Heart Failure With Preserved Ejection Fraction: Mechanisms, Clinical Features, and Therapies
Open accessAbstract
The clinical syndrome comprising heart failure (HF) symptoms but with a left ventricular ejection fraction (EF) that is not diminished, eg, HF with preserved EF, is increasingly the predominant form of HF in the developed world, and soon to reach epidemic proportions. It remains among the most challenging of clinical syndromes for the practicing clinician and scientist alike, with a multitude of proposed mechanisms involving the heart and other organs and complex interplay with common comorbidities. Importantly, its morbidity and mortality are on par with HF with reduced EF, and as the list of failed treatments continues to grow, HF with preserved EF clearly represents a major unmet medical need. The field is greatly in need of a more unified approach to its definition and view of the syndrome that engages integrative and reserve pathophysiology beyond that related to the heart alone. We need to reflect on prior treatment failures and the message this is providing, and redirect our approaches likely with a paradigm shift in how the disease is viewed. Success will require interactions between clinicians, translational researchers, and basic physiologists. Here, we review recent translational and clinical research into HF with preserved EF and give perspectives on its evolving demographics and epidemiology, the role of multiorgan deficiencies, potential mechanisms that involve the heart and other organs, clinical trials, and future directions.
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Cardiac myocyte hypertrophy and cardiac fibrosis are markedly prevalent in patients with HFpEF, as confirmed in a large, prospective analysis of HFpEF myocardial tissue.
“Two pathological characteristics markedly prevalent in patients with HFpEF are cardiac myocyte hypertrophy and cardiac fibrosis, as confirmed in a large, prospective analysis of HFpEF myocardial tissue.8,9”
From Reversal of contractile defects by mediating calcium homeostasis in human mini-heart models of heart failure with preserved ejection fraction (HFpEF) leads to first-in-human gene therapy clinical trial (2024) · cites this paper as [9]
The Myocardial Abnormalities section reports increased collagen in HFpEF endomyocardial biopsy tissue, supporting the fibrosis finding. The Epidemiology section describes hypertrophied hearts, but the copy does not establish that cardiac myocyte hypertrophy and fibrosis were both confirmed in a large, prospective analysis of HFpEF myocardial tissue. Page numbers are unavailable in the indexed copy. (LLM, conf=0.85)
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Mechanisms of atrial fibrillation in aged rats with heart failure with preserved ejection fraction
Mesquita, T., Zhang, R., de Couto, G., Valle, J., Sanchez, L., Rogers, R. G., Holm, K., Liu, W., Marbán, E., & Cingolani, E. (2020) · Heart Rhythm · doi:10.1016/j.hrthm.2020.02.007 · Cited by 62 · see citing works
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Heart Failure with Preserved Ejection Fraction—a Concise Review
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Therapeutic potential of resveratrol in heart failure
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Inflammation in HFpEF: Key or circumstantial?
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Pathophysiology and the Monitoring Methods for Cardiac Arrest Associated Brain Injury
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Nampt Potentiates Antioxidant Defense in Diabetic Cardiomyopathy
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Basigin Promotes Cardiac Fibrosis and Failure in Response to Chronic Pressure Overload in Mice
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Macrophage-based therapeutic approaches for cardiovascular diseases
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- Authors
- Sharma, K., & Kass, D. A.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Circulation Research
- Published
- 2014-06-20
- Volume
- 115
- Issue
- 1
- Pages
- 79-96
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC4146618
- OpenAlex
- W2527933700
- Cited by
- 508
- References
- 178
- Citations by year
- 2026: 21 · 2025: 21 · 2024: 42 · 2023: 31 · 2022: 36 · 2021: 48 · 2020: 53 · 2019: 44 · 2018: 53 · 2017: 63 · 2016: 42 · 2015: 43 · 2014: 10
- FWCI
- 8.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL114910, P01HL077180, R01HL119012, HL-077180, HL-119012, HL114910, T32HL007227)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- heart failure with preserved ejection fraction, left ventricular ejection fraction, heart failure pathophysiology, multiple organ failure, heart failure epidemiology, translational research, clinical trials, unmet medical needs
- MeSH terms
- Diastole, Energy Metabolism, Exercise Therapy, Heart Failure, Humans, Hypertension, Pulmonary, Inflammation, Stroke Volume, Systole, Ventricular Function, Left, Cyclic GMP-Dependent Protein Kinases, Muscle, Skeletal
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