CVI Welcomes 2019 Summer Undergraduate Interns a Diverse Group of Undergrads from Across the Country Join Us to Learn About Cardiovascular Research

SPRING 2019 Donate to the CVI 9

Over 500 people attended the fourth annual Stanford Drug Discovery Symposium. The attendees were a mix of industry and academia. The meeting was a highly successful two days of thought-provoking presentations. It was an opportunity to interact with federal and foundation policy makers, leaders from major pharmaceutical companies, and pioneers in drug discovery research. Dr. John Martin was awarded the Lifetime Achievement Award. More on page 2.

CVI Welcomes 2019 Summer Undergraduate Interns A diverse group of undergrads from across the country join us to learn about cardiovascular research.

Natasha Auer Lauren D'Amico Kelly Lancaster Taylor Montiel UC Santa Barbara Univ. of Washington UC Berkeley San Jose City College Mentor: Dr. de Jesus Mentor: Dr. Bernstein Mentor: Dr. Liao Mentor: Dr. Woo Perez Julianne Ballon Nashielli Diaz Rachel Lippman Raquel Racelis University of Guam Tufts University Cornell University San Francisco State Mentor: Dr. Fishbein Mentor: Dr. Karakikes Mentor: Dr. Mercola Mentor: Dr. Red-Horse

Christian Beke Onana Gabriela Escobar Joseph Lohmann Samantha Roach Univ. of Houston Dtn Stanford University Univ. of Pennsylvania Spelman College Mentor: Dr. Hiesinger Mentor: Dr. Sean Wu Mentor: Dr. Priest Mentor: Dr. Shudo

Lily Cheng Breauna Franklin Sarah Madira Caydin Sablan Univ. Mich. Ann Arbor Clemson University Cal State Los Angeles Univ. of San Francisco Mentor: Dr. Sayed Mentor: Dr. Sayed Mentor: Dr. Anson Lee Mentor: Dr. Liao

Beatrice Choi Roberto Guzman Rachael Mezynski Stanford University Univ. of Puerto Rico North Carolina State Mentor: Dr. Rhee Mentor: Dr. Yuan Mentor: Dr. Joe Wu cvi.stanford.edu | 1 SDDS 2019 Highlights On April 22-23, 2019, the fourth annual Stanford Drug Discovery Symposium was held at the Li Ka Shing Center. The meeting featured presentations and panel discussions from federal and foundation policy makers, leaders from major pharmaceutical companies, and pioneers in drug discovery Participants Adamis, Reed, Horning, Sachs, Shatz, Schekman, Singh, Drucker, Minor, Martin, Milan, research. There was a Showcase Tessier-Lavigne, Wu, Smith, Mammen, Redkar, Dzau, Malhotra, Mercola, Bauchner, and Doroshow panel event with venture capitalists and leaders from Caribou Biosciences, Immune-Onc Therapeutics, and Appollomics. 2019 Featured Speakers: Anthony Adamis, Genetech; Jeffery Bluestone, Parker Institute; Jim Doroshow, NCI; Brian Druker, Knight Cancer Institute; Victor Dzau, National Acad of Medicine; Peter Fitzgerald, Triventures; Sandra Horning, Genentech; Allan Jones, Allen Institute; Crystal Mackall, Stanford, Parker Institute; Mathai Mammen, Janssen Pharmaceuticals; John C. Martin, Gilead; Peter Marks, FDA; Maria Millan, CIRM; Lloyd Minor, Dean, Stanford Medicine; Andrew Plump, Takeda; John Reed, Sanofi; Alan Sachs, Thermo Fisher; Camille Samuels, Venrock; Randy Schekman, HHMI, UC Berkley, Nobel Prize; Orla Smith, Science Translational Medicine; Young Sohn, Samsung Electronics; Marc Tessier-Lavigne, Stanford President; Sandy Weill, Citigroup; George Yancopoulos, Regeneron Pharmaceuticals Meeting organizers Sanjay Malhotra, Mark Mercola, Kuldev Singh, Joseph C. Wu, Amanda Chase, and David Preston hope you will join us next year, April 20-21 2020, for SDDS 2020.

Showcase with A. Adamis (Genentech), W. Myers, Jr. (Myers Ventures), S. Kanner (Caribou), S. Redkar (Appollomics), C. Liao (Immune-Onc), C. Samuels Dr. Paul Berg (right) presented the Lifetime (Venrock), and R. Shriram (Sherpalo). Opening Keynote Address by Dr. Victor Achievement Award to Dr. John Martin (left). Dzau (National Academy of Medicine).

27 poster presentations Government and Philanthropy session. J. Doroshow Dean Minor and President Tessier-Lavigne (NIH), A. Jones (Allen Institute), S. Weill (Citigroup), discuss Stanford innovative medicine. and M. Millan (CIRM).

cvi.stanford.edu | 2 E-Cigarette use, flavorings, may increase heart disease risk, study finds By Krista Conger The flavoring liquid for electronic cigarettes, or e-cigarettes, may increase the risk of cardiovascular disease when inhaled, according to a study led by researchers at the School of Medicine. The scientists investigated the effect of the e-liquids on cells called endothelial cells that line the interior of blood vessels. They found that, when grown in a laboratory, endothelial cells exposed to the e-liquids — or to blood collected from e-cigarette users shortly after vaping — are less viable and exhibit significantly increased levels of molecules implicated in DNA damage and cell death. The cells are also less able to form new vascular tubes and to migrate and participate in wound healing. The severity of the damage, aspects of which occur even in the absence of nicotine, varies among popular flavors, the researchers Won Hee Lee, PhD said. Cinnamon and menthol were found to be particularly harmful. “Until now, we had no data about how these e-liquids affect human endothelial cells,” said Joseph Wu, MD, PhD, director of the Stanford Cardiovascular Institute and professor of cardiovascular medicine and of radiology. “This study clearly shows that e-cigarettes are not a safe alternative to traditional cigarettes. When we exposed the cells to six different flavors of e-liquid with varying levels of nicotine, we saw significant damage. The cells were less viable in culture, and they began to exhibit multiple symptoms of dysfunction.”

The researchers studied human endothelial cells generated in the laboratory from what are called induced pluripotent stem cells, or iPS cells. Human iPS cells can become many different cell types, and they provide an ideal way for researchers to closely study cells that would be difficult to isolate directly from a patient.

This study was the first to use endothelial cells derived from iPS cells to directly investigate the effect of e-liquids with and without nicotine on their viability and function.

A paper describing the findings was published online May 27 in the Journal of the American College of Cardiology. Wu is the senior author. Former postdoctoral scholars Won Hee Lee, PhD, now an assistant professor at the University of Arizona, and Sang-Ging Ong, PhD, now an assistant professor at University of Illinois-Chicago, are the lead authors.

“One in five high school students have tried e-cigarettes, perhaps because they feel they are relatively safe,” Lee said. “But we found the e-liquids caused changes in the endothelial cells that are closely related to those seen during the development of cardiovascular disease.”

The researchers compared the levels of nicotine in the blood serum of people after they had vaped e-cigarettes with the levels in people who smoked traditional cigarettes. They found that the amounts of nicotine in the blood were similar between the two groups after 10 minutes of smoking at a constant rate.

