European Heart Journal – Cardiovascular Imaging (2014) 15, 32–40 doi:10.1093/ehjci/jet112 Two-dimensional echocardiographic features of the inferior right atrial isthmus: the role of vestibular thickness in catheter ablation of atrial flutter Pedro Marcos-Alberca 1*, Damián Sánchez-Quintana 2, José A. Cabrera3, Jerónimo Farré4, José M. Rubio 4, Jose A. de Agustı́n1, Carlos Almerı́a1, Leopoldo Pérez-Isla 1, and Carlos Macaya1 1 Cardiology Department, Instituto Cardiovascular, Hospital Clı́nico San Carlos, c/ Prof. Martı́n Lagos s/n. 28040 Madrid, Spain; 2Department of Human Anatomy, Universidad de Extremadura, Badajoz, Spain; 3Arrhythmia Unit, Hospital Quirón, Madrid, Spain; and 4Cardiac Electrophysiology Unit, Fundación Jiménez Dı́az, Madrid, Spain Received 6 March 2013; revised 12 May 2013; accepted after revision 17 May 2013; online publish-ahead-of-print 9 June 2013 Objectives The aim of this study was to examine the feasibility of transthoracic two-dimensional (2D)-echocardiography in defining the cavo-tricuspid isthmus (CTI) anatomy and its value concerning the ease of catheter ablation of isthmic atrial flutter (AF). ..................................................................................................................................................................................... Methods CTI analysis was accomplished in 39 cases: 16 necropsy specimens and 23 patients. Sixteen were patients with isthmusdependent AF and seven controls with other supraventricular re-entrant tachycardias. Two-dimensional transthoracic echocardiography and a right atrium angiogram were performed before radiofrequency catheter ablation (RFCA). ..................................................................................................................................................................................... Results The measurements of the CTI with angiography were compared with those taken with echocardiography and correlation was excellent (r ¼ 0.91; P , 0.0001). In normal patients, the dimension of the vestibular thickness was successfully compared and validated with the histological examination of the necropsy specimens: histology median 6.8 mm, range 4.4 –10.5 vs. echo median 6.2 mm, range 5.4 –8.7; P: NS. Vestibular thickness was greater in complex than in simple RFCA (13.6 + 1.9 mm vs. 10.0 + 2.3 mm; P ¼ 0.01). When vestibular thickness ≥11.5 mm, the ablation prone to be complex (sensitivity 83.3%, specificity 80%, positive predictive value 71.4%, and negative predictive value 88.9%). ..................................................................................................................................................................................... Conclusions Two-dimensional transthoracic echocardiography clearly depicts the inferior isthmus and, displaying the thickness of the tricuspid vestibule, it was related with complexity of the ablation procedure in isthmus-dependent AF. ----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords Echocardiography † Atrial flutter † Catheter ablation Introduction Isthmus-dependent common atrial flutter (AF) is the most frequent type of macro-re-entrant atrial tachycardia and the treatment of choice is radiofrequency catheter ablation (RFCA) with bidirectional conduction block across the cavo-tricuspid isthmus (CTI).1 – 9 Nevertheless, ablation cannot be easily achieved in some patients, requiring multiple energy applications and prolonged procedure times. Morphological and histological studies have shown the complex endocardial topography and the considerable variation in the content of myocardium and fibro-fatty tissue of the CTI.10 – 12 These architectural factors may make it difficult to obtain complete and transmural linear lesions across the isthmus, thus, resulting in conduction persistence or recovery at the ablation areas. The right atrial angiographic dimensions and topographic configurations of the inferior isthmus have been shown to be related with the complexity of the ablation procedure, but the atrial wall of the isthmus cannot be visualized with this technique.13 – 15 Intracardiac echocardiography may be useful to characterize the isthmus anatomy and wall thickness.16,17 In contrast, there are a paucity of data about the role of transthoracic echocardiography to well define the anatomy and the atrial wall thickness of the inferior right atrial isthmus.18,19 We examined the two-dimensional (2D)-transthoracic echocardiographic features of the isthmus region and their differences with * Corresponding author. Tel: +34 913303290; fax: +34 