Evolving Challenges in Promoting€¦ · welcome you to our conference evolving Challenges in Promoting Cardiovascular Health. Leading and emerging investigators working on the fields

Presented By:

Present

Evolving Challenges in Promoting

Cardiovascular Health

CosmoCaixa Barcelona, Spain

NovemBer 4 - 5, 2011

www.nyas.org/Cardiovascular

2 Promoting Cardiovascular Health

• esteve

• Ferrer

• Fundación ramón Areces

Bronze Sponsors

• Bayer HealthCare

• Laboratorios Servier españa

• Philips Healthcare

• Siemens, S.A.

Academy Friends

ACkNowLedgemeNt oF SuPPort

SCIeNtIFIC orgANIZer

dr. valentin Fuster, Director of both the Zena and Michael A. Wiener Cardiovascular Institute and the Marie-Josée and Henry R. Kravis Center, for Car-diovascular Health at Mount Sinai Medical Center as well as Director of Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) in Madrid, Spain.

grant SupportSupported by an independent education grant from Astellas Pharma global development

Presented by

weLCome

ellis rubinsteinPresident and Chief Executive Officer, The New York Academy of Sciences

monsterrat vendrell, PhDChief Executive Officer, BIOCAT

enric Banda, PhDDirector of Science, Research and Environment, "la Caixa" Foundation

3Promoting Cardiovascular Health

valentin Fuster, MD, PhDMount Sinai Medical Center and Centro Nacional de Investigaciones Cardiovasculares (CNIC)

The scientific organizer and presenting organizations, The New York Academy of Sciences, "la Caixa" Foundation, and the International Center for Scientific Debate (ICSD), are pleased to

welcome you to our conference evolving Challenges in Promoting Cardiovascular Health.

Leading and emerging investigators working on the fields of cardiology, vascular disease, inflammation, metabolic disorders, hematology, imaging, regenerative medicine, stem cell research, epidemiology, and nutrition, among others, have come together at this forum to address novel issues, current challenges, and future directions in the prevention, treatment, and management of the evolving global epidemic of cardiovascular disease. Our goal is to provide you with the most conducive environment for a lively, informed, and synergistic conversation to explore the promotion of cardiovascular health through molecular biology, clinical pathophysiology and population research.

Please see our conference agenda to learn more about the speakers fea-tured in the plenary sessions. Day 1 of this conference will address basic research topics, including a hot-topic Data-Blitz session with presentations selected from abstract submissions; Day 2 will focus on clinical issues. We hope that you will also take full advantage of the special features of this conference by joining us for the poster session, evening reception, and lunch workshop on Scientific Writing for Publication (Day 1).

We are proud to announce that highlights of this conference will be pub-lished as a volume of the Annals of the New York Academy of Sciences and as an open-access multimedia eBriefing report, which will include a selec-tion of slides and audio from the conference speakers. These materials will be available on the New York Academy of Sciences Web site (www.nyas.org) after the conference.

We hope this conference meets your expectations. Please do not hesitate to notify us and our staff of any questions or concerns.

INFormAtIoN For PArtICIPANtS

trANSPortAtIoN Shuttle bus schedule for participants with hotel reservations in downtown Barcelona.

Please arrive 10 minutes prior to departure time.

Hotel Jazz (Pelai, 3) to CosmoCaixa (Isaac Newton, 26) Nov 4: 7:30 Am; Nov 5: 7:15 Am.

CosmoCaixa (Isaac Newton, 26) to Hotel Jazz (Pelai, 3) Nov 4: 8:00 Pm; Nov 5: 6:45 Pm.

we Need Your FeedBACk!

In addition to the meeting agenda and abstracts, this registration packet includes a meeting evaluation questionnaire. Please re-turn your yellow evaluation form to the registration staff be-fore you leave or mail it to the address listed at the bottom of the form.

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Your memBerSHIP to tHe New York ACAdemY oF SCIeNCeS

Included in your registration fee for this conference is a 1-year complimentary membership to the New York Academy of Sciences, enabling you to access our vast library of print and web-based resources and to attend future Academy events for free or at reduced registration rates. We encourage you to become active in our community and to build networks and exchange ideas with leaders like yourself. Our hope is that your experience will convince you to be a member for life. For more information about the Academy’s diverse live and online pro-gramming and your membership, please visit www.nyas.org or email [email protected].

Promoting Cardiovascular Health

All faculty participating in this activity are required to disclose to the audi-ence any significant financial interest and/or other relationship with the manufacturer(s) of any commercial product(s) and/or provider(s) of com-mercial services discussed in his/her presentation and/or the commercial contributor(s) of this activity.

david H. Adams, MD Inventor with Royalties • Edwards Lifesciences, Medtronic

Lina Badimon, PhD None

Josep Brugada terradellas, MD, PhD None

valentin Fuster, MD, PhD None

michael A. gimbrone Jr., MD None

Brooke grindlinger, PhD None

roger J. Hajjar, MD Share Holder/Scientific Founder • CELLADON, Inc.

Jonathan L. Halperin, MD Consultant • Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Johnson & Johnson, Pfizer, Sanofi-Aventis

Steen e. Husted, MD, DSc* Research Support • AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer Consultant • AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly

Borja Ibañez, MD, PhD, FESC None

Carlos macaya, MD, PhD None

Frederick A. masoudi, MD, MPSH Research Support • Agency for Healthcare Research and Quality (AHRQ), American College of Cardiology Foundation, National Heart, Lung, and Blood Institute (NHLBI) Other Financial Support • American College of Cardiology Foundation, Oklahoma Foundation for Medical Quality

FACuLtY dISCLoSureS


Simón méndez-Ferrer, PhD None

Pedro r. moreno, MD, FACC None

marta murcia, PhD None

Jagat Narula, MD, PhD None

robert A. Phillips, MD, PhD None

vivek reddy, MD* Research Support • Atritech, Biosense Webster, CardioFocus, Endosense, Medtronic CryoCath, Philips, SentreHEART, St. Jude Medical, Voyage Consultant • Bioscience Webster, Endosense, St. Jude Medical

Josep rodés-Cabau, MD Consultant • Edwards Lifesciences, St. Jude Medical

James H. F. rudd, MD, PhD None

Javier Sanz, MD* None

Laurence Sperling, MD None

Andre terzic, MD, PhD N/A

miguel torres, PhD None

Clyde w. Yancy, MD None

FACuLtY dISCLoSureS


N/A – not available at time of printing.

An * after the speaker’s name indicates that the speaker intends to discuss unlabeled uses of commercial product, or an investigational use of a product not yet approved for this purpose. The speaker will disclose this information during his/her presentation.


dAY 1: FrIdAY, NovemBer 4, 2011

7:45 Am registration, Breakfast, and Poster Set-up

8:30 Am welcoming remarks

enric Banda, PhD, "la Caixa" Foundation miquel marti, PhD, ICSD-Biocat, BioRegió de Catalunya Brooke grindlinger, PhD, The New York Academy of Sciences valentin Fuster, MD, PhD, Mount Sinai Medical Center and Centro Nacional de Investigaciones Cardiovasculares

SCIeNtIFIC INtroduCtIoN

9:00 AM Cardiovascular Defense Challenges at the Basic, Clinical and Population Levels valentin Fuster, MD, PhD, Mount Sinai Medical Center and Centro Nacional de Investigaciones Cardiovasculares

SeSSIoN I: ArterIAL CHALLeNgeS At tHe BASIC LeveL Session Chair: michael A. gimbrone Jr., MD, Brigham & Women's Hospital, Harvard Medical School

9:30 AM Vascular Endothelium in Health and Disease: New Insights into Its Pathobiology michael A. gimbrone Jr., MD, Brigham & Women’s Hospital, Harvard Medical School

9:55 AM The Adventitia and the Media Vasa Vasorum, Defense vs. Betrayal or a War in Progress Pedro r. moreno, MD, FACC, Mount Sinai Medical Center

10:20 AM The Intimal LDL-C vs. HDL-C, Inflammatory Resolution vs. Thrombotic Chaos Lina Badimon, PhD, Barcelona Cardiovascular Research Center (ICCC-CSIC)

10:45 Am Networking Coffee Break and Poster viewing

11:15 Am Panel discussion drs. Fuster, gimbrone, moreno, and Badimon

12:00 Pm Lunch and Poster viewing

CoNCurreNt SCIeNCe ALLIANCe workSHoP

12:45 PM Writing for Scientific Publication Brooke grindlinger, PhD, The New York Academy of Sciences

