Background
Left atrial (LA) strain is a sensitive measure of LA mechanics. However, its relationship with rhythm outcomes after catheter ablation in patients with atrial fibrillation (AF) is not well established. The aim of this study was to evaluate whether baseline LA global longitudinal strain (LAε) predicts rhythm outcomes in patients who undergo catheter ablation for AF.
Methods
In 256 patients with AF (paroxysmal, 204; persistent, 52), comprehensive echocardiography was performed with assessment of LAε by using Velocity Vector Imaging to calculate average strain values from apical four- and two-chamber views before ablation (median, 41 days; interquartile range, 1–95 days).
Results
After a median of 8.0 months (interquartile range, 4.0–23.3 months) of follow-up, 149 patients (58%) had maintained sinus rhythm and 107 patients (42%) had recurrence of AF. In our study cohort (mean age 59 ± 11 years; mean left ventricular ejection fraction, 58 ± 10%), impaired total LAε (LAε total ) was associated with greater left ventricular mass index ( r = −0.245, P < .001) and worsening left ventricular diastolic function (ratio of transmitral flow peak early diastolic velocity to peak early diastolic velocity of the mitral annulus: r = −0.357, P < .001; maximal LA volume index: r = −0.393, P < .001). Patients with LAε total < 23.2% showed a higher incidence of AF recurrence compared with patients with LAε total ≥ 23.2% (log-rank P < .001). In multivariate Cox proportional-hazards analysis, LAε total was independently related to rhythm outcomes (hazard ratio, 0.944; 95% confidence interval, 0.915–0.975; P < .001) after AF ablation. Moreover, LAε total provided incremental predictive value for rhythm outcomes over clinical features (increment in global χ 2 = 14.63, P < .001).
Conclusions
In patients with AF, baseline LAε total was associated with rhythm outcome after catheter ablation.
During the past decade, catheter ablation for atrial fibrillation (AF) has evolved rapidly from an investigational procedure to its current status as a commonly performed ablation procedure at many major hospitals throughout the world. However, catheter ablation is associated with a considerable AF recurrence rate. In patients with a higher likelihood of recurrence, discontinuation of anticoagulation may be particularly risky. We previously reported that preexisting left atrial (LA) fibrosis evaluated by voltage mapping was associated with the recurrence of atrial arrhythmia. However, a noninvasive marker for LA fibrosis would be preferable for preablation patient selection.
Two-dimensional strain (ε) based on speckle-tracking is a recently developed, innovative method that provides insight into myocardial mechanics. The evaluation of LA mechanics using this technique has been widely accepted, and as assessed with cardiac magnetic resonance imaging, LA ε has been related to LA structural remodeling and fibrosis of the atrial wall. Deformation-based parameters of LA function provide incremental prognostic information over standard parameters in the general population or patients at risk for adverse cardiovascular events ; however, the prognostic value of LA mechanics for rhythm outcomes in patients who undergo catheter ablation for AF has not been well established. Thus, we sought to examine the capability of LA global longitudinal ε (LAε) to predict rhythm outcomes after catheter ablation for patients with AF.
Methods
Study Population
We studied 319 patients with paroxysmal or persistent AF who underwent radiofrequency catheter ablation for AF from June 2008 to May 2010 and underwent preprocedural echocardiography <6 months before the procedure and were in normal sinus rhythm during echocardiography. Of this group, patients were excluded because of valvular heart disease or surgery ( n = 18) or a history of cardiac surgery ( n = 9), absence of clinical follow-up data ( n = 15), and uninterpretable images ( n = 21). This study was approved by the Cleveland Clinic Institutional Review Board.
Transthoracic Echocardiography
Comprehensive transthoracic echocardiography was performed by experienced sonographers using commercially available iE33 (Philips Medical Systems, Bothell, WA) and Vivid 7 and Vivid E9 (GE Medical Systems, Milwaukee, WI) machines. All images were stored digitally and were measured with offline software (Syngo Dynamics version 9.0; Siemens Medical Solutions, Malvern, PA). Standard techniques were used to obtain M-mode, two-dimensional, and Doppler measurements in accordance with American Society of Echocardiography guidelines. LA phasic volumes (maximal, minimal, and precontraction LA volumes) were obtained from the apical four- and two-chamber views by the method of disks and were indexed to body surface area.
