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Review

Atrial septal defect closure is associated with

a reduced prevalence of atrial tachyarrhythmia in
the short to medium term: a systematic review and
meta-analysis
Joshua A Vecht,1 Srdjan Saso,1 Christopher Rao,1 Konstantinos Dimopoulos,2
Julia Grapsa,1 Cesare M Terracciano,3 Nicholas S Peters,4 Petros Nihoyannopoulos,5
Elaine Holmes,6 Michael A Gatzoulis,7 Thanos Athanasiou8

< An additional appendix is ABSTRACT with age (reported incidence for older patients is
published online only. To view Atrial tachyarrhythmias are a common complication of 20e50%).6e8
this file please visit the journal
atrial septal defects. The objective was to determine the Initially, all ASDs were closed surgically but
online (http://heart.bmj.com).
1
effect of atrial septal defect closure on pre-existing atrial percutaneous techniques first described in 1974 by
Surgical Epidemiology Unit, King and Mills9 have become established alterna-
Department of Biosurgery and
tachyarrhythmias and to investigate if such an effect is
Surgical Technology, Imperial present after either surgical or percutaneous closure. tives. According to the National Institute of Clinical
College London, St Mary’s Medline, EMBASE, Cochrane Library, and Google Scholar Excellence and the Joint American Heart Associa-
Hospital, London, UK databases were searched between 1967 and 2009. The tion/American College of Cardiology guidelines,
2
Adult Congenital Heart Centre, search was expanded using the ‘related articles’ function percutaneous techniques are now considered
Royal Brompton Hospital
and reference lists of key studies. All studies reporting ‘acceptable treatment’ (for ostium secundum
National Heart and Lung
Institute, Imperial College pre- and post- closure incidence (or prevalence) of atrial ASD).10 Sinus venosus, coronary sinus, or ostium
London, Royal Brompton tachyarrhythmias in the same patient groups were primum ASD, however, are unsuitable for percuta-
Hospital, London, UK
3
included. Data were independently extracted by two neous closure and thus need to be closed surgically.11
Cellular Electrophysiology Previous studies have examined the impact of ASD
Group, Harefield Heart Science
authors according to a pre-defined protocol. Incongruities
Centre, National Heart and Lung were settled by consensus decision. Twenty six studies closure on AT,12 suggesting that closure may initiate
Institute, Imperial College were identified including 1841 patients who underwent or discontinue AT,6 but comprehensive analysis has
London, Harefield Hospital, UK surgical closure and 945 who underwent percutaneous not been performed to quantitatively review the
4
Cardiac Electrophysiology, closure. Meta-analysis using a random effects model available evidence. To date, there is no randomised
National Heart and Lung
demonstrated a reduction in the prevalence of atrial trial comparing surgical and percutaneous closure
Institute, Imperial College
London, St Mary’s Hospital, tachyarrhythmias following atrial septal defect closure and now that percutaneous management has
London, UK [OR ¼ 0.66 (95% CI 0.57-0.77)]. This effect was become widely established, this is unlikely to occur.
5
Department of Cardiology, demonstrated after both percutaneous [OR ¼ 0.49 (95% Consequently the specific aims of this study
National Heart and Lung
Institute, Imperial College
CI 0.32-0.76)] and surgical closure [OR ¼ 0.72 (95% CI were: (a) to determine the potential antiarrhythmic
London, The Hammersmith 0.60-0.87)]. Immediate (<30 days) and mid-term (30 effect of ASD closure on pre-existing AT; (b) to
Hospital, London, UK days - 5 years) follow-up also demonstrated a reduction determine whether evidence for an antiarrhythmic
6
Department of Biomolecular in AT prevalence [ORs of 0.80 (95% CI 0.66-0.97) and effect is seen following both surgical and percuta-
Medicine, Imperial College 0.47 (95% CI 0.36-0.62) respectively]. Atrial septal neous ASD closure; and (c) to determine whether
London, Sir Alexander Fleming
defect closure, whether surgical or percutaneous, is any antiarrhythmic effect is time dependent.
Building, London, UK
7
Adult Congenital Heart Centre, associated with a reduction in the post-closure
Royal Brompton Hospital prevalence of pre-existing atrial tachyarrhythmias and
National Heart and Lung METHODS
atrial fibrillation in the short to medium term.
Institute, Imperial College Literature search
London, Royal Brompton A multilayer literature search was performed using
Hospital, London, UK Medline, EMBASE, Cochrane Library and Google
8
Department of Cardiothoracic
Surgery, National Heart and Scholar databases for all relevant studies until 2009
Lung Institute, Imperial College INTRODUCTION using the following MeSH search headings: ((Atrial
London, The Hammersmith Atrial septal defects (ASDs) are one of the most Septal Defect (ASD) or ASD closure or ASD Repair)
Hospital, London, UK common congenital cardiac abnormalities in and (Cardiac Surgery or Cardiothoracic surgery or
adulthood associated with arrhythmias, right heart Trans-catheterisation) and (Rhythm or Atrial (Tachy)
Correspondence to
Srdjan Saso, Clinical Research failure, stroke and premature death.1 While large Arrhythmia or Atrial Fibrillation (AFIB) or Flutter)).
Fellow, Department of ASDs may present in childhood with signs of heart The search was expanded using the ‘related articles’
Biosurgery and Surgical failure, a significant proportion of patients present function and by considering reference lists of the
Technology, 10th Floor, QEQM in the 3rde4th decade of life.2 Often asymptomatic key studies. Abstracts from the American Heart
Wing, St Mary’s Hospital,
London W2 1NY, UK;
until the onset of complications, the main cause of Association were also searched. All the review
[email protected] morbidity and mortality in ASD patients is attrib- articles whose subject was ASD closure, as well as
uted to the development of atrial tachyarrhythmia their reference lists were also screened (figure 1).
Accepted 8 September 2010 (AT).1 3 4 Approximately 10% of untreated patients
with ASD develop supraventricular arrhythmias, Outcomes
especially atrial fibrillation (AFIB) by the age of The primary outcome measure is change in the
40 years,3 5 and the incidence continues to increase prevalence of AT following ASD closure. In this

