Stepwise Screening of Atrial Fibrillation in a 75-Year Old Population

DOI: 10.1161/CIRCULATIONAHA.112.126656

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Stepwise Screening of Atrial Fibrillation in a 75-Year Old Population:

Implications for Stroke Prevention

Running title: Engdahl et al.; Screening of Atrial Fibrillation

Johan Engdahl, MD, PhD1; Lisbeth Andersson, RN1; Maria Mirskaya, RN1;

Mårten Rosenqvist, MD, PhD2

1Dept of Medicine, Hallands Hospital Halmstad, Halmstad, Sweden; 2Dept of Clinical Science,

Karolinska Institute, Danderyds Sjukhus, Stockholm, Sweden

Address for Correspondence:

Johan Engdahl, MD, PhD

Department of Medicine

Hallands Hospital Halmstad

SE-301 85 Halmstad, Sweden

Tel: +46-35-131000

Fax: +46-35-131559

E-mail: [email protected]

Journal Subject Codes: [5] Arrhythmias, clinical electrophysiology, drugs; [8] Epidemiology; [193] Clinical studies; [121] Primary prevention; [64] Primary and Secondary Stroke Prevention; [70] Anticoagulants

Mårten Rosenqvist, MD, PhD2

1DeDeptptp oooff f MeMeedid ciciinenen , Hallands Hospital Halmstadd,, , HaHH lmstad, Sweden; ; 2DeDD pt of Clinical Science,

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Abstract:

Background—Atrial fibrillation (AF) is a frequent source of cardiac emboli in patients with

ischemic stroke. AF may be asymptomatic and therefore undiagnosed. Screening for silent AF

seems suitable in risk populations, little is however known on the yield and cost-effectiveness of

such screening.

Methods and Results—All inhabitants in the municipality of Halmstad, Sweden age 75-76 were

invited to a stepwise screening program for AF. As a first step, participants recorded a 12-lead

ECG and reported their relevant medical history. Those with sinus rhythm on 12-lead ECG, no

history of AF and at least two risk factors according to CHADS2 were invited to a 2 week

recording period using a hand-held ECG asked to record 20 or 30 seconds twice daily and if

palpitations occurred. 1330 inhabitants were invited of whom 848 (64%) participated. Previously

undiagnosed silent AF was found in 10 (1%) among 848 individuals who recorded 12-lead ECG.

Among 81 patients with known AF, 35 (43%) were not on OAC treatment. Among 403 persons

with at least two risk factors for stroke, who completed the hand-held ECG event recording, 30

(7.4%) were diagnosed with paroxysmal AF. Thus 75/848 (9%) of the screened population were

candidates for new OAC treatment, of those 57 actually started OAC treatment.

Conclusions—Stepwise risk factor-stratified AF screening in a 75-year old population yields a

large share of candidates for OAC treatment on AF indication.

Key words: atrial fibrillation, screening, anticoagulation, stroke prevention

history of AF and at least two risk factors according to CHADS2 were invited too aaa 222 wweeeeek k k

ecording period using a hand-held ECG asked to record 20 or 30 seconds twice daily and if

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Introduction

Atrial fibrillation (AF) is the most common clinical arrhythmia with a prevalence steeply

increasing with age. The prevalence of AF is often reported to be 6-8% in patients aged 75

years1, 2. AF is also a frequent source of cardiac emboli and a common etiology of ischemic

stroke. The risk of ischemic stroke is increased in patients with AF3, 4. This risk can effectively

be reduced by oral anticoagulation treatment (OAC)5.

AF is sometimes symptomatic, but the correlation with symptoms is weak, thus AF can

be present with a lack of symptoms6-8. Often, an ischemic stroke is the first clinical sign of AF.

Ischemic stroke associated with AF is known to be particularly severe and more frequently fatal

than other ischemic strokes9, 10. AF is present in 25-30% of patients sustaining an acute ischemic

stroke9, 11, 12.

The aim of this study was to explore, by stepwise ECG screening, the prevalence of

previously not diagnosed asymptomatic AF, suitable for OAC treatment in a population aged 75-

76 years and to study to what extent they started OAC treatment.

Methods

Population

Halmstad is a municipality in the south-west part of Sweden with 92 000 inhabitants.

All individuals born in 1934 and 1935 were invited to participate by mail. If there was no

response in 4-6 weeks, a reminder was sent. If there was no response or an active declination, no

further contacts were made.

Index visit

At the index visit, all participants had to sign an informed consent and were asked to report their

han other ischemic strokes9, 10. AF is present in 25-30% of patients sustaining aannn acccututte e isisischchchememe ic

troke9, 11, 12.

