Ó 2014, Wiley Periodicals, Inc. DOI: 10.1111/echo.12647

Echocardiography

Left Atrial Appendage Wall-Motion Velocity Associates with Recurrence of Nonparoxysmal Atrial Fibrillation after Catheter Ablation Miyuki Ariyama, M.D., Ph.D.,* Ritsushi Kato, M.D., Ph.D.,* Makoto Matsumura, M.D., Ph.D.,* Harumi Yoshimoto, M.D., Ph.D.,* Yoshie Nakajima, M.D., Ph.D.,* Shintaro Nakano, M.D.,* Takatoshi Kasai, M.D., Ph.D.,† Jun Tanno, M.D.,* Takaaki Senbonmatsu, M.D., Ph.D.,* Kazuo Matsumoto, M.D., Ph.D.,* and Shigeyuki Nishimura, M.D., Ph.D.* *Department of Cardiology, International Medical Center, Saitama Medical University, Saitama, Japan; and †Department of Cardiology, Juntendo University School of Medicine, Tokyo, Japan

Catheter ablation (CA) for nonparoxysmal atrial fibrillation (AF) is controversial due to its high recurrence rate. The aim of this study was to assess retrospectively the diagnostic value of preprocedural left atrial appendage (LAA) wall-motion velocity in predicting recurrence of AF within 1 year after CA. We hypothesized that tissue Doppler-derived measurement of LAA wall-motion velocity associate with recurrence of AF within 1 year after CA. We retrospectively reviewed 47 consecutive patients with nonparoxysmal AF (defined as AF lasting for 1 week or longer) who underwent both transthoracic and transesophageal echocardiography before their first treatment by CA in a single center. Forty-one patients aged 58
10 years were included, and variables predicting the recurrence of AF within 1 year after CA were evaluated. Seventeen patients (41%) developed recurrence of AF within 1 year after CA. Univariate analyses showed that preprocedural LAA upward wall-motion velocity at the apex assessed by transesophageal echocardiography was significantly lower in patients with recurrence of AF than those without recurrence (OR = 1.45, 95% CI: 1.13–2.01, P = 0.009). Multivariate logistic analyses including other potential predictors (duration of AF, left ventricular ejection fraction, E-wave deceleration time, and left atrial wall-motion velocity) identified LAA upward wall-motion velocity at the apex as an independent predictor of outcome. These data suggest in patients with nonparoxysmal AF, preprocedural LAA upward wall-motion velocity at the apex, as determined by tissue Doppler imaging during transesophageal echocardiography, may be a useful indicator for predicting recurrence of AF within 1 year after CA. (Echocardiography 2015;32:272–280) Key words: atrial fibrillation, left atrial appendage function, tissue Doppler imaging Atrial fibrillation (AF) is a relatively common condition, and is associated with increased risk of heart failure, stroke, and cardiovascular mortality.1 Catheter ablation (CA) is an established therapeutic option for symptomatic and drugrefractory paroxysmal AF.2,3 However, nonparoxysmal AF has a high rate of recurrence after treatment by CA, with a frequent requirement for repeated ablations.2,4,5 Candidates for CA should therefore be carefully selected. When selecting candidates for CA, the variables known to predict recurrence of AF should be considered, including age, duration of AF, left ventricular ejection fraction, left atrial volume and Address for correspondence and reprint requests: Shintaro Nakano, M.D., Department of Cardiology, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan. Fax: +81-42-984-4591; E-mail: [email protected]

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function, atrial natriuretic peptide level, structural heart disease, sleep apnea, obesity, and comorbidities including hypertension and chronic kidney disease.1–4,6–10 A recent preliminary report suggested that left atrial appendage (LAA) peak flow velocity may predict outcomes at 1 year after CA for longstanding persistent AF,11 indicating that LAA function may be an important predictor of recurrence of AF. Distension of the LAA wall is an important aspect of LAA function, as it contributes to modulation of the left atrial pressure– volume curve12 and secretion of atrial natriuretic peptide.13 In theory, LAA wall distension is related to LAA wall-motion velocity, which can be measured using tissue Doppler imaging. We therefore speculated that alteration of LAA wallmotion property could reflect the early stages of cardiac remodeling and predict recurrence of AF

