Central and peripheral determinants of exercise capacity in heart failure patients with preserved ejection fraction
Open accessAbstract
Objectives This study sought to discern which central (e.g., heart rate, stroke volume [SV], filling pressure) and peripheral factors (e.g., oxygen use by skeletal muscle, body mass index [BMI]) during exercise were most strongly associated with the presence of heart failure and preserved ejection fraction (HFpEF) as compared with healthy control subjects exercising at the same workload.Background The underlying mechanisms limiting exercise capacity in patients with HFpEF are not fully understood.Methods In patients with HFpEF (n = 108), the hemodynamic response at peak exercise was measured using right-sided heart catheterization and was compared with that in healthy control subjects (n = 42) at matched workloads to reveal hemodynamic differences that were not attributable to the workload performed. The patients studied were prospectively included in the REDUCE-LAP HF (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trials and HemReX (Effect of Age on the Hemodynamic Response During Rest and Exercise in Healthy Humans) study. Univariable and multivariable logistic regression models were used to analyze variables associated with HFpEF versus control subjects.Results Compared with healthy control subjects, pulmonary capillary wedge pressure (PCWP) and SV were the only independent hemodynamic variables that were associated with HFpEF, a finding explaining 66% (p < 0.0001) of the difference between the groups. When relevant baseline characteristics were added to the base model, only BMI emerged as an additional independent variable, in total explaining of 90% of the differences between groups (p < 0.0001): PCWP (47%), BMI (31%), and SV (12%).Conclusions The study identified 3 key variables (PCWP, BMI, and SV) that independently correlate with the presence of patients with HFpEF compared with healthy control subjects exercising at the same workload. Therapies that decrease left-sided heart filling pressures could improve exercise capacity and possibly prognosis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Exercise intolerance is due to a combination of central factors such as heart rate and stroke volume as well as peripheral factors including skeletal muscle structure and function.
“Exercise intolerance is due to a combination of central factors such as heart rate and stroke volume as well as peripheral factors including skeletal muscle structure and function (Figure 2 ), 32 , 33 , 34”
From Prioritizing symptom management in the treatment of chronic heart failure (2020) · cites this paper as [33]
The Introduction (page unavailable) identifies heart rate and stroke volume as central factors and skeletal-muscle oxygen utilization as a peripheral factor in HFpEF exercise intolerance. The Exercise-limiting factors section also suggests reduced skeletal-muscle oxygen extraction may contribute. The copy does not establish a role for skeletal-muscle structure, and it describes the mechanisms as incompletely understood rather than definitively explaining exercise intolerance. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
McDonagh, T. A., Metra, M., Adamo, M., Gardner, R. S., Baumbach, A., Böhm, M., Burri, H., Butler, J., Čelutkienė, J., Chioncel, O. D., et al. (2021) · PubMed · doi:10.1093/eurheartj/ehab670 · Cited by 19,618 · see citing works
Self-citation2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure
Ponikowski, P., Voors, A. A., Anker, S. D., Bueno, H., Cleland, J. G. F., Coats, A. J. S., Falk, V., González-Juanatey, J. R., Harjola, V.-P., Jankowska, E. A., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw128 · Cited by 11,429 · see citing works
Self-citationObokata, M., Reddy, Y. N. V., Pislaru, S. V., Melenovsky, V., & Borlaug, B. A. (2017) · Circulation · doi:10.1161/circulationaha.116.026807 · Cited by 1,179 · see citing works
Self-citationThe dominance analysis approach for comparing predictors in multiple regression.
