Mechanical and substrate abnormalities of the left atrium assessed by 3-dimensional speckle-tracking echocardiography and electroanatomic mapping system in patients with paroxysmal atrial fibrillation Yoshikazu Watanabe, MD, Yukiko Nakano, MD, PhD, Takayuki Hidaka, MD, PhD, Noboru Oda, MD, PhD, Kenta Kajihara, MD, PhD, Takehito Tokuyama, MD, PhD, Yuko Uchimura, MD, Akinori Sairaku, MD, Chikaaki Motoda, MD, Mai Fujiwara, MD, PhD, Hiroshi Kawazoe, MD, Hiroya Matsumura, MD, Yasuki Kihara, MD, PhD From the Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan. BACKGROUND Left atrial (LA) remodeling progresses to electrical remodeling, contractile remodeling, and subsequently structural remodeling. Little is known about the relationship between LA electrical and anatomical remodeling and LA mechanical function. OBJECTIVES We aimed to clarify the relationship between LA mechanical function using 3-dimensional speckle-tracking echocardiography (3D-STE) and LA electrical remodeling using an electroanatomic mapping system (CARTO 3) and to estimate atrial fibrillation (AF) substrate in patients with paroxysmal AF (PAF).

was an independent determinant of the LVZ (odds ratio 1.21; 95% confidence interval 1.04–1.49; P ¼ .01). In addition, the LA total activation time was weakly correlated with the %SD-TPS. CONCLUSION LA dyssynchrony and conduction delay exist in patients with PAF. The 3D-STE enabled noninvasive estimation of LA electrical remodeling and AF substrate. KEYWORDS Left atrium; Atrial fibrillation; Electroanatomic mapping; Speckle-tracking echocardiography; Conduction delay; Dyssynchrony; Remodeling

METHODS A total of 52 patients with PAF (41 (79%) men; mean age 61 ⫾ 11 years) undergoing their initial pulmonary vein isolation (PVI) were examined. The standard deviation of the time to peak strain in each LA segment (%SD-TPS) was analyzed as an index of LA dyssynchrony using 3D-STE before PVI. Contact LA bipolar voltage and activation maps were constructed during sinus rhythm before PVI using CARTO 3. The LA total activation time was measured and low-voltage zones (LVZs) were determined with a local bipolar electrogram amplitude of o0.5 mV. The patients were divided into those with an LVZ (LVZ group; n ¼ 23) and those without an LVZ (non-LVZ group; n ¼ 29).

ABBREVIATIONS 2D ¼ 2-dimensional; 3D ¼ 3-dimensional; %SDTPS ¼ %standard deviation of the time to peak strain in each left atrial segment; AF ¼ atrial fibrillation; CTI ¼ cavotricuspid isthmus; ICC ¼ intraclass correlation coefficient; LA ¼ left atrium/atrial; LV ¼ left ventricular; LVZ ¼ low-voltage zone; PAF ¼ paroxysmal atrial fibrillation; PV ¼ pulmonary vein; PVI ¼ pulmonary vein isolation; RA ¼ right atrium/atrial; RFCA ¼ radiofrequency catheter ablation; SR ¼ sinus rhythm; STE ¼ speckle-tracking echocardiography; SVC ¼ superior vena cava; TAT ¼ total activation time

RESULTS The %SD-TPS was significantly higher (14.1 ⫾ 5.7 vs 8.0 ⫾ 5.1; P ¼ .0002) in the LVZ group than in the non-LVZ group and

(Heart Rhythm 2015;12:490–497) rights reserved.

Introduction

from non-PV sites.2 Presently, AF usually requires a trigger for initiation and a vulnerable electrophysiological and/or anatomical substrate for maintenance.3 Allessie et al4 reported that left atrial (LA) remodeling progressed in a series of electrical remodeling, subsequent contractile remodeling, and finally structural remodeling. Previous research indicated that LA electrophysiological disorders in AF were represented by low-voltage zones (LVZs) obtained by contact bipolar voltage mapping during sinus rhythm (SR)5 and that LVZs correlated with local conduction delays.6 The recent 3-dimensional speckle-tracking echocardiography (3D-STE) technology allows us to obtain reliable data

The pathogenesis of atrial fibrillation (AF) is multifactorial. Sometimes, AF is accompanied by various pathological conditions; however, it may also occur in normal hearts as lone AF.1 Reportedly, most of the paroxysmal AF (PAF) is triggered by ectopy from pulmonary veins (PVs) and partially This work was not supported by any external funding. Address reprint requests and correspondence: Dr Yukiko Nakano, Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. E-mail address: [email protected].

