Screening for Atrial Fibrillation - AHSN CIA · 2017-05-24 · Screening for Atrial Fibrillation...

STATE OF THE ART

Circulation. 2017;135:1851–1867. DOI: 10.1161/CIRCULATIONAHA.116.026693 May 9, 2017 1851

ABSTRACT: Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country- and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.

WHITE PAPER

Screening for Atrial FibrillationA Report of the AF-SCREEN International Collaboration

© 2017 American Heart Association, Inc.

Ben Freedman, MBBS, PhD et al

Key Words: atrial fibrillation ◼ screening ◼ stroke

The full author list is available on page 1863.

Correspondence to: Ben Freedman, MBBS, PhD, Heart Research Institute, Charles Perkins Centre, Building D17, Level 3, Room 3114, University of Sydney, NSW 2006, Australia. E-mail [email protected]

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Freedman et al

May 9, 2017 Circulation. 2017;135:1851–1867. DOI: 10.1161/CIRCULATIONAHA.116.0266931852

AF-SCREEN: ESTABLISHMENT AND GOALSAF-SCREEN international collaboration was founded in Sep-tember 2015 and includes ˃100 physicians (cardiologists, electrophysiologists, primary care physicians, stroke neu-rologists, and geriatricians), nurses, allied health profes-sionals, epidemiologists, health economists, and patient group representatives from 31 countries. The collaboration seeks to promote discussion and research about screening for unknown or undertreated AF to reduce stroke and death and to provide advocacy for implementation of country-spe-cific AF screening programs (www.afscreen.org).

Although many patients with AF develop symptoms leading to appropriate diagnosis and management, the first manifestation may be a debilitating stroke or death. Finding AF before symptoms are manifested could lead to initiation of appropriate effective therapy, including oral anticoagulants (OACs) to reduce stroke and death1 and potentially initiation of risk-factor modifications to re-duce complications from AF progression.

The past decade has witnessed a surge in the number and sophistication of diagnostic tools, ranging from inex-pensive devices that detect persistent or paroxysmal AF to devices capable of long-term continuous characterization of brief, asymptomatic AF. Those participating in the AF-SCREEN collaboration recognize a unique and timely op-portunity to reexamine the approaches and rationale for AF diagnosis at an early asymptomatic stage. This prompted the development of a white paper on screening for AF, devel-oped from a consensus meeting of AF-SCREEN members held in Rome in August 2016. Full details of the genesis of the white paper and the Delphi process used are provided in the appendix in the online-only Data Supplement.

Incidence of Screen-Detected AF and Cardiac Implanted Electronic Device (CIED)-Detected Atrial High-Rate EpisodesMany terms have been used to describe screen-detected AF, including unrecognized, undiagnosed, silent, subclini-cal AF, and cardiac implanted electronic device (CIED)-de-tected atrial high-rate episodes. In this article, we will refer to AF detected on single-timepoint screening or patient-activated ECG recorders as screen-detected AF, whereas brief transient AF detected by CIEDs with atrial monitoring capability are referred to as CIED-detected atrial high-rate episodes. CIED-detected atrial high-rate episodes could be caused by oversensing or other atrial tachyarrhythmias and need close inspection of the stored electrograms be-fore labeling them AF. CIEDs are not implanted to screen for AF, and CIED-detected atrial high-rate episodes are not included in our definition of screen-detected AF and should not be grouped with screen-detected AF. A full discussion of CIED-detected atrial high-rate episodes has been included in this white paper principally to enhance

our understanding of the significance of screen-detected AF and its relationship with stroke.

The incidence of screen-detected AF strongly depends on the population screened and duration/intensity of screen-ing.2 Single-timepoint screening of a general population ≥65 years of age detects undiagnosed AF in 1.4%,3 and the AF detected is largely persistent. In a large population-based study of individuals 75 to 76 years of age, a more intense 2-week screening program using twice-daily intermittent handheld ECG recordings identified AF in 3.0% (0.5% on the initial ECG4). The identical protocol restricted to those with ≥1 additional stroke risk factor identified 7.4% with AF.5

The incidence of atrial high-rate episodes in patients with CIEDs ranges from 30% to 60% depending on the population and the detection algorithm used.6–15 In 2580 patients with a history of hypertension and no prior AF history, CIED-detected atrial high-rate episodes ≥6 min-utes were found in 35% of patients with implanted de-vices over a mean follow-up of 2.5 years and doubled the risk of stroke.11 Silent AF is more frequent than symp-tomatic AF in patients with a pacemaker or during ex-ternal continuous rhythm monitoring.16 Because patients with CIEDs have a medical condition that may affect the occurrence of atrial high-rate episodes, other studies (ASSERT-II [Subclinical AF in older asymptomatic patients] NCT01694394, REVEAL-AF [Incidence of AF in high risk patients] NCT01727297, GRAF [Graz study on the Risk of Atrial Fibrillation] NCT01461434, Danish Loop study NCT02036450) using subcutaneous long-term continu-ous monitoring in people at risk of AF may provide a more reliable estimate of AF in non-CIED populations and elucidate its clinical significance. The initial report of the ASSERT-II study showed that brief episodes of subclini-cal AF are common among individuals ≥65 years of age who have stroke risk factors and evidence of left atrial enlargement. Among 256 patients with an average left atrial volume of 76.5 mL receiving an implantable cardiac loop recorder, the rate of subclinical AF detection for epi-sodes lasting ≥5 minutes was 34% per year.17 The stud-ies reporting incidence of CIED-detected atrial high-rate episodes8,10–15,18,19 have been summarized in Table 1.

Risk of Stroke and Death in Untreated Screen-Detected AFNo data specifically address the risk of stroke and death in untreated screen-detected AF in the general popula-tion. The closest approximation includes cohort studies of individuals with AF detected incidentally in the ab-sence of symptoms. One study20 showed that individuals who were asymptomatic at presentation were 3 times as likely to have had an ischemic stroke before AF di-agnosis, and in follow-up they had similar risk of stroke and death as those with symptomatic AF. In a later study from this group, 161 out of 476 individuals with new AF were asymptomatic at presentation, and these people



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Screening for Atrial FibrillationSTATE OF THE ART


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Table 1. Incidence of Cardiac Implanted Electronic Device–Detected Atrial High-Rate Episodes in the Population With Cardiac-Implanted Devices

Year TrialDevice

IndicationClinical Profile

of Patients Mean Age % Male % LVEFMean

CHADS2 Follow-UpAF Burden Threshold Incidence of AF

2002 Gillis et al.8

PPMs for sinus node disease

All 70±12 52% NA NA 718±383 days

>1 min 157/231 (68%)

2003 Ancillary MOST10

PPMs for sinus node disease

All Median 73 (68,81) for no

AHRE

Median 75 (68,79) for AHRE

detected

45% NA NA Median 27 mo

>5 min 156/312 (50%)

2010 TRENDS15 PPMs and ICDs

All indications

History of prior stroke

No history of AF

No oral anticoagulant use

≥1 stroke risk factor

72.8±9.9 for no AHRE

74.0±9.1 for AHRE detected

63% for no AHRE

71% for AHRE

detected

NA 4.1±0.8 for no AHRE


Mean 1.4 y >5 min 45/163 (28%)

2012 TRENDS14 PPMs and ICDs

All indications

No history of prior stroke

No history of AF


≥1 stroke risk factor

70.2±11.8 66% NA ≥2 in 70% 1.1±0.7 y >5 min 416/1368 (30%)

2012 ASSERT11 PPMs and ICDs

All indications

History of hypertension

No history of AF


76±7 for no AHRE

77±7 for AHRE detected

59% for no AHRE

56% for AHRE

detected

NA 2.3±1.0 for no AHRE


2.5 y >6 min 895/2580 (34.7%)

2012 Home monitor CRT18

CRTDs and CRTPs

Congestive heart failure

Heart failure

No history of AF

66±10 77% 25 (20–30)

≥2 in 64% 370 days

(253–290)

≥14 min 126/560 (23%)

2013 Healey et al.12

PPMs

All indications

All 71.7±14.4 for no AHRE


59% for no AHRE

58% for AHRE

detected

NA

2.02±1.30 for no AHRE


Single center

Retrospective

>5 min 246/445 (55.3%)

2015 IMPACT19 ICDs and CRTDs

All indications

No permanent AF

No contraindications

for oral anticoagulant

64.2+11.5 for control

64.7+10.8 for intervention

73% for control

74% for intervention

29.4+11.3 for control

29.9+10.8 for

intervention

2 (median) 701 days >4–12 sec

945/2718 (34.8%)

2016 RATE Registry13

PPMs and ICDs

All

No permanent AF

73.6±11.8 for PPMs,

64.5±12.6 for ICDs

54% in PPM

72% in ICDs

57.8±10.5 for PPM

29.2±11.3 for ICDs

1.8±1.0 for PPM

2.0±0.8 for ICDs

22.9 mo (median)

> 3 atrial premature complexes

145/300 (48%) of PPM patients

155/300 (52%) of ICD patients of the representative samples studied

AF indicates atrial fibrillation; AHRE, atrial high-rate episode; ASSERT, Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial; CRT, cardiac resynchronization therapy; CRTD, cardiac resynchronization therapy defibrillator; CRTP, cardiac resynchronization therapy pacemaker; ICD, implanted cardioverter defibrillator; IMPACT, the IMPACT of BIOTRONIK Home Monitoring Guided Anticoagulation on Stroke Risk in Patients With ICD and CRT-D Devices; MOST, Mode Selection Trial; NA, not applicable; PPM, permanent pacemaker; RATE, Registry of Atrial Tachycardia and atrial fibrillation Episodes; and TRENDS, A Prospective Study of the Clinical Significance of Atrial Arrhythmias Detected by Implanted Device Diagnostics.



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had an increased risk for cardiovascular (hazard ratio [HR], 3.12; 95% confidence interval [CI], 1.50–6.45) and all-cause mortality (HR, 2.96; 95% CI, 1.89–4.64) com-pared to those with typical symptoms after adjustment for CHA2DS2-VASc score and age (Figure 1).21

In 5555 patients with asymptomatic clinical AF detect-ed incidentally in general practice, the adjusted stroke rate in the 1460 untreated patients was 4% and all-cause mortality 7% over 1.5 years of follow-up compared with 1% and 2.5%, respectively, in matched controls with-out AF.22,23 In the EORP AF registry (Eurobservational Research Programme), mortality at 1 year was ˃2-fold higher in asymptomatic versus symptomatic AF (9.4% versus 4.2%, P<0.0001).24 In the Belgrade AF study, survival free of AF progression or ischemic stroke was worse in those with an asymptomatic presentation.25

The major studies regarding thromboembolic risk of CIED-detected atrial high-rate episodes in patients with implanted pacemakers, defibrillators, and cardiac resyn-chronization devices all show increased stroke rate with CIED-detected atrial high-rate episodes, but the absolute risk of stroke was much lower than might be expected for patients with clinical AF and similar CHA2DS2-VASc score.6,7,9–11,13,18 A minimum 5-minute duration of atrial high-rate episodes was found to have clinical relevance in the MOST study (Mode Selection Trial).10 Alternative arbitrary or data-derived atrial high-rate episodes burden cut points have been explored over the subsequent 10 years, ranging from 5 minutes to 24 hours.11 Uncer-tainty remains about the minimum burden that increas-es thromboembolic risk. A recent reevaluation of the

ASSERT study indicated that stroke risk was increased only in patients with atrial high-rate episodes duration ≥24 hours.26 These studies are summarized in Table 2.

Key Point 1Screen-detected AF as found on single-timepoint screen-ing or intermittent 30-second recordings over 2 weeks is not a benign condition and, with additional stroke risk factors, carries sufficient risk of stroke to justify consid-eration of screening and therapy to prevent stroke.

Response to Treatment of Screen-Detected AFScreening for a particular disease implies that an effec-tive therapy improves outcomes. For AF, OACs have a major impact on reducing stroke, systemic embolism, and all-cause mortality.28 The nonvitamin-K antagonist OACs further improve outcomes with less intracranial bleeding.29 It has been questioned whether screen-de-tected AF should prompt OAC treatment and whether the response to treatment is the same as for symptomatic AF. An undetermined proportion of asymptomatic pa-tients with incidentally detected AF were included in the pivotal anticoagulant studies, but these studies have not been analyzed separately.28 No randomized controlled trials exist, and it may be unethical to randomize pa-tients with screen-detected AF to no therapy or an inef-fective drug such as aspirin. The treatment decision for a given individual with screen-detected AF is determined by stroke risk factors (CHA2DS2-VASc score) according to guidelines1,30 and by the duration of the AF episode in the case of CIED-detected atrial high-rate episodes.

In the cohort study of 5555 asymptomatic patients with AF detected incidentally in general practice, OAC therapy (n=2492) compared with no antithrombotic thera-py (n=1460) was associated with significantly reduced ad-justed risk of stroke from 4% to 1% and death from 7% to 4% in only 1.5 years, suggesting that screen-detected AF may respond similarly.22,23 Ongoing studies, including AR-TESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibril-lation; NCT01938248) and NOAH (Non-vitamin K Antago-nist Oral Anticoagulants in Patients With Atrial High Rate Episodes; NCT02618577), will help refine the benefit of nonvitamin-K antagonist OACs in CIED-detected atrial high-rate episodes and provide more information on the burden or duration of atrial high-rate episodes that will benefit.

Screen-detected AF (single-timepoint screening or patient-initiated recording) is likely to have the same re-sponse to OAC therapy as incidentally detected AF and symptomatic AF, with significant reduction in stroke and death. The absolute level of stroke risk for CIED-detect-ed atrial high-rate episodes may be lower than screen-detected AF and may modify the risk-benefit of OAC therapy. The burden threshold of CIED-detected atrial

Figure 1. Survival stratified by type of AF presentation. Kaplan-Meier curve for all-cause mortality according to presentation with either typical AF symptoms (palpitations with or without other symptoms), atypical symptoms (fatigue, chest pain, shortness of breath, lightheadedness, syncope, decreased exercise tolerance, but without palpitations), or as-ymptomatic (AF detected incidentally during a routine visit for an unrelated problem). AF indicates atrial fibrillation. Reprinted from Siontis et al21 with permission of the Heart Rhythm Soci-ety. Copyright © 2016, Heart Rhythm Society.



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high-rate episodes/CHA2DS2-VASc score associated with a positive risk-benefit ratio is under investigation.

Role of AF in Ischemic StrokeIn stroke registries, at least a third of patients with isch-emic stroke have either previously known31,32 or newly detected AF at the time of stroke.33 Stroke was the first manifestation of AF in ˃25% of AF-related strokes.31 The association with AF is even higher if prolonged poststroke external or implanted monitoring is performed.34,35 In the Swedish Riks-Stroke register of ˃94 000 ischemic strokes, ≈9% were associated with previously unknown AF and 20% with known but undertreated AF,31,32 whereas in a global registry 10% were caused by previously unknown AF.36

Recent evidence from CIEDs raises questions about the temporal and mechanistic relationship between AF and stroke, and whether AF is necessary for left atrial thrombo-embolism to occur.9,37–39 In several studies, there does not appear to be a proximate temporal relationship between de-vice-detected atrial high-rate episodes and strokes although patients with atrial high-rate episodes are at increased risk for stroke.19,37,38 Only a small minority of patients with CIED-

detected atrial high-rate episodes who have a stroke experi-ence arrhythmia in the month before a stroke.9,37 One third had no atrial high-rate episodes during ≈1 year of rhythm monitoring before their stroke and only manifested atrial high-rate episodes after their stroke.19,37 Furthermore, mul-tiple markers of abnormal atrial substrate have been associ-ated with stroke independently of AF.40 In a small proportion of patients, however, a close proximate relationship exists between a daily atrial high-rate episode burden ≥5.5 hours and stroke, with risk highest in the 5 days before stroke, falling to a nonsignificant increase in risk by 30 days be-fore stroke (Figure 2), pointing to AF being a risk factor in these patients.41 The temporal relationship between CIED-detected atrial high-rate episodes and stroke is summarized in Table 3. A limitation of these studies is the small numbers of strokes and usually lack of adjudication as cardioembolic.

Even short AF episodes can create a prothrombotic state that persists for some time after the episode. Fur-thermore, atrial cardiomyopathy related to aging or sys-temic risk factors43 can lead to AF or atrial thromboem-bolism. Once AF develops, it impairs atrial function and secondarily leads to atrial remodeling, which in addition

Table 2. Summary of Studies Regarding Cardiac Implanted Electronic Device–Detected Atrial High-Rate Episodes and Thromboembolic Risk

Trial (Year)Number of Patients

Duration of Follow-Up

Atrial Rate Cutoff (bpm) AF Burden Threshold

Hazard Ratio for TE Event

TE Event Rate (Below vs. Above AF Burden

Threshold)

Ancillary MOST10 (2003)

312 27 mo (median) >220 5 min 6.7 (P=0.020) 3.2% overall (1.3% vs. 5%)

Italian AT500 Registry7 (2005)

725 22 mo (median) >174 24 h 3.1 (P=0.044) (95% CI, 1.1‒10.5)

1.2% annual rate

Botto et al6 (2009)

568 1 y (mean) >174 CHADS2+AF burden n/a 2.5% overall (0.8% vs.

