Left atrial deformation predicts success of first and second percutaneous atrial fibrillation ablation Sílvia Montserrat, MD,*† Luigi Gabrielli, MD,‡ Bart Bijnens, PhD,§ Roger Borràs, BSc,*† Antonio Berruezo, MD, PhD,*† Sílvia Poyatos, RN,*† Josep Brugada, MD, PhD,*† Lluis Mont, MD, PhD,*† Marta Sitges, MD, PhD*† From the *Cardiology Department, Thorax Institute, Hospital Clinic, †IDIBAPS, University of Barcelona, Barcelona, Spain, ‡Advanced Center for Chronic Diseases, Pontificia Universidad Católica de Chile, Comisión Nacional de Ciencia y Tecnologia FONDAP and §ICREA–Universitat Pompeu Fabra, Barcelona, Spain, and IDIBAPS–Institut d’Investigacions Biomèdiques August Pi i Sunyer. BACKGROUND Predictors of second radiofrequency catheter ablation (RFCA) success are not well known. Surgical ablation is accepted for failed first RFCA, but second RFCA has fewer complications.
independent predictor of arrhythmia suppression after a first RFCA and after a second RFCA, with the best cutoff at LASs 420% (sensitivity 86%, specificity 70%) and LASs 412% (sensitivity 84%, specificity 90%), respectively.
OBJECTIVE The purpose of this study was to evaluate left atrial (LA) size and function as potential predictors of second RFCA for atrial fibrillation (AF).
CONCLUSION LA myocardial deformation imaging is a reliable tool for predicting success after a first and a second RFCA. These parameters could improve candidate selection, especially for a second RFCA.
METHODS Thirty-three healthy volunteers (group I) and 83 patients with symptomatic drug-refractory AF treated with a first RFCA (group II, n ¼ 48) or a second RFCA (group III, n ¼ 35 patients) were included. Echocardiography was performed in all patients in sinus rhythm before RFCA and in all volunteers. LA size and function were measured using longitudinal strain and strain rate during ventricular systole (LASs, LASRs) and during early diastole (LASRe) or late diastole (LASRa) with speckle tracking echocardiography. The effectiveness of RFCA on arrhythmia recurrence was evaluated at 6month follow-up. RESULTS LASs, LASRs, and LASRa were significantly lower in group III patients compared to other groups (P o .001 for all). LA diameter or volumes did not predict success after RFCA. LASs was an
Introduction Radiofrequency catheter ablation (RFCA) has become an important alternative for the treatment of patients with symptomatic drug-refractory atrial fibrillation (AF).1,2 However, potential—albeit infrequent—complications of the procedure and the arrhythmia recurrence rate warrant careful selection of candidates for RFCA.3 Enlarged left atrium (LA)4–9 has been related to AF recurrence after a first RFCA procedure, and LA function assessed by 3-dimensional Address reprint requests and correspondence: Dr. Marta Sitges, Cardiology Department, Thorax Institute, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain. E-mail address: [email protected].
1547-5271/$-see front matter B 2015 Heart Rhythm Society. All rights reserved.
KEYWORDS Atrial fibrillation; Atrial function; Second catheter ablation; Predictors; Strain; Strain rate ABBREVIATIONS AF ¼ atrial fibrillation; LA ¼ left atrial; LASRa ¼ longitudinal left atrial late diastole strain rate with speckle tracking; LASRe ¼ longitudinal left atrial early diastole strain rate with speckle tracking; LASRs ¼ longitudinal left atrial systolic strain rate with speckle tracking; LASs ¼ longitudinal left atrial systolic strain with speckle tracking; LV ¼ left ventricle; RFCA ¼ radiofrequency catheter ablation; ROC ¼ receiver operating characteristic; ST ¼ speckle tracking (Heart Rhythm 2015;12:11–18) rights reserved.
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2015 Heart Rhythm Society. All
echocardiography is a predictor of success in eliminating the arrhythmia after a first RFCA procedure.10 Despite improved RFCA success with repeated procedures, predictors of arrhythmia suppression after a second RFCA procedure are not known.11 In a previous study, LA size and LA function assessed by 3-dimensional echocardiography failed to predict AF recurrence after a second RFCA.10 Myocardial deformation imaging derived from speckle tracking (ST) represents a novel tool for evaluating LA performance.12–14 Accordingly, the aim of the present study was to analyze LA function with myocardial deformation imaging in patients before a first or second RFCA procedure and to http://dx.doi.org/10.1016/j.hrthm.2014.08.032
12 determine if deformation parameters could improve patient selection for second RFCA procedures.
Methods Study subjects and protocol In order to compare values of LA myocardial deformation values between patients with AF and healthy individuals, a group of 33 healthy volunteers (group I) was recruited from the staff of our institution. Volunteers with no record of cardiovascular disease were matched for age, sex, and body surface area with AF patients. Eighty-three patients with symptomatic drug-refractory AF undergoing RFCA were included in the study. A first RFCA was performed in 48 patients (58%, group II), and a second RFCA was carried out in 35 patients (42%, group III). None of the patients underwent electrical cardioversion in the previous 3 months before ablation. Indications for a first RFCA were symptomatic drug-refractory AF or intolerance to at least 1 class I or III antiarrhythmic medication. A second RFCA procedure was indicated in patients with symptomatic drug-refractory AF after a blanking period of 3 months after a first RFCA following current recommendations.15 Patients with significant valvular heart disease or prior valve surgery and those with moderate-to-severe left ventricular (LV) hypertrophy were excluded. All patients provided written informed consent, and the study was approved by the ethics committee of our institution.
Percutaneous radiofrequency ablation Catheter ablation was performed using a 3-dimensional electroanatomic mapping system (CARTO, Biosense Webster, Diamond Bar, CA) to support the creation and validation of radiofrequency lesions. The integration of previously acquired multidetector computed tomography or cardiac magnetic resonance imaging helped to optimize 3dimensional reconstruction. Both an ablation catheter and a circular catheter for registry and stimulation (Lasso, Biosense Webster; or Inquiry Optima, St. Jude Medical, Minnesota) were introduced percutaneously through the femoral vein. A double transseptal puncture was performed to access the LA.3 Radiofrequency was delivered through an irrigated-tip thermocouple-equipped catheter (3.5 mm) using a target temperature of 451C at 40 W. Radiofrequency lesions were delivered surrounding each ipsilateral pulmonary vein as previously described.16,17 The target was reduction of local electrogram to o0.15 mV and elimination of pulmonary vein potentials with establishment of bidirectional conduction block between the LA and pulmonary veins. In patients with persistent AF, additional radiofrequency applications were made along the LA roof, LA posterior wall, and along the mitral isthmus at the discretion of the operator. In repeated RFCA procedures, the first goal was reisolation of the pulmonary veins and then identification of nonpulmonary vein triggers.15
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Clinical follow-up All patients were evaluated at 1-, 3-, and 6-month follow-up after RFCA, including outpatient visits with clinical evaluation, serial ECG, rigorous pharmacologic control of hypertension, and 24-hour Holter monitoring to detect asymptomatic AF episodes.15 After ablation, all patients continued oral anticoagulation for a minimum of 3 months, and continued anticoagulation therapy was based on CHA2DS2-VASc cardioembolic risk score.15 Previous antiarrhythmic therapy was maintained for at least 1 month and then discontinued if no AF recurrences were detected. The procedure was considered successful if there were no recurrences of atrial tachycardia lasting 430 seconds during follow-up, after a blanking period of 3 months.15
Echocardiography All patients underwent transthoracic and transesophageal echocardiography before the RFCA procedure, using a commercially available ultrasound scanner (Philips IE33, Andover, MA) to rule out structural heart disease and LA thrombi and to assess LA size and function. All images were digitally stored and transferred to a workstation for offline analysis. Special care was taken to acquire 2D images with a frame rate 450 frames per second for adequate analysis of myocardial deformation with ST. LA and LV measurements were obtained according to the recommendations of the American Society of Echocardiography.18 LV ejection fraction was determined using the biplane Simpson method.18
LA atrial deformation study Special care was taken during echocardiographic image acquisition to ensure adequate LA tracking and avoid interference with the pulmonary veins and the LA appendage to measure global strain and strain rate of the LA. LA longitudinal myocardial deformation assessed by 2dimensional echocardiography using ST was analyzed offline with a commercially available software package (Qlab version 7.1, Speckle Tracking, Philips, Andover, MA). From the apical 4-chamber view, 3 points in the LA (2 in the mitral annulus and 1 in the LA roof) were marked, and the endocardial border was manually traced using a point-andclick technique. All patients were in sinus rhythm during echocardiography. To assess longitudinal deformation of the LA, the following parameters were calculated, with the reference point set at the onset of the QRS complex of the surface ECG13,14: LASs (LA strain during ventricular systole) (Figure 1), LASRs (LA strain rate during ventricular systole), LASRe (LA strain rate during early ventricular filling phase), and LASRa (LA strain rate during late diastole) (Figure 1). The software divided the LA wall into 6 segments,19 and the average was taken for analysis.
