J Interv Card Electrophysiol DOI 10.1007/s10840-014-9876-0

Left atrial mechanics predict the success of pulmonary vein isolation in patients with atrial fibrillation Sebastian Spethmann & Katharina Stüer & Ivan Diaz & Till Althoff & Bernd Hewing & Gert Baumann & Henryk Dreger & Fabian Knebel

Received: 7 November 2013 / Accepted: 22 January 2014 # Springer Science+Business Media New York 2014

Abstract Background Atrial fibrillation (AF) is a common arrhythmia with relevant impact on mortality and morbidity. Pulmonary vein isolation (PVI) is an established therapy in patients who remain symptomatic under optimal medical therapy. However, up to 70 % of patients present with recurrence of AF after PVI. Therefore, identifying ideal candidates is an unmet clinical need. Left atrial (LA) fibrosis is associated with reduced LA function. Analysis of LA mechanics using 2D speckle tracking echocardiography (STE) might give more insight into LA substrates and be therefore of predictive value. Methods This prospective single-center pilot study included 31 patients (mean age, 62.3±9.1 years; 19 males) with AF who underwent PVI and 20 matched healthy controls (mean age, 60.6±6.6 years; 10 males). 2D STE strain indices of LA reservoir (RLA), conduit, and, if feasible, contractile function, were analyzed before and 6 months after PVI. Assessment of the LV diastolic function was based on standard indices. Responders to PVI were defined as being asymptomatic and free of AF in a 7-day Holter-ECG after 6 months. Results At baseline, all patients with AF had significantly lower reservoir and contractile function compared with controls. After 6 months, 17 patients (54.8 %) were identified as responders. At baseline, the reservoir function was significantly higher in responders compared with nonresponders (32.7± Sebastian Spethmann and Katharina Stüer contributed equally to this manuscript. S. Spethmann (*) : K. Stüer : I. Diaz : T. Althoff : B. Hewing : G. Baumann : H. Dreger : F. Knebel Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charité-Universitätsmedizin Berlin, Charitéplatz 1, Berlin 10117, Germany e-mail: [email protected] S. Spethmann Bundeswehrkrankenhaus Berlin, Abteilung I-Innere Medizin, Scharnhorststr. 13, 10115 Berlin, Germany

11.1 vs. 22.9±10.9 %; P=0.019). Only in responders, RLA and contractile LA function improved and reached normal values whereas LA function remained unchanged in nonresponders. In a ROC analysis, a RLA value of ≥19.5 % discriminated responders and nonresponders in patients with persistent AF with a sensitivity of 86 % and a specificity of 100 % (P=0.012; area under the curve 0.943; CI, 0.81–1.0). Conclusions LA reservoir function helps to predict efficacy of PVI after 6 months. Only in responders, reservoir, and contractile function normalized within 6 months after PVI indicating a lower level of atrial remodeling at baseline. No deleterious effects of ablation were detected in nonresponders. Keywords Left atrium mechanics . 2D strain . Atrial fibrillation . Pulmonary vein isolation

1 Introduction Atrial fibrillation (AF) is the most common clinically relevant arrhythmia with a prevalence of 5–15 % in octogenarians [1] and with high impact on mortality and morbidity [2]. AF is associated with electrical and, in consequence, structural remodeling [3]. Importantly, both seem to be reversible to some extent [4]. In recent guidelines, new aspects regarding catheter ablation have been added. Previously, PVI was recommended to be reserved for patients with AF who remain symptomatic under optimal medical therapy [5]. However, new encouraging data support the strategy to use catheter ablation as firstline therapy for paroxysmal AF rhythm control in selected patients in highly experienced centers [6]. However, even in high-volume centers, catheter ablation of AF conveys a relevant risk of major complications [7, 8] and has yielded varying results in different patient populations [9]. Therefore, appropriate patient selection is mandatory. Even so, up to date the specificity of different clinical parameters is low. Modern

J Interv Card Electrophysiol

echocardiographic methods such as strain imaging allow regional analysis of left atrial (LA) mechanics. LA function comprises three separate components: [10] First, a reservoir for pulmonary venous inflow during ventricular systole. Second, the conduit function for passive emptying during early diastole. At last, in late diastole, the LA contraction completes LV filling. These three distinct phases can be analyzed separately and accurately using strain analysis [10, 11] (Fig. 1). Importantly, the reservoir function is correlated reversely with atrial remodeling and fibrosis [12]. In addition, ablation itself might induce myocardial damage as has been demonstrated by a postprocedural increase of different biomarkers [13]. The objective of this study was therefore to assess LA mechanics using a simple and convenient speckle tracking algorithm to identify potential predictors for the success of PVI in patients with persistent and paroxysmal AF and to analyze effects of PVI on AF.