“When you’re smoking a traditional cigarette, you have a sense of how many cigarettes you’re smoking,” Wu said. “But e-cigarettes can be deceptive. It’s much easier to expose yourself to a much higher level of nicotine over a shorter time period. And now we know that e-cigarettes are likely to have other significantly toxic effects on vascular function as well. It’s important for e-cigarette users to realize that these chemicals are circulating within their bodies and affecting their vascular health.” This work was also covered by The New York Times, Business Insider, CNN, CBS, AP, Fox, and Yahoo. Source: http://med.stanford.edu/news/all-news/2019/05/e-cigarette-use-and-flavorings-may-increase-heart-disease-risk

Stanford-UPenn Cardiovascular Research Conference November 4 - 5, 2019, Li Ka Shing Center, Stanford Keynotes: Paul Yock, Dan Rader Confirmed Speakers: Daria Mochly-Rosen, Sarah Heilshorn , Saman Nazarian, Will Heisinger, Yasuhiro Shudo, Shipra Arya, Tom Cappola, Kiran Khush, Ron Witteles, Bonnie Ky, Marlene Rabinovitch, Vinicio de Jesus Perez, Ed Morrissey, Rajan Jain, James Priest, Kristy Red-Horse, Helen Blau, Ioannis Karakikes, Ngan Huang, Kiran Musunuru, Dan Kelly, Ronglih Liao, Zoltan Arany, Nick Leeper, Scott Damrauer, Elsie Ross tinyurl.com/StanfordPennCV cvi.stanford.edu | 3 Stanford CVI: At the forefront of cardiovascular research Recognized for excellence, the Stanford University School of Medicine has long been at the forefront of cardiovascular research, patient care, and discovery. The Stanford Cardiovascular Institute (CVI) serves as an interdisciplinary nucleus concentrating and coordinating the activities of scientists, bioengineers, educators, and physicians committed to improving cardiovascular health and to training the next generation of leaders in cardiovascular medicine. The history and mission, research, strengths, and future directions of the CVI are featured in Circulation Research in May, 2019, authored by Joseph Wu, MD, PhD, Joseph Woo, MD, Megan Mayerle, PhD, Robert Harrington, MD, and Thomas Quertermous, MD. Source: https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.119.310761?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_ pub%3dpubmed

Congenital heart defects increase risk of heart problems later in life by Mandy Erickson An infant born with a relatively simple heart defect is far more likely to develop heart problems as an adult, researchers at the Stanford University School of Medicine have discovered. The risk is so great that someone born with a heart defect who has a heart-healthy lifestyle is twice as likely to develop heart problems as someone born without a defect who has a heart-averse lifestyle. “All of us in cardiology recognize that people with complex disease need follow-up care throughout their lives," said James Priest, MD, assistant professor of pediatric cardiology. “But for the simple problems, we’ve been thinking that once you close the hole or fix the valve, these patients are good to go.” James Priest, MD The research findings suggest that the medical community should watch adults who were born with heart defects — even minor ones — more carefully. Medications and lifestyle changes may help prevent or delay major heart conditions, such as heart attacks, stroke, heart failure and atrial fibrillation. A paper describing the research was published Feb. 28 in Circulation. Priest is the senior author; Priyanka Saha, a student at Harvard Medical School who was a research fellow at Stanford from 2017 to 2018, is the lead author.

Source: http://med.stanford.edu/news/all-news/2019/02/congenital-heart-defects-increase-risk-of-later-heart-problems.html Women leaders in cardiac transplantation by Megan Mayerle, PhD The first successful heart transplant in the United States was performed at Stanford in 1968. Chief Surgeon Norman Shumway replaced the diseased heart of Mike Kasperak, a retired steelworker. He survived for only 15 days. However, due to innovations in post-transplant patient care, today heart transplantation has become commonplace, and the surgery ensures patients a relatively high quality of life for years and often decades after surgery. Sharon Hunt, MD, was a medical student at Stanford in 1968. By the time she finished her cardiology Sharon Hunt, MD fellowship at Stanford, patient survival rates had begun to improve, and Hunt was one of four cardiologists asked to provide long term care for transplant recipients. Now a Professor Emerita of Cardiovascular Medicine at Stanford, Hunt is well known for her innovations in the care of patients after heart transplantation. In an article published in February 2019 in Circulation, Hunt discusses the impact of women leaders in Cardiac Transplantation. Currently 26% of board-certified transplantation care specialists in the US are women, a ratio that, though not equal, is far better than many other cardiac subspecialties. Hunt is quick to point out that the often-credited work-life balance and flexible hours are not the reason for the relatively high number of women in this subspecialty. She instead points to the fact that “Women have been in the field from the beginning, continue to be successful as specialists, hold leadership positions and have many relatable role models.”

Source: http://med.stanford.edu/cvi/mission/news_center/articles_announcements/sharon-hunt-reflects-on-women-leaders-in-cardiac-transplantation.html cvi.stanford.edu | 4 Grants and Awards Linda Ottoboni, PhD, FHRS, CCDS, was Nicholas Leeper, MD, received the AHA appointed to the Heart Rhythm Society Established Investigator Award. National Governing Committee.

Edda Spiekerkoetter, MD, received Kuninobu Kashiyama, MD, received ACC a Department of Defense grant to Best Poster Award at the 2019 Annual address hereditary hemorrhagic Scientific Session. telangiectasia. Kevin Cyr was awarded Grand Helen Blau, PhD, was elected to the Prize at Stanford Medical School American Institute for Medical and Research Symposium. Biological Engineering (AIMBE). Tim Assimes, PhD, 2019 recipient of the Sharon Paige, MD, joined the AHA Genomic and Precision Medicine Department of Pediatrics Instructor and Epidemiology Mid-Career Research Pipeline Program. Award and Lecturer. Robert Wirka, MD, was awarded the Maedeh Zamani, PhD, was awarded an Irvine H. Page Young Investigator AHA postdoctoral fellowship. Award at 2019 ATVB.

Jason Lee, MD, elected to the Ji Hye Jung, PhD, was awarded an AHA Vascular Surgery Board of the American postdoctoral fellowship. Board of Surgery.

Fatima Rodriguez, MD, MPH, FACC, was awarded an NIH K01 on "SURPASS Mark Nicolls, MD, and Amy Tian, (Statin Use and Risk Prediction of PhD, were awarded an NIH R01 grant to Atherosclerotic Cardiovascular Disease evaluate the role of inflammation in in minority Subgroups)". lymphedema. was awarded a Ngan Huang, PhD, Sangkyun Cho, PhD, was appointed as a Department of Vetern Affairs grant on new Cardiovascular Imaging T32 trainee. "Engineering Vascularized Skeletal Muscle for Treatment of Volumetric Muscle Loss", and an Alliance for Regenerative Rehabilitation and Rsearch Joseph Shrager, MD, received an R01 Training grant on "Stretchable Tissue grant on "A Mechanistic Clinical Trial Chips for Customizable Rehabilitative of JAK Inhibition to Prevent Ventilator- Microenviornments". induced Diaphragm Dysfunction".

Donate to the Stanford Cardiovascular Institute The Institute currently consists of over 240 faculty members representing physicians, surgeons, engineers, basic and clinical researchers. The Institute's mission is integrating fundamental research across disciplines and applying technology to prevent and treat cardiovascular disease. To support cardiovascular research and education at CVI, please contact: Joseph C. Wu, MD, PhD, CVI Director at [email protected] or Cathy Hutton, Senior Associate Director,

Medical Center Development at [email protected]. For more information: http://med. Joseph C. Wu, Cathy Hutton, MBA stanford.edu/cvi/support-our-research.html and http://cvi.stanford.edu MD, PhD | 55 cvi.stanford.edu 2018 Manuscript Award Winners

Jingjing Li, PhD Ning Ma, PhD Decoding the Genomics of Abdominal Aortic Determining the Pathogenicity of a Genomic Variant Aneurysm. Li J, Pan C, Spin JM, Deng A, Leung LLK, of Uncertain Significance using CRISPR/Cas9 and Dalman RL, Tsao PS, Snyder M. Cell 2018 Sept 6; Human-Induced Pluripotent Stem Cells. Ma N, Zhang 174(6):1361-1372. JZ, Itzhaki I, Zhang SL, Chen H, Haddad F, Kitani T, Lab: Michael Snyder, PhD; Phil Tsao, PhD Wilson KD, Tian L, Shrestha R, Wu H, Lam CK, Sayed N, Wu JC. Circulation. 2018 Dec 4;138(23):2666-2681. Lab: Joseph Wu, MD, PhD