Statistical analysis Continuous variables are given as mean value ⫾ SD. Categorical variables are expressed as total number
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Left Atrial Function as a Predictor of Second RFCA
13
Figure 1 Left: Tracing of the left atrial (LA) wall from the apical 4-chamber view obtained by transthoracic bidimensional echocardiography. The tracing is automatically divided into 6 LA wall segments (represented in 6 different colors). Middle: For each segment, a segmental trace of longitudinal myocardial strain and strain rate was obtained. Right: The 6 corresponding segmental curves (one for each LA wall segment that was analyzed) are averaged, and the software depicts an averaged curve of LA strain (global LA strain) and another averaged curve of LA strain rate (global LA strain rate). From the average strain curves, LA peak systolic (LASs) strain, representing LA reservoir function, was identified as the peak positive strain value during LV systole, taking as a reference point the onset of the QRS on ECG.14 From the average strain rate curves, longitudinal LA peak positive strain rate (LASRs) was identified at the beginning of LV systole (QRS onset), with peak negative strain rate during early diastole (LASRe) representing conduction function at the early diastolic phase and during late diastole (LASRa) representing LA active contraction, after the P wave on ECG.
(percentage). Logistic regression analysis was used to study the effects of baseline characteristics on procedure success in our sample. Univariate logistic regression models were fitted for each of the potential predictors. P o .10 was used to screen covariates. Backward stepwise selection algorithms were used to select covariates included in the multivariate logistic regression model. At each step, the least significant variable was discarded from the model. LASs and LASRs were considered dependent variables due to high correlation (r ¼ 0.86, P o .001); therefore, in the multivariate analysis, only LASs is included because it has a more robust reproducibility. Independent covariates with P o .10 remained in the final model. Odds ratio and 95% confidence interval were calculated. Receiver operating characteristic (ROC) analyses were used to establish the optimal cutoff value for predicting recurrence in our sample. Linn concordance coefficient was calculated to study the reproducibility of the measured variables.20 A 2-sided type I error of 5% was used for all tests. Finally, interobserver and intraobserver reproducibility were evaluated by repeating measurements on the same views of the LA by 2 blinded echocardiographers. Statistical analysis was performed using R for Windows (version 2.15.1, R Project for Statistical Computing, Vienna, Austria).
Results Baseline characteristics and follow-up Baseline clinical and echocardiographic characteristics of the study population and pharmacologic therapies are given in Table 1. Patients undergoing second RFCA (group III) were treated with more antiarrhythmic drugs and showed more frequent persistent AF and hypertension. There were no significant differences in baseline LA size between patients undergoing a first (group II) or a second (group III) RFCA procedure, despite both being larger compared to controls (group I). Significant and progressive impairment of LA
function was observed in the control group (group I) through group II to group III, as shown by lower values of LASs, LASRs, and LASRa. Globally, RFCA was successful in 49 of 83 patients (59%) at 6-month follow-up. Success after a first procedure was 27 of 48 (56%) and 22 of 35 (63%) after a second procedure. All patients completed follow-up.
LA myocardial deformation predicts arrhythmia elimination after first RFCA Table 2 gives the univariate and multivariate analysis of potential predictors of arrhythmia recurrence after a first RFCA. Patients with AF recurrence after ablation showed significantly more impaired LA function at baseline, with all LA deformation parameters being worse in the patients with recurrences of atrial arrhythmia. There were no differences in baseline LA diameter or LA volume between both groups. In the multivariate analysis, LASs was the only independent predictor of arrhythmia suppression after a first RFCA procedure. In the ROC analysis [area under the curve 0.82 (0.69–0.95], LASs 420% predicted arrhythmia elimination with sensitivity of 86% and specificity of 70%.
LA myocardial function predicts arrhythmia elimination after a repeated RFCA procedure Reconduction of electrical activity to the previously isolated pulmonary veins was demonstrated in all 35 patients (100%) undergoing a second RFCA procedure. Additionally, in 2 patients (6%) another additional trigger out of the pulmonary vein was also found. Table 3 gives the univariate and multivariate analysis of potential predictors of arrhythmia recurrence after a second RFCA procedure. The type of AF (ie, paroxysmal or persistent) was not a predictor of success of ablation in our population. Additionally, there were no differences in LA
14 Table 1
Heart Rhythm, Vol 12, No 1, January 2015 Clinical and echocardiography baseline
Age (years) Men (%) Hypertension (%) Paroxysmal AF (%) Renin-angiotensin inhibitors (%) Height (cm) Weight (kg) BSA (m2) Time since AF diagnosis (months) 42 Antiarrhythmic drugs (%) Coronary artery disease (%) OSAS (%) LV hypertrophy (11–13 mm) (%) LV EF (%) LV diastolic dysfunction Baseline A-wave velocity (cm/s) LV global peak systolic strain (%) LA anteroposterior diameter (mm) LA AP diameter/BSA index (mm/m2) LA maximal 2D volume (mL) LA maximal 2D volume/BSA (mL/m2) LASs (%) LASRs (s–1) LASRe (s–1) LASRa (s–1)
Group I: healthy volunteers (N ¼ 33)
Group II: first RFCA (N ¼ 48)
Group III: second RFCA (N ¼ 35
50 ⫾ 12 26 (79%) 0 (0%)† 0 (0%)† 0 (0%)† 173 ⫾ 0.1 76 ⫾ 10 1.90 ⫾ 0.14 0† 0 (0%)† 0 (0%)† 0 (0%)† 0 (0%)† 62 ⫾ 4 0 (0%)† 62 ⫾ 17 –17 ⫾ 1 36 ⫾ 3† 19 ⫾ 2† 45 ⫾ 14† 23 ⫾ 7† 30 ⫾ 5† 1.8 ⫾ 0.4† –2.3 ⫾ 0.9† –2.2 ⫾ 0.9†
54 ⫾ 9 35 (73%) 18 (37%)* 46 (96%)* 20 (42%)* 170 ⫾ 1 78 ⫾ 11 1.92 ⫾ 0.16 70 ⫾ 51* 18 (38%)* 4 (1%)* 9 (19%)* 7 (15%)* 61 ⫾ 6 11 (23%)* 63 ⫾ 21 –17 ⫾ 2 41 ⫾ 6* 21 ⫾ 3* 70 ⫾ 24* 38 ⫾ 12.* 20 ⫾ 6* 1.1 ⫾ 0.4* –1. ⫾ 0.6* –1.4 ⫾ 0.6*
54 ⫾ 8 26 (74.3%) 21 (60%)‡ 24 (68.5%)‡ 17 (48.6 %) 171 ⫾ 8.5 82 ⫾ 13 1.98 ⫾ 0.19 76 ⫾ 51 22 (63%)‡ 4 (11%) 7 (20%) 9 (26%) 61 ⫾ 4 8 (22%) 56 ⫾ 23 –17 ⫾ 1 41 ⫾ 5 21 ⫾ 2 67 ⫾ 23 35 ⫾ 13 15 ⫾ 5‡ 0.9 ⫾ 0.3‡ –1.3 ⫾ 0.6 –0.9 ⫾ 0.4‡
2D ¼ 2-dimensional; AF ¼ atrial fibrillation; AP ¼ anteroposterior; BSA ¼ body surface area; EF ¼ ejection fraction; LA ¼ left atrium; LV ¼ left ventricle; OSAS ¼ obstructive sleep apnea syndrome; RFCA ¼ radiofrequency catheter ablation; SRa ¼ late diastolic strain rate, SRe ¼ early diastolic strain rate; SRs ¼ systolic strain rate; Ss ¼ systolic strain. * P o 0.05 difference control vs first RFCA. † P o .05 difference control vs second RFCA. ‡ P o 0.05 difference first RFCA vs second RFCA.
