Description
HFpEF is a major public health problem that is rising in prevalence with the aging population and the ongoing epidemics of obesity, diabetes, and hypertension. HFpEF accounts for nearly half of all heart failure (HF) cases with a prevalence of at least 3 million in the U.S. alone and may be under-diagnosed in the general population. Whereas HFpEF was previously termed “diastolic HF”, it is now well known that HFpEF is a multi-organ, systemic syndrome that involves multiple pathophysiologic abnormalities beyond left ventricular diastolic dysfunction. HFpEF is associated with high morbidity and mortality. After HF hospitalization, the 5-year survival of HFpEF is a dismal 35%, which is worse than most cancers. In addition, quality of life in HFpEF is as poor or worse than HF with reduced ejection fraction (HFrEF) and is associated with physical activity levels that are similar to moderate-to-severe chronic obstructive pulmonary disease.
There are currently no effective therapies for HFpEFas most current therapies for HFrEF have been demonstrated to be ineffective for HFpEF. Recent studies have highlighted both the systemic nature of the HFpEF syndrome and the presence of “sub-phenotypes” within the heterogeneous HFpEF syndrome, highlighting the potential need for better-targeted therapies to specific HFpEF subtypes as a way to improve the track record of HFpEF clinical trials. Furthermore, while myocardial fibrosis, abnormal cardiomyocyte calcium handling, increased passive myocardial stiffness due to altered titin phosphorylation states, impaired cGMP-protein kinase G activity, cardiac and extracardiac metabolic derangements, and other mechanistic hypotheses have been implicated in HFpEF, basic science studies have been limited both by the heterogeneity of human HFpEF and by frequently equating diastolic dysfunction alone with the HFpEF syndrome, with a consequent lack of accepted animal models. Finally, because HFpEF is difficult to treat and carries a poor prognosis once it presents as overt volume overload requiring hospitalization, preventing HFpEF and limiting disease progression is critical.
Participating Division:
Division of Cardiovascular Sciences
Staff contacts:
- Bishow Adhikari, PhD, Bishow.Adhikari@nih.gov, 301-435-0504
- Patrice Desvigne-Nickens, MD, Patrice.Desgivne-Nickens@nih.gov, 301-435-0504
Working Group Members:
Chair:
- Sanjiv Shah, MD, Northwestern University
Session leaders:
- Barry Borlaug, MD, Mayo Clinic
- Burns Blaxall, PhD, Cincinnati Children’s Hospital Medical Center
- Andrew McCulloch, PhD, University of California San Diego
- Dalane Kitzman, MD, Wake Forest School of Medicine
Members:
- Rajiv Agarwal, MD, Indiana University School of Medicine
- Julio Chirinos, MD, PhD, University of Pennsylvania
- Sheila Collins, PhD, Sanford Burnham Prebys Medical Discovery Institute
- Rahul Deo, MD, PhD, University of California San Francisco
- Mark Gladwin, MD, University of Pittsburg School of Medicine
- Henk Granzier, PhD, University of Arizona
- Scott Hummel, MD, University of Michigan
- David Kass, MD, The Johns Hopkins Medical Institutions
- Maggie Redfield, MD, Mayo Clinic
- Flora Sam, MD, Boston University School of Medicine
- Thomas Wang, MD, Vanderbilt University Medical Center
NHLBI Staff:
- Ravi Balijepalli, PhD
- Jerome Fleg, MD
- Vandana Sachdev, MD
- Pothur Srinivas, MPH, PhD
- Emily Tinsley, MS
- Renee Wong, PhD