913303290, Email: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissions please email: [email protected] Two-dimensional echocardiographic features of the inferior right atrial isthmus 33 Figure 1 Echocardiographic and angiographic imaging of the inferior right atrial isthmus. (A): Transthoracic echocardiography: the CTI plane is obtained applying to the transducer a clockwise rotation and simultaneous posterior tilting. This projection permits correctly visualize the area between the opening of the inferior vena cava (IVC) into the RA and the tricuspid valve, at the same level of the opening of the coronary sinus (OsCS); CTI area is clearly depicted. RV, right ventricle; RA, right atrium; LV, left ventricle. (B) Magnification (zoom) of the CTI area emphasized in frame B (dot line). The elements of the CTI are easily disclosed. Asterisk denotes the thickness of the vestibule (endo-epicardial distance, perpendicular to the vestibule length). Double asterisks denote the depth of the recess, as the perpendicular distance from the recess length to the endocardial boundary. (C) Example of an angiography of the right atrium; processing; and measurement of the CTI and their elements, vestibule and recess. Calibration of the pixel length with the known dimension of the electrode of the HALOw catheter (RV catheter in controls) was undertaken (arrow heads) (D) Zoom view over the right inferior isthmus showing their elements (vestibule and recess). Double arrows denotes the dimensions measured as representative of both. Asterisk denotes the measurement of the recess depth. Examples are representatives of all performed. regard to the laboriousness of catheter ablation in patients with isthmic AF. The results were compared with right atrial angiography and human heart specimens. Methods In this observational study, a total of 32 consecutive patients were evaluated for their participation. Sixteen consecutive patients with isthmus-dependent AF and seven control patients (75% men; 68 + 10 years) referred to our institution for RFCA (57% men, 66 + 5 years) who underwent slow pathway ablation for clinically documented AV nodal re-entrant tachycardia. Requirements for inclusion as a control were the absence of any history of AF and inability to induce this arrhythmia at electrophysiological study. Groups were age and sex matched. In all the patients, we performed a complete transthoracic echocardiographic examination before the ablation procedure and, at the time of the ablation, a right atrial angiography before starting to apply radiofrequency pulses. There were nine exclusions: five in whom the echocardiogram was not performed before the RFCA procedure, two patients who declined RFCA for the index arrhythmia, one patient finally diagnosed of non-re-entrant atrial tachycardia, and one patient due to poor acoustic window. Detailed information was given to all the patients and written consent approved by the local ethic committee was obtained. Echocardiographic and angiographic anatomical isthmic variables for the global and the simple or complex procedures of isthmus ablation were compared. Focused to validate the feasibility of 2D-transthoracic echocardiography to analyse the atrial wall thickness across the isthmus, we have included the histological examination of the isthmus in 16 necropsy specimens and compared with normal control patients. Echocardiographic examination of the CTI The 2D-transthoracic echocardiogram was performed using Phillips Sonos 5500 and Sonos 7500 (Koninklijke, Philips-Electronics, The Netherlands) equipped with harmonic fusion imaging and a broad-band S3 transducer operating at a frequency of 1.8 MHz of emission and 3.6 MHz of receipt. The patient was placed over its left side to perform a standard 2D, transthoracic, and Doppler (colour, continuous, and pulsed wave) examination. To visualize the CTI, we have developed a novel echocardiographic projection by means of the modification of the apical four-chamber views (Figure 1A and B).20 This projection 34 permits the visualization of the inferior right atrium (RA), which is proved trough the exhibit of the opening of the coronary sinus and the opening of the inferior vena cava (IVC) into the atria. Thus, between the tricuspid valve (TV) and the Eustachian ridge of the IVC, the inferior CTI and their elements are clearly delineated: the vestibule, as the plateau immediately behind the anterior leaflet of the TV and the recess, as the pouch-like subeustachian zone close to the vestibule. Adjustment of gain settings and grey scale was optimized to allow a precise endocardial