size and function between patients with paroxysmal or persistent AF before a repeated RFCA. Again, baseline LASs, LASRs, and LASRa were significantly reduced in patients with AF recurrence after a second Table 2
RFCA procedure. There were no differences in LA diameter or LA volume between patients with or those without recurrences. In the multivariate analysis, LASs was the only independent predictor of arrhythmia recurrence after a
Predictors of success after a first RFCA Univariate
Age (years) Paroxysmal AF Hypertension (%) Height (cm) Weight (kg) Time since AF diagnosis (months) LV EF (%) AP diameter (mm) Indexed AP diameter (mm/m2) LA max volume 2D (mL) Indexed LA max volume (mL/m2) LASs (%) LASRs (s–1) LASRe (s–1) LASRa (s–1)
Successful RFCA (n ¼ 27)
Recurrent AF (n ¼ 21)
Odds ratio (95% confidence interval)
52 ⫾ 9 27 (100%) 10 (37%) 172 ⫾ 7 78 ⫾ 12. 60 ⫾ 39 61 ⫾ 5 40 ⫾ 6 21 ⫾ 3 65 ⫾ 21 35 ⫾ 10 23 ⫾ 5 1.3 ⫾ 0.3 –1.7 ⫾ 0.6 –1.7 ⫾ 0.4
57 ⫾ 9 19 (90%) 7 (33%) 168 ⫾ 9 79 ⫾ 11 82 ⫾ 62 60 ⫾ 7 42 ⫾ 6 22 ⫾ 3 77 ⫾ 26 41 ⫾ 13 19 ⫾ 6 0.9 ⫾ 0.4 –1.2 ⫾ 0.6 –1.2 ⫾ 0.6
1.08 (0.99–1.16) 0.81 (0.24–2.73) 0.95 (0.87–1.03) 1.00 (0.95–1.06) 1.01 (0.99–1.02) 0.99 (0.89–1.08) 1.07 (0.97–1.18) 1.11 (0.91–1.36) 1.02 (0.99–1.05) 1.05 (0.99–1.11) 0.80 (0.69–0.92) 0.01 (0.001–0.191) 3.62 (1.21–10.87) 9.47 (1.91–47.10)
Multivariate P value .05 .19 .73 .18 .96 .18 .75 .19 .31 .09 .11 o.01 o.02 .021 o.01
Odds ratio (95% confidence interval)
P value
0.80 (0.69–0.92)
o.01
2D ¼ 2-dimensional; AF ¼ atrial fibrillation; AP ¼ anteroposterior; EF ¼ ejection fraction; LA ¼ left atrium; LV ¼ left ventricle; max ¼ maximal; SRa ¼ strain rate late diastolic; SRe ¼ early diastolic strain rate; SRs ¼ systolic strain rate; Ss ¼ strain systolic. Bold values ¼ significant values in univariate and multivariate analysis. Underlined values ¼ Significant values in univariate analysis.
Montserrat et al Table 3
Left Atrial Function as a Predictor of Second RFCA
15
Predictors of success of second RFCA Univariate
Age (years) Men (%) Paroxysmal AF Hypertension (%) Height (cm) Weight (kg) Time since AF diagnosis (months) LV EF (%) AP diameter (mm) Indexed AP diameter (mm/m2) LA max volume 2D (mL) Indexed LA max volume2D (mL/ m2) LASs (%) LASRs(s–1) LASRe(s–1) LASRa(s–1)
Multivariate
Successful RFCA (n ¼ 22)
Recurrent AF (n ¼ 13)
Odds ratio (95% confidence interval)
P value
53 ⫾ 7 17 (77%) 15 (68%) 12 (55%) 172 ⫾ 8 84 ⫾ 14 80 ⫾ 54 61 ⫾ 4 41 ⫾ 5 20.6 ⫾ 3.4 64.2 ⫾ 25.3 32.3 ⫾ 14.4 18 ⫾ 4 1.1 ⫾ 0.3 –1.5 ⫾ 0.6 –1.1 ⫾ 0.3
57 ⫾ 8 11 (85%) 9 (69%) 10 (77%) 170 ⫾ 9 81 ⫾ 12 67 ⫾ 38 61 ⫾ 5 42 ⫾ 3 21.9 ⫾ 2.4 72.0 ⫾ 17.9 37.1 ⫾ 9.6 11 ⫾ 5 0.7 ⫾ 0.2 –1.1 ⫾ 0.4 –0.7 ⫾ 0.4
1.09 (0.98–1.21) 1.51 (0.32–7.07) 0.96 (0.22–4.19) 3.03 (0.64–14.26) 0.97 (0.89–1.06) 0.98 (0.93–1.04) 0.99 (0.98–1.01) 0.98 (0.83–1.16) 1.08 (0.91–1.28) 1.16 (0.90–1.49) 1.02 (0.98–1.05) 1.03 (0.97–1.09) 0.68 (0.52–0.87) 0.002 (0.00–0.11) 5.99 (1.13–31.69) 23.72 (1.71–328.63)
.11 .60 .95 .16 .50 .49 .50 .83 .41 .26 .33 .29 o.01 o.01 .04 .02
Odds ratio (95% confidence interval)
P value
0.68 (0.52–0.87)
.02
2D ¼ 2–dimensional; AF ¼ atrial fibrillation; AP ¼ anteroposterior; EF ¼ ejection fraction; LA ¼ left atrium; LV ¼ left ventricle; max ¼ maximal; SRa ¼ strain rate late diastolic; SRe ¼ early diastolic strain rate; SRs ¼ systolic strain rate; Ss ¼ strain systolic. Bold values ¼ significant values in univariate and multivariate analysis. Underlined values ¼ significant values in univariate analysis.
second RFCA procedure. In the ROC analysis, LASs 412% predicted arrhythmia elimination with sensitivity of 84% and specificity of 90% (Figure 2).
Reproducibility study Reproducibility of LASs measurements was excellent (Figure 3). Interobserver Linn concordance was 0.97 and intraobserver was 0.99 (Figure 3). The value of agreement of Linn concordance was defined as o0.90: poor; 0.90–0.95: moderate; 0.95–0.99: substantial; and 40.99: almost perfect.20
Figure 2 Receiver operating characteristic (ROC) curve of LASs for predicting arrhythmia elimination with a second radiofrequency catheter ablation. AUC ¼ area under the curve; LASs ¼ longitudinal left atrial systolic strain with speckle tracking.
Discussion Our study had 2 main findings: (1) LA function as determined by longitudinal myocardial deformation differed significantly between patients with similar LA size (mildly dilated) undergoing a first and a repeated RFCA procedure; and (2) LA function as determined by LASs, and not LA size, was an independent predictor of arrhythmia elimination after both a first and a repeated RFCA procedure in AF patients with mildly enlarged atria.
