Asymptomatic versus symptomatic atrial fibrillation: A systematic review of age/gender differences and cardiovascular outcomes

doi:10.1016/j.ijcard.2015.05.011

International Journal of Cardiology

Volume 191, 15 July 2015, Pages 172-177

https://doi.org/10.1016/j.ijcard.2015.05.011 Get rights and content

Highlights

•
Asymptomatic atrial fibrillation (AF) is more associated with male sex, irrespective of age.
•
Asymptomatic clinical status doesn't seem to affect death risk as well as thromboembolic risk.
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Clinical status shouldn't determine our approach to pharmacological prevention strategies.

Abstract

Up to 40% of atrial fibrillation (AF) patients are asymptomatic. Despite this, scarce data are available about asymptomatic AF, with regard to its clinical profile and relationship to cerebrovascular and cardiovascular risks. Our objective was to conduct a systematic review and meta-analysis was to study the relationship between age and gender with asymptomatic AF and to establish whether patients with asymptomatic AF have a higher risk of death (all-cause and cardiovascular) and stroke/systemic thromboembolism, when compared to symptomatic AF patients.

After a comprehensive search, 6 studies (2 randomized clinical trials and 4 observational studies) were entered in the meta-analysis.

Despite significant heterogeneity, our data show that the prevalence of females amongst asymptomatic AF group was significantly less compared to the symptomatic AF group (RR, 0.57; 95% CI: 0.52–0.64). No difference in age between asymptomatic and symptomatic AF patients (P = 0.72) was seen.

No differences were found in all-cause death between patients with asymptomatic and symptomatic AF (RR, 1.38; 95% CI: 0.82–2.17), nor in cardiovascular death (RR, 0.85; 95% CI: 0.53–1.36) or stroke/thromboembolism (RR, 1.72 95% CI: 0.59–5.08).

Asymptomatic AF is more associated with male sex, irrespective of age. Both general and cardiovascular death risks as well as thromboembolic risk do not seem to be affected by the asymptomatic clinical status. Symptomatic status should not determine our approach to stroke prevention and other cardiovascular prevention therapies, amongst patients with AF.

Introduction

Atrial fibrillation (AF) represents one of the most diagnosed supraventricular arrhythmia and its prevalence has been estimated to be 1–2% of the general population, with a progressive increase over the next few decades [1]. However, prevalence data of AF could have been underestimated due to the evidence that up to 40% of AF patients are asymptomatic [2].

Despite this, scarce data are available about asymptomatic AF, with regard to its clinical profile and relationship to cerebrovascular and cardiovascular risks.

Recent data from the EORP-AF Pilot Registry confirmed a high prevalence of asymptomatic AF patients, almost 40% [3]. Importantly, the EORP-AF data show that asymptomatic AF patients were at a higher risk for 1-year mortality compared to symptomatic AF patients [3]. Conversely a substudy from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial suggested that there is no difference in mortality risk between asymptomatic and symptomatic AF patients [4]. Furthermore, data from the Cryptogenic Stroke and Underlying AF (CRISTAL AF) study show how it could be possible to detect AF, regardless of symptoms, in about 4% in a cohort of patients diagnosed with cryptogenic stroke [5].

An understanding of the clinical profile of asymptomatic AF patients and the impact on a higher thromboembolic risk could help plan established AF screening programmes that could lead to earlier AF diagnosis and a reduction in the AF-related health burden [6].

The aim of this systematic review and meta-analysis of available evidence was to study the relationship between age and gender with asymptomatic AF and to establish whether patients with asymptomatic AF have a higher risk of death (all-cause and cardiovascular) and stroke/systemic thromboembolism, when compared to symptomatic AF patients.

Section snippets

Inclusion and exclusion criteria

We included eligible studies published in English that focused on the comparison between asymptomatic AF and symptomatic AF, in line with the following criteria:

i.
Types of studies: randomized controlled trials or observational cohort studies;
ii.
Types of participants: AF patients divided into symptomatic and asymptomatic groups;
iii.
Types of outcome measures: endpoints of all-cause mortality, cardiovascular death, stroke, or thromboembolism event; and
iv.
Other variables of interest: available baseline

Results

Based on our search, we identified 530 articles on the Cochrane Database, 3347 on PubMed and 4163 on Scopus. After checking for duplicates we reviewed a total of 4163 articles. Two investigators reviewed all titles, obtaining a list of 35 articles to be reviewed by abstract and full text. Following this, 6 articles were found to be eligible for analysis (Fig. 1).

Discussion

In this systematic review and meta-analysis, our data suggest that male sex is significantly associated with asymptomatic AF, whilst no difference was seen in age. Second, asymptomatic AF was similar to symptomatic AF in the risk of overall risks of death, CV death or stroke/thromboembolic events.

