Moment by Moment: A Decade of Discovery and Healing

Moment by Moment: A Decade of Discovery and Healing 2018 ANNUAL REPORT

Moment by moment, we get closer to solving the mysteries of heart disease. After the first decade of discovery at the Cedars-Sinai Heart Institute, we can clearly see the dramatic cumulative effect of our ability to transform moments of inspiration and insight into remarkable advances in cardiac research and care. The idea that could take us to the next level might emerge at any time a pattern on a dashboard of clinical data, a specimen in a petri dish, sequences of RNA in a cell or a patient s response to a clinical trial. We are always ready to follow the most intriguing and promising clues. This report highlights some of the many exciting developments at the Heart Institute over the past 10 years. We begin a new decade with the conviction that what we have achieved so far is a launchpad for scientific leaps in the years ahead. While changing lives today, we keep moving cardiovascular medicine forward to create a better future for everyone touched by heart disease.

We innovate from within and spread the knowledge we gain.

We advance precision medicine while using our mastery of data to redefine best practices.

10 We do all of this while training tomorrow s clinical and research leaders.

Smaller, Faster, Better: From Invasive to Percutaneous It s a haiku approach to healing. Just as poets pare down their art to three lines for powerful effect, interventional cardiologists prove that less is more with a minimally invasive approach to lifechanging procedures. The Cedars-Sinai Heart Institute is a leader in developing catheter-based techniques that make treatment for heart-valve disease smaller, faster and better for patients. We are one of the world's leading medical centers performing transcatheter aortic valve replacements (TAVRs) for aortic stenosis and MitraClip repairs to treat mitral valve regurgitation. While expanding options for patients Cedars-Sinai became the first to implant the FDA-approved MitraClip in a patient in 2013 we have increased the odds of success for those who are not strong enough to undergo open-heart surgery. Heart Institute studies show that TAVR improves survival even for people in their 90s. Through innovation that reflects the streamlined elegance of poetry, we are adding not just years to life but life to years. 2 CEDARS-SINAI HEART INSTITUTE

Total Interventional Cardiology and Electrophysiology Procedures INCREASE 110% 16,427 FY07 7,840 2018 ANNUAL REPORT 3

Options for Healing: Cutting-Edge Therapies Never say never. This way of thinking makes the Heart Institute an international leader in patient care and research. Prevailing wisdom once said it was not possible for damaged hearts to regrow healthy muscle. We proved it could be done, completing the world s firstin-human infusion of cardiac-derived progenitor cells for repair of the myocardium in 2009. Our Regenerative Medicine Clinic continues to spearhead the development of stem cell therapy s potential to minimize injury to the heart and maximize repair. Another novel approach to therapy addresses the most common cardiac birth defect in extremely premature newborns: Our researchers developed a minimally invasive technique to repair patent ductus arteriosus, eliminating the need for open-chest surgery in fragile preemies. The procedure can be performed with a high success rate in babies as small as 1.6 pounds, just a few days after birth. We always ask: Why not? Where others see impossibility, we see lifesaving potential. 4 CEDARS-SINAI HEART INSTITUTE

Cutting-Edge Procedures 1,132 ECMO MitraClip Other TAVR FY07 54 2018 ANNUAL REPORT 5

Generating Discovery: Innovation From Within When talented musicians get together to improvise, they make a new sound. Heart Institute researchers experience the interplay and creative power of improvisation, too. We encourage our team to brainstorm and follow their curiosity and passions to the far reaches of their investigative talents. The result is a highly productive culture of innovation. Over the past decade, the Heart Institute has relied less and less on existing technology and techniques and stepped up efforts to boldly rewrite the playbook for cardiac care. Heart Institute researchers are publishing more and more papers, many of which are in leading publications such as The Lancet and The New England Journal of Medicine. We ve also seen dramatic growth in patents, peer-reviewed grant funding and clinical trials. All this is a testimony to the promise of new diagnostic tools and therapies that start here and have the potential to change the way medicine is practiced everywhere. 6 CEDARS-SINAI HEART INSTITUTE

Peer-Reviewed Funding FY07 $3m $31m Publications from the Heart Institute FY07 92 467 2018 ANNUAL REPORT 7

Assessing Personal Risk: Imaging, Biomarkers, Genomics This post-one-size-fits-all era of medicine demands a new mindset. In the past 10 years, our focus has shifted from the disease itself to the individual characteristics that put each patient at risk and affect their response to treatment. The Heart Institute s Barbra Streisand Women s Heart Center uses advanced cardiac-imaging techniques to diagnose difficult-to-detect coronary microvascular disease. This has proved lifesaving for women with undiagnosed chest pain. The Heart Rhythm Center has made big strides toward determining risk factors, triggers and genetic defects related to sudden cardiac arrest by creating a large population study and mining its data. The Heart Institute is also a world leader in proteomics. Our team is analyzing thousands of proteins to identify abnormalities and biomarkers for cardiac disease. We are on the leading edge of precision medicine that can predict who is at risk for heart attack, atherosclerosis and other conditions as well as how they will respond to treatments and the best ways to deliver targeted therapies to achieve the best possible outcomes. 8 CEDARS-SINAI HEART INSTITUTE