5%)

TRENDS9 (2009) 2486 1.4 y (mean) >175 5.5 h 2.2 (95% CI, 0.96‒5.05,

P=0.06)

1.2% overall (1.1% vs. 2.4%)

Home Monitor CRT18 (2012)

560 370 days (median)

>180 3.8 h 9.4 (95% CI, 1.8–47,

P=0.006)

2.0% overall

ASSERT11 (2012)

2580 2.5 y (mean) >190 6 min 2.5 (P=0.007) (95% CI, 1.28‒4.85)

(0.69% vs. 1.69%)

SOS27 (2014) 10016 2 y (median) >175 1 h 2.11 (P=0.008) (95% CI, 1.22–3.64)

0.39% per year overall

RATE Registry13 (2016)

5379 (3141 with pacemakers and 2238 with ICDs)

22.9 mo (median)

NA Nonsustained atrial high-rate episodes with a duration from 3 atrial

premature complexes to 15–20 s

0.87 (95% CI, 0.58–1.31,

P=0.51)

For nonsustained atrial high-rate episodes: 0.55%

(0.34%–0.76%) per year for pacemakers and 0.81% (0.50%–1.12%)

per year for ICDs

AF indicates atrial fibrillation; AHRE, atrial high-rate episode; ASSERT, Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial; bpm, beats per minute; CI, confidence interval; CRT, cardiac resynchronization therapy; ICD, implanted cardioverter defibrillator; MOST, Mode Selection Trial; NA, not applicable; RATE, Registry of Atrial Tachycardia and Atrial Fibrillation Episodes; SOS, stroke prevention strategies; TE, thromboembolic; and TRENDS, A Prospective Study of the Clinical Significance of Atrial Arrhythmias Detected by Implanted Device Diagnostics.



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to flow abnormalities further increases thromboembolic risk.43 Atrial cardiomyopathy as a cause of thromboem-bolism before AF could explain why a brief period of AF is associated with stroke months later, why many patients manifest AF for the first time after a stroke, and why one third of strokes are currently of unknown cause. Advanced neurocardiac imaging and continuous monitoring may provide further insights into the pathophysiology in future.

Nevertheless, AF remains an important risk marker as well as risk factor for stroke, with well-documented effica-

cy of OAC for stroke prevention. Anticoagulated patients with AF have residual stroke rates similar to matched individuals without AF, which underlines the efficacy of OACs in prevention of AF-related stroke.23 OACs remain underused in AF patients at risk of stroke: 30% to 50% of eligible patients with AF are not being given OAC, many are mistreated with aspirin monotherapy, and the remain-der are not receiving any antithrombotic therapy.31,34,44

It is likely that both unknown and undertreated AF con-tribute to a substantial proportion of all strokes, which could be prevented by screening strategies. Regarding the role of AF in stroke, it is likely that AF is both a risk factor and a strong risk marker for stroke.

Which Patients or Individuals to Screen?For a screening program to be efficient, the screening technique must have a high positive predictive value us-ing a low-risk tool at low cost. Screening yield depends on disease prevalence and diagnostic test performance. AF increases disproportionally in older adults, rendering age 1 of the best predictors of AF.45 The prevalence of AF ˂50 years of age is negligible in most populations and may not justify screening in this group.45 The preva-lence of AF differs by ethnicity; for example, indigenous Australians have a higher burden of AF and higher risk at much younger ages than Europeans.46

If the screening procedure is inexpensive and easy to use (eg, pulse palpation or single-timepoint handheld de-vices),47,48 screening can be nonselective and just age-based. A threshold ≥65 years of age (a CHA2DS2-VASc score of at least 1 in a male and 2 in a female) will detect undiagnosed AF in 1.4% in clinic or population settings,3 in which case European Society of Cardiology (ESC) guidelines recommend that OAC be considered (Class IIa); OACs are recommended (Class I) for a score of 2 in a male or 3 in a female.30 Opportunistic screening in all patients contacting the health system ≥65 years of age has been adopted in the ESC AF guidelines30 but might

Figure 2. Time trend of risk of stroke for AF in 60 days before stroke. Odds ratio for nonoverlapping 5-day epochs of AF burden in implanted devices ≥5.5 hours in 1 day during the 5-day epoch, from 1 to 5 days before stroke (left-hand point), through 56 to 60 days before stroke (right-hand point). Each stroke case epoch is matched to six 5-day control epochs between 91 and 120 days before stroke. There is a progressive fall in odds ratio of stroke from 17.4 for AF occurring 1 to 5 days before stroke to nonsignificant increases for AF >21 days before stroke. AF indicates atrial fibrillation. Reprinted from Turakhia et al41 with permission of the American Heart Association, Inc. Copyright © 2015, American Heart Association, Inc.

Table 3. Temporal Relationship Between Cardiac Implanted Electronic Device–Detected Atrial High-Rate Episodes and Stroke

Year Trial

Number of Patients With

TE Event Definition of AF EpisodeAny AF Detected Before TE Event

AF Detected Only After TE

Event

No AF in 30 Days Before TE

Event

Any AF in 30 Days Before TE

Event

2012 Boriani et al42 33/3438 5 min 21/33 (64%) NA 12/33 (67%) 11/33 (33%)

2011 TRENDS9 40/2486 5 min 20/40 (50%) 6/40 (15%) 29/40 (73%) 11/40 (27%)

2014 ASSERT11,37 51/2580 6 min 18/51 (35%) 8/51 (16%) 47/51 (92%) 4/51 (8%)

2014 IMPACT19 69/2718 36/48 atrial beats ≥200 beats per minute

20/69 (29%) 9/69 (13%) 65/69 (94%) 4/69 (6%)

2015 Turakhia et al41

187/9850 ≥5.5 h or ≥6 min on any day 120 days previously

36/187 (19%) ≥5.5 h 50/187 (26%) ≥6 min

NA NA NA

AF indicates atrial fibrillation; ASSERT, Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial; IMPACT, the IMPACT of BIOTRONIK Home Monitoring Guided Anticoagulation on Stroke Risk in Patients With ICD and CRT-D Devices; NA, not applicable; TE, thromboembolic; and TRENDS, A Prospective Study of the Clinical Significance of Atrial Arrhythmias Detected by Implanted Device Diagnostics.



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be more efficient if an older age threshold is chosen or an additional stroke risk factor is required.49 Superiority over a simple age-based criterion, however, needs to be proven.

Among individuals 75 years of age in Sweden, a single ECG detected 0.5% to 1% with undiagnosed AF.4,5 Adding 2 weeks of twice-daily patient-activated handheld ECG de-tected an additional 2.5% with undiagnosed AF4 and 7.4% after enrichment with ≥1 additional stroke risk factors.5 Even more AF is detected with continuous recording by external or implanted devices (Table 1), but that technology is costly and may only be justified in populations at high risk and with suf-ficient yield from screening (eg, older age plus additional risk factors or embolic stroke of undetermined source [ESUS]). Adding biomarkers (eg, natriuretic peptides, high-sensitivity troponin) to existing clinical predictors may improve the pre-diction of AF incidence.50,51 However, there is marginal im-provement in model discrimination and reclassification.

Key Point 2Single-timepoint screening of people ≥65 years of age in the clinic or community appears justified based on yield of screening and likely cost-effectiveness. For those ˃75 years of age or in younger age groups at high risk of AF or stroke, 2 weeks of twice-daily intermittent AF screen-ing may be warranted.

Ischemic Stroke and ESUSRandomized controlled trials and observational studies have established the effectiveness of ECG monitoring after stroke for improving AF detection (number needed to screen=8–14), 33,52 with longer monitoring durations increasing AF detection probability. ECG monitoring after stroke is likely cost-effective.53,54 However, randomized controlled trials have not been powered to assess the ef-fect of prolonged ECG monitoring on stroke or mortality.

After an acute ischemic stroke/transient ischemic attack in patients not known to have AF and without contraindica-tions to OACs, a tiered AF ECG monitoring approach is ad-vised. ESC guidelines recommend ≥72 hours ECG monitor-ing in all stroke survivors,30 but more research is required to identify non-ESUS subgroups benefitting most from more prolonged monitoring. Ongoing randomized controlled trials are exploring an alternative strategy of blanket nonvitamin-K antagonist OAC therapy after limited negative Holter moni-toring in ESUS (RE-SPECT [Randomized, Double-Blind, Eval-uation in Secondary Stroke Prevention Comparing the Ef-ficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid] ESUS NCT02239120 and NAVIGATE ESUS [Rivaroxaban Versus Aspirin in Second-ary Prevention of Stroke and Prevention of Systemic Embo-lism in Patients with Recent ESUS] NCT02313909).

Key Point 3Long-term continuous rhythm monitoring using either external or implanted devices or extended intermittent

patient-activated recordings may diagnose clinically im-portant AF in individuals with recent ESUS.

Overview of Screening MethodsPulse palpation to assess pulse irregularity is a readily accessible method for screening in primary care, shown to be effective as a screening strategy in the SAFE study (Screening for Atrial Fibrillation in the Elderly).65 It can also be used in the community, in both high- and low-mid-dle-income countries, but has some limitations.55 In the clinic, it is usually performed by physicians or nurses, whereas in the community, nonphysician health profes-sionals and lay people can be trained to detect pulse irregularity. In routine primary care, the pulse is infre-quently assessed. Cardiac auscultation can also detect AF but is even less frequently performed in primary care.

Innovation in technology has produced new screening devices that improve feasibility and cost-effectiveness of widespread screening (Table 4). These devices are recognized as valid for AF detection by the European Pri-mary Care Cardiovascular Society66 and could be used to complement traditional screening by pulse palpation.

Oscillometric blood pressure monitors with an AF de-tection function based on pulse irregularity offer high sen-sitivity (92% to 100%) and specificity (90% to 97%) and are superior to pulse palpation.57,61,62 The devices can be used by health workers or patients, provide single-timepoint or multiple patient-activated recordings, and have been evalu-ated by health technology assessments.67 Finger photople-thysmography, using a smartphone camera and flash, has sensitivity 93% and specificity 98% for AF detection us-ing proprietary algorithms with variable techniques to deal with ectopic beats.64,68,69 Similar algorithms are being built into smart-watches and fitness bands. The technology is attractive given the wide distribution of smartphones but requires a noise-free trace for optimal performance. Ulti-mately, with all pulse-based detection systems, an ECG is required to confirm AF,1,70 either 12-lead (current gold standard) or single-lead documenting P-waves.

A range of handheld devices produce diagnostic qual-ity lead 1 single-lead ECGs, most with automated algo-rithms more accurate than pulse palpation (sensitivity 94% to 99% and specificity 92% to 97%).57,58,60,71 These devices have been widely used for single-timepoint AF screening.48,58 Repeated handheld ECG recordings over 14 to 28 days have diagnostic accuracy equivalent to standard event recorders, superior to 12-lead ECG and 24-hour Holter for paroxysmal AF,5,60,72 and have been used successfully in large-scale AF screening studies.4,5 Although single-lead ECGs may not always show P-waves, the advantages outweigh this limitation. The accepted ar-bitrary episode duration for defining AF is 30 seconds.

Continuous monitoring coupled with a diagnostic algo-rithm will detect paroxysmal AF more effectively than re-peated patient-activated devices, although the prognos-



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tic significance of brief episodes is uncertain. Continuous monitoring can be accomplished by noninvasive devices (eg, prolonged Holter monitoring, a wearable nonadhe-sive dry-electrode belt,73 or a wearable-patch: feasible for 2 to 4 weeks74 and superior to 24-hour Holter).

The main disadvantages of prolonged external moni-toring are skin irritation from electrodes and patches, leading to reduced patient compliance, and the large amounts of data generated.

All devices with automated AF diagnostic algorithms require low-noise high-quality signals for optimal perfor-mance. This may be difficult when devices are given to patients or used in the community. High sensitivity is desir-able, but there is a trade-off with lower specificity, which can create much extra work and cost in verifying diagnoses with an ECG (if not recorded by the device).70 Device per-formance, therefore, must be tested in the setting where it will be used for screening to optimize performance.

Key Point 4Mass or opportunistic screening for AF can be accom-plished by pulse palpation; oscillometric (blood pressure) or photoplethysmographic (smartphone camera) devices; and handheld ECG devices providing a rhythm strip. Be-cause ECG confirmation is mandated by guidelines for the diagnosis of AF, handheld ECG devices have the advantage

of providing a verifiable ECG trace and would therefore be the preferred screening tool. Prolonged continuous ECG monitoring with external or subcutaneous recorders will diagnose more paroxysmal AF but requires further evalu-ation: cost-effectiveness will be limited by expense and detection of AF with lower absolute stroke risk.

Settings for ScreeningInterest in community screening has increased recently in a number of countries.3–5,75–78 Prospective studies have used pulse palpation, single- or multilead ECG, and single-timepoint or intermittent recordings using systematic or opportunistic approaches across entire populations or age-specific strata of total populations or defined popu-lations in cohort studies. Screening has also been per-formed opportunistically in volunteers during annual events (eg, Heart Rhythm Week in Belgium76). The STROKESTOP study4 invited half of the 75- to 76-year-olds in 2 Swedish regions to attend screening, and 53% accepted, similar to the rate in the SAFE study.65 This approach was stepped, with an initial single-lead ECG, followed by twice-daily inter-mittent patient-activated ECG recordings over a 2-week period in those individuals without AF.

Pharmacies offer an attractive setting for community screening.48,79 People ≥65 years of age with chronic con-

Table 4. Sensitivity and Specificity of Different Methods of Screening for Atrial Fibrillation

Device Method of Interpretation Sensitivity (%) Specificity (%) Reference

Pulse palpation 94 (84–97) 72 (69–75) Cooke et al55

Handheld single-lead ECGs

AliveCor (Kardia) heart monitor Algorithm only (based on presence of P wave and RR irregularity)

98 (89–100) 97 (93–99) Lau et al56

Merlin ECG event recorder Cardiologist interpretation 93.9 90.1 Kearley et al57

Mydiagnostick Algorithm only (based on RR irregularity) 94 (87–98) 93 (85–97) Tieleman et al58

Vaes et al59

Omron HCG-801 Algorithm only (based on RR irregularity) 98.7 (93.2–100) 76.2(73.3–78.9) Kearley et al57

Omron HCG-801 Cardiologist interpretation 94.4 94.6 Kearley et al57

Zenicor EKG Cardiologist interpretation 96 92 Doliwa et al60

Modified blood pressure monitors

Microlife BPA 200 Plus Algorithm only (based on pulse irregularity) 92 97 Marazzi et al61

Microlife BPA 200 Algorithm only (based on pulse irregularity) 97 (81.4–100) 90 (83.8–94.2) Wiesel et al62

Omron M6 Algorithm only (based on pulse irregularity) 100 94 Marazzi et al61

Omron M6 comfort Algorithm only (based on pulse irregularity) 30 (15.4–49.1) 97 (92.5–99.2) Wiesel et al62

Microlife WatchBP Algorithm only (based on pulse irregularity) 94.9 (87.5–98.6) 89.7 (87.5–91.6) Kearley et al57

Plethysmographs

Finger probe Algorithm only (based on pulse irregularity) 100 91.9 Lewis et al63

iPhone photo-plethysmograph Algorithm only (based on pulse irregularity) 97.0 93.5 McManus et al64*

The comparator for all studies was a 12-lead ECG; RR irregularity indicates irregularity of intervals between successive R waves on the ECG.*Three-lead telemetry used.



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ditions in many countries visit their community pharmacy every 1 to 3 months. AF screening with pulse check and smartphone-based ECG in Australian pharmacies was found to be feasible, cost-effective,48 and well accepted.80 The ma-jor issue is ensuring referral and then treatment of detected individuals,79 so an established referral pathway is crucial.

Primary care is an ideal setting: In addition to regu-lar primary care physician visits, nursing support for screening is available, and there is a direct link with the practitioner to prescribe OAC. Two challenges remain: (1) developing a sustainable strategy for detecting un-diagnosed AF, and (2) providing adequate treatment for patients with known or newly discovered AF because undertreatment is common.81

The SAFE study showed that opportunistic screening with pulse palpation in primary care was as effective as sys-tematic 12-lead ECG screening in detecting undiagnosed AF in patients ≥65 years of age, and more cost-effective.65 Although some guidelines recommend screening using pulse palpation,30 pulse taking is not common practice.82 The new ESC guidelines have added ECG rhythm strip to the recommendation on pulse palpation for opportunistic screening.30 For scalability and sustainability, screening could be linked to existing workflow (eg, cardiovascular risk management programs or influenza vaccination).47,58,83–85 Computerized medical records linked to electronic deci-sion support tools86 could provide prompts for regular screening, calculate stroke risk, and advise guideline-rec-ommended therapy to assist workflow and treatment deci-sions (eg, AF SMART ACTRN12616000850471).

