD, Lab

Nazish Sayed, MD, PhD

Modeling Endothe-lial Dysfunction in LMNA-related Dilated Cardiomyopathy

Joseph C. Wu, MD, PhD, Lab

Darshan Trivedi, PhD

Beyond the Myosin Mesa: A Potential Uni-fying Hypothesis on the Molecular Basis of Hyper-contractility

James Spudich, PhD, Lab

Basic Research Poster Award Winners

There were 41 posters presented during the poster session. Faculty and guest judges for the best research posters were Ian Rogers, MD; Fatima Rodriguez, MD; Ngan Huang, PhD; and Lars Magdefessel, MD, PhD. Five posters (listed below) were awarded $750 prizes.

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Improving Outcomes in Pulmonary HypertensionThe Stanford Pulmonary Hypertension Clinic and the American Heart Association partnered with Peking University and organized a joint symposium entitled “Improving Clinical Outcomes in Pulmonary Hypertension: Role of Registries and Precision Medicine” this October at the Great Wall International Congress in Cardiology. The goal of the symposium was to discuss the clinical phenotypes of pulmonary hypertension and how implementation of precision medicine initiatives can provide opportunities for better clinical practices.  The symposium facilitated investigators from Stanford and Uni-versity of Peking to exchange information about pulmonary hypertension practices and establish collaborations that will be of mutual benefit to both institutions.  The symposium featured a keynote presentation by Dr. Bradley Maron from the Brigham and Women's Hospital in Boston. This event was co-organized by Dr. Vinicio de Jesus Perez (Stanford PH clinic) and Dr. Dayi Hu (Chief of Cardiology, Peking University). This activity was sponsored by the American Heart Association

Council of Cardiopulmonary, Critical Care and Resuscitation.

Vinicio de Jesus Perez, MD

By Erin Digitale

For years, pediatric cardiologists have been trying to understand the origin of a puzzling structural defect of the heart muscle wall, a congenital problem called left ventricu-lar non-compaction (LVNC). In people with this defect, the muscle of the heart’s biggest pumping chamber looks spongy rather than smooth and solid.

“For such congenital cardiomyopathies, cur-rently there is no effective therapy, and the only ‘cure’ is heart transplantation,” said Stan-ford’s Joseph Wu, MD, PhD, a cardiologist who led a new study of the condition that pub-lished online in Nature Cell Biology.

His team was looking for a new way to address a very old research problem: They didn’t know how much they could trust studies done on animal models of the disease. Mouse and rat models of LVNC also have spongy heart mus-cle, but it’s not clear if their defect starts the same way as in humans, nor whether findings from rodent studies could help treat humans.

So Wu’s team used innovative stem cell tech-niques instead. They took skin and blood cells donated by four members of a family affected by LVNC and converted them into induced plu-ripotent stem cells, which are stem cells made in a lab from adult cells. Using these stem cells, the researchers then made human heart muscle cells that they could study in a dish.

Researchers already knew that LVNC begins

long before birth, when the heart muscle fails to make an important developmental shift. In the earliest stages of cardiac development, it’s normal for the muscle to be spongy. At about 8 weeks of gestation, the human heart muscle is supposed to compress into a thick, compact mass, but that shift doesn’t happen correctly in LVNC patients.

Another mystery about the dis-ease is its range of severity, which varies from no symptoms at all to complete heart failure. As the new paper describes, the family who agreed to have their cells studied is a good example. Of three siblings who donated cells for research, one had already had a heart transplant, while the other two had hearts that pumped normally in spite of deeper trabeculations (the scientific word for the spongy formations). Meanwhile, their father had an enlarged heart, but no sponginess in his heart muscle and no other symptoms.

Using the heart muscle cells derived from all four people, the researchers identified the gene defect that causes LVNC in this family; it codes for a cardiac transcription factor — or a protein that controls the expression of other genes — called TBX20. The scientists conduct-ed several experiments to figure out how the TBX20 abnormality changes heart muscle cell proliferation — with the abnormality, the cells don’t proliferate enough, it turns out. They

also explored the exact signaling pathways that cause the problem, showing that the magnitude of signaling abnormalities could

explain differences in symptom severity between family mem-bers. They created a mouse mod-el with the family’s gene defect for further characterization, and also showed that blocking the faulty signal from the altered TBX20 could restore the mutated cells’ ability to proliferate.

The new findings still leave unan-swered questions about the origins of LVNC. But the paper does demonstrate how induced pluripotent stem cells can overcome a research hurdle, and suggests that the same methods could help scientists tackling other hard-to-study conditions.

“This study shows the feasibility of modeling such developmental defects using human tis-sue-specific cells, rather than relying on ani-mal cells or animal models,” Wu said.

Co-authors include Kazuki Kodo, Sang-Ging Ong, Fereshteh Jahanbani, Vittavat Termglinchan, Keiichi Hirono, Kolsoum InanlooRahatloo, Anteje D. Ebert, Praveen Shukla, Oscar J. Abilez, Jared M. Churko, Ioannis Karakikes, Gwanghyun Jung, Fukiko Ichida, Seam M. Wu, Michael P. Snyder, and co-senior author Daniel Bernstein.

Full Story: http://scopeblog.stanford.edu/2016/09/20/how-does-a-heart-defect-start-stan-ford-scientists-use-stem-cells-to-find-out/

How Does a Heart Defect Start?Stanford Scientists Use Stem Cells to Find Out

Spongy Heart Muscle

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Gene could help explain insulin resistanceBy Jennie Dusheck, Medical school's Office of Communication & Public Affairs

Health researchers have known for decades that Type 2 diabetes results from a phenomenon called insulin resis-tance, but what causes insulin resistance has remained a mystery. Now, researchers at the Stanford University School of Medicine and the University of Wisconsin-Madison  have begun to untangle a web of connections that includes a gene; mitochondria, which produce energy for cells; insulin resistance; and how well the body’s metab-olism functions.

“We’ve identified a mechanism for insulin resistance that involves a gene that ties insulin resistance to mitochon-drial function,” said Joshua Knowles, MD, PhD, an assistant professor of cardiovascular medicine at Stanford. A paper describing the work was published in the Oct. 4 issue of Cell Reports. Knowles is the senior author, and Indu-mathi Chennamsetty, PhD, a postdoctoral scholar at Stanford, is the lead author.

Insulin is a hormone secreted by the pancreas that helps fat and muscle cells take glucose from the blood. When a person’s cells stop responding to insulin, the person has insulin resistance and glucose builds up in the blood, signaling the pancreas to produce ever more insulin. The new study shows that suppressing the expression of the Nat1 gene in mice interferes with the function of mitochondria — cell structures that make ATP, the energy currency of cells. Without ATP, cells cannot live and function. In addition, mice whose Nat1 gene had been eliminated gained more weight and had larger fat cells and higher levels of biomarkers indicating inflammation than did regular mice, even though all the mice got the same amount of food and water.

Additional co-authors of the study are instructor in pediatric cardiology Michael Coronado, PhD; visiting graduate student John Sandin; research associate Giovanni Fajardo, MD; postdoctoral scholars Kévin Contrepois, PhD, Ivan Carcamo-Orive, PhD, Andrew Whittle, PhD, and Mohsen Fathzadeh, PhD; professor of genetics Michael Snyder, PhD; professor of pediatric cardiology Daniel Bernstein, MD; and pro-fessor of cardiovascular medicine Thomas Quertermous, MD.

Full Story: http://med.stanford.edu/news/all-news/2016/10/gene-could-help-explain-insulin-resistance.html

Stanford Part of New Biohub CollaborationBy Amy Adams

Stanford will be one of three Bay Area universities participating in a new biosciencecollaboration funded through a $600 million commitment by the Chan Zuckerberg InitiativeFacebook founder Mark Zuckerberg and his wife Priscilla Chan, MD, created the Chan Zuckerberg Initiative after the birth of their daughter in 2015. On Sept. 21, the Initiative announced plans for a broader focus on science, its second major initiative, alongside work to improve education for all students. The Chan Zuckerberg Initiative’s goal is to cure, prevent or manage all diseases by the end of the century by accelerating basic science research. The Ini-tiative seeks to support new ways of enabling scientists and engi-neers to work together to build new tools that will empower the whole scientific community and advance progress.

