AT THE FOREFRONT OF CARDIOVASCULAR MEDICINE QUARTERLY | FALL 2016 Welcoming New Faculty! Cardiovascular Koen Nieman, MD, PhD, was recently recruited by the Stanford Faculty Recruitment: Cardiovascular Medicine, Department of Radiology and the Cardio- • Two full-time academic advanced heart vascular Institute, as a new faculty member. He is a pioneer in CT failure and transplant cardiologists in the Medical Center Line. Click for details. coronary angiography, publishing over 90 research articles on car- diac imaging. Prior to joining Stanford he was the Medical Director • One full-time faculty member with an interest of the Intensive Care Unit at Erasmus Medical Center Rotterdam. He in biobanking and the use of biobanked sam- recently published a multi-center randomized trial (BEACON) study ples in population research in the University Koen Nieman, MD, PhD Tenure Line, Medical Center Line, or Non-Ten- measuring the performance of cardiac CT in the emergency ward ure Line (Research). Click for details. entitled, ‘Coronary CT Angiography for Suspected ACS in the Era of High-Sensitivity Troponins: Randomized Multicenter Study,’ in the T32 Imaging Journal American College Cardiology (2016 Jan 5;67(1):16-26). Postdoctoral Fellowship The Division of Stanford Vascular Surgery is pleased to announce the We are seeking highly qualified MD, PhD, or MD/ recruitment of Clinical Assistant Professor Jennifer Avise, MD. Dr. PhD graduates. Applicants must be either a U.S. Avise specializes in open and percutaneous treatment of peripheral citizen or permanent resident to apply. Intended vascular disease including management of claudication and limb start date: January 1, 2017. salvage techniques, vascular trauma, dialysis access, treatment of Application Deadline is Dec. 1, 2016. venous disease, aortic disease including aneurysm and dissection, For information and to apply: and management of carotid artery disease. Jennifer Avise, MD http://tinyurl.com/zz6pkaq

2017 Stanford Drug Discovery Symposium 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 Art by Ryoko Hamaguchi Texas, Southwestern) cvi.stanford.edu | 1 Amber Smith, PhD, T32 postdoc from the lab of Calvin Kuo, MD, PhD, explains her research to Michal Roof, PhD

The Stanford-Karolinska Symposium had 262 (Left) Keynote speaker, Michael Levitt, PhD, (2013 Nobel Laureate in Chemistry). (Center) Ralph Knöll, PhD, from attendees over the full-day event. the Karolinska Institute and AstraZeneca. (Right) Stefan Jovinge, MD, PhD from Spectrum Health Hospitals. 2016 Stanford-Karolinska Cardiovascular Symposium 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.

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. Clinical Research Poster Award Winners

Christopher Kowalewski Vedant Pargaonkar, MD

Evaluating New Imaging Software for Focal The Diagnostic Value of Abnormal Heart Rate Impulse and Rotor Mapping in Atrial Fibrilla- Recovery during Exercise Stress Testing in tion Ablation Procedures Predicting the Presence of Endothelial and Sanjiv Narayan, MD, Lab Microvascular Dysfunction Jennifer Tremmel, MD, Lab Basic Research Poster Award Winners

Milos Pjanic, PhD Nazish Sayed, MD, PhD Darshan Trivedi, PhD

TCF21 Interacts With Modeling Endothe- Beyond the Myosin Aryl-hydrocarbon lial Dysfunction in Mesa: A Potential Uni- Receptor to Modify LMNA-related Dilated fying Hypothesis on Coronary Smooth Mus- Cardiomyopathy the Molecular Basis of cle Cell Response Hyper-contractility Joseph C. Wu, MD, PhD, Thomas Quertermous, Lab James Spudich, PhD, MD, Lab Lab cvi.stanford.edu | 2 Improving Outcomes in Pulmonary Hypertension

The 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

Vinicio de Jesus Perez, MD 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. How Does a Heart Defect Start? Stanford Scientists Use Stem Cells to Find Out By Erin Digitale long before birth, when the heart muscle fails also explored the exact signaling pathways

For years, pediatric cardiologists have been to make an important developmental shift. In that cause the problem, showing that the trying to understand the origin of a puzzling the earliest stages of cardiac development, it’s magnitude of signaling abnormalities could structural defect of the heart muscle wall, normal for the muscle to be spongy. explain differences in symptom a congenital problem called left ventricu- At about 8 weeks of gestation, the severity between family mem- lar non-compaction (LVNC). In people with human heart muscle is supposed bers. They created a mouse mod- this defect, the muscle of the heart’s biggest to compress into a thick, compact el with the family’s gene defect pumping chamber looks spongy rather than mass, but that shift doesn’t happen for further characterization, and smooth and solid. correctly in LVNC patients. also showed that blocking the faulty signal from the altered Another mystery about the dis- “For such congenital cardiomyopathies, cur- TBX20 could restore the mutated ease is its range of severity, which rently there is no effective therapy, and the cells’ ability to proliferate. only ‘cure’ is heart transplantation,” said Stan- varies from no symptoms at all to Spongy Heart Muscle The new findings still leave unan- ford’s Joseph Wu, MD, PhD, a cardiologist who complete heart failure. As the new swered questions about the origins of LVNC. led a new study of the condition that pub- paper describes, the family who agreed to have But the paper does demonstrate how induced lished online in Nature Cell Biology. their cells studied is a good example. Of three siblings who donated cells for research, one pluripotent stem cells can overcome a research His team was looking for a new way to address had already had a heart transplant, while the hurdle, and suggests that the same methods a very old research problem: They didn’t know other two had hearts that pumped normally could help scientists tackling other hard-to- how much they could trust studies done on in spite of deeper trabeculations (the scientific study conditions. animal models of the disease. Mouse and rat word for the spongy formations). Meanwhile, “This study shows the feasibility of modeling models of LVNC also have spongy heart mus- their father had an enlarged heart, but no such developmental defects using human tis- cle, but it’s not clear if their defect starts the sponginess in his heart muscle and no other sue-specific cells, rather than relying on ani- same way as in humans, nor whether findings symptoms. mal cells or animal models,” Wu said. from rodent studies could help treat humans. Using the heart muscle cells derived from all Co-authors include Kazuki Kodo, Sang-Ging Ong, So Wu’s team used innovative stem cell tech- four people, the researchers identified the Fereshteh Jahanbani, Vittavat Termglinchan, niques instead. They took skin and blood cells gene defect that causes LVNC in this family; it Keiichi Hirono, Kolsoum InanlooRahatloo, Anteje donated by four members of a family affected codes for a cardiac transcription factor — or a D. Ebert, Praveen Shukla, Oscar J. Abilez, Jared by LVNC and converted them into induced plu- protein that controls the expression of other M. Churko, Ioannis Karakikes, Gwanghyun Jung, ripotent stem cells, which are stem cells made genes — called TBX20. The scientists conduct- Fukiko Ichida, Seam M. Wu, Michael P. Snyder, and in a lab from adult cells. Using these stem ed several experiments to figure out how the co-senior author Daniel Bernstein. cells, the researchers then made human heart TBX20 abnormality changes heart muscle cell Full Story: http://scopeblog.stanford. muscle cells that they could study in a dish. proliferation — with the abnormality, the cells edu/2016/09/20/how-does-a-heart-defect-start-stan- Researchers already knew that LVNC begins don’t proliferate enough, it turns out. They ford-scientists-use-stem-cells-to-find-out/ cvi.stanford.edu | 3 Stanford Part of New Biohub Collaboration By Amy Adams Stanford will be one of three Bay Area universities participating in a new bioscience collaboration funded through a $600 million commitment by the Chan Zuckerberg Initiative Facebook 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. Gene could help explain insulin resistance By 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 Joshua Knowles, MD, PhD 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 Indumathi more weight and had larger fat cells and higher levels of biomarkers indicating inflammation than did regular Chennamsetty, PhD 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 cvi.stanford.edu | 4 Researchers Launch iPhone App to Study Peripheral Artery Disease By Tracie White join clinical research studies. Since its launch over a year Stanford University School of Medicine researchers have launched a ago, the software has been free iPhone app designed to help them conduct a clinical study to used by researchers to collect discover better treatments for peripheral artery disease and as a con- data on diseases ranging from venient way for people with the disease to monitor their daily activity. Photo by Norbert von der Groeben diabetes to melanoma. Stan- “We hope to gain insights into patterns of disease progression over ford researchers launched one of the first of these studies, MyHeart time by collecting participants’ activity data from their iPhones,” said Counts, in the spring of 2015 to study heart disease. That study has Oliver Aalami, MD, Clinical Associate Professor of vascular surgery enrolled more than 54,000 people so far. and lead investigator of the study. “We will be looking for any chang- Aalami said the goal for the PAD study is to enroll 2,000 to 5,000 es in activity patterns that may indicate disease advancement.” participants, “much more than you can do with a traditional trial.” Peripheral artery disease, which affects about 12 million people in Researchers emphasize that the app is not a medical diagnostic the United States, is a circulatory problem caused by a buildup of tool and isn’t designed to provide medical advice, professional plaque in the peripheral arteries, most commonly in the legs. Symp- diagnosis, opinion, treatment or health-care services. All partic- toms include cramping and pain while walking or climbing stairs. ipants’ data will be stored using military-grade encryption, and Treatment is directed at reducing leg pain and the risk of heart at- participant names will be replaced by random codes, keeping tack and stroke from clogged arteries. identities and medical information confidential, the researchers “One of the key metrics we will look at is the greatest distance that said. With permission from a participant, his or her de-identified people with PAD can walk without stopping,” Aalami said. “It gets data may be shared with researchers at other institutions ap- really painful, and they have to stop and rest before continuing on.” proved by Stanford.