Azen, R., & Budescu, D. V. (2003) · Psychological Methods · doi:10.1037/1082-989x.8.2.129 · Cited by 1,095 · see citing works
Kitzman, D. W., Brubaker, P., Morgan, T., Haykowsky, M., Hundley, G., Kraus, W. E., Eggebeen, J., & Nicklas, B. J. (2016) · JAMA · doi:10.1001/jama.2015.17346 · Cited by 921 · see citing works
Self-citationGlobal Cardiovascular Reserve Dysfunction in Heart Failure With Preserved Ejection Fraction
Borlaug, B. A., Olson, T. P., Lam, C. S. P., Flood, K. S., Lerman, A., Johnson, B. D., & Redfield, M. M. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.03.077 · Cited by 733 · see citing works
Self-citationBorlaug, B. A., Melenovsky, V., Russell, S. D., Kessler, K., Pacak, K., Becker, L. C., & Kass, D. A. (2006) · Circulation · doi:10.1161/circulationaha.106.632745 · Cited by 699 · see citing works
Self-citationKitzman, D. W., Higginbotham, M. B., Cobb, F. R., Sheikh, K. H., & Sullivan, M. J. (1991) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(91)90832-t · Cited by 683 · see citing works
Self-citationHaykowsky, M. J., Brubaker, P. H., John, J. M., Stewart, K. P., Morgan, T. M., & Kitzman, D. W. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.02.055 · Cited by 447 · see citing works
Self-citationMechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction
Dhakal, B. P., Malhotra, R. K., Murphy, R. M., Pappagianopoulos, P. P., Baggish, A. L., Weiner, R. B., Houstis, N. E., Eisman, A. S., Hough, S. S., & Lewis, G. D. (2014) · Circulation Heart Failure · doi:10.1161/circheartfailure.114.001825 · Cited by 433 · see citing works
Borlaug, B. A., Kane, G. C., Melenovský, V., & Olson, T. P. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw241 · Cited by 379 · see citing works
Self-citationAbudiab, M. M., Redfield, M. M., Melenovský, V., Olson, T. P., Kass, D. A., Johnson, B. D., & Borlaug, B. A. (2013) · European Journal of Heart Failure · doi:10.1093/eurjhf/hft026 · Cited by 332 · see citing works
Self-citationHemodynamic Basis of Exercise Limitation in Patients With Heart Failure and Normal Ejection Fraction
Maeder, M. T., Thompson, B. R., Rocca, H. B., & Kaye, D. M. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.04.040 · Cited by 327 · see citing works
Self-citationHasenfuss, G. P., Hayward, C., Burkhoff, D., Silvestry, F. E., McKenzie, S. C., Gustafsson, F., Málek, F., der Heyden, J. V., Lang, I. M., Petrie, M. C., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00704-2 · Cited by 294 · see citing works
Self-citationArterial Stiffening With Exercise in Patients With Heart Failure and Preserved Ejection Fraction
Reddy, Y. N. V., Andersen, M. J., Obokata, M., Koepp, K. E., Kane, G. C., Melenovský, V., Olson, T. P., & Borlaug, B. A. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.05.029 · Cited by 269 · see citing works
Self-citationFeldman, T. E., Mauri, L., Kahwash, R., Litwin, S. E., Ricciardi, M. J., van der Harst, P., Pěnička, M., Fail, P. S., Kaye, D. M., Petrie, M. C., et al. (2017) · Circulation · doi:10.1161/circulationaha.117.032094 · Cited by 269 · see citing works
Self-citationExercise Intolerance in Heart Failure With Preserved Ejection Fraction
Houstis, N. E., Eisman, A. S., Pappagianopoulos, P. P., Wooster, L. T., Bailey, C. S., Wagner, P. D., & Lewis, G. D. (2017) · Circulation · doi:10.1161/circulationaha.117.029058 · Cited by 266 · see citing works
Haemodynamics, dyspnoea, and pulmonary reserve in heart failure with preserved ejection fraction
Obokata, M., Olson, T. P., Reddy, Y. N. V., Melenovský, V., Kane, G. C., & Borlaug, B. A. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy268 · Cited by 264 · see citing works
Self-citationHaykowsky, M. J., Kouba, E., Brubaker, P. H., Nicklas, B. J., Eggebeen, J., & Kitzman, D. W. (2014) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2013.12.031 · Cited by 251 · see citing works
Self-citationPhan, T. T., Shivu, G. N., Abozguia, K., Davies, C., Nassimizadeh, M., Jimenez, D., Weaver, R., Ahmed, I., & Frenneaux, M. P. (2009) · Circulation Heart Failure · doi:10.1161/circheartfailure.109.877720 · Cited by 215 · see citing works
Reddy, Y. N. V., Olson, T. P., Obokata, M., Melenovský, V., & Borlaug, B. A. (2018) · JACC Heart Failure · doi:10.1016/j.jchf.2018.03.003 · Cited by 210 · see citing works
Self-citationKitzman, D. W., & Shah, S. J. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.05.019 · Cited by 195 · see citing works
Self-citationThe Influence of Age on Hemodynamic Parameters During Rest and Exercise in Healthy Individuals
Wolsk, E., Bakkestrøm, R., Thomsen, J. H., et al. (2016) · JACC Heart Failure · doi:10.1016/j.jchf.2016.10.012 · Cited by 179 · see citing works
Self-citationNadruz, W., West, E., Sengeløv, M., Santos, M., Groarke, J. D., Forman, D. E., Claggett, B. L., Skali, H., & Shah, A. M. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.006000 · Cited by 165 · see citing works
