European Heart Journal – Cardiovascular Imaging (2014) 15, 1117–1124 doi:10.1093/ehjci/jeu089
Effects of percutaneous closure of atrial septal defect on left atrial mechanical and conduction functions Muzaffer Aslan, Mehmet Erturk*, Selahattin Turen, Fatih Uzun, Ozgur Surgit, Sinem Ozbay Ozyilmaz, Mehmet Rifat Yildirim, Omer Faruk Baycan, Begum Uygur, Aydin Yildirim, and Abdurrahman Eksik ¨ zal Bulvarı No:11 Ku¨c¸u¨kc¸ekmece, Department of Cardiology, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, ˙Istasyon Mah. Turgut O 34303 Istanbul, Turkey Received 11 February 2014; accepted after revision 18 April 2014; online publish-ahead-of-print 22 May 2014
Aims
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
percutaneous closure † secundum atrial septal defect † atrial electromechanical delay † left atrial mechanical function
Introduction Atrial septal defect (ASD) is the most common type of congenital heart disease in the adults and 65– 70% of all defects are secundum type, which is located at the region of fossa ovalis. This lesion is sometimes associated with the development of pulmonary hypertension, impaired aerobic capacity, and atrial arrhythmias.1 Atrial arrhythmias are the most common type of tachyarrhythmia encountered in the clinical practice and are associated with increased morbidity and mortality.2 Definitive treatment of ASD can be done by surgical closure and more recently by percutaneous closure using atrial septal occluder
(ASO) devices.1 Numerous studies have shown that percutaneous closure with ASOs is a safe technique in appropriately selected patients.3,4 However, the impact of the placement of an occluder device on subsequent atrial function has been investigated only in a limited number of studies.5 – 8 The atrial diameters and the volumes are increased in ASD patients due to volume overload. It is known that increased atrial diameters and volume cause prolongation of conduction time and nonhomogenous propagation of sinus node impulses.9 The prolongation of atrial electromechanical delay (AEMD) and inhomogeneous propagation of the sinus impulses are well-known electrophysiological characteristics of the atria prone to fibrillation.10 AEMD can
* Corresponding author. Tel: +90 212 692 20 00; Fax: +90 212 471 94 94, E-mail: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected].
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Atrial septal defect (ASD) is one of the most common congenital heart diseases in adults. We prospectively evaluated early and mid-term effects of the percutaneous closure of secundum ASD on atrial electromechanical delay (AEMD) and left atrial (LA) mechanical functions at the first day and sixth month in patients undergoing percutaneous closure. ..................................................................................................................................................................................... Methods Forty-one patients were included in this study. Twenty-six (63.4%) of the 41 patients were female and the mean age was and results 41 + 13 years. All the patients had echocardiographic examination before the procedure and at the first day and sixth month after the procedure. LA volumes (maximal, minimal, and presystolic) and EMD (lateral, septal, and tricuspid) were measured. Left and right intra- and inter-AEMD were not changed at the first day but both were significantly shorter at the sixth month. There was no change in the total emptying volume and fraction before and after the procedure. LA maximal, minimal, and pre-systolic volumes, active emptying volume, and fractions were decreased at the first day and at the sixth month compared with pre-procedural volumes. LA passive emptying volume, passive emptying fraction, and conduit volume were increased at the first day and at the sixth month compared with pre-procedural volumes. ..................................................................................................................................................................................... Conclusion Our results revealed that there was no change in the LA mechanical reservoir functions, but improved conduit function and impaired contractility functions early and in the mid-term after percutaneous closure of ASD and decreased AEMD only in the mid-term.
1118 be measured with electrocardiographic, echocardiographic, and electrophysiological methods in patients with ASD.9,11 – 15 The left atrial (LA) mechanical function is an important determinant of left ventricular (LV) filling, especially in patients with end-stage systolic or diastolic ventricular dysfunction, LV hypertrophy, and diminished LV enlargement capacity.16 LA mechanical functions consist of reservoir, conduit, and booster pump functions at different stages of the cardiac cycle.17 Impaired mechanical functions have been associated with increased risk of atrial fibrillation.18 Erturk et al. 13 demonstrated that the LA mechanical functions were impaired and AEMD was prolonged in patients with ASD compared with healthy individuals. However, they did not investigate the effect of the percutaneous ASO device placement on LA mechanical dysfunction and conduction delay. In this study, we aimed to investigate short- and mid-term effects of the percutaneous closure of ASD on atrial mechanical and conduction functions.
Methods
Conventional echocardiographic examination All transthoracic and transesophageal echocardiographic (TTE and TEE) examinations were performed using a machine (GE vivid S6, Horten, Norway) equipped with 2.5– 4 and 7.5 MHz transducers. All patients were examined in the left lateral and supine positions by 2D, M-mode, pulsed, and colour flow Doppler echocardiography. Single lead electrocardiogram was recorded continuously. The average of at least three cardiac cycles was obtained for all measurements. M-mode measurements and conventional Doppler echocardiographic examinations were performed according to the criteria of the European Society of Echocardiography guideline.19 The peak early E and late A mitral inflow velocities, deceleration time (DT), and E/A ratio were obtained from the apical four-chamber view with pulsed-wave (PW)
Doppler by placing a 1 – 2 mm sample volume between the tips of the mitral leaflets during diastole. The left and right atrium (RA) dimensions, LV end-systolic, and LV and RV end-diastolic dimensions were measured in the parasternal long-axis or apical four-chamber views. LV ejection fraction (EF) was estimated by Simpson’s rule. For the calculation of the systemic flow (Qs), mid-systolic LV outflow tract (LVOT) diameter and velocity – time integral (TVI) were obtained from the parasternal long-axis view and apical five-chamber view of LVOT with PW Doppler, respectively. For the calculation of the pulmonary flow (Qp), mid-systolic RV outflow tract (RVOT) diameter and TVI with PW Doppler were obtained from the modified parasternal short-axis view. Flows were calculated by the following formula: Qp ¼ [(RVOT diameter)2 × 0.785 × RVOT TVI] and Qs ¼ [(LVOT diameter)2 × 0.785 × LVOT TVI]. The Qp/Qs ratio was obtained by the division of the flows calculated by this formula.
Assessment of left atrial mechanical function LA volumes were determined at the mitral valve opening (maximal, Vmax), at the onset of atrial systole (P-wave of electrocardiogram, Vp), and at the mitral valve closure (minimal, Vmin) according to the modified Simpson method from the apical four- and two-chamber views. The average of these measurements was obtained. The following LA emptying function parameters were calculated: LA passive emptying volume ¼ Vmax 2 Vp, LA passive emptying fraction ¼ (Vmax 2 Vp)/Vmax, LA active emptying volume ¼ Vp 2 Vmin, LA active emptying fraction ¼ (Vp 2 Vmin)/Vp, conduit volume ¼ [LV stroke volume2 (Vmax 2Vmin)], and LA total emptying volume ¼ Vmax 2 Vmin. All volumes were indexed to the BSA and expressed in millilitres/metres squared.13
Assessment of AEMD and tissue Doppler imaging Doppler tissue echocardiography was performed using transducer frequencies between 3.5 and 4.0 MHz, by adjusting the spectral pulsedDoppler signal filters until a Nyquist limit of 15– 20 cm/s was reached, and using the minimal optimal gain. The monitor sweep speed was set at 50– 100 mm/s to optimize the spectral display of myocardial velocities. In the apical four-chamber view, the pulsed-Doppler sample volume was subsequently placed at the level of LV lateral mitral annulus, septal mitral annulus, and RV tricuspid annulus. Every effort was made to align the PW cursor so that the Doppler angle of incidence was as close to 0 as possible to the direction of these walls. The time interval from the onset of P-wave on surface ECG to the beginning of late diastolic wave (A-wave), which is called (PA) electromechanical delay, was obtained from lateral mitral annulus, septal mitral annulus, and RV tricuspid annulus and named as lateral PA, septal PA, and RV PA, respectively. The difference between septal PA and RV PA was defined as right intra-AEMD (septal PA– RV PA), the difference between lateral PA and septal PA was defined as left intra-AEMD (lateral PA– septal PA), and the difference between lateral PA and RV PA (lateral PA– RV PA) was defined as inter-AEMD (Figure 1).13 Changes (D) in LA and RA medio-lateral diameters, LA active emptying fraction, stroke volume, and LA and RA intra- and inter-AEMD were calculated by subtraction of the baseline values from the sixth month followup values. All echocardiographic evaluations were performed by the same investigator. To detect the intra-observer variability, the same investigator repeated the echocardiographic measurements of 10 patients.