The VascTrac app will collect activity data using Apple’s Research- The trial is being sponsored by the companies Abbott Vascular, Kit, an open-source framework that allows iPhone users to easily Cook Medical, W. L. Gore & Associates and Microsoft. Recipients of Stanford-Intermountain Seed Grants Stanford Medicine and Intermountain Healthcare have announced the cardiovascular medicine; Kirk Knowlton, MD, Intermountain car- recipients of more than $500,000 in seed grants focused on transform- diovascular medicine. ing health care. • Translational approaches to the mechanisms of septic cardiomy- opathy — Euan Ashley, MRCP, DPhil, associate professor of cardio- Earlier this year, the two organizations announced a collaboration to vascular medicine; Samuel Brown, MD, Intermountain critical care enable joint clinical, research and education projects. Intermountain medicine. Healthcare is a not-for-profit health-care system based in Utah. The • Implementation and evaluation of graduating from pediatric to seed grants were awarded to projects that will be jointly led by prin- adult care — Korey Hood, PhD, clinical professor of pediatrics; Ai- cipal investigators from Stanford and Intermountain. The one-year, mee Hersh, MD, Intermountain pediatrics. $75,000 grants took effect on Nov. 1. • Impact of donor-derived BK virus infection and immune recovery Following are the recipients and their project titles: in kidney transplant recipients — Benjamin Pinsky, MD, PhD, as- sistant professor of pathology and of infectious diseases; Diane • Whole-genome DNA sequencing of stage-3 colorectal cancer — Alonso, MD, Intermountain transplant services. James Ford, MD, associate professor of oncology and of genetics at Stanford; Lincoln Nadauld, MD, PhD, Intermountain genomics • Development and implementation of a digital health-care pro- and health precision. gram for patients with atrial fibrillation — Mintu Turakhia, MD, assistant professor of cardiovascular medicine; Jared Bunch, MD, • Baseline assessment of hand hygiene practices and ICU microbi- Intermountain heart-rhythm services. ology — Arnold Milstein, MD, MPH, professor of medicine; Bill Ben- inati, MD, Intermountain critical care medicine. More information about the grant program is available by emailing: [email protected]. • Developing a precision-based approach for the diagnosis and prognosis of heart failure with preserved ejection fraction in the Full Story: https://med.stanford.edu/news/all-news/2016/10/recipients-of-stan- community — Francois Haddad, MD, clinical associate professor of ford-intermountain-seed-grants-announced.html cvi.stanford.edu | 5 Notable Awards

Leah Backhus, MD, Associate Professor of Vinicio de Jesus Perez, MD, Assistant Pro- Cardiothoracic Surgery, was appointed to fessor of Medicine, received a Young Phy- serve as a member of the Patient-Centered sician-Scientist Award from the American Outcomes Research Institute (PCORI) adviso- Society for Clinical Investigation. The award ry panel on Improving Healthcare Systems. recognizes junior researchers whose work is Her expertise will help PCORI refine and pri- notable for its insight into the mechanisms oritize research funding priorities and ensure of disease and the potential for new thera- Leah Backhus, MD Vinicio de Jesus Perez, MD that the research PCORI supports centers on pies. His research and clinical focus is pul- the outcomes that matter to patients and oth- monary hypertension and lung fibrosis. er healthcare decision makers.

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.

PJ Utz, MD

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.

Joshua Knowles, MD, PhD

Jason T. Lee, MD, was elected for a three- John Harris, MD, has been elected as the year terms as Secretary-Treasurer of the 78th President of the San Francisco Surgi- Association of Program Directors in Vascu- cal Society, founded in 1938. Former pres- lar Surgery, a national society comprised of idents have included Stanford Surgeons to surgical educators and program directors include Drs. Harry Oberhelman, James B D that oversee vascular surgery training in the Marks, R Scott Mitchell, Carlos Esquivel, and US. Sherry Wren. Jason T. Lee, MD E. John Harris, MD

Supporting the Stanford Cardiovascular Institute 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. [email protected]) or Dr. Joseph C. Wu, Director CVI ([email protected]).