The new Bay Area research collaboration, called the Chan Zuck-erberg Biohub, is the first scientific investment by the Chan Zuck-erberg Initiative. It will include a combination of research space focused on biotechnology tools development, grants and large-scale collaborative projects.

“The Biohub will be the sinew that ties together these three institu-tions in the Bay Area like never before,” said Stephen Quake, PhD, Stanford professor of bioengineering and of applied physics, who will co-lead the Biohub with Joseph DeRisi, PhD, professor and chair of biochemistry and biophysics at UCSF.

Joshua Knowles, MD, PhD

Indumathi Chennamsetty, PhD

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Researchers Launch iPhone App to Study Peripheral Artery DiseaseBy Tracie White

Stanford University School of Medicine researchers have launched a free iPhone app designed to help them conduct a clinical study to discover better treatments for peripheral artery disease and as a con-venient way for people with the disease to monitor their daily activity.

“We hope to gain insights into patterns of disease progression over time by collecting participants’ activity data from their iPhones,” said Oliver Aalami, MD, Clinical Associate Professor of vascular surgery and lead investigator of the study. “We will be looking for any chang-es in activity patterns that may indicate disease advancement.”

Peripheral artery disease, which affects about 12 million people in the United States, is a circulatory problem caused by a buildup of plaque in the peripheral arteries, most commonly in the legs. Symp-toms include cramping and pain while walking or climbing stairs. Treatment is directed at reducing leg pain and the risk of heart at-tack and stroke from clogged arteries.

“One of the key metrics we will look at is the greatest distance that people with PAD can walk without stopping,” Aalami said. “It gets really painful, and they have to stop and rest before continuing on.”

The VascTrac app will collect activity data using Apple’s Research-Kit, an open-source framework that allows iPhone users to easily

join clinical research studies. Since its launch over a year ago, the software has been used by researchers to collect data on diseases ranging from diabetes to melanoma. Stan-ford researchers launched one of the first of these studies, MyHeart Counts, in the spring of 2015 to study heart disease. That study has enrolled more than 54,000 people so far.

Aalami said the goal for the PAD study is to enroll 2,000 to 5,000 participants, “much more than you can do with a traditional trial.”

Researchers emphasize that the app is not a medical diagnostic tool and isn’t designed to provide medical advice, professional diagnosis, opinion, treatment or health-care services. All partic-ipants’ data will be stored using military-grade encryption, and participant names will be replaced by random codes, keeping identities and medical information confidential, the researchers said. With permission from a participant, his or her de-identified data may be shared with researchers at other institutions ap-proved by Stanford.

The trial is being sponsored by the companies Abbott Vascular, Cook Medical, W. L. Gore & Associates and Microsoft.

Stanford Medicine and Intermountain Healthcare have announced the recipients of more than $500,000 in seed grants focused on transform-ing health care.

Earlier this year, the two organizations announced a collaboration to enable joint clinical, research and education projects. Intermountain Healthcare is a not-for-profit health-care system based in Utah. The seed grants were awarded to projects that will be jointly led by prin-cipal investigators from Stanford and Intermountain. The one-year, $75,000 grants took effect on Nov. 1.

Following are the recipients and their project titles:

• Whole-genome DNA sequencing of stage-3 colorectal cancer — James Ford, MD, associate professor of oncology and of genetics at Stanford; Lincoln Nadauld, MD, PhD, Intermountain genomics and health precision.

• Baseline assessment of hand hygiene practices and ICU microbi-ology — Arnold Milstein, MD, MPH, professor of medicine; Bill Ben-inati, MD, Intermountain critical care medicine.

• Developing a precision-based approach for the diagnosis and prognosis of heart failure with preserved ejection fraction in the community — Francois Haddad, MD, clinical associate professor of

cardiovascular medicine; Kirk Knowlton, MD, Intermountain car-diovascular medicine.

• Translational approaches to the mechanisms of septic cardiomy-opathy — Euan Ashley, MRCP, DPhil, associate professor of cardio-vascular medicine; Samuel Brown, MD, Intermountain critical care medicine.

• Implementation and evaluation of graduating from pediatric to adult care — Korey Hood, PhD, clinical professor of pediatrics; Ai-mee Hersh, MD, Intermountain pediatrics.

• Impact of donor-derived BK virus infection and immune recovery in kidney transplant recipients — Benjamin Pinsky, MD, PhD, as-sistant professor of pathology and of infectious diseases; Diane Alonso, MD, Intermountain transplant services.

• Development and implementation of a digital health-care pro-gram for patients with atrial fibrillation — Mintu Turakhia, MD, assistant professor of cardiovascular medicine; Jared Bunch, MD, Intermountain heart-rhythm services.

More information about the grant program is available by emailing: intermountain-stanford-collab@stanford.edu.

Full Story: https://med.stanford.edu/news/all-news/2016/10/recipients-of-stan-ford-intermountain-seed-grants-announced.html

Photo by Norbert von der Groeben

Recipients of Stanford-Intermountain Seed Grants

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P.J. Utz, MD, Professor of Medicine, has joined the scientific advisory board of the Arthritis National Research Foundation, which provides grants for research on arthritis and other autoimmune disorders. He directs Stan-ford’s Medical Scientist Training Program and is the founder and director of the Stanford Institutes of Medicine Summer Research Program for high school students. His research focuses on improving the understanding and treatment of autoimmune disorders.

Jason T. Lee, MD, was elected for a three-year terms as Secretary-Treasurer of the Association of Program Directors in Vascu-lar Surgery, a national society comprised of surgical educators and program directors that oversee vascular surgery training in the US.

John Harris, MD, has been elected as the 78th President of the San Francisco Surgi-cal Society, founded in 1938. Former pres-idents have included Stanford Surgeons to include Drs. Harry Oberhelman, James B D Marks, R Scott Mitchell, Carlos Esquivel, and Sherry Wren.

Joshua Knowles, MD, PhD, received 2016 Clinical Scientist Development Awards from the Doris Duke Charitable Foundation. Awardees receive $495,000 over three years to launch their research programs and to help balance their clinical and research roles. Knowles, an assistant professor of medicine, is examining the risk factors and mechanisms of statin-associated diabetes.

Leah Backhus, MD, Associate Professor of Cardiothoracic Surgery, was appointed to serve as a member of the Patient-Centered Outcomes Research Institute (PCORI) adviso-ry panel on Improving Healthcare Systems. Her expertise will help PCORI refine and pri-oritize research funding priorities and ensure that the research PCORI supports centers on the outcomes that matter to patients and oth-er healthcare decision makers.

Leah Backhus, MD

PJ Utz, MD

Jason T. Lee, MD E. John Harris, MD

Vinicio de Jesus Perez, MD, Assistant Pro-fessor of Medicine, received a Young Phy-sician-Scientist Award from the American Society for Clinical Investigation. The award recognizes junior researchers whose work is notable for its insight into the mechanisms of disease and the potential for new thera-pies. His research and clinical focus is pul-monary hypertension and lung fibrosis.

Vinicio de Jesus Perez, MD

Joshua Knowles, MD, PhD

Notable Awards

The Institute currently consists of 124 faculty members representing engineers, physicians, surgeons, basic and

clinical researchers. The mission of the Institute is integrating fundamental research across disciplines and

applying technology to prevent and treat cardiovascular disease. To support cardiovascular research and ed-

ucation at CVI, please contact Cathy Hutton, Senior Associate Director, Medical Center Development (cathy.

hutton@stanford.edu) or Dr. Joseph C. Wu, Director CVI ( joewu@stanford.edu).