In some countries, large generalist or specialized out-patient clinics provide an alternative setting to primary care for screening87 but may have similar issues with sustainable delivery of the screening intervention and subsequent treatment.

Key Point 5The setting for AF screening needs to be individualized according to country- and healthcare system-specific requirements and resources and must be linked to a pathway for appropriate diagnosis and management for screening to be effective. Settings that have been used ef-fectively include some that are community-based and oth-ers based in primary care, specialist practices, or general or specialist clinics. Primary care and outpatient clinics have the advantage of offering a direct link with treatment and a potentially sustainable workflow (see online-only Data Supplement for country-specific considerations).

Health-Economic AssessmentsEconomic assessment of AF screening depends on a range of factors, including: (1) rate of undiagnosed AF in the target population, (2) difference in AF detection between the screening intervention and routine practice without screening (3) stroke and mortality risk of the

target population, (4) expected reduction in stroke and mortality and increase in bleeding risk from OAC, (5) cost of the screening methodology, and (6) country-spe-cific “willingness-to-pay” thresholds to avoid 1 stroke.In the first paper on health economic modeling for AF screening,88 both annual ECG screening and pulse pal-pation with confirmatory ECG were cost-effective in a Japanese population. Later, the SAFE study evaluated opportunistic versus systematic screening using pulse palpation followed by ECG65,89 and showed, using proba-bilistic sensitivity analyses, a 60% likelihood that oppor-tunistic screening was cost-effective in both men and women. The Swedish STROKESTOP population screen-ing study4 confirmed that ECG screening was likely to be cost-effective using a lifelong decision-analytic Markov model.90 Two other smaller studies evaluating smartphone ECG screening in community pharmacies48 (relying on estimated stroke and death rates and im-provements with OAC treatment in incidentally detected asymptomatic AF)22 and pulse checking in an influenza vaccination clinic91 also described cost-effectiveness. A simulation of direct medical costs in the United States concluded that costs were greater in those patients with undiagnosed AF than for similar people without AF, jus-tifying strategies to identify and treat undiagnosed AF.92

Most recently, a study of lifetime costs and effects of a single handheld ECG screening of patients ˃ 65 years of age during the annual influenza vaccination in The Neth-erlands83 found that screening would decrease overall costs by €764 (USD$939) and increase quality-adjusted life years by 0.27 per patient. That is, AF screening for patients >65 years of age during the influenza vaccina-tion was likely to be cost-saving.

Reviews of systematic and opportunistic screening for AF detection93,94 indicate that both were more cost-effec-tive than routine practice for those ≥65 years of age, al-though this outcome depends on method chosen, frequen-cy of screening, and age. For example, a formal Health Technology Assessment in Ireland considered a number of models and found costs per quality-adjusted life year varying between €792 619 (USD$936 902) for screening annually from 55 years of age to €8037 (USD$9500) for a single screening at 75 years of age,95 but no data are avail-able on the detection rate for annual or other frequencies of repeated screening. More data are required to compare cost-effectiveness of different screening interventions and the effect of different age cutoffs.

Screening for Undertreated Known AFUndertreatment exposes patients to a significant risk of fatal or disabling strokes. Population surveys96,97 and registries indicate that treatment remains suboptimal with large country differences.31 Population screening using a variety of techniques3,4,76 would identify under-treated patients and may provide an opportunity to refer



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to appropriate physicians or clinics to initiate OACs or reinitiate OACs in those who have discontinued.4,30,31

A prospective, Swedish population-based study found 9.5% of individuals (81/848) were known to have AF on a 12-lead ECG: 43% of these patients were not on OAC.5 Through the screening program, 52% of undertreated individuals had OAC initiated. A similar number of patients had known AF (9.3%) in the STROKESTOP study,4 but only 22% were not on OAC. After cardiologist follow-up, more than half without contraindications commenced OAC therapy. This finding highlights the importance of future implementation research in which AF screening programs incorporate well-defined re-ferral pathways and strategies for initiating OAC therapy, in both newly diagnosed and undertreated known AF.

Patient Preferences and AdvocacyA large patient survey reported that a majority of pa-tients with persistent AF were in favor of AF screening with handheld ECGs (T. Lobban and M. T. Hills, personal communication, September 2016). Patients also be-lieved healthcare professionals needed to be better edu-cated about AF symptoms.

The patient voice is as important as the clinician voice in driving change. Political advocacy from patients, care-givers, and patient-led organizations has demonstrated the need for improved awareness, education, and dis-ease information.98,99 Patient-led organizations can more effectively identify the challenges patients face and engage policymakers to bring about change,98 lead-ing to improved outcomes for patients and healthcare providers (www.stopafib.org, www.heartrhythmalliance.org). Campaigns such as the Arrhythmia Alliance’s Know Your Pulse campaign to screen for AF can be successful in raising awareness and bringing about policy change.

Numerous governing bodies such as the National In-stitute for Health and Care Excellence (UK) and scientific organizations now seek the input of patients and patient organizations in developing clinical guidelines and scien-tific publications.1,30

Patients support screening to detect AF earlier. In-creased education about AF for healthcare professionals is required, ensuring they respond to any reported patient symptoms. Public awareness campaigns will be helpful to educate people about checking their pulse and the ben-efits of OAC for preventing AF-related stroke. It will be beneficial for professional health organizations to work in partnership with professional patient-led organizations to drive AF education and detection programs, advocate for screening, and evidence-based treatment for those with diagnosed AF.

Current GuidelinesThe ESC recommends opportunistic pulse-taking in all patients ≥65 years of age or in high-risk subgroups,

followed by an ECG if irregular, to allow for timely AF detection.30,89 Pulse taking in practice is recommended by the National Institute for Health and Care Excellence (UK) guidelines but only for symptoms. However, the new 2016 ESC guideline30 also includes an ECG rhythm strip as an alternative to pulse palpation, at least 72 hours of ECG monitoring after a transient ischemic at-tack or stroke with additional longer term monitoring considered, and consideration of systematic screening in patients ≥75 years of age or those at high stroke risk. An additional recommendation is to interrogate CIEDs for atrial high-rate episodes and, if detected, prompt further ECG monitoring to document AF before initiating therapy.

The American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines1 make no recommendation on the topic of screening but do state that early detection and treatment of asymptomatic AF before the first complications occur is a recognized pri-ority for the prevention of stroke.

Guidelines address specific subgroups where screen-ing may be worthwhile, including high-risk patients (eg, poststroke, ˃75 years of age), in whom prolonged moni-toring is more likely to detect AF.

Key Point 6There is a need to perform large randomized controlled studies using hard end points (including stroke, system-ic embolism, and death), of strategies for screening, to strengthen the evidence base to inform guidelines and national systematic screening strategies.

CONCLUSIONSIn older individuals with screen-detected AF, the absolute risk of ischemic stroke and death appears sufficient to justify consideration of treatment with OACs. Irregular-ity of the pulse is a simple way to screen for AF, but pulse palpation is seldom done in routine practice, and inexpensive screening devices are available. Because an ECG is required to confirm AF diagnosis, devices that provide a medical quality ECG trace have an advantage over pulse-based devices and would be preferred as screening tools. Single-timepoint screening for AF ap-pears justified based on yield and cost-effectiveness; as a further step, 2 weeks of twice daily intermittent recordings may be justified in people ≥75 years of age or in other groups at high risk of AF or AF-related stroke. Patient differences will modulate the type and intensity of screening (eg, ESUS requires higher intensity). The setting for screening is highly dependent on the health system in each country and needs to be individualized but must crucially be linked to a pathway for appropriate diagnosis and management. Although the World Health Organization criteria for screening appear to be met100 and the evidence is strong for commencing screening ef-



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STATE OF THE ART

forts in many countries, 1 or more large and adequately powered randomized outcomes trials of a strategy of screening would strengthen the evidence for the adop-

tion of larger scale systematic screening programs for AF to reduce ischemic stroke/systemic embolism and death (Figure 3).

Figure 3. Diagrammatic representation of key points on screening. Enrichment is the use of additional risk factors or biomarkers to either increase the proportion with unknown AF in the screened population or increase the risk of stroke in those with AF detected by screening in that population. Patients who are undertreated are patients with known AF who are not receiving oral anticoagulant according to guidelines. (see page 1859 section, Screening for Undertreated Known AF). Although this is not strictly speaking screening, such patients will be detected by population screen-ing for AF, so this has been placed in a different shape with a dotted line connector. BP indicates blood pressure; ESUS, embolic stroke of uncertain source; and PPG, photoplethysmography.



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AUTHORSBen Freedman, MBBS, PhD*; John Camm, MD*; Hugh Calkins, MD*; Jeffrey S. Healey, MD, MSc*; Mårten Rosenqvist, MD, PhD*; Jiguang Wang, MD, PhD*; Christine M. Albert, MD, MPH; Craig S. Anderson, PhD; Sotiris Antoniou, BPharm(Hons), MSc; Emelia J. Benjamin, MD, ScM; Giuseppe Boriani, MD, PhD; Jo-hannes Brachmann, MD, PhD; Axel Brandes, MD, DMSc; Tze-Fan Chao, MD, PhD; David Conen, MD, MPH; Johan Engdahl, MD, PhD; Laurent Fauchier, MD, PhD; David A. Fitzmaurice, MD; Leif Friberg, MD, PhD; Bernard J. Gersh, MB, ChB, DPhil; David J. Glad-stone, MD, PhD; Taya V. Glotzer, MD; Kylie Gwynne, MA; Graeme J. Hankey, MD; Joseph Harbison, MD; Graham S. Hillis, MBChB, PhD; Mellanie T. Hills, BSc; Hooman Kamel, MD; Paulus Kirchhof, MD; Peter R. Kowey, MD; Derk Krieger, MD, PhD; Vivian W. Y. Lee, BSc, PharmD; Lars-Åke Levin, PhD; Gregory Y. H. Lip, MD; Trudie Lobban; Nicole Lowres, PhD; Georges H. Mairesse, MD; Carlos Martinez, MD, MSc; Lis Neubeck, BA(Hons), PhD; Jessica Orchard, BEc/LLB, MPH; Jonathan P. Piccini, MD, MHS; Katrina Poppe, PhD; Tatjana S. Potpara, MD, PhD; Helmut Puererfellner, MD; Michiel Rienstra, MD, PhD; Roopinder K. Sandhu, MD, MPH; Renate B. Schnabel, MD, MSc*; Chung-Wah Siu, MD; Steven Stei-nhubl, MD; Jesper H. Svendsen, MD, DMSc; Emma Svennberg, MD, PhD; Sakis Themistoclakis, MD; Robert G. Tieleman, MD, PhD; Mintu P. Turakhia, MD, MAS; Arnljot Tveit, MD, PhD; Steven B. Uittenbogaart, MD, MSc; Isabelle C. Van Gelder, MD, PhD; Atul Verma, MD; Rolf Wachter, MD; Bryan P. Yan, MBBS.*AF-SCREEN International Collaboration Steering Committee.

APPENDIXAF-SCREEN Members Other Than Coauthors Who Contributed to the Individual Country Profiles and Who Participated in the Delphi ProcessAl Awwad, A; Al-Kalili, F; Berge, T; Breithardt, G; Bury, G; Caorsi, WR; Chan, NY; Chen, SA; Christophersen, I; Connolly, S; Crijns, H; Davis, S; Dixen, U; Doughty, R; Du, X; Ezekowitz, M; Fay, M; Frykman, V; Geanta, M; Gray, H; Grubb, N; Guerra, A; Halcox, J; Hatala, R; Heidbuchel, H; Jackson, R; Johnson, L; Kaab, S; Keane, K; Kim, YH; Kollios, G; Løchen, ML; Ma, C; Mant, J; Martinek, M; Mar-zona, I; Matsumoto, K; McManus, D; Moran, P; Naik, N; Ngarmukos, T; Prabhakaran, D; Reidpath, D; Ribeiro, A; Rudd, A; Savalieva, I; Schilling, R; Sinner, M; Stewart, S; Suwanwela, N; Takahashi, N; Topol, E; Ushiyama, S; Verbiest van Gurp, N; Walker, N; Wijeratne, T.

ACKNOWLEDGMENTSThe authors acknowledge the important role of Ms Kimberley Begley in the organization of the AF-SCREEN meeting and sup-porting the steering committee in all the logistics.

SOURCES OF FUNDINGAF-SCREEN received funding for holding its meeting from: Bayer HealthCare, Bristol-Myers Squibb/Pfizer, Daiichi San-

kyo, Medtronic, C-SPIN (Canadian Stroke Prevention Interven-tion Network), Zenicor, and iRhythm. The sponsors played no role in setting the agenda or the program for the meeting and played no role in this document.

DISCLOSURESDr Freedman reports speakers fees and advisory board honoraria from Bayer Pharma AG (significant), Boehringer Ingelheim (modest), and BMS/Pfizer (significant). Dr Camm reports grants and personal fees from Bayer, Boehringer In-gelheim, and Daichi Sankyo; and personal fees from Pfizer/BMS. Dr Calkins reports a consultancy with BMS/Pfizer (mod-est), speaker fees (significant) from Boehringer Ingelheim, and speaker fees and a consultancy with Medtronic (significant). He has also participated in a multicenter trial supported by Boerhringer Ingelheim (significant). Dr Healey reports grants from Medtronic, grants from Bristol-Meyers-Squibb, grants from Bayer, and grants from Boehringer-Ingelheim, outside the submitted work. Dr Rosenqvist reports grants (significant) and personal fees (modest) from Bayer, grants (significant) and personal (modest) fees from Boehringer-Ingelheim, grants (significant) and personal fees (modest) from BMS, grants and personal fees (modest) from Pfizer, grants (modest) and per-sonal fees (modest) from Medtronic, grants (significant) and personal fees (significant) from St Jude Medical, grants and personal fees (modest) from Zenicor, personal fees (modest) from Sanofi, and grants (significant) from Roche, outside the submitted work.Dr Anderson reports personal fees from Boehringer Ingle-heim, Takeda China, Astra Zeneca, and Medtronic, outside the submitted work. Dr Antoniou reports modest honoraria from Bayer, Boehringer Ingelheim, Pfizer/BMS, and Daiichi Sankyo. Dr Benjamin reports grants from National Institutes of Health and National Institutes of Health/American Heart Association during the conduct of the study and other from American Heart Association and National Institutes of Health/National Center for Biotechnology Information outside the submitted work. Dr Boriani reports modest honoraria (as speaking fees) from Medtronic and Boston Scientific. Dr Brachmann reports modest research grants and modest honoraria from Medtronic, Bayer, and Biotronik. Dr Conen reports grants and personal fees from Bayer and Daiichi-Sankyo, grants from BMS/Pfizer, and personal fees from Boehringer-Ingelheim outside the submitted work. Dr Engdahl reports a significant research grant from Boehringer Ingel-heim and modest honoraria from Pfizer, Bristol Myers Squibb, Roche, Boehringer Ingelheim, Bayer, and Sanofi. Dr Fauchier reports a research grant from Bayer (significant); expert witness fees from Bayer (significant), BMS/Pfizer (modest), Boehringer Ingelheim (significant), Medtronic (modest), and Novartis (modest); and honoraria from Bayer (modest), BMS/Pfizer (modest), Boehringher Ingelheim (modest), and Daiichi Sankyo (modest). Dr Friberg reports substantial consultancy fees from Bayer, Boehringer-Ingelheim, and Pfizer/BMS and substantial consultancy fees for participation in a European post authorization safety program for rivaroxaban in response to a demand from the European Medicines Agency. Dr Gersh reports consultancies (modest) for Janssen Pharmaceuticals, Boston Scientific, Medtronic, and CIPLA pharmaceuticals. Dr



