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Atrial Fibrillation and Risk of Clinical Events in Chronic Heart Failure With and Without Left Ventricular Systolic Dysfunction
Open accessAbstract
Objectives We assessed the risk of adverse cardiovascular (CV) outcomes associated with atrial fibrillation (AF) in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program, which enrolled patients with chronic heart failure (CHF) and a broad range of ejection fractions (EFs).Background Atrial fibrillation is associated with an increased risk of adverse CV outcomes in patients with CHF and reduced EF. The risk of AF in patients with CHF and preserved left ventricular ejection fraction (PEF) is unknown.Methods A total of 7,599 patients with symptomatic CHF were randomized to candesartan or placebo. Patients were divided by baseline EF (< or =40% or >40%) in low or preserved EF groups. Major outcomes were cardiovascular death or hospitalization for worsening heart failure, and all-cause mortality. Median follow-up was 37.7 months.Results A total of 670 (17%) patients in the low EF group and 478 (19%) in the PEF group had AF at baseline. Atrial fibrillation predicted a high risk of cardiovascular morbidity and mortality regardless of baseline EF. Patients with AF and low EF had the highest absolute risk for adverse CV outcomes. However, AF was associated with greater relative increased risk of the major outcomes in patients with PEF than in patients with low EF: hazard ratio 1.72 (95% confidence interval [CI] 1.45 to 2.06) versus 1.29 (95% CI 1.14 to 1.46), respectively. The same was true for the risk of all-cause mortality. Candesartan was associated with similar treatment effects regardless of baseline rhythm.Conclusions Atrial fibrillation is associated with an increased risk of CV outcomes in patients with CHF and either reduced EF or PEF. Candesartan improved outcomes similarly regardless of baseline rhythm.
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“ACE inhibitors or ARBs appear to prevent new-onset AF in patients with LV dysfunction and in hypertensive patients with LV hypertrophy.219,236,237,239,246,250,686”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [219]
In the citing paper
“ACE inhibitors or ARBs appear to prevent new-onset AF in patients with LV dysfunction and in hypertensive patients with LV hypertrophy.219,236,237,239,246,250,686”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [219]
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Self-citationRight heart dysfunction in heart failure with preserved ejection fraction
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Authors Task Force Members, Fuster, V., Rydén, L., Cannom, D. S., Crijns, H. J. G. M., Curtis, A. B., Ellenbogen, K. A., Halperin, J. L., Heuzey, J. L., Kay, G. N., et al. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehl176 · Cited by 646
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“Similarly data from the CHARM cohort of patients suggest that baseline AF is associated with an increased risk of all-cause mortality, hospitalization, cardiovascular (CV) death/ hospitalization, and fatal/non-fatal strokes.(10)”
BackgroundMethodResultInfluentialAtrial Fibrillation in Heart Failure With Preserved, Mid-Range, and Reduced Ejection Fraction
Sartipy, U., Dahlström, U., Fu, M. L. X., & Lund, L. H. (2017) · JACC Heart Failure · doi:10.1016/j.jchf.2017.05.001 · Cited by 386
“Current 345 (14) 347 (8) 443 (15) 385 (10) 1,692 (19) 1,168 (13) Diabetes mellitus 1,031 (31) 1,666 (27) 987 (28) 1,385 (26) 2,944 (27) 3,232 (27)”
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“NYHA class III–IV, n (%) 796 50 (22) 41 (23) 61 (16) 0.”
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“Clinical studies report that AF is associated with an impaired prognosis in heart failure patients with reduced or preserved left ventricular function.(40-43) Right ventricular dysfunction in chronic obstructive pulmonary disease and other non-cardiac causes of pulmonary hypertension should also not be ignored.”
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“AF was also inconsistently defined in existing studies with some using medical history and others using the baseline electrocardiogram (ECG) to identify AF (4,6).”