For more information: http://cvi.stanford.edu/waystogive.html and http://cvi.stanford.edu

Supporting the Stanford Cardiovascular Institute

Cathy Hutton

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2016 Dorothy Dee & Marjorie Helene Boring Trust Award Recipients

Raheel AtaMD candidate, 2nd year

Mentors: Ronald Dalman, MD; Oliver Aalami, MD

"VascTrac – An Apple iPhone ResearchKit Study for Peripheral Artery Disease"

Aditya J. UllalMD candidate, 2nd year

Mentor: Mintu Turakhia, MD

"Development of a Risk Score for Hospital Readmissions in Patients with Atrial Fibrillation"

Francisco Xavier GaldosMD/PhD candidate

Mentor: Sean M. Wu, MD, PhD

"Investigation into Left Ventricular Cardiomyocyte Development in Hypoplastic Left Heart Syndrome"

Andrew Lee

MD candidate, 3rd year

Mentor: Patricia K. Nguyen, MD

"Efficacy of Home-Based Cardiac Rehabilitation for Improving Clinical and Immune Markers of

Cardiovascular Health"

2016 Stanford Cardiovascular Seed AwardsVinicio de Jesus Perez, MDAssistant Professor of Medicine (Pulmonary and Critical Care Medicine)

"Wnt5A: A Master Regulator of Compensatory Angiogenesis in the Right

Ventricle and Lung"

Katharine Edwards, MD, Jennifer Tremmel, MDStanford Women’s Heart Health

"Angiographic and Psychosocial Evaluation of Peripartum vs. Non:Peripartum

Spontaneous Coronary Artery Dissection: A Collaborative Study"

Dominik Fleischmann, MDProfessor of Radiology

Collaborators: Kathrin Baeumler, PhD, Anna M. Karmann Sailer, BS,

Alison L. Marsden, PhD

"Estimation of False- Lumen Pressure in Aortic Dissection using Patient-

Specific Computational Fluid Dynamic Simulations"

Eric Gross, MDAssistant Professor of Anesthesiology, Perioperative and Pain Medicine

"Generation of endothelial cells resistant to hyperglycemia-induced

endothelial cell dysfunction"

Ellen Kuhl, PhDProfessor of Mechanical Engineering and, by courtesy, of Bioengineering

"Developing a Cardiovascular Simulator for the Cardiovascular Institute"

Won Hee Lee, PhDInstructor, Cardiovascular Institute

Collaborators: Kari Nadeau, PhD, Sang Ging Ong, PhD

"Assessing the potential health risk of e-cigarettes in diabetes"

Elena Matsa, PhD Instructor, Cardiovascular Institute

Collaborators: Kenneth Mahaffey, Michael P. Snyder, PhD

"Identification of genetic variation determining patient-specific responses to

anti-diabetic drugs"

Tracey McLaughlin, MDAssociate Professor of Medicine (Endocrinology)

Collaborators: Nazish Sayed, MD, PhD, Ian Chen, MD, PhD

"Predicting Cardiovascular Benefits of Anti-diabetic Drugs"

Ashby Morrison, PhDAssistant Professor of Biology

Collaborators: Kristy Red-Horse, PhD and Will Greenleaf, PhD

"Epigenetic Regulation of Cardiac Development"

Jonathan Myers, PhDMedicine-PAVA

Collaborators: Victor Froelicher, MD, Dominik Fleischmann, MD

"Efficacy of Home-Based Cardiac Rehabilitation for Improving Clinical and

Imaging Markers of Cardiovascular Health"

Sanjiv Narayan, MDProfessor of Medicine (Cardiovascular Medicine)

"Computational Mapping to Guide Therapy In Atrial Fibrillation"

Virginia Winn, MD Associate Professor of Obstetrics and Gynecology

"Endothelial Dysfunction in Preeclampsia"

The Dorothy Dee & Marjorie Helene Boring Trust Award provides a stipend up to $15,000. Stanford MD, PhD, and MD/PhD students are encourage to apply for the next cycle of awards.

Eligibility:• At least one quarter of

MedScholars• Previous research experi-

ence at Stanford• A letter of recommen-

dation from a Stanford research mentor

• A medical or PhD student interested in Cardiovascu-lar Research

To download application and additional information visit:

http://tinyurl.com/ihraward

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Joshua W. Knowles, MD, PhDStatin-associated diabetes: Identifying Risk Factors and

Physiologic Mechanisms

Stanley G. Rockson, MDAIBP Mediates A NOVEL

Interplay between cholesterol and Lymphangiogenesis

James A. Spudich, PhDMyosin Movement in Vitro-Molecular Characterization

National Institutes of Health

Daniel Bernstein, MDhiPSC-Cardiomyocytes to

Screen Variants Predictive of Doxorubicin Cardiotoxicity

National Institutes of Health

Mark R. Nicolls, MDStanford Training Program in

Lung BiologyNational Institutes of Health

Cornelia Weyand, MDJAK-STAT Signaling in Giant

Cell Arteritis

Jennifer R. Cochran, PhDGraduate Training Program

in BiotechnologyNational Institutes of Health

Thomas Quertermous, MDMechanism of the coronary heart disease association at

chromosome 6q23.2National Institutes of Health

PJ Utz, MDACE: Autoimmunity Center

of Excellence (ACE) at Stanford

Recently Awarded Projects

Myriam Amsallem, MD | Francois Haddad, MD, LaboratoryRight Heart End-systolic Remodeling Index Predicts Outcomes in Pulmonary Arterial HypertensionAHA Scientific Session, New Orleans, Nov. 2016

Devon Hunerdosse, PhD | Mary Teruel, PhD LaboratoryOpposing Roles for C/EBPβ in Regulating Adipogenesis and TNFalpha-Induced InflammationKeystone Symposia on Obesity and Adipose

Tissue Biology

Qing Liu, PhD | Michael Snyder, PhD, LaboratoryGenome-wide Transcriptomic And Epigenomic Alterations Of Cardiac DifferentiationSociety of Toxicology - Annual Meeting, Baltimore, 2017

Nilay Shah, MD | David Maron, MD, LaboratoryDietary Pattern and Long-Term Survival: A Cohort Study of Patients in a Preventive Medicine ClinicAHA Scientific Session, New Orleans, Nov. 2016 Jin Li, PhD | Themistocles Assimes, PhD, Laboratory Predictors of fatal incident coronary heart disease in the Women's Health InitiativeAHA Scientific Session, New Orleans, Nov. 2016

Haodi Wu, PhD | Joseph Wu, MD, PhD, LaboratoryRestoring diastolic function in iPSC-cardiomyocytes AHA Scientific Session, New Orleans, Nov. 2016

Kazuya Miyagawa, MD, PhD | Marlene Rabinovitch, MD, Laboratory Smooth Muscle Cells Regulate the Capacity for Endothelial Regeneration AHA Scientific Session, New Orleans, Nov. 2016

2016 Travel & Exchange Ideas Award

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Euan Ashley, MDA Phase 2, Multi-Center, Open-Label, Ascending Dose Study on the Efficacy, Safety and Tolerability of Perhexiline in Patients with Hypertrophic Cardiomy-opathy and Moderate-to Severe Heart Failure with Preserved Left Ventricular Function.

Craig D. Miller, MDA prospective, randomized, controlled, multi-center study to establish the safety and effectiveness of the SAPIEN 3 transcatheter heart valve in low risk pa-tients requiring aortic valve replacement who have severe, calcific, symptomatic aortic stenosis.

Christina Mora-Mangano, MDA Prospective, Multicenter, Randomized, Dou-ble-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Preoperative Antithrombin Supplementation in Patients Undergoing High-Risk Cardiac Surgery with Cardiopulmonary Bypass.

