The Johns Hopkins’ Center for Heart Failure with Preserved Ejection Fraction (HFpEF) provides specialized care for patients diagnosed with this form of heart failure through education, research, and a comprehensive approach to heart failure management.
Heart failure with preserved ejection fraction (HFpEF) is a common, debilitating syndrome which accounts for nearly half of the 6.6 million cases of heart failure in the U.S. yearly and is known to cause nearly 50 % of all hospitalizations for heart failure (HF) in the U.S. It is associated with a high mortality rate of over 50 % at 5 years after hospitalization.
Ejection fraction is a measurement that determines how well your heart pumps blood. It is usually expressed as a percentage and is used to properly diagnose and treat heart failure.
In HFpEF, the main pumping chamber of the heart (left ventricle) is able to contract/pump relatively normally (normal ejection fraction); however, it is unable to relax normally between each heartbeat. This can result in the development of higher pressure within the left ventricle as the blood fills the left ventricle between each beat.
There are a number of clinical and translational research projects ongoing in the Johns Hopkins HFpEF Center that range from studies to investigate mechanisms of disease, to multi-center treatment trials for HFpEF.
- AHA Go Red For Women Network Grant Studies:
- Heart Failure with Preserved EF: Female sex-hormones and cyclic GMP-PKG Modulation of Cardiac Disease and metabolism
- Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction (PARAGON-HF), NCT01920711
- In Vivo Cardiac and Skeletal Muscle Metabolism in Heart Failure with Preserved Ejection Fraction Patients During Rest and Plantar Flexion Exercise
- Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF (INDIE-HFpEF), NCT02742129
- AHA Go Red For Women Network Grant Studies:
The Johns Hopkins HFpEF Center is proud to been one of 5 named AHA Go Red for Women Networks. The objective of the network is to understand the basis for sex differences in development and prevalence of HFpEF. Some of these differences include:
- Sixty percent of patients with HFpEF are women, typically post-menopausal women.
- Women with HFpEF have differences in cardiac structure/function and certain biochemical markers compared to men.
- Animal models suggest that sex differences in biochemical pathways in heart muscle (cyclic guanosine monophosphate - protein kinase G (cGMP-PKG) signaling) may be critical.
- Loss of estrogen at menopause can affect some of these pathways which may have broad adverse effects in the heart, fat tissue, and skeletal muscle.
The AHA Go Red for Women Network aims to better understand and develop personalized approaches for the prevention and management of HFpEF in the following ways:
- Test if the sex bias in HFpEF results from post-menopausal changes by studying the effects of sex hormones on biochemical pathways (cGMP-PKG) that are involved in HFpEF.
- Train a new generation of researchers in translational approaches that consider sex difference in the study of disease states.
- Participate in the national AHA Go Red for Women’s Research Network activities to foster collaboration among researchers from the member institutions.
The Basic Science Project aims to improve targeting of cGMP- PKG HFpEF therapy to circumvent estrogen deficiency.
- Significance: By focusing on sex-hormone dependent biology, we hope to identify novel treatments for HFpEF and improve the possibility to better match therapy for HFpEF to individual patient characteristics
- Innovation: We are exploring novel biochemical pathways that are involved in heart muscle in HFpEF
- Impact: Our goal is to develop female hormone-independent strategies to better personalize treatment of post-menopausal women
The Clinical Science Project focuses on developing a deeper understanding of the way the heart, blood vessels and skeletal muscle function in patients with HFpEF, and to conduct small clinical trials to dissect the role of sex hormones and their influence on the biochemical pathways involving cGMP-PKG in patients with HFpEF. These studies will be conducted at Johns Hopkins Hospital, Hopkins Bayview Medical Center and at Northwestern University Hospital.
- Significance: Studies could lead to novel therapeutic approaches for HFpEF in women that leverage our knowledge of these biochemical pathways
- Innovation: We are conducting novel assessment of heart and skeletal muscle in HFpEF. The clinical studies will explore the effects of new therapies targeted at these biochemical pathways
- Impact: This study looks at whether developing a greater understanding of the biology of sex differences may allow improved understanding of the pathology of HFpEF and provide novel insights into treatments in cardiovascular disease
The Population Science Project will use data obtained in three large studies of individuals who were initially without heart disease and who have been followed for decades. This research will study the role of sex hormones, oxidative stress, and cGMP in the development of HFpEF over the long term follow up of these populations.
- Significance: This will study sex differences and mechanisms leading to subclinical HFpEF in a broad population who have been followed over the span of the adult life course including menopausal transition
- Innovation: The biochemical pathways of interest (cGMP) have not previously studied in population cohorts, nor have they been studied as a sex hormone-related pathway to HFpEF
- Impact: The studies are a first step in identifying potential interventions and treatment targets that we hope may lead to more personalized approaches to treating individuals with HFpEF