LAε Measurements
LAε measurements were performed offline using dedicated software (Velocity Vector Imaging; Siemens Medical Solutions). We used the onset of the P wave as the reference point for the calculation of LAε, as previously proposed. One cardiac cycle was selected for apical four- and two-chamber views, the endocardial border was traced manually in the end-systolic frame, and the software subsequently and automatically traced the borders in the other frames. Graphical displays of deformation parameters for each segment were then generated automatically and were used for the measurement of LAε ( Figure 1 ). The software calculated average ε values for six LA segments for apical four- and two-chamber views. We obtained LAε only in the case of adequate tracking quality in at least five of the six segments per view. We identified peak negative LAε, peak positive LAε, and the sum of these values, total LAε (ε total ).
Pulmonary Vein Isolation Procedure
Our pulmonary vein isolation protocol was previously described in detail. In brief, all antiarrhythmic drugs were stopped four to five half-lives before ablation, except for amiodarone, which was stopped a minimum of 4 to 5 months before the procedure. All pulmonary vein antra were isolated in all patients under intracardiac echocardiographic guidance. Electric isolation was confirmed by the absence of pulmonary vein potentials along the antrum or inside the veins by use of a circular mapping catheter. In all patients, the superior vena cava was mapped, and potentials were ablated when there was no phrenic nerve stimulation.
Follow-Up
Patients had scheduled clinical visits, 12-lead electrocardiography, and 48-hour Holter monitoring at 3, 6, and 12 months after ablation. Atrial arrhythmias that occurred during the first 2 months after catheter ablation were not counted as recurrences. Antiarrhythmic medications were generally continued during the 2-month period. These drugs included sotalol, dofetilide, propafenone, and flecainide, with the managing electrophysiologists making the choice. All patients wore rhythm transmitters for a minimum of 3 months after catheter ablation and were asked to record when they experienced symptoms as well as weekly, even when asymptomatic. Additional event recorder monitoring was obtained beyond the 3-month period if patients had atrial tachyarrhythmia within the first 3 months or developed symptoms consistent with arrhythmia. Interrogation of implanted devices was also used (when available) to confirm arrhythmia recurrence. Antiarrhythmic agents were discontinued in all patients during the third month after ablation unless continuing recurrent arrhythmias indicated the need for continued treatment. Patients with documented arrhythmias and those maintained on antiarrhythmic agents for control of AF beyond the blanking period were counted as experiencing recurrences. Arrhythmia recurrence was identified by electrocardiographic documentation of an atrial tachyarrhythmia lasting ≥30 sec on a 12-lead electrocardiogram, event recording, or Holter monitor recording. All success rates were determined in patients off antiarrhythmic medications.
Inter- and Intraobserver Variability
Inter- and intraobserver variability for LAε total was studied in a group of 10 randomly selected subjects by one observer repeated twice and by two investigators who were unaware of each other’s measurements and of the study time point. Coefficient of variation, intraclass correlation coefficients, bias (mean difference), and limits of agreement (1.96 × standard deviation of difference) between the first and second measurements were determined.
Statistical Analysis
Continuous variables are summarized as mean ± SD if normally distributed and as medians and interquartile ranges if not normally distributed. Receiver operating characteristic (ROC) curves were generated to determine optimal cutoff values of continuous variable, and bootstrap estimation with resampling from 1,000 simulations was used to generate valid estimates of prediction accuracy. The best cutoff value was defined as the upper limit of the confidence interval of the Youden index. Kaplan-Meier plots were calculated from baseline to time of AF recurrence and compared using the log-rank test. The Cox proportional-hazards regression model was used to assess the clinical risk associated with increasing continuous increments of LAε. Covariate selection for model entry was based on clinical experience and identification of known correlates of AF recurrence. On the basis of an AF recurrence rate of approximately 40%, we anticipated being able to develop a stable model with 10 variables from a population of about 250 patients. The proportional-hazards assumption was verified with log (time) versus log (−log [survival]) plots. The incremental value of LAε over baseline clinical and echocardiographic characteristics for assessing the risk for AF recurrence was determined by calculating the improvement in the global χ 2 statistic. For a sample size of about 250, the log-rank test was sufficiently powered (90%) for a hazard ratio of 2.0 and an average probability of 60% for event-free survival to end of follow-up. Statistical analyses were performed using SPSS version 20.0 (SPSS, Inc, Chicago, IL) and MedCalc version 12.3.0 (MedCalc Software, Mariakerke, Belgium). All P values reported are from two-sided tests, and P values < .05 were considered statistically significant.
