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Registration and Breakfast

First Look: The Next Wave of Cardiology Breakthroughs

Harvard Medical School investigators describe their most promising work in rapid fire presentations highlighting commercial opportunities in cardiovascular and cardiometabolic care. Nineteen rising stars from Brigham and Women’s Hospital and Massachusetts General Hospital will present in 10-minute sessions.

For a full look at speakers and presentations, please visit the Highlight’s page.

Early career Harvard Medical School investigators kick-off the World Medical Innovation Forum with rapid fire presentations of their high potential new technologies. Nineteen rising stars from Brigham Health and Massachusetts General Hospital will highlight in ten-minute presentations their discoveries and insights that will be the disruptive cardiovascular care of the future. This session is designed for investors, leaders, donors, entrepreneurs and investigators and others who share a passion for identifying emerging high-impact technologies. The top presenter each from BWH and MGH will be awarded the Austen-Braunwald Innovation Prize on Day 2 of the Forum. The prize carries a $10,000 award.

Novel Target Discovery Pipeline for Calcific Aortic Valve Disease
Elena Aikawa, MD, PhD
Director, Heart Valve Translational Research Program, Brigham and Women’s Hospital; Associate Professor of Medicine, Harvard Medical School

• Aortic stenosis is a progress of Calcific Aortic Valve Disease (CAVD) – 80,000 patients – sole solution is surgery
• Imaging methods for visualization of microcalcification formation: MRI, PET/CT, CAVD Gene network, proteomics heat mapNIRF imaging, microdissection, histology, Tissue layers cells
• Serum Sortilin associated with aortic calcification and CVD risk
• Discovery pipeline and CAVD Mapping

A zebrafish pipeline for cardiovascular precision medicine
Manu Beerens, PhD
Postdoctoral Research Fellow, Brigham and Women’s Hospital; Harvard Medical School

• Cardiomyopathy – group of cardiac disorders: CHF, Atherosclerosis, metabolic syndrome, AF
• Zebrafish at the forefront of CVD Precision Medicine
• Luciferase activity vs ttn
• high throughput screening to identify naxos modifiers
• Endpoints: BNP levels Cardiac contractility

Using zebrafish to understand and harness cardiac regeneration

Caroline Burns, PhD
Associate Biologist, Massachusetts General Hospital; Associate Professor of Medicine, Harvard Medical School

• Heart regeneration
• Regenerative hearts vs Non-Regenerative hearts
• How cardiomyocytes proliferation induced following injury
• Uninjured, 1 day after, 7 days after,
• Failure to regenerate is related to failure of myoocardial proliferation
• Genetic factors required for myocardial proliferation
• myocardial proliferation – by Chromatin – mononuclear >4c ploidy
• Mononuclear in Human Heart – as research target
• How to promote myocardial proliferation
• Small molecule as enhanced to drive proliferation

Bioactive Lipid Profiling Can Identify Potential Targets for Altering Life Course Trajectories Toward Cardiometabolic Disease
Susan Cheng, MD
Associate Physician, Brigham and Women’s Hospital, Partners HealthCare; Assistant Professor, Harvard Medical School

• Bioactive Lipids
• Endogenous and exhaugenous factors
• Biochemical intermediates
• mechanisms
• health and disease outcomes
• Small lipid Mediators of Upstream: Eicosanoids and Incidence of Diabetes as Targets for Present and Future
• cardiometabolic risk in future early vs late prediabetes, and DM
• shared pathways
• Statins favoral response
• Stree or Injury
• Linoleic Acid
• Disease and Phynotyping specific investigations
• dosing

Small Molecule Predictors of Outcome After Cardiac Interventions
Sammy Elmariah, MD
Assistant in Medicine, Massachusetts General Hospital; Assistant Professor of Medicine, Harvard Medical School

• Valvular heart disease – elderly, Aortic valve stenosis leads to failure of compensatory ventricular activity of dysfunction
• small molecule
• fiadnostics biomarkers
• Acute kidney injury due to metabolite, adenohomosestine
• validate the model – after METABOLITE data is added to the risk classification
• Personalizing the timing of Valve Intervention
• Biomarkers in blood predicts systolic function, EF,
• Metabolite-Driven clinical trial of Aortic stenosis
• TAVR

