Atrial fibrillation (AF) is a risk factor for ischemic stroke and congestive heart failure. AF may cause left atrial (LA) dyssynchrony as well as electrical and mechanical remodeling. The aim of this study was to investigate LA dyssynchrony in patients with paroxysmal AF (PAF) and its recovery after pulmonary vein isolation (PVI), using a three-dimensional strain method.
Thirty patients with PAF who underwent PVI were enrolled. Three-dimensional echocardiography was performed before and 3 months after PVI. Twenty subjects in whom AF had never been detected served as controls. LA dyssynchrony was quantified by the standard deviation of time to peak strain (TP-SD) from end-diastole by area tracking. Serial changes in TP-SD, LA volume, and global strain in three-dimensional echocardiography were investigated.
In the PAF group, TP-SD was significantly higher (9.19 ± 4.98% vs 4.80 ± 2.30% in controls, P < .02) and global strain significantly lower (48.2 ± 20.2% vs 84.4 ± 32.9% in controls, P = .0003) than in the control group. TP-SD, global strain, and LA volume all improved significantly from before to after PVI (TP-SD, from 9.19 ± 4.98% to 6.31 ± 2.94%, P = .005; global strain, from 48.2 ± 20.2% to 58.1 ± 21.2%, P = .018; LA volume index, 29.5 ± 10.6 to 25.8 ± 7.1 mL/m 2 , P = .04). Despite the improvement after PVI, TP-SD was still significantly higher and global strain lower than in controls.
In patients with PAF, impaired LA function was documented by three-dimensional echocardiography. Despite early LA structural reverse remodeling, LA dyssynchrony was still observed 3 months after PVI. These results may affect medical therapy after successful PVI.
Atrial fibrillation (AF) is the most frequent arrhythmia in clinical practice, and its prevalence is increasing with advancing age. AF is a strong risk factor not only for ischemic stroke but also for the development of congestive heart failure. In addition, AF may cause tachycardia-induced ventricular as well as atrial dysfunction, resulting in both electrophysiologic and mechanical remodeling of the atrium or left atrial (LA) enlargement.
LA enlargement is accompanied by chronic inflammatory changes, interstitial fibrosis, and myocyte hypertrophy, which increase vulnerability to AF and further lead to LA dysfunction and thrombus formation. Those changes in the atrial myocardium with fibrosis may contribute to the impairment of electrical conduction. Several studies have suggested that either noninvasive or semi-invasive methods can be used to assess LA function. For example, Doppler tissue imaging has been reported to be a useful method in the assessment of regional LA function. However, Doppler tissue imaging is angle dependent, which represents an important limitation. On the other hand, speckle-tracking echocardiography, which is an angle-independent echocardiographic method to assess myocardial strain, has become clinically available and enhanced our ability to evaluate the performance of the left atrium, and associations between LA strain and several clinical events or markers have been reported.
Three-dimensional (3D) strain echocardiography has been developed, and its advantage for the determination of left ventricular (LV) strain and LV synchrony has been shown. Recently, its technique has been applied to left atrium as well. Mochizuki et al . validated the feasibility and reproducibility of 3D strain echocardiography for the determination of LA strain and synchrony, compared with two-dimensional (2D) strain echocardiography. Moreover, they reported the benefit of LA strain assessed by 3D strain echocardiography. During ventricular systole, the atrium acts as a “reservoir,” and the deformation or strain obtained from the LA wall shows lengthening, which is affected mainly by atrial relaxation and stiffness. Time to peak strain in each segment of the left atrium is suggested to be a potential parameter to assess LA function. Therefore, atrial dyssynchrony may be assessed by comparing time to peak strain in each segment. Recently, the standard deviation of time to peak strain (TP-SD) has been used as a novel index to assess dyssynchrony in patients with AF before and after defibrillation.
At the same time, pulmonary vein isolation (PVI) has become an effective therapeutic option for drug-refractory AF, but there are few data on the recovery of atrial function after PVI for AF. In the present study, we assessed geometric and functional recovery, including LA dyssynchrony, of the left atrium in patients who underwent PVI for paroxysmal AF (PAF), using 3D strain speckle-tracking echocardiography.