Gender-related differences in the epidemiology, clinical characteristics and management of AF patients are well described [12], [13], [14]. There is usually a higher incidence of AF in men than in

Conflict of interest

The authors report no relationships that could be construed as a conflict of interest.

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There are more references available in the full text version of this article.

Cited by (113)

Association Between Atrial Fibrillation Symptoms and Clinical Outcomes: A Prospective Multicenter Registry Study
2024, American Journal of Cardiology
The presence of symptoms plays an important role in determining whether to focus on rhythm control or rate control when treating atrial fibrillation (AF). Previous comparative studies on the clinical outcomes of symptomatic and asymptomatic AF have yielded inconsistent results, and a link between AF symptoms and left atrial (LA) remodeling is not established. Patients selected from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, which is a prospective, multicenter study consisting of patients with non-valvular AF, were grouped into 2 groups: symptomatic and asymptomatic. The primary outcome was a composite of the following cardiovascular outcomes: all-cause death, ischemic stroke, transient ischemic attack, systemic embolism, myocardial infarction, and heart failure hospitalization. Of 10,210 patients with AF, 4,327 (42%) had symptomatic AF. The asymptomatic group had an older mean age, more men, and more patients with hypertension and diabetes mellitus than the symptomatic group. The asymptomatic group had a larger left atrium (LA) diameter (43.6 vs 42.2 mm, p <0.001) than the symptomatic group. During a median follow-up of 32.9 (29.5 to 36.4) months, the asymptomatic and symptomatic groups showed similar incidences of the primary outcome (1.44 vs 1.45 per 100 person-years; log-rank, p = 0.8). In conclusion, the absence of AF symptoms is associated with increased LA. However, symptomatic and asymptomatic patients with AF have a similar risk of cardiovascular outcomes. This suggests that beneficial treatment for AF may be considered regardless of whether patients have symptomatic or asymptomatic AF.
Sex Differences in High-Cost Users of Healthcare for Atrial Fibrillation
2024, CJC Open
Healthcare resource use for atrial fibrillation (AF) is high, but it may not be equivalent across all patients. We examined whether sex differences exist for AF high-cost users (HCUs), who account for the top 10% of total acute care costs.
All patients aged ≥ 20 years who presented to the emergency department (ED) or were hospitalized with AF were identified in Alberta, Canada, between 2011 and 2015. The cohort was categorized by sex into HCUs and non-HCUs. Healthcare utilization was defined as ED, hospital, and physician visits, and costs included those for hospitalization, ambulatory care, physician billing, and drugs. All costs were inflated to 2022 Canadian dollars (CAD$).
Among 48,030 AF patients, 45.1% were female. Of these, 31.8% were HCUs, and the proportions of female and male patients were equal (31.9% vs 31.7%). Female HCUs were older, more likely to have hypertension and heart failure, and had a higher stroke risk than male HCUs. Mean healthcare utilization did not differ among HCUs by sex, except for number of ED visits, which was higher in male patients (12.7% vs 9.2%, P < 0.0001). Overall, HCUs accounted for 65.8% of the total costs (CAD$3.4 billion). Almost half of total HCU costs were attributable to female HCUs (CAD$966.1 million). Significant differences were present in the distributions of HCU-related costs (male patients: 74.6% hospitalization, 9.5% ambulatory care, 12.4% physician billing, 3.5% drugs; female patients: 77.7% hospitalization, 7.4% ambulatory care, 11.5% physician billing, 3.5% drugs, P < 0.0001).
Despite having a lower AF prevalence, female patients represent an equal proportion of HCUs, and account for almost half the total HCU costs. Interventions targeted at reducing the number of AF HCU are needed, particularly for female patients.
L’utilisation des ressources en santé est élevée pour la fibrillation auriculaire (FA), mais elle n’est pas forcément équivalente pour tous les patients. Nous avons examiné s’il existait des différences entre les sexes pour ce qui est des cas très coûteux de FA, qui représentent les 10 % supérieurs des coûts totaux de soins de courte durée.
Tous les patients âgés de 20 ans et plus qui se sont présentés au service des urgences ou qui ont été hospitalisés pour une FA ont été répertoriés en Alberta, au Canada, entre 2011 et 2015. La cohorte a été divisée par sexe en fonction des utilisateurs très coûteux et des autres utilisateurs. L’utilisation des soins de santé était définie comme des consultations aux urgences, à l’hôpital ou chez le médecin, et les coûts comprenaient les hospitalisations, les soins ambulatoires, les honoraires des médecins et les médicaments. Tous les coûts ont été convertis en dollars canadiens ($ CA) de 2022.
