Will the Benefits of Personalized Cardiovascular Medicine Outpace the Expected 23.6 Million Deaths by the Next Decade?

Progress towards the goal of eradicating cardiovascular disease has been achieved through the adoption of lifestyle changes as well as evidence-based therapies that aim to modify a recognizable and commonly shared cardiovascular disease or at-risk phenotype. Despite the success of these approaches, complete disease prevention and cure have been elusive. In fact the magnitude of the problem remains considerable as there are about 92.1 million adults (>1 in 3) in the U. S. alone living with some type of a cardiovascular disease or the after effects of stroke. In fact, cardiovascular disease the leading cause of death, is expected to account for more than 23.6 million by 2030. This creates an incredible burden on our healthcare system.
• Today, direct and indirect costs of cardiovascular disease and stroke are estimated at more than $329.7 billion
– Total direct medical costs from cardiovascular disease are projected to increase to $749 billion by 2035

The contribution of attendant comorbidities and traditional heart disease, stroke, and cardiovascular disease risk factors include:
• Traditional risk factors: smoking, physical inactivity, nutrition, obesity/overweight, high cholesterol, diabetes, and high blood pressure
• Immutable factors: family history
• Underlying factors: sex-, age-, race-, ethnic-, regional-, and economic-based differences

All of these factors and their significant impact on disease and its progression underscore the importance of precision phenotyping.

Current reductionism approaches can ameliorate symptoms and mitigate disease progression, but disease outcome is not always certain, especially when targeting a chronic complex illness that does not have a single root cause. Furthermore, reductionism focuses squarely on “traditional” treatment of established cardiovascular disease without addressing health, prevention, timing of disease inception, or cure and eradication. To address this issue, it is necessary to understand the totality of the cardiovascular disease picture at a granular and integrative molecular level. Furthermore, integration of large data points lends itself to a more exacting (patho)phenotype, and specifically one that is amenable to precision medicine. As such, the evolution of precision medicine and its application to cardiovascular disease holds the promise of improving health as well as revolutionizing prevention and treatment options similar to what has been occurring in the field of oncology.

Many new tools are being introduced in cardiology to achieve a personalized approach to diagnosing and managing cardiovascular disease. Examples include:
• Genetic studies have uncovered mutations that have been successfully exploited by the pharmaceutical industry to introduce new, highly effective treatments (e.g. PCSK9 inhibitors for lipid lowering).
• Cardiac amyloidosis now has targeted treatments, improving the lives of afflicted patients.
• Somatic genetic mutations have been discovered in hematopoietic cells that are an important risk factor for coronary heart disease (known as clonal hematopoiesis of indeterminate potential, or CHIP).
• Proteomics is able to identify cardiovascular risk more precisely than using traditional risk factors and is able to predict the benefits or harms of specific medical therapies.
• Remote sensors are being used to screen for cardiovascular disease on a broad scale.
• Non-invasive cardiovascular imaging is replacing more invasive tests (i.e. cardiac catheterization) while interpretation of imaging studies is being automated using machine learning approaches.

Cardiovascular Precision Medicine integrates basic science techniques with genomic information as succinctly summarized in the recent review Cardiovascular Precision Medicine in the Genomics Era:
• Clinical genome sequencing [identifying disease-causing mutations, directing disease treatment, and clarifying disease diagnosis],
• Targeted therapies [tackling molecular underpinnings of specific disease subtypes, and patient selection for appropriate clinical trials],
• Genetic risk scores [defining the risk of complex disease and associating genetic risk with disease outcomes]
• Induced pluripotent stem cells [disease modeling, testing new therapies, and potential source of autologous cells for transplantation] and
• CRISPR genome editing [potential to stop disease at the DNA level and to stop the disease before it manifests itself]

Peter Ganz, Chief of Cardiology at the Zuckerberg San Francisco General Hospital and Maurice Eliaser Distinguished Professor at UCSF –Cardiovascular Disease Track Chair: “The health care community will need to focus on thoughtful implementation of new diagnostic modalities. Much of cardiovascular care and reimbursement is currently based on practice guidelines. Supporting, convincing data will need to be accumulated to qualify novel tests and treatments into guidelines.”

