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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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“However, in the CHARM-HF study cohort, those with AF at baseline had a significantly higher cardiovascular mortality and more frequent HF hospitalisation (14), suggesting that AF does have an impact on prognosis in HF.”
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Left Ventricular Flow Distribution as a Novel Flow Biomarker in Atrial Fibrillation
Kim, H., Sheitt, H., Wilton, S. B., White, J. A., & García, J. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.725121 · Cited by 11
“CHA2DS2VASc score of PAF patients was calculated to assess stroke risk level, using patient medical history prior to MRI examination (Pamukcu et al., 2010).”
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“This might be because the prognosis in coronary artery disease and dilated cardiomyopathy is mainly driven by the reduced ejection fraction, whereas in hypertensive heart disease and preserved left ventricular function the extent of diastolic dysfunction may play an additional prognostic role [15].”
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Is It Time to Treat Depression in Patients With Cardiovascular Disease?
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β blockers, atrial fibrillation, and heart failure
McMurray, J. J. V., & van Veldhuisen, D. J. (2014) · The Lancet · doi:10.1016/s0140-6736(14)62340-0 · Cited by 10
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“The risks of mortality in patients with AF and HF have been discussed in several clinical trials, including patients with all types of HF [23,32,33].”
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SGLT2 inhibitors and the cardiac rhythm: unraveling the connections
Paul, A., Tabaja, C., & Wazni, O. M. (2024) · International Journal of Arrhythmia · doi:10.1186/s42444-024-00109-6 · Cited by 9
“AF alone raises the risk of death and stroke; and HF patients often experience thromboembolism complications and undetected AF [22], which often are the first manifestation of AF in these patients [23].”
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Novel oral anticoagulants and stroke prevention in atrial fibrillation and chronic heart failure
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Contemporary ICD Use in Patients with Heart Failure
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A review of the epidemiological profile of patients with atrial fibrillation and heart failure
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Atrial Fibrillation and Heart Failure with Preserved Ejection Fraction
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Atrial Fibrillation in Heart Failure
Havmöller, R., & Chugh, S. S. (2012) · Current Heart Failure Reports · doi:10.1007/s11897-012-0108-6 · Cited by 9
Berkovitch, A., Mazin, I., Younis, A., Nir, S., Nof, E., Goldenberg, I., & Beinart, R. (2019) · EP Europace · doi:10.1093/europace/euz192 · Cited by 9
Zhang, P., Chamberlain, A. M., Hodge, D. O., Cai, C., Xiao, P., Han, J., Jiang, C., Redfield, M. M., Roger, V. L., & Cha, Y. (2020) · Journal of Cardiovascular Electrophysiology · doi:10.1111/jce.14632 · Cited by 9
“In the Framingham Heart Study, AF was associated with a greater risk of death among patients with HFrEF,2 whereas in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) study, AF‐associated death was higher among patients with HFpEF.7 New‐onset AF was associated with a 2.3‐fold…”
BackgroundInfluentialRhythm control for atrial fibrillation: Non-channel antiarrhythmic drugs are en vogue
VanGelder, I. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2007.02.011 · Cited by 9
“Indeed, the risk of AF is lowered in heart failure patients, both in those with a reduced and those with a preserved left ventricular function, and also in patients with hypertension, but this risk is certainly not abolished [3,4].”
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Luedde, M., Agewall, S., Ambrosio, G., Bayés‐Genís, A., Borghi, C., Cerbai, E., Dan, G. A., Drexel, H., Ferdinándy, P., Grove, E. L., et al. (2025) · European Journal of Heart Failure · doi:10.1002/ejhf.70069 · Cited by 9
Current pharmacotherapeutic strategies for cardiac arrhythmias in heart failure
Correa, A. A., Rochlani, Y. M., & Aronow, W. S. (2020) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2019.1703950 · Cited by 8
Atrial fibrillation in heart failure: catheter and surgical interventional therapies
Rabah, A., & Wazni, O. M. (2013) · Heart Failure Reviews · doi:10.1007/s10741-013-9411-x · Cited by 8
“The prognostic significance of AF in HF is till debatable with some studies showing increased mortality [10, 11], while others do not [12, 13].”