BackgroundResultAtrial Fibrillation and Mortality in Heart Failure
Chamberlain, A. M., Redfield, M. M., Alonso, Á., Weston, S. A., & Roger, V. L. (2011) · Circulation Heart Failure · doi:10.1161/circheartfailure.111.962688 · Cited by 158
Impact of Atrial Fibrillation on Exercise Capacity in Heart Failure With Preserved Ejection Fraction
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“Although there is considerable controversy about the underlying pathophysiology of HF-PEF, the clinical profile and neurohormonal phenotype, including BNPs, resembles patients with impaired Clinical and prognostic effects of AF in HF patients 1117 LVEF.20,21,31,32 Levels of these peptides in stable HF are lower in pre…”
BackgroundResultInfluentialAtrial Fibrillation in Congestive Heart Failure
Lubitz, S. A., Benjamin, E. J., & Ellinor, P. T. (2010) · Heart Failure Clinics · doi:10.1016/j.hfc.2009.11.001 · Cited by 151
“In two large epidemiologic studies (24,25), the prevalence of AF was greater in CHF patients with preserved ejection fractions than in those with left ventricular systolic dysfunction, though the rates of AF were similar in patients with systolic as compared to diastolic CHF in one clinical trial (20).”
ResultBlack‐Maier, E., Ren, X., Steinberg, B. A., Green, C. L., Barnett, A. S., Rosa, N. S., Al‐Khatib, S. M., Atwater, B. D., Daubert, J. P., Frazier‐Mills, C. G., et al. (2017) · Heart Rhythm · doi:10.1016/j.hrthm.2017.12.001 · Cited by 148
Atrial Fibrillation: Mechanisms, Therapeutics, and Future Directions
Pellman, J., & Sheikh, F. (2015) · Comprehensive physiology · doi:10.1002/cphy.c140047 · Cited by 191
Management of Atrial Fibrillation in Patients With Structural Heart Disease
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“We observed that incident AF conveyed a particularly high hazard of ischemic stroke ( 2.5-fold higher adjusted rates compared with no AF), which is consistent with previous analyses.29 Of note, however, preexisting AF was associated with higher adjusted hazard of ischemic stroke in those with HF-PEF but not for those…”
BackgroundResultInfluentialRivero‐Ayerza, M., Reimer, W. J. M. S. O., Lenzen, M. J., Theuns, D. A. M. J., Jordaens, L. J. L. M., Michel Komajda, N., Folláth, F., Swedberg, K. B., & Cleland, J. G. F. (2008) · European Heart Journal · doi:10.1093/eurheartj/ehn217 · Cited by 134
“85 with reduced LVEF).(11) In agreement with these findings, the DIG investigators reported that the development of new-onset supraventricular arrhythmias was independently associated with a reduced survival during the follow-up (HR 1⁄4 2.”
ResultMartin, N., Manoharan, K., Thomas, J., Davies, C., & Lumbers, R. T. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012721.pub2 · Cited by 131
Spotlight on the 2024 ESC/EACTS management of atrial fibrillation guidelines: 10 novel key aspects
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Cardiac Fibrosis and Arrhythmogenesis
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“Patients with AF and heart failure suffer from a worse prognosis with increased mortality whatever the LV ejection fraction [22,23].”
BackgroundAtrial Fibrillation in Heart Failure: A Comprehensive Review
DEEDWANIA, P. C., & Lardizabal, J. A. (2010) · The American Journal of Medicine · doi:10.1016/j.amjmed.2009.06.033 · Cited by 113
Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction
Čikeš, M., Claggett, B. L., Shah, A. M., Desai, A. S., Lewis, E. F., Shah, S. J., Anand, I. S., O’Meara, E., Rouleau, J. L., Sweitzer, N. K., et al. (2018) · JACC Heart Failure · doi:10.1016/j.jchf.2018.05.005 · Cited by 115
Management of atrial fibrillation in patients with heart failure
Neuberger, H., Mewis, C., van Veldhuisen, D. J., Schotten, U., Gelder, I. C. V., Allessie, M. A., & Böhm, M. (2007) · European Heart Journal · doi:10.1093/eurheartj/ehm341 · Cited by 101
Cheng, M., Lu, X., Huang, J., Zhang, J., Zhang, S., & Gu, D. (2014) · European Journal of Heart Failure · doi:10.1002/ejhf.187 · Cited by 101
The Importance of Whether Atrial Fibrillation or Heart Failure Develops First
Smit, M. D., Moes, M. L., Maass, A. H., Achekar, I. D., van Geel, P. P., Hillege, H. L., van Veldhuisen, D. J., & Gelder, I. C. V. (2012) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfs097 · Cited by 100
“Interestingly, AF has been associated with a greater risk of major adverse events in heart failure patients with preserved ejection fraction than in heart failure patients with reduced ejection fraction.(6,32) In heart failure first patients, severe structural remodelling may predominate above functional changes.”
