Left atrial function after epicardial pulmonary vein isolation in patients with atrial fibrillation
Left atrial function after epicardial pulmonary vein isolation in patients with atrial f ibrillation
Louise Bagge 0 1 2
Per Blomström 0 1 2
Lena Jidéus 0 1 2
Stefan Lönnerholm 0 1 2
Carina Blomström-Lundqvist 0 1 2
0 Department of Cardiothoracic Surgery, Institution of Surgical Sciences, Uppsala University , Uppsala , Sweden
1 Department of Cardiology, Institution of Medical Sciences, Uppsala University , 751 85 Uppsala , Sweden
2 Louise Bagge
Purpose Epicardial pulmonary vein isolation has become an increasingly used therapy for medically resistant atrial fibrillation. The purpose of the present study was therefore to evaluate if epicardial pulmonary vein isolation combined with ganglionated plexi ablation affects the size and mechanical function of the left atrium, and whether the effects are dependent on the extensiveness of the ablation applications. Methods A total of 42 patients underwent an echocardiographic examination prior to and 6 months after a minimal invasive epicardial pulmonary vein isolation procedure for the assessment of the effects on left atrial size and function. In 27 patients, who had sinus rhythm both at baseline and follow-up, was a comparison of atrial size and function possible at these time intervals. Fractional area changes were obtained from the left atrial end-systolic and end-diastolic areas in the apical four-chamber view. Pulsed-Doppler was used to assess the transmitral flow velocities to evaluate mechanical function. Results Left atrial size and function at 6-month follow-up had not changed significantly from those at baseline as indicated by left atrial maximal area (17.1 ± 4.6 vs. 18.7 ± 5.3, p = 0.118), minimal area (12.5 ± 3.8 vs. 13.4 ± 4.7, p = 0.248), fractional area change (27.4 ± 8.2 vs. 28.7 ± 10.6, p = 0.670), and E/A ratio (1.49 ± 0.47 vs. 1.54 ± 0.67, p = 0.855).
Atrial function; Atrial fibrillation; Surgical ablation
When choosing the most optimal interventional treatment for
patients with atrial fibrillation (AF), not only the success rate
in eliminating AF, but also the potential risks for
complications, such as adverse effects on adjacent structures, should be
considered. It is already confirmed that the Cox maze III
procedure results in a sustained decrease in atrial contractility [
] but the effect of transvenous catheter-based pulmonary vein
(PV) isolation on left atrial (LA) function is unclear and study
results are conflicting [
]. Preserved atrial function may
have several important implications, an essential contribution
to the ventricular myocardial performance and a lower rate of
AF recurrences and thromboembolic events.
Epicardial PV isolation off-pump combined with
ganglionated plexi (GP) ablation has been used for the treatment of AF
]. Although several studies have reported high success
rates ranging between 74 and 90% in eliminating AF [
the information about the performance of the left atrium after
this type of surgery is still limited. The purpose of the present
study was therefore to assess the effects on size and
mechanical function of the left atrium of combined epicardial PV
isolation and GP ablation, and its relation to the extensiveness
of the ablation applications.
2.1 Patients and investigations
The patients selected for the surgical procedure were all
symptomatic patients with paroxysmal, persistent or longstanding
persistent AF who had either failed catheter ablation or had
chosen this option as first alternative. All patients had failed at
least one class I (86%) or class III (93%) antiarrhythmic agent.
A total of 42 patients who underwent minimal invasive
epicardial PV isolation combined with GP ablation
] during November 2005 and March 2008 were
evaluated with echocardiography prior to and 6 months after
surgery. In three patients, the baseline study was limited to a
transesophageal echocardiography, precluding a comparison
of LA area and E/A ratios at 6 months, thus leaving 39 patients
for the echocardiographic analysis. In nine patients, the
presence of AF at baseline and in three others at 6 months
precluded comparisons during the same rhythm before and after
surgery, leaving 27 patients for such an analysis. The patient
demographics are listed in Table 1.
The outcome and clinical evaluation at baseline and
follow-up has previously been described in detail [
Twelve (44%) of the patients had previously failed a
transvenous catheter-based PV isolation, and five patients
(19%) had previously undergone a tricuspid
isthmusdependent atrial flutter ablation. Four patients (15%)
had a permanent pacemaker preoperatively, although
none of the patients were paced in the ventricles.
