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Quantitative evaluation of different high-density 3D mapping modes for atrial and ventricular substrate assessment of cardiac arrhythmias with the HD grid catheter
Journal of Electrocardiology 63 (2020) 110–114
Contents lists available at ScienceDirect
Journal of Electrocardiology journal homepage: www.jecgonline.com
Quantitative evaluation of different high-density 3D mapping modes for atrial and ventricular substrate assessment of cardiac arrhythmias with the HD grid catheter Felix Hohendanner, MD, PhD a,b,c, Stefan Kuhlmann, MD a,b, Florian Blaschke, MD a,b, Philipp Lacour, MD a,b, Sanzio Dimai e, Burkert Pieske, MD a,b,c,d, Leif-Hendrik Boldt, MD a,b, Abdul S. Parwani, MD a,b,⁎ a
Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany c Berlin Institute of Health (BIH), Berlin, Germany d Department of Internal Medicine and Cardiology, German Heart Institute, Berlin, Germany e Paracelsus Medizinische Privatuniversität Nürnberg, Nuremberg, Germany b
a r t i c l e
i n f o
Available online xxxx
Keywords: Arrhythmias High-density mapping Ablation Atrial fibrillation Ventricular tachycardia
a b s t r a c t Background: Atrial and ventricular arrhythmias significantly contribute to morbidity and mortality of patients with cardiac disease. Ablation of these arrhythmias has shown to improve clinical outcomes, yet targeted ablation strategies rely on proper mapping capabilities. In the present study, we compare different modes of highresolution mapping in clinically relevant arrhythmias using HD grid. Methods and results: Using the Advisor™ HD Grid Mapping Catheter in either the standard, the wave (bipolar along spline and bipolar orthogonal) or the wave diagonal setting, low-voltage areas were determined. Lowvoltage was defined as local electrograms with an amplitude <0.5 mV (bipolar; atria/ventricle) or <4 mV (unipolar; ventricle). Ultra high-density mapping in 47 patients with ventricular tachycardia, ventricular premature beats, atrial fibrillation and atrial tachycardia provided reliable information for the understanding of the arrhythmia mechanism resulting in safe ablation procedures. Regions of low voltage were significantly decreased by 14 ± 2% and 31 ± 3% with wave and wave diagonal settings as compared to standard settings, respectively. Conclusion: Substrate mapping and risk stratification relies on proper low voltage discrimination. Even though the Advisor™ HD Grid Mapping Catheter was safely used in all cases, the extent of low voltage areas was mapping-mode dependent. © 2020 Elsevier Inc. All rights reserved.
Introduction The treatment of atrial and ventricular arrhythmias depends on a thorough understanding of the respective pathophysiology. The introduction of ultra high-density mapping catheters allowed for the first time to differentiate between the mechanisms (i.e. reentry versus focal arrhythmias) and to, for instance, visualize the critical isthmus of a particular rhythm disorder for targeted ablation attempts. The Advisor™ HD Grid is a closed-frame, four-spline catheter with electrodes configured in a grid pattern that allows to record bipolar electrograms in two dimensions. As opposed to conventional (bipolar) catheters with fewer electrodes and mapping capabilities independent of directionality, the HD Grid catheter allows mapping of voltage, activation and directionality of conduction in different fashions. The 3–3⁎ Corresponding author: Charité Universitätsmedizin Berlin, Campus Virchow, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail address: [email protected] (A.S. Parwani).
https://doi.org/10.1016/j.jelectrocard.2020.10.012 0022-0736/© 2020 Elsevier Inc. All rights reserved.
3 mm spacing in a grid pattern leads to bipolar recordings along and across the splines to overcome the fact that a perpendicular wavefront has no effect on bipolar recordings. Due to differential orientations relative to the propagating wavefront, electrogram variability can be assessed [1]. In conjunction with the so-called “best duplicate” algorithm, using orthogonal bipoles to compare signal amplitude for collocated mapping, the highest amplitude signal is displayed for improved visualization of local signals [2]. Aim of the current study was to compare different modes of high-resolution mapping in atria and ventricular 3D mapping as well as the respective extent of low voltage regions in bipolar and unipolar recordings. The extent of low voltage can aid in patient risk stratification for recurrence of arrhythmias. Material and methods Patients: In this single center retrospective study, 47 procedures using the Advisor™ HD Grid Mapping Catheter (Abbott, USA) from March 2018 until June 2020 were included (local ethics committee
