Cited by 574Atrial Fibrillation Management and OutcomesHeart Failure Treatment and ManagementCardiac Health and Mental Health

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Atrial Fibrillation and Risk of Clinical Events in Chronic Heart Failure With and Without Left Ventricular Systolic Dysfunction

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Olsson, Lars G., Swedberg, Karl, Ducharme, Anique, Granger, Christopher B., Michelson, Eric L., McMurray, John J.V., Puu, Margareta, Yusuf, Salim, Pfeffer, Marc A.·2006·Journal of the American College of Cardiology

DOI 10.1016/j.jacc.2006.01.060

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Abstract

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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BackgroundInfluential
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“[7] Due to the mentioned severity of heart failure and stroke, the best prevention is the management of AFIB .”
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“Age (y) 65 (57-72) 67 (62-78) 68 (62-78) Gender (female)⁎ 36% b1% b1% Race (white) 78% Data not available Ejection fraction (%) 40 ± 19 Data not available NYHA class⁎ I 10% 7% 7% II 72% 46% 45% III 16% 36% 37% IV 2% 11% 12% BUN (mg/dL) 22 (16-31) 22 (14-28) 21 (15-29) BNP (pg/mL)⁎ 138 (53-341) 148 (46-439) 174 (51-512…”
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“In patients with LVSD, apixaban was shown to be favourable to warfarin in the primary outcome of SSE (annual rate 0.99% vs. 1.80%, HR 0.55,) and in all other efficacy end points including major, or clinical relevant bleeding (rate 5.05 vs. 6.01%, HR 0.84), ISTH major bleeding (2.77 versus 3.41; HR 0.81), total and int…”
BackgroundInfluential
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Prevalence of Subclinical Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction
Yang, E., Heckbert, S. R., Ding, J., SPRAGG, D. D., Calkins, H. G., Shah, S. J., Szklo, M., Post, W. S., & Sharma, K. (2023) · JACC Heart Failure · doi:10.1016/j.jchf.2023.09.023 · Cited by 17
The role of estrogen in the sex difference for the risk factors of heart failure with preserved ejection fraction
Du, J., Liu, J., Wang, X., Wang, X., Ma, Y., Zhang, S., Li, Z., Ma, J., & Liu, J. (2025) · Biology Direct · doi:10.1186/s13062-025-00618-x · Cited by 22
“Additionally, the development of AF may have a greater impact on patients with HFpEF than those with HFrEF and is highly associated with adverse outcomes in patients with HFpEF [162–166].”
Prognostic role of atrial fibrillation in patients affected by chronic heart failure. Data from the MECKI score research group
Paolillo, S., Agostoni, P., Masarone, D., Corrà, U., Passino, C., Scrutinio, D., Correale, M., Cattadori, G., Metra, M., Girola, D., et al. (2015) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2015.04.023 · Cited by 17
Electrocardiographic characteristics in patients with heart failure and normal ejection fraction: A systematic review and meta‐analysis
Nikolaidou, T., Samuel, N. A., Marincowitz, C., Fox, D. J., Cleland, J. G. F., & Clark, A. L. (2019) · Annals of Noninvasive Electrocardiology · doi:10.1111/anec.12710 · Cited by 17
“…(Cenkerova, Dubrava, Pokorna, Kaluzay, & Jurkovicova, 2016; Danciu et al., 2006; Hendry, Krisdinarti, & Erika, 2016), >40% (Hawkins et al., 2007; Olsson et al., 2006), ≥45% (Adabag et al., 2014; Donal et al., 2014; Joseph et al., 2016; Komajda et al., 2011; Nikolaidou et al., 2017; Shah et…”
BackgroundMethodInfluential
Characterization of acute heart failure hospitalizations in a Portuguese cardiology department
Pinho‐Gomes, A., Silva‐Cardoso, J., Azevedo, L. F., Almeida, R., Pinho, T., & Maciel, M. J. (2013) · Revista Portuguesa de Cardiologia · doi:10.1016/j.repc.2012.10.018 · Cited by 17
Kommentar zu „ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation – executive summary“
Lewalter, T., Tebbenjohanns, J., Wichter, T., Antz, M., Geller, J. C., Seidl, K., Gulba, D. C., Röhrig, F., & Willems, S. (2008) · Der Kardiologe · doi:10.1007/s12181-008-0080-2 · Cited by 16
Heart Failure Complicated by Atrial Fibrillation
Piccini, J. P., & Allen, L. A. (2017) · JACC Heart Failure · doi:10.1016/j.jchf.2016.12.003 · Cited by 17
