Prevalence and prognostic significance of device-detected subclinical atrial fibrillation in patients with heart failure and reduced ejection fraction

https://doi.org/10.1016/j.ijcard.2020.03.008Get rights and content

Highlights

  • Subclinical AF occurred in <5% of patients with HF and an implanted device.

  • New-onset subclinical AF was associated with a three-fold increased risk of stroke.

  • AF longer than 24-hours’ total duration increased CV hospitalisation risk.

  • AF did not increase the risk of mortality in the context of contemporary HF therapy.

Abstract

Background

Cardiac implanted electronic devices (CIEDs) can detect short durations of previously unrecognised atrial fibrillation (AF). The prognostic significance of device-detected subclinical AF, in the context of contemporary heart failure (HF) therapy, is unclear.

Methods

Amongst patients enrolled in the Remote Monitoring in HF with implanted devices (REM-HF) trial, three categories were defined based on total AF duration in the first year of follow-up: no AF, subclinical AF (≥6 min to ≤24 h), and AF >24 h. All-cause mortality, stroke, and cardiovascular hospitalisation were assessed.

Results

1561 patients (94.6%) had rhythm data: 71 (4.6%) had subclinical AF (median of 4 episodes, total duration 3.1 h) and 279 (17.9%) had AF >24 h. During 2.8 ± 0.8 years' follow-up, 39 (2.5%) patients had a stroke. Stroke rate was highest amongst patients with subclinical AF (2.0 per 100-person years) versus no AF or AF >24 h (0.8 and 1.0 per 100-person years, respectively). In the overall cohort, AF >24 h was not an independent predictor of stroke. However, amongst patients with no history of AF (n = 932), new-onset subclinical AF conferred a three-fold higher stroke risk (adjusted HR 3.35, 95%CI 1.15–9.77, p = 0.027). AF >24 h was associated with more frequent emergency cardiovascular hospitalisation (adjusted HR 1.46, 95%CI 1.19–1.79, p < 0.0005). Neither AF classification was associated with mortality.

Conclusions

In patients with HF and a CIED, subclinical AF was infrequent but, as a new finding, was associated with an increased risk of stroke. Anticoagulation remains an important consideration in this population, particularly when the clinical profile indicates a high stroke risk.

Introduction

In patients with heart failure (HF), clinically detected atrial fibrillation (AF) has been associated with reduced life-expectancy [1], more frequent hospitalisation [2], and possible attenuated benefits of proven HF therapies, including beta-blockers [3] and cardiac resynchronisation therapy [4]. Importantly, with greater use and sophistication of cardiac implanted electronic devices (CIEDs) for HF treatment, it has now become possible to detect even short-lived episodes of previously unrecognised atrial arrhythmias in this population. Many of these ‘subclinical’ episodes, which are often <24 h in duration, are verified to be AF but are either asymptomatic or confer few additional symptoms. Limited data exist regarding their association with clinical outcomes amongst patients with HF and, as yet, the optimal management of subclinical AF in the setting of HF remains unclear.

One expectation is that more sensitive detection and quantification of AF may improve the prevention of ischaemic stroke by enabling earlier initiation of oral anticoagulant therapy. To date, however, the minimum duration of AF that poses a stroke risk has not been reproducibly identified. Furthermore, amongst patients with HF, the incidence of stroke and the number of patients without pre-existing anticoagulation, in whom this may be initiated, may be low, thus limiting the benefits of this approach. Alternatively, recent data suggest that incident and worsening HF are more frequent adverse outcomes than stroke, amongst patients with AF [5], and in the ASSERT trial even short durations of AF were associated with an increased risk of HF hospitalisation [6]. Only a minority of patients enrolled in ASSERT (13%) had previous HF, hence this association may be magnified in a HF population and have important implications for therapeutic decision making.

To determine the prevalence and prognostic significance of subclinical AF in a large contemporary cohort of patients with HF and reduced ejection fraction (HFrEF), we analysed CIED-detected rhythm data and adjudicated clinical outcomes for patients enrolled in the Remote Management of Heart Failure Using Implanted Electronic Devices (REM-HF) trial [7]. We hypothesised that subclinical AF, defined as CIED-detected AF lasting between 6 min and 24 h, would not be associated with an increased risk of stroke, but would identify patients at increased risk of cardiovascular (CV) hospitalisation and death, and thereby provide relevant information for risk stratification in HF.