Predictors of response to first RFCA procedure Several previous studies have shown the potential of LA size as a predictor of success in eliminating AF after a first RFCA.4–9 Indeed, in a previous study from our group,10 98% of patients with an anteroposterior LA diameter 451.5 mm had AF recurrence after a first RFCA procedure. In the present study, however, LA diameter or volumes (either absolute or indexed by body size) did not predict success after RFCA. Differences in patient populations, with a wider range of LA dilation in our former study and only mild LA dilation in the present study, could account for these different findings. With the improved results of RFCA for AF, current guidelines also recommend RFCA as first-line therapy in selected patients with symptomatic paroxysmal AF as an alternative to antiarrhythmic drug therapy (IIaB)15 and even in patients with persistent AF.21 Consequently, approaching AF patients with milder LA dilation might become a more usual practice when evaluating candidates for RFCA. In these patients, more sensitive tools, such as those analyzing LA function (myocardial deformation), might be helpful in addition to LA size, as our results indicate. Additionally, LA myocardial deformation with the use of ST requires no additional imaging beyond conventional 2-dimensional
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Figure 3
Heart Rhythm, Vol 12, No 1, January 2015
Bland-Altman analysis of LASs interobserver and intraobserver variability. LASs ¼ longitudinal left atrial systolic strain with speckle tracking.
echocardiography, which usually is indicated to evaluate LA size and potential underlying cardiopathy in AF patients.
Previous studies using LA deformation imaging Recent studies have shown the feasibility and potential use of LA deformation for evaluating LA function. Using ST echocardiography, it has been shown that LA deformation is useful for predicting new AF episodes after an episode of paroxysmal AF22 and for predicting AF after coronary artery bypass surgery.19 Moreover, LA reservoir function predicts AF recurrence after catheter ablation.23 LA global strain parameters were superior to regional LA function analysis for predicting AF recurrences after first catheter ablation.24
LASs and LASRs are inversely related to LA wall fibrosis detected by delayed enhancement magnetic resonance imaging, which in turn predicts success after a first RFCA in patients with paroxysmal and persistent AF.25 Our study adds further evidence that LA reservoir function (LASs, LASRs) and LA contractile function (LASRa) are parameters with adequate sensitivity and specificity for predicting arrhythmia suppression after a first RFCA.
Predictors of success after second RFCA procedures The study of potential predictors of arrhythmia elimination based on clinical or imaging characteristics has been mainly limited to patients undergoing a first procedure of RFCA for AF (at most, mixed patients with first and repeated
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Left Atrial Function as a Predictor of Second RFCA
procedures). Little is known about what would improve the selection of patients who would undergo a second procedure. Prior studies have shown that LA size or even LA function evaluated with 3-dimensional echocardiography failed to predict which patients would have no recurrences after a second RFCA.10 These findings highlight the unique LA scenario of patients undergoing a second RFCA procedure, in whom the LA tissue has different properties related to both the underlying atrial disease and the atrial scarring secondary to the previous ablation.26 Recent data suggest that surgical ablation in patients with recurrent AF after a first percutaneous RFCA is more effective in eliminating the arrhythmia, even though catheter ablation is associated with fewer complications.27 Therefore, detecting predictors of nonrecurrence after repeated RFCA is essential for choosing the correct (percutaneous or surgical) procedure. In the present study, we found that LASRs, LASRa, and particularly LASs were predictors of success after a second RFCA procedure, showing that these could be more sensitive parameters for evaluating LA status and performance. Consequently, they could be useful for improving patient selection as candidates for a second RFCA procedure. To our knowledge, this is the first study with myocardial deformation imaging to separately analyze patients with second RFCA procedures, and it was shown to be a feasible and noninvasive technique for predicting the success of the procedure and potentially improving the selection of candidates for a second procedure. LA reservoir function depends on LV systolic function and LA wall stiffness.28 In our patients, no differences were found with regard to LV systolic function, as shown by LV ejection fraction or LV global strain, between patients with or those without arrhythmia recurrences. Therefore, at least in our population, LASs seems additionally related to LA wall stiffness and potentially to LA fibrosis. This finding also confirms previous reports showing the relationship between LA wall fibrosis visualized by delayed enhancement magnetic resonance imaging and LASs and LASRs25 and provides more evidence for the use of LA strain as a surrogate of LA fibrosis.
Study limitations One limitation of our study was the relatively small sample size, especially the patients with a second RFCA procedure, so further studies are warranted to confirm our findings in this type of patient. Another limitation is related to the technique itself because the software used to measure myocardial deformation is designed for the ventricle. Adequate tracking was obtained in all LA segments in all cases, and the reproducibility was good. Our analysis of LA deformation was limited to the 4-chamber view (septal and lateral walls of the LA), and inclusion of the 2-chamber view (anterior and inferior LA walls) potentially could have added valuable information. LA function was analyzed in all patients while they were in stable, persistent, sinus rhythm. However, no routine
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continuous ECG recordings were obtained, and previous AF burden and duration could indeed be a case where diagnosis was missed as only symptomatic palpitations detected before ablation were registered and considered to be AF.29
Conclusion Evaluation of LA function adds useful information for selection of candidates to receive RFCA for AF. LA function assessment with myocardial deformation echocardiography is feasible and reproducible and could help to select patients before a first and even before a second RFCA procedure.
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17. Pappone C, Rosanio S, Augello G, Vicedomini G, Loricchio ML, Shpun S, Rillo M, Calabrò MP, Conversano A, Ben-Haim SA, Cappato R, Chierchia S. Mortality, morbidity, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled nonrandomized longterm study. J Am Coll Cardiol 2003;42:185–197. 18. Lang RM, Bierig M, Devereux RB, Flachskampf FA, 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. J Am Soc Echocardiogr 2005;18:1440–1463. 19. Gabrielli L, Corbalan R, Córdova S, Enríquez A, Mc Nab P, Verdejo HE, Godoy I, Zalaquett R, Lavandero S. Left atrial dysfunction is a predictor of postcoronary artery bypass atrial fibrillation: association of left atrial strain and strain rate assessed by speckle tracking. Echocardiography 2011;28:1104–1108. 20. McBride GB. A proposal for strength-of-agreement criteria for Lin's concordance correlation coefficient. NIWA Client Report: HAM2005-062, 2005. 21. Mont L, Bisbal F, Hernández-Madrid A, et al. Catheter ablation vs. antiarrhythmic drug treatment of persistent atrial fibrillation: a multicenter, randomized, controlled trial (SARA study). Eur Heart J 2014;35:501–507. 22. Tsai WC, Lee CH, Lin CC, Liu YW, Huang YY, Li WT, Chen JY, Lin LJ. Association of left atrial strain and strain rate assessed by speckle tracking echocardiography with paroxysmal atrial fibrillation. Echocardiography 2009;26: 1188–1194. 23. Mirza M, Caracciolo G, Khan U, Mori N, Saha SK, Srivathsan K, Altemose G, Scott L, Sengupta P, Jahangir A. Left atrial reservoir function predicts atrial
24.