Pharmacological Treatment of Heart Failure with Preserved Ejection Fraction: A Glimpse of Light at the End of the Tunnel?
van Veldhuisen, D. J., & McMurray, J. J. V. (2012) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfs194 · Cited by 16
Observational Studies of Statins in Heart Failure with Preserved Systolic Function
Fukuta, H., & Little, W. C. (2008) · Heart Failure Clinics · doi:10.1016/j.hfc.2008.01.005 · Cited by 16
Dominant frequency differences in atrial fibrillation patients with and without left ventricular systolic dysfunction
Arenal, Á., Datino, T., Atéa, L., Atienza, F., González‐Torrecilla, E., Almendral, J. M., Castilla, L., Sanchez, P. L., & Fernández‐Avilés, F. (2008) · EP Europace · doi:10.1093/europace/eup053 · Cited by 16
IMproved exercise tolerance in patients with PReserved Ejection fraction by Spironolactone on myocardial fibrosiS in Atrial Fibrillation rationale and design of the IMPRESS-AF randomised controlled trial
Shantsila, E., Haynes, R., Calvert, M., Fisher, J. P., Kirchhof, P. F., Gill, P. S., & Lip, G. Y. H. (2016) · BMJ Open · doi:10.1136/bmjopen-2016-012241 · Cited by 16
Persistent atrial fibrillation in heart failure with preserved ejection fraction: Prognostic relevance and association with clinical, imaging and invasive haemodynamic parameters
Schönbauer, R., Duca, F., Kammerlander, A. A., Aschauer, S., Binder, C., Zotter‐Tufaro, C., Koschutnik, M., Fiedler, L., Roithinger, F. X., Loewe, C., et al. (2019) · European Journal of Clinical Investigation · doi:10.1111/eci.13184 · Cited by 16
Influencia de la fibrilación auricular en la mortalidad de los pacientes con insuficiencia cardiaca con fracción de eyección preservada
Franco, J., Formiga, F., Cepeda, J. M., Llàcer, P., Arévalo-Lorido, J., Cerqueiro, J., Franco, Á. G., Epelde, F., Manzano, L., & Montero-Pérez-Barquero, M. (2017) · Medicina Clínica · doi:10.1016/j.medcli.2017.06.065 · Cited by 16
Prognostic Value of Total Atrial Conduction Time Measured with Tissue Doppler Imaging to Predict the Maintenance of Sinus Rhythm after External Electrical Cardioversion of Persistent Atrial Fibrillation
Maffè, S., Paffoni, P., Dellavesa, P., Cucchi, L., Zenone, F., Bergamasco, L., Paino, A. M., Pardo, N. F., Signorotti, F., Baduena, L., et al. (2014) · Echocardiography · doi:10.1111/echo.12702 · Cited by 16
“Although the mortality benefit of the maintenance of sinus rhythm (SR) in patients with AF is controversial, the restoration of SR is favorable to improve the quality of life, to avoid cardiac dysfunction, and to reduce (the risk of systemic thromboembolism and) long-term anticoagulation treatment complications.(2) Tr…”
Background
Atrial Resynchronization Therapy: A New Concept For Treatment of Heart Failure with Preserved Ejection Fraction and Prevention of Atrial Fibrillation?
Maass, A. H., & Gelder, I. C. V. (2012) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfs014 · Cited by 16
“studies suggest that AF is also associated with an impaired outcome(7)in HFPEF patients.(8) Prevention of AF therefore may be of”
Background
Prevalence and Incidence of Atrial Fibrillation in Heart Failure with Mildly Reduced or Preserved Ejection Fraction: (Additive) Value of Implantable Loop Recorders
Gorter, T. M., van Veldhuisen, D. J., Mulder, B. A., Arita, V. A., van Empel, V. P. M., Manintveld, O. C., Tieleman, R. G., Maass, A. H., Vernooy, K., Gelder, I. C. V., et al. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12113682 · Cited by 16
Age-Dependent Prognostic Significance of Atrial Fibrillation in Outpatients with Chronic Heart Failure: Data from the Italian Network on Congestive Heart Failure Registry
Baldasseroni, S., Orso, F., Fabbri, G., Bernardi, A. D., Cirrincione, V., Gonzini, L., Fumagalli, S., Marchionni, N., Midi, P., & Maggioni, A. P. (2010) · Cardiology · doi:10.1159/000315312 · Cited by 15
Left Atrial Expansion Index Predicts Left Ventricular Filling Pressure and Adverse Events in Acute Heart Failure With Severe Left Ventricular Dysfunction
Hsiao, S.-H., Chu, K.-A., Wu, C.-J., & Chiou, K.-R. (2016) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2016.01.009 · Cited by 15
Newly Diagnosed Atrial Fibrillation Is an Independent Factor for Future Major Adverse Cardiovascular Events
