Outcomes of Paroxysmal AF ablation Studies are Affected more by Study Design and Patient Mix than Ablation Technique Short title: Trial design and outcomes in AF ablation João Ferreira-Martins c MRCP PhD, James Howard b MB BChir, Becker Al-khayatt b MBBS, Joseph Shalhoub d MBBS PhD, Afzal Sohaib c MBBS PhD, Matthew Shun-Shin b BM BCh, Paul G Novak a MD, Rick Leather a MD, Laurence D Sterns a MD, Christopher Lane a MD, Phang Boon Lim b,c MBBS PhD, Prapa Kanagaratnam b,c PhD FRCP, Nicholas S Peters b,c MD PhD FHRS, Darrel P Francis b,c1 MA MD, Markus B Sikkel a,b MBBS PhD a Royal Jubilee Hospital, Victoria, Canada V8R 1J8 b National Heart and Lung Institute, Imperial College London, London W12 0NN, UK c Department of Cardiology, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London W12 0HS, UK d Department of Surgery & Cancer, Imperial College London, London SW7 2AZ, UK 1 Corresponding author Prof Darrel Francis International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London 59 North Wharf Road London, W2 1LA 1
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Outcomes of Paroxysmal AF ablation Studies are Affected more by Study Design and Patient Mix than Ablation Technique
Short title: Trial design and outcomes in AF ablation
João Ferreira-Martinsc MRCP PhD, James Howardb MB BChir, Becker Al-khayattb MBBS,
Joseph Shalhoubd MBBS PhD, Afzal Sohaibc MBBS PhD, Matthew Shun-Shinb BM BCh,
Paul G Novaka MD, Rick Leathera MD, Laurence D Sternsa MD, Christopher Lanea MD,
Phang Boon Limb,c MBBS PhD, Prapa Kanagaratnamb,c PhD FRCP, Nicholas S Petersb,c MD
PhD FHRS, Darrel P Francisb,c1 MA MD, Markus B Sikkela,b MBBS PhD
aRoyal Jubilee Hospital, Victoria, Canada V8R 1J8
bNational Heart and Lung Institute, Imperial College London, London W12 0NN, UK
cDepartment of Cardiology, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London W12 0HS, UK
dDepartment of Surgery & Cancer, Imperial College London, London SW7 2AZ, UK
1 Corresponding author
Prof Darrel FrancisInternational Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London59 North Wharf RoadLondon, W2 1LAUKEmail: [email protected]: +447973105394Fax: +442080825109
Total word count: 5024
M.B. Sikkel is supported by a National Institute of Health Research Clinical Lectureship award (#2670).ABSTRACT
1
Objective: We tested whether ablation methodology and study design can explain the
varying outcomes in terms of AF-free survival at 1 year.
Background:
There have been numerous paroxysmal AF ablation trials, which are heterogeneous in
their use of different ablation techniques and study design. A useful approach to
understanding how these factors influence outcome is to dismantle the trials into
individual arms and reconstitute them as a large meta-regression.
Methods: Data was collected from 66 studies (6941 patients). With freedom from AF as
the dependent variable, we performed meta-regression using the individual study arm
as the unit.
Results: Success rates did not change regardless of the technique used to produce
pulmonary vein isolation. Neither were adjunctive lesion sets associated with any
improvement in outcome.
Studies that included more males and fewer hypertensive patients were found more
likely to report better outcomes. ECG method selected to assess outcome also plays an
important role. Outcomes were worse in studies that used regular telemonitoring (by
23%, p<0.001) or in patients who had implantable loop recorders (by 21%, p=0.006),
rather than less thorough periodic Holter monitoring.
Conclusions: Outcomes of AF ablation studies involving pulmonary vein isolation are not
affected by the technologies used to produce PVI. Neither do adjunctive lesion sets
change the outcome. Achieving high success rates in these studies appears to be
dependent more on patient mix and on the thoroughness of AF detection protocols.
2
This should be carefully considered when quoting success rates of AF ablation
with a 3-month rather than a 1-month blanking period will raise success rates at 6
months by 10.8%, an effect that will dissipate by 12 months. This is consistent with data
suggesting that blanking period recurrences, are predictive of later recurrences38 such
that ignoring blanking period recurrences, particularly in months 2 and 3, is unlikely to
improve success rates in the long run. So although these later blanking period
recurrences may not predict further recurrence by the time 6 month outcomes are
measured, by 12 months they almost certainly do.