1547-5271/$-see front matter B 2015 Heart Rhythm Society. All rights reserved.

I

2015 Heart Rhythm Society. All

http://dx.doi.org/10.1016/j.hrthm.2014.12.007

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to calculate global LA mechanical function and synchrony.7,8 Little is known about the relationship between LA electrical and anatomical remodeling and LA mechanical function. We aimed to investigate the relationship between LA electrical remodeling and LA mechanical function and to estimate AF substrate in patients with PAF.

Methods Study population We retrospectively enrolled 52 consecutive patients with PAF (41 men; mean age 61 ⫾ 11 years) who had drugrefractory symptomatic AF, underwent the LA area strain analysis, and were scheduled for the initial radiofrequency catheter ablation (RFCA) of AF at Hiroshima University Graduate School of Biomedical and Health Sciences. Those with concomitant coronary artery disease, cardiomyopathy, heart failure, pacemaker implantations, valvular disease, or inadequate acoustic windows were excluded. Their PAF duration was 49 ⫾ 67 months, and the clinical characteristics are summarized in Table 1. Antiarrhythmic drugs including β-blockers were discontinued at least 5 half-lives before the procedure. No patients were taking amiodarone. This study was approved by the ethics committee of Hiroshima University Graduate School of Biomedical and Health Sciences. Table 1 Clinical characteristics and echocardiographic parameters of patients (N ¼ 52) Clinical characteristics Age (y) Sex: male Body mass index (kg/m2) Hypertension Diabetes mellitus PAF duration (mo) Class I AADs Class II AADs Class III AADs Class IV AADs Conventional echocardiographic parameters LA dimension (mm) LV end-diastolic dimension (mm) LV end-systolic dimension (mm) Interventricular septum thickness (mm) Posterior wall thickness (mm) LV mass index (g/m2) LV ejection fraction (%) E wave (m/s) A wave (m/s) E/A ratio LAVI (mL/m2) Doppler tissue imaging parameters e0 wave (cm/s) a0 wave (cm/s) E/e0 ratio 3D strain echocardiographic parameters GPS %SD-TPS

61 ⫾ 11 41 (79) 23.7 ⫾ 3.1 28 (54) 2 (4) 49 ⫾ 67 20 (38) 14 (27) 0 (0) 13 (25) 35.5 ⫾ 4.9 48.5 ⫾ 4.5 31.6 ⫾ 3.2 8.7 ⫾ 1.2 8.7 ⫾ 1.1 84.8 ⫾ 19.0 63.6 ⫾ 3.2 66.2 ⫾ 16.1 62.4 ⫾ 20.2 1.2 ⫾ 0.5 33.6 ⫾ 8.1 11.0 ⫾ 3.0 10.7 ⫾ 3.1 6.5 ⫾ 2.4 48.5 ⫾ 19.8 10.7 ⫾ 6.1

Values are presented as mean ⫾ SD or n (%). 3D ¼ 3-dimensioanl; %SD-TPS ¼ % standard deviation of time to peak strain; AAD ¼ antiarrhythmic drug; GPS ¼ global peak strain; LA ¼ left atrial; LAVI ¼ left atrial volume index; LV ¼ left ventricular; PAF ¼ paroxysmal atrial fibrillation.

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Echocardiographic measurements The transthoracic echocardiographic examinations, including 2-dimensional (2D), M-mode, pulsed wave, continuous wave, color flow, and 3D-STE, were performed using an Aplio Artida ultrasound system (Toshiba, Tokyo, Japan). We used the PST-30SBT (1–5 MHz) transducer for 2D imaging and the PST-25SX matrix array transducer for 3-dimensional (3D) imaging. All images were obtained in the parasternal short- and long-axis views or the apical 2- and 4-chamber views according to the American Society of Echocardiography guidelines.9 Experienced echocardiographers conducted all echocardiographic examinations and analyzed echocardiographic parameters.