Three of these patients had sick-sinus syndrome and
an AAI pacemaker, which may have resulted in delayed
LA activation but unlikely with any impact on LA
function. The last patient had a DDD pacemaker implanted
for bradycardia protection, but it was not in use.
Antiarrhythmic drugs were withdrawn in patients who
remained in sinus rhythm at 3 months after surgery.
2.2 Procedural technique
The minimal invasive off-pump procedure has been described
] and included epicardial PV isolation, LA GP
ablation, division of the ligament of Marshall if identified
(96%), and left atrial appendectomy. The bipolar
radiofrequency (RF) ablation clamp used for PV isolation was applied
well proximal to the confluence of the veins at the antrum, and
RF energy was applied according to an algorithm that
automatically stopped the ablation when the impedance change
indicated that a transmural lesion was achieved. In case
conduction block was not achieved after the first three
consecutive applications, 1–2 additional RF applications were given
until PV conduction block occurred.
After the PV isolation, GP activity was still present in 14 of
the patients (52%) defined as bradycardia response to
highfrequency electrical stimulation. The activity was abolished
by electrocautery or RF ablation until no vagal response could
be provoked. In nine patients (33%), RF ablation could not
abolish all vagal response. The number of applications for
vagal denervation ranged from 1 to 14 applications (median
1). Isolation of all PVs was completed in all but 3 of the 27
patients and required 3 to 4 applications (median 3) on the
right side and 2 to 4 applications (median 3) on the left side.
PV isolation could not be achieved in one patient despite
seven applications. In two cases, right PV isolation could not be
performed because of bleeding. The ablation procedure was
considered extensive if there were either six or more RF
applications at the PV and/or more than ten GP ablations.
The LA appendage was excised using a stapler, if judged
feasible and safe according to the surgeon, in 22 of the 27
patients (81%). It was not excised if there was a wide base
or thin wall. Complications have been reported elsewhere [
2.3 Echocardiographic examination
The echocardiographic examinations with measurements of
the left ventricular ejection fraction (LVEF), LA diameter
and valve function were made by an experienced technician
supervised by a cardiologist. The LVEF was measured in the
four-chamber view by Simpson’s method. The LA anterior
posterior diameter was measured by M-mode in the
parasternal long-axis view, and valve function was evaluated
by Doppler flows. Maximal LA cavity areas were obtained by
planimetry in the apical four-chamber view at the end of
ventricular systole, defined as the last frame before mitral valve
opening. Minimal LA cavity areas were obtained at end
diastole at the time of the R-wave on the electrocardiogram
(ECG). The mean values were calculated from two to three
consecutive beats. The atrial fractional area change (FAC)
(maximum area − minimum area maximum area × 100) of
the LA was then calculated. Pulsed-Doppler
echocardiography was used to assess the transmitral flow velocities from
an apical four-chamber view with a sample volume for the tip
of the mitral leaflets during diastole. Peak velocities of the
early filling deceleration time of the E-wave were measured
and averaged over two beats and the E/A ratios were
2.4 Statistical analysis
All values are expressed as mean ± SD unless otherwise
stated. Continuous variables for each patient at different time
periods were compared with the use of Wilcoxon
matchedpaired test. To analyze differences in LA function between
patients with enlarged LA and those with normal-sized LA,
the ANOVA test was used. The ANOVA test was also used to
analyze differences in LA function between patients with
extensive PV and/or GP ablations (either six or more PV
applications and/or more than ten GP ablations) compared with
patients with less extensive PV and GP ablations. Statistica
was used for the analyses.
The outcome and clinical evaluation at baseline and follow-up
has been described previously in detail [
], but in brief, 76%
patients had no symptomatic AF recurrences or AF episodes
on 24-h Holter recordings after surgery at 12 months
followup. One patient with longstanding persistent AF who suffered
from a stroke 2 days after surgery had warfarin discontinued
4 days before surgery and did inadvertently not receive
lowmolecular-weight heparin until the day before operation.
3.1 Atrial dimensions
At baseline, the median LA diameter was 4.3 cm (range 2.6–
5.9 cm), and 5 out of 27 patients had enlarged LA, as defined
by an equation for predicting normal echocardiographic
measurements from body weight and age by Henry et al. [
6 months follow-up after surgery, the LA diameter decreased
or normalized in 3 of these 5 patients with enlarged baseline
LA and became enlarged in 2 of the 22 other patients, with
normal LA diameter prior surgery.