More thorough ECG follow-up reduces success rates
Studies use a variety of approaches to detect and define AF recurrence, ranging from a
single Holter monitor to continuous monitoring with an ILR. Quite rightly, each
individual trial only made comparisons between its arms of comparable design, but
outcomes are often compared between trials without adjusting for, or even mentioning,
differences in recurrence detection protocols.
Our data indicate that designing a study to rely on a Holter monitor rather than an ILR or
telemonitoring improves apparent success rate by around 20%. This is in stark
comparison to the absence of influence of technical factors such as method of
producing PVI or adjunctive lesion sets.
14
Limitations
This is not a randomized trial, but rather a meta-regression treating each arm of
published studies as a unit of analysis. It is effectively an observational study. However,
it provides a solution to the practical problem that, although one might suppose that
these non-procedural aspects may have some impact on outcome, as clinicians we have
no idea what the likely magnitudes of such outcomes will be. This study provides an
understanding of these effect sizes.
In addition, we are limited by the data available to us. As an example, there may be
limited variation in physiological parameters such as mean LA size in this group of PAF
patients, limiting our ability to detect a difference in outcomes in this metaregression. A
further example is that some technologies that we have grouped together may not be
completely homogeneous, such as first vs second generation cryoballoons.
We could only study variables disclosed by the authors of the manuscripts. There may
be other variables that are important but were not disclosed, or even not documented.
All we can tell is the apparent effect size of the non-procedural variables that happen to
have been presented are much larger than the effect size of the choice of procedure.
Conclusion
The key practical finding from this analysis is that when we look at the highly varied
results in outcomes of AF ablation studies, study methodology is a bigger determinant
than any modifications to the technique. Clearly performing a pulmonary vein isolation
is important, but how this is done, and the performance of adjunctive lesion sets are
less important to the final outcome than patient characteristics and protocol for
defining AF recurrence. Adjunctive lesion sets and some methods of producing PVI add
15
to procedure and fluoroscopy time without enhancing efficacy across the study arms
assessed.
Non-procedural aspects show much greater potential to increase observed success rate.
Per 20% increase in the proportion of males versus females in a study, one can expect
an 8.6% improvement in final AF-free survival. Per 20% reduction in the proportion of
hypertensive patients, we can expect a 4.9% improvement in success. Finally, using less
thorough methods of follow-up (e.g. Holter monitoring) can result in an apparent 21-
23% improvement in success compared to more thorough methods such as ILR or
telemonitoring.
Acknowledgements
We would like to acknowledge the BRC, BHF, and ElectroCardioMathsProgramme of the
Imperial Centre for Cardiac Engineering.
Author contributions:
João Ferreira-Martins: Concept/design, Data analysis/interpretation, Drafting article,
Critical revision of article, Approval of article.
James Howard: Concept/design, Data analysis/interpretation, Critical revision of article,
Approval of article, Statistics.
Becker Al-khayatt: Concept/design, Data analysis/interpretation, Drafting article, Critical
revision of article, Approval of article.
Joseph Shalhoub: Data analysis/interpretation, Critical revision of article, Approval of
article.
Afzal Sohaib: Data analysis/interpretation, Critical revision of article, Approval of article.
Matthew Shun-Shin: Data analysis/interpretation, Critical revision of article, Approval of
article.
16
Paul G Novak: Data analysis/interpretation, Critical revision of article, Approval of
article.
Rick Leather:Data analysis/interpretation, Critical revision of article, Approval of article.
Laurence D Sterns: Data analysis/interpretation, Critical revision of article, Approval of
article.
Christopher Lane: Data analysis/interpretation, Critical revision of article, Approval of
article.
Phang Boon Lim: Data analysis/interpretation, Critical revision of article, Approval of
article.
Prapa Kanagaratnam: Data analysis/interpretation, Critical revision of article, Approval
of article.
Nicholas S Peters: Data analysis/interpretation, Critical revision of article, Approval of
article.
Darrel P Francis: Concept/design, Data analysis/interpretation, Drafting article, Critical
revision of article, Statistics Approval of article.
Markus B Sikkel: Concept/design, Data analysis/interpretation, Drafting article, Critical
revision of article, Statistics Approval of article.
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Figure 1
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Figure 2
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Figure 3
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Figure 4.1
24
Figure 4.2
25
Figure 5
26
Figure 6
27
Figure Legends
Figure 1. Flow diagram of literature search and study selection. N, number of studies.
Figure 2. The effect of adjunctive strategies in addition to PVI on AF-free survival.