Parmi les 48 030 patients atteints de FA, 45,1 % étaient des femmes et 31,8 % étaient des utilisateurs très coûteux, en proportions égales entre les femmes et les hommes (31,9 % vs 31,7 %). Parmi les utilisateurs très coûteux, les femmes étaient plus âgées, plus susceptibles de présenter de l’hypertension et une insuffisance cardiaque, et leur risque d’AVC était plus élevé comparativement aux hommes. L’utilisation moyenne des soins de santé n’affichait pas de différences chez les utilisateurs très coûteux selon le sexe, à l’exception des consultations aux urgences, qui étaient plus fréquentes chez les hommes (12,7 % vs 9,2 %, p < 0,0001). Dans l’ensemble, les utilisateurs très coûteux représentaient 65,8 % des coûts totaux, qui étaient de 3,4 milliards de dollars canadiens. Les femmes représentaient par ailleurs près de la moitié du total des utilisations très coûteuses (966,1 millions de dollars canadiens). Des différences significatives ont été observées quant à la répartition des coûts liés aux utilisateurs très coûteux (hommes : hospitalisations [74,6 %], soins ambulatoires [9,5 %], honoraires des médecins [12,4 %], médicaments [3,5 %]; femmes : hospitalisations [77,7 %], soins ambulatoires [7,4 %], honoraires des médecins [11,5 %], médicaments [3,5 %], p < 0,0001).
Bien que la FA soit moins fréquente chez les femmes que chez les hommes, celles-ci représentent une proportion tout aussi importante des utilisations très coûteuses et comptent pour presque la moitié des coûts totaux attribuables aux utilisateurs très coûteux. Des interventions visant à réduire les utilisations très coûteuses pour la FA sont donc nécessaires, particulièrement chez les femmes.
Use of Anticoagulation for Thromboembolic Prophylaxis in Patients With Atrial High-Rate Episodes on Device Monitoring: A Narrative Review
2024, American Journal of Cardiology
Ischemic stroke and systemic thromboembolism are primary drivers of significant morbidity and mortality in patients with atrial fibrillation (AF). Although stroke is commonly the first index presentation of clinically silent AF, the growing use of continuous rhythm monitoring through cardiac implanted electronic devices has enabled earlier and increased detection of AF in patients who are otherwise asymptomatic before stroke development. Atrial high-rate episodes (AHREs) are atrial tachyarrhythmias frequently detected by cardiac implanted electronic devices; these events represent subclinical AF and other atrial tachyarrhythmias that can lead to stroke development and AF. Although the presence of AHREs increases the risk of developing both clinical AF and stroke compared with absence of AHREs, there has been a significant clinical variability in anticoagulation initiation in these subjects. In this narrative review, we explore the current evidence and published research surrounding the association between AHREs and stroke development in addition to the utility of anticoagulation in this population for thromboembolic prophylaxis.
Does early detection of atrial fibrillation reduce the risk of thromboembolic events? Rationale and design of the Heartline study
2023, American Heart Journal
The impact of using direct-to-consumer wearable devices as a means to timely detect atrial fibrillation (AF) and to improve clinical outcomes is unknown.
Heartline is a pragmatic, randomized, and decentralized application-based trial of US participants aged ≥65 years. Two randomized cohorts include adults with possession of an iPhone and without a history of AF and those with a diagnosis of AF taking a direct oral anticoagulant (DOAC) for ≥30 days. Participants within each cohort are randomized (3:1) to either a core digital engagement program (CDEP) via iPhone application (Heartline application) and an Apple Watch (Apple Watch Group) or CDEP alone (iPhone-only Group). The Apple Watch Group has the watch irregular rhythm notification (IRN) feature enabled and access to the ECG application on the Apple Watch. If an IRN notification is issued for suspected AF then the study application instructs participants in the Apple Watch Group to seek medical care. All participants were “watch-naïve” at time of enrollment and have an option to either buy or loan an Apple Watch as part of this study. The primary end point is time from randomization to clinical diagnosis of AF, with confirmation by health care claims. Key secondary endpoint are claims-based incidence of a 6-component composite cardiovascular/systemic embolism/mortality event, DOAC medication use and adherence, costs/health resource utilization, and frequency of hospitalizations for bleeding. All study assessments, including patient-reported outcomes, are conducted through the study application. The target study enrollment is approximately 28,000 participants in total; at time of manuscript submission, a total of 26,485 participants have been enrolled into the study.
The Heartline Study will assess if an Apple Watch with the IRN and ECG application, along with application-facilitated digital health engagement modules, improves time to AF diagnosis and cardiovascular outcomes in a real-world environment.
ClinicalTrials.gov Identifier: NCT04276441.
Natural history of ‘silent’ atrial fibrillation from subclinical to asymptomatic: State of the art and need for research
2023, European Journal of Internal Medicine
Representation of Women in Atrial Fibrillation Clinical Practice Guidelines
2022, Canadian Journal of Cardiology
Citation Excerpt :