We evaluated 30 patients with PAF who underwent successful PVI and maintained sinus rhythm for 3 months after PVI. They were determined as maintaining sinus rhythm according to standard 12-lead electrocardiography performed at the time of echocardiography and no reports of palpitation.
Standard 12-lead electrocardiography and echocardiography were performed before and 3 months after PVI in all patients. Twenty subjects who were sent to our echocardiography laboratory for screening but did not have detectable structural cardiac diseases or arrhythmias served as controls.
All echocardiographic studies were performed using a commercially available echocardiographic system (Artida; Toshiba Medical Systems, Tochigi, Japan) and a dedicated software package (Ultra Extend; Toshiba Medical Systems) with a 2.5-MHz variable-frequency harmonic phased-array transducer.
Standard echocardiographic views, including apical four- and two-chamber views, with the patient in the left lateral recumbent position, were obtained in 2D and color tissue Doppler modes. Mitral inflow velocities were recorded by standard pulsed-wave Doppler at the tips of the mitral valve leaflets in an apical four-chamber view. In addition to that, we evaluated LV ejection fraction, derived by using the modified Simpson’s method.
All patients underwent 3D echocardiography from the apical approach to evaluate LA volume and strain analysis. After the entire left atrium was acquired, 3D data were sent to the dedicated software for subsequent offline analysis. Three-dimensional speckle-tracking analysis was done as reported previously. In brief, the endocardial contour of the left atrium was traced manually on an end-diastolic cavitary frame, and after defining the thickness of the region to be considered, the software automatically tracked the atrial wall on subsequent frames. Adequate tracking can be verified and corrected by adjusting the region of interest or the contour ( Figure 1 ). The software automatically divided the LA wall into the following 16 segments: four segments at the roof, six segments in the middle, and six segments in the basal part ( Figure 1 D). While retaining the entire left atrium, depth and sector width were decreased as much as possible to improve the temporal and spatial resolution of the image, resulting in a volume rate of 36.4 ± 6.2 volumes/sec in this study. LA dyssynchrony was quantified using the 3D strain speckle-tracking method. We analyzed area tracking, which is deformation data of the endocardial surface. For each segment, LA wall lengthening (positive strain value) is observed during LV systole ( Figure 2 ). A curve plotting the average of the 16 segments’ strain curves was also automatically generated, referred to as global strain, which is an index of the amount of LA deformation. Global strain was originally established and reported to refer to the average of the each strain value obtained from 16 LV segments throughout the entire cardiac cycle. Global strain is automatically calculated and displayed as a global strain curve by the software in the echocardiographic machine, and similar to global LV strain, LA global strain was derived from the continual averaging of all segmental strain values over time and was automatically calculated and displayed. On the other hand, the averaged peak strain is the average of each peak strain value in all segments. Whereas global strain is influenced by dyssynchrony because it is the average of strain values at the same time, peak strain is not influenced by the timing of their peaks, because peak strain values have nothing to do with the time at which they appear. Time to peak strain was defined as the time from end-diastole (the R wave on the electrocardiogram) to maximal positive deformation or peak strain ( Figure 2 ). As an index of LA dyssynchrony, TP-SD of the area tracking was computed and expressed as a percentage of the R-R′ interval, as reported previously. Higher grades of dyssynchrony were recognized as larger values of TP-SD.
All echocardiographic studies were performed by an experienced cardiologist who was blinded to the patients’ clinical information. Ten subjects, including patients and controls, were randomly selected to test intra- and interobserver variability for strain and TP-SD. Their data were analyzed again 2 to 4 weeks after the first analysis by the same investigator and by a second independent investigator.