Takeshi Nishi, MD David Paik, PhD Fractional Flow Reserve and Quality-of-Life Large-Scale Single-Cell RNA-Seq Reveales Molecular Improvement After Percutaneous Coronary Signatures of Heterogeous Populations of Human Intervention in Patients with Stable Coronary Artery Induced Pluripotent Stem Cell-Derived Endothelial Disease. Nishi T, Piroth Z, De Bruyne B, Jagic N, Cells. Paik DT, Tian L, Lee J, Sayed N, Chen IY, Rhee S, Möbius-Winkler S, Kobayashi Y, Derimay F, Fournier Rhee JW, Kim Y, Wirka RC, Buikema JW, Wu SM, Red- S, Barbato E, Tonino P, Jüni P, Pijls NHJ, Fearon WF. Horse K, Quertermous T, Wu JC. Circulation Reserach. Circulation. 2018 Oct 23;138(17):1797-1804. 2018 Aug 3;123(4):443-450. Lab: William Fearon, MD; Peter Fitzgerald, MD, PhD Lab: Joseph Wu, MD, PhD

Darshan Trivedi, PhD Ke Yuan, PhD Deciphering the Super Relaxed State of Human Loss of Endothelium-Derived Wnt5a is Associated b-cardiac Myosin and the Mode of Action of with Reduced Pericyte Recruitment and Small Vessel Mavacamten from Myosin Molecules to Muscle Loss in Pulmonary Arterial Hypertension. Yuan K, Fibers. Anderson RL, Trivedi DV, Sarkar SS, Henze Shamskhou EA, Orcholski ME, Nathan A, Reddy S, M, Ma W, Gong H, Rogers CS, Gorham JM, Wong Honda H, Mani V, Zeng Y, Ozen MO, Wang L, Demirci FL, Morck MM, Seidman JG, Ruppel KM, Irving TC, U, Tian W, Nicolls MR, de Jesus Perez VA. Circulation. Cooke R, Green EM, Spudich JA. PNAS 2018 Aug 2019 Apr 2;139(14):1710-1724. 28;115(35):E8143-E8152. Lab: Vinicio de Jesus Perez, MD Lab: James Spudich, PhD

AI identifies risk of cholesterol-raising genetic disease by Hanae Armitage A new algorithm can determine whether a patient is likely to have a cholesterol-raising genetic disease that can cause early, and sometimes fatal, heart problems, reports a new study conducted by researchers at the Stanford University School of Medicine and their collaborators. The disease, known as familial hypercholesterolemia (FH), is often misdiagnosed as garden-variety high cholesterol. “We think that less than 10 percent of individuals with FH in the United States actually know that they have it,” said Joshua Knowles, MD, PhD, assistant professor of cardiovascular medicine at Stanford. "It’s a serious oversight, because an FH patient with high cholesterol is three times more likely to develop early heart disease than someone who has high cholesterol but not FH. A person with FH Joshua Knowles, MD, PhD faces 10 times the risk of heart disease as someone with normal cholesterol." Knowles and Nigam Shah, MBBS, PhD, associate professor of medicine and of biomedical data science, have come up with a solution to help catch more cases of FH: a computer algorithm that flags patients who are likely to have the disease. In test runs of the algorithm, it correctly identified 88 percent of the cases it screened. Theoretically, if the algorithm were used in a clinic, any patient it flagged as having FH could undergo further genetic testing to verify the algorithm’s calculation. A paper describing the research was published in npj Digital Medicine. Shah and Knowles, who is the director of the FH clinic at Stanford Health Care’s Center for Inherited Cardiovascular Disease, share senior authorship. Juan Banda, PhD, a former research scientist at Stanford, is the lead author. The project is part of a larger initiative called Flag, Identify, Network, Deliver FH, or FIND FH, a collaborative effort involving Stanford Medicine and established by the nonprofit Familial Hypercholesterolemia Foundation that aims to identify and engage individuals and families affected by the disease by leveraging machine learning and big data. Now, Knowles and Shah are working on ways to implement the algorithm in doctors’ offices. The work is an example of Stanford Medicine’s focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill. Source: http://med.stanford.edu/news/all-news/2019/04/ai-identifies-risk-of-cholesterol-raising-genetic-disease.html cvi.stanford.edu | 6 Understanding metabolism and maturation of iPSC cardiomyocytes by Amanda Chase, PhD Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have been shown to be a great tool for modeling CVD and drug screening, and are also being used for transplantation into injured heart muscle as a potential therapy. A limitation to the use of these iPSC-CMs is that they are considered to be immature, similar to early human embryonic cardiomyocytes. To fully realize the potential of iPSC-CMs, they need to be more mature. It has been shown that iPSC-CMs show maturation over a longer period of time in culture, but no work has been done to characterize events that control transitions of cardiac cells during developmental progression. In a paper recently published in Circulation Research, Stanford Antje Ebert, PhD Cardiovascular Institute researchers sought to understand functional and metabolic transitions of cardiac cells during development, which could provide insight into maturing iPSC-CMs. These efforts were led by Antje Ebert, Ph.D., who is now a group leader at the University of Goettingen, Medical Center in Germany. They used iPSC-CMs that were kept in culture for different lengths of time (early, medium, and late), and then looked at network pathways at each time point and comparing between them. They were able to describe a novel mechanism governing metabolic output during long-term culture. Dr. Ebert explains that “this study shows that iPSC-CMs can serve as a model for studying human cardiomyocyte development progression during maturation. We also show that modulation of cardiomyocyte metabolism during development affects contractility of cardiomyocytes.” That is an important distinction for mature CMs. “Our study provides options for maturing iPSC-CMs, which is extremely useful for disease modeling, drug testing, and future regenerative approaches,” explains senior author Joseph C. Wu, M.D., Ph.D., Director of Stanford Cardiovascular Institute. Source: http://med.stanford.edu/cvi/mission/news_center/articles_announcements/understanding-metabolism-and-maturation-of-ipsc-cardiomyocytes.html

Recruitment for Assistant, Associate, or Full Professor, Stanford BASE Initiative The Stanford Children’s Health Betty Irene Moore Children’s Heart Center is inaugurating a major initiative in Basic Science and Engineering (BASE). Scientists will be appointed to the Children’s Heart Center and as tenure track Assistant, Associate or Full Professors in the Basic Science or Engineering Departments of Stanford University. Our goal is to leverage cutting edge research to address the challenges we face in children with heart disease. Inquiries to: Marlene Rabinovitch, MD c/o Michelle Fox, RA [email protected]. http://www.med.stanford.edu/base Modeling patient-specific responses to common calcium channel blocker using iPS Cells by Megan Mayerle Advances in treatment strategies and therapeutics allow individuals with chronic conditions a high quality of life. The symptoms of a wide variety of diseases can be mitigated simply by taking a pill. Many patients with hypertension are prescribed calcium channel blockers (CCBs) to control their blood pressure, which they take for the rest of their life. Although the acute effects of CCBs are well understood, very little is known about how these drugs impact cardiomyocyte physiology and gene expression patterns. Calcium is very important to heart cell function, and it is possible that CCBs could alter various cardiac cellular processes. Chi Keung Lam, PhD In a paper recently published in Circulation Research, Stanford Cardiovascular Institute researchers led by instructor Chi Keung Lam used cardiomyocytes made from induced pluripotent stem cells (iPSC-CMs) isolated from three individuals to understand how four commonly prescribed CCBs (nifedipine, amlodipine, diltiazem, and verapamil) affected cardiomyocyte function in different people. “iPSC technology allows us the opportunity to study how individual drugs will affect each patient, so we can decide on optimized, individualized treatment strategies”, Lam says. Because they used multiple iPSC-CM cell lines isolated from different patients, Lam and colleagues were able to identify patient specific responses to each of the four CCBs tested. They were also able to determine a drug-specific gene expression signature for each CCB. Combining these findings, Lam and colleagues were able to pinpoint specific genes that could be used to predict how well individual hypertrophic cardiomyopathy patients would respond to verapamil, a specific CCB. Source: http://med.stanford.edu/cvi/mission/news_center/articles_announcements/patient-specific-responses-to-extended-use-of-calcium- channel-bl.html cvi.stanford.edu | 7 Travel Award Winners