F. Hohendanner, S. Kuhlmann, F. Blaschke et al.
Journal of Electrocardiology 63 (2020) 110–114
approval EA1/248/20). All clinical, imaging and procedural data were recorded. Echocardiography was performed during clinical routine at the time of admission for the invasive procedure by an experienced clinical echocardiography physician. Atrial volume was obtained by echocardiography as well as derived from invasively obtained 3D electroanatomic maps. Atrial dilatation was defined as a LAVI of >41 ml/m2 [3]. Prior to procedures targeting the left atrium a transesophageal echocardiogram was performed to exclude atrial thrombus formation. Direct oral anticoagulation was discontinued on the day of the procedure and patients were sedated with midazolame and propofol for mapping and consecutive ablation. X-ray guided transseptal puncture was performed in cases concerning the left atrium or left ventricle and heparin was administered subsequently with a target activated clotting time of >300 s. HD grid was introduced via a long 8.5 F sheet placed in close vicinity to the respective chamber. Voltage mapping: Points collected, points used and scar size detected was compared in bipolar one dimension (standard), bipolar two-dimensional wave (2D wave), bipolar twodimensional wave with additional diagonal wave (2D wave+diagonal) mode and in unipolar ventricular mapping. In standard mode, electrical signals from bipolar pairs along the splines of the HD grid catheter are used. In 2D wave mode, the number of collected points is increased by using all possible bipolar pairs along and across the splines. Using the 2D wave+diagonal mode, additional information is gathered by also using diagonal splines (Suppl. Figure 1). Upon collection of points in the respective mapping modes, the “best duplicate algorithm” (EnSite Precision Cardiac Mapping System, Abbott, USA) was applied. After recording of bipolar electrograms for co-located points along and across splines, the “best duplicate algorithm” eliminates timing annotation outliers and selects the point with the largest voltage to be used by the system for map creation. Atrial low voltage areas were defined as areas <0.5 mV (bipolar). In the ventricle regions <4 mV (unipolar) were considered “low voltage”. In addition, for the ventricle, a bipolar cut-off of <0.5 mV was selected in accordance with animal ex-vivo data corresponding to dense scar and therefore mirroring areas of very “low voltage” [4–6]. Statistical analysis: Statistical analysis was performed using Prism for Windows (Version 6, GraphPad). Data were analyzed using One-Way (repeatedmeasures) ANOVA with Tukey and Holm-Sidak tests as appropriate. Data is shown as mean ± standard deviation. A p value of <0.05 was considered statistically significant.
Table 1 Clinical characteristics by chamber mapped (VT: ventricular tachycardia, VPB: ventricular premature beats, LVEF: left ventricular ejection fraction).
Age (years) Female (%) VT (%) VPB (%) Atrial fibrillation (%) Atrial tachycardia (%) LVEF (%) CHA2DS2-VASc Left atrial dilatation (%) Mapping duration (min)
Total: 47 patients
Atria: 25 patients
Ventricle: 22 patients
62 ± 3 43
61 ± 4 60
62 ± 3 23 86 14
45 ± 2
15 ± 1
40 60 50 ± 2 2.8 ± 0.3 96 14 ± 1
39 ± 3
17 ± 2
wave+diagonal mode, 15 ± 1% of the points were used when the best duplicate algorithm was applied. With the bipolar twodimensional wave mode 27 ± 8% of the points were used and in the bipolar one dimension (standard) mode 39 ± 7% of the collected points were not omitted. The number of points collected in standard mode was significantly lower as compared to wave and diagonal wave modes, amounting to a significant difference of points used for map creation (Fig. 1). Moreover, the extent of low voltage areas was significantly different between standard, 2D wave and 2D wave+diagonal mode (50 ± 7 vs. 48 ± 7 vs. 42 ± 6 cm2, n = 47, p < 0.05). Accounting for different sizes of the respective chamber mapped for this study, the extent of low voltage areas was corrected for inter-individual differences of left atrial or ventricular size and expressed as % scar area. When considering chamber size, in 2D wave and 2D wave diagonal mode, reported scar area was still significantly smaller as compared to standard mode (37 ± 3 vs. 32 ± 3 vs. 31 ± 3%, n = 47, p < 0.05). When studying the subset of patients with atrial bipolar recordings, 33 ± 4, 27 ± 4 and 27 ± 4% of the left atrium were low-voltage in the standard, wave and wave diagonal settings, respectively. In VT/VPB patients 43 ± 5, 38 ± 5 and 35 ± 5% of the left ventricle were low-voltage in the standard, 2D wave and 2D wave+diagonal mapping modes. Overall, regions of low voltage were significantly decreased by 14 ± 2% and 31 ± 3% with wave and wave diagonal settings as compared to standard settings, respectively. Next, we determined low-voltage regions in unipolar recordings: For a quantitative and qualitative assessment of scar areas, a cut-off of 4 mV for ventricular unipolar recordings has been suggested in the literature (see methods). In the subset of patients with unipolar recordings (n = 12 VT patients) reported scar area was 0% when using the same cut-off of 0.5 mV as with bipolar recordings and increased to 35 ± 7% with a cut-off of 4 mV. Using these settings, low-voltage areas where significantly increased in unipolar recordings as compared to standard, wave and diagonal wave modes (bipolar; 21 ± 13, 17 ± 4 and 11 ± 7%). Since atrial and ventricular tissue differs considerably in composition and thickness, we also studied the mere chamber specific effect on reported low-voltage regions: Interestingly, altered low-voltage quantification due to the switch between normal and wave diagonal mode was equal in atria and ventricle (Fig. 2D): When using the 2D wave diagonal mode, reported low-voltage regions in atria were 81 ± 3 vs. 80 ± 3% in ventricle as compared to standard mode (n = 25 and 22 patients, resp. n.s.). In all cases, the procedure was finished successfully without any technical mapping catheter related issues. No mapping related complication occurred during this study.