BackgroundGorter, T. M., van Melle, J. P., Rienstra, M., Borlaug, B. A., Hummel, Y. M., Gelder, I. C. V., Hoendermis, E. S., Voors, A. A., van Veldhuisen, D. J., & Lam, C. S. P. (2017) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2017.11.005 · Cited by 102
Nielsen, J. C., Lin, Y., Figueiredo, M. J. D. O., Shamloo, A. S., Alfie, A., Bovéda, S., Dagres, N., Toro, D. D., Eckhardt, L. L., Ellenbogen, K. A., et al. (2020) · Journal of Arrhythmia · doi:10.1002/joa3.12338 · Cited by 106
Nieuwlaat, R., Eurlings, L. W. M., Cleland, J. G. F., Cobbe, S. M., Vardas, P. E., Capucci, A., Lopez-Sendon, J. L., Meeder, J. G., Pinto, Y. M., & Crijns, H. J. G. M. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.01.055 · Cited by 98
Nielsen, J. C., Lin, Y.-J., de Oliveira Figueiredo, M. J., Sepehri Shamloo, A., Alfie, A., Boveda, S., Dagres, N., Di Toro, D., Eckhardt, L. L., Ellenbogen, K., et al. (2020) · EP Europace · doi:10.1093/europace/euaa065 · Cited by 98
Lip, G. Y. H., Heinzel, F. R., Gaïta, F., González‐Juanatey, J. R., Heuzey, J. Y. L., Potpara, T., Svendsen, J. H., Vos, M. A., Anker, S. D., Coats, A. J. S., et al. (2015) · EP Europace · doi:10.1093/europace/euv191 · Cited by 99
Lip, G. Y. H., Gelder, I. C. V., Bax, J. J., Hylek, E. M., Kääb, S., Schotten, U., Wegscheider, K., Boriani, G., Ezekowitz, M. D., Diener, H. C., et al. (2011) · Thrombosis and Haemostasis · doi:10.1160/th11-07-0517 · Cited by 91
Kirchhof, P. F., Medicine, E. C. R. A. E. A. W. S. O. P., Sipido, K. R., Medicine, E. C. R. A. E. A. W. S. O. P., Cowie, M., Medicine, E. C. R. A. E. A. W. S. O. P., Eschenhagen, T., Medicine, E. C. R. A. E. A. W. S. O. P., Fox, K. A. A., Medicine, E. C. R. A. E. A. W. S. O. P., et al. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu312 · Cited by 93
Enriquez, A. D., Calenda, B. W., Gandhi, P. U., Nair, A. P., Anyanwu, A., & Pinney, S. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.07.989 · Cited by 89
Systemic sclerosis - continuing progress in developing clinical measures of response.
Furst, D. E., Khanna, D., Matucci‐Cerinic, M., Clements, P. J., Steen, V. D., Pope, J. E., Merkel, P. A., Foeldvari, I., Seibold, J. R., Pittrow, D., et al. (2007) · PubMed · Cited by 87
Management of Arrhythmias in Heart Failure
Masarone, D., Limongelli, G., Rubino, M., Valente, F., Vastarella, R., Ammendola, E., Gravino, R., Verrengia, M., Salerno, G., & Pacileo, G. (2017) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd4010003 · Cited by 85
“Atrial fibrillation per se contributes to an increased risk of mortality and morbidity of stroke and thromboembolism, and silent AF is common among patients with HF [4], not infrequently leading to a first presentation of AF with an ischemic stroke [5].”