Dalos, D., Mascherbauer, J., Zotter‐Tufaro, C., Duca, F., Kammerlander, A. A., Aschauer, S., & Bonderman, D. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.04.052 · Cited by 111 · see citing works
Hegde, S. M., Claggett, B., Shah, A., Lewis, E., Anand, I., Shah, S. J., Sweitzer, N., Fang, J. C., Pitt, B., Pfeffer, M., et al. (2017) · Circulation · doi:10.1161/circulationaha.117.028002 · Cited by 96 · see citing works
Self-citationPandey, A., Khera, R., Park, B., Haykowsky, M. J., Borlaug, B. A., Lewis, G. D., Kitzman, D. W., Butler, J., & Berry, J. D. (2018) · JACC Heart Failure · doi:10.1016/j.jchf.2017.10.014 · Cited by 82 · see citing works
Self-citationTranscatheter Interatrial Shunt Device for the Treatment of Heart Failure
Feldman, T. E., Komtebedde, J., Burkhoff, D., Massaro, J. M., Maurer, M. S., Leon, M. B., Kaye, D. M., Silvestry, F. E., Cleland, J. G. F., Kitzman, D. W., et al. (2016) · Circulation Heart Failure · doi:10.1161/circheartfailure.116.003025 · Cited by 58 · see citing works
Self-citationKass, D. A., Kitzman, D. W., & Alvarez, G. E. (2009) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2009.08.008 · Cited by 47 · see citing works
Self-citationHasenfuss, G. P., Gustafsson, F., Kaye, D. M., Shah, S. J., Burkhoff, D., Reymond, M.-C., Komtebedde, J., & Hünlich, M. (2015) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2015.05.008 · Cited by 39 · see citing works
Self-citationTears are words that heart cannot express
Iannaccone, M., Conrotto, F., Pennone, M., & D’Amico, M. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw178 · Cited by 39 · see citing works
Brubaker, P. H., & Kitzman, D. W. (2013) · JACC Heart Failure · doi:10.1016/j.jchf.2013.03.009 · Cited by 9 · see citing works
Self-citationReddy, Y. N. V., Obokata, M., & Borlaug, B. A. (2018) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(18)31455-4 · Cited by 1 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Brubaker PH, Kitzman DW. Chronotropy: the Cinderella of heart failure pathophysiology and management. JACC Heart Fail. 2013;1:267-269.
Cited by
Sorted by citations
Prioritizing symptom management in the treatment of chronic heart failure
Koshy, A. O., Gallivan, E. R., McGinlay, M., Straw, S., Drozd, M., Toms, A. G., Gierula, J., Cubbon, R. M., Kearney, M. T., & Witte, K. K. (2020) · ESC Heart Failure · doi:10.1002/ehf2.12875 · Cited by 66 · see citing works
- Authors
- Wolsk, E., Kaye, D., Komtebedde, J., Shah, S. J., Borlaug, B. A., Burkhoff, D., Kitzman, D. W., Lam, C. S. P., van Veldhuisen, D. J., Ponikowski, P., Petrie, M. C., Hassager, C., Møller, J. E., & Gustafsson, F.
- Affiliations
- Rigshospitalet (DK)
- Baker Heart and Diabetes Institute (AU)
- Northwestern University (US)
- Mayo Clinic (US)
- Cardiovascular Research Foundation (US)
- Wake Forest University Health Sciences (US)
- University Medical Center Groningen (NL)
- Wroclaw Medical University (PL)
- University of Glasgow (GB)
- Odense University Hospital (DK)
- Corresponding author
- Wolsk, Emil
- ORCID
- Venue
- JACC Heart Failure
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 7
- Issue
- 4
- Pages
- 321-332
- ISSN
- 2213-1779 (ISSN-L)
- OpenAlex
- W2920988382
- Cited by
- 43
- References
- 33
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 8 · 2021: 6 · 2020: 15 · 2019: 5
- FWCI
- 10.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- JACC Heart Failure (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, cc-by-nc-nd)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Amgen
- Eli Lilly and Company
- Pfizer
- AstraZeneca (R01 HL107577, R01 HL140731, R01 HL127028)
- GlaxoSmithKline
- Sanofi
- Teva Pharmaceutical Industries
- Ironwood Pharmaceuticals, Incorporated
- MyoKardia
- Abiomed
- Lundbeckfonden (R186-2015-2132)
- Novo Nordisk
- Astellas Pharma
- Servier
- National Institutes of Health
- Medical Research Council
- National Health and Medical Research Council
- National Heart, Lung, and Blood Institute (RO1 HL128526, HL107577, R01HL128526, R01HL127028, U10HL110262, HL128526, R01HL140731, R01HL107577)
- Daiichi Sankyo Europe
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- heart failure with preserved ejection fraction, exercise capacity, exercise hemodynamics, pulmonary capillary wedge pressure, stroke volume, body mass index, left atrial filling pressure, right heart catheterization
- MeSH terms
- Adult, Aged, Aged, 80 and over, Double-Blind Method, Exercise Test, Female, Follow-Up Studies, Cardiac Catheterization, Heart Failure, Heart Rate, Humans, Male, Middle Aged, Prognosis, Prospective Studies, Pulmonary Wedge Pressure, Stroke Volume, Exercise Tolerance, Young Adult, Atrial Pressure, Healthy Volunteers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