Shadi Bagherzadeh, MD Adam Bush, PhD Joscha Mulorz, MD Mentor: Francois Haddad, MD Mentor: Shreyas Vasanawala, MD, PhD Mentor: Philip Tsao, PhD 'Resting Blood Pressure in 2881 Athletes Aged 'Contiguous Rosette Echoes iN Single Highly 'E-cigarette Vapor Accelerates Abdominal 9-35 Years of Age and the Relation to Sex, Age, Accelerated Acquisition (CRENSHAA) for Rapid, Aortic Aneurysm In Mice' Body Size and Afro-American Descent' Motion Resolved T2* Quantification' AHA Vascular Discovery: From Genes to American Collee of Cardiology (ACC.19) Society of Cardiovascular Magnetic Resonance Medicine Sciencific Sessions 2019 March 17, 2019 February 6-9, 2019 May 14-16, 2019 New Orleans, LA Seattle, WA Boston, MA

Takeshi Nishi, MD Pavlos Tsantilas, MD Mentor: Peter Fitzgerald, MD, PhD Mentor: Nicholas Leeper, MD 'Intravascular Ultrasound Predictors of 'Chitinase-3-like Protein 1 is an Inhibitor of 4-Year Clinical Outcomes Following ABSORB Vascular Smooth Muscle Cell Dedifferentiation Bioresorbable Scaffold Implantation: Insights in Advanced Atherosclerosis' from the ABSORB Japan Trial' AHA Vascular Discover 2019 The American College of Cardiology's 68th May 14-16, 2019 Annual Scientific Sesseion Boston, MA March 16-18, 2019 New Orleans, LA 3D nanostructures improve skeletal muscle regeneration by Megan Mayerle, PhD Our muscles get stronger though repeated cycles of injury and repair. Exercise damages muscle, but at the same time activates muscle stem cells that differentiate into new skeletal muscle fibers, repairing and strengthening the tissue. However, sometimes the amount of damage done to muscle is too much, and, unable to properly heal, chronically inflamed scar tissue forms. In order to heal from this type of injury, the body must not only produce new skeletal muscle cells, it must also make sure that these cells orient properly to contract. Ngan Huang, PhD In a study recently published in Communications Biology, Stanford Cardiovascular Institute researchers Karina Nakayama, PhD, Ngan Huang, PhD, and colleagues describe a method to fabricate skeletal muscle using spatially patterned bioengineered scaffolds. These scaffolds help newly formed skeletal cell muscles align, and when implanted into a damaged area, help mice recover from injury. The researchers created aligned nanofibrillar scaffolds and then seeded them with myoblasts and endothelial cells, the cell types that make up skeletal muscle tissue. The nanofibrillar scaffolds organized the cells, producing long skeletal muscle myotubules capable of contracting strongly and consistently. Alignment also affected cellular gene expression, inducing differential transcriptional pathways that may regulate how engineered muscle behaves. To test this engineered muscle, the scientists transplanted their aligned engineered skeletal muscle to a site of injury in the mice. The aligned tissue integrated into the site of injury without significant scarring. It also aided in tissue revascularization, which is critical for recovery from injury. This method shows translational promise, as the researchers were also able to show that human cells aligned on bioengineered scaffolds functioned similarly to the mouse cells and highlights the importance of how cells are positioned in 3D in regenerative medicine approaches. Source: http://med.stanford.edu/cvi/mission/news_center/articles_announcements/3d-nanostructures-improve-skeletal-muscle-regeneration.html

cvi.stanford.edu | 8 Single Ventricle Summit On April 29-30, patients, parents, and distinguished scientists, bioengineers, and clinicians from around the world came together for the Second Annual Stanford Single Ventricle Scientific Summit. This event was an opportunity for synergy across disciplines, with the major focus being on advancing single ventricular science. The summit was organized by: Gail Wright, MD, Erin Hoffmann Medical Director of the Single Ventricle Summit group Comprehensive Single Ventricle Program, Sean Wu, MD, PhD, Associate Professor of Medicine, and Marlene Rabinovitch, MD, Dwight and Vera Dunlevie Professor of Pediatrics. It was made possible by the Hoffmann Schroepfer Foundation.

Development at the heart of science by Jaclyn M. Jansen In a recent conversation with Circulation Research, CVI faculty member Sean Wu, MD, PhD, described his development and career as a scientist. Both in his life and his research, he has taken a uniquely broad and adaptable approach that has helped him become a leader in developmental cardiology. Sean Wu, MD, Source: https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.119.315208 PhD Apple Heart Study demonstrates ability of wearable technology to detect atrial fibrillation Researchers from the Stanford University School of Medicine today presented preliminary results of the Apple Heart Study, an unprecedented virtual study with over 400,000 enrolled participants. The researchers reported that wearable technology can safely identify heart rate irregularities that subsequent testing confirmed to be atrial fibrillation, a leading cause of stroke and hospitalization in the United States. Kenneth Marco Perez, MD Mintu Turakhia, Mahaffey, MD MD The study was launched with sponsorship by Apple Inc. in November 2017 to determine whether a mobile app that uses data from a heart-rate pulse sensor on the Apple Watch can identify atrial fibrillation. The condition often remains hidden because many people don’t experience symptoms. “The results of the Apple Heart Study highlight the potential role that innovative digital technology can play in creating more predictive and preventive health care,” said Lloyd Minor, MD, dean of the Stanford School of Medicine. “Atrial fibrillation is just the beginning, as this study opens the door to further research into wearable technologies and how they might be used to prevent disease before it strikes — a key goal of precision health.” The Stanford principal investigators were Mintu Turakhia, MD, associate professor of cardiovascular medicine, and Marco Perez, MD, associate professor of cardiovascular medicine, and the study chair was Kenneth Mahaffey, MD, professor of cardiovascular medicine. Source: http://med.stanford.edu/news/all-news/2019/03/apple-heart-study-demonstrates-ability-of-wearable-technology.html

Leah Backhus, MD, became a newly inducted member of the American CVI Seed Grant Awards Association for Thoracic Surgery (AATS). Due August 1, 2019 AATS members are recognized as Eligibility: Stanford Faculty and Instructor members of having a record of distinction within the the CVI (become a member at CVI website). field and for having made significant Awards are $15,000 to $40,000 for 1 year and funded contributions towards the treatment of in part by the Maternal and Child Health Research cardiothoracic disease. Dr. Backhus was Institute and the Steven M. Gootter Foundation. Leah Backhus, MD also appointed Director-at-Large of the We encourage new interdisciplinary Society of Thoracic Surgeons (STS) and secretary/treasurer collaborations, work in areas of pediatric and obstetric of Women in Thoracic Surgery. She is a clinically active related research, development of new methods or surgeon, recenlty received a large VA Merit Award, and is the technology for heart and vascular biology, and research Thoracic Residency Program Director, thereby epitomizing on sudden cardiac death. the "triple threat" academic physician. Questions: David Preston at [email protected] cvi.stanford.edu | 9 Drug reduces risk of kidney failure in people with diabetesby Amy Jeter Hansen A new landmark clinical trial shows that a drug lowers the risk of kidney failure by a third in people with Type 2 diabetes and kidney disease. “For the first time in 18 years, we have a therapy for patients with Type 2 diabetes and chronic kidney disease that decreases kidney failure,” said Kenneth Mahaffey, MD, professor of medicine at the School of Medicine and co-principal investigator of the trial. “Now, patients with diabetes have a promising option to guard against one of the most severe risks of their condition.” The trial involved 4,401 participants in 34 countries. Kenneth Mahaffey, The drug, canagliflozin, improves on a nearly two-decades-old therapy that is currently the only treatment MD approved to protect kidney function in people with Type 2 diabetes. In the trial, canagliflozin also was found to reduce the risk of major cardiovascular events. It has already been approved to lower blood glucose in patients with Type 2 diabetes and to reduce the risk of major adverse cardiovascular events in patients with Type 2 diabetes and existing heart disease. A paper describing the findings of the CREDENCE trial was published April 14 in The New England Journal of Medicine and presented at the International Society of Nephrology’s World Congress of Nephrology in Melbourne, Australia. Mahaffey, who is director of the Stanford Center for Clinical Research, is the study’s senior author. The lead author is Vlado Perkovic, MBBS, PhD, executive director of The George Institute for Global Health Australia, and a professor of medicine at the University of New South Wales in Sydney. Other Stanford researchers assisting in the trial were Glenn Chertow, MD, professor of medicine, and Tara Chang, MD, assistant professor of medicine, who were national co-leads; and Sun Kim, MD, associate professor of medicine, who was a site investigator. Source: http://med.stanford.edu/news/all-news/2019/04/drug-reduces-risk-of-kidney-failure-in-people-with-diabetes.html