Percutaneous ASD closure procedure Percutaneous closure of ASD was carried out using devices by Amplatzer Septal Occluder (AGA Medical, Plymouth, MN, USA) in 20 (48.8%)
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A total of 63 consecutive patients with secundum type ASD were evaluated. Ten patients with insufficient rims or large ASD, five patients with coronary artery disease (CAD), and three patients with severe mitral regurgitation were deemed not suitable for percutaneous closure. Also, four patients with atrial fibrillation were excluded from further analysis. Finally, the study consisted of 41 patients (27 female, 14 male, mean age: 41 + 13 years) with secundum type ASD and normal sinus rhythm who underwent successful percutaneous closure procedure. All of the patients were evaluated by clinical, electrocardiographic, and echocardiographic examinations before and after the procedure at the first day and sixth month. All the patients were informed and signed the consent form before the procedure. The institutional ethics committee approved the study protocol. The percutaneous closure procedure was performed in patients with symptomatic secundum type ASD and increased right ventricular (RV) volume overload (right heart chambers dilatation or Qp/Qs . 1.5) if the defect was at least 5 mm away from the mitral valve, tricuspid valve, coronary sinus, right upper pulmonary vein, inferior vena cava, and superior vena cava. Patients with sinus venosus or primum type ASD, other concomitant congenital heart disease, valvular heart disease, CAD, LV systolic dysfunction, atrial arrhythmias, or history of arrhythmia, pacemaker rhythm, on a medication that could affect the LA conduction, diabetes mellitus, hypertension, and obesity [body mass index (BMI) ≥ 30] were excluded from the study.
M. Aslan et al.
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patients, Cardi-o-Fix Septal Occluder (Starway Medical, PR China) in 18 (43.9%) patients and Occlutech Figulla-N septal Occluder (Occlutech GmbH, Germany) in 3 (7.3%) patients. Patients were divided into two groups according to the device type used. Amplatzer Septal Occluder was used in Group 1 and Cardi-o-Fix Septal Occluder or Occlutech Figulla-N septal Occluder was used in Group 2 patients. All procedures were performed under general anaesthesia and with the guidance of TEE. At least two orthogonal diameters of ASD were measured in TEE. Device size was determined by adding 2 – 4 mm depending on whether the defect has a loose edge. In addition, the distance to the defect is required to be at least 5 mm away from the mitral valve, tricuspid valve, coronary sinus, right upper pulmonary vein, inferior vena cava, and superior vena cava. In the case of aortic rim ,5 mm percutaneous closure was performed if the other rims have enough distances. Balloon measurement was not performed routinely.
Statistical analyses Statistical analyses were performed using the SPSS software version 17.0 for Windows (SPSS Inc., Chicago, IL, USA). The variables were investigated using analytical methods (Kolmogorov – Smirnov/Shapiro – Wilk’s test) to determine the normal distribution. Descriptive analyses are presented using means and SD. We assessed continuous variables between groups with Student’s t-test. The categorical variables are expressed as numbers and percentages. Changes in quantitative variables with the normal distribution over the time were analysed using repeated measures analysis of variance. If necessary, pairwise comparisons of dependent groups were compared using Student’s t-test. Changes in non-normally distributed variables (LVEF, Vmin, Vp, PA tricuspid, and left and right intra-AEMD) over the time were analysed using a Friedman test. If
necessary, pairwise comparisons were performed using the Wilcoxon test and the Bonferroni correction was applied. P , 0.017 was considered statistically significant for pairwise group comparisons. Correlation analysis was performed by using Spearman’s test. Intra-observer agreement was assessed with Pearson’s correlation coefficients. Total type-one error level was set at 5% for statistical significance.
Results Patient and procedure-related characteristics are summarized in Table 1. The mean diameter of ASD on echocardiographic evaluation was 20 + 5 mm (ranging from 9 to 32 mm). The average diameter of the devices used in these patients was 25 + 6 mm (ranging 15– 36 mm). There were no significant differences between two groups regarding the patient and procedure-related characteristics. The procedure was successfully completed in all of the 41 patients. Five patients had central shunt after release of the ASD closure device on TTE examination, which was viewed as negligible. No shunt was observed in any of the patients on echocardiographic evaluations at sixth month after the procedure. There were no significant changes in LV systolic diameter, LA diameter and DT after the procedure at the first day and sixth month on follow-up evaluations compared with pre-procedural measurements. RV, RA diameters, and mitral inflow A-waves amplitudes were decreased at the first day and at the sixth month compared with pre-procedural measurements. LV end-diastolic diameter,
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Figure 1: Measurement of the PA duration with TDI from the onset of P-wave on the surface electrocardiogram to the beginning of the late diastolic A′ -wave in lateral mitral annulus. Pre-procedure (A). Post-procedure first day (B). Post-procedure sixth month (C).
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Table 1
M. Aslan et al.
Clinical, demographic characteristics, and echocardiographic parameters of study subjects Total study population (n 5 41)
Variable
Group 1 (n 5 20)
Group 2 (n 5 21)
P-value
............................................................................................................................................................................... Age, years Systolic blood pressure, mmHg Diastolic blood pressure, mmHg
41 + 13
41 + 12
39 + 13
0.650
127 + 17 77 + 11
128 + 14 77 + 8
126 + 18 78 + 13
0.831 0.654
Heart rate, beats/min
79 + 13
81 + 12
78 + 14
0.449
ASD diameter, mm Device diameter, mm
20 + 5 25 + 6
21 + 6 26 + 6
19 + 5 24 + 6
0.182 0.360
Qp/Qs ratio
2.4 + 1.0
2.6 + 1.1
2.2 + 0.9
0.080
BMI, kg/m2 Body surface area, m2
25 + 4 1.75 + 0.17
25 + 4 1.76 + 0.17
25 + 4 1.75 + 0.16
0.942 0.887
Gender, female, n (%)
27 (65.9)
15 (75)
12 (57.1)
0.228
ASD, atrial septal defect; Qp/Qs, pulmonary-to-systemic flow ratio.
Table 2
Effect of ASD device closure on conventional echocardiographic parameters Pre-procedure
Post-procedure first day
Post-procedure sixth month
P-value
............................................................................................................................................................................... 44 + 4 27 + 4
45 + 5 27 + 4
46 + 4 28 + 4
LV EF, %
65 + 2
66 + 2
67 + 3**
0.035
LA diameters, mm Antero-posterior
36 + 7
35 + 6
35 + 6
0.155
40 + 6
38 + 6
38 + 7
0.057
50 + 6
50 + 5
49 + 6
0.088
38 + 7
36 + 6
34 + 5**
49 + 7 41 + 4
46 + 5 39 + 4
44 + 4 37 + 4
Medio-lateral Apico-basal Right atrial diameters, mm Medio-lateral Apico-basal RV end-diastolic diameter, mm
,0.001* 0.120
0.001 ,0.001* ,0.001*
Mitral inflow peak E velocity (m/s)
0.81 + 0.2
0.87 + 0.2
0.93 + 0.2
,0.001*
Mitral inflow peak A velocity (m/s) Mitral E/A ratio
0.72 + 0.2 1.2 + 0.5
0.68 + 0.2 1.4 + 0.5
0.66 + 0.2 1.5 + 0.5
,0.001* ,0.001*
Mitral DT (ms)
220 + 54
223 + 52
224 + 52
0.885
LV, left ventricular; LA, left atrial; RV, right ventricular; DT, deceleration time. *P , 0.01 all groups compared with each other, **P , 0.01 compared with pre-closure.