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Gladstone reports personal fees from Bayer, Boehringer In-gelheim, Bristol-Myers Squibb, and Pfizer outside the submit-ted work; and is the principal investigator on the EMBRACE trial (Event Monitor Belt for Recording Atrial Fibrillation after a Cerebral ischemic Event) and the SCREEN-AF trial and co- principal investigator on the PIAAF-FP study (Program for the Identification of “Actionable” Atrial Fibrillation – Family Prac-tice). Dr Glotzer reports modest speaking honorarium from Medtronic. Dr Hankey has received modest honoraria from Bayer for speaking at sponsored scientific symposia about stroke prevention in AF. Dr Hillis reports a significant grant from the Heart Foundation of Australia. Dr Kamel reports re-ceiving lecture fees from Genentech on the topic of alteplase for acute ischemic stroke and served as an unpaid consul-tant to Medtronic and iRhythm on the subject of heart-rhythm monitoring after stroke. Dr Kirchhof reports grants from sev-eral public funding bodies, including European Union grant agreement no. 633196 (CATCH ME [Characterizing Atrial fi-brillation by Translating its Causes into Health Modifiers in the Elderly]), British Heart Foundation (FS/13/43/30324), and Leducq Foundation; and grants and personal fees from sev-eral industry companies involved in producing AF therapies ESC (European Society of Cardiology), AFNET (Atrial Fibrilla-tion Network), and other professional societies outside the submitted work; In addition, Dr Kirchhof has a patent AF ther-apy and patent markers for AF pending to University of Bir-mingham. Dr Kowey reports moderate consultant fees from Medtronic and has significant equity in Cardionet. Dr Levin re-ports grants and personal fees from Boeringer Ingelheim and personal fees from Pfizer and Bayer outside the submitted work. Dr Lip reports significant consultancies for Bayer/Jans-sen, BMS/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Microlife, and Daiichi-Sankyo; and significant speaker fees for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Micro-life, Roche, and Daiichi-Sankyo. Dr Mairesse reports grants and personal fees from Boehringer Ingelheim and grants from St Jude Médical and Sanofi outside the submitted work. Dr Neubeck reports grants (significant) from Pfizer/BMS and Bayer and honoraria (modest) from Pfizer/BMS, Bayer, and Boehringer Ingelheim. Dr Piccini receives grants for clinical research from Abbott, Boston Scientific, Gilead, JNJ, the Na-tional Heart, Lung, and Blood Institute, and Spectranetics; and serves as a consultant to Allergan, Amgen, GSK, JNJ, Medtronic, Quest Labs, and Spectranetics. Dr Puererfell-ner reports modest honoraria and expert witness fees from Medtronic, St Jude Medical, and Biosense-Webster; and mod-est honoraria from Boehringer-Ingelheim, Bayer, Daiichi-San-kyo, and Bristol-Myers-Squibb. Dr Rienstra reports significant research grants from The Netherlands Organisation of Scien-tific Research and The Netherlands Cardiovascular Research Initiative supported by the Dutch Heart Foundation. Dr Sch-nabel reports funding from the European Research Council under the European Union’s Horizon 2020 research and inno-vation program (grant agreement no. 648131) and German Ministry of Research and Education (BMBF 01ZX1408A). Dr Siu has been a speaker of symposia for Bayer, BMS/Pfizer, and Boehringer Ingelheim (modest). Dr Steinhubl reports a significant research grant from Janssen Pharmaceutical. Dr Svendsen reports research grant (significant) and honoraria (modest) from Medtronic, research grants (modest) and honoraria (modest) from Biotronik, Gilead, Boehringer Ingel-

heim, Astra-Zeneca, and Bayer. Dr Svennberg has received modest honoraria from Merck Sharp & Dohme, Bristol-Myers Squibb/Pfizer, Boehringer-Ingelheim, Bayer, and Sanofi; and a research grant from Roche (significant). Dr Tieleman has a patent as coinventor of the MyDiagnostick with modest royal-ties paid. Dr Turakhia reports grants (>$10K) and personal fees ($<10K) from Medtronic, grants from Janssen (>$10K), personal fees (<$10K) from AliveCor, Daiichi Sankyo, Ar-metheon, and personal fees (>$10K) from St Jude Medical outside the submitted work. Dr Verma reports grants from Medtronic outside the submitted work. Dr Wachter reports a significant research grant from Boehringer Ingelheim and modes honoraria from Boehringer Ingelheim, Bayer, Bristol-Myers-Squibb, Medtronic, and Pfizer. Dr Yan reports modest other research support in terms of AliveCor and Cardiio de-vices. The other authors report no conflicts of interest.

AFFILIATIONSFrom Heart Research Institute, Charles Perkins Centre, and Concord Hospital Cardiology, University of Sydney, Aus-tralia (B.F.); St Georges Hospital, London, UK (J.C.); Johns Hopkins University, Baltimore, MD (H.C.); Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (J.S.H., D.C.); Karolinska Institute, Stockholm, Swe-den (M.R., J.E., L.F., E.S.); The Shanghai Institute of Hyper-tension, Ruijin Hospital, Jiaotong University School of Medi-cine, China (J.W.); Brigham and Womens Hospital, Harvard Medical School, Boston, MA (C.M.A.); The George Institute for Global Health, Sydney, Australia (C.S.A.); Barts Health NHS Trust, London, UK (S.A.); National Heart, Lung, and Blood Institute and Boston University’s Framingham Heart Study, MA (E.J.B.); University of Modena and Reggio Emilia, Italy (G.B.); Klinikum Coburg, Germany (J.B.); Odense Uni-versity Hospital, Denmark (A.B.); Cardiovascular Research Centre, National Yang-Ming University, Taipei, Taiwan (T.-F.C.); University Hospital, Basel, Switzerland (D.C.); Univer-sité François Rabelais, Tours, France (L.F.); University of Birmingham, UK (D.A.F.); Mayo Clinic College of Medicine, Rochester, MN (B.J.G.); University of Toronto, Ontario, Can-ada (D.J.G., A.V.); Hackensack University Medical Centre, NJ (T.V.G.); Poche Centre, University of Sydney, Australia (K.G.); University of Western Australia, Perth (G.J.H.); Trin-ity College, Dublin, Ireland (J.H.); Royal Perth Hospital, Uni-versity of Western Australia (G.S.H.); StopAfib.org, Dallas, TX (M.T.H.); Weill Cornell Medical College, New York (H.K.); Institute of Cardiovascular Sciences, University of Birming-ham, UK (P.K.); SWBH and UHB NHS trusts, Birmingham, UK (P.K.); AFNET, Muenster, Germany (P.K.); Lankenau Institute for Medical Research, Wynnewood, OK (P.R.K.); University Hospital of Zurich, Switzerland (D.K.); Chinese University of Hong Kong (V.W.Y.L., B.P.Y.); University of Linköping, Swe-den (L.-A.L.); University of Birmingham, UK; Aalborg Univer-sity, Denmark (G.Y.H.L.); Arrhythmia Alliance, London, UK (T.L.); Charles Perkins Centre, University of Sydney, Aus-tralia (N.L.); Cliniques du Sud Luxembourg, Arlon, Belgium (G.H.M.); Institute for Epidemiology Statistics and Informat-ics, Frankfurt, Germany (C.M.); Edinburgh Napier University, UK (L.N.); Charles Perkins Centre, University of Sydney, Aus-tralia (J.O.); Duke University, Durham, NC (J.P.P.); University



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of Auckland, New Zealand (K.P.); University of Belgrade, Serbia (T.S.P.); KH der Elisabethinen, Ordensklinikum Linz, Austria (H.P.); University of Groningen, University Medical Centre Groningen, The Netherlands (M.R.); University of Al-berta, Edmonton, Canada (R.K.S.); University Heart Centre, Hamburg, Germany (R.B.S.); The University of Hong Kong (C.-W.S.); Scripps Translational Science Institute, San Diego, CA (S.S.); Rigshospitalet, The Heart Centre, University of Copenhagen, Denmark (J.H.S.); Ospedale dell’Angelo Ven-ice-Mestre, Venice, Italy (S.T.); Martini Hospital, Groningen, The Netherlands (R.G.T.); Stanford University, CA (M.P.T.); VA Palo Alto Health Care System, CA (M.P.T.); The Department of Medical Research, Bærum Hospital, Rud, Norway (A.T.); Department of General Practice, Academic Medical Center, Amsterdam, The Netherlands (S.B.U.); University of Gronin-gen, University Medical Centre Groningen, The Netherlands (I.C.V.G.); and University of Göttingen, Germany (R.W.).

FOOTNOTESThe online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIRCULATIONAHA.116.026693/-/DC1.

Circulation is available at http://circ.ahajournals.org.

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78. Uittenbogaart SB, Verbiest-van Gurp N, Erkens PM, Lucassen WA, Knottnerus JA, Winkens B, van Weert HC, Stoffers HE. Detect-ing and diagnosing atrial fibrillation (D2AF): study protocol for a cluster randomised controlled trial. Trials. 2015;16:478. doi: 10.1186/s13063-015-1006-5.

79. Sandhu RK, Dolovich L, Deif B, Barake W, Agarwal G, Grinvalds A, Lim T, Quinn FR, Gladstone D, Conen D, Connolly SJ, Heal-ey JS. High prevalence of modifiable stroke risk factors identi-fied in a pharmacy-based screening programme. Open Heart. 2016;3:e000515. doi: 10.1136/openhrt-2016-000515.

80. Lowres N, Krass I, Neubeck L, Redfern J, McLachlan A, Bennett A, Freedman SB. Atrial fibrillation screening in pharmacies using an iPhone ECG: a qualitative review of implementation. Int J Clin Pharm. 2015;12:350–360.

81. Proietti M, Nobili A, Raparelli V, Napoleone L, Mannucci PM, Lip GY; REPOSI Investigators. Adherence to antithrombotic therapy guidelines improves mortality among elderly patients with atrial fibrillation: insights from the REPOSI study. Clin Res Cardiol. 2016;105:912–920. doi: 10.1007/s00392-016-0999-4.

82. Willits I, Keltie K, Craig J, Sims A. WatchBP Home A for opportu-nistically detecting atrial fibrillation during diagnosis and monitor-ing of hypertension: a NICE Medical Technology Guidance. Appl Health Econ Health Policy. 2014;12:255–265. doi: 10.1007/s40258-014-0096-7.

83. Jacobs M, Kaasenbrood F, Postma M, van Hulst M, Tieleman RG. Cost-effectiveness of screening for atrial fibrillation in primary care with a hand-held, single-lead ECG device in the Netherlands [published online ahead of print October 12, 2016]. Europace. doi: 10.1093/europace/euw285. https://academic.oup.com/europace/article-abstract/doi/10.1093/europace/euw285/2952432/Cost-effective-ness-of-screening-for-atrial?redirectedFrom=fulltext. Accessed April 17, 2017.

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tool on thromboprophylaxis for atrial fibrillation. Am Heart J. 2016;176:17–27. doi: 10.1016/j.ahj.2016.02.009.

87. Yan B, Chan L, Lee V, Freedman B. Medical outpatient clinics an ideal setting for atrial fibrillation screening using a hand-held single-lead ECG with automated diagnosis. Eur Heart J. 2016;37:888.

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91. Rhys GC, Azhar MF, Foster A. Screening for atrial fibrillation in patients aged 65 years or over attending annual flu vac-cination clinics at a single general practice. Qual Prim Care. 2013;21:131–140.

92. Turakhia MP, Shafrin J, Bognar K, Goldman DP, Mendys PM, Abdulsattar Y, Wiederkehr D, Trocio J. Economic burden of undiagnosed nonvalvular atrial fibrillation in the United States. Am J Cardiol. 2015;116:733–739. doi: 10.1016/j.amjcard. 2015.05.045.

93. Moran PS, Teljeur C, Ryan M, Smith SM. Systematic screening for the detection of atrial fibrillation. Cochrane Database Syst Rev. 2016;6:Cd009586.

94. Health Information and Quality Authority. Health technology as-sessment (HTA) of a national screening programme for atrial fibrillation in primary care. August 6, 2016. https://www.hiqa.ie/reports-and-publications/health-technology-assessments/hta-atrial-fibrillation-screening. Accessed April 22, 2017.

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Isabelle C. Van Gelder, Atul Verma, Rolf Wachter and Bryan P. YanThemistoclakis, Robert G. Tieleman, Mintu P. Turakhia, Arnljot Tveit, Steven B. Uittenbogaart,

Schnabel, Chung-Wah Siu, Steven Steinhubl, Jesper H. Svendsen, Emma Svennberg, Sakis Tatjana S. Potpara, Helmut Puererfellner, Michiel Rienstra, Roopinder K. Sandhu, Renate B.Mairesse, Carlos Martinez, Lis Neubeck, Jessica Orchard, Jonathan P. Piccini, Katrina Poppe,

Y. Lee, Lars-Åke Levin, Gregory Y. H. Lip, Trudie Lobban, Nicole Lowres, Georges H.Mellanie T. Hills, Hooman Kamel, Paulus Kirchhof, Peter R. Kowey, Derk Krieger, Vivian W.

Taya V. Glotzer, Kylie Gwynne, Graeme J. Hankey, Joseph Harbison, Graham S. Hillis,Laurent Fauchier, David A. Fitzmaurice, Leif Friberg, Bernard J. Gersh, David J. Gladstone, Boriani, Johannes Brachmann, Axel Brandes, Tze-Fan Chao, David Conen, Johan Engdahl,

Wang, Christine M. Albert, Craig S. Anderson, Sotiris Antoniou, Emelia J. Benjamin, Giuseppe Ben Freedman, John Camm, Hugh Calkins, Jeffrey S. Healey, Mårten Rosenqvist, Jiguang

CollaborationScreening for Atrial Fibrillation: A Report of the AF-SCREEN International

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2017 American Heart Association, Inc. All rights reserved.

is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Circulation doi: 10.1161/CIRCULATIONAHA.116.026693

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Supplementalmaterial:

SCREENINGFORATRIALFIBRILLATION:AREPORTOFTHEAF-SCREENINTERNATIONALCOLLABORATION a. DelphiProcessforAF-SCREENconsensusdocumentThedocumentcontentandstructurewereagreedbythesteeringcommittee(JohnCamm

UK,HughCalkinsUSA,BenFreedmanAustralia,JeffHealeyCanada,MårtenRosenqvist

Sweden,andJiguangWangChina),andAF-SCREENmembers,inlate2015.Individual

sectionswereallocatedtoandwrittenby18smallgroupsofmemberswithcontent

expertise(co-authors),manyofwhomweretheleadinvestigatorsoftheseminalpapersin

thatparticulararea.Eachgroupwasencouragedtoproduceoneormoredraft

recommendations.ADelphiprocessinvolvedthesteeringcommitteevotingonwhichkey

questionsshouldbeselectedfordiscussionandsecretvotingbythosepresentattheAF-

SCREENconsensusmeeting.ThismeetingwasheldinAugust2016,immediatelybeforethe

ESCannualscientificmeetinginRome.Followingvotingatthemeeting,thosedraft

recommendationswhichreceivedalargenumberofvoteswereworkshoppedover2days,

and7selectedforon-linesecretvotingbyallmembers.Thepanelbelowshowsthefinal

wordingofthekeyquestionsusedintheon-lineballot,andthenumberofvotes,withthe

percentagreementwiththestatement/keyquestion.Allsevenreceived>85%agreement

(Panel1).Theseformedthebasisofthekeypointsusedinthewhitepaper.Noformal

recommendationsareprovidedinthewhitepaper.

Panel1

AF-SCREENKeyIssues

1. Screen-detectedAFasfoundonsingletimepointscreening,orintermittent30secondrecordingsover2weeks,isnotabenigncondition,andwithadditionalstrokeriskfactors,carriessufficientriskofstroketojustifyconsiderationofscreeningandtherapytopreventstroke.105votes,98%agreed

2. Singletimepointscreeningofpeopleaged65oroverintheclinicorcommunityisrecommended,basedonyieldofscreeningandcost-effectiveness.104votes,93%agreed

3. Asafurtherstepaftersingletimepointscreening,twoweeksoftwice-dailyintermittenthandheldECGrecordingshouldbeconsideredforscreeningforAFinpeopleaged75orover,orinyoungeragegroupsathighriskofAForstroke.104votes,86%agreed

4. Long-termcontinuousrhythmmonitoringusingeitherexternalorimplanteddevicesorextendedintermittentpatient-activatedrecordingsisrecommendedforindividualswithrecentembolicstrokeofundeterminedsource(ESUS).104votes,92%agreed

5. ThesettingforAFscreeningneedstobeindividualizedaccordingtocountry-specificandhealthcaresystem-specificrequirementsandresourcesandmustbelinkedtoapathwayforappropriatediagnosisandmanagement.Thiscanbecommunity-basedorinprimarycareorspecialistpracticesorclinics.105votes,99%agreed

6. MassscreeningoropportunisticscreeningforAFcanbeaccomplishedbypulsepalpation;oscillometric(bloodpressure)orphotoplethysmographic(smartphonecamera)devices;andhandheldECGdevicesprovidingarhythmstrip.ECGconfirmationisalwaysrequiredfordiagnosisofAF.HandheldECGdeviceshavetheadvantageofprovidingaverifiableECGtraceandarepreferred.105votes,93%agreed

7. Largerandomizedcontrolledstudiesusinghardendpoints(includingstroke/systemicembolismanddeath),ofstrategiesforscreeningshouldbeperformedtostrengthenevidencetoinformnationalsystematicscreeningstrategies.105votes,97%agreed

NBNoneoftheaboverelatetoCIED-detectedAHREs

b.AFincidenceandfutureprojections IntheUnitedStates,Europe,andChinathelifetimeriskofAFis22%to26%inmenand22%

to23%inwomen.1-3IthasbeenprojectedthatthenumberofpeoplewithAFintheUnited

StatesandEuropewilldoubleby2050.4,5ForChina,ithasbeenestimatedthatin2050,

therewillbe5.2millionmenand3.1millionwomenwithAF.6Acomprehensivelong-term

analysisofAFintheUnitedStates-FraminghamHeartStudycohortfurthersupportsthese

projections.7Theage-adjustedperiodprevalenceandincidenceincreasedthreetofour-fold

over5decadesofobservation(1958-2007).InChina,a20-foldincreaseinAFprevalencein

an11-yeartimeperiodwasobserved.3

Globally,therehasbeenprogressiveincreaseintheincidenceandprevalenceofAF

between1990and2010asassessedintheGlobalBurdenofDisease(GBD2010)Study.8.