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Review

63 additional records identified

analysis, papers were included which referred to ‘atrial tachy-
512 studies identified in initial
through references and related arrhythmia’, ‘atrial fibrillation’, ‘atrial flutter’, ‘atrial tachy-
Identification

search
articles
cardia’, ‘left atrial tachycardia’, ‘atrio-ventricular nodal re-entry
tachycardia’, ‘junctional tachycardia’, ‘Wolff-Parkinson-White’
and ‘supraventricular tachycardia’. Secondary analysis of studies
575 reports fulfilling inclusion criteria (after duplicates removed) which referred only to ‘atrial fibrillation’ was also performed.
Screening

Inclusion and exclusion criteria

575 reports screened 480 reports excluded We included all studies reporting the incidence (or prevalence) of
AT before and after ASD closure (only patients with pre-existing
AT within studies were included). All studies reporting an adult
Eligibility

69 full-text articles excluded

population in which the mean/median age was at least 18 years
95 full-text articles assessed for eligibility
on exclusion criteria prior to intervention were included. Studies of both surgical and
percutaneous closure including all ASD types (sinus venosus,
ostium primum and ostium secundum) were included. Studies
26 studies included in qualitative analysis (meta-analysis)
describing patent foramen ovale closure, those not written in
English and those failing to differentiate between new-onset AT
and a diminution in the prevalence of pre-closure ATwere excluded.
Included

Surgical
Closure
(19 studies) Data extraction
Two reviewers (SS and JV) independently extracted data according
to a predefined search protocol. This included study design, type of
Percutaneous
Closure ASD and AT, number of patients, age of patients, and closure type.
(7 studies) The prevalence of AT and AFIB was recorded pre-closure, post-
closure and at latest follow-up. In the case of discrepancy,
Figure 1 Search strategy and selection of studies (PRISMA statement consensus decision was achieved by discussion, and where
compliant). necessary adjudication by a third reviewer (TA) (tables 1 and 2).