For more information: http://cvi.stanford.edu/waystogive.html and http://cvi.stanford.edu Cathy Hutton cvi.stanford.edu | 6 2016 Dorothy Dee & Marjorie Helene Boring Trust Award Recipients

The Dorothy Dee & Marjorie Helene Boring Trust Award provides a stipend up to $15,000. Stanford MD, PhD, and MD/PhD students are Aditya J. Ullal encourage to apply for the Francisco Xavier Galdos MD candidate, 2nd year next cycle of awards. MD/PhD candidate Mentor: Mintu Turakhia, MD Mentor: Sean M. Wu, MD, PhD Eligibility: "Development of a Risk Score for Hospital "Investigation into Left Ventricular Cardiomyocyte • At least one quarter of Readmissions in Patients with Atrial Fibrillation" Development in Hypoplastic Left Heart Syndrome" 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- Andrew Lee Raheel Ata lar Research MD candidate, 3rd year MD candidate, 2nd year Mentor: Patricia K. Nguyen, MD To download application and Mentors: Ronald Dalman, MD; Oliver Aalami, MD additional information visit: "VascTrac – An Apple iPhone ResearchKit Study for "Efficacy of Home-Based Cardiac Rehabilitation Peripheral Artery Disease" for Improving Clinical and Immune Markers of http://tinyurl.com/ihraward Cardiovascular Health" 2016 Stanford Cardiovascular Seed Awards

Vinicio de Jesus Perez, MD Elena Matsa, PhD Assistant Professor of Medicine (Pulmonary and Critical Care Medicine) Instructor, Cardiovascular Institute "Wnt5A: A Master Regulator of Compensatory Angiogenesis in the Right Collaborators: Kenneth Mahaffey, Michael P. Snyder, PhD Ventricle and Lung" "Identification of genetic variation determining patient-specific responses to anti-diabetic drugs" Katharine Edwards, MD, Jennifer Tremmel, MD Stanford Women’s Heart Health Tracey McLaughlin, MD "Angiographic and Psychosocial Evaluation of Peripartum vs. Non:Peripartum Associate Professor of Medicine (Endocrinology) Spontaneous Coronary Artery Dissection: A Collaborative Study" Collaborators: Nazish Sayed, MD, PhD, Ian Chen, MD, PhD "Predicting Cardiovascular Benefits of Anti-diabetic Drugs" Dominik Fleischmann, MD Professor of Radiology Ashby Morrison, PhD Collaborators: Kathrin Baeumler, PhD, Anna M. Karmann Sailer, BS, Assistant Professor of Biology Alison L. Marsden, PhD Collaborators: Kristy Red-Horse, PhD and Will Greenleaf, PhD "Estimation of False- Lumen Pressure in Aortic Dissection using Patient- "Epigenetic Regulation of Cardiac Development" Specific Computational Fluid Dynamic Simulations" Jonathan Myers, PhD Eric Gross, MD Medicine-PAVA Assistant Professor of Anesthesiology, Perioperative and Pain Medicine Collaborators: Victor Froelicher, MD, Dominik Fleischmann, MD "Generation of endothelial cells resistant to hyperglycemia-induced "Efficacy of Home-Based Cardiac Rehabilitation for Improving Clinical and endothelial cell dysfunction" Imaging Markers of Cardiovascular Health"

Ellen Kuhl, PhD Sanjiv Narayan, MD Professor of Mechanical Engineering and, by courtesy, of Bioengineering Professor of Medicine (Cardiovascular Medicine) "Developing a Cardiovascular Simulator for the Cardiovascular Institute" "Computational Mapping to Guide Therapy In Atrial Fibrillation"

Won Hee Lee, PhD Virginia Winn, MD Instructor, Cardiovascular Institute Associate Professor of Obstetrics and Gynecology Collaborators: Kari Nadeau, PhD, Sang Ging Ong, PhD "Endothelial Dysfunction in Preeclampsia" "Assessing the potential health risk of e-cigarettes in diabetes"

cvi.stanford.edu | 7 Recently Awarded Projects

Daniel Bernstein, MD Jennifer R. Cochran, PhD Joshua W. Knowles, MD, PhD Mark R. Nicolls, MD Thomas Quertermous, MD hiPSC-Cardiomyocytes to Graduate Training Program Statin-associated diabetes: Stanford Training Program in Mechanism of the coronary Screen Variants Predictive of in Biotechnology Identifying Risk Factors and Lung Biology heart disease association at Doxorubicin Cardiotoxicity National Institutes of Health Physiologic Mechanisms National Institutes of Health chromosome 6q23.2 National Institutes of Health National Institutes of Health

Stanley G. Rockson, MD James A. Spudich, PhD PJ Utz, MD Cornelia Weyand, MD AIBP Mediates A NOVEL Myosin Movement in Vitro- ACE: Autoimmunity Center JAK-STAT Signaling in Giant Interplay between cholesterol Molecular Characterization of Excellence (ACE) at Cell Arteritis and Lymphangiogenesis National Institutes of Health Stanford

2016 Travel & Exchange Ideas Award

Myriam Amsallem, MD | Francois Haddad, MD, Nilay Shah, MD | David Maron, MD, Laboratory Laboratory Dietary Pattern and Long-Term Survival: Right Heart End-systolic Remodeling Index A Cohort Study of Patients in a Preventive Predicts Outcomes in Pulmonary Arterial Medicine Clinic Hypertension AHA Scientific Session, New Orleans, Nov. 2016 AHA Scientific Session, New Orleans, Nov. 2016 Jin Li, PhD | Themistocles Assimes, PhD, Devon Hunerdosse, PhD | Mary Teruel, PhD Laboratory Laboratory Predictors of fatal incident coronary heart Opposing Roles for C/EBP in Regulating disease in the Women's Health Initiative Adipogenesis and TNFalpha-Induced AHA Scientific Session, New Orleans, Nov. 2016 β Inflammation Keystone Symposia on Obesity and Adipose Haodi Wu, PhD | Joseph Wu, MD, PhD, Tissue Biology Laboratory Restoring diastolic function in iPSC- Qing Liu, PhD | Michael Snyder, PhD, Laboratory cardiomyocytes Genome-wide Transcriptomic And Epigenomic AHA Scientific Session, New Orleans, Nov. 2016 Alterations Of Cardiac Differentiation Society of Toxicology - Annual Meeting, Kazuya Miyagawa, MD, PhD | Marlene Baltimore, 2017 Rabinovitch, MD, Laboratory Smooth Muscle Cells Regulate the Capacity for Endothelial Regeneration AHA Scientific Session, New Orleans, Nov. 2016

cvi.stanford.edu | 8 New Clinical Trials

Euan Ashley, MD Stanley G. Rockson, MD A Phase 2, Multi-Center, Open-Label, Ascending A Phase 2, randomized, double-blind, placebo-con- Dose Study on the Efficacy, Safety and Tolerability of trolled study of the efficacy, safety, and pharmacoki- Perhexiline in Patients with Hypertrophic Cardiomy- netics of ubenimex in adult patients with secondary opathy and Moderate-to Severe Heart Failure with lymphedema of the lower limb. Preserved Left Ventricular Function.

Craig D. Miller, MD Marcia L. Stefanick, PhD A prospective, randomized, controlled, multi-center Randomized trial of cocoa flavanols and multi-vita- study to establish the safety and effectiveness of the mins in the reduction of cardiovascular disease and SAPIEN 3 transcatheter heart valve in low risk pa- cancer. tients requiring aortic valve replacement who have severe, calcific, symptomatic aortic stenosis.