None of the adjunctive strategies resulted in significant improvements over the basic
PVI lesion set. Routine use of anti-arrhythmic drugs class I/III post-ablation came closest
to reaching significance p=0.07 with a trend towards greater success. CFAE, complex
Stabile 2014excluded no follow-up of AF recurrence
Chierchia 2012excluded no follow-up of AF recurrence
Jaïs 2002excluded no ablation
Bertaglia 2013 Includedexcluded paper not available
Lampe 2012excluded
effects of AV ablation + pacing vs DDD PPM for CHB in HF progression
Aras 2013excluded conference abstract
Fitts 2000excluded
focused on rate of atrial tachyarrhythmia detection by PPM
50
Di Biase 2012excluded conference abstract
Waldo 1999excluded dicussion paper
Tse 2001 Includedexcluded AV node ablation
Knecht 2010excluded conference abstract
Perez-Castellano 2014 Included Included
Jiang 2009excluded no follow-up of AF recurrence
Lau 1995excluded mixed atrial tachyaarhythmias (SVTs)
Stavrakis 2014excluded conference abstract
Marshall 1999excluded overlapp with paper 89
Gao 2007excluded not in english
Gordon 2014excluded paper not available
Ullah 2014excluded conference abstract
Macle 2012excluded study design
Kimura 2014excluded mixed population pAF and persistent AF
Herrera 2012excluded no follow-up
Bittkau 2012excluded conference abstract
Mulder 2013 Included Included
Dorian 1996excluded no ablation
Chilukuri 2011excluded mixed population pAF and persistent AF
Herrera 2012excluded duplicate
Derval 2010 exclude conference abstract
51
d
Haeusler 2011excluded no ablation
Deftereos 2012excluded review
Lyan 2013excluded conference abstract
Kay 1989excluded mixed population pAF and persistent AF
RAAFT-2excluded erratum
Zhang 2007excluded not in english
Bauer 2006excluded no follow-up of AF recurrence
Navistar® 2004excluded no abstract
Manolis 1998excluded no abstract
Fiala 2008 Included Included
Verma 2015excluded duplicate
Stavrakis 2015excluded no follow-up for AF recurrence
Scherr 2015excluded persistent AF
Atienza 2014excluded mixed population pAF and persistent AF
Giannopoulos 2014excluded
subpopulation of hypertensive pts undergoing AF ablation +/- minoxidil
Rolf 2014excluded mixed population pAF and persistent AF
Straube 2014excluded maximum 7 days follow-up
Zellerhoff 2014 Included Included
Nuhrich 2014excluded duplicate
Miller 2014excluded mixed population pAF and persistent AF
52
Wutzler 2014excluded no follow-up for AF recurrence
Uhm 2014excluded no follow-up for AF recurrence
Natale 2014 Included Included
McCready 2014excluded duplicate
Providencia 2014excluded mixed population pAF and persistent AF
Wang 2014excluded mixed population pAF and persistent AF
Oza 2014excluded no follow-up for AF recurrence
Kim 2014excluded no follow-up for AF recurrence
Kimura 2014excluded mixed population pAF and persistent AF
Pokushalov 2014excluded subpopulation of hypertensive pts
Adachi 2014excluded no ablation
DiBiase 2014excluded duplicate
Arbelo 2014excluded mixed population pAF and persistent AF
De Greef 2014excluded mixed population pAF and persistent AF
Bisbal 2014excluded mixed population pAF and persistent AF
Kimura 2014excluded duplicate
Park 2014excluded mixed population pAF and persistent AF
De Ville 2014excluded no follow-up for AF recurrence
Efremidis 2014excluded focused on QoL
Manganiello 2014excluded mixed population pAF and persistent AF
53
Yorgun 2014excluded mixed population pAF and persistent AF
Schmidt 2014excluded mixed population pAF and persistent AF
Krul 2014excluded patient population with previously failed PVI
Sairaku 2014excluded no follow-up for AF recurrence/focus on INR
Kriatselis 2014excluded duplicate
Song 2014excluded non-PAF
Kawakami 2014excluded no follow-up of AF recurrence
kaitani 2014 Includedexcluded
role of ATP in late re-conduction in pts undergoing second AF ablation
Deftereos 2014excluded duplicate
Seitz 2014excluded mixed population pAF and persistent AF
Lakkireddy 2014excluded focused on bleeding complications
Stabile 2014excluded duplicate
Takigawa 2014excluded impact of haemodysis in AF ablation