The LA max and min areas recorded by echocardiography
at 6 months follow-up did not differ significantly from those
obtained at baseline (Table 2).
The LA max and min area recorded during sinus rhythm at
6 months follow-up in patients who had AF at baseline was
larger than those in patients with sinus rhythm at baseline, but
the difference did not reach statistical significance (Table 2).
A significant decrease in LA maximal area was, however,
observed after surgery for patients with enlarged LA at
baseline as opposed to patients with normal-sized LA (Table 3).
The LA maximal and minimal area change in patients with
extensive PV and/or GP ablation lesions (either six or more
PV applications and/or more than ten GP ablations) did not
differ from those in patients with less extensive PV and/or GP
ablations (Table 4).
3.2 Atrial mechanical function
Overall, the measurements of FAC, E-wave and A-wave
velocities, and E/A ratio recorded at 6-month follow-up were not
significantly different from those at baseline (Table 2). The
FAC and E/A ratio changes in patients with enlarged left
atrium at baseline and 6 months did not differ from those in
patients with normal-sized left atrium at baseline and 6 months
(Table 3). The FAC change after surgery did not differ in
patients with extensive PV and/or GP ablations as compared
with those in patients with less extensive PV and GP ablation
The E/A ratio had a restrictive pattern in 10 of the 27
patients at baseline, but normalized in six of these patients at
6 months follow-up. Two (20%) of these 10 patients with
restrictive LA pattern and three (18%) of the 17 patients with
normal E/A ratio had persistent AF. At 6 months follow-up, 9
of 24 patients had a restrictive pattern in the E/A ratio, but only
one of them had been subject to extensive PV and/or GP
None out of the two patients with decreased LVEF at
baseline improved their LVEF at 6 months follow-up. One patient
developed a slightly impaired LVEF after 6 months despite
being in sinus rhythm.
In the past decade, several new surgical AF ablation
procedures have been developed, all of which may result in a
reduced atrial mechanical function related to extensive scarring
of the left atrium, but the effect on LA function has not been
systematically studied. Apart from the fact that atrial
contractility is an essential contribution to ventricular myocardial
performance, that may have important implications for the
wellbeing of the patient, a reduced contractility may also promote
thromboembolic events even if AF is successfully eliminated.
SR at baseline and FU (n = 27)
AF at baseline (n = 9)
Max area cm2a
Min area cm2a
It is therefore important to assess the LA function when
introducing new non-pharmacological procedures for patients with
To the best of our knowledge, the present study is the first
to investigate the LA function after epicardial PV isolation
combined with GP ablation as a stand-alone procedure.
After the more complex and extensive Cox maze III
procedure, a sustained reduction of the atrial mechanical function,
by echocardiographic measures of atrial area fractional change
and E/A ratios, was reported for patients with paroxysmal lone
]. The clinical impact of studies showing severely
compromised LA function may warrant a more restrictive
attitude to refer patients with paroxysmal AF for such surgical
procedures. Catheter-based RF ablation of AF has also
resulted in a reduction in LA function [
] although the reports are
conflicting, as several studies have demonstrated no change or
even an improvement in LA function [
Among the three studies that have reported a reduction in
LA function following catheter-based PV isolation, two were
combined with linear lesions. One of these studies including
linear lesions observed a reduction in LA ejection fraction
(EF) as measured by ECG-gated computed tomography
] while the other reported a reduction in LA EF as
measured by magnetic resonance (MR) imaging already
48 days after the procedure which was limited to PV isolation
and right atrial linear lesion [
]. The sensitivity of detecting a
reduction in LA contractility may be higher with CT than with
echocardiography and the additional lesion sets along the
mitral isthmus and LA roof may have more extensive impact on
LA function. Results are also difficult to interpret in small
series of patients (n = 10) included [
] as compared with our
study with 27 patients. Studies of atrial function made early
after surgery may, however, reflect incomplete atrial
remodeling, although the reduced atrial systolic function seemed
strongly correlated with the volume of LA scar [
]. The third
study reporting an impairment of LA function was an
echocardiographic evaluation of left atrial emptying fraction mean
8 ± 2 months after a catheter-based PV isolation procedure in
patients with paroxysmal AF [
Two other studies evaluating the same type of procedure in
patients with paroxysmal AF [
] or paroxysmal and
nonparoxysmal AF [
] reported no change in LA function as