LVEF, mitral inflow E-wave amplitudes and E/A ratio showed a progressive increase after the procedure (Table 2, Figure 2). Total emptying volume and fraction remained unchanged after the procedure. LA maximum, minimum and pre-systolic volumes, active emptying volume, and fractions were decreased at the first day and at the sixth month compared with pre-procedural volumes. LA passive emptying volume, passive emptying fraction, and conduit volume were increased at the first day and at the sixth month compared with pre-procedural volumes (Table 3). PA septal, PA lateral, PA tricuspid, and left and right intra- and interAEMD durations were not changed significantly at the first day after the procedure. However, these parameters were significantly shorter at the sixth month compared with baseline and postprocedural measurements at the first day (Table 4).
Changes (D) in the stroke volume and LA medio-lateral diameter were not correlated with the change in the LA active emptying fraction (r ¼ 0.081, P ¼ 0.615 and r ¼ 0.087, P ¼ 0.589, respectively). Change (D) in the LA medio-lateral diameter was correlated with left intra-AEMD, but were not correlated with right intra- and inter-AEMD (r ¼ 0.348, P ¼ 0.024, r ¼ 0.027, P ¼ 0.868, and r ¼ 0.039, P ¼ 0.810, respectively). Change in the RA medio-lateral diameter was not correlated with left intra-AEMD, but was correlated with right intra- and inter-AEMD (r ¼ 0.124, P ¼ 0.438, r ¼ 0.449, P ¼ 0.003, and r ¼ 0.411, P ¼ 0.008, respectively). Group 1 and Group 2 were compared for the parameters indicated in Tables 2– 4. No significant differences were found between the two groups regarding these parameters (for all P . 0.05, Figure 3).
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LV end-diastolic diameter, mm LV end-systolic diameter, mm
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Table 3
Effect of ASD device closure on LA volume and mechanical function Pre-procedure
Post-procedure first day
Post-procedure sixth month
P-value
33.7 + 9.8* 15.2 + 8.2*
32.5 + 8.5 14.4 + 6.6**
31.7 + 8.4*** 13.4 + 5.5
0.017 0.007 ,0.001
............................................................................................................................................................................... LA maximal volume at end-systole (Vmax, mL/m2) LA minimal volume at end-diastole (Vmin, mL/m2) Volume at the beginning of atrial systole (Vp, mL/m2)
22.2 + 9.3*
19.6 + 7.5**
17.5 + 6.3***
Total emptying volume (mL/m2) Total emptying fraction (%)
18.5 + 5.8 55.9 + 12.7
18.2 + 5.2 56.7 + 11.1
18.3 + 5.7 57.8 + 10.1
0.808 0.319
Passive emptying volume (mL/m2)
11.5 + 4.5*
12.9 + 4.2**
14.3 + 5.1***
,0.001
Passive emptying fraction (%) Conduit volume (mL/m2)
34.8 + 10.7* 40.1 + 10.4*
40.1 + 10.0** 56.3 + 14.1**
44.8 + 12.1*** 58.6 + 14.3
,0.001 ,0.001
Active emptying volume (mL/m2) Active emptying fraction (%)
7.0 + 3.7*
5.3 + 3.1**
4.1 + 2.5***
,0.001
32.6 + 14.1*
27.5 + 13.4**
23.2 + 9.3***
,0.001
*P , 0.01 compared with post-procedure sixth month, **P , 0.01 compared with pre-procedure, ***P , 0.01 compared with post-procedure first day.
High intra-observer correlation was found between LA volume and PA duration parameters (r ¼ 0.94, P ¼ 0.01 and r ¼ 0.89, P ¼ 0.01, respectively).
Discussion In our study, after percutaneous ASD closure (i) LV diastolic diameter, LVEF, mitral inflow E-wave amplitudes were progressively
increased due to increased preload. Right atrial and RV diameters were progressively decreased due to decreased volume overload on the right heart chambers, (ii) Reservoir function of LA remained unchanged, conduit function was increased and the contractile function was decreased, and (iii) right and left intra- and inter-AEMD were not changed in early post-procedural period but was decreased in mid-term follow-up. These changes were not affected by the device type used.
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Figure 2: Heart chamber diameters in patients with ASD pre-procedure, post-procedure first day and sixth month. LVEDD, left ventricular enddiastolic diameter; RVED, RV end-diastolic diameter; LAMLD, left atrial medio-lateral diameter; RAMLD, right atrial medio-lateral diameter.
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Table 4
M. Aslan et al.
Effect of ASD device closure on LAEMD measured by TDI Pre-procedure
Post-procedure first day
Post-procedure sixth month
P-value
............................................................................................................................................................................... PA lateral (ms)
64.8 + 19.5
64.2 + 19.3
53.5 + 15.2*
,0.001
PA septal (ms) PA tricuspid (ms)
54.2 + 16.8 36.7 + 13.3
54.1 + 16.6 36.4 + 13.3
48.1 + 15.6* 33.9 + 12.7*
,0.001 ,0.001
Left intra-atrial (PA lateral–PA septum) (ms)
10.6 + 10.7
10.2 + 9.7
5.5 + 5.9**
0.024
Right intra-atrial (PA septum– PA tricuspid) (ms) Inter-atrial (PA lateral–PA tricuspid) (ms)
17.5 + 13.9 28.0 + 16.9
17.6 + 13.7 27.7 + 17.2
14.1 + 12.7* 19.6 + 13.1*
,0.001 ,0.001
LA, left atrial. *P , 0.001 compared with pre-procedure and post-procedure first day, **P , 0.01 compared with pre-procedure and post-procedure first day.
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Figure 3: Comparison of the change in the atrial active emptying fraction (A) and change in the inter-AEMD (B) over the time (P , 0.001 and P , 0.001, respectively) and between two groups (P . 0.05 and P . 0.05, respectively).
In healthy subjects all of the blood returning to LA via pulmonary veins pass the mitral valve and fill the left ventricle. However, in untreated ASD patients a portion of this blood pass through the defect to the RA and from there to the right ventricle due to better compliance and lower resistance of LV and cause chronic RV volume overload. Chronic RV overload and reduced LV preload result in decreased early LV filling and systolic function.20,21 RV volume overload decreases and LV filling volume increases after percutaneous closure of ASD, which result in decreased right heart chamber diameter, decreased pulmonary arterial hypertension, and increased LV end-diastolic diameter and EF.12,22,23 Our study also demonstrated that there were significant decrease in the RA and RV diameters and increase in LV diastolic diameter and EF after percutaneous closure at the first day and sixth month follow-up compared with pre-procedural values. In accordance with a study by Santoro et al. we also observed a decrease in LA diameter after the procedure, which was not statistically significant.24 LV filling is regulated by three different functions of the left atrium: storage, conduction, and contraction. In healthy individuals, LA
conduction function which happens in early diastole correlates with diastolic mitral inflow E-wave, whereas contractile function correlates with late diastolic A-wave.25 Contraction of the left atrium in the last phase of the diastole contributes to 15–30% of the LV filling. This compensate for decreased filling volume, especially in patients with impaired LV compliance.26 Enlarged LA due to being exposed to volume overload by increasing the total volume and emptying fraction as an adaptive response ensures the continuity of cardiac stroke volume. However, with progressive dilatation of the LA, which eventually leads to a threshold fibre length, atrial shortening, and contractility begin to decline. Beyond the threshold, further enlargement will only result in the deterioration of atrial function.17 Erturk et al. 13 demonstrated that total and active emptying fractions that are indicators of LA’s mechanical function, mitral E-wave amplitude, and E/A ratio were decreased but maximal, minimal and pre-systolic volumes were increased in patients with ASD compared with the control group.13 Effects of percutaneous closure of ASD with ASO devices on mitral inflow waves and LA volumes have been studied but the mechanical function of LA has not been examined.