van Breugel 2014excluded duplicate
Morillo 2014 (RAAFT-2)excluded duplicate
Marrouche 2014excluded mixed population pAF and persistent AF
Andrade 2014excluded duplicate
Verma 2014excluded duplicate
Mont 2014 (SARA study)excluded duplicate
Bogachev-Prokophiev 2014 exclude duplicate
54
d
Jang 2014excluded chronic AF
Han 2014excluded duplicate
Stazi 2014excluded duplicate
Wang 2014excluded duplicate
Ejima 2014 Includedexcluded atrial remodeling and AF recurrence
Takigawa 2014excluded mixed population pAF and persistent AF
Kirchhof 2014excluded mixed population pAF and persistent AF
De Maat 2014excluded mixed population pAF and persistent AF
Perez-Castellano 2014excluded duplicate
Schmidt 2014excluded no follow-up for AF recurrence
Loghin 2014 Included Included
Katritsis 2013excluded duplicate
Pokushalov 2013excluded duplicate
Aytemir 2013excluded mixed population pAF and persistent AF
Miyazaki 2013excluded no follow-up for AF recurrence
Malmborg 2013excluded mixed population pAF and persistent AF
Linhart 2013excluded mixed population pAF and persistent AF
Ichiki 2013excluded
focus on cerebral microthromboembolism after catheter AF ablation
Brunelli 2013excluded no follow-up for AF recurrence
Efremidis 2013 exclude duplicate
55
d
Brooks 2013 Includedexcluded mixed population pAF and persistent AF
Sebag 2013excluded duplicate
Mantovan 2013excluded duplicate
Verma 2013excluded
focus on asymptomatic cerebral embolism after catheter AF ablation
Hong 2013excluded focus on left atrial remodeling in lone AF
De Bortoli 2013excluded non-PAF
Kobza 2013excluded mixed population pAF and persistent AF
Haines 2013excluded
retrospective study focused on dabigatran vs warfarin complications post AF ablation
Reddy 2013excluded
mixed population pAF and persistent AF/pts with GORD/IBS vs those without
Pokushalov 2013excluded duplicate
Al-Khatib 2013excluded
mixed population pAF and persistent AF/focus on apixaban
Sohns 2013excluded mixed population pAF and persistent AF
Neumann 2013 Included Included
Malcolme-Lawes 2013 Includedexcluded cardiac MRI
Doi 2013excluded duplicate
Ferrero-de Loma-Osorio 2013excluded mixed population pAF and persistent AF
Hussein 2013excluded
look at Spontaneous dissociated firing from the pulmonary veins during ablation
Steven 2013excluded duplicate
Fichtner 2013excluded duplicate
Dukkipati 2013 Included Included
56
Chun 2013excluded pts grouped by age. Mixed PAF and persistent
Ahmed 2013excluded duplicate
Packer 2013excluded duplicate
Adlbrecht 2013excluded duplicate
Neuzil 2013excluded duplicate
Zhao 2013excluded duplicate
Schernthaner 2013excluded mixed population pAF and persistent AF
Hunter 2013excluded duplicate
Schade 2013excluded duplicate
Pokushalov 2013excluded duplicate
Bertaglia 2013excluded duplicate
Mardigyan 2013excluded survey
Narayan 2013excluded mixed population pAF and persistent AF
Blanche 2013excluded mixed population pAF and persistent AF
Bänsch 2013excluded duplicate
Wieczorek 2013excluded no follow-up for AF recurrence
Lickfett 2013excluded duplicate
Uchiyama 2013 Included Included
Wójcik 2013excluded mixed population pAF and persistent AF
Wójcik 2013excluded
mixed population pAF and persistent AF (not the same as 109)
57
Lo 2013excluded mixed population AF and paroxysmal SVT
Wi 2013excluded mixed population pAF and persistent AF
Takigawa 2013excluded duplicate
Rilling 2013excluded duplicate
Metzner 2013 Included Included
Haeusler 2013excluded duplicate
Wieczorek 2013excluded duplicate
Derejko 2013excluded mixed population pAF and persistent AF/HOCM pts
Wang 2013 Included Included
Scharf 2012excluded mixed population pAF and persistent AF
Chierchia 2012excluded duplicate
Nolker 2012excluded duplicate
Wang 2012excluded mixed population pAF and persistent AF
Shivkumar 2012excluded mixed population pAF and persistent AF
Sairaku 2012excluded duplicate
Andrade 2012 STAR AF trialexcluded duplicate
Budera 2012excluded duplicate
Reddy 2012 Includedexcluded some patients had more than 1 ablation
Lin 2012excluded duplicate
Martinek 2012excluded duplicate