Christina Mora-Mangano, MD Phillip C. Yang, MD A Prospective, Multicenter, Randomized, Dou- A Double blind, Randomized, Sham–procedure–con- ble-Blind, Placebo-Controlled Study to Evaluate the trolled, Parallel group Efficacy and Safety Study of Safety and Efficacy of Preoperative Antithrombin Allogeneic Mesenchymal Precursor Cells (rexlemes- Supplementation in Patients Undergoing High-Risk trocel-L) in Patients with Chronic Heart Failure Due Cardiac Surgery with Cardiopulmonary Bypass. to Left Ventricular Systolic Dysfunction of Either Ischemic or Nonischemic Etiology: DREAM HF-1.

Vascular Surgery Clinical Trial Highlights

VorapAccess The 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-CLI The 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 12-04 The 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-V The 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.

cvi.stanford.edu | 9 Faculty Funding Opportunities

JANUARY American Heart Association NHLBI Early Investigator Award (RFA- National Institute of Health Data Mining Grants aimed at uncovering HL-16-025) intended to support a research Bold New Bioengineering Methods and patterns and knowledge from existing program, rather than a research project Approaches for Heart, Lung, Blood data sets Deadline: Feb. 15, 2017 and Sleep Disorders and disease (RFA- Deadline: Jan. 31, 2017 HL-17-015) NHLBI Clinical Trail Pilot Studies (PAR-16- Deadline: Jan. 17, 2017 FEBRUARY 037) National Institute of Health Deadline: Feb. 16, 2017 American Heart Association NHLBI Outstanding Investigator Award Institute Innovative Development Grants (RFA-HL-16-024) intended to support a for identifying novel approaches to research program rather than a research analyzing data project Deadline: Jan. 31, 2017 Deadline: Feb. 15, 2017

Postdoctoral Funding Opportunities

NOVEMBER FEBRUARY K99/R00 NIH Pathway to Independence Research Fellowship Program In National Institute of Health Award (PA-16-077) Cardiovascular Disease Prevention K08 Mentored Clinical Research Deadline: Feb. 12, 2017 Deadline: Nov. 15, 2016 Career Development Award (PA-16- 191) Howard Hughes Medical Institute DECEMBER Deadline: Feb. 12, 2017 Hanna H. Gray Fellows Program National Institute of Health Deadline: Feb. 15, 2017 Ruth L. Kirschstein National Research K23 Mentored Patient-Oriented Service Award (NRSA) Individual Research Career Development Award NHLBI Mentored Career Development Postdoctoral Fellowship (PA-16-307) (PA-16-198) Award to Promote Faculty Diversity Deadline: Dec. 8, 2016 Deadline: Feb. 12, 2017 in Biomedical Research (K01) (RFA- HL-16-006) Deadline: Feb. 18, 2017

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

The guest speaker will be Ralph J. Damiano, MD, the Evarts Vascular Surgery 0+5 A. Graham Professor of Surgery; the Chief, Division of Car- Integrated Residency diothoracic Surgery; and the Co-Chair of the Heart & Vascu- Program Ralph J. Damiano, MD lar Center, at Washington University School of Medicine. Interview Date - January 19, 2017

Registration is encouraged: http://tinyurl.com/cvi-ct-2016. Vascular Surgery Two-year Traditional Fellowship Program Second Annual Dr. Lawrence H. & Mrs. Roberta Cohn Visiting Lecture Interview Date – March – Date TBD 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 cvi.stanford.edu | 10 2016-2017 Frontiers in Cardiovascular Science Li Ka Shing Center for Learning & Knowledge | 291 Campus Drive, Stanford, CA 94305 Tuesdays from 12:30 - 1:20 p.m. (unless otherwise stated)

NOVEMBER 01, 2016 Professor of Medicine, Cardiology MARCH 23, 2017 (THURSDAY) Kirk U. Knowlton, MD University of Wisconsin-Madison School of Maruo Giacca, MD Director of Cardiovascular Research and Medicine and Public Health Director-General International Centre for Co-Chief of Cardiology Genetic Engineering and Biotechnology Intermountain Heart Institute JANUARY 17, 2017 (ICGEB), Trieste, Italy Rui-Ping Xiao, MD, PhD NOVEMBER 08, 2016 Professor at the Institute of Molecular MARCH 28, 2017 Brian H. Annex, MD Medicine, Peking University, Beijing, China Peter J. Mohler, PhD Chief, Division of Cardiovascular Medicine Professor and Chair, Physiology and Cell Chair, George A. Beller, MD JANUARY 24, 2017 Biology Lantheus Medical Imaging Distinguished Mark A. Creager, MD, FAHA Ohio State University Professor of Cardiovascular Medicine Director, Heart and Vascular Center, University of Virginia Health System Dartmouth-Hitchcock Medical Center MAY 9, 2017 Professor of Medicine, Geisel School of Charles E. Murry, MD, PhD NOVEMBER 22, 2016 Medicine at Dartmouth Woods Professor of Pathology, Bioengineering Jake Lusis, PhD and Medicine/Cardiology Professor of Medicine Cardiology and FEBRUARY 28, 2017 Co-Director, Institute for Stem Cell and Microbiology, Immunology & Molecular Gerald W. Dorn, II, MD Regenerative Medicine Genetics Philip and Sima K Needleman Professor Co-Director, Center for Cardiovascular Biology Vice-Chair of Human Genetics Director, Center for Pharmacogenomics University of Washington David Geffen School of Medicine, UCLA Washington University School of Medicine June 6, 2017 DECEMBER 06, 2016 MARCH 7, 2017 John L. Spudich, PhD Ralph J. Damiano, MD Vinicio de Jesus Perez, MD Robert A. Welch Distinguished Chair in Evarts A. Graham Professor, Surgery; Assistant Professor of Medicine (Pulmonary Chemistry Chief, Division of Cardiothoracic Surgery and Critical Care Medicine) Director, Center for Membrane Biology Washington University School of Medicine Stanford University Professor, Biochemistry & Molecular Biology Register: http://tinyurl.com/cvi-ct-2016 and University of Texas, Houston, Texas

DECEMBER 13, 2016 Edda Spiekerkoetter, MD June 6, 2017 Assistant Professor of Medicine (Pulmonary Jonathan M. Graff, MD, PhD Louis J. Dell'Italia, MD Professor, Dept. of Developmental Biology and Critical Care Medicine) Professor, UAB Comprehensive Cardiovascular University of Texas Southwestern Stanford University Center University of Alabama at Birmingham JANUARY 10, 2017 Timothy J. Kamp, MD, PhD Co-director, Stem Cell and Regenerative Medicine Center

National and Global Cardiovascular Conferences

NOVEMBER The Future of Cardiovascular Research DECEMBER AHA Scientific Sessions November 21, 2016 | 12 - 5p World Stem Cell Summit November 12-16, 2016, Orleans, LA Li Ka Shing Center December 6-8, 2016, West Palm Beach, FL Lunch, science, wine & cheese cvi.stanford.edu | 11 Biobank Stanford CVI Human iPSC Biobank Service