Results
Study Population
Of the 277 patients, 256 (92.4%) had LAε that could be measured in both four- and two-chamber views. Echocardiography was performed a median of 41 days (interquartile range, 1–95 days) before catheter ablation. The average frame rate of the clips for LAε analysis was 39 ± 12 frames/sec. The coefficient of variation for intraobserver variability for LAε total was 5.8 ± 4%. The coefficient of variation of interobserver variability was 7.5 ± 4.5%. The bias and limits of agreement of intra- and interobserver variability were 0.5 ± 2.7% and 0.7 ± 3.9%, respectively. Intraclass correlation coefficients of intra- and interobserver variability were 0.940 and 0.876, respectively. The baseline clinical and echocardiographic parameters are summarized in Table 1 . For the study population as a whole, mean peak negative LAε, peak positive LAε, and LAε total were −7.6 ± 4.0%, 15.9 ± 6.6%, and 23.6 ± 8.3%, respectively.
| Variable | Overall ( n = 256) | Sinus ( n = 149) | AF recurrence ( n = 107) | P |
|---|---|---|---|---|
| Demographics | ||||
| Mean age (y) | 59 ± 11 | 59 ± 10 | 60 ± 13 | .792 |
| Male gender | 179 (70%) | 109 (73%) | 69 (64%) | .192 |
| Body mass index (kg/m 2 ) | 29.5 ± 5.6 | 29.2 ± 5.5 | 30.0 ± 5.8 | .286 |
| Heart rate (beats/min) | 61 ± 11 | 61 ± 11 | 62 ± 11 | .407 |
| Systolic blood pressure (mm Hg) | 125 ± 18 | 125 ± 18 | 126 ± 18 | .542 |
| AF history | ||||
| Duration (mo) | 48 (24–84) | 48 (18–84) | 46 (24–96) | .208 |
| Paroxysmal | 204 (80%) | 128 (86%) | 73 (68%) | .004 |
| Number of failed AADs | 1.4 ± 0.9 | 1.4 ± 0.9 | 1.5 ± 0.8 | .162 |
| Prior AF ablation | 76 (30%) | 39 (26%) | 37 (35%) | .147 |
| Comorbidities | ||||
| Congestive heart failure | 38 (15%) | 17 (11%) | 21 (20%) | .068 |
| Hypertension | 138 (54%) | 76 (51%) | 62 (58%) | .272 |
| Diabetes mellitus | 29 (11%) | 14 (9%) | 15 (14%) | .250 |
| Stroke/TIA | 14 (5%) | 6 (4%) | 8 (7%) | .231 |
| CHADS 2 score | 0.95 ± 0.94 | 0.83 ± 0.90 | 1.13 ± 0.97 | .007 |
| PPM/ICD | 33 (13%) | 12 (8%) | 21 (20%) | .006 |
| Coronary artery disease | 37 (14%) | 17 (11%) | 20 (19%) | .102 |
| Medications | ||||
| ACE inhibitors and/or ARBs | 97 (38%) | 59 (40%) | 38 (36%) | .507 |
| β-blockers | 131 (51%) | 75 (50%) | 56 (52%) | .752 |
| Class 1 or 3 AAD | 196 (77%) | 111 (74%) | 85 (79%) | .357 |
| Laboratory data | ||||
| BNP (pg/mL) | 52 (22–117) | 35 (19–84) | 75 (32–135) | <.001 |
| Echocardiographic data | ||||
| Global LAε total (%) | 23.6 ± 8.3 | 26.2 ± 7.9 | 19.9 ± 7.2 | <.001 |
| Global LAε negative (%) | -7.6 ± 4.0 | -8.7 ± 4.0 | -6.2 ± 3.7 | <.001 |
| Global LAε positive (%) | 15.9 ± 6.6 | 17.6 ± 6.6 | 13.7 ± 6.0 | <.001 |
| Maximal LA volume index (mL/m 2 ) | 41 ± 13 | 41 ± 11 | 47 ± 15 | .002 |
| Minimal LA volume index (mL/m 2 ) | 23 ± 12 | 20 ± 10 | 26 ± 14 | <.001 |
