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Should we screen for atrial fibrillation?

BMJ 2019; 364 doi: https://doi.org/10.1136/bmj.l43 (Published 13 February 2019) Cite this as: BMJ 2019;364:l43

Re: Should we screen for atrial fibrillation?

Thank you for an interesting pro et contra account on atrial fibrillation (AF) screening [1]. Although comprehensive and balanced, I would like to add some points that may complement the debate, and that may also be of interest in relation to the SAFER study, the world’s largest randomised controlled trial (RCT) of systematic screening for AF, recently launched in the UK [2, 3].

First, it is stated in the pro-argument that “current evidence provides a strong case for introducing AF screening now”. Still, the author recognizes that “there is likely to be an optimal screening duration and frequency for detecting paroxysmal AF” [1]. The latter is a crucial point, however largely unknown. We simply do not know how we should screen, for how long we should screen or who we should screen – in order to reach the desired outcomes (reduced stroke incidence or mortality). Only RCTs, such as the STROKESTOP and SAFER study [2, 4], can adequately respond to these crucial question.

Meanwhile, data from observational studies may provide us with some hints. In our Akershus Cardiac Examination (ACE) 1950 study in Norway[5], we performed a screening study using the exact same method as in STROKESTOP, and as planned in the SAFER study (Zenicor© handheld one-lead ECG; 30 seconds, twice daily and when symptoms, for two weeks). In the ACE 1950 study, a general population aged 65 years, was recruited. Screening was offered all those with one or more additional risk factor(s) for stroke (other than sex and age), according to the CHA2DS2-VASc score (i.e. ≥2 in men and ≥3 in women) (n=1,510). Still, in this ‘increased risk’ population, we found a relatively low prevalence of previously unknown AF; 0.9% at the age of 65 years [5].

On the other hand, as for the STROKESTOP study, our study demonstrated that handheld ECG seems suitable for the purpose of population screening. It was well accepted; as many as 99.5% of the participants recorded ≥20 ECGs during two weeks, and the rate of ECG ‘incidentalomas’ was negligible. Additional ECG monitoring (Holter or R test), due to low quality of the handheld ECGs, was only needed in 8 out of 1,510 participants [5].

One relevant question of interest with regard to screening by handheld ECG, is: What proportion of all cases of unknown AF is found by a two-week (or more), intermittent ECG strategy? While long-term continuous ECG (e.g. implanted loop recorders) may provide us with the ‘true prevalence’ of AF, we do not know whether all the AF potentially revealed by continuous surveillance, carry the same stroke risk as ‘traditional’, clinically detected AF. Bear in mind, the latter is the kind of AF largely represented in the trials we build our current practice on. In fact, evidence already exists pointing towards a positive association between increased AF burden (i.e. ‘time in AF’) and stroke risk [6, 7].

So, do we want to know of any little irregularity of the atria? No, probably not. And if so, can intermittent handheld ECG be viewed as a reasonable compromise between a single standard ECG and long-term continuous ECG, for the purpose of screening? Yes, probably. We may hypothesize that ‘multiple snapshots’ of 30 seconds during 2 weeks may detect more of the ‘relevant’ (i.e. at increased risk of stroke) unknown AF, while avoiding to pay notice to every single atrial run. The problem is; we do not how low burden of AF it is relevant to find (and treat). Fortunately, there are ongoing RCTs investigating this, but only in selected populations with existing implanted cardiac devices (and only from the comparable case of AHREs; atrial high-rate episodes, as identified from intracardiac electrograms) [8, 9]. Unfortunately, no studies have, to my knowledge, systematically investigated the proportion of ‘total unknown AF’ identified by intermittent handheld ECG, compared to long-term implantable ECG devices. If not already planned for, would it not be of interest to assess this in a subgroup of the SAFER study?

Lastly, I would like to add a point of concern regarding the use, or misuse, of the Wilson and Jungner WHO criteria for disease screening [10]. The apparent fulfilment of all or most of these criteria are widely being used as an argument that AF screening should or must be implemented [11]. However, as pointed out by UK screening experts [12], Wilson and Jungner regarded these principles only as a preliminary checklist, or a prerequisite to justify the search (and funding) of further evidence from RCTs. This is where we stand now, waiting for the evidence.

To conclude, we should not rush into any form of systematic screening for AF, before randomised controlled trials provide us with much needed answers. Meanwhile, we should continue raising awareness of AF and related risks, and at the same time continue the search for AF among our patients – be it by conventional or new methods of recording ECGs.

References:
1. Lown M, Moran P, Should we screen for atrial fibrillation? BMJ, 2019. 364:l43.
2. SAFER study webpage. [Accessed 2019 February 18th,]; Available from: https://www.safer.phpc.cam.ac.uk.
3. NIHR awards £3m for new research to investigate screening to prevent one in ten strokes (press release, 16 May 2018). [Accessed 2019 February 18th,]; Available from: http://www.phpc.cam.ac.uk/pcu/nihr-awards-3m-for-new-research-to-investi....
4. Svennberg E, Engdahl J, Al-Khalili F, Friberg L, Frykman V, Rosenqvist M, Mass Screening for Untreated Atrial Fibrillation: The STROKESTOP Study. Circulation, 2015. 131(25):2176-84.
5. Berge T, Brynildsen J, Larssen HKN, Onarheim S, Jenssen GR, Ihle-Hansen H, . . . Tveit A, Systematic screening for atrial fibrillation in a 65-year-old population with risk factors for stroke: data from the Akershus Cardiac Examination 1950 study. Europace, 2017. 10.1093/europace/eux293 [Epub ahead of print].
6. Van Gelder IC, Healey JS, Crijns H, Wang J, Hohnloser SH, Gold MR, . . . Connolly SJ, Duration of device-detected subclinical atrial fibrillation and occurrence of stroke in ASSERT. Eur Heart J, 2017. 38(17):1339-44.
7. Vanassche T, Lauw MN, Eikelboom JW, Healey JS, Hart RG, Alings M, . . . Connolly SJ, Risk of ischaemic stroke according to pattern of atrial fibrillation: analysis of 6563 aspirin-treated patients in ACTIVE-A and AVERROES. Eur Heart J, 2015. 36(5):281-7a.
8. Lopes RD, Alings M, Connolly SJ, Beresh H, Granger CB, Mazuecos JB, . . . Healey JS, Rationale and design of the Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation (ARTESiA) trial. Am Heart J, 2017. 189:137-45.
9. Kirchhof P, Blank BF, Calvert M, Camm AJ, Chlouverakis G, Diener HC, . . . Vardas P, Probing oral anticoagulation in patients with atrial high rate episodes: Rationale and design of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH-AFNET 6) trial. Am Heart J, 2017. 190:12-8.
10. Wilson JM, Jungner YG, Principles and practice of mass screening for disease. Public Health Papers No. 34. 1968, Geneva: World Health Organization.
11. Neubeck L, Orchard J, Lowres N, Freedman SB, To Screen or Not to Screen? Examining the Arguments Against Screening for Atrial Fibrillation. Heart Lung Circ, 2017. 26(9):880-6.
12. Raffle AE, Gray M, Screening: evidence and practice. 1st ed. 2007, New York, the United States: Oxford University Press Inc (textbook). 317.

Competing interests: The author has received honoraria/speaking fees from Boehringer-Ingelheim, Bayer and Pfizer/Bristol-Myers Squibb.

18 February 2019
Trygve Berge
MD, resident in training (internal medicine). PhD student.
Bærum Hospital (Vestre Viken Hospital Trust), Department of Medical Research and Department of Medicine. University of Oslo, Institute of Clinical Medicine.
Bærum/Oslo, Norway