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fibrillation recurrence after catheter ablation: a two-dimensional speckle strain study. J Interv Card Electrophysiol 2011;31:197–206. Hammerstingl C, Schwekendiek M, Momcilovic D, Schueler R, Sinning JM, Schrickel JW, Mittmann-Braun E, Nickenig G, Lickfett L. Left atrial deformation imaging with ultrasound based two-dimensional speckle-tracking predicts the rate of recurrence of paroxysmal and persistent atrial fibrillation after successful ablation procedures. J Cardiovasc Electrophysiol 2012;23:247. Kuppahally SS, Akoum N, Burgon NS, et al. Left atrial strain and strain rate in patients with paroxysmal and persistent atrial fibrillation: relationship to left atrial structural remodeling detected by delayed-enhancement MRI. Circ Cardiovasc Imaging 2010;3:231–239. Montserrat S, Sitges M, Calvo N, Silva E, Tamborero D, Vidal B, Berruezo A, Bernado C, Mont L, Brugada J. Effect of repeated radiofrequency catheter ablation on left atrial function for the treatment of atrial fibrillation. Am J Cardiol 2011;108:1741–1746. Boersma LV, Castella M, van Boven W, Berruezo A, Yilmaz A, Nadal M, Sandoval E, Calvo N, Brugada J, Kelder J, Wijffels M, Mont L. Atrial fibrillation catheter ablation versus surgical ablation treatment (FAST): a 2-center randomized clinical trial. Circulation 2012;125:23–30. Barbier P, Solomon SB, Schiller NB, Glantz SA. Left atrial relaxation and left ventricular systolic function determine left atrial reservoir function. Circulation 1999;100:427–436. Charitos EI, Pürerfellner H, Glotzer TV, Ziegler PD. Clinical classifications of atrial fibrillation poorly reflect its temporal persistence: insights form 1195 patients continuously monitored with implantable devices. J Am Coll Cardiol 2014;63(25 Pt A):2840–2848.
CLINICAL PERSPECTIVES Left atrial (LA) function measured with deformation imaging (strain and strain rate) predicts elimination of atrial fibrillation (AF) after repeated radiofrequency catheter ablation (RFCA). To our knowledge, this is the first study to detect baseline predictors of success of a repeated RFCA in patients with nonvalvular AF and mildly dilated LA but no other comorbidities. In previous studies, LA size and function evaluated by volumetric changes failed to detect response of second RFCA. Analysis of LA function using deformation imaging is a newer tool that has been shown to be related to LA fibrosis assessed with magnetic resonance and LA histopathology. This new medical knowledge improves patient care because repeated procedures often are necessary and adequate selection of patients is mandatory given that these procedures potentially, although infrequently, could have complications. Moreover, the technique might be helpful for selecting patients undergoing either RFCA or surgical ablation of AF. A surgical ablation approach could be more effective after a failed prior percutaneous ablation but at the cost of a higher rate of complications compared to RFCA. Evaluation of LA function (LA strain and strain rate) is a relatively easy, reproducible, inexpensive, and available tool that permits better selection of these patients. In clinical practice, patients with better LA strain could benefit from a second RFCA, whereas patients with more impaired LA strain should be referred for surgical ablation or kept on rate control therapy rather than undergoing a highly probable unsuccessful repeated ablation.
independent predictor of arrhythmia suppression after a first RFCA and after a second RFCA, with the best cutoff at LASs 420% (sensitivity 86%, specificity 70%) and LASs 412% (sensitivity 84%, specificity 90%), respectively.
OBJECTIVE The purpose of this study was to evaluate left atrial (LA) size and function as potential predictors of second RFCA for atrial fibrillation (AF).
CONCLUSION LA myocardial deformation imaging is a reliable tool for predicting success after a first and a second RFCA. These parameters could improve candidate selection, especially for a second RFCA.
METHODS Thirty-three healthy volunteers (group I) and 83 patients with symptomatic drug-refractory AF treated with a first RFCA (group II, n ¼ 48) or a second RFCA (group III, n ¼ 35 patients) were included. Echocardiography was performed in all patients in sinus rhythm before RFCA and in all volunteers. LA size and function were measured using longitudinal strain and strain rate during ventricular systole (LASs, LASRs) and during early diastole (LASRe) or late diastole (LASRa) with speckle tracking echocardiography. The effectiveness of RFCA on arrhythmia recurrence was evaluated at 6month follow-up. RESULTS LASs, LASRs, and LASRa were significantly lower in group III patients compared to other groups (P o .001 for all). LA diameter or volumes did not predict success after RFCA. LASs was an
Introduction Radiofrequency catheter ablation (RFCA) has become an important alternative for the treatment of patients with symptomatic drug-refractory atrial fibrillation (AF).1,2 However, potential—albeit infrequent—complications of the procedure and the arrhythmia recurrence rate warrant careful selection of candidates for RFCA.3 Enlarged left atrium (LA)4–9 has been related to AF recurrence after a first RFCA procedure, and LA function assessed by 3-dimensional Address reprint requests and correspondence: Dr. Marta Sitges, Cardiology Department, Thorax Institute, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain. E-mail address: [email protected].
1547-5271/$-see front matter B 2015 Heart Rhythm Society. All rights reserved.
KEYWORDS Atrial fibrillation; Atrial function; Second catheter ablation; Predictors; Strain; Strain rate ABBREVIATIONS AF ¼ atrial fibrillation; LA ¼ left atrial; LASRa ¼ longitudinal left atrial late diastole strain rate with speckle tracking; LASRe ¼ longitudinal left atrial early diastole strain rate with speckle tracking; LASRs ¼ longitudinal left atrial systolic strain rate with speckle tracking; LASs ¼ longitudinal left atrial systolic strain with speckle tracking; LV ¼ left ventricle; RFCA ¼ radiofrequency catheter ablation; ROC ¼ receiver operating characteristic; ST ¼ speckle tracking (Heart Rhythm 2015;12:11–18) rights reserved.
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2015 Heart Rhythm Society. All
echocardiography is a predictor of success in eliminating the arrhythmia after a first RFCA procedure.10 Despite improved RFCA success with repeated procedures, predictors of arrhythmia suppression after a second RFCA procedure are not known.11 In a previous study, LA size and LA function assessed by 3-dimensional echocardiography failed to predict AF recurrence after a second RFCA.10 Myocardial deformation imaging derived from speckle tracking (ST) represents a novel tool for evaluating LA performance.12–14 Accordingly, the aim of the present study was to analyze LA function with myocardial deformation imaging in patients before a first or second RFCA procedure and to http://dx.doi.org/10.1016/j.hrthm.2014.08.032
12 determine if deformation parameters could improve patient selection for second RFCA procedures.
Methods Study subjects and protocol In order to compare values of LA myocardial deformation values between patients with AF and healthy individuals, a group of 33 healthy volunteers (group I) was recruited from the staff of our institution. Volunteers with no record of cardiovascular disease were matched for age, sex, and body surface area with AF patients. Eighty-three patients with symptomatic drug-refractory AF undergoing RFCA were included in the study. A first RFCA was performed in 48 patients (58%, group II), and a second RFCA was carried out in 35 patients (42%, group III). None of the patients underwent electrical cardioversion in the previous 3 months before ablation. Indications for a first RFCA were symptomatic drug-refractory AF or intolerance to at least 1 class I or III antiarrhythmic medication. A second RFCA procedure was indicated in patients with symptomatic drug-refractory AF after a blanking period of 3 months after a first RFCA following current recommendations.15 Patients with significant valvular heart disease or prior valve surgery and those with moderate-to-severe left ventricular (LV) hypertrophy were excluded. All patients provided written informed consent, and the study was approved by the ethics committee of our institution.