Table 1 Studies comparing the prevalence of atrial tachyarrhythmia/fibrillation between pre-closure and post-closure groups in a generalised
population
Number Mean age AT prevalence AF prevalence
Study Type(s) Type of patients of patients (pre-, post- (pre-, post- Type of
Author (year) design of ASD of AT (AT, no AT) (years) closure) (%) closure) (%) closure
Taniguchi et al13 (2009) R AS AF 9 (9, 0) 68.1* 100, 100 100, 100 P
Giardini et al14 (2008) R NS AFF 134 (13, 121) 39 10, 3.7 NS P
Wilson et al15 (2008) R NS AFF, AT, SVT, O 202 (22, 180) 33.3 10.9, 5.0 NS P
Spies et al16 (2008) R OS AF 240 (53, 187) 47 22.1, 19.6 22.1, 19.6 P
Silversides et al17 (2008) P OS AFF, SVT 200 (40, 160) 50 20.0, 6.5 NS P
Silversides et al18 (2004) R OS AFF 132 (20, 112) 44 15.0, 8.3 NS P
Suarez de Lezo et al19 (2000) R NS AF 28 (3, 25) 36 10.7, 7.1 10.7, 7.1 P
Erkut et al20 (2007) P OS AF 41 (6, 35) 44 14.6, 12.2 14.6, 12.2 S
Piechowiak et al21 (2006) R OS AF 93 (22, 71) 37 23.7, 23.7 23.7, 23.7 S
Mantovan et al22 (2003) R OP, OS, SV AF, SVT 136 (12, 124) 36.8 8.8, 7.4 8.1, 7.4 S
Ghosh et al23 (2002) R OS AF 89 (29, 60) 48.6 32.6, 18.0 32.6, 18.0 S
Donti et al24 (2001) R OS AFF 53 (14, 39) 57 26.4, 26.4 NS S
Jemielity et al25 (2001) R OS AF 76 (4, 72) 45.8 5.3, 5.3 5.3, 5.3 S
Gatzoulis et al7 (1999) R OP, OS, SV AF, AFl 213 (40, 273) 41 18.8, 11.3 NS S
Berger et al2 (1999) R OS, SV AF, AFl 211 (46, 165) 42.2 21.8, 14.7 13.3, 10.0 S
Shibata et al26 (1996) R OS AF 49 (24, 25) 57.4 49.0, 32.7 49.0, 32.7 S
Konstantinides et al27 (1995) R OP, OS, SV AFF 84 (22, 62) 56 26.2, 26.2 NS S
Shah et al28 (1994) P OS, SV AF 48 (12, 36) 36.2 25.0, 25.0 25.0, 25.0 S
Speechly-Dick et al29 (1993) R OS AF 55 (6, 49) 33 10.9, 10.9 10.9, 10.9 S
Murphy et al4 (1990) R OS, SV AFF 123 (19, 104) 26 15.4, 10.6 NS S
Cowen et al30 (1990) R OS AF 31 (16, 15) 57 51.6, 38.7 51.6, 38.7 S
Brandenburg et al31 (1983) R OS AF, AFl, SVT 188 (27, 161) 52.7 14.4, 10.6 8.5, 8.0 S
Lomholt et al32 (1980) R OS AF, AFl 28 (9, 20) >40 32.1, 21.4 28.6, 21.4 S
Esscher et al33 (1977) R OS AFF 166 (9, 157) 23 5.4, 5.4 NS S
Saksena et al34 (1970) R OS AF 24 (11, 13) 51* 45.8, 45.8 45.8, 45.8 S
Aldridge & Yao35 (1967) R OS AF, AFl 133 (17, 116) 32.1 12.8, 9.8 10.5, 7.5 S
*Age is given as a median.
ASD, atrial septal defect.
Study design: P, prospective; R, retrospective.
Types of atrial tachyarrhythmia: AF, atrial fibrillation; AFl, atrial flutter; AFF, atrial fibrillation and flutter; AT, atrial tachycardia; O, other: AVNRT, junctional tachycardia, Wolff-Parkinson-White;
SVT, supraventricular tachycardia.
Types of atrial septal defect: OP, ostium primum; OS, ostium secundum; SV, sinus venosus.
Types of closure: P, percutaneous; S, surgical; NS, not specified.

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Quality scoring Assessment of data validity and heterogeneity