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SeSSIoN II: mYoCArdIAL CHALLeNgeS At tHe BASIC LeveLSession Chair: Jagat Narula, MD, PhD, Mount Sinai School of Medicine

1:30 PM Evolving Role of Imaging for New Understanding Jagat Narula, MD, PhD, Mount Sinai School of Medicine

1:55 PM Detection of the High-risk Atherosclerotic Plaque -The Role of PET/CT Imaging James H. F. rudd, MD, PhD, MRCP, University of Cambridge

2:20 PM Tissue Regeneration: Bone Marrow Cell-Cell Interaction & Release Simón méndez-Ferrer, PhD, Centro Nacional de Investigaciones Cardiovasculares

2:45 PM Gene Therapy for the Treatment of Heart Failure roger J. Hajjar, MD, Mount Sinai School of Medicine

3:10 Pm Panel discussion drs. Narula, rudd, méndez-Ferrer, and Hajjar

3:40 Pm Networking Coffee Break and Poster viewing

dAtA-BLItZ SeSSIoNPresentations selected from abstract submissions

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4:10 PM β3 Adrenergic Receptor Stimulation Protects the Heart From Ischemia/Reperfusion Injury david Sanz-rosa, PhD, Centro Nacional de Investigaciones Cardiovasculares

4:25 PM Engineering Physiological Models of Arterial Bifurcation to Expedite Treatments mercedes Balcells-Camps, PhD, Massachusetts Institute of Technology

4:40 PM In Vivo Non-Invasive Bioluminence Imaging Monitoring of cTNI Gene Expression in Cardiac Adipose Tissue-Derived Progenitor Cells (ATDPCS) Implanted in a Mouse Model of Myocardial Infarction Carolina Soler-Botija, PhD, Hospital Universitari Germans Trias i Pujol (IGTP)

4:55 PM Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Demonstrate Promising Angiogenic and Vasculogenic Potential for Heart Function Recovery Santiago roura, PhD, Institut d´Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP)


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dAY 2: Saturday, November 5, 2011 7:30 Am registration, Breakfast, and Poster viewing

SeSSIoN Iv: ArterIAL CHALLeNgeS At tHe CLINICAL LeveL Session Chair: Jonathan L. Halperin, MD, Mount Sinai Medical Center

8:00 AM The Future: Therapy of Myocardial Protection Borja Ibañez, MD, PhD, Centro Nacional de Investigaciones Cardiovasculares

8:20 AM STEMI: Clock Time Therapy Challenges the Ambulance, the Metropolitan and the Community Settings Carlos macaya, MD, PhD, Hospital Clínico San Carlos

8:40 AM Antithrombotic Progress — Evolving Oral Agents Steen e. Husted, MD, DSc, Aarhus University Hospital

9:05 AM The Link Between Complex Coronary Disease and/or Significant Carotid Disease, Diabetes and Cerebrovascular Disease valentin Fuster, MD, PhD, Mount Sinai Medical Center and Centro Nacional de Investigaciones Cardiovasculares

9:30 AM Refractory Angina/Ischemia/Carotid Disease in the Elderly Jonathan L. Halperin, MD, Mount Sinai Medical Center

9:55 Am Panel discussion drs. Ibañez, macaya, Husted, Fuster and Halperin

10:20 Am Networking Coffee Break and Poster viewing

SeSSIoN III: deveLoPmeNt & regeNerAtIve CHALLeNgeS At tHe BASIC LeveL Session Chair: roger J. Hajjar, MD, Mount Sinai School of Medicine

5:10 PM Cell Competition during Heart Development miguel torres, PhD, Centro Nacional de Investigaciones Cardiovasculares

5:35 PM Regenerating a New Heart Andre terzic, MD, PhD, Mayo Clinic

6:00 Pm Panel discussion drs. torres and terzic

6:30 Pm Conference reception and Poster Session

8:00 Pm end of dAY 1

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11:30 Am Panel discussion drs. Sperling and Phillips

12:00 Pm Lunch and Poster viewing

SeSSIoN vI: mYoCArdIAL CHALLeNgeS At tHe CLINICAL LeveL Session Chair: Clyde w. Yancy, MD, Northwestern University, Feinberg School of Medicine

1:00 PM Evolving Diagnostic and Prognostic Imaging (MR, CT) of the Various Cardiomyopathies Javier Sanz, MD, Mount Sinai School of Medicine

1:25 PM State-of-the-art Management of Systolic and Diastolic Heart Failure Clyde w. Yancy, MD, MSc, FACC, FAHA, MACP, Northwestern University, Feinberg School of Medicine

1:50 PM The Evolving Landscape of Quality Measurement for Heart Failure Frederick A. masoudi, MD, MPSH, University of Colorado, Denver

2:15 Pm Panel discussion drs. Sanz, Yancy and masoudi

SeSSIoN vII: eLeCtrICAL CHALLeNgeS At tHe CLINICAL LeveL Session Chair: Josep Brugada terradellas, MD, PhD, FESC, Hospital Clinic, University of Barcelona

2:45 PM Atrial Fibrillation, Stroke and the Quality of Life valentin Fuster, MD, PhD, Mount Sinai Medical Center and Centro Nacional de Investigaciones Cardiovasculares

3:10 PM Ventricular Tachycardia and Ventricular Dysfunction, Which to Watch? Josep Brugada terradellas, MD, PhD, FESC, Hospital Clinic, University of Barcelona


SeSSIoN v: treNdS ANd CHALLeNgeS oF PreveNtIoN Session Chair: Carlos macaya, MD, PhD, Hospital Clínico San Carlos

10:40 AM Optimal Lipid Targets (OLT) for the New Era of Cardiovascular Prevention Laurence Sperling, MD, Emory University School of Medicine

11:05 AM Hypertension and Guidelines: Who to Believe? robert A. Phillips, MD, PhD, University of Massachusetts Medical School


SeSSIoN vIII: vALvuLAr dISeASe & AortIC CHALLeNgeS At tHe CLINICAL LeveL Session Chair: david H. Adams, MD, Mount Sinai Medical Center

5:00 PM Future of Transcatheter AVR: The Best Procedure of Choice for an 80-year-Old? Even Younger? How We Protect the Brain from Embolization? Josep rodés-Cabau, MD, Quebec Heart and Lung Institute

5:25 PM It May Be Too Early or Too Late for Surgery in Severe Mitral Regurgitation david H. Adams, MD, Mount Sinai Medical Center

5:50 PM The Dilated Aorta and Its Consequences valentin Fuster, MD, PhD, Mount Sinai Medical Center and Centro Nacional de Investigaciones Cardiovasculares

6:15 Pm Panel discussion drs. rodés-Cabau, Adams, and Fuster

6:45 Pm Adjourn

The New York Academy of Sciences requests that you do not take photographs or make audio or video recordings of the conference presentations, or present unpublished data on any open-access websites, unless specific permission is ob-tained from the speaker.

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3:35 PM Atrial Fibrillation, Catheter Ablation, Increase in Safety and Benefit vivek reddy, MD, Mount Sinai School of Medicine

4:00 Pm Panel discussion drs. Fuster, Brugada and reddy

4:30 Pm Networking Coffee Break and Poster Breakdown

SCIeNtIFIC INtroduCtIoN

Cardiovascular Defense Challenges at the Basic, Clinical and Population Levels

valentin Fuster, MD, PhD, Mount Sinai Medical Center, New York, NY, and Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain

At a basic level, to understand and promote vascular health, we must reduce the aggression to the vessel wall and enhance the physiologic mechanisms leading to restoration of vessel wall function. Three main defense mechanisms are respon-sible for maintaining cardiovascular homeostasis: the regenerative production of endothelial progenitor cells, vessel wall angiogenesis, and macrophage-mediated reverse cholesterol transport. At a clinical level, cardiovascular disease (CVD) has become the most common cause of mortality worldwide. Obesity, insufficient physical exercise, diabetes, and advancing age are major risk factors for develop-ing cardiovascular disease that are currently increasing in prevalence. Neverthe-less, significant progress has recently been made in the treatment of complex cardiovascular and coronary artery disease (CAD), with pharmacological man-agement set to assume an increasingly important role. At a global level, other timely factors, such as the development of the polypill and high-level medical and political interest in advancing cardiovascular health, are driving forces that may help to make inroads into the global cardiovascular disease burden. In this talk, I will critically review the key challenges that we face in the coming decade as we strive to transition and apply our growing knowledge of complex CAD to promot-ing global cardiovascular health.