Percutaneous radiofrequency ablation Catheter ablation was performed using a 3-dimensional electroanatomic mapping system (CARTO, Biosense Webster, Diamond Bar, CA) to support the creation and validation of radiofrequency lesions. The integration of previously acquired multidetector computed tomography or cardiac magnetic resonance imaging helped to optimize 3dimensional reconstruction. Both an ablation catheter and a circular catheter for registry and stimulation (Lasso, Biosense Webster; or Inquiry Optima, St. Jude Medical, Minnesota) were introduced percutaneously through the femoral vein. A double transseptal puncture was performed to access the LA.3 Radiofrequency was delivered through an irrigated-tip thermocouple-equipped catheter (3.5 mm) using a target temperature of 451C at 40 W. Radiofrequency lesions were delivered surrounding each ipsilateral pulmonary vein as previously described.16,17 The target was reduction of local electrogram to o0.15 mV and elimination of pulmonary vein potentials with establishment of bidirectional conduction block between the LA and pulmonary veins. In patients with persistent AF, additional radiofrequency applications were made along the LA roof, LA posterior wall, and along the mitral isthmus at the discretion of the operator. In repeated RFCA procedures, the first goal was reisolation of the pulmonary veins and then identification of nonpulmonary vein triggers.15
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Clinical follow-up All patients were evaluated at 1-, 3-, and 6-month follow-up after RFCA, including outpatient visits with clinical evaluation, serial ECG, rigorous pharmacologic control of hypertension, and 24-hour Holter monitoring to detect asymptomatic AF episodes.15 After ablation, all patients continued oral anticoagulation for a minimum of 3 months, and continued anticoagulation therapy was based on CHA2DS2-VASc cardioembolic risk score.15 Previous antiarrhythmic therapy was maintained for at least 1 month and then discontinued if no AF recurrences were detected. The procedure was considered successful if there were no recurrences of atrial tachycardia lasting 430 seconds during follow-up, after a blanking period of 3 months.15
Echocardiography All patients underwent transthoracic and transesophageal echocardiography before the RFCA procedure, using a commercially available ultrasound scanner (Philips IE33, Andover, MA) to rule out structural heart disease and LA thrombi and to assess LA size and function. All images were digitally stored and transferred to a workstation for offline analysis. Special care was taken to acquire 2D images with a frame rate 450 frames per second for adequate analysis of myocardial deformation with ST. LA and LV measurements were obtained according to the recommendations of the American Society of Echocardiography.18 LV ejection fraction was determined using the biplane Simpson method.18
LA atrial deformation study Special care was taken during echocardiographic image acquisition to ensure adequate LA tracking and avoid interference with the pulmonary veins and the LA appendage to measure global strain and strain rate of the LA. LA longitudinal myocardial deformation assessed by 2dimensional echocardiography using ST was analyzed offline with a commercially available software package (Qlab version 7.1, Speckle Tracking, Philips, Andover, MA). From the apical 4-chamber view, 3 points in the LA (2 in the mitral annulus and 1 in the LA roof) were marked, and the endocardial border was manually traced using a point-andclick technique. All patients were in sinus rhythm during echocardiography. To assess longitudinal deformation of the LA, the following parameters were calculated, with the reference point set at the onset of the QRS complex of the surface ECG13,14: LASs (LA strain during ventricular systole) (Figure 1), LASRs (LA strain rate during ventricular systole), LASRe (LA strain rate during early ventricular filling phase), and LASRa (LA strain rate during late diastole) (Figure 1). The software divided the LA wall into 6 segments,19 and the average was taken for analysis.
Statistical analysis Continuous variables are given as mean value ⫾ SD. Categorical variables are expressed as total number
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Left Atrial Function as a Predictor of Second RFCA
13
Figure 1 Left: Tracing of the left atrial (LA) wall from the apical 4-chamber view obtained by transthoracic bidimensional echocardiography. The tracing is automatically divided into 6 LA wall segments (represented in 6 different colors). Middle: For each segment, a segmental trace of longitudinal myocardial strain and strain rate was obtained. Right: The 6 corresponding segmental curves (one for each LA wall segment that was analyzed) are averaged, and the software depicts an averaged curve of LA strain (global LA strain) and another averaged curve of LA strain rate (global LA strain rate). From the average strain curves, LA peak systolic (LASs) strain, representing LA reservoir function, was identified as the peak positive strain value during LV systole, taking as a reference point the onset of the QRS on ECG.14 From the average strain rate curves, longitudinal LA peak positive strain rate (LASRs) was identified at the beginning of LV systole (QRS onset), with peak negative strain rate during early diastole (LASRe) representing conduction function at the early diastolic phase and during late diastole (LASRa) representing LA active contraction, after the P wave on ECG.
(percentage). Logistic regression analysis was used to study the effects of baseline characteristics on procedure success in our sample. Univariate logistic regression models were fitted for each of the potential predictors. P o .10 was used to screen covariates. Backward stepwise selection algorithms were used to select covariates included in the multivariate logistic regression model. At each step, the least significant variable was discarded from the model. LASs and LASRs were considered dependent variables due to high correlation (r ¼ 0.86, P o .001); therefore, in the multivariate analysis, only LASs is included because it has a more robust reproducibility. Independent covariates with P o .10 remained in the final model. Odds ratio and 95% confidence interval were calculated. Receiver operating characteristic (ROC) analyses were used to establish the optimal cutoff value for predicting recurrence in our sample. Linn concordance coefficient was calculated to study the reproducibility of the measured variables.20 A 2-sided type I error of 5% was used for all tests. Finally, interobserver and intraobserver reproducibility were evaluated by repeating measurements on the same views of the LA by 2 blinded echocardiographers. Statistical analysis was performed using R for Windows (version 2.15.1, R Project for Statistical Computing, Vienna, Austria).
Results Baseline characteristics and follow-up Baseline clinical and echocardiographic characteristics of the study population and pharmacologic therapies are given in Table 1. Patients undergoing second RFCA (group III) were treated with more antiarrhythmic drugs and showed more frequent persistent AF and hypertension. There were no significant differences in baseline LA size between patients undergoing a first (group II) or a second (group III) RFCA procedure, despite both being larger compared to controls (group I). Significant and progressive impairment of LA
function was observed in the control group (group I) through group II to group III, as shown by lower values of LASs, LASRs, and LASRa. Globally, RFCA was successful in 49 of 83 patients (59%) at 6-month follow-up. Success after a first procedure was 27 of 48 (56%) and 22 of 35 (63%) after a second procedure. All patients completed follow-up.
LA myocardial deformation predicts arrhythmia elimination after first RFCA Table 2 gives the univariate and multivariate analysis of potential predictors of arrhythmia recurrence after a first RFCA. Patients with AF recurrence after ablation showed significantly more impaired LA function at baseline, with all LA deformation parameters being worse in the patients with recurrences of atrial arrhythmia. There were no differences in baseline LA diameter or LA volume between both groups. In the multivariate analysis, LASs was the only independent predictor of arrhythmia suppression after a first RFCA procedure. In the ROC analysis [area under the curve 0.82 (0.69–0.95], LASs 420% predicted arrhythmia elimination with sensitivity of 86% and specificity of 70%.