Patient-specific hemodynamics for Stem cell-derived cardiomyocyte the treatment of Kawasaki Disease tool could improve drug safety by Amanda Chase, PhD by Megan Mayerle, PhD Kawasaki disease (KD) causes Patient-derived cardiomyocytes (iPSC- inflammation in arterial walls throughout CMS) provide a platform for better drug the body and is most prevalent in children screening and disease modeling, as well under 5 years of age. While most children as and the first step toward realizing recover, Kawasaki disease can cause the beginnings of a more personalized coronary artery aneurisms, which can approach to studying and treating heart lead to thrombosis. To prevent this, many disease. Furthermore, they can be used Alison Marsden, PhD patients are prescribed anticoagulants. to generate engineered heart tissue (EHT) Joe Zhang, PhD However, guidelines of anticoagulant use rely on anatomical measurements alone, without considering the impact of flow to better mimic the complex environment of a living human patterns. heart. Having a highly homogeneous pool of ventricular or atrial CMs would be beneficial for applications such as: Stanford researchers Noelia Grande Gutierrez, Alison L. determining drug safety, cardiac evaluation, and cell therapy Marsden, and colleagues have come up with an innovative for heart attacks by allowing personalized cardiac repair. solution to this problem. They developed a computational A team of researchers primarily affiliated with the Stanford fluid dynamics simulation that uses information derived from Cardiovascular Institute sought to find a way to make the non-invasive vascular imaging data to provide patient-specific heterogenous iPSC-CMs into more homogenous population hemodynamic measurements. The hemodynamic variables of cells. Led by first author Joe Z. Zhang, PhD., and senior identified by Gutierrez et al. are superior to traditionally used author Joseph C. Wu, M.D., PhD., Director of Stanford anatomical measurements for KD aneurysms assessment and Cardiovascular Institute, they developed an innovative tool can be used to identify aneurysmal regions at higher risk of to helps isolate specific cardiac subpopulations to generate thrombosis. In the future, personalized hemodynamics could a purer population of cells. The work was published in Cell help doctors determine how and when to use anticoagulants Stem Cell. The tool developed by these researchers allows, for Kawasaki disease patients. for the first time, isolation of lineage-specific cardiovascular The study was published in the April 15 issue of the cells. International Journal of Cardiology. Source: http://med.stanford.edu/cvi/mission/news_center/arti- cles_announcements/application-of-patient-specific-hemodynam- Source: http://med.stanford.edu/cvi/mission/news_center/articles_ ics-to-the-treatment-of.html announcements/stem-cell-derived-cardiomyocyte-tool-could-improve- drug-safety.html cvi.stanford.edu | 10 A new role for PPARg in pulmonary arterial hypertension by Megan Mayerle, PhD Pulmonary arterial hypertension (PAH) is a form of pulmonary hypertension that results from the loss and narrowing of the lumen of small arteries of the lungs which causes an increase in blood pressure. Over time, this increased blood pressure can damage the heart. PAH generally affects young and otherwise healthy individuals and strikes women twice as often as men. Estimates indicate that there are between 10,000 and 20,000 PAH patients in the US.

While PAH is not yet understood at the molecular level, dysfunctional peroxisome Marlene Rabinovitch, MD Caiyun Grace Li, PhD proliferator activated receptor g (PPARg), a nuclear receptor that acts as a part of a transcription factor complex in vascular and other cell types, has been linked to many vascular diseases including PAH. Furthermore, in PAH, dysfunction of endothelial cells, the cells that line the interior of blood vessels, has been linked to the loss and narrowing of blood vessels. This leads to increased resistance to pulmonary blood flow and can culminate in heart failure and the need for a lung transplant. In a study recently published in Cell Reports, lead author Dr. Caiyun Grace Li, corresponding author Dr. Marlene Rabinovitch, and colleagues reveal a new role for PPARg, linking it to the cellular DNA damage response and to DNA repair. In addition to providing a clearer understanding of the role that PPARg plays in PAH pathogenesis, these novel findings lay the groundwork for potential new PAH therapeutics and treatment strategies. Source: http://med.stanford.edu/cvi/mission/news_center/articles_announcements/a-new-role-for-ppar-in-pulmonary-arterial-hypertension.html Study shows how big data can be used for personal health by Hanae Armitage Scientists at Stanford and their collaborators followed a cohort of more than 100 people over several years, tracking the biology of what makes them them. Now, after collecting extensive data on the group’s genetic and molecular makeup, the researchers are piecing together a new understanding of what it means to be healthy and how deviations from an individual’s norm can flag early signs of disease. The results point to a need for a paradigm shift, said Michael Snyder, PhD, professor and chair of genetics. “I would argue that the way medicine is practiced is deeply flawed Michael Snyder, PhD Francois Haddad, MD and could be significantly improved through longitudinal monitoring of one’s personal health baseline,” said Snyder, who holds the Stanford W. Ascherman, MD, FACS, Professorship in Genetics. “We generally study people when they’re sick, rarely when they’re healthy, and it means we don’t really know what ‘healthy’ looks like at an individual biochemical level.” The researchers uncovered more than 67 clinically actionable health discoveries that ranged from high blood pressure, arrhythmias, cardiomyopathy and early stage cancer detection, among others. The study intertwined data from wearable technologies, genome sequencing and microbial and molecular profiling to establish a baseline of sorts for each participant. Every person’s broad swath of data painted a picture of their biological baseline, and as scientists tracked how that picture changed, they also kept tabs on any abnormalities that could signal the development of disease. A paper describing the research findings were published May 8 in Nature Medicine. Snyder and Francois Haddad, MD, clinical associate professor of medicine, are co-senior authors. Sophia Miryam Rose, MD, PhD, instructor of neurosurgery, and Kévin Contrepois, PhD, scientific director at Stanford Metabolic Health Center, share lead authorship. Outside of participant health, the researchers think they may have even discovered new biomarkers for certain diseases and possibly new molecular markers for cardiovascular disease risk, among other things. For now, these are preliminary findings; the researchers will have to conduct follow-up studies to confirm their suspicions. “I can’t tell you exactly what we’re going to find if we follow a group of 100 people over time with advanced technologies, but I can tell you we will often find things that are important for their health,” Snyder said. “Right now, we’re pretty much in the dark until we profile people, but this approach could provide us a much better view of people’s norms, what it means to be healthy and what it means when people deviate from that. Ultimately, we want to shift the practice of medicine from treating people when they are ill to a focus on keeping them healthy by predicting disease risk and catching disease before it is symptomatic.” Source: https://med.stanford.edu/news/all-news/2019/05/study-shows-how-big-data-can-be-used-for-personal-health.html cvi.stanford.edu | 11 Lab-grown heart cells reveal Failure to take statins leads to secrets of "kissing bug" disease higher mortality by Krista Conger by Mandy Erickson People infected with the parasite More than a third of patients with Trypanosoma cruzi develop (among other cardiovascular disease who have been symptoms) fever, aches, fatigue, diarrhea prescribed statins to reduce cholesterol failed and vomiting. About 30 percent of those to take them daily. Women and non-whites infected go on to develop chronic Chagas were least likely to take their prescriptions, Fatima disease, which can cause long-term Adriana Bozzi, PhD as were the oldest and youngest patients. Rodriguez, MD health complications including heart failure and digestive “The take-away for clinicians is not to become problems. Varieties of the bug are found in 28 states, mostly complacent about stable patients with cardiovascular in the southern parts of the country. It is widespread in South disease,” said Stanford cardiologist Fatima Rodriguez, MD, America, and Chagas disease is estimated to contribute to the lead author of a study published in JAMA Cardiology. more than 10,000 deaths each year. Rodriguez and colleagues examined the health Now cardiologist and stem cell researcher Joseph Wu, MD, records of 347,104 patients with atherosclerotic PhD, together with visiting scholar Adriana Bozzi, PhD, have cardiovascular disease — caused by fatty deposits in used lab-grown heart muscle cells called cardiomyocytes to their arteries — who had been prescribed statins. Even investigate at a cellular level how the infection spread by the those who were pretty good — but not perfect — at bugs affects cardiac function. They published their findings picking up their prescriptions showed some increased recently in Stem Cell Reports. mortality, Rodriguez said. Stanford cardiologist Paul Heidenreich, MD, the senior author of the study, said that Source: https://scopeblog.stanford.edu/2019/05/21/lab-grown-heart- physicians can often do more to encourage their patients cells-reveal-secrets-of-kissing-bug-disease/ to take their medications daily. Source: Source: https://scopeblog.stanford.edu/2019/02/14/failure-to- take-statins-leads-to-higher-mortality/ Recruitment for T32 Fellowships Multi-Disciplinary Training Program in Cardiovascular Imaging T32 Training Grant - 2 Openings The Multi-Disciplinary Training Program in Cardiovascular Imaging at Stanford is funded by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health. With the impact of cardiovascular disease on U.S. and world health, and the rapid advances in imaging technologies and cardiovascular biology, it is critical that fellows be provided a broad, multi-disciplinary, and collaborative training program to foster their ability to translate CV imaging research into clinical applications. The program is designed to train the next generation of CV imaging investigators by exposing them to three complementary areas—clinical, engineering, and molecular imaging. http://med.stanford.edu/cvi/education/cardiovascular-imaging-t32.html