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medical history including presence of AF, antithrombotic treatment and thromboembolic risk

factors according to the CHADS2 risk classification13. If a patient reported a diagnosis of AF,

this had to be confirmed by ECG recordings in the medical records.

The accuracy of the self-reported medical history was confirmed only in patients with

AF. However, a random subset of 80 out of 727 patients with the questionnaire as the sole source

of medical history was cross-checked against medical records in hospital, in primary care and

against prescriptions. One of the 80 patients had erroneously omitted that he was treated for

hypertension, in the remaining 79 cases, medical history was reported correctly.

The index visit also included recording of a 12-lead ECG. The first 100 12-lead ECGs

were interpreted by a study nurse and a cardiologist; the following were interpreted by a study

nurse who consulted a cardiologist on demand. The ECG interpretations were also checked by

random samples viewed by a cardiologist. ECGs were interpreted only regarding rhythm and

rate. Patients who had atrio-ventricular block grade II or III or a heart rate below 40/min or

above 140/min were referred for further evaluation.

If the participant had a pacemaker or ICD implant, medical records were studied with

regard to the presence of atrial high rate episodes (mode switch) caused by AF. If present and

lasting more than 30 seconds, EGM recordings were studied.

If a 12-lead ECG revealed previously undiagnosed AF the patient was offered a work-up

consisting of blood pressure measurement, blood samples of fasting plasma glucose and thyroid

stimulating hormone at a study nurse visit and an echocardiogram at a cardiologist visit. Serum

glucose was not analysed in previously known individuals with diabetes. Patients with a

previously diagnosed AF without OAC treatment were offered this work-up if not previously

performed. After this work-up, the patient was recommended anticoagulation treatment unless

were interpreted by a study nurse and a cardiologist; the following were interpreetteted dd bybyy aa ssstututuddydy

nurse who consulted a cardiologist on demand. The ECG interpretations were also checked by

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there were contraindications. OAC treatment was managed within routine health care and

initiated in our OAC clinic.

Extended ECG recording

Participants with at least one additional risk factor beside their age (i.e. CHADS2 –score >=2), no

history of AF and sinus rhythm on the 12-lead ECG at the index visit, were asked to make

additional ECG recordings. These were made by a handheld unit, recording ECG via lead I by

application of the users’ thumbs (Zenicor Medical Systems AB, Sweden. www.zenicor.se). Via

an in-built mobile phone, the ECG is transmitted to a website. The participant was instructed to

record 20 or 30 seconds of ECG twice daily during two weeks. The duration of the recording was

decided by a study nurse who judged the participants ability to handle the ECG recorder. All

handheld ECGs were interpreted by a cardiac research nurse and a cardiologist. AF was defined

as 30 seconds or at least two separate recordings with at least 10 seconds each of irregular

rhythm without visible p-waves. The Zenicor ECG system has been validated in previous

reports14, 15. Patients with AF were offered a work-up and offered treatment as described above.

In cases were interpretation of handheld ECGs was hampered by poor signal quality, the

participants were offered an additional 48-hour Holter recording. In participants who displayed

runs of suspected AF on event recording not qualifying according to the definition above,

another two-week period of event recording were offered according to the judgement of the

investigating cardiologist. A study flow chart is depicted in figure 1.

Medical records from inhabitants who did not participate in the screening process were

analysed with respect to AF diagnosis, presence of anticoagulation treatment and risk factors

according to CHADS2. Both hospital and primary care records were studied.

Ethics

decided by a study nurse who judged the participants ability to handle the ECG rereecooordrddereer.. AlAlAlll l

handheld ECGs were interpreted by a cardiac research nurse and a cardiologist. AF was defined

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The study was approved by the regional health research ethics board at Lund University and

conducted according to the declaration of Helsinki. Inhabitants who did not participate in the

screening procedure were informed via letter and newspaper advertising that we intended to

study their medical records in order to characterise this subgroup. They were given the

possibility to withdraw their participation also in this part of the study.

Statistical methods

Continuous variables are reported as mean and range. Selected proportions are reported with a

95% confidence interval. For continuous variables, student t-test was used. For proportions,

Fishers exact test was used. Two-tailed tests were applied. A p-value of < 0.05 was regarded as

significant. In the tables, p-values of < 0.05 are listed.

Results

Of 1330 inhabitants invited to participation, 848 (64%) attended the index screening visit. The

cardiac research nurse spent 30 minutes at index visit per patient including 12-lead ECG

registration and 40 minutes at handheld ECG recording including ECG interpretation per patient.

The cardiologist spent 5-10 minutes per patient for second opinion on handheld ECG recordings

and 60 minutes per visit including echocardiography among patients with newly diagnosed AF.

Characteristics including prevalence of AF among attending and not attending inhabitants

are described in Table. A previous diagnosis of AF was confirmed in 81/848 (9.6%, 95% CI 7.8-

11.7). In the group who did not attend the screening, the prevalence of AF was 39/352 (11.1%,

95% CI 8.2-14.8) (n.s.). Non-attendants had a higher prevalence of diabetes, heart failure and

previous stroke (Table).

Among the 81 patients who were previously diagnosed with AF in the screened group, 35

ignificant. In the tables, p-values of < 0.05 are listed.

ReResususultltltsss

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(43%) were not receiving anticoagulation treatment at study entry. The corresponding figure of

the non-screened group was 56% (n.s.). Of these 35 patients with previously known AF, 17/35

(52%) started anticoagulation treatment.

ECG recording – 12-lead ECG

Previously unknown AF was diagnosed in 10 patients (1.2%, 95% CI 0.5-1.9) with a 12-lead

ECG. The mean heart rate among these 10 patients was 83/min ranging from 64/min to 102/min.

Their mean CHADS2 –score was 1.8.

One participant of 848 was diagnosed with newly detected AV block III on 12-lead ECG

and received a pacemaker implant.

Extended handheld ECG recording

Among the 848 participants there were 419 (49%) with no previous AF, sinus rhythm on 12-lead

ECG at index visit and a CHADS2 –score of at least 2. Of these participants 16 declined further

participation or deceased, leaving 403 who underwent ECG event recording with the hand-held

ECG. These 403 participants in total recorded 12 380 ECG tracings lasting 20 or 30 seconds. The

mean number of recordings per patient was 31. 40 patients recorded less than 28 times but only

six patients recorded less than 20 times. All patients with ambulatory ECG recordings were

included in the final analysis. Ten of the 403 recordings had to be completed with a 48 hour-

Holter recording due to difficulties in interpreting the hand-held ECG recording and most often

with a suspicion of AF. Six of these ten recordings revealed paroxysmal AF. Due to short

episodes of irregular heart rhythm on hand-held ECG raising suspicion of AF but not fulfilling

our criteria, 4 participants undertook another period of two weeks ECG event recording. One of

these four recordings revealed paroxysmal AF.

Thus, 30/403 (7.4%, 95% CI 5.2-10.4) were diagnosed with AF previously unknown. The

Extended handheld ECG recording

Among the 848 participants there were 419 (49%) with no previous AF, sinus rhythm on 12-lead

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mean CHADS2–score of these 30 patients was 2.5 including 6 patients with previous stroke. A

description of patient flow and ECG diagnostics is shown in figure 2.

Most patients with newly detected silent paroxysmal AF were diagnosed during the first

days of their two-week ECG registration period and 22 of the 24 patient diagnosed with AF on

handheld ECG had multiple recordings with AF runs. The duration of ECG recording necessary

for detection of AF is shown in figure 3.

The yield of different methods to identify patients with an indication for OAC treatment

and the proportion actually starting OAC treatment is shown in figure 4.

Prevalence of AF

At baseline, 81/848 (9.6%, 95% CI 7.6-11.6) of participants had a previously confirmed

diagnosis of AF. Another 10 patients with AF diagnosed with 12-lead ECG and 30 were

diagnosed on handheld or Holter ECG, thus the total prevalence in the screened population was

121/848 (14.3%, 95 CI 12.1-16.8). Among participants without a previously known AF

diagnose, 40/767 (5.2%, 95% CI 3.8-7.7) were diagnosed with new AF. However, only 403 of

these 767 participants were examined with extended handheld ECG recording.

Work-up in patients with newly diagnosed and previously diagnosed AF

Among the 40 patients with newly diagnosed AF, 38 underwent echocardiography. Left

ventricular Ejection Fraction (LVEF) was slightly reduced (48%) in one patient and normal (>

50%) in the remaining patients. Mean LVEF was 60%. A majority (26/38) of these patients had

enlarged left atria, defined as an area in apical four-chamber view of 24 cm2 or larger. Mean left

atrium area was 29 cm2. None of these patients revealed significant valvular disease.

Among patients leaving blood samples for glucose, 7/41 (17%) displayed elevated fasting

glucose levels, ranging from 6.4 to 7.4 mmol/l. No patients were diagnosed with previously

At baseline, 81/848 (9.6%, 95% CI 7.6-11.6) of participants had a previously cononnfifirmrmr ededed

diagnosis of AF. Another 10 patients with AF diagnosed with 12-lead ECG and 30 were

diiagagagnononosseseddd onono hanannddhdheld or Holter ECG, thus the totototaaal prevalence iin nn thee scscscrer ened population was

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unknown abnormal level of thyroid stimulating hormone.

Discussion

In this study, stepwise risk factor-stratified AF screening in a 75-76 year old population

identified a total prevalence of 14%, of which 62% had no OAC treatment. Among participants

who were examined with extended handheld ECG recording, 30/403 were diagnosed with

previously unknown paroxysmal AF. The amount of OAC treatment on AF indication more than

doubled among the screened participants. Screening for AF might become an effective method to

prevent stroke by initiation of OAC treatment.

Patient demographics

More than 60% of our community’s inhabitants aged 75 and 76 participated in the study. Since

our invitation process merely included an invitation by letter in combination with the fact that the

study was not accompanied by a media campaign, we are pleased with the participation. In an

AF prevalence study among 75-year old persons by Tveit et al., 82% of the population were

examined16. However, the Norwegian study used telephone reminders and even home visits for

ECG recording.

Interestingly, inhabitants not attending the AF screening programme had a higher burden

of cardiovascular risk factors than those attending since they had higher mean CHADS2-score,

affected by higher prevalence of diabetes, heart failure and stroke. There was no significant

difference in baseline AF prevalence among participants and non-participants.

ECG recording

A single 12-lead ECG-recording in a 75-year old population revealed only 1% of newly

diagnosed persistent or permanent AF, a figure also reported from Tveit et al16. Fitzmaurice et

Patient demographics

More than 60% of our community’s inhabitants aged 75 and 76 participated in the study. Since

ouur r r inininvivivitatatatititiononon prorooccecess merely included an invitaatititiononn by letter in cocoombmbininnatatatioi n with the fact that the

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examined161616. HoHoHowewewevevever,r,r, tttheh NNNoroo wewewegigigianana ssstututudydydy uuuseseedd d tetetelelelephphhononone ee rereremimimindnddererersss ananand d d eveve enenen hhhomomome e visits for


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al.17 found 2% of new AF using this method.

Intermittent ECG recording yielded 7% new AF diagnoses in our study, comparable to

the yield seen in extended ECG recordings in patients with ischemic stroke18, 19. This finding not

only underlines the importance of age in AF prevalence, but also that most patients with AF have

paroxysmal arrhythmia implicating that a single ECG recording with sinus rhythm has a low

negative predictive value in excluding a diagnosis of AF. Hence, among the total of 121 patients

with AF in this study, only 35 (29%) had persistent or permanent arrhythmia.

There are plenty of data on different methods of intermittent ECG-recording to detect

paroxysmal AF, most of it derives from studies on patients with cryptogenic ischemic stroke, on

patients who underwent AF ablation or from studies on antiarrhythmic drugs i.e. patient

populations with previously diagnosed AF or patients with generally high cardiovascular risk.

Studies on ambulant intermittent ECG recordings in the general population are scarce.

Continuous ECG monitoring, which would be regarded as “Gold standard” for ECG screening,

reveal previously undiagnosed paroxysmal AF in as much as 20-30% new AF diagnoses in

populations with high cardiovascular risk20, 21. The evidence for the elevated risk of ischemic

stroke in connection to brief AF episodes is mainly derived from device studies21, 22. The AF

episodes detected in this study are of larger recording proportion than the episodes detected in

device studies. Since the stroke risk is similar in paroxysmal and in permanent or persistent AF23,

24, we hypothesize that patients diagnosed with silent paroxysmal AF in this study has a stroke

risk similar to patients with clinical evident AF. Further long-term evaluation of our patients will

reveal the clinical course of their AF disease.

Technical development has provided several ways of ambulatory ECG recording. Short-

term Holter recordings of 24-48 h was previously the standard method but is hampered by low

patients who underwent AF ablation or from studies on antiarrhythmic drugs i.e.. ppatatatieientntnt

populations with previously diagnosed AF or patients with generally high cardiovascular risk.

Sttudududieieiesss ononn aaambmm ulululaanant t intermittent ECG recordingsgsgs innn the general popopopuulalaatititioon are scarce.

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diagnostic yield, particularly when looking for paroxysmal AF. In addition, Holter monitoring

most often generate a large share of ECG information without diagnostic interest. The efficacy of

detecting silent paroxysmal AF by different ambulant ECG monitoring strategies has been

outlined by Kirchhof and collegues25. Event recorders and loop recorders on the other hand are

activated by the patient when symptoms occur. They can also detect and store asymptomatic

arrhythmias, particularly when the recorder is continuously monitoring which in turn requires

continuously attachment of the recorder to the patient which might affect patient compliance

during longer recordings26. Event recorders not continuously attached to the patient, like the ones

used in this study, must be activated and attached by the patient. Event and loop recorders with

intermittent and continuously ambulatory ECG recording have demonstrated a better diagnostic

yield in comparison to Holter recordings when it comes to detecting paroxysmal AF in stroke

patients15. Rizos et al. reported that automated analyze of continuous ECG recorded in a stroke

unit among patients with ischemic stroke or TIA almost tripled the diagnostic yield with regard

to detection of silent paroxysmal AF in comparison to 24-hour Holter recording27. High

diagnostic yield is demonstrated by Mobile Cardiac Outpatient Telemetry (MCOT) and

implantable loop recorders in preliminary reports. These two modalities are however expensive

and implantable loop recorder requires minor surgery. The optimal ambulatory ECG method is

yet to be defined; the choice of this study is directed by patient compliance and cost

effectiveness. Further screening studies will reveal if there are more suitable ambulatory ECG

modalities.

Work-up

Work-up in patients with newly detected AF yielded a low prevalence of pathological findings

with the exception of 12% elevated fasting glucose levels. No patient had newly detected thyroid

ntermittent and continuously ambulatory ECG recording have demonstrated a bbeeetteteer dididiagagagnononoststiic

yield in comparison to Holter recordings when it comes to detecting paroxysmal AF in stroke

paatitiienenentststs151515. RiRRizzzos s etetet aal. reported that automated aaananan llyyze of continuouoous EEECCGCG recorded in a stroke

uunittt aamong patatieieienttts wwiw ththh iiisscschehehemimicc c sststrorookkee orr TTTIA aalalmomoststs ttririplplp eded ttthehee ddiaiai gngnnosostititiccc yiyieleleld dd wiwiwithth rregeggarrrd

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disease or structural heart disease besides the more or less expected finding of enlarged left atria.

Since we only measured blood pressure at one visit, no patient was diagnosed with hypertension

in the work up.

Initiation of OAC

Patients with a newly diagnosed AF were more inclined to initiate OAC treatment than patients

with a known diagnosis of AF. Some of the patients with known AF without OAC treatment had

previously been treated with OAC in connection to a cardioversion, after which the OAC

treatment was withheld if sinus rhythm seemingly persisted. Patients with known AF without

symptoms seemed less declined to restart OAC treatment after its termination. The change in

2010 AF guidelines28 to recommend long-term OAC after cardioversion if there are

thromboembolic risk factors present was not always applied in patients treated according to

previous recommendations. Patients with newly diagnosed AF were on the other hand easily

motivated to commence OAC treatment, despite that most of them were without symptoms.

Undertreatment with OAC in patients with AF and thromboembolic risk factors is very

common. Among patients with known AF in our study, 43% were not receiving OAC at study

entry. According to nationwide Swedish inpatient-statistics, half of patients with AF are never

treated with OAC29. Similar figures are reported from Go et al.30 and Waldo et al31. A markedly

better guideline adherence with 85% of patients with AF and risk factors treated with OAC was

reported from Tveit et al16. Thus, the widespread OAC undertreatment in patients with AF

contributes to an unnecessary high stroke incidence.

AF prevalence

The baseline prevalence of AF the 75-year old population in this study (9.6%) is higher than

reported from most other studies. A prevalence of 6-8% is often reported in this age group 1, 2, 32,

2010 AF guidelines28 to recommend long-term OAC after cardioversion if theree aaareee ff

hromboembolic risk factors present was not always applied in patients treated according to

prrevevvioioiouusus rrrecececooommememenndations. Patients with newlyyy dddiaaagnosed AF weweerer oonn n tththe other hand easily

mmottitivav ted to ccomommmmemennccee OAOAOAC C C trtreaeaatmtmmeenntt,, dessppite ttthaat momomostst oooff f ththememem wwererre wiwithththoououtt ssysympmpm totommsms.

UnUndededertrtrereatatmmemennnt wwwitith h OAOAOACCC ininin pppatattieieientntnts wiwiw ththh AAAFFF aandndnd tthrhrromomombobooememembobobolilic c ririr sksks fffacacacttorrsrs iiis s veveeryyy

common. Ammmononong g g papapatitienenents wwwititith knknknowowwn n AFAFAF iiin n n ououourr r ststtudududy,, 4443%3%3% wwwererere nononott t rererecececeivivi innng g g OAOAOAC CC at study


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but higher prevalence figures are reported from Nordic countries 16, 33 and from the UK 17. After

including the share of patients who underwent extended ECG recording, the prevalence of AF

rose to 14% in our study. Since only half of the screened population was examined with

handheld ECG recorder, it is not controversial to speculate that such ECG recording in the entire

screened population would have further increased the prevalence.

Screening programmes for AF, mainly in the primary care setting, have been reported

from the UK 17, 34. In a large randomised UK study17 in patients aged above 65, primary care

centres were randomized to systematic or opportunistic screening which was compared to routine

care. In patients invited to systematic screening, 53% registered ECG and a new AF diagnosis

was noted in 52/2357 (2%). The UK study from Fitzmaurice et al. lack data on OAC treatment,

both in patients with known AF and in patients newly diagnosed with AF. Data on OAC is of

importance for calculations of cost effectiveness since the majority of costs for AF stem from

stroke care. 35 Furthermore, single recordings of 12-lead ECG, as used in the UK study, have

severe limitations in detecting paroxysmal AF.

Whether screening for AF in patients with risk factors and initiation of OAC treatment

will significantly reduce the incidence of stroke and be cost effective remains to be shown in

further studies. However, based on the study from the UK17, both American Heart Association

and American Stroke Association Primary Prevention of Stroke Guidelines from 201136 and the

2012 Focused Update of AF Guidelines from the European Society of Cardiology37 recommend

opportunistic screening of AF in individuals at least 65 years of age in the primary care setting

by pulse palpation followed by ECG recording in case of irregular pulse.

As proposed by our study, systematic screening with extended ECG recording in a 75-

year-old population detect a considerable share of high-risk patients with untreated silent AF,

was noted in 52/2357 (2%). The UK study from Fitzmaurice et al. lack data on OOAOACCC ttrtreaaeatmtmtmenene t,t,

both in patients with known AF and in patients newly diagnosed with AF. Data on OAC is of

mmpopoportrtrtaanancecece fffooor ccalalalccuculations of cost effectivenessss ssinnnce the majoriitytyty of f cococosts s for AF stem from

ttroookke care. 3535 FFuuurtttherermomooreree,, sisisinngnglelee rrrecece ororddingggs of 11122--leadadad EECGCGCG, aas uuusesed dd innn tthehehe UUUK K ststs udududyyy, hhhavavee

eevevevererere llimimitititatatatioionnns iiin n dddetteectctinnngg g papaparororoxxyxysmsmsmalalal AAAF.F.F

Whettheheher rr scsccrerereenenninini g g fofofor rr AFAFAF iinnn papaatitit enenentststs wwwitith hh ririr sksks fffacaca tototorsrsr aaandndn iiinininitititiaaatititiononon oof f f OAOAOACCC trtreatment


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partly due to the higher prevalence of AF at age 75 years rather than 65 years and partly due to

the extended ECG recording. The most favourable and cost-effective method for screening of AF

is subject to further studies.

Limitations

This study has several limitations. Since our study was carried out in a single community, the

results are probably not reproducible in all populations. The generalizability to individuals of

other ages, races/ethnicity is uncertain.

The benefit from OAC treatment in patients with AF is so far studied among patients

diagnosed on standard (i.e. 12-lead) ECG recordings and the benefit in patients diagnosed with

shorter episodes of AF in single-lead ECG recordings remains less studied. However, the

following data suggest that these short AF episodes carry a risk similar to permanent and

persistent AF:

- An increased risk for stroke in device patients with short episodes of AF is

reported21, 22.

- Short episodes of AF is a common finding in patients suffering from “cryptogenic”

stroke38-41.

Since handheld ECG recording was intermittent, episodes of AF may have remained

undiagnosed. Data on risk factors according to CHADS2 was self-reported in participants

without a diagnosis of AF and collected from medical records in non-participants. Both methods

of data collection have limitations.

A more comprehensive invitation procedure might have increased participation further.

Persons might have been more willing to take part in an established and routinely performed

screening programme rather than taking part in a clinical study.

horter episodes of AF in single-lead ECG recordings remains less studied. Howeweeveeer, tthehehe

following data suggest that these short AF episodes carry a risk similar to permanent and

peersrssisisistetete tntnt AAAF:FF

- AAnn innncrreeaeaseseeddd riririsksksk ffororr ssstrtrookokee inn deeviccce patttieieentntsss wwiwiththh sshohortrt epppisosoodededess ofofof AAAFF isi

rererepoporrttededd21,21, 2222..

- ShShShororo t t t epepepisissodoo esess ooof f AFAFAF iiss s a cococ mmmmmmononon fffininindididingng ininin pppatata ieieientntn s sususufffffferererinining g g frfrromomom “crcrcrypyy togenic”


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For instance, 83% of invited 65-year old men accepted to participate in aortic abdominal

aneurysm screening in the Uppland region in Sweden 42.

Implications

Undiagnosed AF is often the aetiology behind “cryptogenic” stroke. It is a challenge of

considerable proportions to diagnose patients with silent AF and offer them OAC treatment.

Unfortunately, OAC is withheld among half of patients with already known AF and risk factors.

This study implies than patients with previously diagnosed and not yet diagnosed AF can get

better stroke prevention within a screening programme.

Conclusions

Stepwise risk factor-stratified AF screening in a 75-year old population yields a large share of

candidates for OAC treatment on AF indication. Persons not participating had more

cardiovascular risk factors than those participating. Patients with paroxysmal AF constitute the

majority of the AF population. Repeated handheld ECG recording detected new AF in 7% of

participants, and the total prevalence of AF was 14% in the population who participated in the

screening programme. Most patients with newly diagnosed AF were willing to commence OAC

treatment.

Acknowledgments: We thank Eva Mellberg for her work with administration of the study,

including patient invitation procedures. Contributors: JE and MR conceived the project and

designed it. JE, LA and MM made additional upgrades on the design and were responsible for

data collection. JE analysed the data. JE wrote the first draft of the paper. All authors assisted in

revising the paper and approved the final draft. JE is the guarantor.

Funding Sources: Grants were received from the Scientific Council of the Halland Region,

Conclusions

Stepwise risk factor-stratified AF screening in a 75-year old population yields a large share of

caandndndidididatatatesess fffoorr OOACACAC treatment on AF indication. PePePerrsons not partticici ipatattininingg had more

caardddioi vascularar rrisii kkk fafaf cctc oorors ss thththananan ththhososose e ppaparrticiipi aating.g. Patattieieentntsss wwiwiththh pppararoxoxxyyssmamaal l AFAF ccconononststtittuutute e thththeeh

mamaajojojoririritytyty ooff f thththee AFAFAF ppopoopuululatatioonn.n RRRepepepeeaeateteed dd hahahandndndheheh ldldd EEECGCGCG rrreececororrdidid nngng dddeteteeectteted d nenenew w w AFAFAF inn n 7%7%% ooof d

participants, , ananand d d thththe e e totootataal prprprevevevalallenenencecece ooff f AFAFAF wwwasasas 141414%%% innn ttthehehe pppopopopululu atattioioion n n whwhwhooo papaartrtrticicicipipipatata ed in the


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Southern Regional Health Care Committee and from the Swedish Heart and Lung Foundation.

The researchers were independent from the funders. The funders had no role in conducting the

study, writing the paper, or the decision to submit the paper for publication.

Conflict of Interest Disclosures: All authors have completed the Unified Competing Interest

form at www. Icmje.org/coi_disclosure.pdf (available on request from the corresponding author).

Dr Engdahl has received lecture fees from AstraZeneca and Boehringer Ingelheim and consultant

fees from Sanofi Aventis. Dr Rosenqvist has received lecture fees from Sanofi Aventis, Merck

Sharpe & Dome, Bayer, Boehringer Ingelheim, Pfizer and Medtronic, consultant fees from

Sanofi Aventis, Merck Sharpe & Dome, Nycomed, Bristol Meyers Squibb, Bayer, Medtronic

and research grants from Sanofi Aventis, Merck Sharpe & Dome Boehringer Ingelheim.

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34344. WWhWheelddononon NNM,M,M TTayayayleleerrr DIDI, , , AnAnAnagaga nonoststouou EE, , CoCookokk D, , WaWaWalelel s C,C,C, OOOakakleley y y GDD. ScScScrerer enenining gg fofoorrr atata rir afifiibrrrilillation in prprimimimarryy caaareree.. HeHeHearart.t.t 1119999988;;79::55000-555.

3555. ErErEricici sosonn n L,L,L BBerergfgfg elelldtdtt LL, BjBjBjororrhohoholtltlt II.. AtAtAtriririaalal fffibibibririilllaaatiooon:n:: ttthhhe e cococosstt oooff f ililllnneesss s ininin SSSweweeddeden.. EEuEur r JJJ Healalthth EEcoconn. 2020111;1;122:4779-9 4887.7.

3636 GoGoldldststeieinn LBLB BuBushshnenellll CCDD AAdadamsms RRJJ AAppppelel LJLJ BrBrauaunn LTLT ChChatatururvevedidi SS CrCreaeagegerr MAMA


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38. Jabaudon D, Sztajzel J, Sievert K, Landis T, Sztajzel R. Usefulness of ambulatory 7-day ECG monitoring for the detection of atrial fibrillation and flutter after acute stroke and transient ischemic attack. Stroke. 2004;35:1647-1651.

39. Rizos T, Rasch C, Jenetzky E, Hametner C, Kathoefer S, Reinhardt R, Hepp T, Hacke W, Veltkamp R. Detection of paroxysmal atrial fibrillation in acute stroke patients. CerebrovascDis. 2010;30:410-417.

40. Stahrenberg R, Weber-Kruger M, Seegers J, Edelmann F, Lahno R, Haase B, Mende M, Wohlfahrt J, Kermer P, Vollmann D, Hasenfuss G, Groschel K, Wachter R. Enhanced detection of paroxysmal atrial fibrillation by early and prolonged continuous holter monitoring in patients with cerebral ischemia presenting in sinus rhythm. Stroke. 2010;41:2884-2888.

41. Ziegler PD, Glotzer TV, Daoud EG, Wyse DG, Singer DE, Ezekowitz MD, Koehler JL, Hilker CE. Incidence of newly detected atrial arrhythmias via implantable devices in patients with a history of thromboembolic events. Stroke. 2010;41:256-260.

42. Wanhainen A, Svensjo S, Tillberg M, Mani K, Bjorck M. [Abdominal aortic aneurysm screening in Uppsala. Good experiences from the first four years--the rest of Sweden on its way]. Lakartidningen. 2010;107:2232-2236.

Table 1. Clinical Characteristics n, (%)

Participating Non-participating n=848 n=352 pMale gender 364 (43%) 149 (42%) Previously diagnosed AF 81 (9%) 39 (11%) Heart Failure 30 (4%) 34 (10%) <0.001Hypertension 446 (53%) 185 (53%) Diabetes Mellitus 91 (11%) 60 (17%) 0.004Previous Stroke/TIA 80 (9%) 49 (14%) 0.02CHADS2 –score (mean)* 1.85 2.08 0.05* CHADS2 –score was calculated regardless of diagnosis of AF

Figure Legends:

Figure 1. Study design and flow of participants.

Figure 2. Study flow with regard to ECG diagnostics.

Maalele ggendeder 363 4 (4(43%3%)) 141499 (4(42%%))

42. Wanhainen A, Svensjo S, Tillberg M, Mani K, Bjorck M. [Abdominal aortic aaneneneururu ysysy m m creening in Uppsala. Good experiences from the first four years--the rest of Sweweededeen n onono iiitststs wwwayay]]

Lakartidningen. 2010;107:2232-2236.

TaTaablblble 1. ClC ininniccalal CCChahararaactctterererisistiticscscs nnn, , , (%(%)) )

PPararrtitit ccippatinnng NNononon-p-paararttticippapatting nn==88484848 nn=n=353535222 ppp

Previously ddiaiaagngngnosososededed AAAFF 81818 (((9%9%9%)) 393939 (((111111%)%% HeHearartt FaFaililururee 3030 ((4%4%)) 3434 ((1010%)%) <0<0 000101


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21

Figure 3. Duration of ECG registration needed to diagnose paroxysmal AF. Graph shows

number of patients still undiagnosed as a function of ECG recording days. The six patients that

remained undiagnosed after 14 days were later diagnosed by Holter recording.

Figure 4. Yield of different methods of identifying patients with an indication for OAC

treatment and the proportion actually commencing OAC treatment. Black bars indicate the

proportion commencing OAC treatment, they grey bar denotes the proportion of patients who did

not.


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Invitationletter

Decline

Termination

No response Repeatedinvitation

No response

AcceptParticipation

Index visitMedical history12-lead ECG

History of AFOAC treatment

History of AFNo OAC treatment

New AF Sinus rhythmCHADS >=2

Work-up and OAC treatment

Handheld ECG

No AFNew AF

No response

Sinus rhythmCHADS =1

Termination

Termination Termination

Figure 1

Index visitMedical history12-lead ECG

f AFFmm nent

HiH sts ory y ofof AFNo OAC tt ereat eme tnt

Neww AF SiS nun s hrhyty mhmCHCHADSS >=22

WWoorrkk-uupp aanndd OOAACC HHaannddhheelldd EECCGG

SiS nusCHC A

Te mrm


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Index visit12-lead ECGn=848 (64%)

New AF on 12-lead ECGn=10 (1.2%)

Known AF in medical history

n=81 (9.6%)

Individuals withsinus rhythm

n=757Individuals with

sinus rhythm and CHADS2-score = 1

n=338 (45%)Individuals with

sinus rhythm and CHADS2-score >1

n=419 (55%)

New AF on Event recorder ECG

n=30 (7.4%)

Individuals deceasedor declining furtherparticipation n=16

Invitationn=1330

ParticipationDeclinedn=482

No AF onHandheld ECG

n=373

Figure 2

New AF oon12-lead EECCGGn=10 (1.22%%)

Known AF in medical history

n=81 (9.6%)

Individuals withsinus rhyytthhmm

n=757Inndivviidduuallss wwiitthh

ssinnuss rhhythmm anndd CHADDSS22-scoorre == 1

n=3388 ((445%%))IInnddiivviidduuaallss wwiitthh

ssinuuss rrhhyytthhmm aanndd


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Figure 3


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Figure 4


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Johan Engdahl, Lisbeth Andersson, Maria Mirskaya and Mårten RosenqvistPrevention

Stepwise Screening of Atrial Fibrillation in a 75-Year Old Population: Implications for Stroke

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2013 American Heart Association, Inc. All rights reserved.

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Stepwise Screening of Atrial Fibrillation in a 75-Year Old Population