Speaker abstracts are listed in order of presentation. A gap in the sequence of abstracts indicates that an abstract was not received at the time of printing.

dAY 1: Friday, November 4, 2011

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SeSSIoN I: ArterIAL CHALLeNgeS At tHe BASIC LeveL

Vascular Endothelium in Health and Disease: New Insights into Its Pathobiology

michael A. gimbrone, Jr, MD, Center for Excellence in Vascular Biology, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA

The vascular endothelial lining of the cardiovascular system comprises a vital, multifunctional interface in health, and its dysfunction can contribute to chronic inflammation, hypertension, thrombosis, and atherosclerosis. Endothelial dysfunc-tion can be elicited by humoral stimuli, such as proinflammatory cytokines, bac-terial endotoxins, advanced glycation endproducts, or components of oxidized lipoproteins. Recent work suggests that biomechanical forces generated by the pulsatile flow of blood (wall shear stresses, cyclic strains, hydrostatic pressures) can also directly influence endothelial phenotype at the level of gene regulation. We have applied hi-throughput molecular genetic strategies, such as genome-wide expression profiling via cDNA microarrays and bioinformatic analyses, to



The Adventitia and the Media Vasa Vasorum, Defense vs. Betrayal or a War in Progress

Pedro r. moreno, MD, FACC, Mount Sinai Medical Center, New York, NY

Vasa vasorum–derived microvessels nurture the atherosclerotic plaque, with an organized system regulated by sympathetic and hormonal stimuli. They also provide a permanent communication between the systemic circulation and the atheroma, increasing leukocyte, albumin, and RBC extravasation, leading to ROS generation and tissue damage mediated by the potent oxidative effects of free Hb. Recent studies strengthen the concept that the intraplaque hemorrhage are events that could play a major role in plaque progression and leucocyte infiltration, and may also serve as a measure of risk for the development of future events. The recent advances in our understanding of intra-plaque Hemorrhage as a critical event in triggering acute clinical events, and may have important implications for clinical research and possibly future clinical practice. Furthermore, microvessels may play a role in plaque regression, as suggested by a dramatic reduction of intima-medial blood flow after regression in atherosclerotic monkeys. These results are in agreement with human data showing reduced microvessels in fibrocalcific plaques compared with lipid-rich and ruptured plaques. Recent experimental data suggest that statins preserve the adventitial vasa vasorum architecture and prevent neovascularization development in hypercholesterolaemic pigs, independently of cholesterol lowering. Statins could also influence the consequences of micro-bleeding due to their ability to limit the cholesterol content of RBC membranes. Furthermore, Plaque neovessels may be suitable for in vivo evaluation with the use of molecular imaging. Finally, there is a potential role for treatment of plaque neovascularization with angiogenesis inhibitors. Impressive reductions of athero-sclerosis in apolipoprotein E knockout mice were obtained using endostatin and TNP-470, respectively. Nevertheless, plaque angiogenesis allows for macrophage trafficking with potential for reverse cholesterol transfer, and plaque regression. Inhibiting this defense mechanism may be responsible for the recent, unexpected reports showing that antiangiogenic therapy for cancer or age-related macular degeneration could increase the risk of cardiovascular disease.

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compare the patterns of endothelial gene expression induced by humoral stimuli, such as proinflammatory cytokines, and biomechanical stimuli, such as laminar and disturbed blood flow. This approach has defined distinct and reproducible patterns of gene regulation that are associated with pathophysiologically relevant endothelial activation states, and has identified novel genes encoding cell surface receptors, ion transporters, signaling molecules and transcription factors that have relatively selective endothelial expression. Bioinformatic “pathway” analy-ses have also revealed key transcription factors that serve as nodal regulators in molecular genetic networks that help maintain homeostatic balance across a spectrum of pathophysiologic states. This approach should provide fresh insights into the mechanisms of cardiovascular disease, and, hopefully, reveal novel mo-lecular targets for therapeutic interventions, as well as biomarkers useful in as-sessing disease risk and prevention.

The Intimal LDL-C & HDL-C: Inflammatory Resolution vs. Thrombotic Chaos

Lina Badimon, PhD, Barcelona Cardiovascular Research Center (ICCC-CSIC), IIB-Sant Pau, CIBERobn, UAB, Barcelona, Spain

Low Density Lipoprotein (LDL) cholesterol levels in plasma are associated with the presentation of clinical cardiovascular events. Reduction of plasma LDL, by behavioural and pharmacological interventions, has shown to be highly effec-tive in the prevention of cardiovascular disease. Despite the successful treatment of LDL, residual cardiovascular risk still exists as shown by the presentation of events in the LDL-treated patients. Because of the long-standing epidemiological understanding on the beneficial effects of High Density Lipoprotein (HDL) cho-lesterol, the rationale of trying to increase HDL plasma levels by behavioural and pharmacological means, is the target of the latest investigations. Experimental studies have shown that LDL and HDL have opposed effects in the vessel wall; thus, the pro-atherogenic effects of LDL are counteracted by the anti-atherogenic effects of HDL when both types of micelles are in the appropriate equilibrium in plasma and the vessel wall.

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SeSSIoN II: mYoCArdIAL CHALLeNgeS At tHe BASIC LeveL

Evolving Role of Imaging for New Understanding

Jagat Narula, MD, PhD, Mount Sinai School of Medicine, New York, NY

More often than not, acute coronary events occur as the first manifestation of disease. Therefore, the importance of identification of culprit lesions cannot be


SCIeNCe ALLIANCe workSHoP

Writing for Scientific Publication

Brooke grindlinger, PhD, The New York Academy of Sciences, New York, NY

Publishing is critical to the scientific and medical profession, yet training and guid-ance on the topic is very limited. Brooke Grindlinger, PhD, Director of Scientific Programs at the New York Academy of Sciences and former Science Editor at the Journal of Clinical Investigation, will cover what makes a good paper, discuss strategies for selecting the appropiate journal, and provide an overview of the review process and how to navigate resubmissions.

About Science Alliance: Complementing the Academy's innovative and dynamic scientific programs, the Science Alliance provides programs and services focused on career education, development and training. Through live events, webinars, and a dedicated website, Science Alliance provides unparalleled opportunities to learn and network with individuals across in-stitutions and disciplines. It serves over 7,000 young scientists and the larger Academy membership. A consortium of universities, teaching hospi-tals, independent research facilities, and organizations support the Alliance. Visit Science Alliance at: http://www.nyas.org/sciencealliance


Tissue Regeneration: Bone Marrow Cell-Cell Interaction & Release

Simón méndez-Ferrer, PhD, Ana M. Martín, BTec, and Joan Isern, PhD,Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain

Recently, emerging evidence points towards a key role for mesenchymal stem cells in the regulation of the traffic of hematopoietic stem cells and monocytes.

Hematopoietic stem cell traffic is key for bone marrow transplantation, since he-matopoietic stem cell homing and engraftment in the bone marrow is critical for the success of transplantations, whereas their mobilization allows for non-invasive harvest of peripheral blood hematopoietic stem cells for life-saving transplanta-tion procedures. Mobilization regimes only exacerbate the poorly characterized steady-state hematopoietic stem cell exit from the bone marrow, which follows circadian oscillations, peaking during the resting phase.

Detection of the High-risk Atherosclerotic Plaque - The Role of PET/CT Imaging

James H. F. rudd, MD, PhD, MRCP, University of Cambridge, Cambridge, UK

Atherosclerosis remains the leading cause of death in the Western world. De-spite significant advances in identification of risk factors and therapies over the last three decades, the identification of patients at risk of future cardiovascular events remains a challenge. I will discuss the role of non-invasive atherosclerosis imaging, for this indication, in relation to the pathology of atherosclerosis. I will highlight the role that it is likely to play over the next 10 years for detecting those at high risk, as well as for evaluating the efficacy of novel cardiovascular drugs and devices.

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overemphasized. Histological examination of plaques retrieved from victims of acute coronary events demonstrates thinned fibrous caps associated with the plaques that are more than 75% obstructive to the luminal diameter. Intravascular optical coherence tomography has been successfully employed for the assess-ment of fibrous cap thickness, which measures less than 55 microns in patients presenting clinically with an acute event. However, since invasive assessment is not always possible, after exclusion of the cap thickness from computation selects the extent of inflammation and the necrotic core area as the best discrimi-nators that are discernable by noninvasive imaging.

Necrotic cores have been identified as low attenuation plaque areas on coronary computed tomography angiography imaging in positively remodeled vascular segments. Such plaques in asymptomatic subjects are associated with a 22.5% adverse event rate over a 2-year follow-up, compared to <0.5% in the lesions that lack these characteristics. Although inflammation has been indirectly estimated by an increase in systemic biomarkers, such as high-sensitivity C-reactive pro-teins, localization of metabolically active macrophage infiltration in plaques has become undertaken by FDG-based positron emission tomography imaging.