However,therewassignificantregionalvariation,withhigh-incomecountrieshavinghigher

AFincidenceandprevalence.ThehigherratesofAFmayinpartbeattributabletobetter

detectionorevenopportunisticscreeninginhigh-incomecountries.Furthermore,between

2005and2010,theincreaseinAFprevalencewasminimal,especiallyinhighvs.low-and

middle-incomecountries.8ReasonsforthetemporaltrendsinAFaremultifactorialand

includeincreasedawarenessandsurveillanceleadingtoearlierandmorefrequent

detection,withdecreasedmortalityandstrokecontributingtolongersurvivalafterAF

diagnosis,especiallyinhighincomecountries.7Althoughtheprevalenceofmostriskfactors

changedovertime,thestrengthoftheirassociationwithAFremainedlargelyunchanged,in

bothFraminghamandPREVENDcohorts,79thoughthemajorityofAFepidemiologydata

comesfromNorthAmericaandEurope.ManyAFriskfactorssuchassystolicbloodpressure

(themostcommonriskfactorworldwideforAFishypertension7,9-11),andheartfailure

decreased,duetoimprovedmanagementofhypertensionandincreasedsurvivalafter

myocardialinfarctionandheartfailure,whereasobesityanddiabetesincreased.Thelower

increaseinAFprevalencebetween2005and2010maybeinfluencedbyincreased

awarenessforAFriskfactors,andimprovedmanagementofAFriskfactors.8

PopulationAF-attributableriskofstrokeisdifficulttoestimate,duetounrecognized

asymptomaticand/orparoxysmalAF.Forexample,theFraminghamstudyestimated

populationAF-attributablerisktobe1.5%(ages50-59years)risingto23.5%(80-89years),12

butthisislikelytobeanunderestimate,asitcountedonlypersistent/longstandingAF,

estimatedat0.4%ofthepopulation.13Currentprevalenceestimates,whichinclude

paroxysmalandpersistentAF,aremuchhigher:intheSwedishregistry,almost4%ofthe

adultpopulationreceivedahospitaldiagnosisofAF.14,15Giventherearealsoindividuals

withundiagnosedAF,thepopulationAF-attributablestrokeriskcouldbemuchhigher.

Summarypoint:TheglobalburdenofAFwillcontinuetogrow.Increasingeffortsto

improveearlydetectionandawareness,byregion-specificeffectivescreeningand

treatmentprograms,andrisk-factor-specificpreventionarerequiredtoimprovestroke-free

survival.

b. ConsequencesofundiagnosedAFotherthanstroke

Inadditiontostroke,patientswithundiagnosedAFmaybesusceptibletocardiac

remodeling,heartfailure,silentcerebrovasculareventsanddementia.

AFisassociatedwithatrialandventricularstructuraldamage,16,17whichservesasthe

substrateforAFprogressionandmayleadtoventriculardysfunctionandarrhythmiasthat

mightexplaintheexcessincidenceofsuddencardiacdeathobservedinAFpatientsinRCTs

andregistries.18Whenconductedtotheventricleatrapidrates,AFcausesventricular

dysfunctionandheartfailure,bywayofatachycardia-inducedcardiomyopathythatcanbe

thefirstclinicalmanifestationofthearrhythmia.19

SilentbraininfarctscommonlyoccurinpatientswithAF,20andareofparticularconcern

withcatheterablationprocedures.21Likewise,patientswithAFhaveahigherfrequencyof

prematuredementiaandcognitivedeclinethanmatchedpatientsinsinusrhythm.22The

largecommunity-basedRotterdamstudyhasshownanincreasedriskofdementia,

independentofclinicalstroke,insubjectswithbothprevalentandincidentAF.23Although

directcausalrelationshiphasnotbeenprovenbetweensilentischemiceventsand

dementia,increaseduseofOACinsusceptiblepopulations,orsuccessfuleliminationofAF

forexamplewithcatheterablation,mayultimatelyreducedementia.Whetherpatientswith

undiagnosedAFhaveahigherriskofadverseoutcomessuchasheartfailureordementia

comparedtosymptomalticAFisnotknown.

SummaryPoint:TrialsandregistriesmonitoringasymptomaticpeopleatriskforAFshould

besupported.Theseshouldincorporatecomorbiditiessuchasheartfailureanddementiain

additiontotraditionalendpoints(stroke,death,bleeding).Sincetheseoutcomesare

ubiquitousinAFpopulationsbyvirtueofco-morbidityandage,rigorousendpointdefinition

andexperimentaldesign,withlongerfollow-up(especiallyfordementia),willberequired

forreliableconclusions.

d.AFinthecontextofconcurrentmajorillness:SecondaryAFAFmaybetriggeredbyreversible,acute,secondarycausessuchascardiacandnon-cardiac

surgery,hyperthyroidism,myocarditis/pericarditis,myocardialinfarction,pulmonary

embolism,pneumonia,sepsis,andalcoholintoxication.24In2,275,588hospitalizedpatients,

secondaryAFoccurredin22,780(1%).Themajoritywerepost-surgery(30%cardiothoracic,

20%non-cardiothoracic),infections(23%),orpost-myocardialinfarction(18%).25AF

recurrence,strokeriskandmortalityaresimilarforprimaryandsecondaryAF.26

New-onsetpostoperativeAF(POAF)complicates16-32%ofcardiacsurgery,27andis

associatedwithlongerhospitalizationandmorepostoperativecomplications.27-34POAF

oftenrecurspostdischarge,28,30,35withanabsoluterecurrencerateof~20%during3.5

yearsoffollow-up.35Followingcardiacsurgery,POAFcarriesahigherriskofstroke,hazard

ratio1.3in2yearsafteradjustingforconfounders,36andhighermortality.27,31,32,37POAF

occursafter1-3%ofnon-cardiacprocedures,29,36anddoublesstrokeriskwithin2years.36

ScreeningforrecurrentAFinPOAFfollowingcardiacsurgeryusingpatient-activated

handheldECGs,revealedrecurrentAFin25%within3weeks,mostlyasymptomatic.38The

prognosticsignificanceofrecurrenceisunknown,asistheincidenceafterreturntosinus

rhythmwithothersecondaryAF.

TransientAFoccursfrequentlyduringintercurrentillnesses.Prognosisiscomparableto

commonAF,therefore,targetedscreeningappearswarranted,althoughspecificdataon

silentsecondaryAFarenotavailable.Furtherresearchisneededtodevelopanevidence

basetoguidemanagementofsecondaryAF,andwhetherscreeningforrecurrenceis

warranted.39,40

e: TABLE A: Arguments against screening and AF-SCREEN response

Arguments against screening Potential AF-SCREEN response Individuals with screen-detected AF are at lower risk than patients in the pivotal anticoagulant trials, and the epidemiological studies. Uncertainty over whether it is worth treating these people (UK National Screening Committee)41

Supposition that individuals with predominantly persistent screen-detected AF have outcomes that closely correspond with incidentally-detected asymptomatic or minimally symptomatic AF. Such patients are not low risk, and treatment seems to have same effect as in symptomatic AF. Question remains about whether absolute risk of brief paroxysmal CIED-detected AHREs is high enough to justify treatment.

Don’t need expensive new technology - doctors should just do a pulse check in every consultation, particularly those at risk41

Doctors don’t check the pulse, and new technologies are more accurate, readily available, relatively inexpensive, easy to use, and can provide immediate ECG verification.

Need more information on benefits and cost-effectiveness before screening healthy general population41

All recent cost effectiveness simulations indicate screening for AF alone or including screening for “actionable AF” (known but untreated with OAC) will be cost-effective. An outcomes based randomized trial of screening will strengthen this evidence.

Treatment and care for people with AF is not optimal, why find more. Unlikely to be cost effective if screen-detected AF not treated (UK National Screening Committee)41

This is not an argument against screening, rather it is an argument in favor of improving treatment. Indeed, the cost-effectiveness simulation using UK data with only 55% prescription of OAC according to guideline still shows cost-effectiveness (base case in SEARCH-AF)42

The test needs to be improved and standardized (UK National Screening Committee)

This criticism not valid for the hand-held ECGs, or the oscillometry and PPG pulse methods which have been tested and validated.43-52

Opportunity cost from health care dollars spent on screening instead of treatment of known disease

Common to all screening tests, though health economic assessments indicate this unlikely to be a major factor

Harm can come from the diagnostic cascade arising from the initial test eg echo, stress test etc is well documented, and the harm from “incidentalomas,” uncovered in the diagnostic work-up again well documented

This is common to all screening tests, and risk to benefit calculations might include this, though hard to estimate the cost of this potential harm.

Need a randomized controlled trial to provide definitive evidence for effectiveness in reducing hard endpoints, as screen-detected AF may not have as high a risk as we think, so benefit less, and unscreened people may present with symptoms or be detected incidentally before an event. Event differential between screened and unscreened populations may be less than anticipated, and harms may outweigh benefits.18

Randomized controlled trial may be required to strengthen the evidence base, but current data suggests not low risk, and simulations suggest screening would be both effective and cost-effective. However, this depends on definition of undiagnosed AF, i.e. screen-detected AF vs brief CIED-detected AHREs, or that found in long-term continuous monitoring.

f.COUNTRYPROFILES

AustraliaBenFreedman,KylieGwynne,JessicaOrchard,NicoleLowres,LisNeubeck

AustraliahasapredominantlyCaucasianpopulationwithahighprevalenceandincidenceofatrialfibrillation(AF).Theincidencerateisprojectedtoincrease.53ThereisnosystematicprogramforscreeningforAFbutanumberofpilotstudieshavebeencarriedoutincludingastudyinthecommunityinpharmacies54andtwoingeneralpractice(oneduringthefluvaccination).55,56

ThereiscurrentlynoreimbursementforscreeningforAForforarhythmstripwhichmightbeusedintheprocess,andthiswouldbeabarriertowidespreadadoptionineithercommunity(egpharmacy)oringeneralpractice,wheremostofprimarycaretakesplaceinthiscountry.Itislikelythatgeneralpractitionersareprobablybestplacedtocarryoutscreeningbecauseofthehighrateofvisitsfromtheirpatientsinthepopulationat-riskfordevelopingAF,andtheirroleinbeingabletoprescribeanticoagulantifAFisfound.Therearenolargeprimarycareclinicsoroutpatientservices,sogeneralpracticewouldbethepreferredoptioninthiscountry.Pharmacistsalreadydoperformbloodpressurechecksandarerespectedhealthprofessionalswithawidenationalreach,andbyaddingsimplehand-heldECGscreeningasperformedinthepilot,couldproduceanimpactondetectionofunknownAF,providedtherewassomeremunerationandanadequatepathwaywasdevelopedwithpatients’GPsfortreatment.

Morewidespreadadoptionwouldrequireafairbitofadvocacyfrombothcliniciansandpatientgroups.

AboriginalAustralians

AboriginalAustralianshaveahighrateofAFatanearlyage.Inhospitaldischargestudiesandinotherregistries,theageofincidenceisabout20yearslowerthaninnon-AboriginalAustralians.Moreover,theCHADSVAScriskscoresaremuchhighwhenAFpresentsatanearlyage.57,58

AstudyiscurrentlyunderwaytouseopportunisticscreeningtodetectAFinAboriginaladultsinAustralia.ThisisamixedmethodsstudywhichwillusetheKardiasmartphoneECGtoscreen1500AustralianAboriginalpeoplelivinginNewSouthWales,NorthernTerritoryandWesternAustraliatoestimateprevalenceandagedistributionofAtrialFibrillationoftheAustralianAboriginalpopulation

ThereareanumberofuniquechallengesinidentifyingAboriginalpeoplewithasymptomaticAF:• thepopulationissmall(justunder3%oftheAustralianpopulation);59• theyarenotreliablyidentifiedwithintheheathcaresetting(orpatientrecords)andthe

populationiswidelydispersed;60and• Aboriginalpeoplearelesslikelytoaccesshealthcareservices;likelytohavelowerhealth

literacy;andlesslikelytoseekhealthcareassessmentortreatmentattheearlysigns.61

AustriaHelmutPuererfellner,MartinMartinek,GeorgiosKolliasAustriahasapopulationofcurrently8.7millioninhabitants.AsinmostWesterncountries,atrialfibrillation(AF)isprojectedtoincreaseinprevalence.Forthetimebeing,around150.000to200.000individualsareaffected.Thepublichealthsystemistax-financedwithnoaccessrestrictionsandfreeofcharge.Outpatientsaremainlyseenbythegeneralpractitionerswhohaveanimportantroleasgatekeepers.Patientswithatrialfibrillationwillfurtherbereferredtointernalmedicinespecialistsorcardiologistswhoworkin-officebasedoncontractswiththepublichealthinsurancecompanies.Alternatively,theyaresenttohospitalincaseofemergencies.TheAustrianCardiacSocietyhasendorsedtheESCguidelinesonthemanagementofatrialfibrillation.Accordingly,opportunisticscreeningforAFisrecommended.In2012,theAustrianCardiacSocietyorganizedasymposiumtogetherwiththeAustrianMinistryofHealthtobringtogetherthemostimportantstakeholdersinordertoincreaseawarenessforAFinthepublicandtoincreasethecooperationbetweenthedifferentmedicalspecialties.Consequently,aplatformforAFwasinstalledandapatientbrochureonAFwaspublishedin2015authoredbybothauthorities.AnationwideAFregistrywasdiscussed.Currently,anationwidestrokeregistryaswellasanablationregistryhavebeenestablished.Thereisawell-developedsystemforscreeningpatientsafteranESUS(embolicstrokeofunknownsource)wherelooprecordersareroutinelyimplanted.WearecurrentlystartingaprotocoltolookforsilentAFinaninternationalstudyprojectcalledtheSILENCEstudy.Inthisstudy,highriskpatientsaged>65yearsofagewitheitherconcomitantdiabetesorheartfailurearescreenedwithahand-heldECGdeviceoveraperiodof14daystodetectsilentAF.Resultsareexpectedfor2018-2019.

BalkansTatjanaPotpara AtpresentthereisnostructurednationalstrategyforAFscreeningintheBalkanRegioncountriesincludingSerbia,Bosnia&Herzegovina,Croatia,Montenegro,AlbaniaandBulgaria.Opportunisticscreeningatthegeneralpracticelevelisleftatthediscretionoftheresponsiblephysicians.Recently,theSerbianAFAssociation(anon-profitassociationofthephysiciansinvolvedinthemanagementofAF)hasinitiatedaregionalcollaborativeAFproject62withultimategoaltofacilitatetheformulationoffeasibleapproach(es)todiagnosisandmanagementofAFintheRegion,includingthestrategiesforAFscreening.Theprojectwillalsoinvolvemeasuresofpubliceducationsuchas‘checkyourpulse’andillustratedsummaryofAFessentials.