Translational trials in microRNAs
Mark Feinberg, MD
Physician, Brigham and Women’s Hospital; Associate Professor of Medicine, Harvard Medical School

• non-coding RNA Biologics – 98% of the genome
• 2% are coding
• MiRNA therapeutics for Atherosclerosis
• MiRNA – Replacement Therapy- ApoE-?-NGL
• Cholesterol, LDL
• Vascular endothelium: Inflammation, HF, Diabetic wound healing – tissue thickness
• Example: IncRNA, Example3: miR-26a – BMP-SMAD1-ID1-p21
• 3 platforms for targeting non-coding RNAs in CVD:

New approaches to controlling stem cell fate
Yick Fong, PhD
Research Scientist, Brigham and Women’s Hospital; Assistant Professor of Medicine, Harvard Medical School

• controlling Stem cell fate by Transcription Factors
• Pluripotent, fibroblasts – transformed into Bone, nerve, heart, pancreatic cells
• This process is randon and inefficient
• GOAL: Transplantation, drug/therapeutic screens
• Cellular identity and function
• In Vitro Reconstruction of cell-type specific Transcription
• Identify Disease mechanism of Heart disease by mutation that cause disruptionCo-regulators disruption

Exercise Prescription to Improve Cardiovascular and Cancer Outcomes in Cancer Survivors
John Groarke, MD
Cardiologist, Brigham and Women’s Hospital; Instructor of Medicine, Harvard Medical

• cancer survivers have risk for CVD
  Metabolic Equivalent ((METS)
• METS is the highest to lower CVD in Cancer survivors
• Onco-cardiac rehabilitation
• Increase excercise performance vs physical de-conditioned state
• Cardioprotection to mitigate CV Toxicities of cancer therapy

Personalizing Diabetic Management with Hemoglobin A1c
John Higgins, MD
Associate Pathologist, Massachusetts General Hospital; Associate Professor, Harvard Medical School

• Non glucose factors that affect A1C

1. RBC Age span – if circulate live longer accumulates more glucose
2. AstraZeneca, Eli Lilly, Novo Nordics – ALL conduct clinical trials to lower A1C

• Personalize DM Management
• Using existing assays with the RBC Age adjustment — for achieving better future Outcomes
• Device Manufacturers to adjust the device

Characterizing an Early HeartFailure pulmonary EF (HFpEF) Phenotype: Cardiometabolic Disease and Pulmonary Hypertension
Jennifer Ho, MD
Assistant Physician, Massachusetts General Hospital; Member of the Faculty of Medicine, Harvard Medical School

• Ejection Frunction in Pulmonary Hypertension (PH)
• Obesity >–>>> PH recapitulates human HP
• PAECs – Molecular mechanisms – Pulmonary Artery #Endotheline Cells
• P13K/Akt (Insulin) — AMPK  (Metformin) –>> eNOS — >> Vasodilation
• Study ex-vivo PAEC from patients with HFpEF

1. HFpEF subphenotypes
2. drug therapy
3. screening

Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease
Amit Khera, MD
Cardiologist, Massachusetts General Hospital; Instructor, Harvard Medical School

• Integration of Genetic data and CVD data
• GWAS –>> 60 variants associated with coronary risk
• Polygenic genetic risk score
• Risk for MI: Genetic risk Interpretation: Monogenic vs Polygenic
• High risk comes from polygenic risk: Smoking, Obesity, Excercise, Health diet
• Healthy lifestyle “corrects” genetic factor

Monogenic:

• Hypercholesterolemia
• Trycleceride
• increased lipoproteins _ ASA Lp(a) inhibitors

Polygenic

• life style, diet excercise
• medicationS: Statins

A Novel Epigenetic Complex Implicated in Thoracic Aortic Aneurysm (TAA)
Mark Lindsay, MD, PhD
Physician, Massachusetts General Hospital; Assistant Professor, Harvard Medical School