Stanley G. Rockson, MDA Phase 2, randomized, double-blind, placebo-con-trolled study of the efficacy, safety, and pharmacoki-netics of ubenimex in adult patients with secondary lymphedema of the lower limb.

Marcia L. Stefanick, PhDRandomized trial of cocoa flavanols and multi-vita-mins in the reduction of cardiovascular disease and cancer.

Phillip C. Yang, MDA Double blind, Randomized, Sham–procedure–con-trolled, Parallel group Efficacy and Safety Study of Allogeneic Mesenchymal Precursor Cells (rexlemes-trocel-L) in Patients with Chronic Heart Failure Due to Left Ventricular Systolic Dysfunction of Either Ischemic or Nonischemic Etiology: DREAM HF-1.

New Clinical Trials

VorapAccessThe VorapAccess study is a double-blind placebo-controlled clinical trial examining whether Vorapaxar can improve the functional matu-ration, patency, and cannulation of the arteriovenous fistula to provide a durable source of blood for hemodialysis. The enrollment target is 50 patients who are receiving surgical AV fistulas, do not have a history of stroke, TIAA, or intracranial hemorrhage, and are not taking anti-platelet or anti-coagulant medications.

BEST-CLIThe BEST-CLI study is a multi-site randomized trial that compares endovascular techniques and surgical revascularization for peripheral arterial disease. The goal is to learn which therapy is more suitable for patients who are candidates for open surgery and endovascular treatment. Approximately 700 subjects have been randomized into the trial with the total enrollment target being 2,100 across all sites.

Gore IBE 12-04The GORE® EXCLUDER® AAA Endoprosthesis is an extension intended to isolate the common iliac artery from systemic blood flow and pre-serve blood flow in the external iliac and internal iliac arteries in patients with a common iliac or aortoiliac aneurysm. The device designed to be used in conjunction with the GORE® EXCLUDER® AAA Endoprosthesis. The purpose of The Gore IBE 12-04 study is to determine the safety and effectiveness of the GORE® EXCLUDER® Iliac Branch Endoprosthesis when used for treatment of Common Iliac Artery Aneurysms (CIAA) or Aorto-iliac Aneurysms. The study enrolled 100 patients at all sites. 

Cook Zilver PTX-VThe Zilver® PTX® Drug-Eluting Peripheral Stent has been approved by the U.S. Food and Drug Administration (FDA) to treat narrowing of the femoropopliteal (leg) arteries. The stent is a flexible metal tube used to keep an artery open that is coated with paclitaxel, which is directly absorbed by the artery wall cells. The purpose of this post-approval study is to provide continued evaluation of the stent’s safety and effectiveness by confirming that post-market results are similar to results observed in pre-market testing and by evaluating the long-term device integrity. A total of 200 patients were enrolled across all sites.

Vascular Surgery Clinical Trial Highlights

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JANUARY National Institute of Health Bold New Bioengineering Methods and Approaches for Heart, Lung, Blood and Sleep Disorders and disease (RFA-HL-17-015) Deadline: Jan. 17, 2017

American Heart Association Institute Innovative Development Grants for identifying novel approaches to analyzing data Deadline: Jan. 31, 2017

American Heart Association Data Mining Grants aimed at uncovering patterns and knowledge from existing data sets Deadline: Jan. 31, 2017

FEBRUARY National Institute of Health NHLBI Outstanding Investigator Award (RFA-HL-16-024) intended to support a research program rather than a research project Deadline: Feb. 15, 2017

NHLBI Early Investigator Award (RFA-HL-16-025) intended to support a research program, rather than a research project Deadline: Feb. 15, 2017

NHLBI Clinical Trail Pilot Studies (PAR-16-037) Deadline: Feb. 16, 2017

Faculty Funding Opportunities

Postdoctoral Funding OpportunitiesNOVEMBER Research Fellowship Program In Cardiovascular Disease Prevention Deadline:  Nov. 15, 2016

DECEMBER National Institute of Health Ruth L. Kirschstein National Research Service Award (NRSA) Individual Postdoctoral Fellowship (PA-16-307) Deadline: Dec. 8, 2016

FEBRUARY National Institute of Health K08 Mentored Clinical Research Career Development Award (PA-16-191) Deadline: Feb. 12, 2017

K23 Mentored Patient-Oriented Research Career Development Award (PA-16-198) Deadline: Feb. 12, 2017

K99/R00 NIH Pathway to Independence Award (PA-16-077) Deadline: Feb. 12, 2017

Howard Hughes Medical Institute Hanna H. Gray Fellows Program Deadline:  Feb. 15, 2017

NHLBI Mentored Career Development Award to Promote Faculty Diversity in Biomedical Research (K01) (RFA-HL-16-006) Deadline: Feb. 18, 2017

This year's Dr. Lawrence H. and Mrs. Roberta Cohn Visiting Lecture Series took place on September 26, 2016.

The guest speaker was Tomislav Mihaljevic, MD, Chief Exec-utive Officer of Cleveland Clinic Abu Dhabi.

His talk was titled "Cleveland Clinic Abu Dhabi: Internation-al Growth of the U.S. Hospital Care Industry".

Dr. Lawrence H. Cohn and Mrs. Roberta Cohn

Second Annual Dr. Lawrence H. & Mrs. Roberta Cohn Visiting Lecture

Vascular Residencyand FellowshipInterview DatesVascular Surgery 0+5 Integrated Residency

ProgramInterview Date - January 19, 2017

Vascular Surgery Two-year Traditional Fellowship Program

Interview Date – March – Date TBD

A jointly-sponsored lecture by Stanford's Department of Cardiothoracic Surgery and the Cardiovascular Institute will be held at 12:30 p.m., Tuesday, Dec. 6, at the Li Ka Shing Cen-ter for Learning and Knowledge (room LK130), 291 Campus Drive, Stanford.

The guest speaker will be Ralph J. Damiano, MD, the Evarts A. Graham Professor of Surgery; the Chief, Division of Car-diothoracic Surgery; and the Co-Chair of the Heart & Vascu-lar Center, at Washington University School of Medicine.

Registration is encouraged: http://tinyurl.com/cvi-ct-2016.

Ralph J. Damiano, MD

CT Surgery Translational Surgeon Scientist Distinguished Lecture

c v i . s ta n fo rd .e d u | 11

2016-2017Frontiers in Cardiovascular Science

Li Ka Shing Center for Learning & Knowledge | 291 Campus Drive, Stanford, CA 94305Tuesdays from 12:30 - 1:20 p.m. (unless otherwise stated)

NOVEMBER 01, 2016Kirk U. Knowlton, MDDirector of Cardiovascular Research andCo-Chief of CardiologyIntermountain Heart Institute

NOVEMBER 08, 2016Brian H. Annex, MDChief, Division of Cardiovascular MedicineChair, George A. Beller, MDLantheus Medical Imaging Distinguished Professor of Cardiovascular MedicineUniversity of Virginia Health System

NOVEMBER 22, 2016Jake Lusis, PhDProfessor of Medicine Cardiology andMicrobiology, Immunology & MolecularGeneticsVice-Chair of Human GeneticsDavid Geffen School of Medicine, UCLA

DECEMBER 06, 2016Ralph J. Damiano, MDEvarts A. Graham Professor, Surgery;Chief, Division of Cardiothoracic SurgeryWashington University School of MedicineRegister: http://tinyurl.com/cvi-ct-2016

DECEMBER 13, 2016Jonathan M. Graff, MD, PhDProfessor, Dept. of Developmental BiologyUniversity of Texas Southwestern

JANUARY 10, 2017Timothy J. Kamp, MD, PhDCo-director, Stem Cell and Regenerative Medicine Center

Professor of Medicine, CardiologyUniversity of Wisconsin-Madison School of Medicine and Public Health

JANUARY 17, 2017Rui-Ping Xiao, MD, PhDProfessor at the Institute of MolecularMedicine, Peking University, Beijing, China

