Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction
Open accessAbstract
Heart failure patients are classified by ejection fraction (EF) into distinct groups: heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF). Although patients with heart failure commonly have multiple comorbidities that complicate management and may adversely affect outcomes, their role in the HFpEF and HFrEF groups is not well-characterized. This review summarizes the role of noncardiac comorbidities in patients with HFpEF versus HFrEF, emphasizing prevalence, underlying pathophysiologic mechanisms, and outcomes. Pulmonary disease, diabetes mellitus, anemia, and obesity tend to be more prevalent in HFpEF patients, but renal disease and sleep-disordered breathing burdens are similar. These comorbidities similarly increase morbidity and mortality risk in HFpEF and HFrEF patients. Common pathophysiologic mechanisms include systemic and endomyocardial inflammation with fibrosis. We also discuss implications for clinical care and future HF clinical trial design. The basis for this review was discussions between scientists, clinical trialists, and regulatory representatives at the 10th Global CardioVascular Clinical Trialists Forum.
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Diabetes markedly increases the development, morbidity and mortality of HFpEF.
“Diabetes markedly increases the development, morbidity and mortality of HF with preserved ejection fraction (HFpEF), showing a particularly close link with this clinical entity [14,15].”
From Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes (2022) · cites this paper as [14]
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Prevalence of sleep disordered breathing in diastolic heart failure
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Chronic Kidney Disease and Outcomes in Heart Failure With Preserved Versus Reduced Ejection Fraction
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Diuretics and Ultrafiltration in Acute Decompensated Heart Failure
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Self-citationAdaptive Servoventilation for Treatment of Sleep-Disordered Breathing in Heart Failure
Sharma, B. K., Bakker, J. P., McSharry, D. G., Desai, A. S., Javaheri, S., & Malhotra, A. (2012) · CHEST Journal · doi:10.1378/chest.12-0815 · Cited by 162 · see citing works
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Heart Failure and Chronic Obstructive Pulmonary Disease
Hawkins, N. M., Petrie, M. C., MacDonald, M. R., Jhund, P. S., Fabbri, L. M., Wikstrand, J., & McMurray, J. J. V. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.02.020 · Cited by 143 · see citing works
Aronson, D., & Burger, A. J. (2010) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2010.02.001 · Cited by 138 · see citing works
Increased long-term mortality in heart failure due to sleep apnoea is not yet proven
Roebuck, T., Solin, P., Kaye, D. M., Bergin, P. J., Bailey, M., & Naughton, M. T. (2004) · European Respiratory Journal · doi:10.1183/09031936.04.00060404 · Cited by 138 · see citing works
Blair, J. E. A., Pang, P. S., Schrier, R. W., Metra, M., Traver, B., Cook, T. D., Campia, U., Ambrosy, A. P., Burnett, J. C. J., Grinfeld, L., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr238 · Cited by 133 · see citing works
Self-citationErythropoietin treatment in patients with chronic heart failure: a meta-analysis
van der Meer, P., Groenveld, H. F., Januzzi, J. L., & van Veldhuisen, D. J. (2009) · Heart · doi:10.1136/hrt.2008.161091 · Cited by 130 · see citing works
Sitagliptin Use in Patients With Diabetes and Heart Failure
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Clark, H., Krum, H., & Hopper, I. (2013) · European Journal of Heart Failure · doi:10.1002/ejhf.13 · Cited by 122 · see citing works
Prevalence of anemia and effects on mortality in patients with heart failure
Lindenfeld, J. M. (2005) · American Heart Journal · doi:10.1016/j.ahj.2004.08.039 · Cited by 120 · see citing works
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Relationship between sleep apnoea and mortality in patients with ischaemic heart failure
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Self-citationHsich, E., Grau‐Sepulveda, M. V., Hernandez, A. F., Peterson, E. D., Schwamm, L. H., Bhatt, D. L., & Fonarow, G. C. (2012) · American Heart Journal · doi:10.1016/j.ahj.2011.12.013 · Cited by 110 · see citing works
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Heart failure with preserved left ventricular systolic function: a hospital cohort study
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Anemia in patients with heart failure and preserved systolic function
Felker, G. M., Shaw, L. K., Stough, W. G., & O’Connor, C. M. (2006) · American Heart Journal · doi:10.1016/j.ahj.2005.03.056 · Cited by 99 · see citing works
Self-citationMentz, R. J., Schulte, P. J., Fleg, J. L., Fiuzat, M., Kraus, W. E., Piña, I. L., Keteyian, S. J., Kitzman, D. W., Whellan, D. J., Ellis, S. J., et al. (2012) · American Heart Journal · doi:10.1016/j.ahj.2012.10.029 · Cited by 96 · see citing works
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The prevalence of anemia in chronic heart failure and its impact on the clinical outcomes
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Mentz, R. J., WOJDYLA, D. M., Fiuzat, M., et al. (2012) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2012.10.041 · Cited by 87 · see citing works
Self-citationScrutinio, D., Passantino, A., Santoro, D., & Catanzaro, R. (2010) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfq167 · Cited by 79 · see citing works
Diabetes and the Risk of Heart Failure
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Noncardiac Comorbidities and Acute Heart Failure Patients
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Sleep Disordered Breathing in Heart Failure Patients with Reduced versus Preserved Ejection Fraction
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Metabolic Syndrome and Heart Failure—The Risk, Paradox, and Treatment
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Learning from recent trials and shaping the future of acute heart failure trials
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Bronchodilators in Heart Failure Patients With COPD: Is It Time for a Clinical Trial?