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with the baseline. However, Pac et al. 12 showed that Pd was increased in the early post-operative period and this increase was correlated with device size and device atrial disc diameter. Results of our study were in compliance with the results of both studies. We found that right inter-AEMD and left intra-AEMD was not changed in the early post-operative period but were increased in the mid-term follow-up. Changes in the diameters were correlated with the change in atrial conduction. LA anatomically improved after percutaneous closure in the early post-operative period but there was no change in the electrical conduction of LA, which may result from mechanical stress created by the device or the acute inflammatory reaction developing against the foreign body.
Study limitation The small number of patients included in the study is the main limitation of our study. Percutaneous closure was performed using three different ASOs and one of them was used only in three patients. Therefore, we did not evaluate the effect of the particular device on LA mechanical and conduction functions. We also did not do Holter ECG monitoring but, all of the patients were evaluated by the ECG at baseline, at the first day and sixth month for any arrhythmia. Twenty-four hour Holter ECG monitoring would have been very helpful to discover any arrhythmia, especially the paroxysmal atrial fibrillation.
Conclusion In this study, we found that the LA reservoir function as an indicator of the mechanical function was not affected, conduction function was improved and contractile function was deteriorated in both early and mid-term follow-up. Also, AEMD was decreased in mid-term follow-up after percutaneous closure of ASD. This may provide decreased risk for atrial fibrillation development, which is an important cause of morbidity and mortality in patients with ASD not treated with closure at the later stage. Conflict of interest: none declared.
References 1. Baumgartner H, Bonhoeffer P, De Groot NM, de Haan F, Deanfield JE, Galie N et al. ESC guidelines for the management of grown-up congenital heart disease. Eur Heart J 2010;31:2915 – 57. 2. Bergera F, Vogeld M, Kretschmarb O, Dave H, Preˆtre R, Dodge-Khatami A. Arrhythmias in patients with surgically treated atrial septal defects. Swiss Med Wkly 2005;135: 175 –8. 3. Du ZD, Hijazi ZM, Kleinman CS, Silverman NH, Larntz K. Comparison between transcatheter and surgical closure of secundum atrial septal defect in children and adults: results of a multicenter trial. J Am Coll Cardiol 2002;39:1836 – 44. 4. Masura J, Gavora P, Formanek A, Hijazi ZM. Transcatheter closure of secundum atrial septal defects using the new self-centering Amplatzer septal occluder: initial human experience. Cathet Cardiovasc Diagn 1997;42:388–93. 5. Lange A, Coleman MD, Palka P, Burstow DJ, Wilkinson JL, Godman MJ. Effect of catheter device closure of atrial septal defect on diastolic mitral annular motion. Am J Cardiol 2003;91:104 – 8. 6. Di Salvo G, Drago M, Pacileo G, Rea A, Carrozza M, Santoro G et al. Atrial function after surgical and percutaneous closure of atrial septal defect: a strain rate imaging study. J Am Soc Echocardiogr 2005;18:930–3. 7. Di Salvo G, Pacileo G, Castaldi B, Gala S, Morelli C, D’Andrea A et al. Twodimensional strain and atrial function: a study on patients after percutaneous closure of atrial septal defect. Eur J Echocardiogr 2009;10:256 – 9. 8. Boyd CA, Cooper M, Thomas L. Segmental atrial function following percutaneous closure of atrial septum using occluder device. J Am Soc Echocardiogr 2009;22: 508 –16.
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It is known that mitral inflow E-wave and E/A ratio increases and mitral inflow A-wave decreases after percutaneous ASD closure as it was shown in this study.5 We also showed that, Vmax, Vmin, and Vpre volumes and the contractile function of the LA were decreased, reservoir function remained unchanged and conduction function was increased after percutaneous closure at the first day and sixth month follow-up compared with the baseline in this study. Early diastolic filling is determined by pressure difference between the LV and LA but the late diastolic filling is an active event and determined by the LV compliance, LA relaxation, LA stiffness, mitral annular motion, and LA pump function. Increase in the mitral inflow E-wave and LA conduit function could be resulted from the passage of the all blood in the LA to the LV in the early diastole and from the diminished pressure exerted on LV by the diastolic RV volume overload. And also, the decrease in the mitral inflow A-wave and LA pump function could be related to decreased contractile function of the LA secondary to the device placed in the inter-atrial septum and/or to the decreased need for atrial contribution of the LV diastolic filling. Lange et al. 5 also showed that mitral inflow A-wave amplitude was increased in patients with ASD compared with the control group and A-wave amplitude was decreased after closure of the ASD with the device. Boyd et al. evaluated LA function in 23 ASD patients after percutaneous closure with the device after 6 months follow-up with strain and strain rate and found that the function was decreased being more pronounced in the mid-septal atrial region. They suggested that this localized atrial dysfunction may be due to the direct mechanical effect of the device.8 Di Salvo et al. 7 evaluated children with ASD who underwent percutaneous closure with device at 1 year after the procedure with speckle tracking strain and found that there was no deformation in the region of the device. In two separate studies performed by using echocardiography or cardiac MRI it was discovered that the LA maximal volume was decreased after the procedure compared with baseline but the differences were not statistically significant.27,28 However, a decrease in the LA maximal volume was statistically significant in our study. In comparison with the abovementioned studies performed by using either echocardiography or cardiac MRI, the follow-up period was longer and the mean age of the patients was younger in our study population than in those studies.27,28 Increase in atrial diameter and volume are known to cause increased conduction time and non-homogeneous propagation of sinus impulses. Echocardiographic AEMD measurement with tissue Doppler imaging (TDI) has been used in several disorders and found to be correlated with P-wave dispersion (Pd) measured by electrocardiography.29 Erturk et al. 13 compared the atrial conduction time measured with TDI echocardiography in patients with large secundum type ASD and healthy control group. They found that the left and right intra-and inter-AEMD durations were prolonged in patients with ASD.13 Guray et al. demonstrated that Pd was increased in patients with surgically closed ASD, compared with the control group before the procedure but Pd was decreased during the follow-up at post-operative 6th and 12th months compared with the baseline.30 In a study comparing the effect of surgical vs. percutaneous ASD closure on the Pd at the end of the first postoperative week, a decrease in Pd was observed only in the surgically closed group.31 Kaya et al. 11 showed that Pd was decreased in the mid-term follow-up after ASD closure with a device compared
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21. Masutani S, Senzaki H. Left ventricular function in adult patients with atrial septal defect: Implication for development of heart failure after transcatheter closure. J Cardiac Fail 2011;17:957–63. 22. Pascotto M, Santoro G, Caso P, Cerrato F, Caso I, Caputo S et al. Global and regional left ventricular function in patients undergoing transcatheter closure of secundum atrial septal defect. Am J Cardiol 2005;96:439 –42. 23. Pascotto M, Santoro G, Cerrato F, Caputo S, Bigazzi MC, Iacono C et al. Time-course of cardiac remodeling following transcatheter closure of atrial septal defect. Int J Cardiol 2006;112:348 –52. 24. Santoro G, Pascotto M, Sarubbi B, Cappelli Bigazzi M, Calvanese R, Iacono C et al. Early electrical and geometric changes after percutaneous closure of large atrial septal defect. Am J Cardiol 2004;93:876 –80. 25. Triposkiadis F, Tentolouris K, Androulakis A, Trikas A, Toutouzas K, Kyriakidis M et al. Left atrial mechanical function in the healthy elderly: new insights from a combined assessment of changes in atrial volume and transmitral flow velocity. J Am Soc Echocardiogr 1995;8:801 – 9. 26. Matsuda Y, Toma Y, Ogawa H, Matsuzaki M, Katayama K, Fujii T et al. Importance of left atrial function in patients with myocardial infarction. Circulation 1983;67: 5666 –71. 27. Fang F, Yu CM, Sanderson JE, Luo XX, Jiang X, Yip GW et al. Prevalence and determinants of incomplete right atrial reverse remodeling after device closure of atrial septal defects. Am J Cardiol 2011;108:114 –9. 28. Teo KSL, Dundon BK, Molaee P, Williams KF, Carbone A, Brown MA et al. Percutaneous closure of atrial septal defects leads to normalisation of atrial and ventricular volumes. J Cardiovasc Magn Reson 2008;10:55. 29. Ozer N, Yavuz B, Can I, Atalar E, Akso¨yek S, Ovu¨nc¸ K et al. Doppler tissue evaluation of intra-atrial and inter-atrial electromechanical delay and comparison with P-wave dispersion in patients with mitral stenosis. J Am Soc Echocardiogr 2005;18: 945 – 8. 30. Guray U, Guray Y, Mecit B, Yilmaz MB, Sasmaz H, Korkmaz S. Maximum p wave duration and p wave dispersion in adult patients with secundum atrial septal defect: the impact of surgical repair. Ann Noninvasive Electrocardiol 2004;9: 136 – 41. 31. Bas¸pınar O, Sucu M, Koruk S, Kervancioglu M, Ustunsoy H, Deniz H et al. P-wave dispersion between transcatheter and surgical closure of secundum-type atrial septal defect in childhood. Cardiol Young 2011;21:15–8.