Qualitative data to assess study comparability and enable Several quantitative and graphical methods were used to assess,
quality scoring were also extracted. These data were split into explain and account for important determinants of meta-analytical
two sections: variables previously highlighted to predispose validitydheterogeneity and bias.
surgical patients to AFIB (age, gender, hypertension, diabetes,
ejection fraction, chronic obstructive pulmonary disease, left Bias exploration: publication bias and risk of bias analysis
main stem disease and three vessel coronary artery disease); and Publication bias was assessed graphically with funnel plots to
variables known to positively affect the incidence of post-closure assess for asymmetry and evidence of outliers. The assessment
AT in patients with AT (right atrial dilatation, right ventricular of risk of bias was conducted in line with recommendations
dilatation and pulmonary hypertension).15 36 Table 3 summa- from the Cochrane guidelines.37 We performed a ‘domain-based
rises the distribution of these risk factors. The individual inclu- evaluation’ in which critical assessments were made separately
sion and exclusion criteria utilised by the studies analysed are for different domains where each domain type assessed a specific
shown in the Appendix. bias type. Adequate sequence generation, allocation concealment
and blinding were not considered as we were not directly
Statistical analysis comparing two interventions, and we only considered the effect
Meta-analysis was conducted according to PRISMA, MOOSE of selective reporting, incomplete outcome data and other
and Cochrane Collaboration guidelines.37e39 The OR was used sources of bias.
as the summary statistic. An OR <1 suggested that the preva-
lence of AT was lower following ASD closure. The OR was Sensitivity analysis through examination of subgroups
considered statistically significant at the p<0.05 level if the 95% Sensitivity analysis was performed through examination of
CI did not include the value 1. a number of subgroupsdsurgical ASD closure, percutaneous
Aggregation of the overall rates of the primary and secondary ASD closure, post-closure AFIB prevalence, post-closure AT
outcomes was performed with the ManteleHaenszel method.40 prevalencedduring follow-up (immediate (<30 days), mid-term
We used a random-effects model which assumes that there is (30 dayse5 years), late (>5 years)) and study quality. To quan-
variation between studies as this model better accounts for tify the study quality, we devised a scoring system. We attrib-
heterogeneity between studies.41 42 Analysis was conducted uted a point to each study when compliant with 10 specified
using Review Manager V.5.2 (The Cochrane Collaboration, factors (table 3). This generated a median of 2. The range was
Software Update, Oxford, UK). then divided into thirds which were scored from 1 to 3. Ten

Table 2 Prevalence of atrial tachyarrhythmia (AT) during follow-up period

Mean Immediate AT Mid-term AT Late AT
follow-up prevalence (%) prevalence (%) prevalence (%)
Author (years) (<30 days) (>30 dayse5 years) (>5 years)
Taniguchi et al13 0.9 NS 100 NS
Giardini et al14 4.8 6.0 3.7 NS
Wilson et al15 1.8 NS 5.0 NS
Spies et al16 0.5 22.1 NS NS
Silversides et alz 17 1.9 NS 6.5 NS
Silversides et aly 18 1.4 15.0 8.3 NS
Suarez de Lezo et al19 0.7 7.1 7.1 NS
Erkut et al20 4.2 12.2 12.2 NS
Piechowiak et al21 6.6 23.7 NS 23.7
Mantovan et al22 5.7 NS NS 7.4
Ghosh et al23 4.7 NS 18.0 NS
Donti et al24 9 NS NS 26.4
Jemielity et al25 6.9 NS NS 5.3
Gatzoulis et al7 3.8 13.1 11.3 NS
Berger et al2 NS 21.3 NS NS
Shibata et al26 9.7 40.8 NS 32.7
Konstantinides et al27 8.9 NS NS 26.2
Shah et al28 25.0 NS NS 25.0
Speechly-Dick et al29 2* 10.9 10.9 NS
Murphy et al4 27.2 NS NS 10.6
Cowen et al30 3.0 38.7 NS NS
Brandenburg et al31 12 4.8 NS 10.6
Lomholt et al32 3.7 NS 21.4 NS
Esscher et al33 12 5.4 NS 5.4
Saksena et al34 6 45.8 NS 45.8
Aldridge and Yao35 NS 12.8 NS NS
*Follow-up is given as a median.
yLabelled Silversides - 1 in the figures.
zLabelled Silversides - 2 in the figures.
NS, not specified.