BackgroundPathophysiology of atrial fibrillation
Jalife, J., Allessie, M. A., Antzelevitch, C. N., Iesaka, Y., Jackman, W. M., Scheinman, M. M., & Chen, S. (2011) · Wiley eBooks · doi:10.1002/9781119963868.ch2 · Cited by 86
Sugumar, H., Nanayakkara, S., Vizi, D., Wright, L. M., Chieng, D., Leet, A. S., Mariani, J. A., Voskoboinik, A., Prabhu, S., Taylor, A. J., et al. (2021) · European Journal of Heart Failure · doi:10.1002/ejhf.2122 · Cited by 84
Tolosana, J. M., Hernández‐Madrid, A., Brugada, J., Sitges, M., Bolao, I. G., Lozano, I. F., Ferrer, J. M., Quesada, A., Macı́as, A., Marín, W. V., et al. (2008) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2008.04.008 · Cited by 84
Magnani, G., Giugliano, R. P., Ruff, C. T., Murphy, S. A., Nordio, F., Metra, M., Moccetti, T., Mitrović, V. L., Shi, M., Mercuri, M. F., et al. (2016) · European Journal of Heart Failure · doi:10.1002/ejhf.595 · Cited by 83
Butt, J. H., Docherty, K. F., Jhund, P. S., de Boer, R. A., Böhm, M., Desai, A. S., Howlett, J. G., Inzucchi, S. E., Kosiborod, M., Martínez, F. A., et al. (2021) · European Journal of Heart Failure · doi:10.1002/ejhf.2381 · Cited by 83
Irregular Rhythm Adversely Influences Calcium Handling in Ventricular Myocardium
Ling, L., Khammy, O., BYRNE, M. J., Amirahmadi, F., Foster, A., Li, G., Zhang, L., dos Remedios, C. G., Chen, C., & Kaye, D. M. (2012) · Circulation Heart Failure · doi:10.1161/circheartfailure.112.968321 · Cited by 80
Implications of Atrial Fibrillation for Guideline-Directed Therapy in Patients With Heart Failure
Newman, J. D., O’Meara, E., Böhm, M., Savarese, G., Kelly, P. R., Vardeny, O., Allen, L. A., Lancellotti, P., Gottlieb, S. S., Samad, Z. Z., et al. (2024) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2023.12.033 · Cited by 87
Ahmed, M. I., White, M., Ekundayo, O. J., Love, T. E., Aban, I., Liu, B., Aronow, W. S., & Ahmed, A. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp222 · Cited by 79
Crandall, M. A., Bradley, D. J., Packer, D. L., & Asirvatham, S. J. (2009) · Mayo Clinic Proceedings · doi:10.4065/84.7.643 · Cited by 79
Biomarkers of Inflammation in Left Ventricular Diastolic Dysfunction
Mocan, M., Hognogi, L. D. M., Anton, F. P., Chiorescu, R. M., Goidescu, C. M., Stoia, M. A., & Fărcaș, A. D. (2019) · Disease Markers · doi:10.1155/2019/7583690 · Cited by 79
Prognostic Value of Minimal Left Atrial Volume in Heart Failure With Preserved Ejection Fraction
Shin, S., Claggett, B. L., Inciardi, R. M., Santos, Â. B. S., Shah, S. J., Zile, M. R., Pfeffer, M. A., Shah, A. M., & Solomon, S. D. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.120.019545 · Cited by 77
Cohen, A. A., Donal, E., Delgado, V., Pepi, M., Tsang, T. S. M., Gerber, B. L., Soulat-Dufour, L., Habib, G., Lancellotti, P., Evangelista, A., et al. (2021) · European Heart Journal - Cardiovascular Imaging · doi:10.1093/ehjci/jeab008 · Cited by 76
Fogari, R., Derosa, G., Ferrari, I., Corradi, L., Zoppi, A., Lazzari, P., Santoro, T., Preti, P. S., & Mugellini, A. (2008) · American Journal of Hypertension · doi:10.1038/ajh.2008.217 · Cited by 76
Fung, J. W., Sanderson, J. E., Yip, G. W., Zhang, Q., & Yu, C. (2007) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2007.04.014 · Cited by 76
Hamaguchi, S., Yokoshiki, H., Kinugawa, S., Tsuchihashi‐Makaya, M., Yokota, T., Takeshita, A., Tsutsui, H., & The JCARE-CARD Investigators (2009) · Circulation Journal · doi:10.1253/circj.cj-09-0316 · Cited by 76
Outcomes of Medicare Beneficiaries With Heart Failure and Atrial Fibrillation
Khazanie, P., Liang, L., Qualls, L. G., Curtis, L. H., Fonarow, G. C., Hammill, B. G., Hammill, S. C., Heidenreich, P. A., Masoudi, F. A., Hernandez, A. F., et al. (2014) · JACC Heart Failure · doi:10.1016/j.jchf.2013.11.002 · Cited by 75
“Consistent with findings from clinical trials (4,22), the risk of myocardial infarction in patients with HF and AF was low.”