Li, C.-Y., Lin, C., Lin, Y., Wu, L., Chang, C., & Chu, P. (2015) · PLoS ONE · doi:10.1371/journal.pone.0123211 · Cited by 15
Effect of RAAS blockers on adverse clinical outcomes in high CVD risk subjects with atrial fibrillation
Chaugai, S., Sherpa, L. Y., Sepehry, A. A., Arima, H., & Wang, D. W. (2016) · Medicine · doi:10.1097/md.0000000000004059 · Cited by 15
Validation of Conventional Thromboembolic Risk Factors in a Korean Atrial Fibrillation Population ― Suggestion for a Novel Scoring System, CHA2DS2-VAK ―
Cha, M., Cho, Y., Oh, I., Choi, E., & Oh, S. (2018) · Circulation Journal · doi:10.1253/circj.cj-18-0218 · Cited by 15
Prevention of atrial fibrillation after cardiac surgery
Hakala, T., Halonen, J., Mäkinen, K., & Juha, H. (2006) · Scandinavian Cardiovascular Journal · doi:10.1080/14017430601054076 · Cited by 15
Long-Term Outcomes of Acute Heart Failure
Steinberg, B. A., & Fang, J. C.-T. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.08.075 · Cited by 15
“- , 2 0 1 7 Long-Term HF Outcomes - , 2 0 1 7 :- –- 2 patients with HFpEF (6).”
MethodInfluential
Unmasking Adenosine: The Purinergic Signalling Molecule Critical to Arrhythmia Pathophysiology and Management
Matthews, G. D. K., & Grace, A. A. (2020) · Arrhythmia & Electrophysiology Review · doi:10.15420/aer.2019.05 · Cited by 15
“Patients with heart failure also have increased risks of both SVTs and AF, which increase morbidity and mortality.(13) Catheter ablation of AF in patients with heart failure may reduce mortality.”
Background
Outcomes Associated With Warfarin Use in Older Patients With Heart Failure and Atrial Fibrillation and a Cardiovascular Implantable Electronic Device: Findings From the ADHERE Registry Linked to Medicare Claims
Hess, P. L., Greiner, M. A., Fonarow, G. C., Klaskala, W. I., Mills, R. M., Setoguchi, S., Al‐Khatib, S. M., Hernandez, A. F., & Curtis, L. H. (2012) · Clinical Cardiology · doi:10.1002/clc.22064 · Cited by 14
What are the Thromboembolic Risks of Heart Failure Combined With Chronic or Paroxysmal AF?
Caldwell, J. C., Mamas, M. A., Neyses, L., & Garratt, C. J. (2010) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2009.12.004 · Cited by 14
“Although none of the papers examined the effect of NYHA class or LVEF on stroke event rate, it should be noted that in CHARM, AF tended to increase the incidence of stroke by more in the low EF group than in the preserved AF group (low EF 6% versus 3%, preserved EF 5% versus 4%).(26) It must also be noted that these s…”
Background
A Post hoc analysis on rhythm and high intensity interval training in cardiac resynchronization therapy
Melo, X., Abreu, A., Santos, V., Cunha, P. S., Oliveira, M., Pinto, R., Carmo, M. M., Fernhall, B., & Clara, S. (2019) · Scandinavian Cardiovascular Journal · doi:10.1080/14017431.2019.1630747 · Cited by 16
Atrial fibrillation: a leading cause of heart failure-related hospitalizations; a dual epidemic.
Ahmed, A., Ullah, W., Hussain, I., Roomi, S., Sattar, Y., Ahmed, F., Saeed, R., & Ashfaq, A. A. (2019) · Europe PMC (PubMed Central) · Cited by 14
Insight into Atrial Fibrillation in LVAD Patients: From Clinical Implications to Prognosis
Sisti, N., Mandoli, G. E., Sciaccaluga, C., Valente, S., Mondillo, S., & Cameli, M. (2020) · Pulse · doi:10.1159/000506600 · Cited by 14
Effects of Atrial Fibrillation on Heart Failure Outcomes and NT-proBNP Levels in the GUIDE-IT Trial
Chouairi, F. K., Pacor, J., Miller, P. E., Fuery, M. A., Caraballo, C., Sen, S., Leifer, E., Felker, G. M., Fiuzat, M., O’Connor, C. M., et al. (2021) · Mayo Clinic Proceedings Innovations Quality & Outcomes · doi:10.1016/j.mayocpiqo.2021.02.005 · Cited by 14
Temporal Association of Atrial Fibrillation With Cardiac Implanted Electronic Device Detected Heart Failure Status
Capucci, A., Wong, J. A., Gold, M. R., BOEHMER, J. P., Ahmed, R., Kwan, B., Thakur, P. H., Zhang, Y., Jones, P. W., & Healey, J. S. (2021) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2021.09.015 · Cited by 14
Interleukin‐37 elevation in patients with atrial fibrillation
Li, W., Li, S., Li, X., Jiang, S., & Han, B. (2016) · Clinical Cardiology · doi:10.1002/clc.22630 · Cited by 14