2 Methods 2.1 Study population In this monocentric, prospective pilot study we enrolled 42 consecutive patients with symptomatic AF who underwent pulmonary vein isolation (PVI) in our center between October 2011 and March 2013. Indications for PVI were symptomatic AF despite optimal medical therapy. Written informed consent was obtained from all participants. The Ethics Committee of the Charité Universitätsmedizin, Berlin, Germany, approved the study. Five patients were excluded due to electrical systole

LA longitudinal strain [%]

RLA

1

2

ELA

ALA

3

time

Fig. 1 Left atrial (LA) longitudinal strain: Early LA filling leads to a peak positive strain (RLA) representing reservoir function (1). In early diastole, the longitudinal strain decreases and approaches a plateau (ELA) followed by a further decline because of the active atrial contraction (ALA). The conduit and contractile function are represented by the respective differences between RLA and ELA (2) as well as ELA and ALA (3)

cardioversion and were consequently not scheduled for PVI. One patient refused follow-up examination due to a dermatological infection and one patient because of logistic reasons (relocation to another part of Germany). Two patients had to be excluded due to a reduced acoustic window. One patient declined the PVI and in one patient the ablation had to be interrupted before complete PVI. Taken together, echocardiographic data from 31 patients (19 patients with paroxysmal AF and 12 patients with persistent AF) were analyzed. In all patients, baseline examination was performed one day prior to PVI. The echocardiographic baseline examinations were analyzed prospectively shortly after PVI without knowledge of the clinical outcome of PVI. The follow-up examination was performed 194.6 ± 43.0 days after PVI. The endpoint was defined as the proportion of responders after PVI. Responders were classified as patients without any symptoms due to AF during the evaluation period and a continuous sinus rhythm (SR) in a 7-days Holter-ECG recording at the time of the follow-up examination. For comparison, 20 gender- (ten women and ten men) and age-matched (mean age, 60.6±6.6 years) subjects with a clinical indication for routine echocardiography but without history or symptoms of arrhythmias or known heart disease were used as the control group. 2.2 Pulmonary vein ablation All procedures were performed under conscious sedation with disoprivan and appropriate doses of dipidolor. After double trans-septal puncture was performed, 5000-10000 units of heparin (100 I.U./kg) were injected into the LA, followed by repetitive injection of heparin to maintain the activated clotting time at ≥250 s during the procedure. Two long sheaths were inserted into the LA (St. Jude Medical Agilis small curl and St. Jude Medical SL 0) for the mapping catheter (Thermocool SF irrigated tip 3.5 mm Catheter, Biosense Webster) and for the lasso catheter (Variable Lasso-Catheter 2515 mm, Biosense Webster), respectively. The electroanatomical mapping was performed as fast anatomical mapping and compared to the CT image for the best understanding of the LA-anatomy. Isolation of the four pulmonary veins (PV) was performed directly at the atrial side of the PVostium but only in case of atrial signals (entrance block). The radiofrequency (RF) energy settings at the RF generator (Stokert EP Shuttle) were chosen between 25 (posterior wall) and 30 W (anterior wall). In addition to the elimination of the PV antrum potentials, an exit block was also demonstrated. In patients with persistent AF, the exit block was confirmed after electrical cardioversion. No patient converted during the ablation procedure. In all cases, we used bi-plane fluoroscopy with right-anterior oblique 40° and left-anterior oblique 50° views.

J Interv Card Electrophysiol

2.3 Echocardiography and Doppler measurements

2.5 Inter- and intraobserver variability analysis

Standard 2D, pulsed-wave (pw) Doppler, and pw-tissue Doppler (TDI) echocardiographic parameters were obtained from parasternal and apical acoustic windows according to the guidelines of the American Society of Echocardiography (ASE) [14] on a Vivid 7 Dimension or Vivid E9 (GE Vingmed, Horton, Norway, M4S or M5S 1.5–4.0 MHz transducer). Patients were imaged in the left lateral decubitus position. The LV ejection fraction (LVEF) was obtained using the AutoEF tool (GE Vingmed, Horton, Norway) as described previsoulsy [15]. LA volumes were obtained based on the recommendation of the ASE [16] and indexed to the body surface area (BSA) calculated by the Mosteller formula [17]. Continuous wave Doppler measurements were analyzed for peak instantaneous velocity. Aortic and mitral regurgitation were assessed according to the recommendations of the European Association of Echocardiography [18]. LV diastolic function was assessed based on the ASE recommendations [19]. The transmitral flow was acquired to obtain peak early (E) and, if feasible, atrial (A) flow velocities. Three beats were averaged in SR, and five consecutive beats were averaged in AF. We used the average peak early diastolic (E′) velocity obtained from the septal and lateral mitral annulus in the four-chamber view with proper TDI settings. If feasible, late diastolic velocity (A′) as well as the isovolumic relaxation time were quantified using pw-TDI at the septal insertion sites of the mitral leaflets in the apical four-chamber view. E/E′ ratio was calculated to estimate LV filling pressures [20].

Two echocardiographers, blinded to previously obtained data, separately measured longitudinal strain (LA reservoir, conduit, and contractile function) of ten random patients for interobserver variability analysis. An experienced observer calculated strain values twice with a time interval of 6 months between for analysis of intraobserver variability. To determine inter- and intraobserver variability, the interclass coefficient was used.

3 Statistics All results are expressed as mean±standard deviation. Statistics were calculated using SPSS 21.0 (IBM Corporation, Armonk, NY, USA) and SAS 9.2 (Statistical Analysis System Institute Inc., NC, USA). Mann–Whitney U test was used for the comparison of two independent groups and Wilcoxon test for the comparison of paired observations. Frequencies of different groups were compared with the help of the Chisquare test. Comparisons of the changes of parameters at baseline and at follow-up of both groups were analyzed with baseline variables as covariates. Area under the receiver operating characteristic (ROC) curve was used to describe the prognostic value of SR parameters for the prediction of SR maintenance after catheter ablation. Sensitivity, specificity, and positive and negative predictive values were calculated. Optimal cut-off values were determined by the analysis of the sensitivity and specificity values derived from the ROC curve data. P values of