All analyses were performed using SPSS version 21 (SPSS, Inc, Chicago, IL). All continuous variables are expressed as mean ± SD. The Shapiro-Wilk test was used to assess the distribution of continuous variables. Comparisons between two sets of continuous variables were performed using either t tests or Mann-Whitney U tests, as appropriate. Comparisons between two sets of categorical variables were done using either χ 2 tests or Fisher’s exact tests, as appropriate. Comparisons of continuous variables before and after PVI were performed using either paired t test or Wilcoxon signed rank sum tests, as appropriate. Medications before and after PVI were analyzed using the McNemar test.
Intra- and interobserver variability were assessed in 10 randomly selected subjects, as stated previously. Intraclass correlation coefficients and the absolute difference between two paired measurements divided by the mean of the repeated observation were calculated. P values < .05 were considered significant.
Baseline characteristics are shown in Table 1 . There was no significant difference between the PAF group and the control group, except for a higher incidence of hypertension in the PAF group. In the PAF group, the average duration of PAF was 3.8 years.
|( n = 20)||( n = 30)|
|Age (y)||57 ± 18||64 ± 10||.09|
|Men||11 (55%)||22 (71%)||.88|
|Hypertension||9 (45%)||23 (74%)||.02|
|Dyslipidemia||4 (20%)||11 (35%)||.30|
|Diabetes mellitus||1 (5%)||3 (10%)||.53|
|eGFR (mL/min/1.73 m 2 )||95.0 ± 25.2||79.3 ± 23.8||.08|
We were able to obtain optimal 2D echocardiographic images as well as 3D images, including speckle-tracking waveforms, from all study patients both before and after PVI. The mean 3D volume rate was 36.4 volumes/sec, which was considerably higher than that of a previous study (>15 volumes/sec).
Comparisons of the baseline echocardiographic parameters between the PAF group (before PVI) and the control group are shown in Table 2 . TP-SD, LA volume index (LAVI), and the E/e′ ratio (medial) were significantly larger, and global strain, peak strain, LA emptying fraction (LAEF), and medial e′ were significantly smaller in the PAF group (before PVI) than in the control group ( Table 2 ).
|Variable||Control||Before PVI||After PVI|
|( n = 20)||( n = 30)||( n = 30)|
|HR (beats/min)||60.0 ± 10.6||66.6 ± 12.9||63.3 ± 9.3|
|LAVI (mL/m 2 )||20.7 ± 6.9||29.5 ± 10.6 ∗||25.8 ± 7.1 †|
|LAEF (%)||56.9 ± 9.9||40.2 ± 10.6 ∗||47.1 ± 10.8 † ‡|
|TP-SD (%)||4.80 ± 2.30||9.19 ± 4.98 ∗||6.31 ± 2.94 † ‡|
|Global strain (%)||84.4 ± 32.9||48.2 ± 20.2 ∗||58.1 ± 21.2 † ‡|
|Peak strain (%)||88.5 ± 31.1||52.6 ± 21.2 ∗||59.2 ± 20.2 ‡|
|LVEDV (mL)||100.4 ± 27.7||108.1 ± 23.4||105.0 ± 16.6|
|LVESV (mL)||39.5 ± 19.5||35.8 ± 9.5||36.2 ± 7.5|
|Stroke volume (mL)||63.2 ± 12.6||72.3 ± 16.7||68.8 ± 13.2|
|LVEF (%)||65.5 ± 3.2||67.4 ± 5.1||66.6 ± 4.3|
|E (m/sec)||0.70 ± 0.19||0.72 ± 0.19||0.78 ± 0.21|
|A (m/sec)||0.71 ± 0.21||0.79 ± 0.23||0.68 ± 0.23|
|E/A ratio||1.13 ± 0.57||0.94 ± 0.32||1.23 ± 0.35 †|
|Medial e′ (cm/sec)||8.92 ± 3.11||6.66 ± 1.75 ∗||7.05 ± 2.02 ‡|
|Medial a′ (cm/sec)||9.99 ± 1.24||9.73 ± 2.04 ∗||8.22 ± 2.33 ‡|
|E/e′ ratio||8.34 ± 2.41||11.22 ± 3.95 ∗||11.9 ± 4.02 ‡|