Uncovering Unrecognized Heart Failure With Preserved Ejection Fraction Among Individuals With Obesity and Dyspnea
Open accessAbstract
BACKGROUND: Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. HFpEF diagnosis is particularly challenging in the setting of obesity given the limitations of natriuretic peptides and resting echocardiography. We examined invasive and noninvasive HFpEF diagnostic criteria among individuals with obesity and dyspnea without known cardiovascular disease to determine the prevalence of hemodynamic HFpEF in the community. METHODS: Research volunteers with dyspnea and obesity underwent resting echocardiography; participants with possible pulmonary hypertension qualified for invasive cardiopulmonary exercise testing. HFpEF was defined using rest or exercise pulmonary capillary wedge pressure criteria (≥15 mm Hg or Δpulmonary capillary wedge pressure/Δcardiac output slope, >2.0 mm Hg·L −1 ·min − 1). RESULTS: Among n=78 participants (age, 53±13 years; 65% women; body mass index, 37.3±6.8 kg/m 2 ), 40 (51%) met echocardiographic criteria to undergo invasive cardiopulmonary exercise testing. In total, 24 participants (60% among the cardiopulmonary exercise testing group, 31% among the total sample) were diagnosed with HFpEF by rest or exercise pulmonary capillary wedge pressure (n=12) or exercise criteria (n=12). There were no differences in NT-proBNP (N-terminal pro-B-type natriuretic peptide; 79 [62–104] versus 73 [57–121] pg/mL) or resting echocardiography (mitral E/e′ ratio, 9.1±3.1 versus 8.0±2.7) among those with versus without HFpEF ( P >0.05 for all). Distributions of HFpEF diagnostic scores were similar, with the majority classified as intermediate risk (100% versus 93.75% [H 2 FPEF] and 87.5% versus 68.75% [HFA-PEFF (Heart Failure Association Pretest assessment, echocardiography and natriuretic peptide, functional testing, and final etiology)] in those with versus without HFpEF). CONCLUSIONS: Among adults with obesity and dyspnea without known cardiovascular disease, at least a third had clinically unrecognized HFpEF uncovered on invasive cardiopulmonary exercise testing. Clinical, biomarker, resting echocardiography, and diagnostic scores were similar among those with and without HFpEF. These results suggest clinical underdiagnosis of HFpEF among individuals with obesity and dyspnea and highlight limitations of noninvasive testing in the identification of HFpEF.
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In patients with HFpEF and obesity, a large proportion have circulating NT-proBNP levels in the normal range or lower than those used to qualify patients for large-scale HFpEF trials.
“A large proportion of patients with HFpEF and obesity have circulating levels of NT-proBNP in the normal range33–35 or lower than those that have been used to qualify patients for participation in large-scale HFpEF trials.”
From Effects of Tirzepatide on the Clinical Trajectory of Patients With Heart Failure, Preserved Ejection Fraction, and Obesity (2025) · cites this paper as [33]
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Research works printed but not linked: 2
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Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity
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Zile, M. R., Borlaug, B. A., Kramer, C. M., Baum, S. J., Litwin, S. E., Menon, V., Ou, Y., Weerakkody, G. J., Hurt, K. C., Kanu, C., et al. (2025) · Circulation · doi:10.1161/circulationaha.124.072679 · Cited by 74 · see citing works
- Authors
- Kosyakovsky, L. B., Liu, E. E., Wang, J. K., Myers, L., Parekh, J. K., Knauss, H., Lewis, G. D., Malhotra, R., Nayor, M., Robbins, J. M., Gerszten, R. E., Hamburg, N. M., McNeill, J. N., Lau, E. S., & Ho, J. E.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Massachusetts General Hospital (US)
- Boston University (US)
- Duke University (US)
- ORCID
- Venue
- Circulation: Heart Failure
- Published
- 2024-05
- Volume
- 17
- Issue
- 5
- Pages
- e011366-e011366
- ISSN
- 1941-3289 (ISSN-L)
- 1941-3297
- PMC
- PMC11214582
- OpenAlex
- W4396896680
- Cited by
- 43
- References
- 37
- Citations by year
- 2026: 18 · 2025: 20 · 2024: 5
- FWCI
- 12.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Heart Failure (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL140224, R01HL134893, K23HL150327, K24HL153669, R01HL168889, R01HL160003, T32HL160522, K23HL159243)
- 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, obesity, dyspnea, pulmonary capillary wedge pressure, cardiopulmonary exercise testing, resting echocardiography, NT-proBNP, underdiagnosis, prevalence, natriuretic peptides, E/e' ratio, pulmonary hypertension
- MeSH terms
- Adult, Aged, Dyspnea, Echocardiography, Exercise Test, Female, Heart Failure, Humans, Male, Middle Aged, Obesity, Peptide Fragments, Pulmonary Wedge Pressure, Stroke Volume, Biomarkers, Prevalence, Ventricular Function, Left, Natriuretic Peptide, Brain
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