Risk Factors for Sudden Cardiac Arrest Identified Electrical Abnormalities Structural Abnormalities Genetic Markers FY07 0 4 Blood Biomarkers 2018 ANNUAL REPORT 9

Knowledge at Work: Mastering Clinical Data It s the world s most sophisticated report card. Heart Institute cardiologists and cardiothoracic surgeons are the best of the best, and they get even better by paying close attention to feedback from our customized biome database. Every day, we monitor a dashboard of clinical data that keeps track of details such as how much time patients spend in intensive care, how long they are under anesthesia and how many pints of blood they receive during surgery. Such information helps physicians optimize resource utilization and meet new benchmarks for best practices. For example, when the data revealed that many patients were having postoperative episodes of atrial fibrillation, we implemented a new protocol to administer a dose of anti-arrhythmic medication after cardiac surgery. This reduced the length of stay in the ICU, and overall morbidity, as well as costs of care. But mastery of clinical data is not just about numbers it s about constantly raising the bar for high-value patient care. 10 CEDARS-SINAI HEART INSTITUTE

Cardiac Surgery Length of Stay -8.9% FY15 Cardiology Service Length of Stay -6.1% FY15 2018 ANNUAL REPORT 11

Laying the Groundwork: Training Tomorrow s Leaders The next generation of cardiologists is already shaping the future of medicine. At the Heart Institute, cardiology fellows from top residency programs including Johns Hopkins University, Brigham and Women s Hospital, and the University of California, San Francisco work with our renowned faculty in Cedars-Sinai laboratories and clinics, contributing to major studies in areas such as stem cell therapy, women s heart disease and biomarker development. Our fellowship programs are among the most prestigious in the nation, and patients benefit from the chemistry between our pioneering investigators and the up-and-coming physicians they train. For the better part of a decade, the Heart Institute has offered robust research opportunities for fellows, with support from a National Institutes of Health T32 training grant. While developing specialized clinical skills, cardiology fellows are an instrumental part of the Heart Institute s powerful discovery engine that is bringing new hope to patients with heart disease. Training programs in cardiac surgery, vascular surgery and advanced heart disease are equally strong parts of our portfolio. 12 CEDARS-SINAI HEART INSTITUTE

Number of Peer-Review-Funded Fellowship Slots Per Year 31 FY07 3 2018 ANNUAL REPORT 13

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All Procedures FY10 109,629 94,555 6,406 TOTAL 167,019 Noninvasive Diagnostics 137,571 Advanced Imaging 14,450 Cardiac Catheterizations 11,146 5,730 1,933 1,005 Electrophysiology Procedures 2,382 Cardiothoracic Surgeries 1,470 2018 ANNUAL REPORT 15

Cardiac Catheterizations Electrophysiology 11,146 FY12 6,537 FY07 4,630 PROCEDURE FY07 FY12 Angiography 2,636 3,266 6,388 Percutaneous Coronary Intervention 1,219 1,087 1,844 Transcatheter Aortic Valve Replacement (TAVR) 0 217 579 MitraClip 12 26 199 Transcatheter Pulmonary Valve Replacement (TPVR) 0 2 9 Transcatheter Mitral Valve Repair (TMVR) 0 0 26 PROCEDURE FY08 FY12 Ablation Procedures (SVT/Other SVT/A-FIB/A-Flutter) 365 420 707 Electrophysiology Studies 391 478 768 Pacemaker and Cardioverter Defibrillator Implantation Ablation Procedures (SVT/Other SVT/A-FIB/A-Flutter) 707 Electrophysiology Studies 768 Pacemaker and Cardioverter Defibrillator Implantation 907 903 704 907 TOTAL 1,659 1,602 2,382 Valvuloplasty Adult Aortic Valvuloplasty (AVP) 18 97 5 Peds AVP 13 1 2 Cutting-Edge Procedures Adult Mitral Valvuloplasty (MVP) 0 6 3 Adult Pulmonary Valvuloplasty (PVP) 0 1 2 1,132 Peds PVP 0 0 3 Carotid Angiography/Carotid Stent 3 26 16 Endomyocardial Biopsy 485 1,138 1,136 54 356 Intracoronary Stem Cell Injection/Therapy 2 9 17 Intravascular Ultrasound 158 504 599 Percutaneous Alcohol Septal Ablation for Hypertrophic Cardiomyopathy 7 9 11 Percutaneous Closure of Paravalvular Leak 0 3 13 Percutaneous Closure of Septal Defects Adult Atrial Septal Defect (ASD) 5 30 21 Peds ASD 17 5 11 Adult Patent Foramen Ovale (PFO) 11 12 24 Adult Ventricular Septal Defect (VSD) 2 4 6 Adult Patent Ductus Arteriosus (PDA) 0 0 2 Peds PDA 8 1 7 Percutaneous Left Ventricular Assist Devices 3 17 57 FY07 FY12 PROCEDURE FY07 FY12 TAVR 0 217 579 MitraClip 12 26 199 TPVR 0 2 9 TMVR 0 0 26 Intracoronary Stem Cell Injection/Therapy 2 9 17 Percutaneous Closure of Septal Defects Adult Atrial Septal Defect (ASD) 5 30 21 Peds ASD 17 5 11 Adult Patent Foramen Ovale (PFO) 11 12 24 Adult Ventricular Septal Defect (VSD) 2 4 6 Percutaneous Closure of Left Atrial Appendage Occlusion 1 14 121 Coronary Reactivity Testing 30 62 45 TOTAL 4,630 6,537 11,146 Percutaneous Left Ventricular Assist Devices Percutaneous Closure of Left Atrial Appendage Occlusion Extracorporeal Membrane Oxygenation (ECMO) 3 17 57 1 14 121 1 20 62 TOTAL 1 54 356 1,132 16 CEDARS-SINAI HEART INSTITUTE