Gene Therapy for the Treatment of Heart Failureroger J. Hajjar, MD, Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY

Congestive heart failure remains a progressive disease with a desperate need for innovative therapies to reverse the course of ventricular dysfunction. Recent advances in understanding the molecular basis of myocardial dysfunction, to-gether with the evolution of increasingly efficient gene transfer technology, have placed heart failure within reach of gene-based therapies. One of the key abnor-malities in both human and experimental heart failure is a defect in sarcoplasmic reticulum (SR) function, which is responsible for abnormal intracellular Ca2+ han-dling. Deficient SR Ca2+ uptake during relaxation has been identified in failing hearts from both humans and animal models and has been associated with a de-crease in the activity of the SR Ca2+-ATPase (SERCA2a). Over the last ten years, we have undertaken a program of targeting important calcium cycling proteins in experimental models of heart by somatic gene transfer. This has led to the completion of a first-in-man phase 1 clinical trial of gene therapy for heart failure using adeno-associated vector (AAV) type 1 carrying SERCA2a. In this Phase I trial, there was evidence of clinically meaningful improvements in functional status and/or cardiac function which were observed in the majority of patients at various time points. The safety profile of AAV gene therapy along with the positive bio-logical signals obtained from this phase 1 trial has led to the initiation and recent completion of a phase 2 trial of AAV1.SERCA2a in NYHA class III/IV patients. In the phase 2 trial, gene transfer of SERCA2a was found to be safe and associated with benefit in clinical outcomes, symptoms, functional status, NT-proBNP and cardiac structure.

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Bone marrow-resident monocytes traffic into the bloodstream upon localized in-flammation in the periphery. Until very recently it has remained unclear how focal inflammation is able to trigger monocyte emigration from remote bone marrow compartments.

Mesenchymal stem cells have been recently shown to directly sense and inte-grate signals that either keep or attract hematopoietic stem cells and monocytes in the bone marrow, or direct their physiological egress and also their enforced mobilization to the bloodstream. Monocytes, in turn, modulate the capacity of mesenchymal stem cells to keep hematopoietic stem cells in the bone marrow compartment and might also regulate other mesenchymal stem cell functions.

These interactions among bone marrow cells have broad implications in tissue regeneration because they impact the number of circulating hematopoietic stem cells and monocytes during the resting phase (when organs undergo physiologi-cal repair) and during inflammatory and stress situations. Elucidation of these interactions could lead to new pharmacological approaches to stimulate tissue regeneration.


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Adrenergic Receptor Stimulation Protects the Heart from Ischemia/Reperfusion Injurydavid Sanz-rosa, PhD1, Jaime García-Prieto, BSc1, Alberto Osuna, BSc1, Valentín Fuster, MD, PhD1,3, and Borja Ibañez, MD, PhD1,2; 1Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. 2Hospital Clínico San Carlos, Madrid, Spain. 3Mount Sinai School of Medicine, New York, NY

β3 adrenergic receptors (β3AR) have been recently identified in the heart. Cat-echolamine signaling via β3AR results in nitric oxide (NO) production and negative inotropic effect. β3AR stimulation has been newly shown to have beneficial ef-fects in models of heart failure; however, the role of β3AR stimulation on ischemia/reperfusion (I/R) has not been explored to date, being the objective of our work.

methods and results: Cardiomyocytes (HL1 cell line) were in vitro exposed to 6/18h of hypoxia/reoxygenation, observing a significant decrease in cell viability (propidium iodine staining in flow cytometry), explained in part by a significant increase of apoptotic cell death (flow cytometry, western blot and fluorescence microscopy for cleaved-Caspase 3). Pre-treatment of cardiomyocytes with the β3AR agonist (BRL-37344; 25-100µM) resulted in a dramatic ≈25% increase in cell viability and a consistent ≈20% reduction of apoptotic cell death.

The cardioprotection afforded by β3AR stimulation is explained, to a big extent, by NO production, since the co-treatment of cardiomyocytes with the β3AR ago-nist plus the NO inhibitor L-NAME (1mM), partially reverted the cardioprotective effects of β3AR agonist alone. Subsequently C57/bl6 mice were subjected to I/R by 45 min coronary ligation followed by 24h of reperfusion. Ten min before reper-fusion a β3AR agonist (BRL-37344, 5µ/kg) or matching placebo was administered intravenously. Preliminary analyses showed that infarct size (normalized to area at risk) was significantly smaller in animals receiving the β3AR agonist before reperfusion.

Conclusion: β3AR stimulation results in a significant cardioprotection during I/R, representing a novel promising target to be tested in relevant larger animals models.

Engineering Physiological Models of Arterial Bifurcation to Expedite TreatmentsJordi Martorell1,2, José Javier Molins2, Andrés. A. García-Granada2, José An-tonio Bea3, Elazer R. Edelman, MD, PhD1,4, and mercedes Balcells, PhD1,2*; 1Massachusetts Institute of Technology, Cambridge, MA. 2Institut Químic de Sarria, Barcelona, Spain. 3Universidad de Zaragoza, Zaragoza, Spain. 4Brigham and Women’s Hospital, Boston, MA

Shear stress gradients along the vessel wall have been linked to endothelial dysfunc-tion, leading to loss of vasoreactivity, high levels of platelet aggregation, and induction of tissue factor expression. In vitro and computational models that mimic arterial con-ditions are cheaper, more reproducible and easier to handle than animal models. They constitute an alternative platform to design cost-effective and high throughput assays in the early stages of development of new therapies to combat arterial disease.


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We have developed an automated platform to manufacture biocompatible poly-meric arterial bifurcations that allow for layer-by-layer cell assembly and closely recapitulate the arterial trilaminate architecture. Scaffolds were first coated with human adventitial fibroblasts and then with human smooth muscle cells followed by a monolayer of human coronary artery endothelial cells that layered the lumen. Computational simulations were performed in parallel as a predictive tool to map zones of flow stagnation and high shear stress regions along the coronary and carotid geometries under study. We applied the simulated shear stress maps to guide in vitro experiments performed using the above described trilaminate cell-seeded scaffolds after exposure to defined flow regimes in a perfusion bio-reactor developed in our laboratory. Our results confirmed that in areas of flow separation, where cells were exposed to stagnant and oscillatory flow regimes, endothelial cells doubled their Ox-LDL absorption, expression of ICAM-1 and VCAM-1, and monocyte attachment levels in comparison to endothelial cells in areas of steady high shear stress. In addition, injured models where vascular smooth muscle cells were directly exposed to oscillatory flow showed a 2.5-fold increase of tissue factor expression compared to those exposed to steady flow. This platform may serve to answer fundamental cell physiology questions that link flow with health and disease, but also with stent performance, re-endothelial-ization and late stent thrombosis. Only integrated approaches, computational, in vitro and in vivo will enable us to bridge the gap between scientific findings and clinical applications.

In Vivo Non-Invasive Bioluminescence Imaging Monitoring Of Ctni Gene Expression In Cardiac Adipose Tissue-Derived Progenitor Cells (Atdpcs) Implanted In a Mouse Model of Myocardial Infarction Carolina Soler-Botija, PhD1, Juli R Bagó2, Aida Llucià-Valldeperas1, Jerónimo Blanco2, Santiago Roura, PhD1, Núria Rubio2, Carolina Gálvez-Montón, DVM1, Cristina Prat-Vidal, PhD1, and Antoni Bayés-Genís, MD, PhD, FESC1; 1Heart Failure and Cardiac Regeneration (ICREC) Research Program, Health Sciences Institute Germans Trias i Pujol (IGTP), Cardiology Service, Hospital Universi-tari Germans Trias i Pujol, Badalona, Spain. 2Cardiovascular Research Center (CSICICCC), CIBER BN, Barcelona, Spain