and epicardial definition, avoiding blooming or drop-out echoes which could influence an accurate quantitation. Echocardiographic images were digitally acquired and stored on a magneto-optical disk for subsequent retrieval and detailed analysis of the total dimension of the CTI and their elements. Measurements were carried out using the GPL Java-based-software ImageJ-v1.3, based on the software NIH-Image of National Institutes of Health. Similar to our previously reported angiographic method13, we have measured the distances between the anterior leaflet of the TV and the Eustachian valve as representative of the total echocardiographic dimensions of the CTI, the length of the vestibule and the depth and length of the posterior recess. In addition, the harmonic 2D-echocardiogram allows to disclose the epicardial and endocardial boundaries of the atrial wall at the vestibular area, being the quantification of this distance representative of the wall thickness of the anterior isthmus. The measurement of isthmus length and their elements were performed using the image immediately before the opening of the TV (end-diastolic), similar to those obtained with the right atrial angiograms. The post-procedural echocardiogram and measurement of the vestibular thickness was not performed taking into account the potential effect of the oedema in the dimension obtained. Angiography of the RA: technique, analysis, and measurement of the right atrial isthmus As previously described13, right atrial angiography was performed through an 8F sheath, 40 cm long, inserted into the right internal femoral vein. The inferior CTI was profiled as the area between the Eustachian valve and the plane of the TV annulus. We distinguish the two isthmic components: the ‘pouch-like’ posterior recess and the anterior vestibule of the TV. Angiographic studies were acquired as a serial of frames in the 458 RAO view and digitally recorded on PC-workstation and magneto-optical disk. The frame representative of the inferior isthmus and their elements were selected by the agreement of two experienced investigators. The measure of the CTI and their elements was performed as follows (Figure 1C and D). The digital image in format TIFF of the angiogram was stored and transferred to a personal computer. Thereafter, a postprocessing of the image was carried out to correct visualize and quantify the CTI, using the GPL Java-based-software Image J v1.3. Spatial calibration was accomplished previously to any measurement using as reference the length in pixels of the electrode (7-French HALO catheter) closer to the isthmic area. In controls, calibration was performed over the 5-French bipolar endocavitary ventricular catheter, the nearest to the CTI. We selected these references to minimize the effect of foreshortening in fluoroscopic images. In the full image, the CTI were measured as the distance between the Eustachian valve and the tricuspid plane. Applying a zoom view over the CTI, the vestibule was correctly identified and measured. The recess was measured as the distance between the end of the vestibule at the hinge point of the TV and the opening of the inferior caval vein (ICV). The depth of the recess was measured as the distance between the imaginary line that defines the recess and the bottom of this. Using the methodology reported elsewhere, 14,15 we labelled the CTI as straight if the perpendicular distance from the line traced from P. Marcos-Alberca et al. the TV to the ICV to the deepest point of the recess was ,2 mm, concave for distances from 2 to 5 mm and pouche-like if distance was .5 mm. Electrophysiological study and isthmus ablation The mapping, pacing, and ablation protocols in AF has been published elsewhere.4 – 8,21 – 25 Briefly, if the patient was in AF, electrical recordings of right atrial activity were obtained, ensuring a counter-clockwise activation. Thereafter, conventional entrainment was accomplished using the ablation catheter. If re-entry was confirmed and excitable gap identified over the CTI area, an ablation line was performed at the central/inferior isthmus (at the 6 o’clock region in a fluoroscopic left anterior oblique view). It is worth emphasizing that standard 8-mm tip and four electrodes ablation catheter was used in all patients. A dragging technique starting at the ventricular side of the CTI and pulling the catheter back to the ICV after predetermined timed application was used. When sequential activation was interrupted, pacing from both sides of the ablation line (coronary sinus and right atrial free wall) was performed, ensuring