The Association Between Atrial Fibrillation and Sudden Cardiac Death

Reinier, Kyndaron; Marijon, Éloi; Uy‐Evanado, Audrey; Teodorescu, Carmen; Narayanan, Kumar; Chugh, Harpriya; Gunson, Karen; Jui, Jonathan; Chugh, Sumeet S.

doi:10.1016/j.jchf.2013.12.006

Cited by 50 publications

(41 citation statements)

References 47 publications

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“…Regardless of the reason for prescribing digoxin in patients with AF without HF, our study emphasizes the concern with the use of therapy, which is not supported by adequately sized randomized clinical trials. Consistent with prior data,1, 27 our findings highlight the complex intersection between digoxin use, HF, and worse clinical outcomes, and raise a concern of a possible association between digoxin use and SCD. This study highlights the unmet need for examining digoxin use in patients with AF with, but particularly without, HF in a randomized trial.…”

Section: Discussionsupporting

confidence: 90%

Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial

Eisen

Ruff

Braunwald

et al. 2017

JAHA

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BackgroundDigoxin is widely used in patients with atrial fibrillation despite the lack of randomized controlled trials. Observational studies report conflicting results regarding its association with mortality, perhaps because of residual confounding by the presence of heart failure (HF).Methods and ResultsIn the ENGAGE AF‐TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation‐Thrombolysis in Myocardial Infarction 48) trial, clinical outcomes of patients with atrial fibrillation with and without HF were examined by baseline digoxin use during a median follow‐up of 2.8 years. HF was defined at baseline as prior or current clinical stage C or D HF. Of 21 105 patients enrolled, 6327 (30%) were treated with digoxin at baseline. Among patients without HF (n=8981), digoxin use (20%) was independently associated with sudden cardiac death (adjusted hazard ratio, 1.51; 95% CI, 1.10–2.08), with no significant interaction by age, sex, left ventricular ejection fraction, renal function, or concomitant medications (P>0.05 for each). Consistent results were observed using propensity matching (adjusted hazard ratio for sudden cardiac death, 1.90; 95% CI, 1.36–2.65). Among patients with HF (n=12 124), digoxin use (37%) was associated with an increase in all‐cause death, cardiovascular death, sudden cardiac death, and death caused by HF/cardiogenic shock (P<0.01 for each), but not with noncardiovascular death, stroke/systemic embolism, or myocardial infarction.ConclusionsIn this observational analysis of patients with atrial fibrillation without investigator‐reported HF, digoxin use was significantly associated with sudden cardiac death. While residual confounding cannot be excluded, the association between digoxin use and worse clinical outcomes highlights the need to examine digoxin use, particularly when prescribed to control heart rate in patients with atrial fibrillation in a randomized trial.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00781391.

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Section: Discussionsupporting

confidence: 90%

Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial

Eisen

Ruff

Braunwald

et al. 2017

JAHA

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“…26, 34 The Oregon-Sudden Unexpected Death Study recently reported that in multivariate analysis without considering HF, AF was a significant predictor of SCD. However, in a model that included HF, the AF-SCD association was no longer significant.…”

Section: Possible Mechanisms Underlying the Association Of Af With Scdmentioning

confidence: 99%

“…However, in a model that included HF, the AF-SCD association was no longer significant. 34 To further assess this issue of confounding or mediation by shared risk factors, we conducted a secondary analysis in the ARIC study by updating covariates to the end of followup. Although the association between AF and SCD was attenuated in the analysis, AF remained significantly associated with SCD after adjustment for factors potentially in the causal pathway.…”