Results The Advisor™ HD Grid catheter was used in 47 cases with an indication for catheter-based ablation (ventricular tachycardia (VT) [19], ventricular premature beats (VPB) [3], atrial fibrillation [10] and atrial tachycardia [15]). All patients underwent endocardial mapping. Mean age of patients was 62 ± 3 years with a BMI of 26 ± 1 kg/m2. 40% of patients were male and CHA2DS2-VASc-Score was 2.9 ± 0.3. 17% of patients had diabetes mellitus type II and 53% had documented arterial hypertension. 31% had a history of previous coronary artery disease, previous strokes were reported in 2 patients. 96% of patients that underwent atrial mapping had left atrial dilatation as derived from invasive contact 3D mapping. However left atrial dilatation was only reported in 64% of echocardiography reports, indicating either considerable catheter-push during mapping or higher precision of 3D anatomic map acquisition with HD grid as compared to transthoracic echocardiography. Mean LVEF in patients with VT or VPB was 39 ± 3%. Mapping was performed within 17 ± 2 min in the VT/VPB group and 14 ± 1 min in the AT/PVI group without complications or adverse events in any of the studied patients (Table 1). Overall, 7158 ± 645 mapping points were collected per procedure amounting to a total of 336,449 points in standard settings. All maps were obtained during sinus rhythm. Different modes of voltage mapping were applied retrospectively to compare the amount of tissue reported to be low-voltage (i.e. below 0.5 mV in bipolar or below 4 mV in unipolar recordings). In the 2D
Discussion In this study we investigated the impact of different catheter signal processing modes on the extent of low-voltage regions with the novel high-density 3D mapping catheter Advisor™ HD Grid. We show for a variety of cases that the catheter can be used to map different rhythm 111
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Journal of Electrocardiology 63 (2020) 110–114
Fig. 1. A. Left atrial 3D map as obtained with the HD grid catheter in either wave diagonal (right) or standard mode (left) in a patient with atrial fibrillation after pulmonary vein isolation (map obtained during sinus rhythm). B. Number of points (left) and points used (right) collected to obtain 3D maps with the respective HD grid settings (see methods for details). C. Extent of low voltage regions with different HD grid settings in patients with AT/atrial fibrillation.
disorders from VT, VPB, atrial fibrillation to atrial tachycardia. In all cases, 3D mapping provided a reliable way to guide the ablation catheter to the respective ablation sites. In line with this, the HD grid catheter has been reported to be safe for endo- and epicardial mapping of the left ventricle [7,8] and pulmonary vein isolation [9] previously. Additionally, it has been reported that the catheter is able to detect the presence of local electrocardiogram signals, which were not visible on other nonhigh density mapping catheters and might aid in the understanding of the tachycardia mechanism [10]. HD grid was, for instance, able to identify gaps after pulmonary vein isolations that were not visible on local electrograms of the Tacticath ablation catheter [10]. We have previously
shown that the size of low voltage regions correlates with the mechanical myocardial function using the high-density Rhythmia® basket catheter [4]. Atrial low-voltage and fibrosis are determinants of the so called atrial cardiomyopathy and a more thorough assessment of myocardial fibrosis allows for a better clinical risk stratification of patients [11]. It is therefore of importance to have reliable measures of the extent of low voltage regions. It has been reported that the configuration of the HD grid mapping catheter might impact the reported total scar area (i.e. increased scar in the standard setting) in VT ablation [12]. The reported smaller low-voltage regions with the wave mode might argue for more efficient point acquisition and better substrate determination. 112
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Journal of Electrocardiology 63 (2020) 110–114
Fig. 2. A. Left ventricular 3D map as obtained with the HD grid catheter in either unipolar recording (top), standard mode (center) or 2D wave+diagonal mode (bottom) in a patient with ischemic cardiomyopathy and ventricular tachycardia (map obtained during sinus rhythm and shown in anterior-posterior [left] and posterior-anterior [right] projection). Ba.: Number of points (left) and points used (right) collected to obtain 3D maps with the respective HD grid settings (see methods for details). Bb.: Extent of low voltage regions with different HD grid settings in patients with VT or VPB (see methods for details). *p < 0.05 vs standard, **p < 0.05 vs. 2d wave. C.: Extent of low voltage regions derived from unipolar and bipolar (standard, 2D wave, 2D wave+diagonal) recordings in patients with VT or VPB. *p < 0.05 vs unipolar, **p < 0.05 vs. standard. D: Atrial and ventricular low voltage regions obtained with 2Dwave + diagonal as % of standard mode.