ResultCrandall, M. A., Horne, B. D., DAY, J. D., Anderson, J. L., Muhlestein, J. B., Crandall, B. G., Weiss, J. P., OSBORNE, J. S., LAPPE, D. L., & Bunch, T. J. (2009) · Pacing and Clinical Electrophysiology · doi:10.1111/j.1540-8159.2009.02427.x · Cited by 74
Tzeis, S. E., Gerstenfeld, E. P., Kalman, J. M., Saad, E., Shamloo, A. S., Andrade, J. G., Barbhaiya, C. R., Baykaner, T., Bovéda, S., Calkins, H. G., et al. (2024) · Journal of Arrhythmia · doi:10.1002/joa3.13082 · Cited by 76
Tomasoni, D., Vitale, C., Guidetti, F., Benson, L., Braunschweig, F., Dahlström, U., Melin, M., Rosano, G. M. C., Lund, L. H., Metra, M., et al. (2023) · European Journal of Heart Failure · doi:10.1002/ejhf.3112 · Cited by 78
Eapen, Z. J., Greiner, M. A., Fonarow, G. C., Yuan, Ž., Mills, R. M., Hernandez, A. F., & Curtis, L. H. (2013) · American Heart Journal · doi:10.1016/j.ahj.2013.12.001 · Cited by 71
Toma, M., Ezekowitz, J. A., Bakal, J. A., O’Connor, C. M., Hernandez, A. F., Sardar, M. R., Zolty, R., Massie, B. M., Swedberg, K. B., Armstrong, P. W., et al. (2013) · European Journal of Heart Failure · doi:10.1002/ejhf.19 · Cited by 69
Mulder, B. A., van Veldhuisen, D. J., Crijns, H. J. G. M., Böhm, M., Solal, A. C., Babalis, D. S., Roughton, M., Flather, M. D., Coats, A. J. S., & Gelder, I. C. V. (2012) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfs100 · Cited by 69
“However, a subanalysis of CHARM showed that the presence of AF as an adverse prognostic indicator was of a greater magnitude in those with preserved ejection fraction.(11,34) Consistent with this subanalysis, a recently published study showed that AF was independently related to death or heart failure hospitalization…”
BackgroundMethodResultCombination of Circulating Type I Collagen-Related Biomarkers Is Associated With Atrial Fibrillation
Ravassa, S., Ballesteros, G., López, B., Ramos, P., Bragard, J. R., González, A., Moreno, M. U., Querejeta, R., Vives, E., García‐Bolao, I., et al. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.12.074 · Cited by 67
Metadata
- Authors
- Olsson, L. G., Swedberg, K., Ducharme, A., Granger, C. B., Michelson, E. L., McMurray, J. J. V., Puu, M., Yusuf, S., & Pfeffer, M. A.
- Affiliations
- Sahlgrenska University Hospital (SE)
- Montreal Heart Institute (CA)
- Duke Medical Center (US)
- AstraZeneca (United States) (US)
- Western Infirmary (GB)
- AstraZeneca (Sweden) (SE)
- Brigham and Women's Hospital (US)
- Corresponding author
- Swedberg, Karl
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 47
- Issue
- 10
- Pages
- 1997-2004
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W104425974
- Cited by
- 574
- References
- 35
- Citations by year
- 2026: 17 · 2025: 25 · 2024: 26 · 2023: 17 · 2022: 18 · 2021: 37 · 2020: 33 · 2019: 24 · 2018: 22 · 2017: 39 · 2016: 37 · 2015: 32 · 2014: 25 · 2013: 44 · 2012: 29
- FWCI
- 23.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Keywords
- atrial fibrillation, chronic heart failure, left ventricular systolic dysfunction, preserved ejection fraction, candesartan, cardiovascular mortality, hospitalization for worsening heart failure, all-cause mortality, CHARM trial, angiotensin receptor blockers
- MeSH terms
- Aged, Atrial Fibrillation, Benzimidazoles, Biphenyl Compounds, Cardiovascular Diseases, Chronic Disease, Female, Heart Failure, Hospitalization, Humans, Male, Middle Aged, Prognosis, Risk, Stroke Volume, Tetrazoles, Ventricular Dysfunction, Left, Angiotensin II Type 1 Receptor Blockers
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