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9. Morton JB, Sanders P, Vohra JK, Sparks PB, Morgan JG, Spence SJ et al. Effect of chronic right atrial stretch on atrial electrical remodeling in patients with an atrial septal defect. Circulation 2003;107:1775 –82. Epub 10 March 2003. 10. Deniz A, Yavuz B, Aytemir K, Hayran M, Kose S, Okutucu S et al. Intra-left atrial mechanical delay detected by tissue Doppler echocardiography can be a useful marker for paroxysmal atrial fibrilation. Echocardiography 2009;26:779 – 84. 11. Kaya MG, Ozdog˘ru I, Baykan A, Dog˘an A, Inanc¸ T, Dog˘du O et al. Transcatheter closure of secundum atrial septal defects using the Amplatzer septal occluder in adult patients: our first clinical experiences. Arch Turk Soc Cardiol 2008;36:287 –93. 12. Pac FA, Balli S, Topalog˘lu S, Ece I, Oflaz MB. Analysis of maximum P-wave duration and dispersion after percutaneous closure of atrial septal defects: comparison of two septal occluders. Anadolu Kardiyol Derg 2012;12:249 –54. 13. Erturk M, Aslan M, Aksu HU, Akturk IF, Gul M, Uzun F et al. Evaluation of atrial electromechanic delay and left atrial mechanical functions in the patients with secundum type atrial septal defect. Echocardiography 2013;30:699 – 705. 14. Oflaz MB, Karapinar H, Kucukdurmaz Z, Guven AS, Gumrukcuoglu HA, Sarikaya S et al. Is atrial electromechanical coupling delayed in patients with secundum atrial septal defect. Echocardiography 2013;30:706 –11. 15. Bolens M, Freidli B. Sinus node function and conduction system before and after surgery for secundum atrial septal defect: an electrophysiologic study. Am J Cardiol 1984;53:1415 – 20. 16. Priorli A, Marino P, Lanzoni L, Zardini P. Increasing degrees of left ventricular filling impairment modulate left atrial function in humans. Am J Cardiol 1998;82:756 –61. 17. Tsang TSM. Echocardiography in cardiovascular public health: the Fheigenbaum Lecture 2008. J Am Soc Echocardiogr 2009;22:649–56. 18. Abhayaratna WP, Fatema K, Barnes ME, Seward JB, Gersh BJ, Bailey KR et al. Left atrial reservoir function as a potent marker for first atrial fibrillation or flutter in persons . or¼65 years of age. Am J Cardiol 2008;101:1626 – 9. 19. Lang RM, Biering M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, Developed in Conjunction with the European Association of Echocardiography, a branch of the European Society Of Cardiology. Eur J Echocardiogr 2006;7:79 –108. 20. Papio KA, Gorlin R, Teichholz LE, Cohn PF, Bechtel D, Herman MV. Abnormalties of left ventricular and geometry in adults with an atrial septal defect. Ventriculographic, hemodynamic and echocardiographic studies. Am J Cardiol 1975;36:302 –8.
M. Aslan et al.
Effects of percutaneous closure of atrial septal defect on left atrial mechanical and conduction functions Muzaffer Aslan, Mehmet Erturk*, Selahattin Turen, Fatih Uzun, Ozgur Surgit, Sinem Ozbay Ozyilmaz, Mehmet Rifat Yildirim, Omer Faruk Baycan, Begum Uygur, Aydin Yildirim, and Abdurrahman Eksik ¨ zal Bulvarı No:11 Ku¨c¸u¨kc¸ekmece, Department of Cardiology, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, ˙Istasyon Mah. Turgut O 34303 Istanbul, Turkey Received 11 February 2014; accepted after revision 18 April 2014; online publish-ahead-of-print 22 May 2014
Aims
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
percutaneous closure † secundum atrial septal defect † atrial electromechanical delay † left atrial mechanical function
Introduction Atrial septal defect (ASD) is the most common type of congenital heart disease in the adults and 65– 70% of all defects are secundum type, which is located at the region of fossa ovalis. This lesion is sometimes associated with the development of pulmonary hypertension, impaired aerobic capacity, and atrial arrhythmias.1 Atrial arrhythmias are the most common type of tachyarrhythmia encountered in the clinical practice and are associated with increased morbidity and mortality.2 Definitive treatment of ASD can be done by surgical closure and more recently by percutaneous closure using atrial septal occluder
(ASO) devices.1 Numerous studies have shown that percutaneous closure with ASOs is a safe technique in appropriately selected patients.3,4 However, the impact of the placement of an occluder device on subsequent atrial function has been investigated only in a limited number of studies.5 – 8 The atrial diameters and the volumes are increased in ASD patients due to volume overload. It is known that increased atrial diameters and volume cause prolongation of conduction time and nonhomogenous propagation of sinus node impulses.9 The prolongation of atrial electromechanical delay (AEMD) and inhomogeneous propagation of the sinus impulses are well-known electrophysiological characteristics of the atria prone to fibrillation.10 AEMD can
* Corresponding author. Tel: +90 212 692 20 00; Fax: +90 212 471 94 94, E-mail: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected].
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Atrial septal defect (ASD) is one of the most common congenital heart diseases in adults. We prospectively evaluated early and mid-term effects of the percutaneous closure of secundum ASD on atrial electromechanical delay (AEMD) and left atrial (LA) mechanical functions at the first day and sixth month in patients undergoing percutaneous closure. ..................................................................................................................................................................................... Methods Forty-one patients were included in this study. Twenty-six (63.4%) of the 41 patients were female and the mean age was and results 41 + 13 years. All the patients had echocardiographic examination before the procedure and at the first day and sixth month after the procedure. LA volumes (maximal, minimal, and presystolic) and EMD (lateral, septal, and tricuspid) were measured. Left and right intra- and inter-AEMD were not changed at the first day but both were significantly shorter at the sixth month. There was no change in the total emptying volume and fraction before and after the procedure. LA maximal, minimal, and pre-systolic volumes, active emptying volume, and fractions were decreased at the first day and at the sixth month compared with pre-procedural volumes. LA passive emptying volume, passive emptying fraction, and conduit volume were increased at the first day and at the sixth month compared with pre-procedural volumes. ..................................................................................................................................................................................... Conclusion Our results revealed that there was no change in the LA mechanical reservoir functions, but improved conduit function and impaired contractility functions early and in the mid-term after percutaneous closure of ASD and decreased AEMD only in the mid-term.
1118 be measured with electrocardiographic, echocardiographic, and electrophysiological methods in patients with ASD.9,11 – 15 The left atrial (LA) mechanical function is an important determinant of left ventricular (LV) filling, especially in patients with end-stage systolic or diastolic ventricular dysfunction, LV hypertrophy, and diminished LV enlargement capacity.16 LA mechanical functions consist of reservoir, conduit, and booster pump functions at different stages of the cardiac cycle.17 Impaired mechanical functions have been associated with increased risk of atrial fibrillation.18 Erturk et al. 13 demonstrated that the LA mechanical functions were impaired and AEMD was prolonged in patients with ASD compared with healthy individuals. However, they did not investigate the effect of the percutaneous ASO device placement on LA mechanical dysfunction and conduction delay. In this study, we aimed to investigate short- and mid-term effects of the percutaneous closure of ASD on atrial mechanical and conduction functions.