BackgroundAtrial Fibrillation in Heart Failure: An Innocent Bystander?
Khan, M. A., Neyses, L., & Mamas, M. A. (2012) · Current Cardiology Reviews · doi:10.2174/157340312803760839 · Cited by 8
“Similarly, the Candesartan in Heart FailureAssessment of Re duction in Mortality and Morbidity (CHARM) investigators showed an increased and independent effect of AF on cardiovascular outcomes in patients with either reduced or preserved LV systolic function [18].”
Schryver, N. D., Scavée, C., Marchandise, S., Pasquet, A., de Meester, C., & de Waroux, J. L. P. (2014) · EP Europace · doi:10.1093/europace/euu033 · Cited by 8
“Atrial fibrillation increases by two-fold the risk of cardiac death and by three-fold the risk of heart failure.(3,4) Moreover, it has also been independently associatedwith afive-fold increasedriskof stroke, with an increased incidenceof cognitive impairmentandwitha reducedquality of life.”
BackgroundCandesartan cilexetil: an update
Joost, A., Schunkert, H., & Radke, P. W. (2011) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2011.587000 · Cited by 8
“However, the study was prematurely terminated mainly due to the fact that the incidence of confirmed progression of CHF was significantly lower in the candesartan cilexetil group (7.4”
BackgroundInfluentialTang, W. H. W., & Francis, G. S. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.09.019 · Cited by 8
Atrial fibrillation in heart failure syndromes: does it matter more in some than in others?
Siontis, K. C., Yao, X., & Noseworthy, P. A. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy727 · Cited by 8
Sp, G., Панченко, Е. П., Mironov, N. Y., Михайловна, Б. М., Gagloeva, D. A., Elfimova, E. M., Станиславовна, К. Е., Laiovich, L. I., Litvin, A. Y., Maykov, E. B., et al. (2025) · Eurasian heart journal · doi:10.38109/2225-1685-2025-3-6-77 · Cited by 8
Insuffisance cardiaque à fraction d’ejection preservee en afrique sub-saharienne: à propos de 32 cas
Mboup, M. C., Dia, K., & Fall, P. D. (2013) · Pan African Medical Journal · doi:10.11604/pamj.2013.16.100.2323 · Cited by 7
“Elle constituait un facteur pronostique péjoratif indépendant dans l'étude CHARM (Candesartan in Heart Failure) [26].”
Antiarrhythmic Treatment in Heart Failure
Könemann, H., Güler-Eren, S., Ellermann, C., Frommeyer, G., & Eckardt, L. (2024) · Current Heart Failure Reports · doi:10.1007/s11897-023-00642-w · Cited by 7
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Koniari, I. C., Artopoulou, E., Velissaris, D., Kounis, N. G., & Tsigkas, G. (2021) · PubMed Central · doi:10.11909/j.issn.1671-5411.2021.05.003 · Cited by 8
“The detection of the tachycardia-induced ventricular dysfunction requires high index of suspicion, as the clinical evidence of progressive ventricular damage is not always sufficient to lead to the correct diagnosis([16]) While the diagnosis could be considered in a patient with no history of cardiovascular diseases,…”
BackgroundResultInfluentialVinter, N., Cordsen, P., Lip, G. Y. H., Benjamin, E. J., Trinquart, L., Johnsen, S. P., & Frost, L. (2021) · ESC Heart Failure · doi:10.1002/ehf2.13668 · Cited by 6
“Based on data from the CHARM trial, incident AF was associated HF hospitalization both among patients with preserved ejection fraction (LVEF > 40%) and patients with low ejection fraction (LVEF < 40).(26) A study based on data from the COMET trial has reported an association between baseline AF and the composite of ho…”
Bouali, Y., Galli, E., Paven, E., Clément, L., Hubert, A., Oger, E., & Donal, E. (2021) · Advances in Clinical and Experimental Medicine · doi:10.17219/acem/143433 · Cited by 7
Sherazi, S., McNitt, S. A., Choudhary, N., Shah, A. H., Aktaş, M. K., Asgher, A., Schwarz, K. Q., & Zaręba, W. (2015) · Cardiology Journal · doi:10.5603/cj.a2015.0003 · Cited by 7
“CHARM sub-group analysis showed that patients with AF and preserved LVEF had higher risk for adverse cardiovascular outcome (34% with cardiovascular death or CHF hospitalization) relative to those with preserved LVEF and sinus rhythm (21%) [20].”