Deftereos 2012 exclude duplicate
58
d
Cosedis Nielsen 2012excluded duplicate
Lim 2012excluded duplicate
Lampe 2012excluded duplicate
Koch 2012 MACPAF studyexcluded duplicate
Pokushalov 2012excluded focused on pts with resistant hypertension
Narayan 2012excluded mixed population pAF and persistent AF
Arbelo 2012excluded
mixed population pAF and lone AF/no follow-up AF recurrence
Scaglione 2012excluded duplicate
Beukema 2012excluded duplicate
von Bary 2012 Includedexcluded
does not distinguish outcomes od 2 different ablation techniques. Results based on LA dimensions
Solheim 2012excluded duplicate
Liu 2012 Includedexcluded focus on inducibility of AF after ablation
Pozzoli 2012excluded 3 weeks follow-up only
Pison 2012excluded survey
Chierchia 2012 Included Included
Rivard 2012excluded persistent AF
Pokushalov 2012 Included Included
Dukkipati 2012 Includedexcluded 2 ablations
Santini 2012excluded mixed population pAF and persistent AF
Duncan 2012excluded duplicate
59
Kasirajan 2012excluded mixed population pAF and persistent AF
Miller 2012excluded mixed population pAF and persistent AF
Bayrak 2012excluded mixed population pAF and persistent AF
Cheung 2012excluded mixed population pAF and persistent AF
Berkowitsch 2012excluded mixed population pAF and persistent AF
Golden 2012excluded mixed population pAF and persistent AF
Metzner 2012excluded duplicate
Lakkireddy 2012excluded
mixed population pAF and persistent AF/focus in anticoagulation
Erdei 2012 Included Included
Macle 2012excluded duplicate
Pokushalov 2012excluded duplicate
Mun 2012excluded duplicate
Finlay 2012excluded duplicate
Calo 2012excluded duplicate
Herrera 2012excluded duplicate
Suleiman 2012excluded duplicate
Mulder 2012 Included Included
Tang 2012 Includedexcluded paper not available
Hunter 2012excluded mixed population pAF and persistent AF
Gavin 2012excluded duplicate
Pappone 2011 APAF study exclude duplicate
60
d
Pokushalov 2011excluded duplicate
Nedios 2011excluded duplicate
Chilukuri 2011excluded duplicate
Meinertz 2011excluded AF management in primary care in Germany
Gu 2011excluded duplicate
Bittner 2011excluded duplicate
to ACexcluded duplicate
Chen 2011excluded duplicate
Narducci 2011excluded
mixed population pAF and persistent AF/no follow-up/focus on tissue inflammation
Wang 2011excluded duplicate
Bonnemeier 2011excluded mixed population pAF and persistent AF
Katritsis 2011excluded duplicate
Kidouchi 2011excluded multiple atrialarrhythmias
Piorkowski 2011excluded duplicate
Pratola 2011excluded duplicate
Haeusler 2011excluded duplicate
Di Biase 2011excluded duplicate
Chierchia 2011excluded duplicate
Spertus 2011excluded QoL questionnaire
61
Leong-Sit 2011excluded duplicate
Nagashima 2011excluded mixed population pAF and persistent AF
Chao 2011 Includedexcluded
focus on renal function and recurrence of AF after ablation
Kettering 2011excluded persistent AF
Osmancik 2011excluded mixed population pAF and persistent AF
Reynolds 2010excluded duplicate
Reddy 2010excluded no follow-up/acute safety study
Schmidt 2010excluded duplicate
Gaita 2010excluded mixed population pAF and persistent AF
Koyama 2010excluded duplicate
Patel 2010excluded mixed population pAF and persistent AF
Edgerton 2010excluded non-randomized
Kojodjojo 2010excluded duplicate
Kim 2010excluded duplicate
Bulava 2010excluded duplicate
Park 2010excluded mixed population pAF and persistent AF
Caponi 2010excluded duplicate
Haeusler 2010excluded duplicate
Di Biase 2010excluded mixed population pAF and persistent AF
Veasey 2010 exclude mixed population pAF and persistent AF
62
d
Sawhney 2010excluded duplicate
Yamaguchi 2010excluded mixed population pAF and persistent AF
Verma 2010excluded duplicate
Tamborero 2010excluded duplicate
Luik 2010excluded duplicate
Beukema 2010excluded mixed population pAF and persistent AF
Tuan 2010excluded mixed population pAF and persistent AF
Knecht 2010excluded duplicate
Wieczorek 2010excluded duplicate
Nam 2010excluded mixed population pAF and persistent AF
Kirch 2010excluded QoL study/no ablation
