Heart Failure with Preserved Ejection Fraction: A Therapeutic Brick Wall

Sponsored by: Covance

Focused on:

  • Heart Failure

Date: 1 November


Time: 3PM London/11AM New York

Tailoring Mechanisms of Action to Disease Phenotypes

Originally termed "diastolic heart failure" or "stiff heart syndrome", what is currently termed heart failure with preserved ejection fraction (HFpEF) is believed to account for at least 50% of heart failure cases in Western countries and the incidence appears to be growing. Despite this epidemic, no pharmacologic treatments have demonstrated clear clinical benefits and none have been approved for marketing. While smaller studies looking at surrogate biomarkers have suggested efficacy, all large scale outcome trials have been negative. The reason may be that HFpEF is a syndrome comprised of multiple, heterogeneous disease processes. Thus, appropriate treatment may require matching pharmacologic mechanisms of action to disease pathophysiology.

In this webinar we will present the pathophysiologies of HFpEF, history of therapeutic trials and suggest targeted approaches that are likely to better secure therapeutic success in drug development.

Presentation 1. What Exactly is HFpEF and What Have We Learned About it in the Past 40 Years?

In this discussion, Dr. Plehn will review the almost 40 year history of HFpEF research, the approaches to diagnosis of the disease and the various underlying processes leading to the clinical syndrome. Potential targets for novel pharmacologic approaches will be described as well and early surrogate metrics predictive of clinical success will be reviewed.

Presentation 2. Approaching HFpEF in the Era of Precision Medicine

Dr. Shah will focus upon the heterogeneous etiology of the HFpEF syndrome and how focused targeting of selected populations based upon a molecule's mechanism of action may improve the results of HFpEF drug development. Study design determined by potential outcome benefits most appropriate to this population will be addressed.

In this webinar we will review the possible causes of unrelenting failure in HFpEF drug development and suggest new approaches more likely to garner success. This is a wide-open field of opportunity which must be approached with eyes wide open. We look forward to sharing our vision with you at this webinar!

Presented by

Jonathan Plehn, MD, FACC,

Vice President, Cardiovascular Medicine, Covance Clinical Professor of Medicine, Drexel University School of Medicine

Dr. Jonathan Plehn joined Covance in 2008 following 25 years in academic medicine. Prior to joining Covance, he served as a principal investigator in the Translational Medicine Branch of the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) and as a medical officer in the cardiovascular division of the National Naval Medical Center, both in Bethesda, Maryland. He directed heart failure programs at both of these institutions as well as the George Washington University Medical Center.

Dr. Plehn has a wide range of clinical research experience ranging from early epidemiologic work at the Framingham Heart Study to therapeutic trial experience in the areas of hypertension, congestive heart failure and the design and management of cardiovascular outcomes trials. He is an expert in cardiac imaging and has directed core laboratories for multicenter trials. He is a Clinical Professor of Medicine at the Drexel University School of Medicine in Philadelphia.

Sanjiv Shah,

Professor of Medicine and Director of the T1 Center for Cardiovascular Therapeutics, Northwester University Feinberg School of Medicine

Dr. Shah is Professor of Medicine and Director of the T1 Center for Cardiovascular Therapeutics at Northwestern University Feinberg School of Medicine. Dr. Shah is also
Director of the Heart Failure with Preserved Ejection Fraction (HFpEF) Program at Northwestern Memorial Hospital in Chicago, Illinois, USA.

Dr. Shah's research interests include understanding the epidemiology, mechanisms, and treatment of HFpEF. Dr. Shah started the first dedicated HFpEF clinical program at Northwestern University in 2007, and has been a leading enroller in clinical trials for HFpEF since that time. Dr. Shah's research interests also include the study of acquired and genetic risk factors for abnormal cardiac mechanics, and novel machine learning techniques for improved classification and therapeutic targeting of heart failure syndromes.

Dr. Shah's research is currently funded by 2 NIH R01 grants and a Strategically Focused Research Network (SFRN) grant from the American Heart Association. Dr. Shah is also a steering committee member for 8 ongoing international heart failure clinical trials, and is principal investigator of 3 of those trials. Dr. Shah has published over 250 original papers, abstracts, book chapters, and review articles. His work has been published in high-impact journals including the New England Journal of Medicine, JAMA, Lancet, Circulation, and the Journal of the American College of Cardiology. He is the editor of a textbook entitled, "Cardiovascular Genetics and Genomics in Clinical Practice", and he is an Associate Editor for JAMA Cardiology. He has also received several teaching awards throughout his career, including the W. Proctor Harvey Teaching Award from the American College of Cardiology.

Key Learning Objectives

  • To understand the definition and pathophysiology of heart failure with preserved ejection fraction (HFpEF)
  • To learn the historical background of research into the syndrome
  • To understand the challenges confronting development of treatment modalities
  • Developing trial designs that include deep population phenotyping and appropriate therapeutic endpoints


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