JANUARY 24, 2017Mark A. Creager, MD, FAHADirector, Heart and Vascular Center,Dartmouth-Hitchcock Medical CenterProfessor of Medicine, Geisel School ofMedicine at Dartmouth

FEBRUARY 28, 2017Gerald W. Dorn, II, MDPhilip and Sima K Needleman ProfessorDirector, Center for PharmacogenomicsWashington University School of Medicine

MARCH 7, 2017Vinicio de Jesus Perez, MDAssistant Professor of Medicine (Pulmonary and Critical Care Medicine)Stanford University

and

Edda Spiekerkoetter, MD Assistant Professor of Medicine (Pulmonary and Critical Care Medicine)Stanford University

MARCH 23, 2017 (THURSDAY)Maruo Giacca, MDDirector-General International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy

MARCH 28, 2017Peter J. Mohler, PhDProfessor and Chair, Physiology and Cell BiologyOhio State University

MAY 9, 2017Charles E. Murry, MD, PhDWoods Professor of Pathology, Bioengineering and Medicine/CardiologyCo-Director, Institute for Stem Cell and Regenerative MedicineCo-Director, Center for Cardiovascular Biology University of Washington

June 6, 2017John L. Spudich, PhDRobert A. Welch Distinguished Chair in ChemistryDirector, Center for Membrane BiologyProfessor, Biochemistry & Molecular BiologyUniversity of Texas, Houston, Texas

June 6, 2017Louis J. Dell'Italia, MDProfessor, UAB Comprehensive Cardiovascular CenterUniversity of Alabama at Birmingham

NOVEMBER AHA Scientific Sessions November 12-16, 2016, Orleans, LA

The Future of Cardiovascular Research November 21, 2016 | 12 - 5p Li Ka Shing Center Lunch, science, wine & cheese

DECEMBER World Stem Cell Summit December 6-8, 2016, West Palm Beach, FL

National and Global Cardiovascular Conferences

c v i . s ta n fo rd .e d u | 12

Our MissionWe provide quantitative assessment of clinical cardiovascular phenotypes for translational research and clinical tri-als. These cardiovascular phenotypes include evaluating cardiac structure and function, measuring carotid intimal thickness and arterial stiffness, and test-ing endothelial function and cardiopul-monary exercise testing.

In collaboration with the Human Im-mune Monitoring Center at Stanford and members of the Cardiovascular Institute, we also offer central blood processing and banking capabilities. We are also de-veloping new biomarker platforms and imaging modalities.

Key Initiatives1. Stanford Athletic Screening Program. The BPCL is the core laboratory responsible for the echocar-diographic studies of Stanford Athletic Screening Program and has imaged more than 500 athletes.

2. Stanford Immune Aging Longitudinal Study. The BPCL is the core providing clinical cardiovascular phenotypes for collaboration through the NIH funded projects of the Immunity Transplantation and Infection Institute led by Mark Davis, MD.

3. The Pulmonary Hypertension Wall Center Outcome and Physiology Studies. The BPCL works closely with the Vera Moulton Wall Center for Pulmonary Vascular Disease to provide quantitative echocardiographic assessment of the right heart.

4. The CCML-Stanford Collaborative Effort. Through a close collaboration with the University of Paris and the Marie-Lannelongue surgical center (CCML), the BPCL is providing quantitative analysis of experimental and clinical studies focused on right heart physiology. The CCML is a recognized worldwide center of expertise in pulmonary hypertension (Elie Fadel MD PhD and Olaf Mercier MD PhD).

Clinical Biomarker & Phenotyping Core Lab (BPCL)

Biobank

Stanford CVI Human iPSC Biobank ServiceNormal and patient-derived reprogrammed cardiomyocytes is a tremendous resource for re-searchers and physicians here at Stanford and around the country. Understanding the disease process directly at the population level and observing these cells as surrogates under a myr-iad conditions has the potential to be a game-changer for cardiovascular medical research.

To facilitate research in a dish that allows screening of new compounds or characterization of human disease phenotypes using cardiomyocytes, the Institute created a service by which de-identified PBMC samples from selected patients can be sent to Stanford CVI for repro-gramming free of cost. Please contact Joseph Wu, MD, PhD ( joewu@stanford.edu) with any questions.

SCVI biobank is supported in part by National Heart, Lung and Blood Institute (NHLBI), the California Institute for Regenerative Medicine (CIRM), and the Stanford Cardiovascular Insti-tute (CVI). Stanford iPSC Biobank was recently mentioned in Nature Methods news: http://www.nature.com/nmeth/journal/v12/n2/full/nmeth.3263.html.

Lab Resources

Contact Us

Francois Haddad, MD, Clinical Associate Professor of Medicine (Cardiovascular Medicine): fhaddad@stanford.edu.

3DQ Imaging LaboratoryStanford’s 3DQ Imaging Laboratory was established in 1996 at Stanford by Geof-frey Rubin, MD, and Sandy Napel, PhD, Professor of Radiology (General Radiol-ogy) and, by courtesy, Electrical Engi-neering. Today the center is co-directed by Dominik Fleischmann, MD, Profes-sor of Radiology (General Radiology) and Roland Bammer, PhD, Associate Professor (Research) of Radiology.

Currently the lab processes over 1,200 clinical cases per month. Linda Horst, Marc Sofilos, and Shannon Walters are an integral part of the 3DQ Lab manage-ment team.

For more visit: http://3dqlab.stanford.

edu/

c v i . s ta n fo rd .e d u | 13

Communication is at the heart of scientific advancement and innovation. This quarter the Stanford Cardiovascular Institute members published over 146 original manuscripts and reviews further contributing to our understanding of cardiovascular biology and disease. In the following pages, we highlight selected manuscripts by our members.

Member Publications

JULY 2016

Defining and refining indications for transcatheter pulmonary valve replace-ment in patients with repaired tetralogy of Fallot: Contributions from anatomi-cal and functional imaging. Tretter JT, Friedberg MK, Wald RM, McElhinney DB. Int J Cardiol. 2016.

A Prospective Evaluation of Systemic Biomarkers and Cognitive Function Associated with Carotid Revascularization. Zuniga MC, Tran TB, Baughman BD, Raghuraman G, Hitchner E, Rosen A, Zhou W. Ann Surg. 2016.

Advances in pediatric cardiology 2016. Bernstein D. Curr Opin Pediatr. 2016.

Perioperative management of pediatric en-bloc combined heart-liver trans-plants: a case series review. Navaratnam M, Ng A, Williams GD, Maeda K, Mendoza JM, Concepcion W, Hollander SA, Ramamoorthy C. Paediatr Anaesth. 2016.

Increased Pyruvate Dehydrogenase Kinase 4 Expression in Lung Pericytes Is As-sociated with Reduced Endothelial-Pericyte Interactions and Small Vessel Loss in Pulmonary Arterial Hypertension. Yuan K, Shao NY, Hennigs JK, Discipulo M, Orcholski ME, Shamskhou E, Richter A, Hu X, Wu JC, de Jesus Perez VA. Am J Pathol. 2016.

Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis Is Associated With Downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM. Perisic Mat-ic L, Rykaczewska U, Razuvaev A, Sabater-Lleal M, Lengquist M, Miller CL, Er-icsson I, Röhl S, Kronqvist M, Aldi S, Magné J, Paloschi V, Vesterlund M, Li Y, Jin H, Diez MG, Roy J, Baldassarre D, Veglia F, Humphries SE, de Faire U, Tremoli E, Odeberg J, Vukojević V, Lehtiö J, Maegdefessel L, Ehrenborg E, Paulsson-Berne G, Hansson GK, Lindeman JH, Eriksson P, Quertermous T, Hamsten A, Hedin U. Arterioscler Thromb Vasc Biol. 2016.