Di Donna 2010excluded subpopulation of pts with HOCM
Pokushalov 2010excluded persistent AF
Rillig 2010excluded mixed population pAF and persistent AF
Chierchia 2010excluded no follow-up/study to assess effusion post ablation
Tsao 2010excluded duplicate
Neumann 2010excluded mixed population pAF and chronic AF
Steinwender 2010excluded duplicate
Bertaglia 2010excluded mixed population pAF and persistent AF
63
Wilber 2010excluded duplicate
Schrickel 2010excluded no follow-up/study on acute silent cerebral embolism
De Potter 2010excluded duplicate
Patel 2010excluded
mixed population pAF and persistent AF/females only study on complications
Steven 2010excluded duplicate
Corrado 2010excluded duplicate
Crawford 2010excluded duplicate
Wieczorek 2010 Included Included
Chierchia 2009excluded duplicate
Yamada 2009excluded duplicate
Klinkenberg 2009excluded no follow-up/effects of adenosin after ablation
Linhart 2009excluded duplicate
Jiang 2009excluded mixed population pAF and persistent AF
Baman 2009excluded duplicate
Cagli 2009excluded duplicate
Shamiss 2009excluded duplicate
Jensen-Urstad 2009excluded AF ablation in WPW syndrome patients
Nori 2009excluded mixed population pAF and persistent AF
Hwang 2009excluded atrial tachycardia
Khaykin 2009excluded duplicate
64
Schmidt 2009 Included Included
Abecasis 2009excluded mixed population pAF and persistent AF
Bhargava 2009excluded mixed population pAF and persistent AF
Joshi 2009excluded mixed population pAF and persistent AF
Fredersdorf 2009excluded mixed population pAF and persistent AF
Ninomiya 2009excluded
no follow-up/acute effect of ATP in reconduction post ablation
Roux 2009excluded duplicate
Pokushalov 2009excluded duplicate
Hof 2009excluded mixed population pAF and persistent AF
Meissner 2009excluded mixed population pAF and persistent AF
Han 2009excluded mixed population pAF and persistent AF
Chun 2009excluded no follow-up/effect of rapid pacing of RV
Bencsik 2009excluded duplicate
Pratola 2009excluded no follow-up
Schmidt 2009excluded duplicate
Reddy 2009 Included Included
Jons 2009excluded duplicate
Chilukuri 2009excluded
questionnaire on obstructive sleep apnoea and outcomes of AF ablation
Martinek 2009excluded duplicate
Edgerton 2009excluded mixed population pAF and persistent AF
Sohara 2009 exclude mixed population pAF and persistent AF
65
d
Pontoppidan 2009excluded duplicate
Yokoyama 2009excluded no follow-up
Van belle 2009excluded no follow-up
Kettering 2009excluded mixed population pAF and persistent AF
Miyanaga 2009excluded duplicate
Deisenhofer 2009excluded duplicate
Schmidt 2009excluded mixed population pAF and persistent AF
Di Biase 2009excluded duplicate
DiBiase 2009excluded duplicate
Yoshida 2009 Includedexcluded multiple ablations
Della Bella 2009excluded duplicate
Park 2009excluded mixed population pAF and persistent AF
Dong 2009excluded duplicate
Laurent 2009excluded ablation of atrial flutter
Beyer 2009excluded mixed population pAF and persistent AF
Kautzner 2009excluded duplicate
Tamborero 2009excluded duplicate
Kumagai 2009excluded mixed population pAF and persistent AF
Kriatselis 2009excluded mixed population pAF and persistent AF
66
Tang 2009excluded duplicate
Khaykin 2009excluded duplicate
Forleo 2009excluded duplicate
Jais 2008 (A4 study)excluded duplicate
Knecht 2008excluded duplicate
Malmborg 2008excluded mixed population pAF and persistent AF
Van Belle 2008 Included Included
Luria 2008excluded duplicate
Gaita 2008excluded duplicate
Yoshida 2008excluded mixed population pAF and persistent AF
Muller 2008excluded mixed population pAF and chronic AF
Piorkowski 2008excluded mixed population pAF and persistent AF
Shimano 2008excluded duplicate
Satomi 2008 Included Included
Richmond 2008excluded duplicate
Corrado 2008excluded mixed population pAF and persistent AF
Fiala 2008excluded duplicate
Neumann 2008excluded mixed population pAF and persistent AF
Khadjooi 2008excluded effects of CRT in AF and SR
Jongnarangsin 2008excluded mixed population pAF and chronic AF
Shah 2008 exclude mixed population pAF and persistent AF
67
d
Wu 2008excluded duplicate