Purpose. The population of progenitor cells isolated from human cardiac adipose tissue (cardiac ATDPCs) proved to be a valid cell source for cardiac regeneration in rodent models of myocardial infarction. These cells, however, do not express cardiac troponin I (cTnI) in basal conditions in culture, although de novo expres-sion was achieved in co-culture with neonatal cardiomyocytes. Whether cTnI ex-pression is upregulated in vivo after cell delivery in cardiac regeneration protocols is unclear. The purpose of this study was to monitor in vivo cTnI gene expres-sion of cardiac ATDPCs delivered through a fibrin patch in the murine model of myocardial infarction by means of non-invasive Bioluminiscence Imaging (BLI). methods. ATDPCs of cardiac and subcutaneous origin were transduced with two lentiviral vectors for bioluminescence and fluorescence monitoring: CMV-Rluc-RFP-ttk (constitutive expression) and cTnIpr-Pluc-eGFP (human-specific cTnI ex-pression). Next, cells were loaded in a 3-D fibrin patch (bioimplant) and transplantedcovering injured myocardium in a mouse model of myocardial infarction. Sham-


operated animals (cells implantation and no infarction) were also performed. In vivo bioluminescent images were obtained and light was quantified at 0, 1, 2 and 3 weeks post-implantation. results. BLI quantification results indicated that de novo expression of cTnI was already induced one week post-implantation in both cardiac and subcutaneous ATDPCs. However, bioluminescence images revealed a 38-fold increase of cTnI expression in cardiac ATDPCs, while only a 4.8-fold increase was found in subcutaneous ATDPCs (p=0.018). Although the cTnI levels in cardiac ATDPCs tended to decrease over time, in all time points analyzed they were superior to those of subcutaneous origin. Conclusions. Our work indicates that de novo expression of cTnI in cardiac ATDPC implanted into a mouse in-farcted myocardium already occurred one week post-implantation. Comparative analysis showed that cardiac ATDPCs had a greater capability to express cardiac marker such as cTnI than subcutaneous ATDPCs.

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Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Demonstrate Promising Angiogenic and Vasculogenic Potential for Heart Function RecoverySantiago roura, PhD1, Juli Rodríguez Bagó2, Carolina Gálvez-Montón, DVM1, Cristina Prat-Vidal, PhD1, Carolina Soler-Botija, PhD1, Aida Llucià-Valldeperas1, Jerónimo Blanco2, and Antoni Bayes-Genis, MD, PhD, FESC,1,3,4; 1Heart Failure and Cardiac Regeneration (ICREC) Research Program, Health Sciences Institute Germans Trias i Pujol (IGTP), Badalona, Spain. 2Cardiovascular Research Center, CSIC-ICCC, CIBERBBN, Barcelona, Spain. 3Cardiology Service, Hospital Univer-sitari Germans Trias i Pujol, Badalona, Spain. 4Department of Medicine, Universi-tat Autònoma de Barcelona, Barcelona, Spain

Stem cell therapies open up a hopeful possibility to restore function following heart fail-ure. Since stem cell-mediated revascularization might improve myocardial blood sup-ply with functional enhancement of remaining cardiac muscle in near future therapeutic interventions, we here examined whether umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) demonstrated angiogenic and/or vasculogenic potential. Cells were differentiated in endothelial cell (EC)-specific growth medium (EGM-2). Gene and protein expression were assessed by RT-PCR, immunofluorescence and Western blot. Migration and formation of capillary-like structures were analyzed in cell invasion assays and in Matrigel, respectively. Chemotaxis of peripheral endothelial progenitor cells (EPCs) was tested in Transwells. Experiments using an in vivo an-giogenesis murine model based on the co-implantation of Matrigel and UCBMSCs transfected with a CD31-promoter reporter construct were also carried out. CD31-promoter activation was monitored over time using non-invasive bioluminescence, and Matrigel plugs were finally removed to analyze microvessel growth following fluo-rescent angiography. Expression of EC, angiogenic and vasculogenic markers as well as migratory capacity (p=0.004) were promoted in EGM-2. Differentiated cells devel-oped capillary-like networks in Matrigel. Moreover, UCBMSC-derived ECs positively attracted EPCs (p=0.02) in a SDF-1a-dependent manner (p=0.016). In vivo, both activation of a CD31 promoter-luciferase reporter (p<0.001) and growth of mature microvessels were detected within Matrigel plugs containing UCBMSCs.Our results demonstrate that UCBMSCs differentiate into EC both in vitro and in vivo. These cells could also activate vasculogenesis through EPC recruitment.


Cell Competition during Heart DevelopmentCristina Villa, Cristina Clavería, Giovanna Giovinazzo, Rocío Sierra, and miguel torres, PhD, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain

Cell competition is a tissue homeostasis mechanism described in Drosophila that promotes the expansion of the fittest cells through the apoptotic elimination of suboptimal, but otherwise viable, cells. Recent evidence suggests that cell com-petition is a general strategy used in metazoan development, tissue homeostasis and regeneration. Myc is an important promoter of cell competition ability through its action on the cell anabolic machinery. Using a new inducible genetic mosaic approach, we have manipulated Myc levels and apoptosis patterns in the mouse embryo. Our results indicate that epiblast cells actively compete for survival and that the level of Myc expression is an essential determinant of endogenous and induced cell competition. To explore whether cell competition remains an active process during cardiogenesis, we induced Myc overexpression mosaics in differ-entiating cardiomyocytes during embryogenesis. Our results indicate that mosaic hearts are enriched at birth in Myc-overexpressing versus WT cardiomyocytes. Apoptosis inhibition in WT cardiomyocytes prevents this enrichment, indicating that the Myc-overexpressing population displaces the WT cardiomyocytes by in-ducing their death. Our study shows that the mammalian epiblast optimizes its cellular composition by eliminating the less active cells through cell competition. The differentiated embryonic cardiomyocyte population is as well able to elimi-nate less active cells through cell competition, indicating that the phenomenon is not restricted to embryonic stem cell populations. We are currently exploring the ability of cell competition to induce the displacement of less active postmitotic cardiomyocyte populations in homeostatic and injured adult hearts.

SeSSIoN III: deveLoPmeNt & regeNerAtIve CHALLeNgeS At tHe BASIC LeveL

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The Future: Therapy of Myocardial ProtectionBorja Ibañez, MD, PhD, FESC, Centro Nacional de Investigaciones Cardiovas-culares (CNIC), and Hospital Clínico San Carlos, Madrid, Spain

Seminal studies in the early 1980s demonstrated that the main determinant of myocardial necrosis following a coronary occlusion was time of ischemia. It was proven that early coronary reperfusion is able to limit the extent of ne-crotic myocardium. The classical dogma “time is muscle” was then adopted and this has significantly impacted the care of patients having an acute myo-cardial infarction (AMI). As a result, interventions shortening the time from symptoms onset to coronary flow restoration have been widely adopted and have significantly reduced the morbid-mortality associated with AMI. Infarct size has been recently shown to be a strong independent predictor of post-AMI repetitive cardiovascular events, including mortality. Despite the big effort in reducing time of ischemia, infarct size is still large in most of AMI patients, being the consequences of great magnitude in terms of cardiovascular mortality and eco-nomic burden associated with post-AMI disability. As a result interventions able to protect the myocardium from death during an AMI (cardioprotection) are desper-ately needed.

Recently, it has been demonstrated that, in many cases, the myocardial injury as-sociated with reperfusion (ischemia/reperfusion injury [I/R]) itself can further con-tribute to the final necrotic size. Time from ischemia onset to coronary reperfusion can only be reduced by social and EMS-hospital collaborative programs. However, for a given time of ischemia, one attractive target to reduce infarct size is the dimin-ishment of I/R injury. Despite that many therapies have been shown to be able to reduce this type of myocardial death in animal models, that translation to humans has been frustrating. The cost of developing new drugs able to reduce I/R injury are huge and this is a major hamper on the field of cardioprotection.

Recent studies have proposed that old inexpensive drugs, in human use for de-cades, could reduce I/R injury when administered intravenously before coronary opening (β-blockers and cyclosporine among others). The demonstration of such a cardioprotective effect should have a significant impact in the care of AMI patients.

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dAY 2: Saturday, November 5, 2011

SeSSIoN Iv: ArterIAL CHALLeNgeS ANd tHe CLINICAL LeveL


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Antithrombotic Progress – Evolving Oral Agents

Steen e. Husted, MD, DSc, Aarhus University Hospital, Aarhus, Denmark

Antiplatelet drugs.Two reversibly-binding oral P2Y12 inhibitors ticagrelor and elinogrel are in clini-cal development. Ticagrelor has a rapid onset of action and the inhibitory an-tiplatelet effect is more consistent and greater than with clopidogrel. In the PLATO trial, ticagrelor compared to clopidogrel in patients with acute coronary syndromes (ACS) reduced cardiovascular death, myocardial infarction and stroke without an increased risk of major bleeding complications. Furthermore, cardiovascular mortality as well as total mortality were significantly reduced.Eli-nogrel is a reversible-binding P2Y12 inhibitor, which can be administered both orally and intravenously. The drug has been evaluated in phase 2 trials and a major phase 3 trial including patients with coronary artery disease is ongoing. Antagonism of the platelet thrombin receptor protease-activated receptor-1 (PAR-1) represents a new strategy to reduce residual ACS cardiovascular risk. Rein-forcement of platelet activation by thrombin occurs after initiation of clot forma-tion by collagen, suggesting that PAR-1 antagonists may be associated with a low bleeding risk. Dose-dependent antithrombotic effects have been shown with the PAR-1 antagonist vorapaxar, which is being tested for clinical efficacy and safety in the ongoing phase 3 TRACER and TRA2-P trials.