Lack of Left Ventricular Ejection Fraction Measurement Following a High B-type Natriuretic Peptide Value. Heidenreich PA, Gholami P, Lin S. Crit Pathw Cardi-ol. 2016.

Right heart imaging in patients with heart failure: a tale of two ventricles. Am-sallem M, Kuznetsova T, Hanneman K, Denault A, Haddad F. Curr Opin Cardiol. 2016.

1-Year Outcomes of FFRCT-Guided Care in Patients With Suspected Coronary Disease: The PLATFORM Study. Douglas PS, De Bruyne B, Pontone G, Patel MR, Norgaard BL, Byrne RA, Curzen N, Purcell I, Gutberlet M, Rioufol G, Hink U, Schuchlenz HW, Feuchtner G, Gilard M, Andreini D, Jensen JM, Hadamitzky M, Chiswell K, Cyr D, Wilk A, Wang F, Rogers C, Hlatky MA; PLATFORM Investiga-tors. J Am Coll Cardiol. 2016.

Surgical Technique for Repair of Peripheral Pulmonary Artery Stenosis and Other Complex Peripheral Reconstructions. Mainwaring RD, Ibrahimiye AN, Hanley FL. Ann Thorac Surg. 2016.

Standards of Evidence and Mechanistic Inference in Autosomal Recessive Hypercholesterolemia. Priest JR, Knowles JW. Arterioscler Thromb Vasc Biol. 2016.

Can Cardiac Conduction System Disease Be Prevented? Narayan SM, Baykaner T, Maron DJ. JAMA Intern Med. 2016.

Transcatheter valve implantation for right atrium-to-right ventricle conduit obstruction or regurgitation after modified Björk-fontan procedure. Shah AH, Horlick EM, Eicken A, Asnes JD, Bocks ML, Boudjemline Y, Cabalka AK, Fagan TE, Schubert S, Mahadevan VS, Dvir D, Osten M, McElhinney DB. Catheter Cardiovasc Interv. 2016 Jul 28.

Critical Role of Coaptive Strain in Aortic Valve Leaflet Homeostasis: Use of a Novel Flow Culture Bioreactor to Explore Heart Valve Mechanobiology. Maeda K, Ma X, Hanley FL, Riemer RK. J Am Heart Assoc. 2016 Jul 27;5(8).

Cellular Taxonomy of the Mouse Striatum as Revealed by Single-Cell RNA-Seq. Gokce O, Stanley GM, Treutlein B, Neff NF, Camp JG, Malenka RC, Rothwell PE, Fuccillo MV, Südhof TC, Quake SR. Cell Rep. 2016 Jul 26;16(4):1126-37.

Attenuated-Signal Plaque Progression Predicts Long-Term Mortality After Heart Transplantation: IVUS Assessment of Cardiac Allograft Vasculopathy. Okada K, Fearon WF, Luikart H, Kitahara H, Otagiri K, Tanaka S, Kimura T, Yock PG, Fitzgerald PJ, Yeung AC, Valantine HA, Khush KK, Honda Y. J Am Coll Cardiol. 2016 Jul 26;68(4):382-92.

Statins, familial hypercholesterolemia, and type 2 diabetes. Reaven GM. J Intern Med. 2016 Jul 25.

Lung transplantation following death by drowning: a review of the current literature. Pasupneti S, Patel K, Mooney JJ, Chhatwani L, Dhillon G, Weill D. Clin Transplant. 2016 Jul 22.

Management of Patients With NSTE-ACS: A Comparison of the Recent AHA/ACC and ESC Guidelines. Rodriguez F, Mahaffey KW. J Am Coll Cardiol. 2016 Jul 19;68(3):313-21.

Statins in Familial Hypercholesterolemia: Translating Evidence to Action. Knowles JW. J Am Coll Cardiol. 2016 Jul 19;68(3):261-4.

Terminating atrial fibrillation by cooling the heart. Narayan SM, Baykaner T, Sahli Costabal F, Kuhl E. Heart Rhythm. 2016 Jul 17. pii: S1547-5271(16)30547-1.

Defining a Mobile Health Roadmap for Cardiovascular Health and Disease. Eapen ZJ, Turakhia MP, McConnell MV, Graham G, Dunn P, Tiner C, Rich C, Harrington RA, Peterson ED, Wayte P. J Am Heart Assoc. 2016 Jul 12;5(7).

Spatiotemporal Reconstruction of the Human Blastocyst by Single-Cell Gene-Expression Analysis Informs Induction of Naive Pluripotency. Durruthy-Durruthy J, Wossidlo M, Pai S, Takahashi Y, Kang G, Omberg L, Chen B, Nakau-chi H, Reijo Pera R, Sebastiano V. Dev Cell. 2016 Jul 11;38(1):100-15.

Pediatric Echocardiography by Work Relative Value Units: Is Study Complex-ity Adequately Captured? Balasubramanian S, Kipps AK, Smith SN, Tacy TA, Selamet Tierney ES. J Am Soc Echocardiogr. 2016 Jul 9.

Fractional Flow Reserve and Coronary Computed Tomographic Angiography: A Review and Critical Analysis. Hecht HS, Narula J, Fearon WF. Circ Res. 2016 Jul 8;119(2):300-16.

Vorapaxar: emerging evidence and clinical questions in a new era of PAR-1 inhibition. Ungar L, Rodriguez F, Mahaffey KW. Coron Artery Dis. 2016 Jul 8.

Integrative functional genomics identifies regulatory mechanisms at coronary artery disease loci. Miller CL, Pjanic M, Wang T, Nguyen T, Cohain A, Lee JD, Perisic L, Hedin U, Kundu RK, Majmudar D, Kim JB, Wang O, Betsholtz C, Ruu-salepp A, Franzén O, Assimes TL, Montgomery SB, Schadt EE, Björkegren JL, Quertermous T. Nat Commun. 2016 Jul 8;7:12092.

Allogeneic Mesenchymal Stromal Cells Overexpressing Mutant Human Hypoxia-Inducible Factor 1-α (HIF1-α) in an Ovine Model of Acute Myocardial Infarction. Hnatiuk AP, Ong SG, Olea FD, Locatelli P, Riegler J, Lee WH, Jen CH, De Lorenzi A, Giménez CS, Laguens R, Wu JC, Crottogini A. J Am Heart Assoc. 2016 Jul 6;5(7).

On-Treatment Outcomes in Patients With Worsening Renal Function With

c v i . s ta n fo rd .e d u | 14

Rivaroxaban Compared With Warfarin: Insights From ROCKET AF. Fordyce CB, Hellkamp AS, Lokhnygina Y, Lindner SM, Piccini JP, Becker RC, Berkowitz SD, Breithardt G, Fox KA, Mahaffey KW, Nessel CC, Singer DE, Patel MR; ROCKET AF Steering Committee and Investigators. Circulation. 2016 Jul 5;134(1):37-47.

Patterns of Carotid Intima-Media Thickness Progression in Kawasaki Patients: A Crystal Ball for Long-Term Vascular Health? Haley J, Selamet Tierney ES. J Am Heart Assoc. 2016 Jul 5;5(7).

The Impact of Fitness on Surgical Outcomes: The Case for Prehabilitation. Myers JN, Fonda H. Curr Sports Med Rep. 2016 Jul-Aug;15(4):282-9.

Notch-independent RBPJ controls angiogenesis in the adult heart. Díaz-Trelles R, Scimia MC, Bushway P, Tran D, Monosov A, Monosov E, Peterson K, Rentschler S, Cabrales P, Ruiz-Lozano P, Mercola M. Nat Commun. 2016 Jun 30;7:12088.

Effects of cellular origin on differentiation of human induced pluripotent stem cell-derived endothelial cells. Hu S, Zhao MT, Jahanbani F, Shao NY, Lee WH, Chen H, Snyder MP, Wu JC. JCI Insight. 2016.