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Table 3 Distribution of risk factors for atrial tachyarrhythmia within patient groups
Author A B C D E F G H I J Total matched factors Study score
Taniguchi et al13
* * * * 4 3
Giardini et al14 * * 2 2
Wilson et al15 * * * 3 2
Spies et al16 * * * * * 5 3
Silversides et al17 * * * * * 5 3
Silversides et al18 * * * 3 2
Suarez de Lezo et al19 * * 2 2
Erkut et al20 * * * * * 5 3
Piechowiak et al21 * * * * 4 3
Mantovan et al22 * * 2 2
Ghosh et al23 * * * * 4 3
Donti et al24 * * 2 2
Jemielity et al25 * * * * 4 3
Gatzoulis et al7 * * 2 2
Berger et al2 * * 2 2
Shibata et al26 * * * 3 2
Konstantinides et al27 * * * * 4 3
Shah et al28 * * 2 2
Speechly-Dick et al29 * 1 1
Murphy et al4 * * 2 2
Cowen et al30 * * * 3 2
Brandenburg et al31 * * * 3 2
Lomholt et al32 * * * 3 2
Esscher et al33 * * 2 2
Saksena et al34 * * * * * 5 3
Aldridge and Yao35 * * * * 4 3
*Indicates that a particular factor has been reported.
Variables predisposing to atrial tachyarrhythmia in surgical patients: A, age; B, male gender; C, hypertension;, D, diabetes mellitus; E, ejection fraction; F, chronic obstructive pulmonary
disease; G, advanced coronary artery disease.
Variables that affect the incidence of post-closure atrial tachyarrhythmia in patients with diagnosed pre-closure atrial tachyarrhythmia: H, right atrial dimension/dilatation; I, right
ventricular dimension/dilatation; J, pulmonary hypertension.
Study score: 1, matched for 0e1 factors; 2, matched for 2e3 factors; 3, matched for 4e5 factors.

studies qualified for the ‘top’ third (4e5 matched factors) and calculated OR for AFIB was 0.77 (95% CI 0.63 to 0.95), with an
these studies were analysed separately. I2 of 0% throughout (figure 3).

Heterogeneity assessment through the I2 statistic Sensitivity analysis

Heterogeneity of treatment effects between studies was assessed Effect of closure method
using the I2 statistic. This represents the proportion of total Seven studies reported percutaneous ASD closure.13e19 An OR
variation observed between the trials attributable to differences of 0.49 (95% CI 0.32 to 0.76) was calculated, with a moderate
between trials rather than sampling error or chance. The degree heterogeneity I2 of 45% (figure 2B). Similarly when analysis of
of heterogeneity was graded as low (I2<25%), moderate the 19 studies reporting surgical ASD closure was performed,
(I2¼25e75%) or high (I2>75%).43 the calculated OR was 0.72 (95% CI 0.60 to 0.87), with
a non-significant I2 heterogeneity of 0% (figure 2C).2 4 20e35 44
The results were similar in the surgical group when only AFIB
RESULTS was considered with an OR of 0.75 (95% CI 0.60 to 0.95).
Selected studies However, in the percutaneous closure group, while the OR
Literature search identified 575 manuscripts. On screening
was similar (OR 0.85), this did not reach statistical significance
the abstracts 480 were excluded. A further 69 were excluded
(95% CI 0.55 to 1.30).
after full text review. This resulted in a final study group of
26 studies published between 1967 and 2009 being selected Duration of effect
for the meta-analysis. In total 2786 patients were included Fifteen studies2 7 14 16 18e21 26 29e31 33e35 reported AT prevalence
from 3 prospective observational and 23 retrospective studies immediately after the procedure (<30 days), with an OR for ASD
(figure 1).2 4 7 13e35 Table 1 shows characteristics of individual closure of 0.80 (95% CI 0.66 to 0.97). Eleven studies7 13e20 23 29 30 32
studies included. reported AT prevalence at mid-term follow-up (30 dayse
5 years), with an OR of 0.47 (95% CI 0.36 to 0.62). Eleven
Meta-analysis studies4 21 22 25e28 31 33 34 reported the results of long-term
Four of the 26 studies showed a statistically significant reduction follow-up (>5 years). In these, the effect of ASD closure on AT
in the prevalence of AT following ASD closure.7 15 17 23 Meta- prevalence was not significant (OR 0.84, 95% CI 0.65 to 1.07).
analysis of all 26 studies showed a significant reduction in the
prevalence of AT (figure 2A), with an OR of 0.66 (95% CI 0.57 to Study quality
0.77) and an I2 of 0% indicating non-significant heterogeneity. Table 3 shows the number of risk factors for post-closure
Seventeen of 26 studies reported the prevalence of AFIB as AT that are matched in each study. This table also shows the
a subset of overall AT prevalence.2 13 16 19e23 25 26 28e32 34 35 The ‘quality score’ assigned, based on the number of factors

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Figure 2 Meta-analysis of studies

comparing prevalence of atrial
tachycardia pre- and post-closure. (A)
All studies. (B) Percutaneous closure
studies only. (C) Surgical closure studies
only.

matched. Ten studies matched $4 factors scoring 3 points Risk of bias was presented as methodological quality
for quality.13 16 17 20 21 23 25 27 34 35 In this group the OR for graphs. Figure 4B represents the risk of bias in which each
prevalence of post-closure AT was 0.70 (95% 0.51 to 0.97). methodological quality domain is presented as a percentage
across all included studies. Figure 4C is a methodological
Publication bias and risk of bias quality summary depicting the scoring for each domain across
Publication bias was explored with a funnel plot (figure 4A) all the included studies, demonstrating mixed potential risk
which shows mild asymmetry with one outlier. of bias.