LA myocardial function predicts arrhythmia elimination after a repeated RFCA procedure Reconduction of electrical activity to the previously isolated pulmonary veins was demonstrated in all 35 patients (100%) undergoing a second RFCA procedure. Additionally, in 2 patients (6%) another additional trigger out of the pulmonary vein was also found. Table 3 gives the univariate and multivariate analysis of potential predictors of arrhythmia recurrence after a second RFCA procedure. The type of AF (ie, paroxysmal or persistent) was not a predictor of success of ablation in our population. Additionally, there were no differences in LA
14 Table 1
Heart Rhythm, Vol 12, No 1, January 2015 Clinical and echocardiography baseline
Age (years) Men (%) Hypertension (%) Paroxysmal AF (%) Renin-angiotensin inhibitors (%) Height (cm) Weight (kg) BSA (m2) Time since AF diagnosis (months) 42 Antiarrhythmic drugs (%) Coronary artery disease (%) OSAS (%) LV hypertrophy (11–13 mm) (%) LV EF (%) LV diastolic dysfunction Baseline A-wave velocity (cm/s) LV global peak systolic strain (%) LA anteroposterior diameter (mm) LA AP diameter/BSA index (mm/m2) LA maximal 2D volume (mL) LA maximal 2D volume/BSA (mL/m2) LASs (%) LASRs (s–1) LASRe (s–1) LASRa (s–1)
Group I: healthy volunteers (N ¼ 33)
Group II: first RFCA (N ¼ 48)
Group III: second RFCA (N ¼ 35
50 ⫾ 12 26 (79%) 0 (0%)† 0 (0%)† 0 (0%)† 173 ⫾ 0.1 76 ⫾ 10 1.90 ⫾ 0.14 0† 0 (0%)† 0 (0%)† 0 (0%)† 0 (0%)† 62 ⫾ 4 0 (0%)† 62 ⫾ 17 –17 ⫾ 1 36 ⫾ 3† 19 ⫾ 2† 45 ⫾ 14† 23 ⫾ 7† 30 ⫾ 5† 1.8 ⫾ 0.4† –2.3 ⫾ 0.9† –2.2 ⫾ 0.9†
54 ⫾ 9 35 (73%) 18 (37%)* 46 (96%)* 20 (42%)* 170 ⫾ 1 78 ⫾ 11 1.92 ⫾ 0.16 70 ⫾ 51* 18 (38%)* 4 (1%)* 9 (19%)* 7 (15%)* 61 ⫾ 6 11 (23%)* 63 ⫾ 21 –17 ⫾ 2 41 ⫾ 6* 21 ⫾ 3* 70 ⫾ 24* 38 ⫾ 12.* 20 ⫾ 6* 1.1 ⫾ 0.4* –1. ⫾ 0.6* –1.4 ⫾ 0.6*
54 ⫾ 8 26 (74.3%) 21 (60%)‡ 24 (68.5%)‡ 17 (48.6 %) 171 ⫾ 8.5 82 ⫾ 13 1.98 ⫾ 0.19 76 ⫾ 51 22 (63%)‡ 4 (11%) 7 (20%) 9 (26%) 61 ⫾ 4 8 (22%) 56 ⫾ 23 –17 ⫾ 1 41 ⫾ 5 21 ⫾ 2 67 ⫾ 23 35 ⫾ 13 15 ⫾ 5‡ 0.9 ⫾ 0.3‡ –1.3 ⫾ 0.6 –0.9 ⫾ 0.4‡
2D ¼ 2-dimensional; AF ¼ atrial fibrillation; AP ¼ anteroposterior; BSA ¼ body surface area; EF ¼ ejection fraction; LA ¼ left atrium; LV ¼ left ventricle; OSAS ¼ obstructive sleep apnea syndrome; RFCA ¼ radiofrequency catheter ablation; SRa ¼ late diastolic strain rate, SRe ¼ early diastolic strain rate; SRs ¼ systolic strain rate; Ss ¼ systolic strain. * P o 0.05 difference control vs first RFCA. † P o .05 difference control vs second RFCA. ‡ P o 0.05 difference first RFCA vs second RFCA.
size and function between patients with paroxysmal or persistent AF before a repeated RFCA. Again, baseline LASs, LASRs, and LASRa were significantly reduced in patients with AF recurrence after a second Table 2
RFCA procedure. There were no differences in LA diameter or LA volume between patients with or those without recurrences. In the multivariate analysis, LASs was the only independent predictor of arrhythmia recurrence after a
Predictors of success after a first RFCA Univariate
Age (years) Paroxysmal AF Hypertension (%) Height (cm) Weight (kg) Time since AF diagnosis (months) LV EF (%) AP diameter (mm) Indexed AP diameter (mm/m2) LA max volume 2D (mL) Indexed LA max volume (mL/m2) LASs (%) LASRs (s–1) LASRe (s–1) LASRa (s–1)
Successful RFCA (n ¼ 27)
Recurrent AF (n ¼ 21)
Odds ratio (95% confidence interval)
52 ⫾ 9 27 (100%) 10 (37%) 172 ⫾ 7 78 ⫾ 12. 60 ⫾ 39 61 ⫾ 5 40 ⫾ 6 21 ⫾ 3 65 ⫾ 21 35 ⫾ 10 23 ⫾ 5 1.3 ⫾ 0.3 –1.7 ⫾ 0.6 –1.7 ⫾ 0.4
57 ⫾ 9 19 (90%) 7 (33%) 168 ⫾ 9 79 ⫾ 11 82 ⫾ 62 60 ⫾ 7 42 ⫾ 6 22 ⫾ 3 77 ⫾ 26 41 ⫾ 13 19 ⫾ 6 0.9 ⫾ 0.4 –1.2 ⫾ 0.6 –1.2 ⫾ 0.6
1.08 (0.99–1.16) 0.81 (0.24–2.73) 0.95 (0.87–1.03) 1.00 (0.95–1.06) 1.01 (0.99–1.02) 0.99 (0.89–1.08) 1.07 (0.97–1.18) 1.11 (0.91–1.36) 1.02 (0.99–1.05) 1.05 (0.99–1.11) 0.80 (0.69–0.92) 0.01 (0.001–0.191) 3.62 (1.21–10.87) 9.47 (1.91–47.10)
Multivariate P value .05 .19 .73 .18 .96 .18 .75 .19 .31 .09 .11 o.01 o.02 .021 o.01
Odds ratio (95% confidence interval)
P value
0.80 (0.69–0.92)
o.01
2D ¼ 2-dimensional; AF ¼ atrial fibrillation; AP ¼ anteroposterior; EF ¼ ejection fraction; LA ¼ left atrium; LV ¼ left ventricle; max ¼ maximal; SRa ¼ strain rate late diastolic; SRe ¼ early diastolic strain rate; SRs ¼ systolic strain rate; Ss ¼ strain systolic. Bold values ¼ significant values in univariate and multivariate analysis. Underlined values ¼ Significant values in univariate analysis.
Montserrat et al Table 3
Left Atrial Function as a Predictor of Second RFCA
15
Predictors of success of second RFCA Univariate
Age (years) Men (%) Paroxysmal AF Hypertension (%) Height (cm) Weight (kg) Time since AF diagnosis (months) LV EF (%) AP diameter (mm) Indexed AP diameter (mm/m2) LA max volume 2D (mL) Indexed LA max volume2D (mL/ m2) LASs (%) LASRs(s–1) LASRe(s–1) LASRa(s–1)
Multivariate
Successful RFCA (n ¼ 22)
Recurrent AF (n ¼ 13)
Odds ratio (95% confidence interval)
P value
53 ⫾ 7 17 (77%) 15 (68%) 12 (55%) 172 ⫾ 8 84 ⫾ 14 80 ⫾ 54 61 ⫾ 4 41 ⫾ 5 20.6 ⫾ 3.4 64.2 ⫾ 25.3 32.3 ⫾ 14.4 18 ⫾ 4 1.1 ⫾ 0.3 –1.5 ⫾ 0.6 –1.1 ⫾ 0.3
57 ⫾ 8 11 (85%) 9 (69%) 10 (77%) 170 ⫾ 9 81 ⫾ 12 67 ⫾ 38 61 ⫾ 5 42 ⫾ 3 21.9 ⫾ 2.4 72.0 ⫾ 17.9 37.1 ⫾ 9.6 11 ⫾ 5 0.7 ⫾ 0.2 –1.1 ⫾ 0.4 –0.7 ⫾ 0.4
1.09 (0.98–1.21) 1.51 (0.32–7.07) 0.96 (0.22–4.19) 3.03 (0.64–14.26) 0.97 (0.89–1.06) 0.98 (0.93–1.04) 0.99 (0.98–1.01) 0.98 (0.83–1.16) 1.08 (0.91–1.28) 1.16 (0.90–1.49) 1.02 (0.98–1.05) 1.03 (0.97–1.09) 0.68 (0.52–0.87) 0.002 (0.00–0.11) 5.99 (1.13–31.69) 23.72 (1.71–328.63)
.11 .60 .95 .16 .50 .49 .50 .83 .41 .26 .33 .29 o.01 o.01 .04 .02
Odds ratio (95% confidence interval)
P value
0.68 (0.52–0.87)
.02
2D ¼ 2–dimensional; AF ¼ atrial fibrillation; AP ¼ anteroposterior; EF ¼ ejection fraction; LA ¼ left atrium; LV ¼ left ventricle; max ¼ maximal; SRa ¼ strain rate late diastolic; SRe ¼ early diastolic strain rate; SRs ¼ systolic strain rate; Ss ¼ strain systolic. Bold values ¼ significant values in univariate and multivariate analysis. Underlined values ¼ significant values in univariate analysis.
second RFCA procedure. In the ROC analysis, LASs 412% predicted arrhythmia elimination with sensitivity of 84% and specificity of 90% (Figure 2).