Clinical predictors of outcome in patients with inflammatory dilated cardiomyopathy
Karatolios, K., Holzendorf, V., Hatzis, G., Tousoulis, D. M., Richter, A., Schieffer, B., & Pankuweit, S. (2017) · PLoS ONE · doi:10.1371/journal.pone.0188491 · Cited by 7
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“Some studies have suggested AF is associated with increased mortality in heart failure with preserved ejection fraction (HFpEF) but not HFrEF [17,22] while other studies show AF worsens outcomes in both HFpEF and HFrEF [8,23].”
ResultBeta-blocker Therapy at Discharge in Patients with Acute Heart Failure and Atrial Fibrillation
Ahn, M., Yoo, B., Son, J., Yu, M. H., Kang, D. R., Lee, H., Jeon, E., Kim, J., Chae, S. C., Baek, S. H., et al. (2020) · Journal of Korean Medical Science · doi:10.3346/jkms.2020.35.e278 · Cited by 7
Focus on renin–angiotensin system modulation and atrial fibrillation control after GISSI AF results
Durin, O., Pedrinazzi, C., & Inama, G. (2010) · Journal of Cardiovascular Medicine · doi:10.2459/jcm.0b013e32833cdd6f · Cited by 7
Cardiac Resynchronization Therapy
Breithardt, O. A., & Stellbrink, C. (2003) · Circulation · doi:10.1161/01.cir.0000092032.32016.96 · Cited by 7
Predictors of mortality and burden of arrhythmias in endstage heart failure
Evbayekha, E. O., Antia, A. U., Dixon, B., Reiss, C. K., & LaRue, S. (2024) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2024.102541 · Cited by 6
Preventing Thrombosis to Improve Outcomes in Heart Failure Patients
Shantsila, E., & Lip, G. Y. H. (2015) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2015.09.005 · Cited by 6
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Ruipérez, F. G. C., Consuegra‐Sánchez, L., Félix-Redondo, F. J., Mera, L. L., Mellado-Delgado, P., Martínez-Díaz, J. J., López-Mínguez, J. R., & Fernandez-Berges, D. J. (2017) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2017.03.026 · Cited by 6
Atrial Fibrillation in Patients with Heart Failure: Current State and Future Directions
Mene-Afejuku, T. O., Lopez, P. D., Akinlonu, A. A., Dumancas, C. Y., Visco, F., Mushiyev, S., & Pekler, G. (2018) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-018-0276-1 · Cited by 6
“In fact, AF is an independent factor for long-term all-cause cardiovascular mortality [15, 16] and HF hospitalizations [15].”
BackgroundHow arrhythmias weaken the ventricle: an often underestimated vicious cycle
Körtl, T., Schach, C., & Sossalla, S. T. (2023) · Herz · doi:10.1007/s00059-022-05158-y · Cited by 6
“the coexistence of HF and AFib is of high clinical relevance, as it is associated with an elevated risk of cardiovascular morbidity and mortality [16, 17].”
BackgroundAtrial arrhythmias and heart failure: A “modern view” of an old paradox
Pagliaro, B., Mincione, G., Taormina, A., Ceriotti, C., Poggio, L., Cannata, F., Monaco, G. D., Gitto, M., Battaglia, V., Pinna, G., et al. (2023) · Pacing and Clinical Electrophysiology · doi:10.1111/pace.14697 · Cited by 7
Zhang, M.-J., & Zhou, J. (2024) · BMC Cardiovascular Disorders · doi:10.1186/s12872-024-04133-1 · Cited by 5
The importance of interactions between atrial fibrillation and heart failure
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Embedded system-on-chip design of atrial fibrillation classifier
Lim, H. W., Hau, Y. W., Othman, M. A., & Lim, C. W. (2017) · International SoC Design Conference · doi:10.1109/isocc.2017.8368784 · Cited by 6
“Consequently, it increases the economic cost to the society and mortality of the population [5].”