Cardiothoracic Surgery Advanced Imaging FY09 1,134 FY12 1,172 1,470 Nuclear Cardiology PET Exams 1,679 Cardiac CT Exams 7,101 Magnetic Resonance (MRI, MRA, MRV) 555 Nuclear Cardiology (SPECT Exams and MRV) 5,115 PROCEDURE FY09 FY12 PROCEDURE FY10 FY12 Coronary Artery Bypass Grafting (CABG) (Isolated) 119 102 146 Nuclear Cardiology PET Exams 1,135 479 1,679 Mitral Valve (MV) Procedures, Including CABG 134 154 188 MV Replacement 50 61 61 MV Repair 84 93 127 Aortic Valve Procedures, Including CABG 246 258 243 AV Replacement 227 228 203 Cardiac CT Exams 1,398 2,992 7,101 Magnetic Resonance (MRI, MRA, MRV) Nuclear Cardiology (SPECT Exams and MRV) 375 366 555 3,498 3,337 5,115 TOTAL 6,406 7,174 14,450 AV Repair 19 30 40 CABG With Valve Replacement/Repair 75 57 71 CABG With Other Non-Valve Procedure 0 3 8 Lung Transplant 23 17 14 Ventricular Assist Device 33 49 93 ECMO 5 20 62 Congenital 161 42 32 Electrical 106 115 178 Myocardial 12 12 36 Inpatient Discharges 5,993 5,762 6,805 Pericardial 8 14 14 FY08 FY12 Other Noncardiac 33 53 24 Thoracic Aortic Surgery 152 180 239 Ascending Aorta/Dissection 106 91 131 Arch 37 27 61 Descending and Thoracoabdominal 9 62 47 Miscellaneous (Total Artificial Heart Transplants for FY) 27 96 122 TOTAL 1,134 1,172 1,470 HEART TRANSPLANT-RELATED CY09 CY12 CY17 Outpatient Visits 32,687 FY12 20,636 FY10 13,966 Heart Transplant 27 95 104 Total Artificial Heart 0 1 7 2018 ANNUAL REPORT 17

Noninvasive Diagnostics Peer-Reviewed Articles Echo Studies 23% Other Heart Rhythm Procedures 77% 467 ECHO STUDIES TOTAL IN* OP** 2-D Echocardiogram Complete With Doppler With or Without Contrast 27,026 15,503 11,523 FY12 263 Rest and Stress Echocardiogram and CV Stress Test and Dobutamine Echocardiogram With or Without Contrast 1,126 164 962 FY07 92 Transesophageal Echocardiogram With or Without Contrast; May Include 3-D Imaging 3,750 2,872 878 Intellectual Property TO DATE Intima-Media Thickness (IMT) Study 14 0 14 TOTAL 31,916 18,539 13,377 United States International OTHER HEART RHYTHM PROCEDURES ECG 98,423 43,553 54,870 200 146 Filed Copyright Registrations Cardiovascular Monitoring Services (Holter Monitor, BPM, Mobile Cardiovascular Telemetry) 3,850 978 2,872 32 43 Issued 12 Tilt Table 40 6 34 Cardioversion 426 122 304 Pacemaker/ICD Device Interrogation and Programming Enhanced External Counterpulsation Therapy (EECP) 2,360 609 1,751 556 0 556 TOTAL 105,655 45,268 60,387 *IN - Inpatient **OP - Outpatient Clinical Trials 365 43 198 Research Funding Soon to Enroll 68 114 30 124 Federal and State $12,907,576 Industry $6,535,409 Enrolling Follow-Up Phase 37 31 FY09 60 24 FY12 Other Peer-Reviewed $11,641,843 Outcomes FY07 FY12 Federal and State $1,458,644 $9,898,012 $12,907,576 Industry $1,668,719 $2,587,226 $6,535,409 Other Peer-Reviewed $584,475 $6,019,306 $11,641,843 National Cedars-Sinai Heart Attack 13.6% 9.8% 15 12 9 6 3 Heart Failure 11.9% 6.5% National Cedars-Sinai TOTAL $3,711,838 $18,504,544 $31,084,828 0 18 CEDARS-SINAI HEART INSTITUTE

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