Fiala 2008excluded duplicate
Kettering 2008excluded duplicate
Wang 2008excluded duplicate
Lutomsky 2008excluded duplicate
Pak 2008excluded duplicate
Oral 2008excluded duplicate
Khan 2008excluded duplicate
Mortada 2008excluded anticoagulation for AF ablation
Perea 2008excluded mixed population pAF and persistent AF
Chang 2008excluded SVT and AF/ no follow-up
Tang 2008excluded duplicate
Chen 2008excluded mixed population pAF and persistent AF
Yamada 2008excluded AF ablation in Brugada syndrome patients
Verma 2008excluded mixed population pAF and persistent AF
Dixit 2008excluded duplicate
Maly 2008excluded duplicate
Phillips 2008excluded no follow-up
Crawford 2008excluded duplicate
68
Liakishev 2013excluded duplicate
Moreira 2008excluded mixed population pAF and atrial flutter
Yao 2007excluded mixed population pAF and persistent AF
McClelland 2007excluded mixed population pAF and persistent AF
Pruitt 2007excluded mixed population pAF and persistent AF
Narayan 2007excluded mixed population pAF and persistent AF
Knecht 2007excluded mixed population pAF and flutter
Issa 2007excluded no follow-up/AV node ablation + PPM
Wang 2007excluded duplicate
Arentz 2007excluded duplicate
Gaita 2007excluded mixed population pAF and persistent AF/HOCM pts
Chang 2007excluded no follow-up
Yamane 2007excluded duplicate
Haïssaguerre 2007excluded mixed population pAF and persistent AF
Sra 2007excluded mixed population pAF and persistent AF
Suwalski 2007 Includedexcluded surgical PVI with VATS
Gao 2007excluded duplicate
Kurosaki 2007excluded mixed population pAF and persistent AF
Atarashi 2007excluded duplicate
Verma 2007 exclude duplicate
69
d
Nakagawa 2007excluded mixed population pAF and persistent AF
Turco 2007excluded mixed population pAF and persistent AF
Solheim 2007excluded mixed population pAF and persistent AF
Papone 2006excluded duplicate
Willems 2006excluded duplicate
Bauer 2006excluded duplicate
Liu 2006excluded duplicate
Richter 2006excluded mixed population pAF and persistent AF
Sheikh 2006excluded duplicate
Kistler 2006excluded mixed population pAF and persistent AF
Cheema 2006excluded mixed population pAF and persistent AF
Di Biase 2013excluded duplicate
Dixit 2006excluded duplicate
Heist 2006excluded no follow-up
Nilsson 2006excluded duplicate
Wongcharoen 2006excluded no follow-up
Scanavacca 2006 Includedexcluded no PVI
Estner 2006excluded mixed population pAF and persistent AF
Yu 2006excluded not in english
70
Calo 2006excluded duplicate
Obergassel 2006excluded pts with HOCM
Oral 2006 Included Included
Akpinar 2006excluded mixed population pAF and persistent AF
Cheema 2006 excluded duplicate
Risius 2006excluded no follow-up
Stabile 2006excluded mixed population pAF and persistent AF
Hocini 2005excluded duplicate
Tojo 2005excluded no follow-up
Kumagai 2005excluded duplicate
Mantovan 2005excluded mixed population pAF and persistent AF
Jiang 2005 Includedexcluded CT guided AF ablation
Reant 2005excluded mixed population pAF and chronic AF
Fassini 2005excluded duplicate
Liu 2005excluded duplicate
Tse 2005excluded duplicate
Lickfett 2005excluded ablation of atrial flutter
Ninet 2005excluded mixed population pAF and persistent AF
Mack 2005excluded mixed population pAF and persistent AF
Rao 2005excluded persistent and permanent AF
71
Liu 2005excluded duplicate
Molloy 2005excluded mixed population pAF and persistent AF
Kocheril 2005 Includedexcluded right atrial ablation
Cappato 2005excluded survey
Tsao 2005excluded duplicate
Tondo 2005excluded duplicate
Oral 2004excluded duplicate
Mokadam 2004excluded mixed population pAF and persistent AF
Sacher 2004excluded not in english
Tanner 2004excluded ablation of atrial tachycardias
Brembilla-Perrot 2004excluded
effect of transoesophageal pacing in the diagnostic evaluation of patient with unexplained syncope
Oral 2004excluded duplicate
Katritsis 2014excluded duplicate
Schwartzman 2004excluded
study of pulmonry veins as source of arrhythmogenic atrial ectopy
Gillinov 2004excluded mixed population pAF and persistent AF