PMWC, January 21-24, 2020 Silicon Valley is poised to address the formidable challenge of cardiovascular disease. Key CVD stakeholders across the academic, medical, and pharmaceutical industry have signed on to this PMWC dedicated track to share the most recent advancements, to discuss challenges and obstacles, and to provide an overview of current implementations of clinical applications.

Peter Ganz, UCSF “This is an exciting time when cardiology is finally catching up to oncology in personalizing the care of its patients!”

The scheduled PMWC program promises to deliver a great set of sessions and talks that address the latest developments in cardiovascular disease:

The Genetics of Heart Disease
• A talk by Calum MacRae (Department of Medicine at Brigham and Women’s Hospital and Harvard Medical School) discussing recent discoveries that hold the promise of better detection and treatment of heart disease

Deriving Clinical Insight from Remote Sensors That Capture Cardiovascular Data:
• Geoff Tison (UCSF) chairs this panel, which examines both existing applications of remote sensors that derive actionable clinical insights and the future potential for these tools for precision medicine.
• This panel includes: Michael V. McConnell (Google Health), Gregory M. Marcus (UCSF), and Liviu Klein (UCSF)

Navigating the Challenges of Reimbursement with a Focus on Cardiovascular Disease:
• A panel discussion that focuses on the reimbursement of diagnostic tests, a core component of precision medicine; chaired by John J. Sninsky (Consultant in Translational Sciences)
• This panel includes: Bruce Quinn (Quinn Associates), Susan Xu (Association of American Medical Colleges), Steve Anderson (LabCorp), and Gabriel A. Bien-Willner (Palmetto GBA)

Clonal Hematopoiesis: Linking Age-Related Inflammation to Cardiovascular Disease:
• Siddhartha Jaiswal (Stanford University) discusses the need for biomarkers for the diagnosis, prognosis, and therapeutic monitoring and risk stratification of acute injury and chronic diseases.

Emerging Cardiomyopathy Therapeutics:
• The session covers regulatory approval and clinical trial strategies with a focus on using stem cell therapy, gene therapy, interfering RNA, and small molecules in the area of cardiomyopathy with Marc Semigran (MyoKardia).

Cardiovascular Imaging for a Precision Medicine Future:
• This panel discussion focuses on how machine learning is revolutionizing the potential of imaging for precision medicine highlighting several use cases, as well as bigger challenges such as data security and sharing, models for federated development of machine learning solutions, and the need for shared platforms and tools.
– This panel includes: Rimar Arnaout (UCSF), Carla R. Leibowitz (NVIDIA), Bimba Rao (Siemens Healineers), Michael D. Lesh (UCSF), and Maulik Majmudar (Amazon)

Gut Microbiome and Cardiovascular Diseases:
• This session will focus on newly discovered gut microbial communities and metabolic pathways, including the production of dietary nutrient metabolites and secondary bile acids that appear to participate in the development and progression of cardiometabolic diseases.

Emerging Cardiac Amyloidosis Therapeutics:
• Sandi See Tai (Pfizer) will review two different therapeutic approaches, a gene silencing drug that interferes with specific messenger RNA to block the production of the protein causing cardiac amyloidosis, as well as a small molecule approach.

Cardiovascular Proteomics:
• This session includes talks by Peter Ganz (UCSF) and Steve Williams (Somalogic) discussing recent findings that demonstrate that large-scale measurement of proteins in a single blood test coupled with machine learning can provide important information about our health and can help predict a range of different diseases and risk factors, including the risk for developing type 2 diabetes and cardiovascular disease.

Investment Perspective in Emerging Cardiovascular Therapeutics:
• A panel discussion chaired by Matthias Kleinz (UPMC Enterprises), Nicholas J. Simon (Blackstone) and Abraham Bassan (Samsara BioCapital)n Chair Profile
Emerging Therapeutics Showcase includes a talk by Campbell Rogers of HeartFlow.

Don’t miss out on this timely discussion to learn more about:
• novel approaches to assessing the risk of heart disease, through genetic and proteomic factors;
• new approaches to cardiovascular imaging;
• targeted therapies for cardiac amyloidosis;
• use of remote sensors to diagnose cardiovascular disease broadly in the population; and
• solving the reimbursement challenges that come with new diagnostic tools and therapies.

Register by today for the best rates, see more here: www.pmwcintl.com/registration/