Normal 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 ([email protected]) 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 3DQ Imaging Clinical Laboratory Biomarker Stanford’s 3DQ Imaging Laboratory was established in 1996 at Stanford by Geof- & Phenotyping frey Rubin, MD, and Sandy Napel, PhD, Professor of Radiology (General Radiol- Core Lab (BPCL) ogy) and, by courtesy, Electrical Engi- neering. Today the center is co-directed by Dominik Fleischmann, MD, Profes- Our Mission sor of Radiology (General Radiology) We provide quantitative assessment of Key Initiatives and Roland Bammer, PhD, Associate clinical cardiovascular phenotypes for Professor (Research) of Radiology. translational research and clinical tri- 1. Stanford Athletic Screening Program. The BPCL is the core laboratory responsible for the echocar- als. These cardiovascular phenotypes diographic studies of Stanford Athletic Screening Currently the lab processes over 1,200 include evaluating cardiac structure Program and has imaged more than 500 athletes. clinical cases per month. Linda Horst, and function, measuring carotid intimal Marc Sofilos, and Shannon Walters are 2. thickness and arterial stiffness, and test- Stanford Immune Aging Longitudinal Study. The BPCL is the core providing clinical an integral part of the 3DQ Lab manage- ing endothelial function and cardiopul- cardiovascular phenotypes for collaboration ment team. monary exercise testing. through the NIH funded projects of the Immunity Transplantation and Infection Institute led by Mark For more visit: http://3dqlab.stanford. In collaboration with the Human Im- Davis, MD. edu/ mune Monitoring Center at Stanford and 3. The Pulmonary Hypertension Wall Center members of the Cardiovascular Institute, Outcome and Physiology Studies. The BPCL we also offer central blood processing works closely with the Vera Moulton Wall Center for Pulmonary Vascular Disease to provide quantitative and banking capabilities. We are also de- echocardiographic assessment of the right heart. veloping new biomarker platforms and imaging modalities. 4. The CCML-Stanford Collaborative Effort. Through a close collaboration with the University of Paris and the Marie-Lannelongue surgical center Contact Us (CCML), the BPCL is providing quantitative analysis of experimental and clinical studies focused on Francois Haddad, MD, Clinical Associate right heart physiology. The CCML is a recognized Professor of Medicine (Cardiovascular worldwide center of expertise in pulmonary Medicine): [email protected]. hypertension (Elie Fadel MD PhD and Olaf Mercier MD PhD). cvi.stanford.edu | 12 Member Publications

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.

JULY 2016 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). Defining and refining indications for transcatheter pulmonary valve replace- ment in patients with repaired tetralogy of Fallot: Contributions from anatomi- Cellular Taxonomy of the Mouse Striatum as Revealed by Single-Cell RNA-Seq. cal and functional imaging. Tretter JT, Friedberg MK, Wald RM, McElhinney DB. Gokce O, Stanley GM, Treutlein B, Neff NF, Camp JG, Malenka RC, Rothwell PE, Int J Cardiol. 2016. Fuccillo MV, Südhof TC, Quake SR. Cell Rep. 2016 Jul 26;16(4):1126-37.

A Prospective Evaluation of Systemic Biomarkers and Cognitive Function Attenuated-Signal Plaque Progression Predicts Long-Term Mortality After Associated with Carotid Revascularization. Zuniga MC, Tran TB, Baughman BD, Heart Transplantation: IVUS Assessment of Cardiac Allograft Vasculopathy. Raghuraman G, Hitchner E, Rosen A, Zhou W. Ann Surg. 2016. 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 Advances in pediatric cardiology 2016. Bernstein D. Curr Opin Pediatr. 2016. Cardiol. 2016 Jul 26;68(4):382-92.

Perioperative management of pediatric en-bloc combined heart-liver trans- Statins, familial hypercholesterolemia, and type 2 diabetes. Reaven GM. J plants: a case series review. Navaratnam M, Ng A, Williams GD, Maeda K, Intern Med. 2016 Jul 25. Mendoza JM, Concepcion W, Hollander SA, Ramamoorthy C. Paediatr Anaesth. 2016. 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 Increased Pyruvate Dehydrogenase Kinase 4 Expression in Lung Pericytes Is As- Transplant. 2016 Jul 22. sociated with Reduced Endothelial-Pericyte Interactions and Small Vessel Loss in Pulmonary Arterial Hypertension. Yuan K, Shao NY, Hennigs JK, Discipulo M, Management of Patients With NSTE-ACS: A Comparison of the Recent AHA/ACC Orcholski ME, Shamskhou E, Richter A, Hu X, Wu JC, de Jesus Perez VA. Am J and ESC Guidelines. Rodriguez F, Mahaffey KW. J Am Coll Cardiol. 2016 Jul Pathol. 2016. 19;68(3):313-21.

Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis Is Associated Statins in Familial Hypercholesterolemia: Translating Evidence to Action. With Downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM. Perisic Mat- Knowles JW. J Am Coll Cardiol. 2016 Jul 19;68(3):261-4. 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 Terminating atrial fibrillation by cooling the heart. Narayan SM, Baykaner T, H, Diez MG, Roy J, Baldassarre D, Veglia F, Humphries SE, de Faire U, Tremoli E, Sahli Costabal F, Kuhl E. Heart Rhythm. 2016 Jul 17. pii: S1547-5271(16)30547- Odeberg J, Vukojević V, Lehtiö J, Maegdefessel L, Ehrenborg E, Paulsson-Berne 1. G, Hansson GK, Lindeman JH, Eriksson P, Quertermous T, Hamsten A, Hedin U. Arterioscler Thromb Vasc Biol. 2016. Defining a Mobile Health Roadmap for Cardiovascular Health and Disease. Eapen ZJ, Turakhia MP, McConnell MV, Graham G, Dunn P, Tiner C, Rich C, Lack of Left Ventricular Ejection Fraction Measurement Following a High B-type Harrington RA, Peterson ED, Wayte P. J Am Heart Assoc. 2016 Jul 12;5(7). Natriuretic Peptide Value. Heidenreich PA, Gholami P, Lin S. Crit Pathw Cardi- ol. 2016. Spatiotemporal Reconstruction of the Human Blastocyst by Single-Cell Gene-Expression Analysis Informs Induction of Naive Pluripotency. Durruthy- Right heart imaging in patients with heart failure: a tale of two ventricles. Am- Durruthy J, Wossidlo M, Pai S, Takahashi Y, Kang G, Omberg L, Chen B, Nakau- sallem M, Kuznetsova T, Hanneman K, Denault A, Haddad F. Curr Opin Cardiol. chi H, Reijo Pera R, Sebastiano V. Dev Cell. 2016 Jul 11;38(1):100-15. 2016. Pediatric Echocardiography by Work Relative Value Units: Is Study Complex- 1-Year Outcomes of FFRCT-Guided Care in Patients With Suspected Coronary ity Adequately Captured? Balasubramanian S, Kipps AK, Smith SN, Tacy TA, Disease: The PLATFORM Study. Douglas PS, De Bruyne B, Pontone G, Patel Selamet Tierney ES. J Am Soc Echocardiogr. 2016 Jul 9. 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, Fractional Flow Reserve and Coronary Computed Tomographic Angiography: A Chiswell K, Cyr D, Wilk A, Wang F, Rogers C, Hlatky MA; PLATFORM Investiga- Review and Critical Analysis. Hecht HS, Narula J, Fearon WF. Circ Res. 2016 Jul tors. J Am Coll Cardiol. 2016. 8;119(2):300-16.