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Self-citationThe Cardiorenal Syndrome: What the Cardiologist Needs to Know
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Epidemiology of Cardiorenal Syndrome
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Self-citationAtrial Fibrillation and Heart Failure: A Bad Combination
Lau, Y. C., Lane, D. A., & Lip, G. Y. H. (2014) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2014.01.002 · Cited by 16 · see citing works
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- [109]Kasai T Bradley TD Obstructive sleep apnea and heart failure: pathophysiologic and therapeutic implications J Am Coll Cardiol 2011 57 119 27 21211682
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2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure
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Evaluation and management of heart failure with preserved ejection fraction
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Self-citationPatient selection in heart failure with preserved ejection fraction clinical trials
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Follistatin like 1 regulates hypertrophy in heart failure with preserved ejection fraction
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De Marco, C., Claggett, B. L., de Denus, S., Zile, M. R., Huynh, T., Desai, A. S., Sirois, M. G., Solomon, S. D., Pitt, B., Rouleau, J. L., et al. (2021) · ESC Heart Failure · doi:10.1002/ehf2.13153 · Cited by 29 · see citing works
Self-citation
- Authors
- Mentz, R. J., Kelly, J. P., von Lueder, T. G., Voors, A. A., Lam, C. S. P., Cowie, M. R., Kjeldsen, K., Jankowska, E. A., Atar, D., Butler, J., Fiuzat, M., Zannad, F., Pitt, B., & O’Connor, C. M.
- Affiliations
- Duke University (US)
- University of Groningen (NL)
- Boston University (US)
- Copenhagen University Hospital (DK)
- Wroclaw Medical University (PL)
- Oslo University Hospital (NO)
- Emory University (US)
- Inserm (FR)
- University of Michigan (US)
- Corresponding author
- Mentz, Robert J.
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 64
- Issue
- 21
- Pages
- 2281-2293
- ISSN
- 0735-1097 (ISSN-L)
- PMC
- PMC4254505
- OpenAlex
- W2093350841
- Cited by
- 546
- References
- 128
- Citations by year
- 2026: 20 · 2025: 34 · 2024: 49 · 2023: 35 · 2022: 56 · 2021: 41 · 2020: 75 · 2019: 50 · 2018: 64 · 2017: 47 · 2016: 45 · 2015: 30
- FWCI
- 6.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- PubMed Central (acceptedVersion)
- VBN Forskningsportal (Aalborg Universitet) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Pfizer
- AstraZeneca
- Alere
- University of Pittsburgh
- Celladon Corporation
- ResMed
- National Institute for Health and Care Research
- European Commission
- Bayer HealthCare
- Vifor Pharma
- Uniwersytet Medyczny im. Piastów Slaskich we Wroclawiu
- Servier
- National Institutes of Health
- Health Resources and Services Administration
- National Institute of General Medical Sciences (T32GM086330)
- 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 › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
- Keywords
- heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, lung disease, diabetes mellitus, anemia, obesity, kidney disease, sleep-disordered breathing, inflammation, myocardial fibrosis, morbidity and mortality risk, clinical trial design
- MeSH terms
- Age Factors, Anemia, Arthritis, Diabetes Mellitus, Heart Failure, Humans, Kidney Diseases, Obesity, Sex Factors, Sleep Apnea Syndromes, Stroke Volume, Comorbidity, Pulmonary Disease, Chronic Obstructive, Racial Groups, Mobility Limitation
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