Section: Possible Mechanisms Underlying the Association Of Af With Scdmentioning

confidence: 99%

Atrial Fibrillation and Its Association With Sudden Cardiac Death

Chen

Benditt

Alonso

2014

Circ J

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2588CHEN LY et al. Circulation JournalOfficial Journal of the Japanese Circulation Society http://www. j-circ.or.jp are only starting to understand -SCD. We will review the evidence for an independent relationship between AF and SCD in different contexts: recipients of implantable cardioverterdefibrillators (ICDs), patients with MI, HF, or hypertension (HT), and finally, in the general population. We will also examine the determinants of SCD in patients with AF and postulate on the mechanisms underlying this novel and intriguing association. AF and Ventricular Tachyarrhythmias in Recipients of ICDsOne of the earliest lines of evidence to suggest that AF may inherently increase the incidence of ventricular tachycardia (VT) or ventricular fibrillation (VF) comes from patients who have received an ICD. In a study comprising 229 patients who received ICDs between 1995 and 1999 for secondary prevention of SCD, 19 those who had persistent AF (n=38) at the time of ICD implant experienced appropriate device therapy for recurrent ventricular tachyarrhythmias more frequently than patients who were in sinus rhythm at the time of ICD implantation (n=191) (63% vs. 38%, P=0.01). From multivariable analysis, AF was an independent predictor of both appropriate ICD therapy (relative risk 1.8; 95% confidence interval [CI] 1.2-2.9) and inappropriate device therapy (relative risk 2.3; 95% CI 1.2-4.5). Analysis of device-stored electrograms revealed a higher incidence of short-long-short cycles preceding ventricular arrhythmias in AF compared with patients in sinus trial fibrillation (AF) is the most common sustained cardiac arrhythmia, and with the aging population its prevalence is increasing over time. 1-3 Additionally, AF is associated with an increased risk of stroke, 4 heart failure (HF), 5 and death. 6-11 The Framingham Heart Study reported that AF increases the risk of death by 1.5-fold in men and 1.9-fold in women. 6 Similarly, the reported Olmsted County, Minnesota experience showed that new-onset AF doubles the risk of mortality. 7 More recently, the Women's Health Study revealed that the risk of all-cause death was doubled and cardiovascular death quadrupled by new-onset AF in initially healthy women. 8 Although the evidence for an independent association of AF with an increased risk of mortality is compelling, there are few data on the causes of death in patients with AF; the most common causes of death in the aforementioned studies were coronary artery disease (CAD) and stroke. 6,7 There is evidence from post-myocardial infarction (MI) or HF patients that AF is associated with an increased risk of sudden cardiac death (SCD). 12-14 However, SCD was not specifically reported in previous population-based studies; 6-8 hence, it is unknown whether AF increases the risk of SCD in the general population. Moreover, because AF and SCD share many common risk factors, such as HF 15,16 and CAD, 17,18 it is possible that any possible association between AF and SCD is confounded or mediated by these shared risk factors.This narrativ...

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“…1 In response to their comments, we would like to point out that although our data show that a large proportion of deaths are attributable to cardiac mortality, either sudden cardiac death or heart failure, caution needs to be exercised in presuming any direct causal relationship between atrial fibrillation and either sudden cardiac death or heart failure death. The inter-relationship between these entities is likely to be complex, 2 and clearly more research is needed to delineate the most appropriate management strategies, including the question of whether catheter ablation would be of significant benefit in terms of mortality reduction in such a population. Indeed, the fact that optimal heart failure medical management was associated with a 45% lower rate of cardiac mortality in Randomized Evaluation of Long-Term Anticoagulant Therapy Study (RE-LY) suggests that addressing the common underlying substrate predisposing to heart failure as well as atrial fibrillation are critical.…”

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confidence: 99%

Response to Letter Regarding Article, “Causes of Death and Influencing Factors in Patients With Atrial Fibrillation: A Competing-Risk Analysis From the Randomized Evaluation of Long-Term Anticoagulant Therapy Study”

Marijon¹,

Heuzey²,

Connolly

et al. 2014

Circulation

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The Association Between Atrial Fibrillation and Sudden Cardiac Death

Abstract: Our findings suggest that a history of CHF, including both systolic and diastolic symptomatic dysfunction, may partially explain the AF-SCD association.

Cited by 50 publications

References 47 publications

Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial

Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial

Atrial Fibrillation and Its Association With Sudden Cardiac Death

Response to Letter Regarding Article, “Causes of Death and Influencing Factors in Patients With Atrial Fibrillation: A Competing-Risk Analysis From the Randomized Evaluation of Long-Term Anticoagulant Therapy Study”

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