Surgical Technique for Repair of Peripheral Pulmonary Artery Stenosis and Vorapaxar: emerging evidence and clinical questions in a new era of PAR-1 Other Complex Peripheral Reconstructions. Mainwaring RD, Ibrahimiye AN, inhibition. Ungar L, Rodriguez F, Mahaffey KW. Coron Artery Dis. 2016 Jul 8. Hanley FL. Ann Thorac Surg. 2016. Integrative functional genomics identifies regulatory mechanisms at coronary Standards of Evidence and Mechanistic Inference in Autosomal Recessive artery disease loci. Miller CL, Pjanic M, Wang T, Nguyen T, Cohain A, Lee JD, Hypercholesterolemia. Priest JR, Knowles JW. Arterioscler Thromb Vasc Biol. Perisic L, Hedin U, Kundu RK, Majmudar D, Kim JB, Wang O, Betsholtz C, Ruu- 2016. salepp A, Franzén O, Assimes TL, Montgomery SB, Schadt EE, Björkegren JL, Quertermous T. Nat Commun. 2016 Jul 8;7:12092. Can Cardiac Conduction System Disease Be Prevented? Narayan SM, Baykaner T, Maron DJ. JAMA Intern Med. 2016. Allogeneic Mesenchymal Stromal Cells Overexpressing Mutant Human Hypoxia-Inducible Factor 1-α (HIF1-α) in an Ovine Model of Acute Myocardial Transcatheter valve implantation for right atrium-to-right ventricle conduit Infarction. Hnatiuk AP, Ong SG, Olea FD, Locatelli P, Riegler J, Lee WH, Jen CH, obstruction or regurgitation after modified Björk-fontan procedure. Shah AH, De Lorenzi A, Giménez CS, Laguens R, Wu JC, Crottogini A. J Am Heart Assoc. Horlick EM, Eicken A, Asnes JD, Bocks ML, Boudjemline Y, Cabalka AK, Fagan 2016 Jul 6;5(7). TE, Schubert S, Mahadevan VS, Dvir D, Osten M, McElhinney DB. Catheter Cardiovasc Interv. 2016 Jul 28. On-Treatment Outcomes in Patients With Worsening Renal Function With

cvi.stanford.edu | 13 Rivaroxaban Compared With Warfarin: Insights From ROCKET AF. Fordyce CB, Notch: A multi-functional integrating system of microenvironmental signals. Hellkamp AS, Lokhnygina Y, Lindner SM, Piccini JP, Becker RC, Berkowitz SD, LaFoya B, Munroe JA, Mia MM, Detweiler MA, Crow JJ, Wood T, Roth S, Sharma Breithardt G, Fox KA, Mahaffey KW, Nessel CC, Singer DE, Patel MR; ROCKET AF B, Albig AR. Dev Biol. 2016 Aug 24. Steering Committee and Investigators. Circulation. 2016 Jul 5;134(1):37-47. Adult Stem Cell Therapy and Heart Failure, 2000 to 2016: A Systematic Review Patterns of Carotid Intima-Media Thickness Progression in Kawasaki Patients: A Nguyen PK, Rhee JW, Wu JC. JAMA Cardiol. 2016 Aug 24. Crystal Ball for Long-Term Vascular Health? Haley J, Selamet Tierney ES. J Am Heart Assoc. 2016 Jul 5;5(7). Multiple allogeneic progenitors in combination function as a unit to support early transient hematopoiesis in transplantation. Ishida T, Takahashi S, Lai CY, The Impact of Fitness on Surgical Outcomes: The Case for Prehabilitation. Nojima M, Yamamoto R, Takeuchi E, Takeuchi Y, Higashihara M, Nakauchi H, Myers JN, Fonda H. Curr Sports Med Rep. 2016 Jul-Aug;15(4):282-9. Otsu M. J Exp Med. 2016 Aug 22;213(9):1865-80.

Notch-independent RBPJ controls angiogenesis in the adult heart. Díaz-Trelles Use of Dual Antiplatelet Therapy and Patient Outcomes in Those Undergoing R, Scimia MC, Bushway P, Tran D, Monosov A, Monosov E, Peterson K, Rentschler Percutaneous Coronary Intervention: The ROCKET AF Trial. Sherwood MW, S, Cabrales P, Ruiz-Lozano P, Mercola M. Nat Commun. 2016 Jun 30;7:12088. 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 Effects of cellular origin on differentiation of human induced pluripotent stem MR. JACC Cardiovasc Interv. 2016 Aug 22;9(16):1694-702. cell-derived endothelial cells. Hu S, Zhao MT, Jahanbani F, Shao NY, Lee WH, Chen H, Snyder MP, Wu JC. JCI Insight. 2016. Real-world performance of paclitaxel drug-eluting bare metal stenting (Zilver PTX) for the treatment of femoropopliteal occlusive disease. Tran K, Ullery BW, Intracoronary Gene Transfer of Adenylyl Cyclase 6 in Patients With Heart Failure: Kret MR, Lee JT. Ann Vasc Surg. 2016 Aug 20. 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, Pulling the RIPCORD: FFRCT to Improve Interpretation of Coronary CT Angiogra- Bhargava V, Maisel A, Barnard DD, Lai NC, Dalton ND, Lee ML, Narayan SM, phy. Fearon WF, Lee JH. JACC Cardiovasc Imaging. 2016 Aug 20. Blanchard DG, Gao MH. JAMA Cardiol. 2016. STAMS: STRING-assisted module search for genome wide association studies Sudden Cardiac Death After Non-ST-Segment Elevation Acute Coronary and application to autism. Hillenmeyer S, Davis LK, Gamazon ER, Cook EH, Cox Syndrome. Hess PL, Wojdyla DM, Al-Khatib SM, Lokhnygina Y, Wallentin L, Arm- NJ, Altman RB. Bioinformatics. 2016 Aug 19. 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. Alternative approaches to generating cardiomyocytes are under development. JAMA Cardiol. 2016. Chen IY, Matsa E, Wu JC. Nat Rev Cardiol. 2016 Aug 19.