The p value is tested whether the differences from baseline to 6 months differ significantly between those with normal preop LAd versus those with
Preop, preoperatively; LAd, left atrial diameter; FAC, fractional area change; mo, months
a n = 20
b n = 3
Table 4 Left atrial areas and
fractional area changes, at
baseline and 6 months follow-up,
in patients with non-extensive PV
and GP ablation as compared with
those with extensive PV and GP
ablation after surgery
Non-extensive ablation (n = 12)
Extensive ablation (n = 7)
The p value is tested whether the differences from baseline to 6 months differ significantly between those with
normal non-extensive ablation versus those with extensive ablation
PV, pulmonary vein; GP, ganglionated plexi; FAC, Fractional area change; mo, months
indicated by preserved LA active emptying fraction as
measured by echocardiography [
] and by stable LA EF according
to cardiac MR 12 months after PV isolation [
]. Others have
reported an improved LA EF and a decrease in LA area (end
systolic and end diastolic) in patients with symptomatic
paroxysmal or persistent AF at 6 months after an AF ablation as
assessed by cine electron beam computed tomography
]. A significant decrease in LA size was also seen
in patients with the largest LA at baseline in the present study
and may either be related to the effect of remodeling after
maintenance of sinus rhythm or as a result of the scar tissue
shrinkage, the latter of which is contradicted by lack of effect
on atrial contractility. Although, normal values for LA area
] were recently presented, comparisons are not
recommended as the literature is scarce [
]. We therefore preferred
to refer to the standard LA diameter.
These diverse results observed in the literature may be
related to the patient’s age, type of AF, the duration of
followup, the type and the extent of ablation lesions, and also the
methods used for evaluation. The previous studies have used
diverse techniques for the evaluation of LA size and function,
including echocardiography, EBCT, CT, or MR; comparisons
of studies are difficult. Most of these imaging techniques are
associated with limitations, for example, an asymmetric
dilatation of the left atrium may under- or overestimate the LA
area or volume. Echocardiographic calculations of LA volume
rely on geometrical assumptions, which per se is an inherent
limitation. CT may be more sensitive to detect small
reductions in LA function but is associated with a burden of X-ray,
and therefore not widely applied. A meta-analysis recently
concluded that successful RF catheter ablation in patients with
AF significantly decreases LA size and volumes but does not
seem to adversely affect LA function . Theoretically, the
epicardial AF ablation approach might result in a more
extensive scar since the RF clamp is applied well outside the PV
pairs in the LA antrum. There are some studies examining the
LA function after epicardial PV isolation and limited LA
surgical ablation concomitant to cardiac surgery, a procedure that
is difficult to compare with the results in our study since the
cardiac surgery itself most likely affect the LA function
Compier et al.  concluded that even limited LA
ablation decreased LA volume, contraction, transport function,
and compliance, indicating both reverse remodeling
combined with significant functional deterioration. In contrast,
surgical PV isolation alone decreased LA volume while
function remained unchanged. They made limited LA ablation as a
concomitant procedure for patients scheduled for valve
surgery and/or coronary revascularization and had a control
group consisting of patients undergoing concomitant
epicardial PV isolation only. Signs of atrial dysfunction were also
reported after combined mitral valve surgery and left atrial
cryoablation for AF as opposed to with mitral valve surgery
], although in that procedure extra linear lesions were
Others, Buber J et al. , concluded that absence of
LA contraction resulted in a fivefold increase and a LA
volume index ≥ 33 ml/m2 in a threefold increase in the
risk for thromboembolic stroke after the concomitant RF
and cryoablation maze procedure, even when accounting
for CHADS-VASc, in patients in sinus rhythm at 2 years
According to our study, the mEPVI-GPabl does not seem
to affect LA mechanical function or LA size, as assessed
6 months after the procedure. Neither were there signs of
LA function deterioration with the extent of surgical ablation
applications. The relatively small number of patients and the
missing data may have affected the result.
As described previously [
], 76% had no symptomatic AF
recurrences or AF episodes on 24-h Holter recordings at
12 months follow-up. The success rate is important since AF
may cause significant structural remodeling and decreased
contractility of the left atrium [
]. In our study, there were no thromboembolic events
during 12 months follow-up except for in the one patient in
whom an adequate anticoagulation medication had not been
followed which emphasizes the importance of adequate
anticoagulation throughout the procedure.