LA area strain analysis For 3D-STE analysis, a volumetric image of LA from the apical view was obtained and stored on the 3D wall motion tracking software (Toshiba, Tokyo, Japan). LA area strain analysis was performed according to the methods described by other researchers.7,8 By manually tracing the LA endocardial border in both 4- and 2-chamber views during the left ventricular (LV) enddiastolic phase (minimum LA cavity area), the software automatically tracked endocardial contours and divided the LA image into 16 segments. Area strain was obtained as a ratio of endocardial area change during a cardiac cycle, and the area strain curves of each segment and global strain curve were obtained. We defined the first peak value of the LA global area strain curve as global peak strain, representing the total amount of LA reservoir function. To quantify the dispersed motion between each LA segment (dyssynchrony), we used the standard deviation of the time to peak of each area strain curve and expressed it as the percentage of the interbeat (R-R) interval (%SD-TPS) (Figure 1). All measurements were taken during SR before RFCA. The independent investigators who analyzed clinical information performed echocardiographic examinations. We examined intraclass correlation coefficients (ICCs) for %SD-TPS measurements in the randomly selected 15 patients to check the reproducibility. ICC(2, 1) was .86, and ICC(1, 1) was .92.

Detection of the LVZ and measurement of LA total activation time A 64-slice multidetector computed tomography (LightSpeed VCT, GE Healthcare, Little Chalfont, Buckinghamshire, UK) was performed before the procedure to evaluate LA anatomy. Briefly, a 6-F 16-pole catheter (Irvine Biomedical, Irvine, CA) was used, with the distal poles placed within the coronary sinus and proximal poles located from the superior vena cava (SVC) to the superior right atrium (RA) via the right internal jugular vein. Before RFCA, a 3D anatomical contact voltage map and an activation map of LA were constructed during SR with a 3.5-mm irrigated-tip electrode catheter (ThermoCool, Biosense Webster Inc, Diamond Bar, CA) in a point-by-point

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Heart Rhythm, Vol 12, No 3, March 2015 We discriminated LA potentials by timing of potentials or from capture by SVC, RA, or LA pacing.

Electrophysiological study and RFCA

Figure 1 Example of area strain curves of each left atrial (LA) segment (colored) and global strain curve of the LA (white) during a cardiac cycle. Global peak strain was defined as the first peak area strain value in the global strain curve, representing the total amount of LA reservoir function. To quantify LA dyssynchrony, we used the standard deviation of the time to peak of each area strain curve and expressed it as the percentage of the R-R interval.

recording using the 3D electroanatomic mapping system (CARTO 3, Biosense Webster) and merged with computed tomography integration (CARTOMERGE, Biosense Webster). The peak-to-peak contact bipolar voltages filtered between 30 and 400 Hz were obtained. The electrogram from the proximal electrode of the coronary sinus catheter was used for the reference signal during contact voltage mapping. For an equal distribution of points, we used a fill threshold of 10 mm and covered LA thoroughly.6,10 The mapping points within PVs were excluded from the analysis. The endocardial contact was confirmed carefully by the fluoroscopic motion of the catheter, electrogram stability,10,11 and distance to LA surface geometry of the mapping system. The points over 5 mm from the LA surface were excluded.12 To discriminate the low-voltage electrograms from the electrograms by insufficient wall contact, we delicately moved catheter around the captured low-voltage electrograms, used different catheter maneuvers to change contact angulations and low-voltage electrograms were double-checked by another doctor, and we analyzed a mean of 102 ⫾ 29 points per patient in all over the LA. On the basis of previous studies,11,13,14 we defined LVZ as the cluster of low-voltage points extended more than 3% of the LA surface in which the bipolar electrogram amplitude was o0.5 mV. We divided the subjects into 2 groups: those with an LVZ (LVZ group) and those without an LVZ (non-LVZ group). On the basis of previous researches,12,14 we defined LA total activation time (LA-TAT) as the time from the largest point of the earliest electrogram to the terminal point of the latest electrogram in the LA (Figure 2). If the far-field potential was recorded with LA potential as double potentials, we placed catheters in the SVC, RA septum, and LA septum.