LAA Wall-Motion Velocity for AF Recurrence

caused by these hormonal and physiological aspects. The purpose of this study was to assess the usefulness of assessing LAA function, in particular LAA wall-motion velocity on tissue Doppler imaging, for predicting recurrence of AF within 1 year after the first CA for nonparoxysmal AF. Methods: Study Design: A retrospective review of medical records revealed 47 consecutive patients with nonparoxysmal AF who underwent both transthoracic and transesophageal echocardiography before their first treatment by CA at our institute between May 2008 and September 2011. Nonparoxysmal AF was defined as AF lasting for 1 week or longer. We excluded patients with left ventricular ejection fraction 30 sec on 24-hour Holter electrocardiography or surface electrocardiography between 3 and 12 months after CA. Patients in the SR group maintained SR for 12 months after CA, without documented AF as described above. A blanking period of 3 months after CA was used, as recurrence of AF during this period may be transient.13 The primary outcome was the maintenance of SR at 1 year after CA, with no documented AF. Patient Characteristics: Baseline patient characteristics including age, gender, body mass index, coexisting conditions, and history of congestive heart failure, stroke, or transient ischemic attack were recorded. Hypertension was defined as treatment with antihypertensive medication or a blood pressure of >140/ 90 mmHg at rest. Diabetes mellitus was defined as treatment with antidiabetic medication (insulin or oral hypoglycemic drugs) or a hemoglobin A1c level of ≥6.5% (National Glycohemoglobin Standardization Program). Baseline heart rate was measured at rest. Duration of AF was recorded according to patients’ statements. Laboratory findings described included plasma brain natriuretic peptide, serum urea nitrogen, creatinine, and hemoglobin A1c levels. Drugs administered for the treatment of AF were recorded, including sodium channel blockers, nondihydropyridine calcium channel blockers, b-blockers, and multichannel blockers. Bepridil was classified

into multichannel blockers.14 Renin–angiotensin system inhibitors, which have shown preventive effects in selected patients with AF, were also recorded.15,16 Transthoracic Echocardiography: Transthoracic echocardiography was performed prior to CA using a Vivid-7 system (General Electric Vingmed, Milwaukee, WI, USA) or a Prosound a10 system (Hitachi Aloka, Tokyo, Japan), equipped with a sector transducer (carrier frequency 2.5 or 3.5 MHz), according to the American Society of Echocardiography guidelines.1 Patients were placed in the left lateral decubitus position. Two-dimensional (2D) and color Doppler data were obtained in the parasternal long- and short-axis views and the apical four- and twochamber views. Left ventricular dimensions were measured in the parasternal long-axis view. Left ventricular end-diastolic volume, end-systolic volume, and ejection fraction were obtained from apical views and calculated by the modified biplane Simpson’s method. Left ventricular diastolic function was assessed by the mitral valve inflow pattern (E-wave velocity and E-wave deceleration time) using pulsed-wave Doppler recordings, and septal and lateral wall-motion velocity in proximity to the mitral valve annulus (septal and lateral E0 -wave velocity) using tissue Doppler imaging. Left atrial volumes were obtained from the apical four- and two-chamber views in 2 phases of the cardiac cycle, and left atrial enddiastolic and end-systolic volume were calculated by the modified Simpson’s method. Left atrial emptying fraction was calculated according to the following formula: left atrial emptying fraction (%) = (left atrial end-systolic volume  left atrial end-diastolic volume)/left atrial end-systolic volume 9 100. Left atrial wall-motion velocity was measured by positioning a sample volume at the midpart of the left atrial free wall in the apical four-chamber view using tissue Doppler imaging; left atria s0 -wave velocity was measured at the maximal velocity directed toward the left ventricular apex, and left atrial e0 -wave velocity was measured at the maximal velocity directed away from the left ventricular apex (Supplementary Figure S2). All volumetric data were indexed to body surface area. Transesophageal Echocardiography: Multiplane transesophageal echocardiography was performed prior to CA using a 5 MHz Probe (UST-5293S; Aloka) without sedation. In the midesophageal view, the longest dimension of the LAA was visualized with rotation of the imaging sector from 40° to 90°. The Doppler beam was aligned as parallel as possible to the longitudinally contracting appendage so that no angle 273

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correction was necessary. To minimize the influence of varying velocities during AF, the LAA data were described as the average of 3 consecutive cardiac cycles. Using pulsed Doppler, LAA blood flow velocities were measured by positioning the sample volume at 5 mm from the orifice of the LAA. LAA emptying flow velocity was measured at maximal upward flow velocity and LAA filling flow velocity was measured at maximal downward flow velocity (Fig. 1). In the same view, using tissue Doppler imaging, the LAA wallmotion velocity was measured by positioning sample volumes at 3 points: the medial, lateral, and apical walls. Upward velocity represents the maximal LAA wall-motion velocity directed toward the orifice of the LAA, and downward velocity represents the maximal LAA wall-motion velocity directed away from the orifice of the LAA (Fig. 2). CA Procedure: All patients gave written informed consent for CA. After appropriate anticoagulation therapy for at least 4 weeks, pulmonary vein isolation using the box isolation technique, and ablation of any extra pulmonary vein foci, was performed in all patients. Radiofrequency ablation was performed using a saline-irrigated ablation catheter (Navistar Thermocool; Biosense Webster, Inc., Diamond Bar, CA, USA). The settings were as follows: 20– 25 W for the posterior wall, 30 W for the anterior wall, target temperature 40–42°C. We performed box isolation procedure by making the roof and bottom linear lesions after wide area pulmonary vein isolation for right- and left-sided pulmonary veins. The endpoint of box ablation was the elimination of pulmonary vein potentials and lack of posterior wall capture during pacing at the tip of