Reproducibility study Reproducibility of LASs measurements was excellent (Figure 3). Interobserver Linn concordance was 0.97 and intraobserver was 0.99 (Figure 3). The value of agreement of Linn concordance was defined as o0.90: poor; 0.90–0.95: moderate; 0.95–0.99: substantial; and 40.99: almost perfect.20
Figure 2 Receiver operating characteristic (ROC) curve of LASs for predicting arrhythmia elimination with a second radiofrequency catheter ablation. AUC ¼ area under the curve; LASs ¼ longitudinal left atrial systolic strain with speckle tracking.
Discussion Our study had 2 main findings: (1) LA function as determined by longitudinal myocardial deformation differed significantly between patients with similar LA size (mildly dilated) undergoing a first and a repeated RFCA procedure; and (2) LA function as determined by LASs, and not LA size, was an independent predictor of arrhythmia elimination after both a first and a repeated RFCA procedure in AF patients with mildly enlarged atria.
Predictors of response to first RFCA procedure Several previous studies have shown the potential of LA size as a predictor of success in eliminating AF after a first RFCA.4–9 Indeed, in a previous study from our group,10 98% of patients with an anteroposterior LA diameter 451.5 mm had AF recurrence after a first RFCA procedure. In the present study, however, LA diameter or volumes (either absolute or indexed by body size) did not predict success after RFCA. Differences in patient populations, with a wider range of LA dilation in our former study and only mild LA dilation in the present study, could account for these different findings. With the improved results of RFCA for AF, current guidelines also recommend RFCA as first-line therapy in selected patients with symptomatic paroxysmal AF as an alternative to antiarrhythmic drug therapy (IIaB)15 and even in patients with persistent AF.21 Consequently, approaching AF patients with milder LA dilation might become a more usual practice when evaluating candidates for RFCA. In these patients, more sensitive tools, such as those analyzing LA function (myocardial deformation), might be helpful in addition to LA size, as our results indicate. Additionally, LA myocardial deformation with the use of ST requires no additional imaging beyond conventional 2-dimensional
16
Figure 3
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Bland-Altman analysis of LASs interobserver and intraobserver variability. LASs ¼ longitudinal left atrial systolic strain with speckle tracking.
echocardiography, which usually is indicated to evaluate LA size and potential underlying cardiopathy in AF patients.
Previous studies using LA deformation imaging Recent studies have shown the feasibility and potential use of LA deformation for evaluating LA function. Using ST echocardiography, it has been shown that LA deformation is useful for predicting new AF episodes after an episode of paroxysmal AF22 and for predicting AF after coronary artery bypass surgery.19 Moreover, LA reservoir function predicts AF recurrence after catheter ablation.23 LA global strain parameters were superior to regional LA function analysis for predicting AF recurrences after first catheter ablation.24
LASs and LASRs are inversely related to LA wall fibrosis detected by delayed enhancement magnetic resonance imaging, which in turn predicts success after a first RFCA in patients with paroxysmal and persistent AF.25 Our study adds further evidence that LA reservoir function (LASs, LASRs) and LA contractile function (LASRa) are parameters with adequate sensitivity and specificity for predicting arrhythmia suppression after a first RFCA.
Predictors of success after second RFCA procedures The study of potential predictors of arrhythmia elimination based on clinical or imaging characteristics has been mainly limited to patients undergoing a first procedure of RFCA for AF (at most, mixed patients with first and repeated
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Left Atrial Function as a Predictor of Second RFCA
procedures). Little is known about what would improve the selection of patients who would undergo a second procedure. Prior studies have shown that LA size or even LA function evaluated with 3-dimensional echocardiography failed to predict which patients would have no recurrences after a second RFCA.10 These findings highlight the unique LA scenario of patients undergoing a second RFCA procedure, in whom the LA tissue has different properties related to both the underlying atrial disease and the atrial scarring secondary to the previous ablation.26 Recent data suggest that surgical ablation in patients with recurrent AF after a first percutaneous RFCA is more effective in eliminating the arrhythmia, even though catheter ablation is associated with fewer complications.27 Therefore, detecting predictors of nonrecurrence after repeated RFCA is essential for choosing the correct (percutaneous or surgical) procedure. In the present study, we found that LASRs, LASRa, and particularly LASs were predictors of success after a second RFCA procedure, showing that these could be more sensitive parameters for evaluating LA status and performance. Consequently, they could be useful for improving patient selection as candidates for a second RFCA procedure. To our knowledge, this is the first study with myocardial deformation imaging to separately analyze patients with second RFCA procedures, and it was shown to be a feasible and noninvasive technique for predicting the success of the procedure and potentially improving the selection of candidates for a second procedure. LA reservoir function depends on LV systolic function and LA wall stiffness.28 In our patients, no differences were found with regard to LV systolic function, as shown by LV ejection fraction or LV global strain, between patients with or those without arrhythmia recurrences. Therefore, at least in our population, LASs seems additionally related to LA wall stiffness and potentially to LA fibrosis. This finding also confirms previous reports showing the relationship between LA wall fibrosis visualized by delayed enhancement magnetic resonance imaging and LASs and LASRs25 and provides more evidence for the use of LA strain as a surrogate of LA fibrosis.
Study limitations One limitation of our study was the relatively small sample size, especially the patients with a second RFCA procedure, so further studies are warranted to confirm our findings in this type of patient. Another limitation is related to the technique itself because the software used to measure myocardial deformation is designed for the ventricle. Adequate tracking was obtained in all LA segments in all cases, and the reproducibility was good. Our analysis of LA deformation was limited to the 4-chamber view (septal and lateral walls of the LA), and inclusion of the 2-chamber view (anterior and inferior LA walls) potentially could have added valuable information. LA function was analyzed in all patients while they were in stable, persistent, sinus rhythm. However, no routine
17
continuous ECG recordings were obtained, and previous AF burden and duration could indeed be a case where diagnosis was missed as only symptomatic palpitations detected before ablation were registered and considered to be AF.29
Conclusion Evaluation of LA function adds useful information for selection of candidates to receive RFCA for AF. LA function assessment with myocardial deformation echocardiography is feasible and reproducible and could help to select patients before a first and even before a second RFCA procedure.
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CLINICAL PERSPECTIVES Left atrial (LA) function measured with deformation imaging (strain and strain rate) predicts elimination of atrial fibrillation (AF) after repeated radiofrequency catheter ablation (RFCA). To our knowledge, this is the first study to detect baseline predictors of success of a repeated RFCA in patients with nonvalvular AF and mildly dilated LA but no other comorbidities. In previous studies, LA size and function evaluated by volumetric changes failed to detect response of second RFCA. Analysis of LA function using deformation imaging is a newer tool that has been shown to be related to LA fibrosis assessed with magnetic resonance and LA histopathology. This new medical knowledge improves patient care because repeated procedures often are necessary and adequate selection of patients is mandatory given that these procedures potentially, although infrequently, could have complications. Moreover, the technique might be helpful for selecting patients undergoing either RFCA or surgical ablation of AF. A surgical ablation approach could be more effective after a failed prior percutaneous ablation but at the cost of a higher rate of complications compared to RFCA. Evaluation of LA function (LA strain and strain rate) is a relatively easy, reproducible, inexpensive, and available tool that permits better selection of these patients. In clinical practice, patients with better LA strain could benefit from a second RFCA, whereas patients with more impaired LA strain should be referred for surgical ablation or kept on rate control therapy rather than undergoing a highly probable unsuccessful repeated ablation.