• Thoracic Aortic Aneurysm
• Aortic dissection
• VSCULAR SMOOOTH MUSCLE CELLS in the aorta’s leaves – neo-intima damage vs knockout MALAT1 – nepangiogenesis
• GENETIC MUTATIONS as Biologic Probes
• GENE: HDAC9 – BRG1, MALAT1 (RNA) – STRESS in aortic homeostasis
• Aortic root and Ascending Aorta
• Elastin and colagen

Atrial Fibrillation: Genetic Basis and Clinical Implications
Steven Lubitz, MD
Cardiac Electrophysiologist, Massachusetts General Hospital

• 6 million in US 34 Million WOrldwide
• Leading cause of stroke
• AF is hard to diagnose
• preventable with anticoagulation
• AF is Familial and inheritable
• Genetic Variation associated with AF – genetics stratified risk
• AF Screening: as Stroke prevention – AliveCor
• electronic health records are powerful repositories
• AF genetic risk – as a Biomarker
• Technologies for screening

Targeting Vascular Calcification to Prevent Cardiovascular Disease
Rajeev Malhotra, MD
Staff Cardiologist, Associate Medical Director of the Cardiac Intensive Care Unit, Associate Director of the Cardiopulmonary Exercise Laboratory, Massachusetts General Hospital; Instructor in Medicine, Harvard Medical School

• Vascular Classification: Atherocalcification Vascula r disease
• plaque destabilization
• coronary and aortic
• HUMAN GENETICS Studies: GWAS

1. Genotype
2. Aortic CT
3. Identify Potential Genes, increase expression associated with classification
4. Functional-Mechanical Studies: smooth muscle cell – more proliferative vs more contractile
5. control vs inhibition
6. Human model of Vascular classification vs Mouse Model
7. Disease of Vascular classification: Calxiphylaxis – HEMODialysis patients – >50% mortality within 1 year of diagnosis
8. Drug development and Clinical Trials

Stratifying Exercise Dysfunction
Bradley Maron, MD
Association Physician, Brigham and Women’s Hospital; Assistant Professor, Harvard Medical School

• Exercise Dysfunction: Complex Pathophynotype
• iCPET: O2, exercise capacity, Pulmonary function, Hemodynamics, Invesive cardiac performance,
• NEW SYSTEM DESIGNED: Network-Based Clinical Risk Calculator by Four Clusters – Network determine cluster assignment
• Point of care tool – integrate into iCPET
• Provides insights into HTN, Valvular, Myocaritis, cardiomyopathy

1. Pulmonary
2. exercise capacity
3. ventilation perf
4. o2 transport
5. Invasive cardiac

Novel Mouse Models of Remote Cardioprotection
Benjamin Olenchock, MD, PhD
Cardiovascular Medicine Specialist, Brigham and Women’s Hospital; Instructor in Medicine, Harvard Medical School

• Ischemic Preconditing
• Remote limb BP Cuff in pig prevented Ischemia in heart
• Cell death is multi cell types and cell death
• EGLN – succinate +CO2 – Transciptional Hypoxia responses
• EGLN Inhibitor: Systemic Egln1 deletion vs Skeletal Muscle Egln1 Deletion – Study of Cardiac Protection
• Cardioprotective Mediators: Tissue Hypoxia ++>> Altered hepatic Tryptophan Metabolism —>> Cardioprotection
• Tumor xenograph

Harnessing Endogenous Mechanisms of Programmed Gene Expression for Therapeutic Benefit In Cardiometabolic Disorders
Jorge Plutzky, MD
Director, Preventive Cardiology, Cardiovascular Medicine, Brigham and Women’s Hospital

• PPARs
• RXR, RAR – Retinohyde –>> Retinoic Acid
• Transcription factors: Physiology and Pathology
• PPARalpha  <<<<—- Lipase, Lipid sustrate
• Epigenetic Code
• Histone Readers: Selective Inhibition of Tumor Oncogenes by DIsruption Enhancing ranked by BRD4 signal: Chemotaxis, adhesion, Migration, Thrombosis, Inflammation
• Atherosclerosis: Knows protein, Unknown protein: Promoters, enhancers