Pulmonary vein isolation (PVI) and bidirectional cavotricuspid isthmus (CTI) ablation were performed as previously reported.15 PVI was continuously performed on prepared CARTOMERGE image using the ThermoCool. We performed a bidirectional CTI ablation with an end point of bidirectional conduction block in all patients after PVI. After PVI and CTI ablation, a quadripolar electrode catheter (Bard Medical, Covington, GA) was positioned on the lateral wall of the RA and a decapolar electrode catheter (Boston Scientific Corporation, Natick, MA) was placed at the bundle of His. The AA, AH, and HV intervals, sinus node recovery time, and corrected sinus node recovery time were measured by the baseline electrocardiogram.

Statistical analysis Normally distributed continuous variables are presented as means ⫾ SDs. Comparisons between the groups were performed using the unpaired Student t test or MannWhitney U test when appropriate. A univariate analysis of patient characteristics and echocardiographic parameters was performed to compare the 2 groups, and a logistic regression analysis was performed to detect any independent significant indicator by adjusting multiple variables. The Pearson or Spearman correlation test was used to evaluate the relationship between %SD-TPS and each parameter. Moreover, to assess the independent indicators for %SD-TPS, a multiple regression analysis was performed. The JMP statistical package, version 10.0 (SAS Institute Inc, Cary, NC) was used for all statistical tests.

Figure 2 Example of left atrial (LA) isochronal (A) and propagation (B) maps during sinus rhythm. The first breakthrough area from the right atrium was observed in the upper septum of the LA. The wavefront spread out to the LA and finished in the lower lateral portion. The LA total activation time in this case was measured as 94 ms. AP ¼ anteroposterior; PA ¼ posteroanterior.

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Results Patient characteristics and echocardiographic parameters Clinical characteristics and echocardiographic parameters of all the subjects are presented in Table 1. The mean LA volume index was 33.6 ⫾ 8.1 mL/m2, suggesting that LA structural remodeling was not so severe. The LVZ was detected in 23 patients (44.2%) by voltage mapping using CARTO 3. We compared clinical characteristics and echocardiographic parameters between the LVZ (n ¼ 23) and non-LVZ (n ¼ 29) groups, and the results are presented in Table 2. In univariate analysis, patients in the LVZ group were older than those in the non-LVZ group (65 ⫾ 11 years vs 58 ⫾ 11 years; P ¼ .03). In 3D-STE analysis, %SDTPS was significantly higher in the LVZ group than in the nonLVZ group (14.1 ⫾ 5.7 vs 8.0 ⫾ 5.1; P ¼ .0002), suggesting that LA dyssynchrony potentially existed in the LVZ group. The other clinical parameters and routine echocardiographic parameters, including LV ejection fraction, LV dimension, LA volume index, and E/A and E/e0 ratios, were similar in both groups. In the multivariate analysis of clinical, routine echocardiographic, and 3D-STE analysis parameters, %SD-TPS was the only independent indicator of LVZ in patients with PAF (odds ratio 1.21; 95% confidence interval 1.04–1.49; P ¼ .01). Table 2

493 Figure 3 shows representative cases of 3D-STE analysis from both LVZ and non- LVZ groups. The peaks of each area strain curve were discrete in the LVZ group (Figure 3A); conversely, the peaks were close together in the non-LVZ group (Figure 3D).

Correlation of %SD-TPS and other parameters Figure 4 shows the correlations between %SD-TPS and several parameters. Age and LA-TAT were positively correlated (r ¼ 0.44, P ¼ .001 and r ¼ 0.57, P ¼ .0001) with %SD-TPS, whereas mean LA voltage and %SD-TPS were negatively correlated (r ¼ 0.42, P ¼ .002). A multivariate linear regression analysis of the clinical, echocardiographic, and electrophysiological parameters suggested that the LA-TAT was weakly correlated with the % SD-TPS in patients with PAF (r ¼ 0.57; P ¼ .0001; Table 3).