STEMI: Clock Time Therapy Challenges the Ambulance, the Metropolitan and the Community Settings

Carlos macaya, MD, PhD, Hospital Clínico San Carlos, Madrid, Spain

The recognition of the temporal progression of myocardial necrosis during an ST-segment elevation acute myocardial infarction (STEMI) is the basis for the early interventions in this context. Early studies in the late 1970s showed that irreversible injury of ischemic myocardium develops as a transmural wavefront which begins in the subendocardial myocardium and moves progressively toward the subepicardial myocardium. It has consistently been demonstrated that the best strategy to limit myocardial death during an STEMI is an early coronary reperfusion, preferably by primary angioplasty.

Early analyses of quality control of STEMI programs focused on time from entry in hospital to coronary reperfusion (door-to-balloon or door-to-needle). However, time of patient transport from site of STEMI diagnosis to the hospital also accounts for a significant delay of STEMI treatment. As a result the system delay (covering the time from first medical contact to coronary reperfusion) has become the best evaluator of the quality of the medical system.

Modern approach of STEMI patients requires a close interaction between emer-gency medical systems, hospitals and interventional cardiology laboratories. Treat-ments with proven benefits should be given as early as possible, ideally in the ambulance setting.

The Link between Complex Coronary Disease and/or Significant Carotid Disease, Diabetes and Cerebrovascular Disease

valentin Fuster, MD, PhD, Mount Sinai Medical Center, New York, NY, andCentro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain

Four aspects to be discussed:1) The development of drug-eluting stents has raised great hopes that percutane-ous coronary intervention has a potential role in the revascularization of patients with three-vessel disease and left main coronary artery disease. However, recent results from the SYNTAX clinical trial have shown that, compared with drug-elut-ing stents, bypass surgery is associated with a lower restenosis rate and a re-duced incidence of major cardiovascular events. This study used an index that quantifies the severity of coronary artery disease on the basis of a number of anatomical criteria of lesion complexity (i.e., the SYNTAX score). The study results indicate that the higher the index (i.e., the more complex the lesion), the greater the benefits of surgery.

2) Of interest, similar information is evolving in carotid disease when endarterec-tomy is being compared to stenting. However in coronary and carotid disease, the sum of the evidence available shows that therapeutic approaches to complex disease should take into account, not only the anatomical and structural character-istics of lesions, but the functional parameters as well.

3) In diabetic patients with multivessel disease, the results of the FREEDOM study (currently ongoing) could be crucial for incorporating this new knowledge into prac-tice and for defining the optimum management for this group of high-risk patients.

4) Finally, in regards to degenerative brain disease, particularly Alzheimer’s disease, a large body of literature now exists revealing the strong association of hyper-tension and other cardiac risk factors with the cerebral microvasculature and cognative dysfunction in such disease entities.

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Anticoagulants.Dabigatran etexilate, a direct thrombin inhibitor, as well as the direct factor Xa inhibitors apixaban, rivaroxaban and edoxaban are all in late clinical development for use in thromboprophylaxis, atrial fibrillation, venous thromboembolism and ACS. Against standard therapy these drugs have demonstrated promising effi-cacy data and similar or even lower bleeding risk when administered in a fixed daily dose without the need of laboratory monitoring.

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Refractory Angina/Ischemia/Carotid Disease in the Elderly

Jonathan L. Halperin, MD, Mount Sinai Medical Center, New York, NY

Data to guide therapy in elderly patients with refractory ischemia are relatively lim-ited. Subgroup analyses of trials in patients with acute myocardial infarction (MI) reflect evolution of treatment. Primary percutaneous coronary intervention (PCI) supersedes thrombolytic therapy acute ST-elevation myocardial infarction (STE-MI), even when patients must be transferred to facilities with PCI capability if the transfer time is brief. When mechanical revascularization is unavailable, thrombo-lytic therapy must be used in patients without contraindications, but the risk of bleeding is higher in those over 75 years old. Studies investigating thrombolysis plus platelet glycoprotein receptor antagonists show questionable benefit in the elderly. Observations in the SYNTAX trial show differential outcomes according to mode of revascularization in elderly patients with severe chronic coronary disease.Observational reports of carotid endarterectomy (CEA) among octogenarians documented 30-day stroke and death rates no different from those in younger patients. Other analyses suggest 3-fold increased risk among octogenarians undergoing carotid artery stenting (CAS) that is not mediated by symptomatic status, anatomic factors, protective devices, or degree of stenosis. Observations in the the Carotid Revascularization Endarterectomy versus Stent Trial (CREST). trial suggest that younger patients have slightly better outcomes with CAS and older patients have better outcome with CEA. Hence, while age alone should not determine candidacy for intervention, the results recent clinical trials suggest that patient age may have important implica-tions for the selection of the optimum mode of revascularization.

SeSSIoN v: treNdS ANd CHALLeNgeS oF PreveNtIoN

Optimal Lipid Targets (OLT) for the New Era of Cardiovascular Prevention

Laurence Sperling, MD, Emory University School of Medicine, Center for Heart Disease Prevention, Atlanta, GA

OLT should be the goal for all individuals treated in the new era of cardiovas-cular (CV) prevention. Evidence supports that average LDL cholesterol (LDL-C) values are not optimal. Lessons from both nature and science support a physi-ologic LDL-C target (< 70 mg/dl). Clinical trial evidence further supports optimal LDL-C targets, although several critical questions remain unanswered. Using a calculated LDL-C may have limitations in clinical practice. Importantly, the non-HDL cholesterol may be a better predictor of outcome, and this value should be provided on all laboratory reports. Specific HDL cholesterol (HDL-C) targets are significantly more complicated. An HDL-C level > 50 mg/dl is associated with lower CV risk, and a low HDL-C predicts a less favorable outcome (even when LDL-C is at goal). Nonetheless, clinical trials focused on HDL-C have been thus far disappointing. OLT should be the goal for all individuals as an important part of addressing global CV risk.


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Hypertension and Guidelines: Who to Believe?

robert A. Phillips, MD, PhD, University of Massachusetts Medical School, Worcester, MA

The objectives of this presentation are to review the value and limitations of current guidelines for identification and management of patients with essential hyperten-sion. Guidelines are primarily based on clinical trials that measured clinic/office BP. In uncomplicated hypertension, <140/90 mm Hg is the treatment goal for individu-als aged 18-79 and systolic BP (SBP) between 140-150 mm Hg in those 80 years of age. Because at similar BP levels African Americans have more target organ damage (TOD) than whites, a lower goal of <135/85 mm Hg is recommended. In patients with coronary artery disease (CAD), diabetes and chronic kidney disease (CKD), <130/80 mm Hg is recommended. The ongoing U.S. National Heart, Lung and Blood Institute-sponsored Systolic BP Intervention Trial (SPRINT), is testing the hypothesis that goal SBP <120 mm Hg is superior to SBP <140 mm Hg on the composite endpoint of non-fatal MI, stroke and heart failure, as well as on pres-ervation of cognitive function and normal brain architecture. Because of their reli-ance on clinic/office BP, current guidelines are not comprehensive enough to guide treatment in many patients. Masked hypertension, defined as normal clinic BP with a high average self-monitored or ambulatory BP, is highly prevalent in those with CKD, diabetes, left ventricular hypertrophy or obstructive sleep apnea. Masked hy-pertension is associated with TOD and worse outcome. Ambulatory BP monitoring and self-monitoring of BP needs to be incorporated into guidelines to identify those with masked hypertension, and new treatment paradigms must be implemented to treat masked hypertension.