Intracoronary Gene Transfer of Adenylyl Cyclase 6 in Patients With Heart Failure: A Randomized Clinical Trial. Hammond HK, Penny WF, Traverse JH, Henry TD, Watkins MW, Yancy CW, Sweis RN, Adler ED, Patel AN, Murray DR, Ross RS, Bhargava V, Maisel A, Barnard DD, Lai NC, Dalton ND, Lee ML, Narayan SM, Blanchard DG, Gao MH. JAMA Cardiol. 2016.

Sudden Cardiac Death After Non-ST-Segment Elevation Acute Coronary Syndrome. Hess PL, Wojdyla DM, Al-Khatib SM, Lokhnygina Y, Wallentin L, Arm-strong PW, Roe MT, Ohman EM, Harrington RA, Alexander JH, White HD, Van de Werf F, Piccini JP, Held C, Aylward PE, Moliterno DJ, Mahaffey KW, Tricoci P. JAMA Cardiol. 2016.

Oral Anticoagulant Therapy Prescription in Patients With Atrial Fibrillation Across the Spectrum of Stroke Risk: Insights From the NCDR PINNACLE Registry. Hsu JC, Maddox TM, Kennedy KF, Katz DF, Marzec LN, Lubitz SA, Gehi AK, Tura-khia MP, Marcus GM. JAMA Cardiol. 2016.

AUGUST 2016

Consistent Reduction in Periprocedural Myocardial Infarction With Cangrelor as Assessed by Multiple Definitions: Findings From CHAMPION PHOENIX (Cangre-lor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibi-tion). Cavender MA, Bhatt DL, Stone GW, White HD, Steg PG, Gibson CM, Hamm CW, Price MJ, Leonardi S, Prats J, Deliargyris EN, Mahaffey KW, Harrington RA; CHAMPION PHOENIX Investigators*. Circulation. 2016.

Modeling the Myxomatous Mitral Valve With Three-Dimensional Echocardiogra-phy. Pouch AM, Jackson BM, Lai E, Takebe M, Tian S, Cheung AT, Woo YJ, Patel PA, Wang H, Yushkevich PA, Gorman RC, Gorman JH 3rd. Ann Thorac Surg. 2016.

Transcriptome Profiling of Patient-Specific Human iPSC-Cardiomyocytes Pre-dicts Individual Drug Safety and Efficacy Responses In Vitro. Matsa E, Burridge PW, Yu KH, Ahrens JH, Termglinchan V, Wu H, Liu C, Shukla P, Sayed N, Churko JM, Shao N, Woo NA, Chao AS, Gold JD, Karakikes I, Snyder MP, Wu JC. Cell Stem Cell. 2016 Sep 1;19(3):311-25.

Kank2 activates talin, reduces force transduction across integrins and induces central adhesion formation. Sun Z, Tseng HY, Tan S, Senger F, Kurzawa L, Ded-den D, Mizuno N, Wasik AA, Thery M, Dunn AR, Fässler R. Nat Cell Biol. 2016.

3D Graphitic Foams Derived from Chloroaluminate Anion Intercalation for Ultrafast Aluminum-Ion Battery. Wu Y, Gong M, Lin MC, Yuan C, Angell M, Huang L, Wang DY, Zhang X, Yang J, Hwang BJ, Dai H. Adv Mater. 2016 Aug 29.

VCP recruitment to mitochondria causes mitophagy impairment and neuro-degeneration in models of Huntington’s disease. Guo X, Sun X, Hu D, Wang YJ, Fujioka H, Vyas R, Chakrapani S, Joshi AU, Luo Y, Mochly-Rosen D, Qi X. Nat Commun. 2016 Aug 26;7:12646.

Can heavy isotopes increase lifespan? Studies of relative abundance in various organisms reveal chemical perspectives on aging. Li X, Snyder MP. Bioessays. 2016 Aug 24.

Notch: A multi-functional integrating system of microenvironmental signals. LaFoya B, Munroe JA, Mia MM, Detweiler MA, Crow JJ, Wood T, Roth S, Sharma B, Albig AR. Dev Biol. 2016 Aug 24.

Adult Stem Cell Therapy and Heart Failure, 2000 to 2016: A Systematic Review Nguyen PK, Rhee JW, Wu JC. JAMA Cardiol. 2016 Aug 24.

Multiple allogeneic progenitors in combination function as a unit to support early transient hematopoiesis in transplantation. Ishida T, Takahashi S, Lai CY, Nojima M, Yamamoto R, Takeuchi E, Takeuchi Y, Higashihara M, Nakauchi H, Otsu M. J Exp Med. 2016 Aug 22;213(9):1865-80.

Use of Dual Antiplatelet Therapy and Patient Outcomes in Those Undergoing Percutaneous Coronary Intervention: The ROCKET AF Trial. Sherwood MW, Cyr DD, Jones WS, Becker RC, Berkowitz SD, Washam JB, Breithardt G, Fox KA, Halperin JL, Hankey GJ, Singer DE, Piccini JP, Nessel CC, Mahaffey KW, Patel MR. JACC Cardiovasc Interv. 2016 Aug 22;9(16):1694-702.

Real-world performance of paclitaxel drug-eluting bare metal stenting (Zilver PTX) for the treatment of femoropopliteal occlusive disease. Tran K, Ullery BW, Kret MR, Lee JT. Ann Vasc Surg. 2016 Aug 20.

Pulling the RIPCORD: FFRCT to Improve Interpretation of Coronary CT Angiogra-phy. Fearon WF, Lee JH. JACC Cardiovasc Imaging. 2016 Aug 20.

STAMS: STRING-assisted module search for genome wide association studies and application to autism. Hillenmeyer S, Davis LK, Gamazon ER, Cook EH, Cox NJ, Altman RB. Bioinformatics. 2016 Aug 19.

Alternative approaches to generating cardiomyocytes are under development. Chen IY, Matsa E, Wu JC. Nat Rev Cardiol. 2016 Aug 19.

Structure-based discovery of opioid analgesics with reduced side effects. Manglik A, Lin H, Aryal DK, McCorvy JD, Dengler D, Corder G, Levit A, Kling RC, Bernat V, Hübner H, Huang XP, Sassano MF, Giguère PM, Löber S, Da Duan, Scherrer G, Kobilka BK, Gmeiner P, Roth BL, Shoichet BK. Nature. 2016 Aug 17;537(7619):185-190.

Standardization of Fractional Flow Reserve Measurements. Toth GG, Johnson NP, Jeremias A, Pellicano M, Vranckx P, Fearon WF, Barbato E, Kern MJ, Pijls NH, De Bruyne B. J Am Coll Cardiol. 2016 Aug 16;68(7):742-53.

Predicting non-small cell lung cancer prognosis by fully automated microscopic pathology image features. Yu KH, Zhang C, Berry GJ, Altman RB, Ré C, Rubin DL, Snyder M. Nat Commun. 2016 Aug 16;7:12474.

Towards precision medicine. Ashley EA. Nat Rev Genet. 2016 Aug 16;17(9):507-22.

An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease. Horvath S, Gurven M, Levine ME, Trumble BC, Kaplan H, Allayee H, Ritz BR, Chen B, Lu AT, Rickabaugh TM, Jamieson BD, Sun D, Li S, Chen W, Quintana-Murci L, Fagny M, Kobor MS, Tsao PS, Reiner AP, Edlefsen KL, Absher D, Assimes TL. Genome Biol. 2016 Aug 11;17(1):171.

Electroanatomic Properties of the Myocardium Predict Response to CD34+ Cell Therapy in Patients With Ischemic and Nonischemic Heart Failure. Zemljic G, Poglajen G, Sever M, Cukjati M, Frljak S, Androcec V, Cernelc P, Haddad F, Vrtovec B. J Card Fail. 2016 Aug 11.