Mechanisms and Innovations in Cardiovascular Disease T32 Training Grant This program provides training in the following areas of vascular medicine and research: Vascular Reactivity and Thrombosis, Vascular Regeneration and Development, Metabolic or Lifestyle Influences on Vascular Outcomes, Proteomic Markers & Genetic Determinants of Vascular Disease, Gender and Ethnicity Differences in Vascular Disease, and Vascular Bioengineering. Twenty-nine faculty mentors from eighteen different departments within the School of Medicine and the University provide a variety of angles from which to address fundamental questions about vascular disease. http://med.stanford.edu/cvi/education/mechanisms-and-innovations-t32.html Research Training in Myocardial Biology T32 Training Grant - 2 Openings The Multi-Disciplinary Research Training Program in Myocardial Biology is funded by the National Institutes of Health to bring together post-doctoral fellows and faculty from six complementary areas – genetics and genomics, cellular signaling, molecular imaging, physiology and phenotyping, cardiac development and regeneration and outcomes research and population science. Although many possible divisions exist in the spectrum of cardiovascular investigators, one of the most discrete is the division between those researchers interested in blood vessels and those primarily interested in the biology of the heart muscle itself. Myocardial biologists at Stanford are found in diverse departments and divisions within the wider Stanford community and this provides a natural vehicle for multidisciplinary training. http://med.stanford.edu/cvmedicine/education/timbs.html cvi.stanford.edu | 12 Funding Opportunities

June 2019 2020 Sanofi Innovation Awards (iAwards). Eligibility: faculty NIH NHLBI Clinical Ancillary Studies (R01 Clinical Trial with PI eligibility and CE faculty (with an approved CE faculty Optional). Deadline: August 24, 2019. PAR-18-643. PI waiver) involved in multi-therapeutic areas including: NIH Director’s New Innovator Award Program (DP2 Clinical immune-oncology, molecular oncology, immunology and Trial Optional). Supports early stage investigators of inflammation, rare diseases, neurosciences, diabetes, and exceptional creativity who propose highly innovative cardiovascular diseases. Deadline: June 29, 2019 to Lisa research projects with the potential to produce a major Chen at [email protected]. impact on broad, important problems relevant to the July 2019 mission of NIH. Deadline: August 26, 2019. RFA-RM-19-006. AHA Merit Award. $200,000 per year for 5 years. Eligability: September 2019 Stanford tenured or tenure-track Associate Professors or NIH Director's Pioneer Award (DP1 Clinical Trial Optional). higher, PhD and/or MD, PI on multiple active, national, peer- Amount: $700,000. Deadline: September 6, 2019. RFA- reviewed awards. Must devote 75% effort. Deadline: July 11, RM-19-005. 2019 Letter of Intent; September 24, 2019 full proposal. Fondation Leducq: Transatlantic Networks of Excellence in NIH Pathway to Independence Award. (Parent K99/R00 Cardiovascular and Neurovascular Research. Amount: up to Independent Clinical Trial Required). Deadline: July 12, $6M over 5 yrs (up to 5 to be awarded). Eligibility: Stanford 2019. PA-19-129. faculty with PI eligibility and CE faculty (with an approved CE NIH Mentored Research Scientist Development Award. faculty PI waiver). Deadline: Letter of Intent (required): Sept. (Parent K01 - Independent Clinical Trial Not Allowed). Paris Time (via proposal central). Full proposal (by invitation Deadline: July 12, 2019. PA-19-126. only): Feb. via proposal central. NIH R21 Exploratory/Developmental Research Grant. Nina Starr Braunwald Research Award. Amount: up to $40,000 Improving Outcomes in Cancer Treatment-Related per year for 2 years. Eligibility: faculty with PI eligibility and Cardiotoxicity (R21 Clinical Trial Optional). Deadline: July CE faculty (with an approved CE faculty PI waiver); early- 16, 2019. PA-19-111. career women cardiac surgeon. Deadline: Sept. 15, 2019. NIH/NHLBI R34 Planning Grant. Clinical Trial Pilot Studies Nina Starr Braunwald Research Fellowship Award. Amount: (R34 Clinical Trial Optional). Deadline: July 16, 2019. PAR-19- up to $30,000 per year for 2 years. Eligibility: woman resident 155. working in a cardiac surgical clinic or laboratory research program who has not yet completed cardiothoracic surgical NIH/NHLBI Notice of Special Interest (NOSI): Bold New training. Deadline: Sept. 15, 2019. Bioengineering Research for Heart, Lung, Blood and Sleep Disorders and Diseases. Area of special interest in exploring TSF Every Heartbeat Matters Award. Amount: $37,500. bold, new bioengineering approaches or concepts that are Eligibilty: faculty with PI eligibility and CE faculty (with an important to a substantive heart, lung, blood or sleep area. approved CE faculty PI waiver). Applicants must be ABTS Applications in response to this Notice must be submitted (or equivalent) certified cardiothoracic surgeons. Deadline: through NIH Parent Announcement: NIH Exploratory/ Sept. 15, 2019. Developmental Research Grant Program (Parent R21 Clinical NIH Director’s Transformative Research Awards (R01 Clinical Trial Not Allowed). Deadline: July 16, 2019. PA-19-053 Trial Optional) (no budget limit). Deadline: Sept. 20, 2019. AHA Institute for Precision Cardiovascular Medicine. AHA RFA-RM-007. Grand Challenge: Precision Health and Precision Medicine. $250,000 per year for 4 years. Eligibility: Stanford faculty with PI eligibility and CE faculty (with an approved CE faculty PI waiver). Deadline: July 31, 2019. August 2019 NIH Ruth L. Kirschstein National Research Service Award (NRSA). Individual Postdoctoral Fellowship (Parent F32). Deadline: August 8, 2019. PA-19-188. American Heart Association Postdoctoral Fellowship. Amount: $51,484 - $125,120. See guidelines for budget information. Deadline: August 15, 2019 cvi.stanford.edu | 13 National and Global Cardiovascular Conferences

JUNE 2019 SEPTEMBER 2019

American College of Cardiology Care of the Athletic Heart: American Heart Association Hypertension 2019 Scientific From Elite to Exercise Enthusiasts. June 20-22, 2019. Heart Sessions. September 5–8, 2019. New Orleans Marriott, New House, Washington, DC. Orleans, Louisiana.