Discussion Major findings

In this study, we clarified the following findings: (1) LA LVZ potentially exists even in the early remodeling phase in patients with PAF whose LA has not been dilated; (2) LA dyssynchrony was especially pronounced in patients with

Independent determinants for the identification of patients with an LVZ

Variable Clinical characteristics Age (y) Sex: male Body mass index (kg/m2) Hypertension Diabetes mellitus PAF duration (mo) Class I AADs Class II AADs Class III AADs Class IV AADs Conventional echocardiographic parameters LA dimension (mm) LV end-diastolic dimension (mm) LV end-systolic dimension (mm) Interventricular septum thickness (mm) Posterior wall thickness (mm) LV mass index (g/m2) LV ejection fraction (%) E wave (m/s) A wave (m/s) E/A ratio LAVI (mL/m2) Doppler tissue imaging parameters e0 wave (cm/s) a0 wave (cm/s) E/e0 ratio (lateral) 3D strain echocardiographic parameters GPS (%) %SD-TPS

Univariate analysis

Multivariate analysis

P

OR

95% CI

P

1.02

0.94–1.12

.57

0.81

0.56–1.08

.15

1.26 0.66

0.84–1.96 0.35–1.16

.27 .15

LVZ group (n ¼ 23)

Non-LVZ group (n ¼ 29)

65 ⫾ 11 18 (78) 23.0 ⫾ 2.9 12 (52) 1 (4) 59 ⫾ 64 11 (48) 8 (35) 0 (0) 4 (17)

58 ⫾ 11 23 (79) 24.3 ⫾ 3.3 16 (57) 1 (4) 40 ⫾ 69 9 (31) 6 (21) 0 (0) 9 (31)

.03 .93 .14 .72 .89 .32 .22 .26

35.3 ⫾ 5.7 47.5 ⫾ 4.9 30.7 ⫾ 3.3 8.6 ⫾ 1.2 8.7 ⫾ 1.0 83.5 ⫾ 18.8 63.6 ⫾ 3.2 68.0 ⫾ 16.9 62.0 ⫾ 22.3 1.2 ⫾ 0.6 34.1 ⫾ 10.0

35.7 ⫾ 4.4 49.3 ⫾ 4.1 32.3 ⫾ 3.0 8.7 ⫾ 1.3 8.7 ⫾ 1.1 85.9 ⫾ 19.5 63.7 ⫾ 3.3 64.8 ⫾ 15.6 62.7 ⫾ 18.8 1.1 ⫾ 0.4 33.2 ⫾ 6.3

.81 .15 .07 .73 .81 .65 .96 .49 .9 .39 .67

11.0 ⫾ 2.8 9.9 ⫾ 3.8 6.6 ⫾ 2.5

10.9 ⫾ 3.1 11.4 ⫾ 2.4 6.4 ⫾ 2.3

.91 .08 .78

0.76

0.49–1.04

.09

40.6 ⫾ 17.4 14.1 ⫾ 5.7

55.0 ⫾ 19.6 8.0 ⫾ 5.1

.008 .0002

0.98 1.21

0.92–1.03 1.04–1.49

.48 .01

.25

CI ¼ confidence interval; LVZ ¼ low-voltage zone; OR ¼ odds ratio; other abbreviations as in Table 1.

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Figure 3 Examples of area strain curves (A and D) and bipolar voltage maps (B and E) in subjects from low-voltage zone (LVZ) and non-LVZ groups. A subject from the LVZ group had discrete LVZs (orange to blue area) in anterior and left posterior walls of the left atrium (panel B) and strain curves were dispersed (panel A). Representative electrograms recorded in the LVZ (left: in orange area; right: in blue area) are shown in panel C. In contrast, the voltage map was electrically normal (purple area) in a subject from the non-LVZ group (panel E) and strain curves were uniform (panel D). AP ¼ anteroposterior; PA ¼ posteroanterior.

PAF who had LVZ in their LA; (3) the LA conduction delay was weakly correlated with LA dyssynchrony. These results suggested that LA mechanical dysfunction became apparent in an early stage of LA remodeling in patients with PAF. LA mechanical dysfunction and electrical disorder may arise from the regional scar, and these heterogeneous properties of the LA create a vicious circle of vulnerability for AF occurrence. To our knowledge, this is one of the first studies to explain the relationship between LA electrophysiological parameters and LA mechanical dysfunction using 3D-STE in patients with AF.