Methods
Conventional echocardiographic examination All transthoracic and transesophageal echocardiographic (TTE and TEE) examinations were performed using a machine (GE vivid S6, Horten, Norway) equipped with 2.5– 4 and 7.5 MHz transducers. All patients were examined in the left lateral and supine positions by 2D, M-mode, pulsed, and colour flow Doppler echocardiography. Single lead electrocardiogram was recorded continuously. The average of at least three cardiac cycles was obtained for all measurements. M-mode measurements and conventional Doppler echocardiographic examinations were performed according to the criteria of the European Society of Echocardiography guideline.19 The peak early E and late A mitral inflow velocities, deceleration time (DT), and E/A ratio were obtained from the apical four-chamber view with pulsed-wave (PW)
Doppler by placing a 1 – 2 mm sample volume between the tips of the mitral leaflets during diastole. The left and right atrium (RA) dimensions, LV end-systolic, and LV and RV end-diastolic dimensions were measured in the parasternal long-axis or apical four-chamber views. LV ejection fraction (EF) was estimated by Simpson’s rule. For the calculation of the systemic flow (Qs), mid-systolic LV outflow tract (LVOT) diameter and velocity – time integral (TVI) were obtained from the parasternal long-axis view and apical five-chamber view of LVOT with PW Doppler, respectively. For the calculation of the pulmonary flow (Qp), mid-systolic RV outflow tract (RVOT) diameter and TVI with PW Doppler were obtained from the modified parasternal short-axis view. Flows were calculated by the following formula: Qp ¼ [(RVOT diameter)2 × 0.785 × RVOT TVI] and Qs ¼ [(LVOT diameter)2 × 0.785 × LVOT TVI]. The Qp/Qs ratio was obtained by the division of the flows calculated by this formula.
Assessment of left atrial mechanical function LA volumes were determined at the mitral valve opening (maximal, Vmax), at the onset of atrial systole (P-wave of electrocardiogram, Vp), and at the mitral valve closure (minimal, Vmin) according to the modified Simpson method from the apical four- and two-chamber views. The average of these measurements was obtained. The following LA emptying function parameters were calculated: LA passive emptying volume ¼ Vmax 2 Vp, LA passive emptying fraction ¼ (Vmax 2 Vp)/Vmax, LA active emptying volume ¼ Vp 2 Vmin, LA active emptying fraction ¼ (Vp 2 Vmin)/Vp, conduit volume ¼ [LV stroke volume2 (Vmax 2Vmin)], and LA total emptying volume ¼ Vmax 2 Vmin. All volumes were indexed to the BSA and expressed in millilitres/metres squared.13
Assessment of AEMD and tissue Doppler imaging Doppler tissue echocardiography was performed using transducer frequencies between 3.5 and 4.0 MHz, by adjusting the spectral pulsedDoppler signal filters until a Nyquist limit of 15– 20 cm/s was reached, and using the minimal optimal gain. The monitor sweep speed was set at 50– 100 mm/s to optimize the spectral display of myocardial velocities. In the apical four-chamber view, the pulsed-Doppler sample volume was subsequently placed at the level of LV lateral mitral annulus, septal mitral annulus, and RV tricuspid annulus. Every effort was made to align the PW cursor so that the Doppler angle of incidence was as close to 0 as possible to the direction of these walls. The time interval from the onset of P-wave on surface ECG to the beginning of late diastolic wave (A-wave), which is called (PA) electromechanical delay, was obtained from lateral mitral annulus, septal mitral annulus, and RV tricuspid annulus and named as lateral PA, septal PA, and RV PA, respectively. The difference between septal PA and RV PA was defined as right intra-AEMD (septal PA– RV PA), the difference between lateral PA and septal PA was defined as left intra-AEMD (lateral PA– septal PA), and the difference between lateral PA and RV PA (lateral PA– RV PA) was defined as inter-AEMD (Figure 1).13 Changes (D) in LA and RA medio-lateral diameters, LA active emptying fraction, stroke volume, and LA and RA intra- and inter-AEMD were calculated by subtraction of the baseline values from the sixth month followup values. All echocardiographic evaluations were performed by the same investigator. To detect the intra-observer variability, the same investigator repeated the echocardiographic measurements of 10 patients.
Percutaneous ASD closure procedure Percutaneous closure of ASD was carried out using devices by Amplatzer Septal Occluder (AGA Medical, Plymouth, MN, USA) in 20 (48.8%)
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A total of 63 consecutive patients with secundum type ASD were evaluated. Ten patients with insufficient rims or large ASD, five patients with coronary artery disease (CAD), and three patients with severe mitral regurgitation were deemed not suitable for percutaneous closure. Also, four patients with atrial fibrillation were excluded from further analysis. Finally, the study consisted of 41 patients (27 female, 14 male, mean age: 41 + 13 years) with secundum type ASD and normal sinus rhythm who underwent successful percutaneous closure procedure. All of the patients were evaluated by clinical, electrocardiographic, and echocardiographic examinations before and after the procedure at the first day and sixth month. All the patients were informed and signed the consent form before the procedure. The institutional ethics committee approved the study protocol. The percutaneous closure procedure was performed in patients with symptomatic secundum type ASD and increased right ventricular (RV) volume overload (right heart chambers dilatation or Qp/Qs . 1.5) if the defect was at least 5 mm away from the mitral valve, tricuspid valve, coronary sinus, right upper pulmonary vein, inferior vena cava, and superior vena cava. Patients with sinus venosus or primum type ASD, other concomitant congenital heart disease, valvular heart disease, CAD, LV systolic dysfunction, atrial arrhythmias, or history of arrhythmia, pacemaker rhythm, on a medication that could affect the LA conduction, diabetes mellitus, hypertension, and obesity [body mass index (BMI) ≥ 30] were excluded from the study.
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patients, Cardi-o-Fix Septal Occluder (Starway Medical, PR China) in 18 (43.9%) patients and Occlutech Figulla-N septal Occluder (Occlutech GmbH, Germany) in 3 (7.3%) patients. Patients were divided into two groups according to the device type used. Amplatzer Septal Occluder was used in Group 1 and Cardi-o-Fix Septal Occluder or Occlutech Figulla-N septal Occluder was used in Group 2 patients. All procedures were performed under general anaesthesia and with the guidance of TEE. At least two orthogonal diameters of ASD were measured in TEE. Device size was determined by adding 2 – 4 mm depending on whether the defect has a loose edge. In addition, the distance to the defect is required to be at least 5 mm away from the mitral valve, tricuspid valve, coronary sinus, right upper pulmonary vein, inferior vena cava, and superior vena cava. In the case of aortic rim ,5 mm percutaneous closure was performed if the other rims have enough distances. Balloon measurement was not performed routinely.
Statistical analyses Statistical analyses were performed using the SPSS software version 17.0 for Windows (SPSS Inc., Chicago, IL, USA). The variables were investigated using analytical methods (Kolmogorov – Smirnov/Shapiro – Wilk’s test) to determine the normal distribution. Descriptive analyses are presented using means and SD. We assessed continuous variables between groups with Student’s t-test. The categorical variables are expressed as numbers and percentages. Changes in quantitative variables with the normal distribution over the time were analysed using repeated measures analysis of variance. If necessary, pairwise comparisons of dependent groups were compared using Student’s t-test. Changes in non-normally distributed variables (LVEF, Vmin, Vp, PA tricuspid, and left and right intra-AEMD) over the time were analysed using a Friedman test. If
necessary, pairwise comparisons were performed using the Wilcoxon test and the Bonferroni correction was applied. P , 0.017 was considered statistically significant for pairwise group comparisons. Correlation analysis was performed by using Spearman’s test. Intra-observer agreement was assessed with Pearson’s correlation coefficients. Total type-one error level was set at 5% for statistical significance.