BelgiumGeorgesH.MairesseandHeinHeidbüchelBelgiumisamid-sizeEuropeancountrywithapopulationof11,000,000inhabitantsandBrusselsasitscapitalcity.Accesstohigh-qualityhealthservicesisgoodwithuniversalprotectionagainsttheriskofillness.However,preventivemedicineandhealthpromotionarenottheresponsibilityofthenationalgovernment,butarehandledatregionalorcommunitylevel.ScreeningforAFhasnotyetbeenrecognizedasaprioritybyhealthauthorities.TheBelgianHeartRhythmAssociation(BeHRA),aworkinggroupoftheBelgianSocietyofCardiology,hasstartedin2010nationalawarenesscampaigns.ThesecampaignsareruninMayorJune,duringtheWorldHeartRhythmWeek.63Duringthatweek,AFawarenessispromotedthroughnationalandregionalmedia,includingtheaudiovisualpress,anddistributionofinformativeleafletsviageneralpractionersandpharmacies.Politicalorsportfiguresaresolicitedtohighlightthesecampaignsinthemedia.Fundinghadtobesupportedthroughindustrygrants.Duringthisweek,inalmostallBelgianhospitals,afreescreeningisorganizedusingsingle-lead,handheldECGrecorders.Thepopulationof>40yistargetedwiththemessagethat“From40yearsold,one-in-fouradultswillbeconfrontedatleastoncewithAF”.Nevertheless,allparticipantsarewelcomeforAFscreeningiftheywish.Since2016,theuseoftheMyDiagnostickECGstickallowedrecordingsalsooutsidehospitals,likeinshoppingmalls.DemographicsandCHA2DS2-VAScscoresarecollectedatthetimeofscreening.TheprevalenceofAFfoundduringthesecampaignswas1.4%,withaclearincreasewithage.64Womenparticipatedmoreinthescreeningprogram,butprevalenceofAFwashigherinmen.AFwasfoundmainlyinpatientswithanintermediatetohighstrokerisk.Adequateanticoagulationwaslowinthosepatients.Inadditiontothisscreeningprogram,awebsite(http://www.monrythmecardiaque.be)wasdesignedtoalloweveryBelgiancitizentocalculatehis/herriskfordevelopingAF,basedonsexandageprobabilities.ItalsoallowscalculationofstrokeriskbasedontheCHA2DS2-VAScscore.Duringthesecampaignsover7years,informationaboutAFwasdeliveredto>250.000people,eitherduringthescreeningsessionsorviatheWebsite.IncontrasttotheBeHRAinitiativedescribedabove,thereisnonationalorregionalefforttoorganizesystematicscreeningforAFinriskpopulations(likethoseoveracertainage,orwithriskfactorslikediabetesorhypertension).Althoughsomeclinicalspecialists(likeneurologists)havedevelopedclinicalpathwaysincludinglong-termECGrecording(uptoimplantablelooprecorders),thereisnostandardpathwayimplementedthroughouttheBelgianhealthcaresystemtoperformsystematicscreening.Tofurtherdevelopsuchscreeninginitiatives,healthauthorities’supportandfinancingwouldbeneeded.

Brazil AntonioLuizPinhoRibeiroCardiovasculardiseaseshavebeenBrazil´sleadingcauseofdeathforhalfacenturyand,in2011,wereresponsiblefor31%ofthedeaths.Coronaryarterydisease,strokeandhypertensivecardiopathyarethemainspecificcausesofdeath,butdiseasesrelatedtopoverty,asChagasdiseaseandrheumaticheartdisease,arestillprevalent65.Brazilianpublicnationalhealthsystem(SUS)providesuniversalaccesstoalllevelsofcare,butproblemsrelatedtounderfunding,difficultaccessofthemoredeprivedpopulationsandqualityoftheassistanceinthepublicsystemarestillmajorproblemsofSUS.65Thereisnonationwidesurveyontheprevalenceofatrialfibrillation,butastudyconductedusingalargestate-wideprogramofECGdatabase(n=262,685primarycarepatients>5years-old)showedaprevalenceof2.4%formenand1.3%forwomen;66ageandsexdistributionwasnotverydifferentfromtheobservedinotherWesternWorldsurveys(table1).MostofatrialfibrillationpatientsinBrazildonotreceiveanticoagulationtherapy:intheprimaryhealthcarecenters,only1.5%reportedtheuseofwarfarin,theonlyanticoagulationdrugavailableintheSUS66.In162consecutivepatientswithatrialfibrillationwhoperformedECGatUniversityhospital,50.6%knewthattheyhadatrialfibrillationandonly35.5%ofthoseclassifiedashighriskwereusingoralanticoagulation67.InanotherBraziliantertiaryoutpatientclinic,only55%ofpatientsathighriskwerereceivingdose-adjustedwarfarin68.AlthoughstrokestandsasthesecondcauseofdeathinBrazil,thereisnopublicpolicytodetectortreatatrialfibrillationinBrazil.BrazilianSocietyofCardiologyguidelinesonthemanagementofatrialfibrillationalsodoesnotincludeachapteronscreening.ThemainbarrierstoscreeningprogramsforatrialfibrillationinBrazilaretheunevenaccesstoECGexamsandthepaucityofresourcesforanticoagulationofthenewpatients,especiallyinthepublichealthsystem.Onlywarfarinisavailableinthelistofessentialmedicinesandthereisaverylimitednumberofactiveanticoagulationclinics.69-71TheaccesstoECGtestarebeingimprovedbysomelargescale,publicteleECGsystemsavailableinsomestatesofthecountry.72,73Specificnationalprotocolsforrecognition,riskstratificationandtreatmentofatrialfibrillationintheprimaryhealthcareshouldbeestablished,includingconditionsforsafeanticoagulationusingwarfarinortheneworalanticoagulants.Table1:Prevalenceofatrialfibrillationin262,685patientsfromprimaryhealthcarecentersinMinasGerais,Brazil,2011Agegroup(years) Males(%) Females(%)05-19 0,0 0,120-29 0,2 0,130-39 0,3 0,240-49 0,7 0,350-59 1,6 0,760-69 3,2 1,970-79 6,3 4,180-89 9,8 6,7≥90 14,6 8,7

CanadaRoopinderSandhu,StuartConnolly,AtulVerma,DavidGladstone,JeffHealey Asinothercountries,theprevalenceofAFinCanadaisincreasing;74althoughthelocationofAFdiagnosisappearstobeshifting.InCanada,incidentAFcasesdiagnosedinhospitalhavedeclined21%,whereastheproportionofcasesdiagnosedintheoutpatientsettinghaverisenby50%between2000and2005.75Regardlessofthehealthcaresetting,OACtherapyisunder-utilized.76,77TheageingpopulationwillgreatlyimpactAFratesandimplementationofstrokepreventiontherapy;inCanadathelargestgrowingsegmentofthepopulationarethose65yearsandolder(see:StatisticsCanadawww.statcan.gc.ca/eng/start ).AtpresenttheCanadianCardiovascularSocietyAFguidelines78recommendsOACforindividuals>65years;however,therearenospecificrecommendationforAFscreening.TheCanadianStrokePreventionInterventionNetwork(C-SPIN)isleadingseveralscreeningstudiestobetterunderstandthenatureofundiagnosedandundertreatedAFinCanada.TheProgramforIdentificationof‘Actionable’AF(PIAAF)willevaluatetheoptimalsetting,screeningmethodsandcost-effectivenessofAFscreening.ThePIAAF-Pharmacystudycompletedenrollmentof1145subjects,andemployedacomprehensiveapproachtoscreeningstrokeriskfactorsincluding:usingasingleleadhandheldECGdevicetodetectAF;bloodpressuremeasurementandadiabetesriskassessmentquestionnaire.ThePIAAF-FamilyPracticestudyisamulticentercohortstudyofpatientsattendingfamilypracticeclinicswhowillundergosingletimepointAFscreeningwitha30secondpulsecheck,singleleadhandheldECGdeviceandBPmachinewithautomatedAFdetectionalgorithm;enrollmentistargetedforcompletionthisfall.TherearetworandomizedAFscreeningtrialsinolderpatientswithmultiplestrokeriskfactors.TheSCREEN-AFstudyamongfamilypracticepatients>75yearswithahistoryofhypertensionandnoknownAFcomparesstandardcaretostandardcareplus2-weekECGpatchmonitorandconcurrentAF-BPmonitorandASSERT-3randomizedpatients>80yearswithoutknownAFtohaveasingle24-hrHoltermonitorvs.a24-hrHoltermonitorfollowedbya30-dayexternalECGlooprecorderwithautomaticAF-detection.ThedatafromthePIAAFprogramwillhelptoinformthedesignofaclusterrandomizedtrialofacommunity-wideinterventiontopreventstrokebydetectionandtreatmentofAFandhypertension.ThistrialwillprovideabetterunderstandingofhowAFscreeningprogramscanbeimplementedinacountrywithsuchgeographicanddemographicdiversity.Beyondscreening,AFdetectionmustbelinkedtostrategiesusingexistingornovelcarepathwaystoimproveOACuse.ThePIAAFRxstudywillbethefirstrandomizedtrialofpharmacist’sprescribingOACcomparedtousualcareforthose>65yearswithoneadditionalstrokeriskfactorand‘actionable’AFinthecommunity.

China

JiguangWang,ChangshengMa,XinDu

In2014,undertheauspicesoftheChineseCommissionofHealthandFamilyPlanningandtheChinesePreventiveMedicineAssociation(withitsStrokePreventionandControlCouncil),agroupofexperts,mainlystrokeneurologists,publishedinabookletaconsensusdocumentonAFscreeningandsubsequentanticoagulanttherapyinpatientswithanacutestrokeandtransientischaemicattack.Thisconsensusdocumentrecommendedthatinpatientswithanacuteischaemicstrokeortransientischaemicattack,AFshouldbescreenedroutinelybydiseasehistoryinquisition,physicalexamination,and12leadsECGrecording,andifpossiblebya24-hourHolterECGmonitoring.InpatientswithunidentifiablecausesofAForwithsuspectedcardiogenicembolism,a24-hourHolterECGmonitoringisrequired.IftheScorefortheTargetingofAtrialFibrillation(STAF)is≥5pointsortheLeftAtrialDiameterScore(LADS)is≥4points,multipleAFscreeningapproaches,including24-hourorlongerHolterECGmonitoringorrepeated12leadsECGrecordingsarerequired.Untilrecently,therehasnotbeenanyreportontheimplementationoftheserecommendationsontheidentificationofAFinpatientswithanacutestrokeortransientischaemicattack.

Inthepastaboutadecade,severalmulti-centreandsingle-centresurveysontheprevalenceofAFwereconducted.3,79-85TheprevalenceofAFvariedbetweenthesestudies.However,theprevalenceofAFinconsistentlyincreasedwithageadvancing.Inaddition,theAFpatientswereonaverageafewyearsyoungerthaninNorthAmericanandEuropeanpopulations.Thisearlyonsetmayberelatedtopoorerbloodpressurecontrolandotherunidentifiableriskfactors.Althoughheathcarehasbeensubstantiallyimprovedinthepastyearsintheruralareas,peopleintheremotecountrysidestillhaveverylimitedaccesstoscreeningservices.AnotherlimitingfactoristhatapparentlymoreefficientscreeningdevicesortechniquesthanHolterarenotyetreimbursedinclinicalpractice.

StartingAFscreeningfromhighriskpopulations,suchaspatientshospitalizedforacuteischaemicstrokeortransientischaemicattackandelderlypatientswithhypertensionandothercardiovascularriskfactors,maybearealisticapproach.HandheldECGrecordingdeviceswithvalidatedalgorithmscanbeausefulandefficientscreeningtool,andshouldbeinvestigatedincontrolledclinicaltrials.Self-pulsemeasurementeducationandhomebloodpressuremonitoringusingbloodpressuremonitorwithanadditionalfunctionofirregularheartbeatdetectionwouldalsohelpinimprovingawarenessforAFscreening.

DenmarkAxelBrandes,JesperSvendsen,UlrikDixen

Denmarkhasatax-financedpublichealthsystem,whichisfreeofchargeforallpatients.Thegeneralpractitioners(GPs)haveagatekeeperfunctionforoutpatients.Cardiologistsarealmostexclusivelyhospital-based.TheDanishSocietyofCardiologyhasendorsedtheESCguidelinesonthemanagementofAFand,thus,recommendsopportunisticscreeningforAF,astheDanishStrokeSociety(DSS)doesforallpatientswithstrokeorTIA.86,87Moreover,theDSSrecommendslong-termECGmonitoringinallpatientswithstrokeorTIA,buthasnospecificrecommendationsforthemonitoringmethodused.87SomepatientorganisationsliketheStrokeAssociationalsorecommendopportunisticscreeningwithpulse-takingfollowedbyanECG.88

Todate,therehasbeennoco-ordinatednationalAFscreeningcampaignforthegeneralpopulation,butalmostallstrokeandTIApatientsreceivelong-termECGmonitoringeitherduringtheirstayatthestrokeunitsorbyreferraltoacardiologyoutpatientclinic.TherearenodataonthenumberofundetectedAFcasesavailable.AllstakeholdersintheDanishhealthsystemhavelargelyfocussedonAFtreatment,whichcanbefollowedusingthedifferentnation-wideregistries.Severalyearsagoanation-widestrokeregistryandanablationregistryhavebeenestablished.AnationalAFregistryisindevelopmentandwillbelaunchedbytheendof2016.Inparticular,GP’sandDanishcardiologistshavehadmuchfocusontheintroductionofNOACsduringthelastyearsand,therefore,alsoonthereferralofnewlydiagnosedAFpatientstocardiologistsoranticoagulationclinics.

ItisexpectedthattheLOOPstudy,whichwillinclude6,000high-riskpatientsandidentifyunrecognizedAFusingimplantablelooprecordersand,thus,isaimingatreducingstrokerisk,willputAFscreeningmoreintothespotlight.Resultsofthislargerandomizedstudyareexpectedin2019-2020.

FranceLaurentFauchierAsinmanycountries,AFinFranceisoftenoverlookedanddiagnosedtoolate.In20%ofcases,AFisdiagnosedwhenastrokeoccurs.PROFILFAwasaFrenchAFawarenesscampaigningeneralpracticepresentedbyDavyalin2014.89Participatinggeneralpractitioners(GPs)wereasked,onagivenday,tolookforseveralclinicalitemsinalltheirconsecutivepatientsover65years,accordingtoadedicatedandsimplequestionnaireincludingthe7criteriaofthethromboembolicriskscoreCHA2DS2VAScscore,theexistenceof4symptoms,transientandsuggestiveofAFepisodes:palpitations,chestpain,dyspnoea(shortnessofbreath)andasthenia(weakness),andfinallypalpationofanirregularradialpulse.WhenAFwassuspected,GPsreferredpatientstoacardiologistfordiagnosticconfirmation.Thestudyincluded603physiciansand4592patients.AFhadalreadybeendiagnosedin840patients(18%ofcases).Theremaining3752patientswereevaluatedonasingledayusingthequestionnaire.Ofthese,AFwasclinicallysuspectedin585patients(1in6)andtheywerereferredtoacardiologist.Outofthe585patientsinwhomAFwassuspectedbytheGP,129patients(nearly1in4)hadtheexistenceofAFconfirmedbythespecialistwhothenprescribedappropriatetreatment.AnirregularpulsewaslinkedtoadiagnosisofAFinonly1outof2cases.Forpatientswithoutirregularheartbeat,thepresenceoftwosymptomsand/orapreviousstrokehistorywerealsopredictorsofAF.AnotherstudydemonstratedthatidentificationofAFafterischemicstrokewascloselyrelatedtothenumberofriskfactorsfromtheCHA2DS2VAScscoreinFrenchpatients.90ThedetectionofsilentAFtopreventischaemicstrokemayrequiretheuseoflongtermexternalorinternalelectrocardiogram(ECG)monitors.However,symptomaticAForAFwithfastventricularratewasnotidentifiedbyimplantablelooprecordersinpatientsunder75yearswithunexplainedcerebralischemiaandnocardiovascularriskfactors.91Theuseofsuchdeviceshouldnotbegeneralizedinthesystematicevaluationofthesepatients.Bycontrast,unknownAFcanbeidentifiedinthepopulationover65yearsusingasimpleprecisepathwayandamultidisciplinaryapproach.