At the same time, a population-level study conducted by Samuel et al. demonstrated that women were much less likely than men to undergo catheter ablation.30 Though women have a lower incidence of AF compared with men, they typically have more severe symptoms upon onset and are less likely to have asymptomatic AF.31,32 In addition, women are more likely to present with “atypical” symptoms, including weakness, dyspnea, and anxiety.33
Atrial fibrillation (AF) is the most common arrhythmia in men and women worldwide, and its prevalence is increasing. Management of AF is guided by evidence-based clinical practice guidelines which provide recommendations based on available evidence. The extent of sex-specific data in the AF literature used to provide guideline recommendations has not been investigated. Therefore, using the 2020 Canadian Cardiovascular Society (CCS) AF management guidelines as an example, the purpose of this study was to review female representation and the reporting of sex-disaggregated data in the studies referenced in AF guidelines.
Randomised controlled trials (RCTs) and prospective and retrospective cohorts were screened to calculate the proportion of study participants who were female and to establish whether studies provided sex-disaggregated analyses. The participant-prevalence ratio (PPR), a quotient of the female participant rate and the prevalence of women in the AF population, was calculated for each study.
A total of 885 studies included in the CCS guidelines were considered. Of those, 467 met the inclusion criteria. Overall, women represented 39.1% of the population over all of the studies and RCTs had the lowest proportions of women (33.8%, PPR 0.70). Of studies with sex-disaggregated analyses (n = 140; 29.9%), single-centre RCTs and retrospective cohorts had the lowest and highest rates of sex-specific analyses, respectively (11.5% and 32.5%).
The evidence used to derive guideline recommendations may be inadequate for sex-specific recommendations. Until enough data can support women-specific guidelines, increased inclusion of females in AF studies, may aid in the precision of recommendations.
À l'échelle mondiale, la fibrillation auriculaire (FA) est l'arythmie la plus fréquente chez les hommes et les femmes, et sa prévalence est en augmentation. La prise en charge de la FA est guidée par des directives de pratique clinique, fondées sur des données probantes, qui fournissent des recommandations basées sur les données disponibles. L'étendue des données sexospécifiques issues de la littérature sur la FA, et utilisées pour formuler des recommandations, n'a pas été étudiée. Aussi, en utilisant les lignes directrices 2020 de la Société canadienne de cardiologie (SCC) relatives à la prise en charge de la FA à titre d'exemple, l'objectif de cette étude était d'examiner la représentativité des femmes et de rapporter des données ventilées par sexe issues des études référencées dans les lignes directrices en matière de FA.
Des essais contrôlés randomisés (ECR) et des études de cohortes prospectives et rétrospectives ont été examinés afin de calculer la proportion de femmes parmi les participants aux études et d'établir si ces études fournissaient des analyses ventilées par sexe. Le ratio de prévalence des participants (RPP), quotient du taux de la participation féminine et de la prévalence des femmes dans la population souffrant de FA, a été calculé pour chaque étude.
Un total de 885 études incluses dans les lignes directrices de la SCC ont été prises en compte. Parmi celles-ci, 467 répondaient aux critères d'inclusion. Globalement, les femmes représentaient 39,1 % de la population sur l'ensemble des études et les ECR présentaient les proportions les plus faibles de femmes (33,8 %, RPP 0,70). Parmi les études comportant des analyses ventilées par sexe (n = 140 ; 29,9 %), les ECR monocentriques et les cohortes rétrospectives présentaient respectivement les taux les plus faibles et les plus élevés d'analyses sexospécifiques (11,5 % et 32,5 %).
Les preuves utilisées pour orienter les recommandations des lignes directrices peuvent être inadéquates en ce qui concerne les recommandations propres au sexe. Jusqu'à ce que des données suffisantes puissent soutenir des recommandations spécifiques aux femmes, l'inclusion accrue des femmes dans les études sur la FA peut contribuer à la précision des recommandations.

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¹: Both authors equally contributed to the study.

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ReviewAsymptomatic versus symptomatic atrial fibrillation: A systematic review of age/gender differences and cardiovascular outcomes

Highlights

Abstract

Introduction

Section snippets

Inclusion and exclusion criteria

Results

Discussion

Conflict of interest

Int. J. Cardiol.

Am. J. Med.

Am. Heart J.

Heart Rhythm.

Int. J. Cardiol.

J. Am. Coll. Cardiol.

Int. J. Cardiol.

Heart Disease and Stroke Statistics — 2015 update: a report from the American Heart Association

Cryptogenic stroke and underlying atrial fibrillation

N. Engl. J. Med.

Screening to identify unknown atrial fibrillation. a systematic review

Thromb. Haemost.

Review
Asymptomatic versus symptomatic atrial fibrillation: A systematic review of age/gender differences and cardiovascular outcomes