Results Patient and procedure-related characteristics are summarized in Table 1. The mean diameter of ASD on echocardiographic evaluation was 20 + 5 mm (ranging from 9 to 32 mm). The average diameter of the devices used in these patients was 25 + 6 mm (ranging 15– 36 mm). There were no significant differences between two groups regarding the patient and procedure-related characteristics. The procedure was successfully completed in all of the 41 patients. Five patients had central shunt after release of the ASD closure device on TTE examination, which was viewed as negligible. No shunt was observed in any of the patients on echocardiographic evaluations at sixth month after the procedure. There were no significant changes in LV systolic diameter, LA diameter and DT after the procedure at the first day and sixth month on follow-up evaluations compared with pre-procedural measurements. RV, RA diameters, and mitral inflow A-waves amplitudes were decreased at the first day and at the sixth month compared with pre-procedural measurements. LV end-diastolic diameter,
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Figure 1: Measurement of the PA duration with TDI from the onset of P-wave on the surface electrocardiogram to the beginning of the late diastolic A′ -wave in lateral mitral annulus. Pre-procedure (A). Post-procedure first day (B). Post-procedure sixth month (C).
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Table 1
M. Aslan et al.
Clinical, demographic characteristics, and echocardiographic parameters of study subjects Total study population (n 5 41)
Variable
Group 1 (n 5 20)
Group 2 (n 5 21)
P-value
............................................................................................................................................................................... Age, years Systolic blood pressure, mmHg Diastolic blood pressure, mmHg
41 + 13
41 + 12
39 + 13
0.650
127 + 17 77 + 11
128 + 14 77 + 8
126 + 18 78 + 13
0.831 0.654
Heart rate, beats/min
79 + 13
81 + 12
78 + 14
0.449
ASD diameter, mm Device diameter, mm
20 + 5 25 + 6
21 + 6 26 + 6
19 + 5 24 + 6
0.182 0.360
Qp/Qs ratio
2.4 + 1.0
2.6 + 1.1
2.2 + 0.9
0.080
BMI, kg/m2 Body surface area, m2
25 + 4 1.75 + 0.17
25 + 4 1.76 + 0.17
25 + 4 1.75 + 0.16
0.942 0.887
Gender, female, n (%)
27 (65.9)
15 (75)
12 (57.1)
0.228
ASD, atrial septal defect; Qp/Qs, pulmonary-to-systemic flow ratio.
Table 2
Effect of ASD device closure on conventional echocardiographic parameters Pre-procedure
Post-procedure first day
Post-procedure sixth month
P-value
............................................................................................................................................................................... 44 + 4 27 + 4
45 + 5 27 + 4
46 + 4 28 + 4
LV EF, %
65 + 2
66 + 2
67 + 3**
0.035
LA diameters, mm Antero-posterior
36 + 7
35 + 6
35 + 6
0.155
40 + 6
38 + 6
38 + 7
0.057
50 + 6
50 + 5
49 + 6
0.088
38 + 7
36 + 6
34 + 5**
49 + 7 41 + 4
46 + 5 39 + 4
44 + 4 37 + 4
Medio-lateral Apico-basal Right atrial diameters, mm Medio-lateral Apico-basal RV end-diastolic diameter, mm
,0.001* 0.120
0.001 ,0.001* ,0.001*
Mitral inflow peak E velocity (m/s)
0.81 + 0.2
0.87 + 0.2
0.93 + 0.2
,0.001*
Mitral inflow peak A velocity (m/s) Mitral E/A ratio
0.72 + 0.2 1.2 + 0.5
0.68 + 0.2 1.4 + 0.5
0.66 + 0.2 1.5 + 0.5
,0.001* ,0.001*
Mitral DT (ms)
220 + 54
223 + 52
224 + 52
0.885
LV, left ventricular; LA, left atrial; RV, right ventricular; DT, deceleration time. *P , 0.01 all groups compared with each other, **P , 0.01 compared with pre-closure.
LVEF, mitral inflow E-wave amplitudes and E/A ratio showed a progressive increase after the procedure (Table 2, Figure 2). Total emptying volume and fraction remained unchanged after the procedure. LA maximum, minimum and pre-systolic volumes, active emptying volume, and fractions were decreased at the first day and at the sixth month compared with pre-procedural volumes. LA passive emptying volume, passive emptying fraction, and conduit volume were increased at the first day and at the sixth month compared with pre-procedural volumes (Table 3). PA septal, PA lateral, PA tricuspid, and left and right intra- and interAEMD durations were not changed significantly at the first day after the procedure. However, these parameters were significantly shorter at the sixth month compared with baseline and postprocedural measurements at the first day (Table 4).
Changes (D) in the stroke volume and LA medio-lateral diameter were not correlated with the change in the LA active emptying fraction (r ¼ 0.081, P ¼ 0.615 and r ¼ 0.087, P ¼ 0.589, respectively). Change (D) in the LA medio-lateral diameter was correlated with left intra-AEMD, but were not correlated with right intra- and inter-AEMD (r ¼ 0.348, P ¼ 0.024, r ¼ 0.027, P ¼ 0.868, and r ¼ 0.039, P ¼ 0.810, respectively). Change in the RA medio-lateral diameter was not correlated with left intra-AEMD, but was correlated with right intra- and inter-AEMD (r ¼ 0.124, P ¼ 0.438, r ¼ 0.449, P ¼ 0.003, and r ¼ 0.411, P ¼ 0.008, respectively). Group 1 and Group 2 were compared for the parameters indicated in Tables 2– 4. No significant differences were found between the two groups regarding these parameters (for all P . 0.05, Figure 3).
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LV end-diastolic diameter, mm LV end-systolic diameter, mm
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Percutaneous closure of atrial septal defect and left atrial function
Table 3
Effect of ASD device closure on LA volume and mechanical function Pre-procedure
Post-procedure first day
Post-procedure sixth month
P-value
33.7 + 9.8* 15.2 + 8.2*
32.5 + 8.5 14.4 + 6.6**
31.7 + 8.4*** 13.4 + 5.5
0.017 0.007 ,0.001
............................................................................................................................................................................... LA maximal volume at end-systole (Vmax, mL/m2) LA minimal volume at end-diastole (Vmin, mL/m2) Volume at the beginning of atrial systole (Vp, mL/m2)
22.2 + 9.3*
19.6 + 7.5**
17.5 + 6.3***
Total emptying volume (mL/m2) Total emptying fraction (%)
18.5 + 5.8 55.9 + 12.7
18.2 + 5.2 56.7 + 11.1
18.3 + 5.7 57.8 + 10.1
0.808 0.319
Passive emptying volume (mL/m2)
11.5 + 4.5*
12.9 + 4.2**
14.3 + 5.1***
,0.001
Passive emptying fraction (%) Conduit volume (mL/m2)
34.8 + 10.7* 40.1 + 10.4*
40.1 + 10.0** 56.3 + 14.1**
44.8 + 12.1*** 58.6 + 14.3
,0.001 ,0.001
Active emptying volume (mL/m2) Active emptying fraction (%)
7.0 + 3.7*
5.3 + 3.1**
4.1 + 2.5***
,0.001
32.6 + 14.1*
27.5 + 13.4**
23.2 + 9.3***
,0.001
*P , 0.01 compared with post-procedure sixth month, **P , 0.01 compared with pre-procedure, ***P , 0.01 compared with post-procedure first day.
High intra-observer correlation was found between LA volume and PA duration parameters (r ¼ 0.94, P ¼ 0.01 and r ¼ 0.89, P ¼ 0.01, respectively).
Discussion In our study, after percutaneous ASD closure (i) LV diastolic diameter, LVEF, mitral inflow E-wave amplitudes were progressively
increased due to increased preload. Right atrial and RV diameters were progressively decreased due to decreased volume overload on the right heart chambers, (ii) Reservoir function of LA remained unchanged, conduit function was increased and the contractile function was decreased, and (iii) right and left intra- and inter-AEMD were not changed in early post-procedural period but was decreased in mid-term follow-up. These changes were not affected by the device type used.