Hypertriglyceridemia: A simple approach to identify insulin resistance and enhanced cardio-metabolic risk in patients with prediabetes. Abbasi F, Kohli P, Reaven GM, Knowles JW. Diabetes Res Clin Pract. 2016 Aug 6;120:156-161.

The All-Chemical Approach: A Solution for Converting Fibroblasts Into Myo-cytes. Liu Y, Mercola M, Schwartz RJ. Circ Res. 2016 Aug 5;119(4):505-7.

Functional Neurologic Outcomes Change Over the First 6 Months After Cardiac Arrest. Tong JT, Eyngorn I, Mlynash M, Albers GW, Hirsch KG. Crit Care Med. 2016 Aug 5.

Combinatorial Extracellular Matrix Microenvironments Promote Survival and Phenotype of Human Induced Pluripotent Stem Cell-Derived Endothelial Cells in Hypoxia. Hou L, Coller J, Natu V, Hastie TJ, Huang NF. Acta Biomater. 2016 Aug 4.

c v i . s ta n fo rd .e d u | 15

Computing disease incidence, prevalence and comorbidity from electronic medical records. Bagley SC, Altman RB. J Biomed Inform. 2016 Aug 4.

Implications of different criteria for percutaneous coronary intervention-relat-ed myocardial infarction on study results of three large phase III clinical trials: The CHAMPION experience. Leonardi S, Lopes RD, Steg PG, Abnousi F, Menozzi A, Prats J, Mangum S, Wilson M, Todd M, Stone GW, Gibson CM, Hamm CW, Price MJ, White HD, Harrington RA, Bhatt DL, Mahaffey KW. Eur Heart J Acute Cardiovasc Care. 2016 Aug 2.

Apelin-13 infusion salvages the peri-infarct region to preserve cardiac function after severe myocardial injury. Chung WJ, Cho A, Byun K, Moon J, Ge X, Seo HS, Moon E, Dash R, Yang PC. Int J Cardiol. 2016 Aug 2;222:361-367.

Effect of age on efficacy and safety of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome: Insights from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial. Armaganijan LV, Alexander KP, Huang Z, Tricoci P, Held C, Van de Werf F, Armstrong PW, Aylward PE, White HD, Moliterno DJ, Wallentin L, Chen E, Harrington RA, Strony J, Mahaffey KW, Lopes RD. Am Heart J. 2016 Aug;178:176-84.

Blood pressure control and stroke or bleeding risk in anticoagulated pa-tients with atrial fibrillation: Results from the ROCKET AF Trial. Vemulapalli S, Hellkamp AS, Jones WS, Piccini JP, Mahaffey KW, Becker RC, Hankey GJ, Berkowitz SD, Nessel CC, Breithardt G, Singer DE, Fox KA, Patel MR. Am Heart J. 2016 Aug;178:74-84.

Albuminuria and cardiovascular events in patients with acute coronary syndromes: Results from the TRACER trial. Åkerblom A, Clare RM, Lokhnygina Y, Wallentin L, Held C, Van de Werf F, Moliterno DJ, Patel UD, Leonardi S, Armstrong PW, Harrington RA, White HD, Aylward PE, Mahaffey KW, Tricoci P. Am Heart J. 2016 Aug;178:1-8.

Syncope While Driving in Denmark-Reply. Numé AK, Hlatky MA, Ruwald MH. JAMA Intern Med. 2016 Aug 1;176(8):1230-1.

Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Recapitulate Patient Specific Properties. Lombardo DM, Fenton FH, Narayan SM, Rappel WJ. PLoS Comput Biol. 2016 Aug 5;12(8):e1005060.

Considering Cost-Effectiveness in Cardiology Clinical Guidelines: Progress and Prospects. Hlatky MA. Value Health. 2016 Jul-Aug;19(5):516-9.

Noninvasive Tracking of Quiescent and Activated Muscle Stem Cell (MuSC) En-graftment Dynamics In Vivo. Ho AT, Blau HM. Methods Mol Biol. 2016;1460:181-9.

Protein Corona Influences Cell-Biomaterial Interactions in Nanostructured Tissue Engineering Scaffolds. Serpooshan V, Mahmoudi M, Zhao M, Wei K, Sivanesan S, Motamedchaboki K, Malkovskiy AV, Gladstone AB, Cohen JE, Yang PC, Rajadas J, Bernstein D, Woo YJ, Ruiz-Lozano P. Adv Funct Mater. 2015 Jul 22;25(28):4379-4389.

SEPTEMBER 2016

Novel Therapies for Familial Hypercholesterolemia. Parizo J, Sarraju A, Knowles JW. Curr Treat Options Cardiovasc Med. 2016 Nov;18(11):64.

Rationale and design of Apo-I Event Reduction in Ischemic Syndromes I (AEGIS-I): A phase 2b, randomized, placebo-controlled, dose-ranging trial to investigate the safety and tolerability of CSL112, a reconstituted, infusible, human apoA-I, after acute myocardial infarction. Gibson CM, Korjian S, Tricoci P, Daaboul Y, Alexander JH, Steg PG, Lincoff AM, Kastelein JJ, Mehran R, D'An-drea D, Merkely B, Zarebinski M, Ophius TO, Harrington RA. Am Heart J. 2016 Oct;180:22-8.

NETs Activate Pulmonary Arterial Endothelial Cells. Rabinovitch M. Arterio-scler Thromb Vasc Biol. 2016 Oct;36(10):2035-7.

Romidepsin for the treatment of relapsed/refractory cutaneous T-cell lympho-ma (mycosis fungoides/Sézary syndrome): Use in a community setting. Reddy SA. Crit Rev Oncol Hematol. 2016 Oct;106:99-107.

Genetics and Genomics of Coronary Artery Disease. Pjanic M, Miller CL, Wirka R, Kim JB, DiRenzo DM, Quertermous T. Curr Cardiol Rep. 2016 Oct;18(10):102.

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Fractional Flow Reserve in Acute Coronary Syndromes. Fearon WF, De Bruyne B, Pijls NH. J Am Coll Cardiol. 2016 Sep 13;68(11):1192-4.

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Leadership

Joseph C. Wu, MD, PhDDirector, Stanford Cardiovascular Institute Simon H. Stertzer, MD, Professor, Dept. of Medicine (Cardiovascular) & Radiology

Robert A. Harrington, MDArthur L. Bloomfield Professor of Medicine Chair, Dept. of Medicine

Stephen J. Roth MD, MPHProfessor of Pediatrics (Cardiology) at Lucile Salter Packard Children's HospitalChief, Division of Pediatric Cardiology James Baxter & Yvonne Craig Wood Medical Director CVICU, LPCH

Ronald L. Dalman, MDWalter C. and Elsa R. Chidester Professor of SurgeryChief, Division of Vascular Surgery

Michael Snyder, PhDStanford W. Ascherman, MD, FACS, Professor in Genetics Chair, Department of GeneticsDirector, Stanford Center for Genomics and Personalized Medicine

Dominik Fleischmann, MDProfessor, Dept. of RadiologyChief, Cardiovascular Imaging

Y. Joseph Woo, MDNorman E. Shumway Professor in Cardiothoracic SurgeryChair Department of Cardiothoracic Surgery

Kenneth Mahaffey, MDProfessor, Dept. of MedicineVice Chair of Medicine for Clinical Research

Alan Yeung, MDLi Ka Shing Professor of MedicineCo-Chief (Clinical), Division of Cardiovascular Medicine

Mark Nicolls, MDProfessor of MedicineChief, Pulmonary and Critical Care Medicine

Paul Yock, MDMartha Meier Weiland Professor of Bioengineering and MedicineProfessor, by courtesy, of Mechanical EngineeringDirector of Biodesign

Tom Quertermous, MDWilliam G. Irwin Professor of MedicineCo-Chief (Research), Division of Cardiovascular Medicine

Marlene Rabinovitch, MDDwight and Vera Dunlevie Professor in Pediatric Cardiology cvi.stanford.edu