Section snippets

Methods

The design [8] and results [7] of REM-HF have been reported previously. Briefly, 1650 patients with stable HFrEF (NYHA class II–IV) and a CIED implanted within 6 months [7], were randomised 1:1 to receive usual care or management informed by remote monitoring. The primary composite endpoint of death or unplanned CV hospitalisation was not different between treatment groups [7]. All patients provided written informed consent and the trial conforms to the ethical guidelines of the 1975

Prevalence of subclinical atrial fibrillation

During the first year of enrolment, CIED-detected rhythm data were available for 1561 patients (94.6% of REM-HF cohort; mean age [±SD] 69.4 ± 10.2, 14% female). Since REM-HF was designed as a pragmatic trial, representing real-world clinical practice, in 89 patients the treating physician had judged that management of atrial rhythm status was of insufficient clinical priority to warrant implantation of an atrial lead, therefore accurate rhythm assessment was not possible. Patients without

Discussion

In this large contemporary HF cohort from the REM-HF trial, <5% of patients exhibited CIED-detected subclinical AF lasting between 6 min and 24 h (and 18% of patients exhibited AF > 24 h). Most cases of subclinical AF were new diagnoses. The absolute number of stroke events was low (2.5% of total cohort). In the overall analysis there was no association between persistent AF > 24 h and stroke risk. However, amongst the subset of patients with newly detected subclinical AF (i.e. no history of AF

Conclusions

In a contemporary cohort of patients with HFrEF and a CIED, detection of subclinical AF lasting less than or equal to 24 h, which did not progress to longer AF durations, was infrequent (<5%population), and was not associated with an overall increased risk of stroke, CV hospitalisation or mortality. However, for the subset of patients in whom subclinical AF was a new finding, the stroke rate was increased, emphasising the importance of considering anticoagulation when a patient's clinical

Funding

This work was supported by the British Heart Foundation (grant 28479) and Boston Scientific Ltd. (Arden Hills, St Paul MN, USA), Medtronic Ltd. (Minneapolis, MN, USA), and St. Jude Medical (Minneapolis, MN, USA). The Faculty of Medicine, University of Southampton, (Southampton, Hampshire, UK) was the recipient of the study's grants. The study sponsor was the University of Southampton NHS Foundation Trust. The study funders and sponsor had no role in study design, collection, analysis, and

Declaration of competing interest

JMM reports previous consultancy fees and research fellow support from Boston Scientific Ltd., Medtronic Ltd. and Abbott Ltd., during the time course of the study and after study completion, full time employment with Boston Scientific Ltd. SK reports receiving salary support via her host institution from Boston Scientific Ltd., Medtronic Ltd. and Abbott (formerly St Jude Medical Ltd). GAN reports research fellow support from Boston Scientific Ltd. and Abbott Ltd. JMc reports support for a

References (30)

  • R. Santhanakrishnan et al.

    Atrial fibrillation begets heart failure and vice versa: temporal associations and differences in preserved versus reduced ejection fraction

    Circulation

    (2016)
  • J.M. Morgan et al.

    Remote management of heart failure using implantable electronic devices

    Eur. Heart J.

    (2017)
  • J.M. Morgan et al.

    Rationale and study design of the REM-HF study: remote management of heart failure using implanted devices and formalized follow-up procedures

    Eur. J. Heart Fail.

    (2014)
  • W.M. Pollak et al.

    Clinical utility of intraatrial pacemaker stored electrograms to diagnose atrial fibrillation and flutter

    Pacing Clin. Electrophysiol.

    (2001)
  • B.C. Gorenek et al.

    Device-detected subclinical atrial tachyarrhythmias: definition, implications and management-an European Heart Rhythm Association (EHRA) consensus document, endorsed by Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS) and Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia (SOLEACE)

    Europace

    (2017)
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    All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

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