Oral Anticoagulant Therapy Prescription in Patients With Atrial Fibrillation Structure-based discovery of opioid analgesics with reduced side effects. Across the Spectrum of Stroke Risk: Insights From the NCDR PINNACLE Registry. Manglik A, Lin H, Aryal DK, McCorvy JD, Dengler D, Corder G, Levit A, Kling RC, Hsu JC, Maddox TM, Kennedy KF, Katz DF, Marzec LN, Lubitz SA, Gehi AK, Tura- Bernat V, Hübner H, Huang XP, Sassano MF, Giguère PM, Löber S, Da Duan, khia MP, Marcus GM. JAMA Cardiol. 2016. 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 AUGUST 2016 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. Consistent Reduction in Periprocedural Myocardial Infarction With Cangrelor as Assessed by Multiple Definitions: Findings From CHAMPION PHOENIX (Cangre- Predicting non-small cell lung cancer prognosis by fully automated microscopic lor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibi- pathology image features. Yu KH, Zhang C, Berry GJ, Altman RB, Ré C, Rubin tion). Cavender MA, Bhatt DL, Stone GW, White HD, Steg PG, Gibson CM, Hamm DL, Snyder M. Nat Commun. 2016 Aug 16;7:12474. CW, Price MJ, Leonardi S, Prats J, Deliargyris EN, Mahaffey KW, Harrington RA; CHAMPION PHOENIX Investigators*. Circulation. 2016. Towards precision medicine. Ashley EA. Nat Rev Genet. 2016 Aug 16;17(9):507-22.

Modeling the Myxomatous Mitral Valve With Three-Dimensional Echocardiogra- An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease. phy. Pouch AM, Jackson BM, Lai E, Takebe M, Tian S, Cheung AT, Woo YJ, Patel Horvath S, Gurven M, Levine ME, Trumble BC, Kaplan H, Allayee H, Ritz BR, Chen PA, Wang H, Yushkevich PA, Gorman RC, Gorman JH 3rd. Ann Thorac Surg. 2016. 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. Transcriptome Profiling of Patient-Specific Human iPSC-Cardiomyocytes Pre- Genome Biol. 2016 Aug 11;17(1):171. 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 Electroanatomic Properties of the Myocardium Predict Response to CD34+ JM, Shao N, Woo NA, Chao AS, Gold JD, Karakikes I, Snyder MP, Wu JC. Cell Cell Therapy in Patients With Ischemic and Nonischemic Heart Failure. Zemljic Stem Cell. 2016 Sep 1;19(3):311-25. G, Poglajen G, Sever M, Cukjati M, Frljak S, Androcec V, Cernelc P, Haddad F, Vrtovec B. J Card Fail. 2016 Aug 11. Kank2 activates talin, reduces force transduction across integrins and induces central adhesion formation. Sun Z, Tseng HY, Tan S, Senger F, Kurzawa L, Ded- Hypertriglyceridemia: A simple approach to identify insulin resistance and den D, Mizuno N, Wasik AA, Thery M, Dunn AR, Fässler R. Nat Cell Biol. 2016. 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. 3D Graphitic Foams Derived from Chloroaluminate Anion Intercalation for Ultrafast Aluminum-Ion Battery. Wu Y, Gong M, Lin MC, Yuan C, Angell M, Huang The All-Chemical Approach: A Solution for Converting Fibroblasts Into Myo- L, Wang DY, Zhang X, Yang J, Hwang BJ, Dai H. Adv Mater. 2016 Aug 29. cytes. Liu Y, Mercola M, Schwartz RJ. Circ Res. 2016 Aug 5;119(4):505-7.