GermanyRenateSchnabel,JohannesBrachmann,GuenterBreithardt,StefanKaab,CarlosMartinez,MoritzSinner,RolfWachter GermanyhasanagingWesternsocietywithaprojectedsignificantincreaseinatrialfibrillationprevalence.92,93MostresultsfrompriorstudiesinWesternpopulationsshouldbeapplicabletoGermanconditions.Thereisahighpotentialtodetectuntreatedatrialfibrillation,inparticular,inolderadults.Basedonhealthinsurancedata,annualdirectcostsofatrialfibrillationare3300EUR.94,95Almost10,000strokesannuallycouldbepreventedinGermanybyoptimalatrialfibrillationdiagnosisandtreatment(https://www.dak.de/dakonline/live/dak/download/Chartbook_DAK_-_Versorgungsreport-1439116.pdf).Inaddition,screeningforatrialfibrillationaftercryptogenicstrokemightfurtherimprovesecondarystrokepreventioninthesepatients.96FewGermantrialshaveaddressedthisissue.TheFIND-AFstudycoulddemonstratethat7-dayHoltermonitoringforatrialfibrillationscreeningafterstrokeismostefficientinolderadults.97OneofthelargesteffortscurrentlyisthestandardizedMONitoringforDetectionofAtrialFibrillationinIschemicStroke(MonDAFIS)study.ItwillevaluatewhetheraprolongedandsystematicECGmonitoringduringtheinitialinhospitalstayhasanimpactonsecondarystrokeprevention.98Todate,nonationwidepolicyorcountry-specificrecommendationsoftheGermanCardiacSocietyexistthatatrialfibrillationscreeninginprimarypreventionshouldbeoffered.PhysiciansfollowtheguidelinesforopportunisticscreeningoftheEuropeanSocietyofCardiology.99Ninety-ninepercentofgeneralpractitionersofferrestingelectrocardiograms.100Thus,nationwideimplementationoftheguidelinesshouldbefeasible.Nodataexistontheactualguidelineadherence.Thenewpreventionlawof25July2015(Präventionsgesetz-PrävG)doesnotspecificallyaddressatrialfibrillationasadiseaseforhealthpromotionandscreening.Statutoryhealthinsurancesofferanannualcheck-upfromage35yearsonforcardiovasculardisease,renaldysfunctionandtype2diabetesmellituswhichdoesnotexplicitlyincluderhythmassessmentoratrialfibrillation.Fewhealthinsurancedrivenprojectshaveaddressedscreeningforatrialfibrillationinshort-termandregionalprojects.E.g.since2008theKKH(KaufmännischeKrankenkasse)hasofferedascreeningprograminindividualsaged50yearsorolderwithadditionalatrialfibrillationriskfactors.InaregionalprojectinRhineland-Palatinatewithabout1,000,000inhabitantssystemicscreeningforatrialfibrillationwillbeperformedover4weeksperparticipantwithahand-helddevice.ParticipantswithnoprioratrialfibrillationwillbeincludediftheyhaveaCHA2DS2-VAScscore>1orsymptomsofanirregularpulseorhadhaveapriorstrokeofunknownorigin.TheAtrialFibrillationNetwork(AFNET,http://www.kompetenznetz-vorhofflimmern.de/de/afnet),aregisteredsocietyinitiallyfundedbytheFederalMinistryofEducationandResearch,isintendedtoimprovethemanagementofatrialfibrillation.Ithasanationwideimpact.Partofitsmissionistoincreasetheawarenessofatrialfibrillation,e.g.duringtheinternationalAFAwareWeek.ToimproveatrialfibrillationawarenessandscreeninginGermanystructurednationwideactionwouldneedtobetakenthatshouldthenbeimplementedatthefederalandlocalstateandincommunities.

Greece

ThereisonememberfromGreece.PopulationscreeningforAFhasbeenreportedbyNtaiosetalintheArcadiastudyperformedin5villagesinruralGreece,using12-leadECGandclinicalexaminationandhistory.101

HongKongBryanYan,Chung-Wah(David)Siu InHongKong,>90%ofthe7millionpopulationareservicedbythepublichealthcaresectorwhichinclude41hospitalsandinstitutions,47specialistout-patientclinics,and73generalout-patientClinicsmanagedbytheHongKongHospitalAuthority.PublicmedicaloutpatientclinicshaveahighvolumeofelderlypatientsandseemideallyplacedforscreeningforAF.In2014-2015,~5.9millionattendedpublicgeneralmedicaloutpatientsclinicsacrossHongKongofwhich~30%(1.77million)are>65yearsold(SeeHospitalAuthorityStatisticalReport2014-2015:http://www.ha.org.hk/haho/ho/stat/HASR1415_1.pdf).Currently,thereareatleast3largeAFscreeningprogramsinHongKong(eachinvolvingmorethan20,000patients)usingahandheldECGand/orphotoplethysmorgraphic(PPG)devices.OnegroupledbySiuCW,recentlypublishedtheirresultsusingtheCardiioRhythm(CardiioInc.Cambridge,MA)smartphonePPGapplicationforAFscreeningin1,098patientsinaprimarycaresettingandfoundAFin2.76%ofpatients.102AnothergroupledbyYanBP,hasanongoingprogramwhichusestheAliveCorsingle-leadECGdeviceforAFscreeningin>25,000patientsaged65yearsandaboveattendingmedicaloutpatientclinics(NCT02409654).PreliminaryresultsshowedthatnewlyidentifiedAFwasfoundin1.5%(n=121/9046)onasinglescreen,andanadditional1.2%(n=15/973)wasdetectedinthosescreenedonmultipleoccasions.

IndiaDorairajPrabhakaran,NitishNaikThere is a dearth of reliable data on population prevalence of atrial fibrillation in India. There ispresently no systematic published data that has documentedwith reasonable precision the exactburdenofatrialfibrillationinthecountry.Publisheddataislargelyrepresentativeoftheclinicalprofileof patients with established atrial fibrillation. For example, the RE-LY Atrial Fibrillation Registryreported demographic data on 15, 400 patients from high, medium and low income countriespresentingtotheemergencydepartmentwithatrialfibrillationoratrialflutteraseithertheprimaryreasonfortheirvisitorasasecondarydiagnosis.103Atotalof2536patientswereenrolledfromIndiawithameanageof57years,nearlyadecadeyoungerthanpatientsenrolledfromthewest.Patientswithvalvularheartdiseaseconstituted31.5%ofthesepatients.SincerheumaticheartdiseaseisstillasignificantcontributortothecardiovasculardiseaseburdeninIndia,youngpatientsaccountforasizeableproportionofatrialfibrillationinIndia.Sinceatrialfibrillationcanoftenbeasymptomaticandnotrequirehospitalvisits,screeningprogramsthatarecommunitybasedmayofferamorerealisticassessmentof its theburden.Asurveyofalladults over 50 years through a representative proportionate sampling (such asmultistage clusterrandomsampling)inmultipledistrictsindifferentstateswouldbeabletocapturedataonpersistentandchronicatrialfibrillation.Inaddition,systematicsamplingofadults(>20years)attendinghospitalswould provide opportunistic screening for persistent and chronic atrial fibrillation. We haveestablishedacohortofnearly70,000adults>20yearsspreadover9districtsin5states(Delhi,TamilNadu,Haryana,AndhraPradeshandUttarPradesh) acrossnorth, south, central andwest India inaddition toanetworkofphysicians spreadovernearly200hospitalacross thecountry. ThisdualapproachwouldprovideareasonablestrategyforassessingprevalenceofatrialfibrillationinIndia.

IrelandJosephHarbison,DavidKeane,GerardBuryIrelandisperceivedashavingasubstantialproblemwithatrialfibrillationandAFrelatedstroke.TheIrishLongitudinalStudyofAgeing(TILDA)studiedarepresentativepopulationofIrishpeople>50yearsandfoundanoverallprevalenceofAFof3%butaprevalenceof19.3%inmenand5.9%ofwomenaged80yearsandolder.104TheNorthDublinPopulationStrokeStudyreportedthat31.2%ofstrokesreportedwereassociatedwithAFandthat54.2%ofsubjectshadknownAFbutwerefrequentlynotadequatelyanticoagulated.105MorerecentlytheNationalStrokeAuditpublishedinJanuary2016showedthat44%ofpatientshadAFidentifiedoninvestigation(McElwaine,P.McCormack,J.Harbison,J.onbehalfoftheNationalStrokeProgrammeAuditSteeringGroupIrishHeartFoundation/HSENationalStrokeAudit:http://www.lenus.ie/hse/handle/10147/596575).AnAFscreeningstudywith7262participantswasperformedunderthedirectionoftheNationalStrokeProgrammein2014.ThestudywasconductedinapredominantlyruralareaoftheWestofIrelandandfounda10.9%prevalenceofAF(0.8%unknown,10.1%known).106Anotherstudywith566participantsbyBuryandcolleaguesusinga3leadECGingeneralpracticesfounda2.1%prevalenceofnewAFand9.5prevalenceofknownAF.107AhealthtechnologyassessmentofAFscreeningbydigitalpulsecheckinginprimarycarewasconductedbyPatrickMoranandcolleaguesoftheHealthInformationandQualityauthorityshowedthatAFscreeningwaslikelytobeeffectiveandaproposalhasbeendevelopedtointroducethisaspartofanewprimarycarecontractforfamilypractitionersbasedonprotocolsdevelopedforthescreeningstudy.108

ItalyGiuseppeBoriani,IreneMarzona,SakisThemistoclakisInItalyhealthcareisprovidedtoallcitizensandresidentsbyanationalhealthservice,whichisorganizedundertheMinistryofHealthandisadministeredonaregionalbasis.Thenationalhealthserviceprovidesuniversalcoverageandisbasedontaxfunding.LifeexpectancyatbirthinItalywas82.3yearsin2012,whichisovertwoyearsabovetheOECDaverage.ThetypeoforganizationoftheHealthcaresystem,whichisorganizedformanygeneralaspectsatanationallevel,butfinanciallyadministeredonaregionalbasis,makesdifficulttheplanninginthewholecountryofinitiativesofprevention/screeningthatrequirespecificpublicfunding.ArecentsurveypromotedinItalyby233generalpractitioners(GPs)109foundamong295,906screenedpatientsaprevalenceofdiagnosedAFof2,04%thatwas2timesgreaterthanpreviouslyreported.AFoccurredin0.16%ofpatientsaged16to50years,9.0%ofthoseaged76to85years,and10.7%ofthoseaged≥85years.AFwassymptomaticdespitetherapyin74.6%ofpatientsandwasassociatedwithheartdiseasein75%.AdedicatedHTA(HealthTechnologyAssessment)document,deliveredin2014byanAgencyoftheItalianMinisterofHealth(AdaptedHTAREPORTEfficaciadelloscreeningsistematicoperladiagnosidifibrillazioneatriale,Roma,Luglio2014)concludedthatinthe12ItalianRegionsbelongingtotheItalianNetworkofHTAnoscreeningprogramsfordetectionofasymptomaticAFwasplannedatthetimeofdocumentrelease.Inthe2011anawarenesscampaignontheimportancetocheckthepulseforAFscreeninginordertodetectAFwasperformedinseveralItaliancities(http://www.alleanzalfa.org/stopfa_day.htm)Morerecentlythegeneralpractitioners(GPs)inBologna110screenedforAF12,294patientsusinganautomaticsphygmomanometerswithembeddedalgorithmstodetectirregularheartbeatandpossibleAF.TheuseofthesedeviceimprovedthedetectionofAFascomparedtonormalpractice.AnotherprojectiscurrentlyongoinginsomeItaliancities,onalocalbasis,foropportunisticscreeningofAF,withafirstselectioninpharmaciesonthebasisofbloodpressure(BP)deviceswithalgorithmsforAFdetection,followedbyin-hospitalECGforsubjectswithsuspectedAF.OtherinitiativesforAFscreeninghavebeenproposedonalocalbasis:http://www.aliceitalia.org/ictus_alice_italia_articolo_mese.php?id_contenuto_pagina=451&attiva_blog=1SeveralotherItalianinitiativesonAFscreeninghavebeenpublished.48,111,112

MexicoArturoGuerraInMexicotheCEREBRALVASCULARDISEASE(CVD),isaveryseriouspublichealthproblem.Infact,amongthediseasesofvascularorigin,CVDisconsideredthethirdleadingcauseofdeath,afterdiabetesmellitusandischemicheartdisease.

Accordingtonationalstatisticsfromgovernmentalsources,in2014,morethan60thousanddeathswererecorded for this cause. In Mexico, the systemic arterial hypertension is among the factors fordevelopmentof thisdisease. Smoking,diabetesmellitusandatrial fibrillationare consideredasmainfactors.Wehavecarriedoutnationwidesystemicarterialhypertensiondetectioncampaignsformorethan10years,aswellasdetectionofdiabetesmellituscampaigns;butverylittlehasbeendonetoeducatethephysicians in general aswell as the population about the serious consequences that peoplemay besuffering from atrial fibrillation. It is estimated that at least 1 million Mexicans suffer from atrialfibrillation,howeverexactnumbersarenotcompletelyknown.Againstthisbackground,webelievethatwemustmakemassivecampaignstodisseminatethisseriousdisease.Thiswouldconsiston:1.-Allianceswithgovernmentagencies(tosensitizethemoftheproblem).2. - Partnerships with different medical societies of all levels (cardiologists, neurologists,electrophysiologists,butinaspecialwaywithphysiciansoffirstcontact).3.-Massmediacampaigns,toteachthepublicingeneralhowtochecktheirpulse.4.-Trainnurses,socialworkers,andfirstcontactphysicians,todevelopcampaignsforAtrialFibrillationdetection.5.-Makebrochurestodeliverinallgovernmentandprivateclinicsandhospitals,withclearandsimpleinformationabouthowtodetectarrhythmia.These5measurescouldcauseanimpactinMexico,ofsufficientmagnitudetodecreasemorbidityandmortalityresultingfromthiscondition.

NetherlandsN.Verbiest-vanGurp,S.B.Uittenbogaart,I.C.vanGelder,M.Rienstra,R.Tieleman,H.G.J.M.CrijnsFamilyphysiciansandcardiologistssharetheresponsibilityfordetectinganddiagnosingatrialfibrillation(AF).Thistaskbecomesincreasinglyimportant,asthepopulationisageing;18%is65yearsorolder85.TheoverallprevalenceofAFinmedicalfilesoffamilyphysiciansis0,5%andincreasestorespectively4,5%and4,3%amongmenandwomenaged75yearsandover113.AFisprobablyunderreported,becauseasymptomaticand/orparoxysmalAFaredifficulttodetect.TheguidelineonAFforfamilyphysiciansdoesnotrecommendsystematicscreening,butadvisestojudgetheheartrhythmwhenmeasuringbloodpressure114.Acasevignettestudyshowedthat40%oftherespondingcardiologistsscreensforAFwitha12-leadrestingECGinhighriskpatients115.Europeanguidelinesforcardiologistsmentionthatscreeningmaybeusefulbutthereisnogeneralschemeforscreening86,116,117.Currentscreeningstudiesinprimarycare:

- D2AF:DetectingandDiagnosingAtrialFibrillation,amulticenterclusterrandomizedcontrolledtrial(RCT)inprimarycare.118Case-findingusingpulsepalpation,WatchBPHomeAandMyDiagnostickiscomparedwithusualcare.

- IDEAL-MD:ImprovingDEtectionofAtrialfibriLlationinfamilypracticeswiththeMyDiagnostick,anRCTevaluatingthenumberofnewcasesofAFdetectedwiththeMyDiagnostickcomparedtocareasusualinprimarycare.119

- Kaasenbroodetal.screenedaDutchpopulation(n=3.269)duringthefluvaccinationbymeansofahandheldECGdeviceandfound37(1,1%)newcasesofAF.120Thisprogramsaved€2660,-and0,28QALY’sforeachAFpatientdetected.

Currentscreeningstudiesinsecondarycare:

- CRYSTAL-AF:arandomizedprospectivestudyinEurope,Canada,andtheUnitedStatesevaluatinglong-termmonitoringforAFdetectionwithRevealSubcutaneousCardiacMonitorinpatientswithcryptogenicstroke121-124.

- REVEALAF:aprospective,single-arm,open-labelstudyintheUS,Austria,SloveniaandtheNetherlands,evaluatingtheincidenceofAFinhighriskpatientsbasedonsymptomsand/ordemographicareabyimplantingtheReveal125.

- SCARF:ExtendedRhythmScreeningforAtRialFibrillationinCryptogenicStrokePatients,evaluatingthepercentageofpatientswithdocumentedAFbasedonRevealregistrationaftercryptogenicstroke126.

- RATEPALM:scReeningforAtrialfibrillaTionofundiagnosEdPatientsinchronicheArtfaiLureoutpatientclinicthroughMydiagnostick127.

- VIP-HF:VentricularTachyarrhythmiaDetectionbyImplantableLoopRecordinginPatientsWithHeartFailureandPreservedEjectionFraction128.

Currently,thereisnonationalscreeningprogramforAF,buttherearesomeregionalinitiatives.InGroningenscreeningforAFwiththeMyDiagnostickbyfamilyphysiciansispartof‘KetenzorgAF’(integratedcareforAF).Furthermorefamilyphysicianswillscreen50.000patientsduringthenextfluvaccination(2016).InordertoestablishanationalscreeningprogramforAF,theresultsofD2AFandIDEAL-MDmustbeavailable.Moreoverthelocalinitiativesmustbesuccessfulandhealthinsurersmustsupportanationalscreeningprogram.

NewZealandKatrinaPoppe,RobertNDoughty,NWalker,RJacksonNewZealandisamulti-ethnicislandnationintheSouthwestPacificregion.Ofthe4.67millionpeople,74.6%areNZEuropean,15.6%Māori(indigenouspopulation),12.2%Asianand7.8%Pacificpeoples(www.stats.govt.nz).CardiovasculardiseaseistheleadingcauseofdeathinNZdespiteadeclineinagestandardizedmortalityrates.Therearelong-standingethnicandsocioeconomicdisparitiesinNZ,withMāoriandPacificpeoplehavinghigherprevalenceofCVDatyoungagesandwithworseoutcomes.SeveralsourcesofdataareavailablewithregardtoAFinNZ:

• AmongruralMāori,urbanMāoriandurbannon-Māoriwithameanageof46years,AFwaspresentin2%,1.2%and0.4%respectively.129

• Amongpatientsinaprimarycarecohortaged>55years(n=31,607),AFwaspresentin7.3%ofMāori,4%ofPacificand4.1%non-Māori/non-Pacific.(GuH,personalcommunication)

• Amongaprimarycarecohort(12,500people)aged35-74years,AFwaspresentin4.4%ofMāori,2.5%Pacificand2.8%ofNZEuropean.130

• Amongpeopleofadvancedage(>80years,n=937)),theprevalenceofAFwas30%amongMāori,comparedwith21%amongnon-Māori.131

PatientswithAFarepredominatelymanagedinprimarycarehealthservices(fee-for-servicebasis),medications,suchasanticoagulants,arepubliclysubsidizedbyanationalfundingagency(PHARMAC),andspecialistevaluation/investigationsareavailablebyreferraltopubliclyfundedsecondarycareservices.AvailabledatasuggestasignificantburdenofAFamongpeopleinNZ,particularlyforMāoriandPacificpeoples,inwhomAFcanoccur20yearsearlierthannon-Māori/non-Pacific.Currently,nosystematicscreeningprogramsforAFareavailableinNZ.SeveralresearchstudiesareplannedtodetermineoptimalscreeningapproachesforthedetectionofAFinNZ.