| Precontraction LA volume index (mL/m 2 ) | 32 ± 12 | 29 ± 10 | 35 ± 14 | .001 |
| Total LA emptying fraction (%) | 50 ± 13 | 52 ± 13 | 46 ± 13 | <.001 |
| Active LA emptying fraction (%) | 30 ± 15 | 32 ± 16 | 26 ± 13 | .002 |
| Passive LA emptying fraction (%) | 28 ± 11 | 29 ± 11 | 27 ± 10 | .062 |
| LV EF (%) | 58 ± 10 | 58 ± 9 | 57 ± 11 | .415 |
| LV EDV index (mL/m 2 ) | 55 ± 18 | 53 ± 15 | 56 ± 20 | .199 |
| LV mass index (g/m 2 ) | 96 ± 29 | 93 ± 27 | 99 ± 30 | .101 |
| LA area (cm 2 ) | 22 ± 6 | 21 ± 5 | 23 ± 6 | .007 |
| TMF E (cm/sec) | 81 ± 20 | 80 ± 18 | 84 ± 23 | .147 |
| TMF A (cm/sec) | 61 ± 22 | 64 ± 20 | 56 ± 23 | .008 |
| TMF E-DT (msec) | 213 ± 57 | 213 ± 52 | 212 ± 62 | .836 |
| PVF S (cm/sec) | 55 ± 14 | 58 ± 12 | 50 ± 14 | <.001 |
| PVF D (cm/sec) | 57 ± 17 | 55 ± 15 | 59 ± 18 | .034 |
| PVF Ar (cm/sec) | 25 ± 6 | 26 ± 5 | 24 ± 6 | .004 |
| S/D ratio | 1.0 ± 0.4 | 1.1 ± 0.4 | 0.9 ± 0.4 | <.001 |
| DTI s′ average (cm/sec) | 7.9 ± 1.9 | 8.2 ± 1.8 | 7.6 ± 2.1 | .028 |
| DTI e′ average (cm/sec) | 9.1 ± 2.8 | 9.1 ± 2.5 | 9.2 ± 3.1 | .863 |
| DTI a′ average (cm/sec) | 8.0 ± 2.8 | 8.6 ± 2.5 | 7.1 ± 2.9 | <.001 |
Relationship between LAε, Clinical Features, and Cardiac Structure and Function
In univariate linear regression analysis, lower magnitude LAε total was correlated with age and CHADS 2 score ( Table 2 ). More impaired LAε total was associated with greater left ventricular (LV) hypertrophy and worsening LV diastolic function. Worse LAε total was also associated with larger maximal LA volume index, more impaired total LA emptying fraction, and higher natural logarithm of B-type natriuretic peptide. In multivariate analysis with a forward stepwise algorithm, age, heart rate, LV mass index, ratio of transmitral flow peak early diastolic velocity to peak early diastolic velocity of the mitral annulus (E/e’′), and total LA emptying fraction were significantly associated with LAε total ( Table 2 ).
| Variable | Univariate | Multivariate | |||
|---|---|---|---|---|---|
| r | P | β (95% CI) | Standardized β | P | |
| Age | −0.282 | <.001 | −0.091 (−0.163 to −0.019) | −0.111 | .013 |
| Heart rate | −0.206 | .001 | −0.117 (−0.184 to −0.050) | −0.149 | .001 |
| Systolic blood pressure | −0.104 | .096 | |||
| CHADS 2 score | −0.273 | <.001 | |||
| Duration of AF | −0.077 | .224 | |||
| LV EDV index | −0.074 | .238 | |||
| LV mass index | −0.245 | <.001 | −0.039 (−0.065 to −0.013) | −0.131 | .003 |
| LV EF | 0.177 | .004 | |||
| E/e′ average | −0.357 | <.001 | −0.367 (−0.563 to −0.171) | −0.168 | <.001 |
| Maximal LA volume index | −0.398 | <.001 | |||
| Total LA emptying fraction | 0.729 | <.001 | 0.403 (0.350 to 0.456) | 0.656 | <.001 |
| Natural log BNP) | −0.469 | <.001 | |||
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