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Figure 3 Meta-analysis of studies

comparing prevalence of atrial fibrillation
pre- and post-closure.

DISCUSSION channel expression has been shown to revert in those who

This study shows that ASD closure, whether surgical or percu- electrically cardiovert,52 53 and reversal of electrical remodelling
taneous, reduces the post-closure prevalence of pre-existing AT is known to occur sooner than structural reversal,57 with animal
in the short to mid term (OR 0.66, 95% CI 0.57 to 0.77). A studies showing almost immediate electrical reverse remodelling
similar effect is also seen in the surgical but not the percuta- but persistent structural remodelling at four months.58 This is
neous group, when only AFIB was considered (OR 0.77, 95% CI supported by our finding of a larger effect of ASD closure on AT
0.63 to 0.95), but does not seem to persist when studies with at mid-term follow-up (OR 0.47, 95% CI 0.36 to 0.62) compared
longer-term follow-up are analysed. to the immediately post-repair period (OR 0.80, 95% CI 0.66 to
0.97), when remodelling has not yet occurred.57 60 However, the
Interpretation effect of ASD repair was lost at longer follow-up, suggesting
The presence of an ASD alone has been shown to be associated that other mechanisms are in action (eg, ageing). We propose
with the development of AT in 10% of patients by the age that such changes may be associated with the type of structural
of 40 years. Preclosure incidence of AT is estimated to be remodelling which is not reversible. This is with the acknowl-
approximately 20%.3 6 7 edgement that the long term data was not available for the
AT in patients with ASD is the result of cardiac remodelling majority of the larger and higher quality studies. This may have
secondary to longstanding haemodynamic overload. Sizeable had a consequential statistical effect, so this interpretation is
ASD results in increased atrial size and stretch,7 12 45e50 right proposed with caution.
ventricular dilatation and dysfunction,7 elevation in pulmonary Care should also be exercised when comparing results from
arterial pressure7 and tricuspid and mitral regurgitation.51 these different populations as studies with longer follow-up
Atrial remodelling results in interstitial fibrosis and endo- periods were more likely to include patients who underwent
epicardial dissociation which predisposes to arrhythmias surgical closure, and had larger defects and more long-lasting ATs.
(electrophysiological and structural remodelling).45 48 Electro- In fact 29% of patients undergoing ASD closure have persistently
physiological remodelling manifests as non-uniform changes in increased right ventricular dimensions late after repair.7 56 This is
the atrial effective refractory periods, conduction delays at the likely to be due to incomplete reverse remodelling and could
crista terminalis and impaired sinus node function.45 48e50 In account for the persistence of AT in numerous patients.
addition, specific ion channel expression profiles representing ion A reduction in the prevalence of AT was seen after both
channel remodelling have been demonstrated in AFIB.52e54 surgical and percutaneous closure. This is consistent with
The effect of ASD closure on the risk of arrhythmia is likely to previous studies which have not demonstrated any difference in
be the result of negative remodelling of the atria and right remodelling between closure methods.56
ventricle, which occurs after repair. Dramatic changes such as
a reduction in right atrial and ventricular volume, an increase in Strengths and limitations
right ventricular ejection fraction and an increase in left This study is the first systematic review and quantitative anal-
ventricular volume have been described following ASD ysis of the evidence on the antiarrhythmic effect of ASD closure.
closure.55 56 As ASD closure appears to result in partial or As the best available evidence was evaluated within a robust
complete reversal of the associated haemodynamic changes, it is statistical framework, this study provides accurate estimates of
possible that it may also initiate reverse remodelling processes, treatment effects in a clinical group in which adequately
and may explain the antiarrhythmic effect of ASD closure. Ion powered experimental studies are impossible due to the low