VCP recruitment to mitochondria causes mitophagy impairment and neuro- Functional Neurologic Outcomes Change Over the First 6 Months After Cardiac degeneration in models of Huntington’s disease. Guo X, Sun X, Hu D, Wang YJ, Arrest. Tong JT, Eyngorn I, Mlynash M, Albers GW, Hirsch KG. Crit Care Med. 2016 Fujioka H, Vyas R, Chakrapani S, Joshi AU, Luo Y, Mochly-Rosen D, Qi X. Nat Aug 5. Commun. 2016 Aug 26;7:12646. Combinatorial Extracellular Matrix Microenvironments Promote Survival and Can heavy isotopes increase lifespan? Studies of relative abundance in various Phenotype of Human Induced Pluripotent Stem Cell-Derived Endothelial Cells in organisms reveal chemical perspectives on aging. Li X, Snyder MP. Bioessays. Hypoxia. Hou L, Coller J, Natu V, Hastie TJ, Huang NF. Acta Biomater. 2016 Aug 4. 2016 Aug 24. cvi.stanford.edu | 14 Computing disease incidence, prevalence and comorbidity from electronic Efficacy and Safety of Cangrelor in Preventing Periprocedural Complications in medical records. Bagley SC, Altman RB. J Biomed Inform. 2016 Aug 4. Patients With Stable Angina and Acute Coronary Syndromes Undergoing Per- cutaneous Coronary Intervention: The CHAMPION PHOENIX Trial. Abtan J, Steg Implications of different criteria for percutaneous coronary intervention-relat- PG, Stone GW, Mahaffey KW, Gibson CM, Hamm CW, Price MJ, Abnousi F, Prats ed myocardial infarction on study results of three large phase III clinical trials: J, Deliargyris EN, White HD, Harrington RA, Bhatt DL; CHAMPION PHOENIX The CHAMPION experience. Leonardi S, Lopes RD, Steg PG, Abnousi F, Menozzi Investigators. JACC Cardiovasc Interv. 2016 Sep 26;9(18):1905-13. A, Prats J, Mangum S, Wilson M, Todd M, Stone GW, Gibson CM, Hamm CW, Is There a Difference in Tachycardia Cycle Length During SVT in Children with Price MJ, White HD, Harrington RA, Bhatt DL, Mahaffey KW. Eur Heart J Acute AVRT and AVNRT? Mills MF, Motonaga KS, Trela A, Dubin AM, Avasarala K, Cardiovasc Care. 2016 Aug 2. Ceresnak SR. Pacing Clin Electrophysiol. 2016 Sep 22. Apelin-13 infusion salvages the peri-infarct region to preserve cardiac function Near-infrared spectroscopy for detection of a significant patent ductus arterio- after severe myocardial injury. Chung WJ, Cho A, Byun K, Moon J, Ge X, Seo HS, sus. Chock VY, Rose LA, Mante JV, Punn R. Pediatr Res. 2016 Sep 21. Moon E, Dash R, Yang PC. Int J Cardiol. 2016 Aug 2;222:361-367. High-Resolution Analysis of Antibodies to Post-Translational Modifications Using Peptide Nanosensor Microarrays. Lee JR, Haddon DJ, Gupta N, Price JV, Effect of age on efficacy and safety of vorapaxar in patients with non-ST- Credo GM, Diep VK, Kim K, Hall DA, Baechler EC, Petri M, Varma M, Utz PJ, Wang segment elevation acute coronary syndrome: Insights from the Thrombin SX. ACS Nano. 2016 Sep 20. Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial. Armaganijan LV, Alexander KP, Huang Z, Tricoci P, Held C, Van Translating Research into Improved Patient Care in Pulmonary Arterial Hyper- de Werf F, Armstrong PW, Aylward PE, White HD, Moliterno DJ, Wallentin L, tension. Bonnet S, Provencher S, Guignabert C, Perros F, Boucherat O, Scher- Chen E, Harrington RA, Strony J, Mahaffey KW, Lopes RD. Am Heart J. 2016 muly RT, Hassoun PM, Rabinovitch M, Nicolls MR, Humbert M. Am J Respir Crit Aug;178:176-84. Care Med. 2016 Sep 20. Predicting inpatient clinical order patterns with probabilistic topic models vs Blood pressure control and stroke or bleeding risk in anticoagulated pa- conventional order sets. Chen JH, Goldstein MK, Asch SM, Mackey L, Altman tients with atrial fibrillation: Results from the ROCKET AF Trial. Vemulapalli RB. J Am Med Inform Assoc. 2016 Sep 20. 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. Pro-inflammatory and anti-inflammatory T cells in giant cell arteritis. Wata- 2016 Aug;178:74-84. nabe R, Hosgur E, Zhang H, Wen Z, Berry G, Goronzy JJ, Weyand CM. Joint Bone Spine. 2016 Sep 20. Albuminuria and cardiovascular events in patients with acute coronary GIS-measured walkability, transit, and recreation environments in relation syndromes: Results from the TRACER trial. Åkerblom A, Clare RM, Lokhnygina to older Adults'physical activity: A latent profile analysis. Todd M, Adams MA, Y, Wallentin L, Held C, Van de Werf F, Moliterno DJ, Patel UD, Leonardi S, Kurka J, Conway TL, Cain KL, Buman MP, Frank LD, Sallis JF, King AC. Prev Med. Armstrong PW, Harrington RA, White HD, Aylward PE, Mahaffey KW, Tricoci P. 2016 Sep 20. Am Heart J. 2016 Aug;178:1-8. Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcription- ally controlled by the endothelial Brg1-FoxM1 complex. Yang J, Feng X, Zhou Syncope While Driving in Denmark-Reply. Numé AK, Hlatky MA, Ruwald MH. Q, Cheng W, Shang C, Han P, Lin CH, Chen HS, Quertermous T, Chang CP. Proc JAMA Intern Med. 2016 Aug 1;176(8):1230-1. Natl Acad Sci U S A. 2016 Sep 20;113(38):E5628-35. Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Decompressing vein and bilateral superior venae cavae in a patient with hypo- Recapitulate Patient Specific Properties. Lombardo DM, Fenton FH, Narayan plastic left heart syndrome. Stauffer KJ, Arunamata A,Vasanawala SS, Behera SM, Rappel WJ. PLoS Comput Biol. 2016 Aug 5;12(8):e1005060. SK, Kipps AK, Silverman NH. Echocardiography. 2016 Sep 19. iPSC-derived cardiomyocytes reveal abnormal TGF-β signalling in left ven- Considering Cost-Effectiveness in Cardiology Clinical Guidelines: Progress and tricular non-compaction cardiomyopathy. Kodo K, Ong SG, Jahanbani F, Prospects. Hlatky MA. Value Health. 2016 Jul-Aug;19(5):516-9. Termglinchan V, Hirono K, InanlooRahatloo K, Ebert AD, Shukla P, Abilez OJ, Churko JM, Karakikes I, Jung G, Ichida F, Wu SM, Snyder MP, Bernstein D, Wu Noninvasive Tracking of Quiescent and Activated Muscle Stem Cell (MuSC) En- JC. Nat Cell Biol. 2016. 18(10): 1031-42. graftment Dynamics In Vivo. Ho AT, Blau HM. Methods Mol Biol. 2016;1460:181-9. Engineered knottin peptides as diagnostics, therapeutics, and drug delivery ve- Protein Corona Influences Cell-Biomaterial Interactions in Nanostructured hicles. Kintzing JR, Cochran JR. Curr Opin Chem Biol. 2016 Sep 16;34:143-150. Tissue Engineering Scaffolds. Serpooshan V, Mahmoudi M, Zhao M, Wei K, Challenging the complementarity of different metrics of left atrial function: Sivanesan S, Motamedchaboki K, Malkovskiy AV, Gladstone AB, Cohen JE, Yang insight from a cardiomyopathy-based study. Kobayashi Y, Moneghetti KJ, PC, Rajadas J, Bernstein D, Woo YJ, Ruiz-Lozano P. Adv Funct Mater. 2015 Jul Boralkar K, Amsallem M, Tuzovic M, Liang D, Yang PC, Narayan S, Kuznetsova T, 22;25(28):4379-4389. Wu JC, Schnittger I, Haddad F. Eur Heart J Cardiovasc Imaging. 2016 Sep 16. Use of the triglyceride/high-density lipoprotein cholesterol ratio to identify cardiometabolic risk: impact of obesity? Salazar MR, Carbajal HA, Espeche WG, SEPTEMBER 2016 Aizpurúa M, Marillet AG, Leiva Sisnieguez CE, Leiva Sisnieguez BC, Stavile RN, March CE, Reaven GM. J Investig Med. 2016 Sep 16. Novel Therapies for Familial Hypercholesterolemia. 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In vivo Post-Cardiac Arrest Myocardial Dysfunction is Supported by CaMKII-Me- diated Calcium Long-Term Potentiation and Mitigated by Alda-1, an Agonist cvi.stanford.edu | 16 Leadership

Joseph C. Wu, MD, PhD Director, Stanford Cardiovascular Institute Simon H. Stertzer, MD, Professor, Robert A. Harrington, MD Dept. of Medicine (Cardiovascular) Arthur L. Bloomfield Professor of Medicine & Radiology Chair, Dept. of Medicine

Stephen J. Roth MD, MPH Professor of Pediatrics (Cardiology) at Ronald L. Dalman, MD Lucile Salter Packard Children's Hospital Walter C. and Elsa R. Chidester Chief, Division of Pediatric Cardiology Professor of Surgery James Baxter & Yvonne Craig Wood Chief, Division of Vascular Surgery Medical Director CVICU, LPCH

Michael Snyder, PhD Stanford W. Ascherman, MD, FACS, Professor in Genetics Dominik Fleischmann, MD Chair, Department of Genetics Professor, Dept. of Radiology Director, Stanford Center for Genomics Chief, Cardiovascular Imaging and Personalized Medicine

Kenneth Mahaffey, MD Y. Joseph Woo, MD Professor, Dept. of Medicine Norman E. Shumway Professor Vice Chair of Medicine in Cardiothoracic Surgery for Clinical Research Chair Department of Cardiothoracic Surgery

Mark Nicolls, MD Alan Yeung, MD Professor of Medicine Li Ka Shing Professor of Medicine Chief, Pulmonary and Critical Co-Chief (Clinical), Care Medicine Division of Cardiovascular Medicine

Paul Yock, MD Martha Meier Weiland Professor Tom Quertermous, MD of Bioengineering and Medicine William G. Irwin Professor of Medicine Professor, by courtesy, of Mechanical Co-Chief (Research), Engineering Division of Cardiovascular Medicine Director of Biodesign

Marlene Rabinovitch, MD Dwight and Vera Dunlevie Professor in Pediatric Cardiology cvi.stanford.edu cvi.stanford.edu | 17