the total interruption of the electrical conduction into the circuit of the flutter in basal conditions and with isoprenaline infusion. Data collected included the number of radiofrequency applications, total duration of them, and total duration of fluoroscopy, including positioning of the sheaths and all the endocavitary catheters (skin-to-skin). All procedures were performed in an unselected basis by one of two senior cardiac arrhythmologist, blinded to the result of the echocardiogram. Anatomic dissection and microscopic examination of the isthmus We examined 16 formalin-fixed hearts from patients who died of noncardiac causes (69% male, mean age 56 + 14 years). The walls of the RA were dissected to display the isthmic area between the TV anteriorly and the Eustachian valve and ridge posteriorly (Figure 2). As previously described, the endocardial surface of the isthmus showed a smooth anterior region that corresponds to the vestibule of the TV, which posteriorly continues with a subeustachian pouch with irregular muscular trabeculations.10,12 Full thickness of the atrial wall at the isthmus area were prepared for light microscopic studies. The sections were then dehydrated and embedded in paraffin, cut into 10-mm-thick slides, and stained with Masson or Jones trichrome for histological analysis. We measured the isthmus wall thickness from the endocardium to the epicardium along the isthmus. Statistical analysis All continuous measurements were expressed as means + SD and categorical variables in absolute values and percentage, except for the comparison of echocardiographic and histological subanalysis of the vestibular thickness, expressed as median and range. The measurements obtained from the echocardiographic and the angiographic exams were compared using the Wilcoxon test for paired-data, Pearson’s bivariate correlation, and the bias with lineal regression and Bland – Altman plots. With the non-parametric test Mann– Whitney U test and receiveroperator characteristic curve, we analyse the accuracy of the echocardiographic and angiographic parameters in the ablation procedure. Categorical variables were analysed using the x2 test or Fisher’s exact test, when necessary. Software used was SPSS (SPSS 15, Inc., Chicago, IL, USA) and Medcalc (MedCalc Soft, Mariakerke, Belgium). Statistical significance was established in a P-value ,0.05. 35 Two-dimensional echocardiographic features of the inferior right atrial isthmus Table 1 Base-line characteristics of the study patients Atrial flutter Control P-value ................................................................................ 67.6 + 10.3 66.0 + 5.4 0.34 Sex, male (%) LA diameter, echo (mm) 75 41 + 4a 57 32 + 6a 0.35 0.04 RA diameter, echo (mm) 55 + 7a 47 + 5a 0.04 LVEF (%) Hypertension (%) 60 + 13 50 68 + 6 57 0.54 0.55 Age (years) COPD (%) 31 0 — Cardiomyopathy (%) Ischaemic (%) 50 25 0 — — — Hypertrophic (%) 6 — — 6 56 — 0 — — Valvular (%) Current AAD (%) a Figure 2 Top: heart specimen with the isthmus viewed in profile. Bottom: histological section of the isthmus with Masson’s trichrome stain (myocardium in red and fibrous tissue in green). The anterior sector corresponds to the vestibule of the tricuspid valve (TV) and is related to the right coronary artery. The posterior sector is closest to the orifice of the inferior cava vein and contains the Eustachian ridge or valve. Absolute values and percentages, except age (means + SD). LA, left atrium, antero-posterior axis; RA, right atrium, supero-inferior axis; LVEF, left ventricular ejection fraction; COPD, chronic obstructive pulmonary disease; AAD, anti-arrhythmic drugs. Results Patient characteristics and ablation procedure Patients relevant clinical characteristic of the study are given in Table 1. Successful radiofrequency ablation was achieved in all the patients without complications. In patients with isthmus-dependent AF, bi-directional conduction block through the CTI was demonstrated at baseline and after infusion of isoprenaline. Procedural parameters for isthmus ablation were as follows: total procedural duration 54.6 + 29.6 min; total fluoroscopic time 44.9 + 29.3 min; the average number of RF applications/patient was 4.1 + 3. The cumulative duration of RF applications was 991 + 762 s, and those of the successful application was 227 + 124 s. The cumulative duration of RF applications, adjusted to the number of applications, showed differences amid 1– 4 applications and 5 applications through the highest value, which were 11 applications in our group. The mean RF-time was 508.5 + 204 s in the former (n ¼ 