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Figure 2: Heart chamber diameters in patients with ASD pre-procedure, post-procedure first day and sixth month. LVEDD, left ventricular enddiastolic diameter; RVED, RV end-diastolic diameter; LAMLD, left atrial medio-lateral diameter; RAMLD, right atrial medio-lateral diameter.
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Table 4
M. Aslan et al.
Effect of ASD device closure on LAEMD measured by TDI Pre-procedure
Post-procedure first day
Post-procedure sixth month
P-value
............................................................................................................................................................................... PA lateral (ms)
64.8 + 19.5
64.2 + 19.3
53.5 + 15.2*
,0.001
PA septal (ms) PA tricuspid (ms)
54.2 + 16.8 36.7 + 13.3
54.1 + 16.6 36.4 + 13.3
48.1 + 15.6* 33.9 + 12.7*
,0.001 ,0.001
Left intra-atrial (PA lateral–PA septum) (ms)
10.6 + 10.7
10.2 + 9.7
5.5 + 5.9**
0.024
Right intra-atrial (PA septum– PA tricuspid) (ms) Inter-atrial (PA lateral–PA tricuspid) (ms)
17.5 + 13.9 28.0 + 16.9
17.6 + 13.7 27.7 + 17.2
14.1 + 12.7* 19.6 + 13.1*
,0.001 ,0.001
LA, left atrial. *P , 0.001 compared with pre-procedure and post-procedure first day, **P , 0.01 compared with pre-procedure and post-procedure first day.
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Figure 3: Comparison of the change in the atrial active emptying fraction (A) and change in the inter-AEMD (B) over the time (P , 0.001 and P , 0.001, respectively) and between two groups (P . 0.05 and P . 0.05, respectively).
In healthy subjects all of the blood returning to LA via pulmonary veins pass the mitral valve and fill the left ventricle. However, in untreated ASD patients a portion of this blood pass through the defect to the RA and from there to the right ventricle due to better compliance and lower resistance of LV and cause chronic RV volume overload. Chronic RV overload and reduced LV preload result in decreased early LV filling and systolic function.20,21 RV volume overload decreases and LV filling volume increases after percutaneous closure of ASD, which result in decreased right heart chamber diameter, decreased pulmonary arterial hypertension, and increased LV end-diastolic diameter and EF.12,22,23 Our study also demonstrated that there were significant decrease in the RA and RV diameters and increase in LV diastolic diameter and EF after percutaneous closure at the first day and sixth month follow-up compared with pre-procedural values. In accordance with a study by Santoro et al. we also observed a decrease in LA diameter after the procedure, which was not statistically significant.24 LV filling is regulated by three different functions of the left atrium: storage, conduction, and contraction. In healthy individuals, LA
conduction function which happens in early diastole correlates with diastolic mitral inflow E-wave, whereas contractile function correlates with late diastolic A-wave.25 Contraction of the left atrium in the last phase of the diastole contributes to 15–30% of the LV filling. This compensate for decreased filling volume, especially in patients with impaired LV compliance.26 Enlarged LA due to being exposed to volume overload by increasing the total volume and emptying fraction as an adaptive response ensures the continuity of cardiac stroke volume. However, with progressive dilatation of the LA, which eventually leads to a threshold fibre length, atrial shortening, and contractility begin to decline. Beyond the threshold, further enlargement will only result in the deterioration of atrial function.17 Erturk et al. 13 demonstrated that total and active emptying fractions that are indicators of LA’s mechanical function, mitral E-wave amplitude, and E/A ratio were decreased but maximal, minimal and pre-systolic volumes were increased in patients with ASD compared with the control group.13 Effects of percutaneous closure of ASD with ASO devices on mitral inflow waves and LA volumes have been studied but the mechanical function of LA has not been examined.
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Percutaneous closure of atrial septal defect and left atrial function
with the baseline. However, Pac et al. 12 showed that Pd was increased in the early post-operative period and this increase was correlated with device size and device atrial disc diameter. Results of our study were in compliance with the results of both studies. We found that right inter-AEMD and left intra-AEMD was not changed in the early post-operative period but were increased in the mid-term follow-up. Changes in the diameters were correlated with the change in atrial conduction. LA anatomically improved after percutaneous closure in the early post-operative period but there was no change in the electrical conduction of LA, which may result from mechanical stress created by the device or the acute inflammatory reaction developing against the foreign body.
Study limitation The small number of patients included in the study is the main limitation of our study. Percutaneous closure was performed using three different ASOs and one of them was used only in three patients. Therefore, we did not evaluate the effect of the particular device on LA mechanical and conduction functions. We also did not do Holter ECG monitoring but, all of the patients were evaluated by the ECG at baseline, at the first day and sixth month for any arrhythmia. Twenty-four hour Holter ECG monitoring would have been very helpful to discover any arrhythmia, especially the paroxysmal atrial fibrillation.
Conclusion In this study, we found that the LA reservoir function as an indicator of the mechanical function was not affected, conduction function was improved and contractile function was deteriorated in both early and mid-term follow-up. Also, AEMD was decreased in mid-term follow-up after percutaneous closure of ASD. This may provide decreased risk for atrial fibrillation development, which is an important cause of morbidity and mortality in patients with ASD not treated with closure at the later stage. Conflict of interest: none declared.
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It is known that mitral inflow E-wave and E/A ratio increases and mitral inflow A-wave decreases after percutaneous ASD closure as it was shown in this study.5 We also showed that, Vmax, Vmin, and Vpre volumes and the contractile function of the LA were decreased, reservoir function remained unchanged and conduction function was increased after percutaneous closure at the first day and sixth month follow-up compared with the baseline in this study. Early diastolic filling is determined by pressure difference between the LV and LA but the late diastolic filling is an active event and determined by the LV compliance, LA relaxation, LA stiffness, mitral annular motion, and LA pump function. Increase in the mitral inflow E-wave and LA conduit function could be resulted from the passage of the all blood in the LA to the LV in the early diastole and from the diminished pressure exerted on LV by the diastolic RV volume overload. And also, the decrease in the mitral inflow A-wave and LA pump function could be related to decreased contractile function of the LA secondary to the device placed in the inter-atrial septum and/or to the decreased need for atrial contribution of the LV diastolic filling. Lange et al. 5 also showed that mitral inflow A-wave amplitude was increased in patients with ASD compared with the control group and A-wave amplitude was decreased after closure of the ASD with the device. Boyd et al. evaluated LA function in 23 ASD patients after percutaneous closure with the device after 6 months follow-up with strain and strain rate and found that the function was decreased being more pronounced in the mid-septal atrial region. They suggested that this localized atrial dysfunction may be due to the direct mechanical effect of the device.8 Di Salvo et al. 7 evaluated children with ASD who underwent percutaneous closure with device at 1 year after the procedure with speckle tracking strain and found that there was no deformation in the region of the device. In two separate studies performed by using echocardiography or cardiac MRI it was discovered that the LA maximal volume was decreased after the procedure compared with baseline but the differences were not statistically significant.27,28 However, a decrease in the LA maximal volume was statistically significant in our study. In comparison with the abovementioned studies performed by using either echocardiography or cardiac MRI, the follow-up period was longer and the mean age of the patients was younger in our study population than in those studies.27,28 Increase in atrial diameter and volume are known to cause increased conduction time and non-homogeneous propagation of sinus impulses. Echocardiographic AEMD measurement with tissue Doppler imaging (TDI) has been used in several disorders and found to be correlated with P-wave dispersion (Pd) measured by electrocardiography.29 Erturk et al. 13 compared the atrial conduction time measured with TDI echocardiography in patients with large secundum type ASD and healthy control group. They found that the left and right intra-and inter-AEMD durations were prolonged in patients with ASD.13 Guray et al. demonstrated that Pd was increased in patients with surgically closed ASD, compared with the control group before the procedure but Pd was decreased during the follow-up at post-operative 6th and 12th months compared with the baseline.30 In a study comparing the effect of surgical vs. percutaneous ASD closure on the Pd at the end of the first postoperative week, a decrease in Pd was observed only in the surgically closed group.31 Kaya et al. 11 showed that Pd was decreased in the mid-term follow-up after ASD closure with a device compared
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