In conclusion, the minimal invasive epicardial off-pump PV
isolation combined with GP ablation resulted in no significant
alteration of the atrial contractility, mechanical function, or
size of the left atrium. Hence, this minimally invasive
procedure with the elimination of AF recurrences and preserved
atrial function may decrease the risk for thromboembolic
events which may have implications for the risk evaluation
of thromboembolic complications after this surgery.
Since there are multiple factors, including left atrial pressure,
volume status, heart rate, and many others, which affect the
Ewave, A-wave velocities, and E/A ratios as surrogates for
mechanical function, it is difficult to draw conclusions
regarding mechanical function based on these variables.
Funding The work was supported by the Swedish Heart and Lung
Foundation  and the Swedish Research Council
Compliance with ethical standards The study was approved by the
local Ethics Review Board (ERB approval 2008-05-09 Dnr 2008/072).
Conflict of interest The authors declare that they have no conflicts of
Ethical approval All procedures performed in studies involving
human participants were in accordance with the ethical standards of the
institutional and/or national research committee and with the 1964
Helsinki declaration and its later amendments or comparable ethical
standards. The patients gave their consent to the study, which was approved
by the local Ethics Review Board.
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1. Lonnerholm S , Blomstrom P , Nilsson L , Blomstrom-Lundqvist C . Atrial size and transport function after the Maze III procedure for paroxysmal atrial fibrillation . Ann Thorac Surg . 2002 ; 73 ( 1 ): 107 - 11 .
2. Lonnerholm S , Blomstrom P , Nilsson L , Blomstrom-Lundqvist C . Long-term effects of the maze procedure on atrial size and mechanical function . Ann Thorac Surg . 2008 ; 85 ( 3 ): 916 - 20 . https://doi.org/10.1016/j.athoracsur. 2007 . 10 .090.
3. Lemola K , Desjardins B , Sneider M , Case I , Chugh A , Good E , et al. Effect of left atrial circumferential ablation for atrial fibrillation on left atrial transport function . Heart Rhythm . 2005 ; 2 ( 9 ): 923 - 8 .
4. Wylie JV Jr, Peters DC , Essebag V , Manning WJ , Josephson ME , Hauser TH . Left atrial function and scar after catheter ablation of atrial fibrillation . Heart Rhythm . 2008 ; 5 ( 5 ): 656 - 62 .
5. Rodrigues AC , Scannavacca MI , Caldas MA , Hotta VT , Pisani C , Sosa EA , et al. Left atrial function after ablation for paroxysmal atrial fibrillation . Am J Cardiol . 2009 ; 103 ( 3 ): 395 - 8 .
6. Reant P , Lafitte S , Jais P , Serri K , Weerasooriya R , Hocini M , et al. Reverse remodeling of the left cardiac chambers after catheter ablation after 1 year in a series of patients with isolated atrial fibrillation . Circulation . 2005 ; 112 ( 19 ): 2896 - 903 .
7. Verma A , Kilicaslan F , Adams JR , Hao S , Beheiry S , Minor S , et al. Extensive ablation during pulmonary vein antrum isolation has no adverse impact on left atrial function: an echocardiography and cine computed tomography analysis . J Cardiovasc Electrophysiol . 2006 ; 17 ( 7 ): 741 - 6 .
8. Jahnke C , Fischer J , Gerds-Li JH , Gebker R , Manka R , Fleck E , et al. Serial monitoring of reverse left-atrial remodeling after pulmonary vein isolation in patients with atrial fibrillation: a magnetic resonance imaging study . Int J Cardiol . 2011 ; 153 ( 1 ): 42 - 6 .
9. Bagge L , Blomstrom P , Nilsson L , Einarsson GM , Jideus L , Blomstrom-Lundqvist C . Epicardial off-pump pulmonary vein isolation and vagal denervation improve long-term outcome and quality of life in patients with atrial fibrillation . J Thorac Cardiovasc Surg . 2009 ; 137 ( 5 ): 1265 - 71 . https://doi.org/10.1016/j.jtcvs. 2008 . 12 .017.