10, 63%) and 1797.5 + 650 s in the later (n ¼ 6, 37%), P , 0.001. A cut value of 1200 s of RF established in this group a clear division between the simple procedure and the complex procedure. (Figure 3). The ratio of simple/complex procedures according to the operator leading the ablation procedure was proportionate: operator A (n ¼ 10), rate of complex ablation 0.33 and operator B (n ¼ 6), rate of complex ablation 0.4 (P ¼ 0.79). Figure 3 Bars chart showing the mean cumulative RF time grouped by number of applications. A time value of 1200 s (20 min) was chosen as the red line dividing simple from complex procedures. Cut value is in consonance with others published elsewhere. Imaging dimensions of the inferior RA: angiographic and echocardiographic comparisons The overall angiographic and echocardiographic features of CTI were similar, with a posterior pouch-like recess and the anterior linear ( plateau) vestibule of the TV. The correlation and the lineal regression of all echocardiographic and angiographic measures obtained (Figure 4) disclosed an excellent result. The Bland– Altman plot was in consonance with the global correlation. Angiographic and 2D echocardiographic dimensions of the isthmus and their elements are showed in Table 2. Difference between 2D echocardiographic and angiographic measurement was statistically significant for the depth of the posterior recess. As expected, angiographic and 2D echocardiographic dimensions of the CTI were large in AF patients 36 P. Marcos-Alberca et al. total time of RF during ablation trended to be longer whether the CTI exceeds 35 mm (1207 + 968 s vs. 776 + 449 s; P ¼ 0.09). CTI length did not differ between complex (.20 min) and simple (,20 min of RF) subgroups in patients with AF: (37 + 8 vs. 37 + 5 mm; P ¼ NS). CTI was concave in 25% of the angiographies and pouch-like in the remaining 75%. There were no patients with straight morphologies or differences when complexity analysis was performed considering CTI qualitative morphology, concave or pouchlike (P ¼ 0.56, Fisher’s exact test). The exclusive echocardiographic feature, the thickness of the vestibule, disclosed a greater value in the complex group, 13.6 + 1.9 vs. 10.0 + 2.3 mm; P ¼ 0.01 (Table 3 and Figure 5, top). The Receiveroperator characteristic curve pointed out an absolute value of vestibular thickness ≥11.5 mm as related with a complex procedure with a sensitivity of 83.3% and a specificity of 80%, a positive predictive value of 71.4% and a negative predictive value 88.9% (Figure 5, bottom). Intra-observer and inter-observer variability Figure 4 Top: bivariate correlation of 2D-echocardiographic measures and angiographic measures, fitted to a lineal regression equation. Dot line represents the identity line. All measures in millimetres. Bottom: Bland – Altman plot of the 2D-echocardiographic measures vs. angiographic dimensions. Continuous line points out the bias and dot line + 2SD. All measures in millimetres. opposite to the controls: 34 + 6 vs. 28 + 5 mm, P ¼ 0.05 for angiography and 37 + 8 vs. 30 + 5 mm, P ¼ 0.04 for 2D echocardiography. Echocardiographic and histological wall thickness of the inferior isthmus 12 As we previously described in the histological examination, the smooth vestibular area showed the thickest overall atrial wall and muscular content. We included as noteworthy, in echocardiography, the vestibular thickness from the endocardium to the epicardium. In control patients, and compared with structurally normal heart specimens, no significant differences were found in the wall thickness of the vestibule of TV between echocardiographic and histological dimensions: median 6.2 mm (range: 5.4 – 8.7) for echocardiography vs. median 6.8 mm (range 4.4 – 0.5) for histological dimension; P ¼ NS. Echocardiography revealed that patients with AF disclosed a thicker vestibule of the TV than controls (11.4 + 2.8 vs. 6.6 + 1.2; P , 0.0001). Complexity of isthmus ablation procedure: echocardiographic predictors The echocardiographic CTI was large in patients with AF (37 + 8 mm vs. controls 30 + 5 mm.; P ¼ 0.04) and the duration of the In our current practice, the best adherence to accepted standards for the measurements of two-dimensional echo images is encouraged. It was expected an intra-observer and inter-observer variability equal to overall measurements accomplished in 2D echocardiographic examinations using harmonic imaging. To better approach, the obtained result to the real-anatomic dimension, vestibular wall thickness, and distances between endocardial boundaries (i.e. the CTI) were measured from