Pappone 2004 Includedexcluded effect of vagal denervation + PVI
Jansens 2004 Includedexcluded paper not available
Calo 2004excluded mixed population pAF and persistent AF
Todd 2003excluded longstanding AF
Gillis 2003 exclude duplicate
72
d
Oral 2003excluded no follow-up
Lemke 2003excluded duplicate
Arentz 2003excluded mixed population pAF and persistent AF
Oral 2003excluded duplicate
Weerasooriya 2003excluded no follow-up
Duff 2003excluded duplicate
Raman 2003excluded mixed population pAF and persistent AF
Wang 2003excluded paper not available
Tada 2003 Includedexcluded focused on QoL
Berkowitsch 2013 Includedexcluded focused on QoL
Hocini 2003excluded AF pts with sinus pauses (>=3sec) after fast AF
Oral 2003excluded duplicate
Tse 2003excluded mixed population pAF and persistent AF
Stabile 2003excluded mixed population pAF and persistent AF
Sanchez 2003excluded no follow-up
Lin 2003 Includedexcluded ablation of non PV ectopies
Padeletti 2003excluded duplicate
Patel 2003excluded no follow-up
Brignole 2003excluded duplicate
73
Marchlinski 2003excluded mixed population pAF and persistent AF
Dill 2003excluded focus on PV stenosis post ablation
Pürerfellner 2003excluded focus on PV stenosis post ablation
Camm 2003excluded no ablation
Stabile 2003excluded duplicate
Jaïs 2002excluded duplicate
Brembilla-Perrot 2003excluded not in english
Goya 2002excluded PAF post AF ablation
Tada 2002excluded duplicate
Epstein 2002excluded duplicate
Takahashi 2002excluded no follow-up
Brignole 2002excluded duplicate
Katritsis 2002excluded no follow-up
Oral 2002excluded mixed population pAF and persistent AF
Brembilla-Perrot 2002excluded not in english
Brembilla-Perrot 2002excluded not in english
Pappone 2001excluded mixed population pAF and persistent AF
Tse 2001excluded duplicate
Simpson 2001excluded duplicate
Bailin 2001 exclude duplicate
74
d
Hindricks 2001excluded no follow-up
Stabile 2001excluded duplicate
Sueda 2001excluded chronic AF
Dagres 2001excluded duplicate
Ashar 2000excluded no follow-up
Padeletti 2000excluded chronic AF
Pappone 2000excluded mixed population pAF and persistent AF
Gasparini 2000excluded mixed population pAF and chronic AF
Chan 2000excluded focus in coagulum formation during ablation
Gasparini 2000excluded mixed population pAF and persistent AF
Hocini 2000excluded no follow-up
Tai 2000excluded no ablation
Gilis 2000excluded duplicate
Tsai 2000 Includedexcluded ablation of SVC ectopies
Fitts 2000excluded duplicate
Lee 2000excluded duplicate
Jais 2000 Includedexcluded paper not available
chen 1999excluded duplicate
Gasparini 1999excluded focus on thromboembolic events
75
Waldo 1999excluded duplicate
Gillis 1999excluded duplicate
Proclemer 1999excluded duplicate
Marshall 1999excluded duplicate
Hsieh 1999 Includedexcluded paper not available
Gillis 2009excluded duplicate
Marshall 1999excluded duplicate
Brignole 1999excluded duplicate
Furlanello 1999excluded AF in athletes
Kuck 1998excluded no ablation
Fitts 1998excluded duplicate
Herz 1998excluded not in english
Chen 1998excluded no follow-up
Kalman 1997excluded ablation of atrial flutter
Kim 1997excluded mixed population pAF and atrial flutter
Brignole 1997excluded duplicate
Leitch 1997excluded EP study
Kamalvand 1997excluded duplicate
Schuchert 1997excluded not in english
Chen 1996 exclude AV ablation
76
d
Dorian 1996excluded duplicate
Tai 1995excluded ablation of AV accessory pathways
Lau 1995excluded duplicate
Xang 1995excluded ablation of atrial flutter
Iesaka 1994excluded ablation of AV accessory pathways
Kay 1989excluded duplicate
Pokushalov 2010excluded mixed population pAF and persistent AF
Eitel 2011 Included Included Podd 2015 Included Included mixed population pAF and persistent AFPood 2016 Included Included Bjorkenheim 2016 Included Included Kuck et al 2016 Included Included Verma et al 2010 Included Included
Martinek 2007excluded mixed population pAF and persistent AF
Kapa 2013excluded mixed population pAF and persistent AF
Veasey et al 2010excluded mixed population pAF and persistent AF
Yang et al 2016excluded mixed population pAF and persistent AF