NorwayTveitA,MD,PhD,ChristophersenIE,MD,PhD.Todate,therehasbeennoattempttoimplementscreeningforAFinNorway.Oneresearchprojectinvestigatedthebenefitofsystematic12-leadECGscreeningamong75yearsoldindividualsintwocountieswestofOslo,identifying10previouslyundiagnosedAFcasesinthe916individualsscreened(1.1%).132Anotherongoingstudyisinvestigatingthebenefitofatwo-weekintermittent“thumb”-ECGscreeningin65yearsoldsubjects.Compliancewithnationalandinternationalguidelinesforantithrombotictreatmentisrelativelyhigh.Norwayhasawell-organizedprimaryhealthcaresystem,whereallcitizenshavebeenassignedtoapersonalprimarycarephysician.Ofnote,thereishighawarenessofAFamongprimarycarephysicians.AllNorwegiancitizenshavetheirownunique11-digitnationalidentifierandareregisteredinanationalcivilregistrywithnameandcurrentaddress,facilitatingaccesstoallcitizens.However,centralizationofAFscreeningmaybecomplicatedbythefactthatmostofNorwayisrural,withfewdenselypopulatedareas.AFscreeningiscurrentlyunderevaluationinNorway;however,moredataisneededtodefinethepreferredmethodofAFdetection,agegroupstotarget,andscreeningintervals.Thus,itistooearlytogivefirmrecommendationsregardingscreeningforAFinNorway.

SingaporeTherearenoAF-SCREENmembersinSingapore,buttherehasbeenacommunityscreeningstudyperformedadecadeagousingastandardECGaspartofalongitudinalageingstudy,butwithayoungerpatientpopulationthanusual,startingatage55.133

SwedenEmmaSvennberg,MartenRosenqvist,LeifFriberg,JohanEngdahlCountry: SwedenPopulation:9.9millionScreeningPopulation-basedAFscreeninginSwedenwasinitiatedbyastepwiseAFscreeningprograminvitingall75/76-yearolds,n=1330,residinginthemunicipalityofHallandinthesouthwestregionofSwedentoAFscreening134.Theattendancewas64%,andscreeningwasperformedbyoneinitial12-leadECGfollowedbyintermittentECGrecordingsforafortnightinindividualswithCHADS2≥2.Ofthe403participantswhocompletedtheentirescreeningprogrammenewAFwasdetectedin7.4%.ScreeningusingtwicedailyhandheldECGsfor28daysin928individualsintheprimarycare/out-patientsettingwithCHADS2≥1,meanage70.7years,detected3.8%AF135.Inclusioninarandomisedmass-screeningstudyin75/76-yearolds,theSTROKESTOPstudy,wascompletedinJune2014andincludedresidentsinthecapitalregionofStockholmandtheruralHallandregion136,137.Of13331participantsinvitedtoscreening54%(7173)attendedthescreeningprogram,whichincluded14daystwicedailyintermittent1-leadECGrecordings.OfthescreenedpopulationnewAFwasdetectedin218participants(3%),andinaddition2.1%werefoundtohaveundertreatedknownAF.OfparticipantswithnewAF>90%werecommencedonoralanticoagulants.Thescreeningprogramwasfoundtobecost-efficient,withacostof€4313pergainedQALY138.TheSwedishgovernmentagencyofDentalandPharmaceuticalBenefitsconcludedthatthebenefitsofprimarypreventivescreeningwiththumbECGin75-yearoldsislargeenoughtojustifycostsofscreening139. NationalimplementationHealthcareinSwedenisfundedbythegovernment,andfinancedmainlythroughtaxesfromthemunicipalitiesandcountycouncils.Screeningwouldlikelyreducecostsfortheentiresociety,howevertheinitialcostsforthecountycouncils(whopayforscreeningandacutestrokecare)mightincrease.Thecostsforrehabilitationafterstrokeiscarriedbythemunicipalitiesandwouldlikelybereduced.TheSwedishNationalBoardofHealthandWelfareareintheprocessofdecidingifpopulationscreeningforatrialfibrillationshouldbeinitiated.OnecaveatisthatthefinalresultsfromtheSTROKESTOPstudyarenotyetcomplete,andtheendpointofreductionofischemicstrokeandmortalityareyettobeaddressed.

SwitzerlandDavidConen,DerkKriegerSwitzerlandhasoneofthehighestlifeexpectanciesworldwide,itisthereforeexpectedthatAFisandwillbeamajorpublichealthissue.Unfortunately,specificdataonAFprevalenceandincidenceinSwitzerlandarecurrentlylacking.OnemajorcurrenteffortistheestablishmentofalargenationalcohortstudyofpatientswithAF,focusingontheassociationbetweenAF,structuralbraindamageandcognitivedecline.Swiss-AFisfundedbytheSwissNationalScienceFoundationandmostlargehospitalsinSwitzerlandareparticipating.WearenotawareofanycurrentorpreviouseffortstoscreenforpreviouslyunknownAFinSwitzerland.EuropeanguidelinesforAFmanagementcurrentlyrecommendtakingthepulseinindividualsaged65yearsorolder,andtheserecommendationsareregularlyhighlightedinanon-systematicwaybyexpertsinSwitzerland.IffutureeffortsforAFscreeninginSwitzerlandwanttobesuccessful,theyhavetoinvolvehealthcareproviders,professionalorganizations,healthinsurancecompaniesandpoliticalstakeholders.OneoftheadvantagesoftheSwisshealthcaresystemiscompulsoryhealthinsurancecoverageforallindividualslivinginSwitzerland.Oneofthekeydisadvantagesisthefederalstructuregivingalotofindependencetoindividualstatesfordecidingonhealthrelatedissues,suchthatanationalcampaignorpolicywillbemoredifficulttoimplement.

ThailandTachapongNgarmukos IncidenceofAF,unknownAFinThailand&useofOACAbout30%ofThaielderlyage>65yearsislikelytohaveasymptomaticAF.PhrommintikulArintayasurveyedandobtainedECGfrom1,277of10,805whoowereolderthan65yearsfromMaerindistrictedinChiangMai.Themeanage73.1±6.4yearsandfemale46.4%.AFwasfoundin24subjectswiththeprevalenceof1.9%(95%CI:1.12%-2.48%).17oftheses24werepreviouslyknowtohaveAF.IncidenceofAFincreasewithage1.5%for65-74years,2.2%for75-84yearsand2.8%forpatientolderthan85years.PatientswithAFweresignificantlyolder(75.4±6.5yearsvs.73.1±6.4years),hadhigherprevalenceofheartfailure(20.8%vs.0.1%),ischemicheartdisease(16.7%vs.1.1%),valvularheartdisease(29.2%vs.0.1%),chronicobstructivepulmonarydisease(16.7%vs.2.6%),hyperthyroidism(8.3%vs.0.9%)andpriorstroke(16.7%vs.0.8%),allP-value<0.05.17of24patienthadNVAFamongthese,16/17hasCHA2DS2VASc>2,mean3.4+1.2.OftheseNVAFpatients3(17.6%)hadpreviousstroke/TIA,only7(41.2%)wereonOAC.140ClosetohalfofpatientwithacutestokeandAFarelikelytobeasymptomaticAF.Sutamnartponglookedat204consecutivepatientwithacutestoke,46(22%)werefoundtobeinAForPAFfromECGorduringmonitoring.Ofthese46patients22(47%)werenotknowofAF,141presumablythesewereasymptomaticpatients.AFisoneofamajormedicalissuesinThailand.NarongritKasemsapstudiedtheThailandnationalreimbursementdatabasesfromtheuniversalcoveragesystem(cover75.2%ofThaipopulation)duringthefiscalyear2004-2012.Thetotalnumberofischemicstrokeinin-patientswas277,291patientsand30149(8.1%)of277,291patientswhosufferedischemicstrokehadAF.MortalityrateinAFgroupwassignificanthigherthannon-AFgroup(14.1%vs6.2%;p<0.001).TheexpenditureperpatientinAFgroupwassignificanthigherthannon-AFgroup(36,192bathvs18,816bath;p<0.001).142 ApiyasawatalsolookedattheThaigovernmentprovidedhealthinsurancedatabasefrom2005-2010.ThehospitalizationrateforAFwas15.5per100,000person-years.Bythe72-monthfollow-up(average46months),3948patients(44.0%)haddied.143TheuseofOACisreasonable,Jedsadayanmataidentified369NVAFfrom531AFpatients,therewere138(37.4%)hadCHADS2score>or=2.Amonghigh-riskpatients,70.3%wereprescribedwarfarinwhile19.6%receivedonlyantiplateletsand10.1%receivednoantithrombotictherapy.144AFscreeningprogramandresultsAspartofAPHRSefforttoincreasepublicawarenessonatrialfibrillation(AF)inAsia-pacificregion,APHRSinitiatedajointcollaborationwithitsmembercountriestoachievetheobjective.SimultaneouslyonJuly2,2016,Taiwan,SingaporeandBangkokorganizedaneventtoraisedpublicawarenessonAFanditsassociationwithstroke.InBangkok,undertheleadershipofAssociatedprofessorKhanchitLikkitthanasombat,thechiefofThaiEPclubandpresidentelectedoftheThaiheartassociationofThailandundertheroyalpatronageofH.M.theKing,arrangedthe1st“AFday”

a5kmfreewalk/runeventwithpublicforumintheearlyhourofJuly2,2016.Toreachouttomorepopulation,pre-eventprogramswereusedincludingTVandradiointerviews,morningTVnews,andhealthmagazinearticleonAF.AswellassocialnetworkingtoreachoutWecoinedanewterminThaiforAF“huijaitenrarik”amorecatchyterm,tomakeAFmorememorableforthepublic.Duringthecampaigntherewere3keymessages:

1. AFisacommoncauseofseverestroke2. StrokefromAFispreventable3. AFcoulddetectbycheckingone’spulse145

Theresultofthecampaignwasdifficulttodetermine,consideringthecostofassessingAFharnesssurveywouldbequitecostly.Howeverweaplanningtodothiseventannually.RecommendationsaboutAFscreeninginThailand:

• anythingthatinvolvedcostlytechnologywouldbeproblematic.• WeshouldraisepublicawarenessofAFandstroke.• Weshouldteachhighriskpopulationtochecktheirpulsedailyis.

UruguayWalterReyesCaorsiUruguaybordersonthewestwithArgentinaandonthenorthandnortheastwithBrazil;ontheeastandsouthitborderstheAtlanticOceanandRiodelaPlata. Ithasa landareaof176.215km2andtopography of low, rolling hills, vast plains, and a fertile coastline. Its climate is temperate. Thegovernment is a representative democracy, with executive, legislative and judicial branches. ThecapitalisMontevideo,andthereare19administrativedepartmentsand89municipalities.See:HealthintheAmericas.PanAmericanHealthOrganization(PAHO),WorldHealthOrganization(WHO).2012Uruguay.www.who.int.GlobalHealthObservatory(GHO)DataAFscreeningattemptsWith the support andbackgroundofArrhythmiaAlliance (www.aa-international.org/uy), a “CheckyourPulse”programwasinitiatedin2012inaschooloftheDepartmentofColonia(westcoastofthecountry) teaching children of 10-12y.o. about this maneuver and its importance. Children werecommittedtocheckthepulseoftheirrelativesandneighbors.MaterialofsupportfromArrhythmiaAlliancewastranslatedandhandedoffineveryactivity.Withthemostmotivatedchildren,“CheckyourPulse”activitieswereperformedinShoppingMalls,Fairs, etc. The program won an award from the University of the Republic and the project waspresentedandpublishedinthe“VIJointConferenceaboutLearningTechnologies”inJune2014intheHumboldtInternationalUniversity,Miami,USA.Also,theprogramwasdeclaredofspecialinterestbylocalpoliticalauthorities.SomeisolatedexperienceswerealsoperformedinMontevideo(CapitalCity)schools.Thetargetistotryandimplementthisprograminalltheschoolsacrossthecountry.Inaddition,Iperformedactivitiestopromotetheprogramsuchas:themedia,indiversenon-MedicaleventsandFairs,inCardiologyMeetings,aswellaswithrelativesofpatientsadmittedintheHospital.Wehavealwaysreceivedthesupportofthe“UruguayanSocietyofCardiology”andofthe“HonoraryCommissionofCardiovascularHealth”.TomyknowledgetherearenotothersprogramsofAFscreeninginthecountry.LimitationsLimited budget support: a pharmaceutical company covered the cost of printing brochures andorganizingafewevents.Weareyettoreceivesupportfromgovernmententities.Sofarithasbeenapersonalproject.

UK

SotirisAntoniou,JohnCamm,DavidFitzmaurice,NeilGrubb,HuonGray,JulianHalcox,PaulusKirchhof,GregoryLip,TrudieLobban,IreneSavalieva,RichardSchilling

Approximately 925,000 patients are recorded on general practitioners register (QOF - 2014/2015:http://www.hscic.gov.uk/catalogue/PUB18887)withadiagnosisofAF–prevalenceof1.63%.PublicHealth England and the National Cardiovascular Intelligence Networks (http://www.ncvin.org)estimate the true prevalence closer to 2.4%. Therefore, approaching half a million patients areestimatedtohaveasyetundiagnosedAF.

Nationally, National Institute for Health and Clinical Excellence (NICE) produced guidance on themanagementofatrialfibrillationandwhilstgeneralpopulationscreeningwasbeyondthescope,theguidelines state that targeted/opportunistic screening of symptomatic patients or thosewith riskfactorsmayallowidentificationofAFpatients.146

However,inMay2014,areportforthenationalscreeningcommitteeonscreeningforatrialfibrillationinpeopleaged65recognisedthatwhilsttheproposalwouldproducemorebenefitthanharmatpopulationlevel,therewasuncertaintyastowhethersuchaprogrammewouldbecost-effective(http://legacy.screening.nhs.uk/policydb_download.php?doc=446.).TheyalsoraisedthatcurrentNHSmanagementofAFthatisdetectedthroughroutineclinicalpracticeisknowntobefrequentlypoor,bothbecausepatientswhoshouldreceiveanticoagulantsdonotreceiveanticoagulants,andbecausetreatmentwithwarfarinisoftenproblematic.

Theysummarisedthatbeforeintroducingascreeningprogramme,theNHSshouldfirstdemonstratethat it is managing AFmuch better than it has done to date, because it would be unethical tointroduceascreeningprogrammewithoutbeingconfidentthatscreen-detectedpatientswouldbewellmanaged.Thepolicyisscheduleforreviewin2017.

However, despite the formal position, there arenumerous researchprojects todemonstrate thecost-effectiveness andhighprevalenceofAF, and regional variationswithin theUK. Scotland forexamplehasundertakenanationalAFscreeningpilotwhichisbeingreportedtoNationalAdvisoryCommittees,whereasacross theremaininghomecountries, therearebetterand lessperformingareas. The Arrhythmia Alliance and AF association has led on ‘know your pulse’ campaigns(http://www.heartrhythmalliance.org/aa/uk/know-your-pulse) working in partnership with GPsurgeries,pharmaciesandschoolstoraiseawarenessofAF.

Withtheinterestofmedicaltechnology,NICEhasproducedamedicaltechnologyguidanceonWatchBP(WatchBPHomeAforopportunisticallydetectingatrialfibrillationduringdiagnosisandmonitoringofhypertensionNICEmedicaltechnologyguidance[MTG13]Publisheddate:January2013)andamedtechinnovationbriefing(MIB)ontheAliveCorHeartMonitorandAliveECGappfordetectingatrialfibrillation.AliveCorwasalsoselectedtobepartoftheNHSInnovationAccelerator.TheaimofwhichistocreateconditionsandculturalchangenecessaryforproveninnovationstobeadoptedfasterandmoresystematicallythroughtheNHS,andtodeliverexamplesintopracticefordemonstrablepatientandpopulationbenefit.

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