SeSSIoN vI: mYoCArdIAL CHALLeNgeS At tHe CLINICAL LeveL

Evolving Diagnostic and Prognostic Imaging (MR, CT) of the Various Cardiomyopathies

Javier Sanz, MD, Mount Sinai Medical Center, New York, NY

Several noninvasive imaging modalities, particularly magnetic resonance imag-ing (MRI), have of late provided important diagnostic and prognostic insights into various cardiomyopathies. Myocardial delayed enhancement on MRI after ad-ministration of gadolinium-based contrast agents accurately delineates scar, and recent evidence suggests that myocardial scarring is a powerful marker of poor prognosis in both ischemic and non-ischemic dilated cardiomyopathy, including patients with severe LV dysfunction. In this context, loss of integrity of the cardiac sympathetic nervous system, as demonstrated by reduced myocardial uptake of the radioisotope meta-iodo-benzylguanidine (MIBG) with nuclear imaging tech-niques, has also been shown to provide additive prognostic information. More-over, techniques for quantification of diffuse interstitial myocardial fibrosis (as op-posed to focal replacement scar) with MRI are being developed and validated.

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The presence/absence of scar on MRI has emerged as an important diagnostic tool for specific cardiomyopathies, such as Tako-Tsubo or sarcoidosis. In cases where the pattern of scar may suggest ischemic etiology, coronary angiography with computed tomography may be very useful in ruling out underlying coronary disease noninvasively. In the setting of hypertrophic cardiomyopathy, several re-cent studies have shown scar to be a predictor of heart failure and, although less consistently, ventricular arrhythmic events. Regarding noncontrast MRI, the quantification of the myocardial parameter T2* has been validated not only for ac-curate quantification of iron concentration in myocardial siderosis, but also as the strongest predictor for incident heart failure in this clinical context. Finally, new di-agnostic criteria for arrhythmogenic cardiomyopathy that include ultrasound and MRI have been recently developed and validated.

State-of-the-art Management of Systolic and Diastolic Heart Failure

Clyde w. Yancy, MD, MSc, FACC, FAHA, MACP, Northwestern University, Feinberg School of Medicine, Chicago, IL

Increasingly, heart failure is becoming the lead manifestation of cardiovascular dis-ease. Within the United States, those affected now number more than 6 million, and worldwide, that number is greater than 20 million persons affected. The subsequent cost of care and loss of both quality and quantity of life have become almost non-sustainable and clearly a much more concerted focus is now warranted.

Though heart failure can be classified according to any one of several hierarchal templates, the approach that is most meaningful in the clinical context is to sepa-rate heart failure according to the concomitant measurement of ventricular func-tion. Heart failure with reduced ejection fraction is akin to systolic dysfunction, though abnormalities of systolic performance may be present with both a reduced or preserved ejection fraction measurement.

Similarly, heart failure with preserved ejection fraction is in parallel with diastol-ic dysfunction, but again, parameters of altered ventricular compliance may be present when the ejection fraction is preserved or reduced.

The importance of this distinction based on ventricular function cannot be over-emphasized. Evidence-based guideline driven care has been clearly identified for systolic heart failure, and optimal compliance with best quality measures is as-sociated with markedly improved outcomes. Those evidence-based interventions known to improve outcomes in systolic heart failure include:

1. ACE-Inhibitors or Angiotensin receptor antagonists [but not both together]2. Beta blockers3. Aldosterone antagonists4. Isosorbide dinitrate/hydralazine5. Implantable defibrillators6. Cardiac resynchronization therapy with our without defibrillators


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Other potentially helpful interventions include: cardiac rehabilitation, ivabra-dine, continuous monitoring and left ventricular assist systems. This robust list of known and potentially helpful interventions provides an array of therapies that allow for a best care approach for patients with heart failure that is tailored according to presentation and certain manifestations of the disease.

Such is not the case for diastolic heart failure, as no therapies to date have been demonstrated to modify the natural history of this major component of heart failure. Currently, at least 50% of those affected with the clinical syndrome of heart failure have preserved measurements of ventricular function and/or diastolic dysfunction. As such, the best care, pending novel biological discoveries, is an approach focused on the often associated assortment of important co-morbidi-ties. Up to 90% of those with diastolic heart failure will have either: hypertension, coronary artery disease, diabetes or atrial fibrillation. Therapy after deconges-tion should be focused on these important co-morbidities for which an evidence based approach can be followed. It is important to recognize that the natural history for diastolic heart failure is no less worrisome than it is for systolic heart failure. The mortality risk for both is similar but the reasons for death vary with sudden death and pump failure prominent in systolic heart failure while those plus other cardiac and especially non-cardiac conditions are implicated for diastolic heart failure.

The take home message is to assess ventricular function in all patients with heart failure at the time of onset of symptoms and repeat those measurements if there is an important change in clinical status. Aligning therapy according to one of these two iterations of heart failure is the most important initial step in treating the patient with heart failure.


The Evolving Landscape of Quality Measurement for Heart Failure

Frederick A masoudi, MD, MPSH, Division of Cardiology, University of Colorado Denver, Aurora, CO

Heart failure (HF) is the most common cause of hospitalization among elderly per-sons in the US and is a major cause of mortality, morbidity, and increased costs of care in the developed world. Advances in science have generated effective interventions to reduce adverse outcomes in HF, and guidelines recommend the use of a number of these interventions. However, it has been increasingly noted that effective therapies for heart failure are often not used and that adverse out-comes for HF remain high. The last decades have witnessed the growth of efforts to measure and improve the care and outcomes of patients with HF. These efforts have evolved in two respects: 1) what is measured, and 2) how the measures are employed. With respect to what is measured, initial efforts typically focused on processes of care (e.g. the prescription of particular medications) and have expanded to include measures of outcomes (e.g. mortality) and efficiency (e.g. readmission). The use of measures has also evolved, initially from internal use for

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SeSSIoN vII: eLeCtrICAL CHALLeNgeS At tHe CLINICAL LeveL

Atrial Fibrillation, Stroke and the Quality of Life


The incidence and prevalence of atrial fibrillation (AF) are increasing worldwide. AF is of public health importance because it accounts for substantial morbid-ity, mortality, and health-care costs. AF may be transient initially, but many pa-tients have progressive disease marked by increasing frequency and duration of episodes. We will address gaps in knowledge that present opportunities to re-examine the current pattern-based classification of AF. A future classification scheme should ideally combine elements such as the risk of stroke, an assess-ment of symptoms, and the degree of impairment of the atrial substrate. From a stroke perspective, atrial fibrillation is a major risk factor for ischemic stroke. Antithrombotic therapy using vitamin K antagonists (VKA) is currently prescribed for prevention of ischemic stroke in patients with AF. Recently developed anti-coagulants include the direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors rivaroxaban, apixaban, edoxaban, to name those in the most advanced stages of clinical development. Accordingly, we will also focus on advances in the development of novel antithrombotic agents.

Ventricular Tachycardia and Ventricular Dysfunction, Which to Watch?

Josep Brugada terradellas, MD, PhD, FESC, Hospital Clinic, University of Barcelona, Barcelona, Spain

Sudden cardiac death affects a significant number of patients after a myocardial infarction. Identification of patients at risk has been the subject for a large num-ber of studies. Patients with a previous history of ventricular arrhythmias, spe-cially sustained ventricular tachycardia or ventricular fibrillation, are considered to have the worst outcome. However, only a minority of patients finally suffer-ing from sudden cardiac death presented previously with ventricular arrhythmias. Left ventricular dysfunction has been shown to be directly related to the occur-rence of sudden cardiac death. Identification of the patients with a low ejection fraction allows recognition of a large group of candidates for primary prevention strategies. At the same time, enlarging the potential population at risk, in which implantable defibrillators can protect them, implies treatment of an increasing


quality improvement, to the public realm, where performance measures are used as part of public reporting and pay-for-performance programs. This talk will re-view the past and present of heart failure quality measurement efforts—focusing on the US as an example—and will provide a perspective on the possible future of initiatives to measure and improve the quality of care and outcomes of patients with HF.

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number of patients that will not benefit from the device. Refining the final population to protect probably requires the use of a combination of factors: age, left ventricular ejection fraction with or without heart failure symptoms, QRS width, previous arrhyth-mias and associated conditions. A review of the current concepts on prevention of sudden cardiac death will be covered.

SeSSIoN vIII: vALvuLAr dISeASe & AortIC CHALLeNgeS At tHe CLINICAL LeveL

Future of Transcatheter AVR: The Best Procedure of Choice for an 80-year-Old? Even Younger? How We Protect the Brain from Embolization?