Advantage of 3D-STE in estimating LA mechanics According to previous studies,16 LA voltage properties correlate with the conventional LA functions such as A-wave velocity, LA appendage flow, and PV flow in patients with AF. However, these hemodynamic indices do not directly reflect LA mechanics. Two-dimensional speckletracking echocardiography (2D-STE) is a promising technique to directly analyze the mechanical deformation because

it has already been used to measure LA function in different cohorts of normal subjects and patients with pathological conditions.17,18 However, 2D-STE was limited to the determination of global LA mechanics by single-plane assessment.19,20 Recently, a 3D-STE technique has been developed and reported to reflect global wall motion more precisely and enable accurate assessment of LA global mechanics, including dyssynchrony.7,8

Course of the progression of LA remodeling in AF In this study, we clarified that LA dyssynchrony reflected by %SD-TPS using 3D-STE was significantly increased in patients with PAF with an LVZ and that %SD-TPS was an independent determinant for identifying LVZ by using multivariate analysis. Furthermore, the severity of LA dyssynchrony was related to the LA conduction delay. Our results suggested some important observations. First, LA dyssynchrony existed even in patients with almost normal LA size, and no significant correlation was observed between LA dyssynchrony and LA volume. One reason may

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Figure 4 Correlations between % standard deviation of time to peak strain (%SD-TPS) and age (A), left atrial (LA) volume index (B), mean LA voltage (C), and LA total activation time (D) in all patients (N ¼ 52).

be that we enrolled only patients with PAF with quite an early phase of LA structural remodeling and they had no variation in their LA sizes. However, the fact that LA dyssynchrony preceded the appearance of LA dilatation is an important finding when we consider the pathogenesis and course of the progression of LA remodeling in patients with AF. Second, LA dyssynchrony may arise from a patchy LVZ in the LA in patients with PAF. Lin et al12 reported that the mean LA voltage decreased and the incidence of LA LVZ increased progressively parallel to the progression of AF type. Sung et al16 reported that the LA LVZ index (LVZ index, area with voltage o0.5 mV, divided by the total LA surface area) showed a significant correlation with A-wave velocity and LA ejection fraction. In this study, we could not confirm the direct relationship between LA strain and fibrosis. However, previous reports20–22 showed that LA LVZ and LA mechanical dysfunction corresponded to LA fibrosis suggested by LA delayed-enhancement area on magnetic resonance imaging. Kostin et al23 reported an increased amount of LA fibrosis in patients with AF by histological examinations,

and Her et al24 showed a direct correlation between histological LA fibrosis and 2D-STE. In this study, LA dyssynchrony was especially pronounced in patients with PAF who had an LVZ in their LA. The patchy LVZ recognized by voltage mapping in this study may be a result of the regional fibrosis of the LA myocardial tissue. Regional fibrosis may lead to the heterogeneity of LA wall stiffness, result in dyssynchrony in the reservoir phase, and also cause the local conduction delay by separating atrial myocytes.25 Previous reports14,26 showed that these abnormal electrophysiological substrates contributed to the development and progression of AF. Finally, we infer that LA electrophysiological remodeling closely correlated with LA mechanical dysfunction because the LA-TAT weakly correlated with %SD-TPS. The LA conduction speed and LA wall motion have been reported to decrease in dilated LA in patients with AF.27–29 Miyamoto et al6 reported that local conduction disturbance existed in patients with LA LVZ. In addition, we found that LA electrophysiological disorder correlated with LA dyssynchrony even in patients with AF with less advanced anatomical remodeling.