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Figure 4 Publication bias and risk of

bias assessments. (A) Funnel plot test
exploring publication bias. (B)
Methodological quality graph: review
authors’ judgements about each
methodological quality item presented
as percentages across all included
studies. (C) Methodological quality
summary: review authors’ judgements
about each methodological quality item
for each included study.

prevalence of this condition and the established role of ASD specified the duration of each AT. Only four studies used the
closure in the management of these patients, which would not same AT monitoring method before and after closure. Further-
allow randomisation to a non-repair (placebo) arm.36 60 more, significant intraoperative factors exist which are known
The validity of any meta-analytical review can potentially be to potentially influence postoperative arrhythmia outcome, such
compromised by heterogeneity in patient characteristics, thera- as differing surgical practice and variation in the incidence and
peutic intervention or design between studies. The pathophys- management of postoperative complications.
iological complexity of AT makes reviews in this area A random-effects model was used to better account for the
particularly prone and vulnerable to heterogeneity. We could not inevitable clinical and methodological heterogeneity, however
compare the outcomes for specific ASD sizes or types. Moreover, we were unable to demonstrate significant statistical heteroge-
the duration of AT is known to affect the response to therapy, neity This can be interpreted in two ways: either the various
but this information was not available and the analysis may sources of heterogeneity ‘cancel each other out’ and the absence
have included heterogeneous patient groups. Arrhythmia inter- of statistical heterogeneity is merely an artefact of the analysis;
vention prior to or during surgical intervention is also not or the antiarrhythmic effect that we demonstrate following
uncommon nowadays and will certainly influence the risk of ASD closure is readily generalisable to most ASD populations
arrhythmia after repair. It was not possible to report on the pre- and closure methods. Examination of the study characteristics
or post-closure antiarrhythmic pharmacological regimes used or (table 1) suggests the latter.
their impact, since only two studies (Gatzoulis et al and Giardini
et al) provided detailed and specific descriptions of this. Implication for further research
Variation in clinical end-points, their definitions, monitoring Several questions are raised by this study. First, it is important to
and reporting can also introduce error. Gatzoulis et al, establish if the lack of significant statistical heterogeneity among
for example, excluded asymptomatic patients who had studies with different patient characteristics, therapeutic inter-
non-sustained AFIB on Holter monitoring.7 Most of the studies ventions and study designs truly represents the generalisability
did not report the monitoring methods used for AT and none of the antiarrhythmic effect of ASD closure or whether it is