Josep rodés-Cabau, MD, Quebec Heart and Lung Institute, Quebec City, Canada

The first human transcatheter aortic valve implantation (TAVI) for the treatment of symptomatic severe stenosis was performed in 2002, and was followed by sev-eral single-center series showing the feasibility of this new approach for the treat-ment of patients considered at very high or prohibitive risk for standard surgical aortic valve replacement (SAVR). Recent large multicenter registries using either balloon-expandable or self-expandable transcatheter valve systems have con-firmed the safety and efficacy of this procedure, with procedural successes >90% and 30-day mortality rates <10% in most series, despite a very high-risk patient profile. The occurrence of stroke (0.6% to 6.7%), major vascular complications (0.6% to 19%), or conduction disturbances leading to permanent pacemaker implantation (3.5% to 40%) remain among the most concerning peri-procedural complications. The PARTNER trial has recently confirmed both the superiority of TAVI compared to medical treatment in patients considered non-candidates for SAVR (20% absolute reduction in mortality at 1-year follow-up) and the non-inferiority of TAVI compared to SAVR (mortality rates of 24.2% and 26.8% at 1-year follow-up, respectively). The hemodynamics of transcatheter valves are usually excellent, with very low residual transvalvular gradients, though re-sidual paravalvular aortic regurgitation is very frequent (~70-80%, trivial or mild in most cases). Finally, there are promising preliminary data on the long-term outcomes following TAVI as well as on TAVI for the treatment of surgical pros-thesis dysfunction (“valve-in-valve”) and lower risk patients. Continuous im-provements in transcatheter valve technology, optimization of procedural and midterm results, and confirmation of the long-term durability of transcatheter valve prostheses will determine the expansion of TAVI towards the treatment of a broader spectrum of patients with severe aortic stenosis in the near future.

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It May Be Too Early or Too Late for Surgery in Severe Mitral Regurgitation

david H. Adams, MD, and Javier Castillo, MD, Mount Sinai Medical Center, New York, NY

There is still a current disagreement among experts about the need and timing for surgical intervention in patients with severe mitral valve regurgitation, particularly in the setting of asymptomatic severe mitral regurgitation. This disparity is also reflected in the current management guidelines. The occurrence of severe NYHA class III or IV preoperative symptoms confers a postoperative poor prognosis after mitral surgery even if the left ventricular function is preserved. Therefore, it is im-portant to correct mitral regurgitation at the onset of even mild clinical manifesta-tions, avoiding physiological and geometrical cardiac changes as well as the con-comitant risk of sudden death in symptomatic patients. In asymptomatic patients with preserved left ventricular function, the main indications for mitral surgery are the onset of symptoms and left ventricular dysfunction. However, although new indications for mitral surgery still remain debatable for many cardiovascular specialists, guidelines now also recommend early mitral valve repair based on the accomplishment of two tenets: >90% probability of repair based on preoperative assessment of the valve anatomy and a mortality rate ≤ 1%. These conditions are additionally supported by recent data which suggest a survival benefit to early surgery. During the lecture, indications, referral patterns and timing of surgery for severe mitral regurgitation will be extensively discussed. Finally, the current adhesion of cardiologists to the management guidelines and the creation of mitral valve reference centers with highly specialized teams will be evaluated.

The Dilated Aorta and Its Consequences


The pathophysiology of thoracic aortic aneurysm (TAA) formation involves a com-plex interplay of genetic predisposition, cardiovascular risk factors, and hemody-namic forces. The medical community has resorted to the use of pharmacologic agents based on weak data transplanted from either abdominal aortic aneurysm (AAA) or Marfan syndrome. However, aneurysms differ significantly based on anatomic location and etiology. Epidemiologic and experimental data demon-strate that different genetic and nongenetic risk factors as well as diverse patho-physiologic processes are responsible for the development and progression of sporadic TAA, familial TAA (such as those found in Marfan syndrome), and AAA. Therefore, these disease processes need to be considered as distinct entities and not hastily grouped together. The extrapolation of data from one aneursymal disease process to another is ill founded and potentially harmful. Clinical trials in TAA are required before medical therapies, such as beta-blockers, ACE receptor blockers, statins, and macrolide antibiotics, can be recommended.


NoteS


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PromotIoNAL PArtNerS


AddItIoNAL INFormAtIoN

ANALYSIS oF CArdIAC deveLoPmeNt:

From emBrYo to oLd Age

Purchase this volume and receive an 80% discount using this promotional code ACd11.

Visit www.wiley.com/go/acdThis Annals issue opens with manuscripts on cardiogenesis during embryonic development, including development of the cardiac excitatory system and the fate of progenitor cells

in postnatal cardiac develpment, cell signaling during development, vasculogenesis, and stem cells in cardiac repair. Contributions also include micro-scale phenomena (sodium channel blockers, extracellular matrix, and intracellular mechanisms) and macro-scale phenomena (predictive cardiac modeling, virtual circulation of the aging heart, and biomechanics of early cardiac morphogenesis). The final manuscripts of this issue discuss cardiac-related aging phenomena, such as cardiovascular remodeling, arrhythmogenesis, and anti-aging interference agents.

Edited by Rafael Beyar and Amir Landesberg (Technion, Israel Institute of Technology, Haifa, Israel)

Volume 1188, February 2010, 29 Papers

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The Academy invites conference proposals in a variety of fields: biomedi-cal sciences, chemistry, physical sciences, engineering, technology, and others. The Academy will give priority to conferences in cutting edge, prob-lem-oriented, multidisciplinary subject areas, as well as on issues faced by the public and private sectors at the interface of science, technology and society. Proposals are accepted throughout the year; there is no spe-cific deadline. To submit a conference proposal or for more information on organizing a conference with the Academy, please contact dr. Brooke grindlinger at [email protected].

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Research

We are broadening the paths of medical research

Further information at: www.laCaixa.es/ObraSocial · 902 22 30 40

• National Biotechnology Centre (CNB-CSIC)

• IrsiCaixa Laboratory (Institute for Re-

search into AIDS and its Treatment)

• National Centre for Cardiovascular

Research

• The Vall d’Hebron Oncology Institute (VHIO) Foundation

• National Centre for Oncological Research (CNIO)

• Genome Regulation Centre (CRG)

• Institute for Biomedical Research (IRB)

• WIDER-Barcelona Centre (World Instit- ute for Digestive Endoscopy Research)

• BarcelonaBeta Centre – Barcelona Research Complex for Better Aging

COLLABORATING CENTRES

From ”la Caixa” Welfare Projects we pro-mote medical research in various fields, jointly with prestigious centres. Our aim is to support researchers and to help improve the treatment of some of the most serious diseases that afflict humanity, such as AIDS, cancer, Alzheimer’s disease and cardiovas-cular illnesses.

A commitment to people’s health.

From “la Caixa” Foundation we pro-mote medical research in various fields, jointly with other prestigious centres. Our aim is to support researchers and to help improve the treatment of some of the most serious diseases that afflict humanity, such as AIDS, cancer, Alzheimer’s disease and cardiovascular illnesses.

A commitment to people's health.

"la Caixa" Foundation is the largest private foundation in Spain, the second largest in Europe, and the fifth larg-

est worldwide. One in every four Spaniards benefits directly from social outreach projects of "la Caixa" Foundation.The cultural and scientific initiatives of "la Caixa" Foundation, devel-oped both through its own centers and as traveling exhibitions around Spain, are integrated into the Foundation’s profound social vocation. The exhibits and activities organized by the Foundation’s department of Science, Research and Environment aim at fostering 1) scientific knowledge, 2) scientific method, and 3) scientific opinion; so that citizens are provided with tools to be democratically involved in the decisions affecting their lives. In addition, "la Caixa" Foundation awards research grants and pre-doctoral fellowships in collaboration with world-renowned centers such as IrsiCaixa, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Fundació Vall d’Hebron Investigació Oncològica – VHIO, Fundació Pasqual Maragall, Fundació Institut Investigació Biomèdica de Girona, Fundación General del Consejo Superior de Investigaciones Científicas, Associació Catalana d’Universitats Públiques (ACUP, Projecte Recer-Caixa), and CRESIB – Institut de Salut Global.Visit la caixa at www.lacaixa.es/obrasocial

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Biocat is the organization that coordinates, dynamizes and promotes the biotechnology, biomedi-cine and medical technology sectors in Catalonia. It is fostered by the Government of Catalonia and the Barcelona City Council. Biocat’s main objectives are to facilitate relationships and syn-ergies among members of the BioRegion of Catalonia, to foster the biotechnological sector as one of the main drivers of the economy, to promote the sector on an international level and to improve the public’s knowledge and perception of biotechnology.Visit the International Center for Scientific Debate at: www.biocat.cat/en/icsd

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Evolving Challenges in Promoting€¦ · welcome you to our conference evolving Challenges in Promoting Cardiovascular Health. Leading and emerging investigators working on the fields