496 Table 3

Heart Rhythm, Vol 12, No 3, March 2015 Correlation between %SD-TPS and other parameters Univariate analysis

Multivariate analysis

Parameter

r

P

Age Body mass index PAF duration LA dimension LV end-diastolic dimension LV mass index LV ejection fraction E wave A wave E/A ratio LAVI e0 wave a0 wave E/e0 ratio AA interval AH interval HV interval CSNRT Mean LA voltage LA-TAT

0.44 0.12 0.15 0.08 0.33 0.11 0.19 0.21 0.09 0.26 0.02 0.23 0.003 0.01 0.21 0.19 0.12 0.01 0.42 0.57

.001 .41 .3 .57 .02 .43 .18 .13 .52 .06 .87 .1 .98 .94 .14 .18 .42 .5 .002 .0001

β

P .16

Conclusion LA dyssynchrony exists in patients with PAF in an early remodeling phase. We are able to detect the early phase of LA electrical remodeling and AF substrate using a noninvasive %SD-TPS with 3D-STE.

.42

Acknowledgments .16

.2

.12 .1

.32 .45

.03

.86

.11

.52

.09 .04

.49 .76

.09 .45

.55 .0014

CSNRT ¼ corrected sinus node recovery time; LA-TAT ¼ left atrial total activation time; other abbreviations as in Table 1.

The clinical implication of our study is that LA dyssynchrony is latent in patients with AF in the early remodeling phase. These results are relevant when considering the progression of LA remodeling and AF pathogenesis. The most important finding in the present study was that we were able to detect the early phase of LA electrical remodeling and AF substrate using a noninvasive %SD-TPS with 3D-STE.

Study limitations There were several limitations to the present study. First, the main limitation of our study was the small sample size from only a single institution in a nonrandomized retrospective manner and patients with AF with structural diseases and severe LA remodeling were excluded. Therefore, the present findings need to be validated in a larger prospective and multicenter study. Second, the point density in our study was relatively low and we could not exclude low-voltage electrograms due to poor catheter contact. We should perform more high-density contact mapping by using other methods such as contact force catheter for the accurate estimation of LA electrical substrate. In addition, 3D-STE and LA voltage could be assessed only during SR. Finally, the accuracy of 3D-STE and time resolution were also limitations of this study. However, there were some previous reports7,8 examining the LA mechanical function using 3D-STE, and to our knowledge, this is the first report demonstrating relationship between LA dyssynchrony and conduction disturbance of LA in patients with PAF.

We thank the members of the clerical and medical staff at Hiroshima University Hospital for their assistance. We also thank Mr John Martin for checking the manuscript.

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Left Atrial Mechanics in Atrial Fibrillation

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CLINICAL PERSPECTIVES This study aimed to clarify the relationship between left atrial (LA) mechanical dysfunction using 3-dimensional strain echocardiography (3D-STE) and LA electrical remodeling using electroanatomic mapping in patients with paroxysmal atrial fibrillation (PAF). We concluded that LA dyssynchrony exists in patients with PAF in an early remodeling phase, and we could detect the early phase of LA electrical remodeling and atrial fibrillation (AF) substrate using a noninvasive standard deviation of the time to peak strain in each LA segment with 3D-STE. If we could predict LA remodeling using 3D-STE, we may be able to predict AF recurrence after radiofrequency catheter ablation (RFCA). This information may also be useful for determining the RFCA strategy and need for anticoagulation after RFCA. A more important issue is the prevention of cerebral infarctions (CIs) in patients with AF. The European Society of Cardiology guidelines recommend opportunistic screening in patients older than 65 years for early detection of AF to prevent CIs. Through the early detection of LA remodeling using 3D-STE, we may be able to implement an early intervention in high-risk patients and prevent CIs. This is highly significant from the perspective of medical economics. We examined only a small number of patients with PAF in a nonrandomized retrospective manner. We need a long-term follow-up survey of patients with PAF who had undergone RFCA to clarify the importance of LA mechanics in AF recurrence. We need to retrospectively estimate LA mechanics in patients with a history of CI in spite of low CHADS2 scores. A prospective multicenter trial is needed to predict AF occurrence in a normal cohort for the clinical appreciation.

Mechanical and substrate abnormalities of the left atrium assessed by 3-dimensional speckle-tracking echocardiography and electroanatomic mapping system in patients with paroxysmal atrial fibrillation.

Left atrial (LA) remodeling progresses to electrical remodeling, contractile remodeling, and subsequently structural remodeling. Little is known about...
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