Aging and the activin type II receptor pathway: a new target for heart failure therapy?
Jason Roh, MD
Assistant in Medicine, Massachusetts General Hospital; Instructor, Harvard Medical School

• AGING and CVD – it is part of pathophysiology – CATABOLIC PROCESSES
• Organ level

muscle waist, atropy –>> impaired function: Hand grip strength, walk speed —->> HF, systolic and diastolic Strain rate

• Cell level: Isotype Abvs ActRII Ab

contractility, Seen in HF models and HFpEF

• Activin-A decreases with AGE

Signaling and pulmonary vascular disease – PAH
Paul Yu, MD, PhD
Physician, Brigham and Women’s Hospital; Associate Professor of Medicine, Harvard Medical School

• FIBROSIS: TGF
• OSTEOGENESIS ANTI-APOPTOSIS
• Activin/TGFBeta —>>> BMP9 (ALK1c)
• Loss od signaling
• Inflammation
• high shear stress
• PAH

1. Idiopathic: Sporadic or heritable
2. Associated PAH: Scleroderma or lupus

• Dysregulated angiogenesis– Anti VEGF165 – Zr-bevacizumab – Using PET-CT

Break and Move to Discovery Café Breakout

Discovery Café Breakout Sessions: Sharing Perspectives

Seven intensive workshops led by our top faculty will address cutting-edge cardiovascular topics. Seating is reserved at the point of registration. Lunch included.

Topics to be covered include:

• Cardiac Replacement Therapy: The Next Ten Years
• Heart Failure: Back in The Game through New Pathways
• Payment Models: Provider’s Perspective
• Molecular Imaging: New Biological Endpoints – Function Over Structure
• Open Innovation in Medical Devices: What is it? What Are the Barriers?
• Wearables for Cardiovascular Health:  How to Validate and Integrate in Care Paths?
• Image Based Artificial Intelligence: Which Cardiac Disease Segments and Why?

For a full list of speakers, please visit the Highlight’s page.

Break

Opening Remarks Christopher Coburn

Reinventing Cardiac Care

Two renowned clinical leaders provide an overview of the medical and economic challenges that cardiovascular and cardiometabolic disorders present.

They will highlight strategic direction in cardiac research and clinical care at Partners, and address how recent trends in investment, regulation, and policy may be dovetailed with efforts at Partners.

The experts also spotlight for attendees the various therapies, diagnostics, devices, and critical issues that will be discussed throughout the upcoming 2.5 days of the World Medical Innovation Forum.

1. Aging and longevity of CVD Patients will increase the expense on CVD as disease

CEO Roundtable: Today’s Learning, Tomorrow’s Opportunities

Discussion on contribution of technology innovation to the treatment of cardiovascular disease reflecting on lessons and how they shape investment decisions.

Tackling the AFib Epidemic

Evolving trends in diagnosis, prevention, and treatment of atrial fibrillation. Factors that will influence patient care over the next 5 years are considered, including risk stratification, procedure and technology options, and potential implications of CMS policies, such as bundling.

1:1 Fireside Chat: Omar Ishrak, PhD, CEO, Medtronic

Heart Failure’s Therapeutic Mandate

One million patients are hospitalized annually for HF—80% of total US cost of HF management. After discharge from HF hospitalization, 24% are rehospitalized within 30 days, greater than 50% within 6 months. Perspective on disease management, addressing the issues of hospital readmission and optimizing therapies.

CLINICAL HIGHLIGHT: A New Chapter of PAD

PAD is the most challenging atherosclerotic syndrome, largely due to the technological challenges of managing peripheral artery disease through minimally invasive strategies. Top physician, governmental, and industry leaders in the field discuss the potential for new breakthroughs including novel implantable devices, pharmacologic approaches, and reductions in associated cardiovascular morbidity and mortality.

The panel will also discuss, Below The Knee: The Persisting Unmet Need

Opening Reception