23rd Annual Hypertension, Diabetes and Dsylipidemia Interventional Cardiology Review Course for Boards and Conference. June 21 - 23, 2019. Hyatt Place + Hyatt House Recertification. September 6-8, 2019. Hilton Rochester Mayo Historic District, Charleston, SC. Clinic, Rochester, MN.

Cardiac Rhythm Devise: Implantation, Management and Advanced Catheter Ablation: New Tips, Techniques and Follow Up. June 21-23, 2019. Sofitel, New York, NY. Technologies for Complex Arrhythmias. September 7-10, 2019. Swissotel Chicago, Chicago, IL. International Society for Stem Cell Research. June 26-29, 2019. Los Angeles Convention Center, Los Angeles, CA. American College of Cardiology 2019 Cardiovascular Service Lines 101 Webinar. 12-1 pm September 12, 2019. Heart Failure Up North: Practical Approaches to the Management of Congestive Heart Failure. June 29-30, 2019. Stanford University Electrophysiology in the West 2019: The Maddens on Gull Lake, Brainerd, Minnesota. Latest Advances in Arrhythmia Care. Li Ka Shing Center for Learning and Knowledge, September 13, 2019. JULY 2019 Cardiac Rehabilitation Workshop: The Mayo Clinic Model. Stanford University 27th Annual Pediatric Update and September 23-25, 2019. Rochester, MN. Pre-Conference: What’s New in Allergy and Pulmonology 2019. July 18-20, 2019. The Frances C. Arrillaga Alumni Center, Advanced Cardiovascular Implantable Electronic Device Stanford, CA. (CIED) Management: Case-Based Approach. September 26- 28, 2019. Siebens Building - Phillips Hall, Rochester, MN. Current Applications and Future of Artificial Intelligence in Cardiology. July 19-20, 2019. Intercontinental San Francisco, Challenges in Clinical Cardiology: A Case-Based Update. San Francisco, CA. September 27-29, 2019. Swissotel Chicago, Chicago, IL.

Echocardiographic Symposium at Vail: State-of-the-Art OCTOBER 2019 Review, Live Scanning With Emphasis on Multimodality Imaging With Cardiac CT & MRI. July 22-25, 2019. Vail Marriott, Echo in Congenital Heart Disease: Special Emphasis on Adult Vail, CO. Congenital Heart Disease: Including Uses of Multimodality Imaging. October 2-5, 2019. Hyatt Regency Coconut Point, American Heart Association Basic Cardiovascular Sciences Bonita Springs, FL. Scientific Sessions. July 29-August 1, 2019. Westin Boston Waterfront, Boston, MA. American College of Cardiology Core Curriculum for the Cardiovascular Clinician. October 2- 5, 2019. Washington, DC. AUGUST 2019 American College of Cardiology Heart Valve Summit: Cardiology Update: The Heart of the Matter 2019. August 1-4, Medical, Surgical and Interventional Decision Making. 2019. Sedona, AZ. October 3- 5, 2019. Chicago, IL.

Success With Failure: Strategies for the Evaluation and The Genetics of Heart & Vascular Disease. October 10-12, Treatment of Heart Failure. August 2-4, 2019. The Greenbrier, 2019. The Meritage Resort, Napa, CA. White Sulphur Springs, WV. Innovations in Atrial Fibrillation Management: Impacting American College of Cardiology ACC/SCAI Premier Quality of Life and Stroke Risk. October 18-19, 2019. Grand Interventional Cardiology Overview and Board Preparatory Hyatt Seattle, Seattle, Washington. Course. August 8-11, 2019. Cases in Echocardiography, Cardiac CT, and MRI. October 23- Cardiovascular Board Review for Initial Certification 26, 2019. The Meritage Resort, Napa, CA. and Recertification. August 24-29, 2019. Mayo Civic Center, Rochester, MN. Vascular Biology 2019. October 27-31, 2019. Asilomar Conference Grounds, Monterey, CA.

cvi.stanford.edu | 14 CVI Cores Stanford CVI Human iPSC Biobank Service Normal and patient-derived reprogrammed cardiomyocytes are a tremendous resource for researchers and physicians here at Stanford and around the country. Understanding the disease process directly at the population level and observing these cells as Cardiovascular Pharma- surrogates under a myriad conditions has the potential to be a game-changer for cardiovascular medical research. cology (BioADD)

To facilitate research in a dish that allows screening of new compounds or characterization of The Cardiovascular Pharmacology/ human disease phenotypes using cardiomyocytes, the Institute created a service by which Biomaterials and Advanced Drug Delivery de-identified peripheral blood mononuclear cell (PBMC) samples from selected patients (BioADD) Laboratory is a cutting edge can be sent to Stanford CVI for reprogramming free of cost. research facility that specializes in the creation of biomaterials and drug delivery SCVI biobank is supported in part by National Heart, Lung and Blood Institute (NHLBI) and the agents. The lab lends its expertise toward Stanford Cardiovascular Institute (CVI). designing and analyzing biomaterials, developing drug delivery devices and Stanford iPSC Biobank was recently mentioned in Nature Methods news: nature.com/nmeth/ formulations, pharmacokinetic and journal/v12/n2/full/nmeth.3263.html. pharmacodynamic studies, and developing Contact: Joseph Wu, MD, PhD / [email protected] smart materials for biomedical applications. or Biobank manager, Yan Zhuge, PhD / [email protected] with any questions. The CVI Cardiovascular Pharmacology also offers trainings and lectures.

Clinical Biomarker & Phenotyping Core Lab (BPCL) Contact: Jayakumar Rajadas, PhD [email protected] BPCL provides quantitative assessment of clinical cardiovascular phenotypes for translational research and clinical trials. These cardiovascular phenotypes include evaluating cardiac structure and function, measuring carotid intimal thickness and arterial stiffness, and testing endothelial function and cardiopulmonary exercise testing.

In collaboration with the Human Immune Monitoring Center at Stanford and members of the Cardiovascular Institute, we also offer central blood processing and banking capabilities. In addition, we develop new biomarker platforms and imaging modalities. Contact: Francois Haddad, MD / [email protected] 3DQ Imaging Laboratory

Stanford’s 3DQ Imaging Laboratory CVI Clinical Trials Core develops new approaches to exploration, analysis and quantitative assessments The CVI Clinical Trials Core provides full spectrum of support to CVI members and their clinical of diagnostic images that result in new trials. The coordinators has extensive clinical research experience in both industry and academia. and/or more cost-effective diagnostic The team provides services and support to principal investigators and sponsors, including: approaches, and new techniques for the design and monitoring of therapy. The • Consultation • Data management lab processes over 1,200 clinical cases to • Study start-up management, including • Regulatory compliance and documen- deliver relevant visualization and analysis IRB applications, budget development tation of medical imaging data at Stanford. The • Subject recruitment, site visits, and • Closeout lab is co-directed by Dominik Fleischmann, follow-ups (AE reporting and queries) MD, Roland Bammer, PhD and Sandy Napel, PhD. Contact: Ed Finn, Clinical Trials Manager at [email protected] Contact: Dominik Fleischmann, MD, at [email protected]

cvi.stanford.edu | 15 Member Publications

Communication is at the heart of scientific advancement and innovation. This quarter, the Stanford Cardiovascular Institute members published over 350 original manuscripts and reviews, further contributing to our understanding of cardiovascular biology and disease. Here, we highlight selected manuscripts by our members.