that chamber thickness has no significant effect on the acquisition mode dependent difference of reported low voltage regions and that mere electrode spacing might be of higher relevance [16,17]. Only recently an algorithm combining unipolar and bipolar voltage acquisition modes was proposed to further qualitatively and quantitatively characterize scars and to distinguish different scar forming entities (i.e. sarcoidosis versus ARVC) [18]. In addition unipolar recordings might aid in substrate determination [19] and by that allow to better refine ablation strategies e.g. for the treatment of scar related VT [20]. We therefore also assessed unipolar signals in a subset of patients with a cut-off of 0.5 and 4 mV [5,19]. In these maps, low-voltage was either not reported at all (0.5 mV) or significantly increased (4 mV) as compared to bipolar mapping. This indicates that unipolar recordings provide only little additional aid in scar quantification, while they might help considerably in a qualification of the substrate.
This is especially important to avoid unnecessary RF ablation in patients with extensive substrate as it can be seen in advanced cases of arrhythmias. RF ablation based on an overestimation of low-voltage areas might result in unnecessary ablation, which in turn might represent a culprit for new rhythm disorders. In addition, more accurate mapping capabilities allow to determine ablation target zones more effectively to aid in substrate modification or ablation line completion [13]. This principle is exemplified in Fig. 2A, were the HD grid standard mode points towards roof line ablation or pulmonary vein gaps, which are not visible in the more accurate diagonal wave mode (Fig. 2A). This further underscores the improved accuracy especially in border zones, were rather low voltage meets normal myocardium. Moreover, novel ablation approaches especially for the treatment of persistent atrial fibrillation specifically target low-voltage zones. These zones were only recently confirmed as a strong predictor of arrhythmia recurrence [14]. An improved detection of these regions using high density mapping systems might aid in decreased arrhythmia burden. Interestingly, the relative size of low voltage regions reported in the current study, even though highly affected by acquisition mode, was not significantly different between atria and ventricle. Ventricular myocardium is thicker and the reported low voltage potentially biased towards higher or lower values. In support of this notion, Chrispin et al. reported a correlation between wall thickness and local electrogram determination [15]. However, switching between standard and wave diagonal modes showed no difference between atria and ventricle, indicating
Conclusions In conclusion, the HD grid mapping catheter allowed assessment of the electrical substrate and the “state of cardiomyopathy” with high accuracy dependent on the mode (i.e. wave, wave diagonal, standard) and recording modality (i.e. unipolar, bipolar) used. Regions of low voltage in atrial/ventricular procedures were significantly decreased by 14 ± 2% and 31 ± 3% with wave and wave diagonal settings as compared to standard settings, respectively. When using 0.5 mV as cut-off for 113
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Journal of Electrocardiology 63 (2020) 110–114 [4] Hohendanner F, Romero I, Blaschke F, Heinzel FR, Pieske B, Boldt LH, et al. Extent and magnitude of low-voltage areas assessed by ultra-high-density electroanatomical mapping correlate with left atrial function. Int J Cardiol. 2018;272:108–12. [5] Tschabrunn CM, Roujol S, Dorman NC, Nezafat R, Josephson ME, Anter E. Highresolution mapping of ventricular scar: comparison between single and multielectrode catheters. Circ Arrhythm Electrophysiol. 2016;9(6). [6] Letsas KP, Efremidis M, Vlachos K, Georgopoulos S, Karamichalakis N, Asvestas D, et al. Right ventricular outflow tract high-density endocardial unipolar voltage mapping in patients with Brugada syndrome: evidence for electroanatomical abnormalities. Europace. 2018;20(FI1):f57–63. [7] Bellmann B, Plenge T, Sultan A, Steven D. First endocardial mapping of the left ventricle using the AdvisorTM HD Grid Catheter in a patient with a mitral valve clip. Eur Heart J. 2018;39(31):2911. [8] Bellmann B, Luker J, Steven D, Sultan A. First epicardial mapping of the left ventricle using the Advisor HD Grid catheter. J Interv Card Electrophysiol. 2018;53(1):103–4. [9] