Detection of Atrial Fibrillation After Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis Amit Kishore, Andy Vail, Arshad Majid, Jesse Dawson, Kennedy R. Lees, Pippa J. Tyrrell and Craig J. Smith Stroke. published online January 2, 2014; Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0039-2499. Online ISSN: 1524-4628
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Original Contribution Detection of Atrial Fibrillation After Ischemic Stroke or Transient Ischemic Attack A Systematic Review and Meta-Analysis Amit Kishore, MRCP; Andy Vail, MSc; Arshad Majid, MD; Jesse Dawson, MD; Kennedy R. Lees, MD; Pippa J. Tyrrell, MD; Craig J. Smith, MD Background and Purpose—Atrial fibrillation (AF) confers a high risk of recurrent stroke, although detection methods and definitions of paroxysmal AF during screening vary. We therefore undertook a systematic review and meta-analysis to determine the frequency of newly detected AF using noninvasive or invasive cardiac monitoring after ischemic stroke or transient ischemic attack. Methods—Prospective observational studies or randomized controlled trials of patients with ischemic stroke, transient ischemic attack, or both, who underwent any cardiac monitoring for a minimum of 12 hours, were included after electronic searches of multiple databases. The primary outcome was detection of any new AF during the monitoring period. We prespecified subgroup analysis of selected (prescreened or cryptogenic) versus unselected patients and according to duration of monitoring. Results—A total of 32 studies were analyzed. The overall detection rate of any AF was 11.5% (95% confidence interval, 8.9%– 14.3%), although the timing, duration, method of monitoring, and reporting of diagnostic criteria used for paroxysmal AF varied. Detection rates were higher in selected (13.4%; 95% confidence interval, 9.0%–18.4%) than in unselected patients (6.2%; 95% confidence interval, 4.4%–8.3%). There was substantial heterogeneity even within specified subgroups. Conclusions—Detection of AF was highly variable, and the review was limited by small sample sizes and marked heterogeneity. Further studies are required to inform patient selection, optimal timing, methods, and duration of monitoring for detection of AF/paroxysmal AF. (Stroke. 2014;45:00-00.) Key Words: atrial fibrillation ◼ ischemic attack, transient ◼ stroke
C
ardioembolism accounts for 17% to 30% of all ischemic strokes.1,2 Some data suggest that >50% of these are because of atrial fibrillation (AF).3 Paroxysmal AF (PAF) is often undetected because characteristics such as short duration, episodic, and frequently asymptomatic nature make it challenging to diagnose at the bedside, leading to suboptimal secondary prevention.4 It is likely that a proportion of strokes labeled as cryptogenic are cardioembolic in origin because of occult AF.5,6 Furthermore, ≥2 factors contributing to stroke risk may coexist: even patients with an identified risk factor for nonembolic stroke may have occult cardioembolism. Detection rate of new AF from a standard 12-lead ECG after ischemic stroke/transient ischemic attack (TIA) is ≈2% to 5%7,8 and from 24-hour Holter is 2% to 6%.9–11 The European Stroke Organization12 and the American Heart Association (AHA)/ American Stroke Association13 recommend that 24-hour
Holter monitoring is used to detect occult AF/PAF when suspected, and no other cause for stroke is found. However, the optimum timing, duration, setting (outpatient or inpatient), and method of monitoring to maximize the detection of PAF after stroke/TIA are unclear. Furthermore, diagnostic criteria used for PAF during monitoring may vary and have implications for risk of recurrence. We therefore undertook a systematic review and meta-analysis with the following objectives: 1. To determine the overall rate of detection of any new AF with cardiac monitoring (invasive and noninvasive) after ischemic stroke/TIA. 2. To evaluate detection rates of AF in selected versus unselected patients with stroke/TIA. 3. To explore the influence of duration of monitoring on detection rates of AF.
Received September 3, 2013; accepted October 28, 2013. From the Stroke and Vascular Research Centre, Institute of Cardiovascular Sciences (A.K., P.J.T., C.J.S.) and Centre for Biostatistics (A.V.), University of Manchester, Manchester Academic Health Science Centre, Salford Royal Foundation Trust, Salford, United Kingdom; Greater Manchester Comprehensive Stroke Centre, Department of Medical Neurosciences, Salford Royal Foundation Trust, Salford, United Kingdom (A.K., A.M., P.J.T., C.J.S.); and Institute of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary, Glasgow, United Kingdom (J.D., K.R.L.). Guest Editor for this article was Markku Kaste, MD, PhD. The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA. 113.003433/-/DC1. Correspondence to Craig J. Smith, MD, Clinical Sciences Bldg, University of Manchester, Manchester Academic Health Science Centre, Salford Royal Foundation Trust, Salford M6 8HD, United Kingdom. E-mail [email protected] © 2014 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.113.003433
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2 Stroke February 2014
Methods Eligibility Criteria Studies (English and non-English language) including patients with ischemic stroke, TIA, or both, who underwent invasive or noninvasive cardiac monitoring for a minimum of 12 hours, in prospective observational studies or randomized controlled trials up to January 1, 2013, were considered. Original abstracts without fully published data were considered. Patients with known history of AF or diagnosed with AF during routine inpatient screening were excluded from analyses. Retrospective studies, cardiac monitoring for 30 seconds of duration of AF (64%).
Patient Characteristics A total of 5038 participants were included (mean age, 68.4 years; 41.6% women). Summary data for baseline vascular risk factors were available for only 61% of studies (Table III in the online-only Data Supplement).
Detection of Any New AF The overall detection rate of any new AF was 11.5% (95% confidence interval [CI], 8.9%–14.3%), with high heterogeneity between studies (I2=88.2%). Because criteria for PAF were frequently not reported, we were unable to undertake further analyses of detection rates based on differing diagnostic criteria.
Patient Selection and Duration of Monitoring Detection rate of any new AF among unselected patients was 6.2% (95% CI, 4.4%–8.3%; I2=86.3%; Figure 2) and among selected patients was 13.4% (95% CI, 9.0%–18.4%; I2=88.8%; Figure 3). In cryptogenic strokes, new AF was detected in 15.9% (95% CI, 10.9%–21.6%). Using inpatient monitoring, higher detection rates were seen in the selected group (3 studies; Figure 3) compared with the unselected group (9 studies; Figure 2), with new AF detected even after 10 days of continuous inpatient monitoring in 1 study of selected patients.42 In comparison with standard telemetry, monitors with software algorithms for automatic detection of AF (5.4% versus 7.7%)45 or a systematic analysis of saved data from recordings (2.6× increase) seemed to improve detection rates.25 Higher detection rates were also seen in the selected group (8 studies; Figure 3) compared with the unselected group (6 studies; Figure 2) using 24-hour Holter monitoring. From the available data, the type of Holter monitor—2,23,37 3,47 or 6-channel45—did not materially alter detection rate. Prolonged monitoring (>24 hours) had a comparable yield of new AF in selected (12 studies; Figure 3) and unselected patients (3 studies; Figure 2). When monitoring was extended to 72 hours, detection rates increased by 2% to 4% with each additional 24 hours of monitoring.17,20,39 One study of selected patients used periodic 48-hour Holter (every 6 months) to increase yield of new AF.26 External loop recorders were used in 2 studies for ≤7 days, detecting new AF in 6% to 8% of patients,20,39 and when repeated at 3 and 6 months, the yield increased to 14%.19 A recently completed randomized study35 in an unselected patient group reported a higher detection rate soon after admission (using a 7-day Novocor R test external loop recorder) compared with standard investigations that included a standard 12-lead ECG and 24-hour Holter (40% versus 4%; P24 hours) is likely to increase yield of AF detection. Furthermore, selecting a high-risk population (eg, older age and cryptogenic strokes), using multiple interventions and periodic follow-up (repeating the intervention), is likely to improve detection rates. However, the optimum method and duration remain unclear, and further appropriately designed studies are required to determine the most cost-effective strategies and inform clinical practice. Several ongoing studies evaluating prolonged monitoring32,33,46,50,51 are likely to provide more clarity in the near future.
Acknowledgments We are grateful to Valerie Haigh for assistance with the literature searches and Drs Gerhard and Herbert for their contribution to translation of non-English articles.
Sources of Funding A. Kishore is funded by the North Western Deanery; C.J. Smith, A. Vail, and A. Majid are funded by Salford Royal NHS Foundation Trust; P.J. Tyrrell is funded by the University of Manchester; and K.R. Lees and J. Dawson are funded by the University of Glasgow.
Disclosures None.
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Kishore et al Detection of Atrial Fibrillation After Stroke or TIA 7 46. Christensen LM, Krieger D, Hojberg S, Pedersen OD, Karlsen FM, Worch R, et al. Long-term monitoring for paroxystic atrial fibrillation in cryptogenic stroke: preliminary results of the surprise study. Stroke. 2012;43:A153. Abstract. 47. Sobocinski PD, Rooth EA, Kull VF, Arbin M, Wallen H, Rosenqvist M. Improved screening for silent atrial fibrillation after ischaemic stroke. Europace. 2012;14:1112–1116. 48. Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise
the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006;114:e257–e354. 49. Seet RC, Friedman PA, Rabinstein AA. Prolonged rhythm monitoring for the detection of occult paroxysmal atrial fibrillation in ischemic stroke of unknown cause. Circulation. 2011;124:477–486. 50. Gladstone DJ, Blakely J, Dorian P, Spring M, Fang J, Silver FL, et al. Detecting paroxysmal atrial fibrillation after ischaemic stroke and transient ischaemic attack: if you don’t look, you won’t find. Stroke. 2008;39:e78–e79. 51. Sinha AM, Diener H, Morillo CA, Sanna T, Bernstein RA, Di Lazzaro V, et al. Cryptogenic Stroke and underlying Arial Fibrillation (CRYSTAL AF): design and rationale. Am Heart J. 2010; 160: 36–41.
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SUPPLEMENTAL MATERIAL Detection of Atrial Fibrillation after Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Meta-analysis
Amit Kishore1,2 MRCP, Andy Vail3 MSc, Arshad Majid2 MD, Jesse Dawson4 MD, Kennedy R. Lees4 MD; Pippa J. Tyrrell1,2 MD, Craig J. Smith1,2 MD 1
Stroke and Vascular Research Centre, Institute of Cardiovascular Sciences, University of
Manchester, Manchester Academic Health Science Centre, Salford Royal Foundation Trust M6 8HD, UK; 2Greater Manchester Comprehensive Stroke Centre, Department of Medical Neurosciences, Salford Royal Foundation Trust M6 8HD, UK; 3Centre for Biostatistics, University of Manchester, Manchester Academic Health Science Centre, Salford Royal Foundation Trust, Salford M6 8HD, UK; 4Institute of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary, Glasgow G11 6NT
Corresponding author Dr Craig J. Smith Clinical Sciences Building, University of Manchester, Manchester Academic Health Science Centre, Salford Royal Foundation Trust M6 8HD E-mail: [email protected] Tel: +44 161 707 6534 206 0623 Fax: +44 161 707 6534
Online Supplement Table I: Search methodology Search Areas
Thesaurus terms
Free Text Terms
MEDLINE Subject Search in MESH: exp cerebrovascular disorders/; exp atrial fibrillation/; exp monitoring, physiologic/ or exp electrocardiography/;
Holter monitoring*, loop recorder*, stroke* and transient ischemic attack*
EMBASE
Subject Search on EMTREE: exp cerebrovascular disease/ exp patient monitoring/ exp heart atrium fibrillation/.
Holter monitoring*, loop recorder*, stroke* and transient ischemic attack*
Cochrane Library
Not Applicable
‘Atrial fibrillation’, ‘Stroke’, ‘cardiac monitoring’
Clinical Trials Registry
Not Applicable
‘Atrial fibrillation’, ‘Stroke or transient ischemic attack’ and ‘cardiac monitoring’
Google Scholar
Not Applicable
‘Atrial fibrillation’ ‘stroke’ or ‘transient ischemic attack’, ‘cardiac monitoring’
Online Supplement Table II: Characteristics of included studies Author
Design
Size (n)
Mean Age (Y)
F (%)
Type of index Event
Mode of monitoring
Unselected Or Selected or both?
Criteria for Selection
Definition of PAF
Simova, 2012*
POS1
15
54
0
S
Selected
POS
20
63.4
NR
S
NR
20.0
Dion, 2011
POS
24
49
37.5
S
Invasive
Selected
NR
4.2
Gunalp, 2006
POS
26
66
44
S
Selected
POS
27
68
44
S
Intermittent episodes of AF30 sec of AF
14.3
POS
42
65
50
S
Noninvasive Invasive
PAF > 2 min duration
16.7
Christensen, 2012* Higgins, 2012*
POS
43
NR
NR
S/T
Invasive
Selected
Cryptogenic strokes Cryptogenic strokes Cryptogenic strokes Excluded carotid stenosis Excluded minor strokes or posterior circulation strokes Cryptogenic Stroke Cryptogenic strokes Cryptogenic strokes
NR
Peiro, 2011*
Non Invasive Invasive
Rate of New AF/PAF (%) 20.0
NR
18.6
RCT2
50
NR
NR
S/T
Noninvasive
Unselected
Any duration AF
40.0
Dangayach, 2011 Schuchert, 1999
POS
51
58.2
53.5
S
Selected
Sustained AF>20 sec NR
16.0 29.4
POS
82
60.5
42.7
S
Noninvasive Noninvasive
Irregular baseline undulations of variable amplitude and morphology at >350/min with irregular ventricular response
6.1
Selected
Selected
Selected
Selected
Cryptogenic strokes Excluded structural causes
18.5
Kar, 2009*
POS
95
77.2
NR
T
a
62
b Kessler, 1994
POS
71 93
64
2
S
Tonet, 1981
POS
100
50
43
S/T
Callero, 2012*
POS
101
69.8
44.7
S
Kral, 2012*
POS
114
75.4
50
S
Bansil, 2000
POS
121
68.3
45.3
S
Wallman, 2007 Rizos, 2010 a
POS
127
63
30.6
S
POS
136 136
72
41.2
S/T
Noninvasive
Selected High risk TIA and Negative IP monitoring Low risk TIA
Noninvasive Noninvasive Noninvasive Noninvasive Noninvasive Noninvasive NonInvasive
Jabaudon, 2004 a b
POS
139
69
32.2
S/T
Rem, 1985
POS
169
63.5
33.7
S/T
Stahrenberg, 2010 Flint, 2012
POS
220
65
60.5
S/T
POS
236
64.6
39.5
S
NonInvasive
139 32
6.5
Unselected
NR
Unselected
NR
1.0
NR
25
Unselected
NR
8.8
Unselected
NR
4.9
>30 sec of AF
14.1
>30 sec of AF
21.3 19.1
Selected
Selected Selected
Cryptogenic Strokes
Negative 24h Holter Age>60 IP monitoring only Negative IP monitoring
Both Unselected Selected
Noninvasive Noninvasive Noninvasive
23.6
30.9 0
120
b
NR
Selected
NR
Negative 24h Holter Negative IP monitoring
Unselected Selected
2.5
Cryptogenic Strokes
5.7 5 3.8
NR
2.3
>30 sec of AF
12.5
>30 sec of AF
11
Irregular baseline undulations of variable amplitude and morphology at 300-350/min with irregular ventricular response >30 sec of AF
6.4
AF at least 10 sec
2
Unselected
NR
3.9
Both
>30 sec of AF
5.3
Tagawa, 2007
POS
241
72.3
39
S
Non invasive
Unselected
Kallmunzer, 2011 Sobocinskidoliwa, 2012
POS
245
72
47
S
Unselected
POS
249
72
43
S/T
Noninvasive Noninvasive
Hornig , 1996
POS
266
59.1
38.7
S/T
Gumbinger, 2012
POS
281
71
44.1
S/T
Noninvasive Noninvasive
Selected
a
281
Unselected
b
192
Selected
Madsen, 2009* MartinezSanchez, 2012* a
POS
310
NR
NR
S
POS
430
69
40.4
S/T
b Vivanco Hidalgo, 2007 Rizos, 2012
Noninvasive Noninvasive
Both
NR
11.2
Selected NR
S/T
POS
496
69
38.5
S/T
Noninvasive Noninvasive
1 5.8
156 79.1
Negative IP Monitoring NR
Unselected
461
4.6
Unselected
430
POS
Age>70y, Index event within 14 days
7.3
2.8 Negative IP monitoring
23.1
Unselected
>30s30 sec of AF
13.7
POS=Prospective Observational Study, RCT=Randomized Controlled Trial, S=Stroke, TIA=Transient Ischemic Attack, NR=Not Reported, * Abstract only, Y=years, IP=Inpatient monitoring, AF=Atrial Fibrillation
Online Supplement Table III: Patient characteristics Risk Factors (%) Author, Year
DM
HTN
Previous Stroke/TIA
IHD
Smoker
Dyslipaedemia
Rizos, 2010
30.1
79.4
NR
22.8
8.6
34.3
Tagawa, 2007
37.6
76.3
NR
36
34
37.4
Jabaudon, 2004
16
58.3
16.7
NR
NR
50
Barthelemy, 2003
5
50
23
27
NR
41
Hornig, 1996
34
43.5
30
40
28.7
64.3
Schuchert, 1999
NR
36.6
NR
17.5
NR
NR
Rem, 1985
16.3
56.5
31.5
36.5
39.5
NR
Stahrenberg, 2010
24.6
77.5
15.4
15.8
24.6
NR
Flint, 2012
14.7
66
18.8
10.5
NR
90.8
Kallmunzer, 2011
42
84
NR
21
24
49
Bansil, 2000
23.3
62
9.3
32
24
44
Dangayach, 2011
16
35.3
NR
20
NR
47.1
Gunalp, 2006
26
61
NR
31
NR
13
Rizos, 2012
24.6
78.8
19.6
NR
NR
NR
Dion, 2011
N
29.2
NR
NR
41.
33.3
Kral, 2012
NR
NR
22
28.9
NR
NR
Simova, 2012
20
70
NR
NR
30
80
Sandin, 2012
14
57
NR
NR
40
36
Sobocinski-doliwa, 2012
65
65
25
20
NR
NR
Higgins, 2012
8
56
NR
16
24
56
Mean
29.6
66.9
21.4
25.6
27.9
52.9
DM= Diabetes Mellitus, HTN=Hypertension, IHD=Ischemic Heart Disease, TIA= Transient Ischemic Attack
Online Supplement Table IV: Excluded Studies and accompanying references
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38
Author
Reason for exclusion
Britton, 1979 Rizzon, 1963 Abdon, 1982 Safieddine, 2002 Elkins, 2002 Dogan, 2004 Shafqat, 2004 Vandenbroucke, 2004 Douen, 2008 Elijovich, 2009 Haft, 2009 Sposato, 2009 Yu, 2009 Atmuri, 2009 Eitel, 2009 Gomis,2009 Kelly, 2009 Alhadramy, 2010 Ziegler, 2010 Bartko, 2010 Portilla, 2010 Riccio 2010 Gaillard, 2010 Tayal, 2010 Galiana, 2011 Mahagne, 2011 Ritter, 2011 Ustrell, 2011 Ba, 2011 Wnuk, 2011 Hoppe, 2011 Attygalle, 2011 Poisson, 2011 Thomas, 2011 Gupta, 2011 Kamel, 2011 Sousa, 2012 Lazzaro, 2012
Retrospective observational study Retrospective observational study Retrospective observational study Retrospective observational study
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://stroke.ahajournals.org/content/early/2014/01/02/STROKEAHA.113.003433
Data Supplement (unedited) at: http://stroke.ahajournals.org/content/suppl/2014/01/02/STROKEAHA.113.003433.DC1.html
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Original Contribution Detection of Atrial Fibrillation After Ischemic Stroke or Transient Ischemic Attack A Systematic Review and Meta-Analysis Amit Kishore, MRCP; Andy Vail, MSc; Arshad Majid, MD; Jesse Dawson, MD; Kennedy R. Lees, MD; Pippa J. Tyrrell, MD; Craig J. Smith, MD Background and Purpose—Atrial fibrillation (AF) confers a high risk of recurrent stroke, although detection methods and definitions of paroxysmal AF during screening vary. We therefore undertook a systematic review and meta-analysis to determine the frequency of newly detected AF using noninvasive or invasive cardiac monitoring after ischemic stroke or transient ischemic attack. Methods—Prospective observational studies or randomized controlled trials of patients with ischemic stroke, transient ischemic attack, or both, who underwent any cardiac monitoring for a minimum of 12 hours, were included after electronic searches of multiple databases. The primary outcome was detection of any new AF during the monitoring period. We prespecified subgroup analysis of selected (prescreened or cryptogenic) versus unselected patients and according to duration of monitoring. Results—A total of 32 studies were analyzed. The overall detection rate of any AF was 11.5% (95% confidence interval, 8.9%– 14.3%), although the timing, duration, method of monitoring, and reporting of diagnostic criteria used for paroxysmal AF varied. Detection rates were higher in selected (13.4%; 95% confidence interval, 9.0%–18.4%) than in unselected patients (6.2%; 95% confidence interval, 4.4%–8.3%). There was substantial heterogeneity even within specified subgroups. Conclusions—Detection of AF was highly variable, and the review was limited by small sample sizes and marked heterogeneity. Further studies are required to inform patient selection, optimal timing, methods, and duration of monitoring for detection of AF/paroxysmal AF. (Stroke. 2014;45:00-00.) Key Words: atrial fibrillation ◼ ischemic attack, transient ◼ stroke
C
ardioembolism accounts for 17% to 30% of all ischemic strokes.1,2 Some data suggest that >50% of these are because of atrial fibrillation (AF).3 Paroxysmal AF (PAF) is often undetected because characteristics such as short duration, episodic, and frequently asymptomatic nature make it challenging to diagnose at the bedside, leading to suboptimal secondary prevention.4 It is likely that a proportion of strokes labeled as cryptogenic are cardioembolic in origin because of occult AF.5,6 Furthermore, ≥2 factors contributing to stroke risk may coexist: even patients with an identified risk factor for nonembolic stroke may have occult cardioembolism. Detection rate of new AF from a standard 12-lead ECG after ischemic stroke/transient ischemic attack (TIA) is ≈2% to 5%7,8 and from 24-hour Holter is 2% to 6%.9–11 The European Stroke Organization12 and the American Heart Association (AHA)/ American Stroke Association13 recommend that 24-hour
Holter monitoring is used to detect occult AF/PAF when suspected, and no other cause for stroke is found. However, the optimum timing, duration, setting (outpatient or inpatient), and method of monitoring to maximize the detection of PAF after stroke/TIA are unclear. Furthermore, diagnostic criteria used for PAF during monitoring may vary and have implications for risk of recurrence. We therefore undertook a systematic review and meta-analysis with the following objectives: 1. To determine the overall rate of detection of any new AF with cardiac monitoring (invasive and noninvasive) after ischemic stroke/TIA. 2. To evaluate detection rates of AF in selected versus unselected patients with stroke/TIA. 3. To explore the influence of duration of monitoring on detection rates of AF.
Received September 3, 2013; accepted October 28, 2013. From the Stroke and Vascular Research Centre, Institute of Cardiovascular Sciences (A.K., P.J.T., C.J.S.) and Centre for Biostatistics (A.V.), University of Manchester, Manchester Academic Health Science Centre, Salford Royal Foundation Trust, Salford, United Kingdom; Greater Manchester Comprehensive Stroke Centre, Department of Medical Neurosciences, Salford Royal Foundation Trust, Salford, United Kingdom (A.K., A.M., P.J.T., C.J.S.); and Institute of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary, Glasgow, United Kingdom (J.D., K.R.L.). Guest Editor for this article was Markku Kaste, MD, PhD. The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA. 113.003433/-/DC1. Correspondence to Craig J. Smith, MD, Clinical Sciences Bldg, University of Manchester, Manchester Academic Health Science Centre, Salford Royal Foundation Trust, Salford M6 8HD, United Kingdom. E-mail [email protected] © 2014 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.113.003433
Downloaded from http://stroke.ahajournals.org/1 at Universitaet Duesseldorf on January 9, 2014
2 Stroke February 2014
Methods Eligibility Criteria Studies (English and non-English language) including patients with ischemic stroke, TIA, or both, who underwent invasive or noninvasive cardiac monitoring for a minimum of 12 hours, in prospective observational studies or randomized controlled trials up to January 1, 2013, were considered. Original abstracts without fully published data were considered. Patients with known history of AF or diagnosed with AF during routine inpatient screening were excluded from analyses. Retrospective studies, cardiac monitoring for 30 seconds of duration of AF (64%).
Patient Characteristics A total of 5038 participants were included (mean age, 68.4 years; 41.6% women). Summary data for baseline vascular risk factors were available for only 61% of studies (Table III in the online-only Data Supplement).
Detection of Any New AF The overall detection rate of any new AF was 11.5% (95% confidence interval [CI], 8.9%–14.3%), with high heterogeneity between studies (I2=88.2%). Because criteria for PAF were frequently not reported, we were unable to undertake further analyses of detection rates based on differing diagnostic criteria.
Patient Selection and Duration of Monitoring Detection rate of any new AF among unselected patients was 6.2% (95% CI, 4.4%–8.3%; I2=86.3%; Figure 2) and among selected patients was 13.4% (95% CI, 9.0%–18.4%; I2=88.8%; Figure 3). In cryptogenic strokes, new AF was detected in 15.9% (95% CI, 10.9%–21.6%). Using inpatient monitoring, higher detection rates were seen in the selected group (3 studies; Figure 3) compared with the unselected group (9 studies; Figure 2), with new AF detected even after 10 days of continuous inpatient monitoring in 1 study of selected patients.42 In comparison with standard telemetry, monitors with software algorithms for automatic detection of AF (5.4% versus 7.7%)45 or a systematic analysis of saved data from recordings (2.6× increase) seemed to improve detection rates.25 Higher detection rates were also seen in the selected group (8 studies; Figure 3) compared with the unselected group (6 studies; Figure 2) using 24-hour Holter monitoring. From the available data, the type of Holter monitor—2,23,37 3,47 or 6-channel45—did not materially alter detection rate. Prolonged monitoring (>24 hours) had a comparable yield of new AF in selected (12 studies; Figure 3) and unselected patients (3 studies; Figure 2). When monitoring was extended to 72 hours, detection rates increased by 2% to 4% with each additional 24 hours of monitoring.17,20,39 One study of selected patients used periodic 48-hour Holter (every 6 months) to increase yield of new AF.26 External loop recorders were used in 2 studies for ≤7 days, detecting new AF in 6% to 8% of patients,20,39 and when repeated at 3 and 6 months, the yield increased to 14%.19 A recently completed randomized study35 in an unselected patient group reported a higher detection rate soon after admission (using a 7-day Novocor R test external loop recorder) compared with standard investigations that included a standard 12-lead ECG and 24-hour Holter (40% versus 4%; P24 hours) is likely to increase yield of AF detection. Furthermore, selecting a high-risk population (eg, older age and cryptogenic strokes), using multiple interventions and periodic follow-up (repeating the intervention), is likely to improve detection rates. However, the optimum method and duration remain unclear, and further appropriately designed studies are required to determine the most cost-effective strategies and inform clinical practice. Several ongoing studies evaluating prolonged monitoring32,33,46,50,51 are likely to provide more clarity in the near future.
Acknowledgments We are grateful to Valerie Haigh for assistance with the literature searches and Drs Gerhard and Herbert for their contribution to translation of non-English articles.
Sources of Funding A. Kishore is funded by the North Western Deanery; C.J. Smith, A. Vail, and A. Majid are funded by Salford Royal NHS Foundation Trust; P.J. Tyrrell is funded by the University of Manchester; and K.R. Lees and J. Dawson are funded by the University of Glasgow.
Disclosures None.
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telemetric detection of atrial fibrillation after acute ischemic stroke. Stroke. 2012;43:994–999. 26. Dangayach NS, Kane K, Moonis M. Paroxysmal atrial fibrillation in cryptogenic stroke. Ther Clin Risk Manag. 2011;7:33–37. 27. Piero S, Rodriguez-Luna D, Pagola J, Ribo M, Rubiera M, Maisterra O, et al. Impact of implantable Holter ecg monitoring on detection of paroxysmal atrial fibrillation in patients with cryptogenic stroke. Cerebrovasc Dis. 2011;31:287–288. Abstract. 28. Dion F, Saudeau D, Bonnaud I, Friocourt P, Bonneau A, Poret P, et al. Unexpected low prevalence of atrial fibrillation in cryptogenic ischemic stroke: a prospective study. J Interv Card Electrophysiol. 2010;28:101–107. 29. Flint AC, Banki NM, Ren X, Rao VA, Go AS. Detection of paroxysmal atrial fibrillation by 30-day event monitoring in cryptogenic ischemic stroke: the Stroke and Monitoring for PAF in Real Time (SMART) Registry. Stroke. 2012;43:2788–2790. 30. Kral M, Sanak D, Hutyra M, Veverka T, Bartkova A, Herzig R, et al. The benefit of early Holter-ECG monitoring for the detection of paroxysmal atrial fibrillation in patients with acute ischemic stroke: a pilot study. Eur J Neurol. 2012;19:181. Abstract. 31. Callero EC, Martinez-Sanchez P, Gomar DP, Gimeno BF, Ares GR, Martinez MM, et al. Utility a second 24-hours Holter monitoring for the diagnosis of paroxysmal atrial fibrillation after an acute stroke. Stroke. 2012;43:A3735. Abstract. 32. Simova I, Mateev H, Katova T, Haralanov L, Dimitrov N. Detection of asymptomatic atrial fibrillation episodes during ECG telemonitoring in stroke patients. Cardiovasc Res. 2012;93:103. Abstract. 33. Sandin M, Malpica Cervantes F, Rubio Sanz J, Garcia Moran E, Villadeamigo Romero JM, Rojo E, et al. Subclinical atrial fibrillation: a missing link in the etiology of cryptogenic ischemic stroke? Eur Heart J. 2012;33:373. Abstract. 34. Kar A, Ragavan S, Brown S, Ellis A, Guyler PC, O’Brien AO. Intensive cardiac monitoring after transient ischemic attack identifies a significant number of previously unknown paroxysmal atrial fibrillation. Cerebrovasc Dis. 2009;27:203. Abstract. 35. Higgins P, Macfarlane PW, Mclanes GT, Ford J, Boggs AH, Langhorne P, et al. Evaluation of electrocardiographic monitoring strategy to identify atrial fibrillation in patients with acute ischaemic stroke or TIA. Cerebrovasc Dis. 2012;33:47. Abstract. 36. Tonet JL, Frank R, Ducardonnet A, Fillette F, Fontaine G, Komajda M, et al. Holter monitoring in patients with focal cerebral ischaemic attacks (author’s transl). Nouv Presse Med. 1981;10:2491–2494. 37. Rem JA, Hachinski VC, Boughner DR, Barnett HJ. Value of cardiac monitoring and echocardiography in TIA and stroke patients. Stroke. 1985;16:950–956. 38. Hornig CR, Haberbosch W, Lammers C, Waldecker B, Dorndorf W. Specific cardiological evaluation after focal cerebral ischemia. Acta Neurol Scand. 1996;93:297–302. 39. 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. 40. Vivanco Hidalgo RM, Rodríguez Campello A, Ois Santiago A, Cuadrado Godia E, Pont Sunyer C, Roquer J. Cardiac monitoring in stroke units: importance of diagnosing atrial fibrillation in acute ischemic stroke. Rev Esp Cardiol. 2009;62:564–567. 41. Gumbinger C, Krumsdorf U, Veltkamp R, Hacke W, Ringleb P. Continuous monitoring versus HOLTER ECG for detection of atrial fibrillation in patients with stroke. Eur J Neurol. 2012;19:253–257. 42. Rizos T, Rasch C, Jenetzky E, Hametner C, Kathoefer S, Reinhardt R, et al. Detection of paroxysmal atrial fibrillation in acute stroke patients. Cerebrovasc Dis. 2010;30:410–417. 43. Stahrenberg R, Weber-Krüger M, Seegers J, Edelmann F, Lahno R, Haase B, et al. 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. 44. Martinez-Sanchez PM, Correas E, Cruz-Herranz A, Gimeno BF, Montes AM, Angeles M, et al. Detection of paroxysmal atrial fibrillation in patients with acute brain ischemia combining cardiac and Holter monitoring: prevalence and predictors. Stroke. 2012;43:A3648. Abstract. 45. Rizos T, Güntner J, Jenetzky E, Marquardt L, Reichardt C, Becker R, et al. Continuous stroke unit electrocardiographic monitoring versus 24-hour Holter electrocardiography for detection of paroxysmal atrial fibrillation after stroke. Stroke. 2012;43:2689–2694.
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Kishore et al Detection of Atrial Fibrillation After Stroke or TIA 7 46. Christensen LM, Krieger D, Hojberg S, Pedersen OD, Karlsen FM, Worch R, et al. Long-term monitoring for paroxystic atrial fibrillation in cryptogenic stroke: preliminary results of the surprise study. Stroke. 2012;43:A153. Abstract. 47. Sobocinski PD, Rooth EA, Kull VF, Arbin M, Wallen H, Rosenqvist M. Improved screening for silent atrial fibrillation after ischaemic stroke. Europace. 2012;14:1112–1116. 48. Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise
the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006;114:e257–e354. 49. Seet RC, Friedman PA, Rabinstein AA. Prolonged rhythm monitoring for the detection of occult paroxysmal atrial fibrillation in ischemic stroke of unknown cause. Circulation. 2011;124:477–486. 50. Gladstone DJ, Blakely J, Dorian P, Spring M, Fang J, Silver FL, et al. Detecting paroxysmal atrial fibrillation after ischaemic stroke and transient ischaemic attack: if you don’t look, you won’t find. Stroke. 2008;39:e78–e79. 51. Sinha AM, Diener H, Morillo CA, Sanna T, Bernstein RA, Di Lazzaro V, et al. Cryptogenic Stroke and underlying Arial Fibrillation (CRYSTAL AF): design and rationale. Am Heart J. 2010; 160: 36–41.
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SUPPLEMENTAL MATERIAL Detection of Atrial Fibrillation after Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Meta-analysis
Amit Kishore1,2 MRCP, Andy Vail3 MSc, Arshad Majid2 MD, Jesse Dawson4 MD, Kennedy R. Lees4 MD; Pippa J. Tyrrell1,2 MD, Craig J. Smith1,2 MD 1
Stroke and Vascular Research Centre, Institute of Cardiovascular Sciences, University of
Manchester, Manchester Academic Health Science Centre, Salford Royal Foundation Trust M6 8HD, UK; 2Greater Manchester Comprehensive Stroke Centre, Department of Medical Neurosciences, Salford Royal Foundation Trust M6 8HD, UK; 3Centre for Biostatistics, University of Manchester, Manchester Academic Health Science Centre, Salford Royal Foundation Trust, Salford M6 8HD, UK; 4Institute of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary, Glasgow G11 6NT
Corresponding author Dr Craig J. Smith Clinical Sciences Building, University of Manchester, Manchester Academic Health Science Centre, Salford Royal Foundation Trust M6 8HD E-mail: [email protected] Tel: +44 161 707 6534 206 0623 Fax: +44 161 707 6534
Online Supplement Table I: Search methodology Search Areas
Thesaurus terms
Free Text Terms
MEDLINE Subject Search in MESH: exp cerebrovascular disorders/; exp atrial fibrillation/; exp monitoring, physiologic/ or exp electrocardiography/;
Holter monitoring*, loop recorder*, stroke* and transient ischemic attack*
EMBASE
Subject Search on EMTREE: exp cerebrovascular disease/ exp patient monitoring/ exp heart atrium fibrillation/.
Holter monitoring*, loop recorder*, stroke* and transient ischemic attack*
Cochrane Library
Not Applicable
‘Atrial fibrillation’, ‘Stroke’, ‘cardiac monitoring’
Clinical Trials Registry
Not Applicable
‘Atrial fibrillation’, ‘Stroke or transient ischemic attack’ and ‘cardiac monitoring’
Google Scholar
Not Applicable
‘Atrial fibrillation’ ‘stroke’ or ‘transient ischemic attack’, ‘cardiac monitoring’
Online Supplement Table II: Characteristics of included studies Author
Design
Size (n)
Mean Age (Y)
F (%)
Type of index Event
Mode of monitoring
Unselected Or Selected or both?
Criteria for Selection
Definition of PAF
Simova, 2012*
POS1
15
54
0
S
Selected
POS
20
63.4
NR
S
NR
20.0
Dion, 2011
POS
24
49
37.5
S
Invasive
Selected
NR
4.2
Gunalp, 2006
POS
26
66
44
S
Selected
POS
27
68
44
S
Intermittent episodes of AF30 sec of AF
14.3
POS
42
65
50
S
Noninvasive Invasive
PAF > 2 min duration
16.7
Christensen, 2012* Higgins, 2012*
POS
43
NR
NR
S/T
Invasive
Selected
Cryptogenic strokes Cryptogenic strokes Cryptogenic strokes Excluded carotid stenosis Excluded minor strokes or posterior circulation strokes Cryptogenic Stroke Cryptogenic strokes Cryptogenic strokes
NR
Peiro, 2011*
Non Invasive Invasive
Rate of New AF/PAF (%) 20.0
NR
18.6
RCT2
50
NR
NR
S/T
Noninvasive
Unselected
Any duration AF
40.0
Dangayach, 2011 Schuchert, 1999
POS
51
58.2
53.5
S
Selected