leading to leading echoes, so trying to exclude any fat of the AV groove. Mean bias, intraclass correlation, and 95% confidence intervals of the variability analysis are displayed in Table 4. A good correlation was found; the confidence intervals, similar for intra-observer and inter-observer analysis, were high due to limitations inherent to sample size. Quantification of the angiographic images is not subject to the limitations of those of the transthoracic echocardiography, mainly due to its fixed reference points for the acquisition.13 – 15 Discussion This study evaluates the feasibility of transthoracic 2D echocardiography to characterize the complex anatomical structures of the CTI. Our finding showed that (i) transthoracic echocardiography was able to easily visualize the endocardial topography of the isthmus and their elements as accurately as right atrial angiography; (ii) an unique echocardiographic feature, the wall thickness of the vestibule, was an anatomic marker in our series, related with a difficult isthmus ablation procedure. Our study also produced excellent correlation between thickness measurements of the isthmus made during life and at post-mortem examination, thus establishing the validity of the echocardiographic technique. Anatomy of the CTI: role of the imaging techniques The RA angiography was the first imaging technique used to determine the gross morphology and dimensions of the CTI both in normal and patients with common AF.13 Angiography permits the 37 Two-dimensional echocardiographic features of the inferior right atrial isthmus Table 2 Angiographic and 2D echocardiographic results Angiography 2D echocardiography P-value* Correlation P-value** ............................................................................................................................................................................... No patients 23 23 Right atrium, supero-inferior axis Cavo-tricuspid isthmus 53.0 + 9.5 32.0 + 6.0 50.9 + 6.7 34.8 + 7.6 NS NS 0.64 0.73 ,0.01 ,0.001 Vestibule 13.0 + 2.8 14.4 + 4.1 NS 0.62 ,0.001 Recess Recess, depth 19.2 + 3.9 7.3 + 2.2 22.0 + 7.5 9.9 + 3.4 NS ,0.01 0.54 0.50 0.01 0.02 Measures are length in millimetres and expressed as means + SD. *P-value for comparison of means, ANOVA. **P-value for correlation of paired-data. Pearson’s bivariate correlation. Table 3 Anatomical variables and RF time RF time .............................. <1200 s P-value ≥1200 s ................................................................................ Two-dimensional echocardiography CTI Vestibule 37.3 + 8.4 14.4 + 2.8 37.3 + 5.8 15.5 + 5.6 0.87 1.0 Recess, length 24.0 + 9.8 22.3 + 6.4 0.95 Recess, depth 10.1 + 4.2 13.1 + 3.7 0.15 Vestibule, thickness RA, length 10.0 + 2.3 52.1 + 6.5 13.6 + 1.9 56.6 + 7.2 0.01 0.38 33.7 + 6.0 13.5 + 2.5 33.3 + 5.3 14.4 + 1.4 1.0 0.71 Recess, length 19.7 + 4.6 18.1 + 3.4 1.0 Recess, depth RA, length 8.4 + 2.4 51.6 + 9.7 7.1 + 1.4 58.9 + 2.3 0.5 0.14 Angiography CTI Vestibule RF, radiofrequency. Data are means + SD, in millimetres. visualization of the structures such as the Eustachian valve, caval veins, and TV with an excellent correlation with post-mortem cardiac specimens.13 Two subsequent studies have confirmed the utility of the angiography to disclose the particular characteristics of the inferior RA. It could facilitate ablation in difficult cases due to the highly variable anatomy of the CTI. For instances, these studies point out an enlarged inferior isthmus, prominent eustachian valve, and a welldeveloped pouch-like recess as predictors of difficult isthmus ablation procedures.14,15 In our analysis, most patients had an isthmus concave and especially pouch-like configuration. However, the morphology of the CTI was not related with the complexity of the procedure, but probably is unpowered for this categorical variable. In previous studies, we have demonstrated by histological examination the non-uniform wall thickness of the CTI area.10,12 Thus, according to these anatomic observations, interest merges focused in the visualization of the isthmus wall thickness during the ablation Figure 5 Top: Boxplot (median, maximum, and minimum) of the dimension of the thickness of the vestibule in simple vs. complex procedures. Difference was statistically significant. Bottom: the ROC curve and analysis showed the best result to predict the complexity of the procedure for a cut value of 11.5 mm of vestibular thickness: sensitivity 83.3 (95% CI: 36.1 – 97.2); specificity 80.0 (95% CI: 44.4 – 96.9). 