KEY TERMS
HEART FAILURE
This refers to a condition in which the heart muscle cannot pump enough blood or pump blood effectively to the rest of the body to meet the body’s needs. It can take years to develop and often develops as a result of other conditions such as other heart conditions (e.g. heart attack, valve disease), diabetes, obesity, and drugs. Heart failure is one of the most common reasons older adults are admitted to hospital. For more information you can visit the HFSA Patient Hub or the AAHFN Patient Resources.
This refers to a syndrome of multisystem physiological decline and increased vulnerability to stressors such as hospitalization. Using the physical frailty phenotype definition, the manifestations are unintentional weight loss (or loss of muscle mass), weakness, slowness, physical exhaustion, and low physical activity. Even though frailty is associated with older age, it can affect anyone across the lifespan. In heart failure, it affects about 1 out of every 2 patients. You can learn more about frailty through the Johns Hopkins University Frailty Science resource.
FRAILTY (OR PHYSICAL FRAILTY)
SYMPTOMS
This refers to what the patient perceives as an indicator of something going on in the body; sometimes this can be a noticeable acute change (e.g. sudden sharp pain) or sometimes it can be gradual (e.g. fatigue). Symptoms can be physical (e.g. shortness of breath, chest pain) or they can be affective/psychological (e.g. depression, anxiety). Often times, they “cluster” together meaning that if you have one symptom, you may be more likely to have another symptom. Symptoms are incredibly important because not only do they tell us that something is going on in the body, but they also affect quality of life. You can read more about symptoms in cardiovascular disease in this American Heart Association Scientific Statement.
ONGOING STUDIES
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Biological and Physiological Mechanisms of Symptom Clusters in Heart Failure (BIOMES-HF) Study
(2021-2026)
In this cohort study (n = 231), we are examining how symptoms change after a hospitalization for heart failure and working to understand how markers in the blood and levels of frailty affect how symptoms change. Our protocol paper was published in the Journal of Cardiac Failure, and we have had multiple subsequent follow-up papers published in the Journal of Cardiac Failure, the Journal of Cardiovascular Nursing, and JACC: Advances. This study is closed to enrollment, and our primary aim results will be forthcoming.
Funded by the NIH/National Institute of Nursing Research (R01NR019054).
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Physical Frailty and Symptom Monitoring and Management Behaviors in Heart Failure (PRISM-HF) Study
(2023-2025)
In this cohort study (n = 128), we are examining how physical frailty affects self-care behaviors in heart failure, particularly how patients monitor and manage their symptoms. Our protocol paper was published in International Journal of Nursing Studies: Advances, and we published a review paper in the Journal of Nutrition, Health, and Aging.
This study is closed to enrollment, and our primary aim results will be forthcoming.
Funded by the NIH/National Institute of Nursing Research (R21NR020059).
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Identifying Predictors of Frailty Among Women with Cardiovascular Disease: An Application of the Women’s Health Across the Lifespan Framework Study
(2024-2025)
For this project, we conducted a secondary analysis of data from a large national dataset called the National Health and Aging Trends Study (NHATS) to identify factors associated with frailty in older adults with cardiovascular disease, including if they are different between women and men. We are also seeking focus group feedback from older women with cardiovascular disease on our recently developed theory on women’s health across the lifespan and how this theory might help advance our understanding of older women’s heart health. The focus groups are open for enrollment.
Funded by the OHSU Hartford Award for Research and Practice.
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Biological and Physiological Mechanisms of Symptom Clusters in Methamphetamine-Associated Heart Failure (BIOMES-MethHF) Study
(2025-2026)
In this small ancillary study to our larger BIOMES-HF study, we are examining symptoms, biomarkers, social factors, and frailty in patients who have methamphetamine-associated heart failure and are still using methamphetamine. This study is open for enrollment.
Funded by the Sanjiv and Cindy T. Kaul Foundation.
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Characterizing Social Factors and Post-Hospitalization Sleep in Heart Failure
(2025-2026)
In this pilot study (sample size goal n = 40), we are examining how social factors (e.g. loneliness, social isolation) are related to heart failure symptoms. We are also looking at how patients are sleeping after heart failure hospitalization using devices that collect sleep data from the patient’s bedside. This study will be open for enrollment soon.
Funded by the Medical Research Foundation.