Sustained AF>20 sec NR
16.0 29.4
POS
82
60.5
42.7
S
Noninvasive Noninvasive
Irregular baseline undulations of variable amplitude and morphology at >350/min with irregular ventricular response
6.1
Selected
Selected
Selected
Selected
Cryptogenic strokes Excluded structural causes
18.5
Kar, 2009*
POS
95
77.2
NR
T
a
62
b Kessler, 1994
POS
71 93
64
2
S
Tonet, 1981
POS
100
50
43
S/T
Callero, 2012*
POS
101
69.8
44.7
S
Kral, 2012*
POS
114
75.4
50
S
Bansil, 2000
POS
121
68.3
45.3
S
Wallman, 2007 Rizos, 2010 a
POS
127
63
30.6
S
POS
136 136
72
41.2
S/T
Noninvasive
Selected High risk TIA and Negative IP monitoring Low risk TIA
Noninvasive Noninvasive Noninvasive Noninvasive Noninvasive Noninvasive NonInvasive
Jabaudon, 2004 a b
POS
139
69
32.2
S/T
Rem, 1985
POS
169
63.5
33.7
S/T
Stahrenberg, 2010 Flint, 2012
POS
220
65
60.5
S/T
POS
236
64.6
39.5
S
NonInvasive
139 32
6.5
Unselected
NR
Unselected
NR
1.0
NR
25
Unselected
NR
8.8
Unselected
NR
4.9
>30 sec of AF
14.1
>30 sec of AF
21.3 19.1
Selected
Selected Selected
Cryptogenic Strokes
Negative 24h Holter Age>60 IP monitoring only Negative IP monitoring
Both Unselected Selected
Noninvasive Noninvasive Noninvasive
23.6
30.9 0
120
b
NR
Selected
NR
Negative 24h Holter Negative IP monitoring
Unselected Selected
2.5
Cryptogenic Strokes
5.7 5 3.8
NR
2.3
>30 sec of AF
12.5
>30 sec of AF
11
Irregular baseline undulations of variable amplitude and morphology at 300-350/min with irregular ventricular response >30 sec of AF
6.4
AF at least 10 sec
2
Unselected
NR
3.9
Both
>30 sec of AF
5.3
Tagawa, 2007
POS
241
72.3
39
S
Non invasive
Unselected
Kallmunzer, 2011 Sobocinskidoliwa, 2012
POS
245
72
47
S
Unselected
POS
249
72
43
S/T
Noninvasive Noninvasive
Hornig , 1996
POS
266
59.1
38.7
S/T
Gumbinger, 2012
POS
281
71
44.1
S/T
Noninvasive Noninvasive
Selected
a
281
Unselected
b
192
Selected
Madsen, 2009* MartinezSanchez, 2012* a
POS
310
NR
NR
S
POS
430
69
40.4
S/T
b Vivanco Hidalgo, 2007 Rizos, 2012
Noninvasive Noninvasive
Both
NR
11.2
Selected NR
S/T
POS
496
69
38.5
S/T
Noninvasive Noninvasive
1 5.8
156 79.1
Negative IP Monitoring NR
Unselected
461
4.6
Unselected
430
POS
Age>70y, Index event within 14 days
7.3
2.8 Negative IP monitoring
23.1
Unselected
>30s30 sec of AF
13.7
POS=Prospective Observational Study, RCT=Randomized Controlled Trial, S=Stroke, TIA=Transient Ischemic Attack, NR=Not Reported, * Abstract only, Y=years, IP=Inpatient monitoring, AF=Atrial Fibrillation
Online Supplement Table III: Patient characteristics Risk Factors (%) Author, Year
DM
HTN
Previous Stroke/TIA
IHD
Smoker
Dyslipaedemia
Rizos, 2010
30.1
79.4
NR
22.8
8.6
34.3
Tagawa, 2007
37.6
76.3
NR
36
34
37.4
Jabaudon, 2004
16
58.3
16.7
NR
NR
50
Barthelemy, 2003
5
50
23
27
NR
41
Hornig, 1996
34
43.5
30
40
28.7
64.3
Schuchert, 1999
NR
36.6
NR
17.5
NR
NR
Rem, 1985
16.3
56.5
31.5
36.5
39.5
NR
Stahrenberg, 2010
24.6
77.5
15.4
15.8
24.6
NR
Flint, 2012
14.7
66
18.8
10.5
NR
90.8
Kallmunzer, 2011
42
84
NR
21
24
49
Bansil, 2000
23.3
62
9.3
32
24
44
Dangayach, 2011
16
35.3
NR
20
NR
47.1
Gunalp, 2006
26
61
NR
31
NR
13
Rizos, 2012
24.6
78.8
19.6
NR
NR
NR
Dion, 2011
N
29.2
NR
NR
41.
33.3
Kral, 2012
NR
NR
22
28.9
NR
NR
Simova, 2012
20
70
NR
NR
30
80
Sandin, 2012
14
57
NR
NR
40
36
Sobocinski-doliwa, 2012
65
65
25
20
NR
NR
Higgins, 2012
8
56
NR
16
24
56
Mean
29.6
66.9
21.4
25.6
27.9
52.9
DM= Diabetes Mellitus, HTN=Hypertension, IHD=Ischemic Heart Disease, TIA= Transient Ischemic Attack
Online Supplement Table IV: Excluded Studies and accompanying references
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38
Author
Reason for exclusion
Britton, 1979 Rizzon, 1963 Abdon, 1982 Safieddine, 2002 Elkins, 2002 Dogan, 2004 Shafqat, 2004 Vandenbroucke, 2004 Douen, 2008 Elijovich, 2009 Haft, 2009 Sposato, 2009 Yu, 2009 Atmuri, 2009 Eitel, 2009 Gomis,2009 Kelly, 2009 Alhadramy, 2010 Ziegler, 2010 Bartko, 2010 Portilla, 2010 Riccio 2010 Gaillard, 2010 Tayal, 2010 Galiana, 2011 Mahagne, 2011 Ritter, 2011 Ustrell, 2011 Ba, 2011 Wnuk, 2011 Hoppe, 2011 Attygalle, 2011 Poisson, 2011 Thomas, 2011 Gupta, 2011 Kamel, 2011 Sousa, 2012 Lazzaro, 2012
Retrospective observational study Retrospective observational study Retrospective observational study Retrospective observational study