38 P. Marcos-Alberca et al. Table 4 Variability analysis Intraclass Mean Dispersion 95% CI (%) (%) correlation bias (mm) ................................................................................ Intra-observer Wall 0.87 thickness Endocardial 0.82 boundaries Inter-observer 0.3 1.0 231.1 to +33.1 1.7 3.8 219.5 to +27.1 0.70 20.1 21.8 235.6 to 32.0 Endocardial 0.88 boundaries 20.8 21.8 222.5 to 19.0 Wall thickness procedure in patients with AF. However, current imaging techniques used in AF ablation are limited in this context. Fluoroscopic angiography only delineates the endocardial boundary, not allowing visualization of the wall thickness. Intracardiac echocardiography allows the observation and measurement of the isthmus thickness and found that the CTI was significantly thicker adjacent to the tricuspid annulus (vestibular area).16,17 Nonetheless, and opposite to transthoracic echocardiography, its use not precludes invasive catheterization, is expensive and not widely accessible. Transthoracic echocardiography in atrial flutter and implications for catheter ablation The feasibility of transthoracic echocardiograpy to provide anatomic information of the isthmus architecture remains to be systematically analysed. The length of the CTI quantified by means of echocardiography influenced several parameters of the ablation procedure, such as the duration and number of applications of RF.18 However, the components and the wall thickness of the CTI were not analysed in this study. A plane very similar to the right ventricular inflow view, but clearly different to our named CTI-plane, has observed an association between the extension of the Eustachian ridge and difficult ablation, but measurements were not compared with RA angiography and the wall thickness was not evaluated.19 Novel echocardiographic techniques using real-time three-dimensional echocardiography remark this association of Eustachian valve with more laborious RFCA. However, it implies transoesophageal intubation, it was only used in patients under general anaesthesia, quantitative correlations with RA angiography are lacking and the low spatial resolution of 3D imaging not allows wall thickness analysis.26 Other non-invasive imaging techniques, such as cardiac MRI or cardiac computed tomography, could better depict the CTI, their elements and the vestibular thickness, but the experience is either very limited 27,28 or implies exposure to ionizing radiation and iodine contrast.29 Our work characterizes and facilitates the echocardiographic technique to study the anatomy of the RA through the use of the tissue harmonic technology and improves the visualization of the inferior RA with the modified apical view, so-called by us CTI plane.20 Harmonic imaging displays a higher signal-to-noise ratio and an increase of the spatial resolution of the structures more lateral and distant of the transducer, such as the RA and the opening of the IVC. In addition, it reduces side-lobe artefacts, resulting in a darker cavity and brighter walls, thereby improving image contrast and the visualization of the endocardial and the epicardial wall boundaries.30 The advantages of tissue harmonic imaging is clearly remarked by the fact that in our analysis, in spite of a 31% of patients with a past history of chronic obstructive pulmonary diseases, only one patient was excluded due to poor acoustic window, highlighting the feasibility of harmonic transthoracic 2D echocardiography for our purposes. The CTI and their principal elements were clearly delineated and the measurements obtained correlated significantly with those obtained by angiographic studies. Differences in the ortogonality of the cross-sectional echocardiographic plane (apical and posterior) opposite to the fluoroscopic plane (right anterior oblique at 458) account for the overestimation with the 2D echocardiography. This different cut-angle in relation to the CTI is evident in the estimate of recess depth, as indicated by a correlation index of only 0.54. Vestibular thickness and isthmus ablation complexity Noteworthy, our transthoracic echocardiographic approach allowed us to visualize the epicardial and endocardial edges of the vestibule and, therefore, the thickness of this isthmus component. The vestibular thickness in normal patients was closely related with those found in post-mortem specimens, contributing to validate it. In addition to the variable angiographic morphologies and length of the CTI,14,15 the echocardiographic quantification of the vestibular thickness merges as an unique non-invasive anatomic landmark related to the complexity of the ablation procedure. Recently, cardiac