COMPLETED STUDIES
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Symptom Biology and Accelerated Aging in Heart Failure (SPEED-HF) Study
(2015-2016)
In this small study (n = 49), which was part of Dr. Denfeld’s dissertation in the lab of Dr. Chris Lee, we examined how physical frailty is associated with both the “numbers” from a right heart catheterization procedure and the symptoms that patients experience. We found that those who are physically frail have higher heart rates and lower output from the heart, and they are more short of breath, more depressed, and have more sleep problems.
You can read more about these studies in the American Journal of Cardiology and the Journal of Cardiovascular Nursing. We also examined how markers of sympathetic activation that are measured in the blood are linked with physical symptoms in HF, which was published in Heart and Lung.
Funded by the NIH/National Institute of Nursing Research (F31NR015936).
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Sympathetic Markers of Quality of Life in Left Ventricular Assist Device Study
(2016-2017)
This small study was part of Dr. Denfeld’s post-doctoral fellowship in the lab of Dr. Beth Habecker. This was a secondary analysis of data from a previously completed study (R01NR013492; PI: Lee), and we examined how markers of sympathetic function are linked with quality of life in patients who were implanted with a support device called a left ventricular assist device. Sympathetic markers, such as adrenaline and noradrenaline, are increased when we are in a “fight or flight” mode, but sometimes these can stay high for a long time and cause more problems. We found that those patients who had worse quality of life after implantation had persistently high levels of these markers.
You can read more about these results in the Journal of Cardiovascular Nursing and the methodology in BMC Research Notes.
Funded by the NIH/National Heart, Lung, and Blood Institute (T32HL094294).
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Gender-Associated Differences in Physical Frailty Phenotypes in Heart Failure (GAP-FRAIL-HF) Study
(2018-2020)
In this study (n = 115), we explored how physical frailty presents in women vs. men with heart failure. We found that physical frailty affects women significantly more than men and that the factors and outcomes associated with frailty may be different between women and men. We also found that physical frailty may be linked with markers in the blood that reflect breakdown of the skeletal muscle and increased fat tissue. The results of this study were published in Circulation: Heart Failure, European Journal of Cardiovascular Nursing, Journal of Cardiac Failure, and Heart & Lung.
Funded by the NIH/Office of Research in Women’s Health and the NIH/Eunice Kennedy Shriver National of Child Health and Human Development (K12HD043488) and Sigma Theta Tau Beta Psi Chapter Naomi Ballard Research Award.
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Proteomic Biomarkers of Physical Frailty in Heart Failure (PRO-FRAIL-HF) Study
(2020-2022)
In this secondary analysis of a subset of the GAP-FRAIL-HF Study (n = 40), we explored how small proteins in the blood are associated with physical frailty. Working with the Pacific Northwest National Laboratory in Richland, WA, we used an approach called proteomics to identify small proteins in the blood that were either higher or lower in frail patients with heart failure compared with non-frail patients. We found markers related to the immune system, growth factors, and stress response associated with frailty. The results of this work were published in BMC Cardiovascular Disorders.
Funded by the Medical Research Foundation.
FUNDING / GRANT ACKNOWLEDGEMENTS
Our lab has been fortunate to have received funding from multiple sources, including through the NIH and several foundations, and support through interdisciplinary mentorship and collaborations:
F31NR015936 (PI/Pre-Doctoral Scholar: Denfeld; Mentors: Lee, Mudd, Winters-Stone, and Hasan)
T32HL094294 (Post-Doctoral Scholar: Denfeld; Training Grant PI: Thornburg/Alkayed; Mentors: Habecker, Alkayed, Lee, and David)
K12HD043488 (PI/Career Development Scholar: Denfeld; Career Development Grant PI: Guise; Mentors: Habecker, Lee, Winters-Stone, and Purnell)
R01NR019054 (PI: Denfeld; Co-Is: Lee, Dieckmann, Camacho, and Habecker)
R21NR020059 (PI: Denfeld; Co-Is: Hansen, Dieckmann, Camacho, and Chien; Consultants: Riegel and Lee)
Achievement Rewards for College Scientists (PI: Denfeld)
Medical Research Foundation (PI: Denfeld)
Sigma Theta Tau (PI: Denfeld)
Hartford Award for Research & Practice (MPI: Roberts Davis & Denfeld; Co-I: Song; Consultant: Bidwell)