The Benefit of Atrioventricular Junction Ablation for Permanent Atrial Fibrillation and Heart Failure Patients Receiving Cardiac Resynchronization Therapy: An Updated Systematic Review and Meta-analysis
Waranugraha, Y., Rizal, A., Setiawan, D., & Aziz, I. J. (2021) · Indian Pacing and Electrophysiology Journal · doi:10.1016/j.ipej.2020.12.005 · Cited by 14
“The presence of AF is correlated with increased HF severity, cardiovascular death, and rehospitalization due to the worsening of HF [2,3].”
Background
Hyponatremia in patients with atrial fibrillation and heart failure: The difficult triangle
Oikonomou, E. K., Mystakidi, V. C., & Tousoulis, D. (2019) · Hellenic Journal of Cardiology · doi:10.1016/j.hjc.2019.03.012 · Cited by 14
Management of patients with arterial hypertension and atrial fibrillation
Chazova, I. E., Голицын, С. П., Zhernakova, Y. V., Zheleznova, E. A., Станиславовна, К. Е., Миронов, Н. Ю., Kostyukevich, M. V., Laiovich, L. I., Utsumueva, M. D., Александровна, Ю. Ю., et al. (2021) · Systemic Hypertension · doi:10.26442/2075082x.2021.3.201077 · Cited by 13
Prognostic Significance of New-Onset Atrial Fibrillation in Heart Failure with Preserved, Mid-Range, and Reduced Ejection Fraction Following Acute Myocardial Infarction: Data from the NOAFCAMI-SH Registry
Hao, C., Luo, J., Liu, B., Xu, W., Li, Z., Gong, M., Qin, X., Shi, B., & Wei, Y. (2022) · Clinical Interventions in Aging · doi:10.2147/cia.s358349 · Cited by 13
“Clinical Interventions in Aging 2022:17 https://doi.org/10.2147/CIA.S358349 DovePress 489 Powered by TCPDF (www.tcpdf.org) https://doi.org/10.2147/CIA.S358349 DovePress Clinical Interventions in Aging 2022:17490 Powered by TCPDF (www.tcpdf.org) 3.1–3.4).20 Mentias et al also demonstrated that in AF patients HFrEF was…”
ResultInfluential
Spectral Microvolt T-Wave Alternans Testing has no Prognostic Value in Patients Recently Hospitalized with Decompensated Heart Failure
Jackson, C. E., Myles, R. C., Tsorlalis, I. K., Dalzell, J. R., Rocchiccioli, P., Rodgers, J. R., Spooner, R. J., Greenlaw, N., Ford, I., Gardner, R. S., et al. (2013) · European Journal of Heart Failure · doi:10.1093/eurjhf/hft085 · Cited by 13
“Patients were ineligible because of AF, demand ventricular pacing, and an inability to exercise, conditions commonly associated with adverseoutcomes inHF.(18,19)Therewasa greaterprevalenceof prognostically unfavourable clinical characteristics amongst patients ineligible forMTWAtesting.”
Background
Atrial fibrillation in heart failure: drug therapies for rate and rhythm control
Tadros, R., Khairy, P., Rouleau, J. L., Talajic, M. R., Guerra, P. G., & Roy, D. (2013) · Heart Failure Reviews · doi:10.1007/s10741-013-9395-6 · Cited by 13
“Other studies have validated that ACEI and ARBs have similar benefits in AF and non-AF patients [58, 60].”
Heart failure progression and mortality in atrial fibrillation patients with preserved or reduced left ventricular ejection fraction
Slee, A. E., Saad, M. S., & Saksena, S. V. (2019) · Journal of Interventional Cardiac Electrophysiology · doi:10.1007/s10840-019-00534-x · Cited by 13
The impact of myocardial fibrosis biomarkers in a heart failure population with atrial fibrillation—The HARVEST-Malmö study
Nezami, Z., Holm, H., Ohlsson, M. A., Molvin, J., Korduner, J., Bachus, E., Zaghi, A., Dieden, A., Platonov, P. G., Jujić, A., et al. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.982871 · Cited by 14
Epidemiología de la fibrilación auricular y comorbilidades asociadas
García‐Seara, J., & González‐Juanatey, J. R. (2012) · Revista Española de Cardiología Suplementos · doi:10.1016/s1131-3587(12)70045-6 · Cited by 13

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: Swedberg, Karl
Ducharme, Anique
Granger, Christopher B.
McMurray, John J.V.
Yusuf, Salim
Pfeffer, Marc A.
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)
DOI: 10.1016/j.jacc.2006.01.060
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2670 d)
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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Atrial Fibrillation and Risk of Clinical Events in Chronic Heart Failure With and Without Left Ventricular Systolic Dysfunction

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