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Review

merely an artefact of the analysis. This could take the form of 8. John Sutton MG, Tajik AJ, McGoon DC. Atrial septal defect in patients ages 60
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Second, we found that a significant proportion of patients 1974;75:383e8.
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management of these patients needs to be established. Ablation 11. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 Guidelines for the
for chronic AFIB at the time of surgical ASD closure is well Management of Adults with Congenital Heart Disease: a report of the American
visited in the literature.7 12 51 61 Giamberti et al describe a series College of Cardiology/American Heart Association Task Force on Practice Guidelines
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frequency ablation during surgical ASD closure, achieving a 93% 12. Berger F, Vogel M, Kretschmar O, et al. Arrhythmias in patients with surgically
reduction in pre-closure AT.62 Joint American Heart Association/ treated atrial septal defects. Swiss Med Wkly 2005;135:175e8.
American College of Cardiology guidelines recommend consid- 13. Taniguchi M, Akagi T, Ohtsuki S, et al. Transcatheter closure of atrial septal defect
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eration of concomitant Maze procedures in those with inter- 2009;73:682e6.
mittent or chronic AT.11 The experience with concomitant 14. Giardini A, Donti A, Sciarra F, et al. Long-term incidence of atrial fibrillation and
surgical ablation and ASD closure suggests that ablation may flutter after transcatheter atrial septal defect closure in adults. Int J Cardiol
2009;134:47e51.
have a role in patients with persistent AT after ASD closure. 15. Wilson NJ, Smith J, Prommete B, et al. Transcatheter closure of secundum atrial
However, further research is required to delineate what should septal defects with the Amplatzer septal occluder in adults and children-follow-up
be the indications and timing, especially given the findings in the closure rates, degree of mitral regurgitation and evolution of arrhythmias. Heart Lung
literature, supported by this study, which suggest that reverse Circ 2008;17:318e24.
16. Spies C, Khandelwal A, Timmermanns I, et al. Incidence of atrial fibrillation
remodelling processes are active and that these may not achieve following transcatheter closure of atrial septal defects in adults. Am J Cardiol
their maximal effect until some time following ASD closure. 2008;102:902e6.
Third, this study suggests that reverse remodelling processes 17. Silversides CK, Haberer K, Siu SC, et al. Predictors of atrial arrhythmias after device
closure of secundum type atrial septal defects in adults. Am J Cardiol
may have a tangible clinical effect on AT caused by ASD when 2008;101:683e7.
the haemodynamic changes resulting from ASD are reversed. 18. Silversides CK, Siu SC, McLaughlin PR, et al. Symptomatic atrial arrhythmias and
The impact of these reverse remodelling processes on the transcatheter closure of atrial septal defects in adult patients. Heart 2004;90:1194e8.
19. Suarez De Lezo J, Medina A, Pan M, et al. Transcatheter occlusion of complex
cessation of AT at a molecular and cellular level needs to be atrial septal defects. Catheter Cardiovasc Interv 2000;51:33e41.
better understood and characterised as this could yield novel 20. Erkut B, Becit N, Unlu Y, et al. The effect of surgical treatment for secundum atrial
therapeutic approaches for AT. septal defect in patients more than 30 years old. Heart Surg Forum 2007;10:
Finally, this study does not provide any evidence of a differ- E376e80.
21. Piechowiak M, Banach M, Ruta J, et al. Risk factors for atrial fibrillation in adult
ential efficacy in surgical and percutaneous closure techniques patients in long-term observation following surgical closure of atrial septal defect
for the termination of AT. As the anatomical indications for both type II. Thorac Cardiovasc Surg 2006;54:259e63.
techniques are different and well defined, further comparison of 22. Mantovan R, Gatzoulis MA, Pedrocco A, et al. Supraventricular arrhythmia before
and after surgical closure of atrial septal defects: spectrum, prognosis and
the antiarrhythmic effect of these interventions cannot be management. Europace 2003;5:133e8.
justified.11 23. Ghosh S, Chatterjee S, Black E, et al. Surgical closure of atrial septal defects in
adults: effect of age at operation on outcome. Heart 2002;88:485e7.
Conclusions 24. Donti A, Bonvicini M, Placci A, et al. Surgical treatment of secundum atrial septal
defect in patients older than 50 years. Ital Heart J 2001;2:428e32.
ASD closure, whether surgical or percutaneous, is associated 25. Jemielity M, Dyszkiewicz W, Paluszkiewicz L, et al. Do patients over 40 years
with a decrease in the post-closure prevalence of pre-existing AT. of age benefit from surgical closure of atrial septal defects? Heart
A similar effect was seen in patients after surgical ASD closure 2001;85:300e3.
26. Shibata Y, Abe T, Kuribayashi R, et al. Surgical treatment of isolated secundum
when only AFIB was considered. Further research is required to atrial septal defect in patients more than 50 years old. Ann Thorac Surg
establish whether this effect is seen in all patient groups, to 1996;62:1096e9.
better understand the mechanisms that underlie this treatment 27. Konstantinides S, Geibel A, Olschewski M, et al. A comparison of surgical
and medical therapy for atrial septal defect in adults. N Engl J Med
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1994;71:224e7; discussion 8.
Funding This work was supported by the National Institute of Health Research 29. Speechly-Dick ME, John R, Pugsley WB, et al. Secundum atrial septal defect
Biomedical Research Centre and British Heart Foundation (RG05/009). repair: long-term surgical outcome and the problem of late mitral regurgitation.
Competing interests None declared. Postgraduate Med J 1993;69:912e15.
30. Cowen ME, Jeffrey RR, Drakeley MJ, et al. The results of surgery for atrial septal
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31. Brandenburg RO Jr, Holmes DR Jr, Brandenburg RO, et al. Clinical follow-up study
of paroxysmal supraventricular tachyarrhythmias after operative repair of a secundum
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Heart 2010;96:1789e1797. doi:10.1136/hrt.2010.204933 1797

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Atrial septal defect closure is associated with

a reduced prevalence of atrial
tachyarrhythmia in the short to medium term:
a systematic review and meta-analysis
Joshua A Vecht, Srdjan Saso, Christopher Rao, Konstantinos
Dimopoulos, Julia Grapsa, Cesare M Terracciano, Nicholas S Peters,
Petros Nihoyannopoulos, Elaine Holmes, Michael A Gatzoulis and
Thanos Athanasiou

Heart 2010 96: 1789-1797

doi: 10.1136/hrt.2010.204933

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