10. Mehall JR , Kohut RM Jr, Schneeberger EW , Taketani T , Merrill WH , Wolf RK . Intraoperative epicardial electrophysiologic mapping and isolation of autonomic ganglionic plexi . Ann Thorac Surg . 2007 ; 83 ( 2 ): 538 - 41 . https://doi.org/10.1016/j.athoracsur. 2006 . 09 .022.
11. McClelland JH , Duke D , Reddy R . Preliminary results of a limited thoracotomy: new approach to treat atrial fibrillation . J Cardiovasc Electrophysiol . 2007 ; 18 ( 12 ): 1289 - 95 . https://doi.org/10.1111/j. 1540- 8167 . 2007 . 00977 .x.
12. Edgerton JR , Jackman WM , Mack MJ . Minimally invasive pulmonary vein isolation and partial autonomic denervation for surgical treatment of atrial fibrillation . J Interv Card Electrophysiol . 2007 ; 20 ( 3 ); 89 - 93 .
13. Edgerton JR , Edgerton ZJ , Weaver T , Reed K , Prince S , Herbert MA , et al. Minimally invasive pulmonary vein isolation and partial autonomic denervation for surgical treatment of atrial fibrillation . Ann Thorac Surg . 2008 ; 86 ( 1 ): 35 - 38 ; discussion 9. https://doi.org/ 10.1016/j.athoracsur. 2008 . 03 .071.
14. Matsutani N , Takase B , Ozeki Y , Maehara T , Lee R . Minimally invasive cardiothoracic surgery for atrial fibrillation: a combined Japan-US experience . Circ J . 2008 ; 72 ( 3 ): 434 - 6 .
15. Henry WL , Gardin JM , Ware JH . Echocardiographic measurements in normal subjects from infancy to old age . Circulation . 1980 ; 62 ( 5 ): 1054 - 61 .
16. Kou S , Caballero L , Dulgheru R , Voilliot D , De Sousa C , Kacharava G , et al. Echocardiographic reference ranges for normal cardiac chamber size: results from the NORRE study . Eur Heart J Cardiovasc Imaging . 2014 ; 15 ( 6 ): 680 - 90 . https://doi.org/10.1093/ ehjci/jet284.
17. Lang RM , Badano LP , Mor-Avi V , Afilalo J , Armstrong A , Ernande L , et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging . Eur Heart J Cardiovasc Imaging . 2015 ; 16 ( 3 ): 233 - 70 . https://doi.org/10.1093/ehjci/jev014.
Zhuang Y , Yong YH , Chen ML . Updating the evidence for the effect of radiofrequency catheter ablation on left atrial volume and function in patients with atrial fibrillation: a meta-analysis . JRSM open . 2014 ; 5 ( 3 ): 2054270414521185 .
Compier MG , Tops LF , Braun J , Zeppenfeld K , Klautz RJ , Schalij MJ , et al. Limited left atrial surgical ablation effectively treats atrial fibrillation but decreases left atrial function . Europace . 2016 ; https://doi.org/10.1093/europace/euw106.
Buber J , Luria D , Sternik L , Raanani E , Feinberg MS , Goldenberg I , et al. Left atrial contractile function following a successful modified Maze procedure at surgery and the risk for subsequent thromboembolic stroke . J Am Coll Cardiol . 2011 ; 58 ( 15 ): 1614 - 21 .
https://doi.org/10.1016/j.jacc. 2011 . 05 .051.
21. Johansson B , Bech-Hanssen O , Berglin E , Blomstrom P , Holmgren A , Jensen SM , et al. Atrial function after left atrial epicardial cryoablation for atrial fibrillation in patients undergoing mitral valve surgery . J Interv Card Electrophysiol . 2012 ; 33 ( 1 ): 85 - 91 . https://doi.org/10.1007/s10840-011-9605-x.
22. Kazui T , Henn MC , Watanabe Y , Kovacs SJ , Lawrance CP , Greenberg JW , et al. The impact of 6 weeks of atrial fibrillation on left atrial and ventricular structure and function . J Thorac Cardiovasc Surg . 2015 ; 150 ( 6 ): 1602 - 8 . https://doi.org/10.1016/j. jtcvs. 2015 . 08 .105.
23. Stewart S , Hart CL , Hole DJ , McMurray JJ . A population-based study of the long-term risks associated with atrial fibrillation: 20- year follow-up of the Renfrew/Paisley study . Am J Med . 2002 ; 113 ( 5 ): 359 - 64 .