Figure 1. Measurement of left atrial appendage (LAA) blood flow velocities by transesophageal echocardiography. Using pulsed Doppler, LAA blood flow velocities were measured by positioning the sample volume at 5 mm from the orifice of the LAA. LAA emptying flow velocity was measured at the maximal upward flow velocity (arrowhead), and LAA filling flow velocity was measured at the maximal downward flow velocity (arrows). LAA = left atrial appendage.

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Figure 2. Measurement of LAA wall-motion velocities by transesophageal echocardiography. Using tissue Doppler imaging, LAA wall-motion velocities were measured by positioning a sample volume at 3 points: the medial, lateral, and apical walls (arrowheads). Upward velocity represents the maximal LAA wall-motion velocity directed toward the orifice of the LAA, and downward velocity represents the maximal LAA wall-motion velocity away from the orifice of the LAA (arrows). LAA = left atrial appendage.

the ablation catheter with maximal output at 20 V. Additional procedures during CA included cavotricuspid isthmus ablation (n = 32), complex fragmented atrial electrogram ablation (n = 28), and linear ablation between the posterior wall and the mitral valve annulus (lateral isthmus ablation between the left inferior pulmonary vein and the mitral valve annulus or medial isthmus ablation between the right pulmonary vein and the mitral valve annulus) (n = 38). If SR was not restored during CA, electrical defibrillation was performed. Follow-Up: All patients were followed up with routine surface electrocardiography at our institute every 1–3 months after CA. Patients were also instructed to present to our cardiology or emergency department if they experienced prolonged palpitations. Patients who complained of frequent or sustained palpitations without documented AF underwent 24-hour Holter electrocardiography. Our protocol for drug withdrawal was as follows. All patients took at least one arrhythmic drug for up to 3 months after CA. From 3 to 12 months after CA, drugs for AF were sequentially withdrawn if patients stayed free of symptoms and no arrhythmias were documented on routine electrocardiography examinations. Statistical Analysis: Continuous data are described as the mean
SD or the median (first quartile-third quartile) and categorical data as number (proportion). Shapiro–Wilk test was performed for normality. Data were compared between the AF

LAA Wall-Motion Velocity for AF Recurrence

and SR groups using the unpaired t-test or Mann–Whitney U-test for continuous variables and the chi-square test or Fisher’s exact probability test for categorical variables. Multivariate analyses using logistic regression models were performed to identify the variables independently associated with recurrence of AF. The variables for inclusion in the multivariate models were selected as follows. In Model 1, variables with P < 0.15 on the univariate analyses were initially included, including duration of AF period, and several echocardiographic variables related to LAA function. Considering the potential multicollinearities, we removed most of the echocardiographic variables from the multivariate analyses, except for LAA upward wall-motion velocity at the apex, which had the highest OR (1.45). In contrast, the correlation between LAA upward wall-motion velocity at the apex and natural logarithm of duration of AF was not strong (Pearson’s correlation coefficient 0.27). In Model 2, we first included LAA upward wall-motion velocity at the apex, and also included left ventricular ejection fraction, E-wave deceleration time, and left atrial wall-motion velocity e0 -wave. As some parameters of left ventricular systolic function, left ventricular diastolic function, and left atrial function and volume are known to be associated with recurrence of AF after CA, we included left ventricular ejection fraction (representing left ventricular systolic function), E-wave deceleration time (representing left ventricular diastolic function or volume), and left atrial wallmotion velocity e0 -wave (representing left atrial function), because these echocardiographic parameters had the highest odds ratios in their respective groups. The accuracy of the potential predictor to discriminate the AF group from SR group was evaluated using receiver operating characteristic (ROC) curve analysis. Intra-observer variability and inter-observer variability were assessed by Pearson’s correlation analysis. Survival analysis was performed, including multivariate Cox proportional hazard analyses and Kaplan–Meier analysis with a log-rank test. A P- value