Predicting Future Cardiovascular Events in Patients With Peripheral Artery MARCH Disease Using Electronic Health Record Data. Ross EG, Jung K, Dudley JT, Li L, Leeper NJ, Shah NH. Circ Cardiovasc Qual Outcomes. 2019 Mar;12(3):e004741. Cardiac Segmental Strain Analysis in Pediatric Left Ventricular Noncompaction Lymphatic endothelial cell calcium pulses are sensitive to spatial gradients in Cardiomyopathy. Arunamata A, Stringer J, Balasubramanian S, Tacy TA, wall shear stress. Surya VN, Michalaki E, Fuller GG, Dunn AR. Mol Biol Cell. 2019 Silverman NH, Punn R. J Am Soc Echocardiogr. 2019 Mar 26. Mar 21;30(7):923-931. 4-Methylumbelliferyl glucuronide contributes to hyaluronan synthesis The 2019 update of the European abdominal aortic aneurysm guidelines. inhibition. Nagy N, Gurevich I, Kuipers HF, Ruppert SM, Marshall PL, Xie BJ, Sun Dalman RL. J Vasc Surg. 2019 Mar;69(3):633-634. W, Malkovskiy AV, Rajadas J, Grandoch M, Fischer JW, Frymoyer AR, Kaber G, Bollyky PL. J Biol Chem. 2019 Mar 26. A Biocompatible Therapeutic Catheter-Deliverable Hydrogel for In Situ Tissue Engineering. Steele AN, Stapleton LM, Farry JM, Lucian HJ, Paulsen MJ, Proposed achievable levels of dose and impact of dose-reduction systems Eskandari A, Hironaka CE, Thakore AD, Wang H, Yu AC, Chan D, Appel EA, Woo for thrombectomy in acute ischemic stroke: an international, multicentric, YJ. Adv Healthc Mater. 2019 Mar;8(5):e1801147. retrospective study in 1096 patients. Guenego A, Mosimann PJ, Pereira VM, Nicholson P, Zuber K, Lotterie JA, Dobrocky T, Marcellus DG, Olivot JM, Piotin M, Discovery of Distinct Immune Phenotypes Using Machine Learning in Gralla J, Fahed R, Wintermark M, Heit JJ, Cognard C; RADON Investigators. Eur Pulmonary Arterial Hypertension. Sweatt AJ, Hedlin HK, Balasubramanian Radiol. 2019 Mar 22. V, Hsi A, Blum LK, Robinson WH, Haddad F, Hickey PM, Condliffe R, Lawrie A, Nicolls MR, Rabinovitch M, Khatri P, Zamanian RT. Circ Res. 2019 Mar Gene-Environment Interaction in the Era of Precision Medicine. Li J, Li X, Zhang 15;124(6):904-919. S, Snyder M. Cell. 2019 Mar 21;177(1):38-44. Absent or Excessive Corpus Luteum Number Is Associated With Altered Preoperative Laboratory Studies for Pediatric Cardiac Surgery Patients: A Maternal Vascular Health in Early Pregnancy. von Versen-Höynck F, Narasimhan Multi-Institutional Perspective. Jones SE, Jooste EH, Gottlieb EA, Schwartz P, Selamet Tierney ES, Martinez N, Conrad KP, Baker VL, Winn VD. Hypertension. J, Goswami D, Gautam NK, Benkwitz C, Downey LA, Guzzetta NA, Zabala L, 2019 Mar;73(3):680-690. Latham GJ, Faraoni D, Navaratnam M, Wise-Faberowski L, McDaniel M, Spurrier E, Machovec KA. Anesth Analg. 2019 Mar 14. Death or resolution: the "natural history" of pulmonary hypertension in bronchopulmonary dysplasia. Altit G, Bhombal S, Hopper RK, Tacy TA, Short-Term Outcomes of en bloc Combined Heart and Liver Transplantation Feinstein J. J Perinatol. 2019 Mar;39(3):415-425. in the Failing Fontan. Vaikunth SS, Concepcion W, Daugherty T, Fowler M, Lutchman G, Maeda K, Rosenthal DN, Teuteberg J, Joseph Woo Y, Lui GK. Clin Parental Acquisition of Echocardiographic Images in Pediatric Heart Transplant Transplant. 2019 Mar 20:e13540. Patients Using a Handheld Device: A Pilot Telehealth Study. Dykes JC, Kipps AK, Chen A, Nourse S, Rosenthal DN, Selamet Tierney ES. J Am Soc Echocardiogr. Outcomes of pulmonary artery reconstruction in Williams syndrome. Collins RT 2019 Mar;32(3):404-411. 2nd, Mainwaring RD, MacMillen KL, Hanley FL. Ann Thorac Surg. 2019 Mar 15. Characteristics and outcomes of patients requiring bailout use of glycoprotein Transthyretin Stabilization by AG10 in Symptomatic Transthyretin Amyloid IIb/IIIa inhibitors for thrombotic complications of percutaneous coronary Cardiomyopathy. Judge DP, Falk RH, Maurer MS, Shah SJ, Witteles RM, Grogan intervention: An analysis from the CHAMPION PHOENIX trial. Abtan J, Ducrocq M, Selby VN, Jacoby D, Hanna M, Nativi-Nicolau J, Patel J, Rao S, Sinha U, Turtle G, Steg PG, Stone GW, Mahaffey KW, Gibson CM, Hamm C, Price MJ, Prats J, CW, Fox JC, Heitner SB. J Am Coll Cardiol. 2019 Mar 12. Elkin S, Deliargyris EN, White HD, Menozzi A, Harrington RA, Bhatt DL; MPH Comparing phase and electrographic flow mapping for persistent atrial on Behalf of the CHAMPION PHOENIX Investigators. Int J Cardiol. 2019 Mar fibrillation. Swerdlow M, Tamboli M, Alhusseini MI, Moosvi N, Rogers AJ, Leef 1;278:217-222. G, Wang PJ, Rillig A, Brachmann J, Sauer WH, Ruppersberg P, Narayan SM, Understanding health disparities. Stevenson DK, Wong RJ, Aghaeepour N, Baykaner T. Pacing Clin Electrophysiol. 2019 Mar 18. Angst MS, Darmstadt GL, DiGiulio DB, Druzin ML, Gaudilliere B, Gibbs RS, B Practice Variation in Anticoagulation Prescription and Outcomes after Device- Gould J, Katz M, Li J, Moufarrej MN, Quaintance CC, Quake SR, Relman DA, Detected Atrial Fibrillation: Insights from the Veterans Health Administration. Shaw GM, Snyder MP, Wang X, Wise PH. J Perinatol. 2019 Mar;39(3):354-358. Perino AC, Fan J, Askari M, Heidenreich PA, Keung E, Raitt MH, Piccini JP, Ziegler Heart transplantation in two adolescents with Danon disease. Oren D, Chau PD, Turakhia MP. Circulation. 2019 Mar 17. P, Manning M, Kwong J, Kaufman BD, Maeda K, Rosenthal DN, Hollander SA. A Human iPSC Double-Reporter System Enables Purification of Cardiac Lineage Pediatr Transplant. 2019 Mar;23(2):e13335. Subpopulations with Distinct Function and Drug Response Profiles. 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cvi.stanford.edu | 18 Leadership

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

Ronald L. Dalman, MD Walter C. and Elsa R. Chidester Stephen J. Roth, MD, MPH Professor of Surgery Professor and Chief, Pediatric Cardiology Chief, Division of Vascular Surgery Director, Children’s Heart Center

Michael Snyder, PhD Dominik Fleischmann, MD Professor and Chair, Dept. 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, Dept. of Cardiothoracic Surgery

Mark Nicolls, MD The Stanford Professor of Pulmonary and Alan Yeung, MD Critical Care Medicine, Dept. 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 Bioengineering and Medicine; William G. Irwin Professor of Medicine and Professor, by courtesy, Co-Chief (Research), of Mechanical Engineering, Division of Cardiovascular Medicine Director, Byers Center for Biodesign

Marlene Rabinovitch, MD Dwight and Vera Dunlevie Professor in Pediatric Cardiology cvi.stanford.edu | 19 © STANFORD CARDIOVASCULAR INSTITUTE 265 Camus Drive West, G1120 Stanford, CA 94305

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