BackgroundTackling Patient-Reported Outcomes in Atrial Fibrillation and Heart Failure
Steinberg, B. A., & Piccini, J. P. (2019) · Cardiology Clinics · doi:10.1016/j.ccl.2019.01.013 · Cited by 7
Comorbidities in Heart Failure
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Pathophysiology of atrial fibrillation: Insights into the renin–angiotensin system
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Development and validation of prediction models for incident atrial fibrillation in heart failure
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Low plasma renin activity is associated with “Apparently” idiopathic atrial fibrillation
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“However, the evidence supporting of RAAS inhibitors as the upstream therapy of AF primarily comes from patients with structural heart disease or hypertension [25 – 29].”
BackgroundWang, C., Guan, L., Su, H., Tong, F., Li, Y., Li, Z., Sun, H., & Sun, Z. (2024) · ESC Heart Failure · doi:10.1002/ehf2.15008 · Cited by 5
Nagumo, S., Ebato, M., Tsujiuchi, M., Mizukami, T., Maezawa, H., Omura, A., Kubota, M., Ohmi, M., Numajiri, Y., Kitai, H., et al. (2024) · ESC Heart Failure · doi:10.1002/ehf2.15023 · Cited by 5
Recent advances in management of atrial fibrillation in patients with heart failure
Shantsila, E., & Lip, G. Y. H. (2013) · Current Opinion in Cardiology · doi:10.1097/hco.0b013e32835bd465 · Cited by 5
“In a study of 58 consecutive patients with atrial fibrillation and congestive HF (LVEF 45%), PVI led to significant improvement in LV contractility and dimensions, exercise capacity and quality of life [29].”
BackgroundMethodInfluentialPulmonary Vein Isolation for the Treatment of Atrial Fibrillation: Past, Present and Future
de Waroux, J. L. P., Talajic, M. R., Khairy, P., Guerra, P. G., Roy, D., Thibault, B., Dubuc, M., & Macle, L. (2009) · Future Cardiology · doi:10.2217/fca.09.55 · Cited by 6
Current Issues in the Diagnosis and Management of Peripartum Cardiomyopathy
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Ruipérez, F. G. C., Consuegra‐Sánchez, L., Félix-Redondo, F. J., Lozano, L., Mellado-Delgado, P., Martínez-Díaz, J. J., López-Mínguez, J. R., & Fernandez-Berges, D. J. (2017) · Revista Española de Cardiología · doi:10.1016/j.recesp.2017.03.010 · Cited by 5
Natale, M., Behnes, M., Kim, S., Hoffmann, J., Reckord, N., Hoffmann, U., Budjan, J., Lang, S., Borggrefe, M. M., Papavassiliu, T., et al. (2017) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/0004563217714004 · Cited by 5
“It has been shown earlier that HFrEF is characterized by greater eccentric LA remodeling, whereas HFpEF is characterized by increased LA stiffness and greater LA pressure pulsatility, which might contribute to greater AF burden.8 AF correlated with an increased risk of morbidity and mortality in patients with HFrEF an…”
InfluentialRhythm Control of Atrial Fibrillation in Heart Failure with Reduced Ejection Fraction
Burkman, G. M., & Naccarelli, G. V. (2020) · Current Cardiology Reports · doi:10.1007/s11886-020-01336-8 · Cited by 5
Chourdakis, E., Koniari, I. C., Velissaris, D., Tsigkas, G., Kounis, N., & Osman, N. (2021) · PubMed Central · doi:10.11909/j.issn.1671-5411.2021.05.008 · Cited by 6
“Generally, the presence of AF is associated with a higher rate of cardiovascular morbidity and mortality in symptomatic patients with HFrEF or HFpEF, attributable to co-existing AF.([31]) The stroke risk seems almost equal in both groups.”
BackgroundResultAtrial Fibrillation in Patients with Ischemic and Non-Ischemic Left Ventricular Dysfunction.
Ducas, R., & Ariyarajah, V. (2013) · Europe PMC (PubMed Central) · doi:10.4022/jafib.535 · Cited by 5
“Val-HeFT [23] Retrospective analysis, non-prespecified variable Patients with EF <40%, NYHA class II - IV 5010 Valsartan (160 mg BID) vs.”
Method
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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