computed tomography has demonstrated the close relation between isthmus wall thickness and complex ablation supporting our results.31 The present study demonstrated that a vestibular thickness ≥11.5 mm was related with a superior complexity of the isthmus ablation procedure. Previous studies have shown the presence of ‘gaps’ or remnant tissue from isthmus ablated areas, commonly occurring in the vestibule of TV.32 It has been suggested that transmural ablation of the atrial wall could be required to achieve success.33 Our past anatomical study showed a thicker musculature and criss-crossing muscular fibres at the vestibular isthmus area that may require deeper lesion.12 In addition blood flow of the right coronary artery near the radiofrequency ablation area in the vestibule of the TV may reduce lesion size by convective cooling. In the same way, an intramyocardial ‘small coronary vein’ extending through the vestibule may produce similar cooling preventing transmural lesion formation, and even preserving myocardial tissue in the isthmic scar.12,34 Practical implication of anatomic differences of the CTI for RFCA of AF also has been investigated to enhance the efficacy of the procedure. Hence, when angiography revealed a straight isthmus morphology, ablation using a 8-mm tip catheter (the standard technique) was superior to externally cooled-tip catheter while the opposite tends to take place if the isthmus was concave, although the latter not achieve a significant difference.35 A strategy of RFCA based on targeting high-voltages electrograms obviating a complete ablation 39 Two-dimensional echocardiographic features of the inferior right atrial isthmus line appears very attractive.36 – 38 It establishes a plausible link between difficult RFCA and more or less prominent muscle bundles and with our observed influence of the vestibular thickness, supported with the close relation of echocardiography and necropsy. A full contact of ablation catheter with the isthmus when the vestibule is thicker could be anticipated with recent technologies.39 Limitations of the study Although the patients were consecutive, the feature of structural differences between simple and complex procedures at the level of the vestibular thickness is the result of a post hoc hypothesis based on the differences observed in radiofrequency times, the feasibility of CTI echo visualization and our previous experience with necropsy specimens10,12 or hystopathological examinations of RFCA lesions.40 Since, our hypothesis needs to be specifically tested. The exposition to fluoroscopy seems to be high, but it is necessary to consider that the time reflects the complete skin-to-skin procedure. When only ablation-related fluoroscopic time is analysed, that was similar to previously reported (13.3 + 6.6 min).14,35 Our protocol of RFCA of common atrial flutter usually not includes the use of electroanatomic mapping, which has also been described to have a good correlation with RA angiography.41 Nonetheless, electroanatomic mapping not allows to depict how gross is the vestibule, opposite to echocardiography. We are aware of the general reservation in the medical community related to the accuracy of transthoracic echocardiography in the clinical setting due to its strong dependence of personal skills and optimal acoustic window, as such as possible interanatomic differences if other populations are studied. As a feasibility study, further prospective studies are mandatory to widely accept any novel diagnostic or prognostic utility using transthoracic echocardiography, ideally evaluating intercentre reproducibility. Intrinsic difficulties to design a multicentre study could limit to test any innovative echocardiographic plane. Conclusion Two-dimensional echocardiography implemented with tissue harmonic imaging is a useful and valid cardiac imaging technique to clearly disclose and measure the CTI and their elements. It emerges as a non-invasive approach to study the morphology of the inferior RA, without the risks inherent to the current invasive procedure, the RA angiography using contrast. In addition, it permits the visualization of a novel structural feature, the thickness of the vestibule, which measurements were closely related with the complexity of the ablation procedure. Funding Funding received from Grant SAF2004-06864 (J.A.C. and D.S.-Q.) from Ministerio de Educaión y Ciencia, Spain, Fondo de Investigaciones de la Seguridad Social and Redes Temáticas de Cooperación; Red Cardiovascular C01/03 (J.A.C and J.F.) 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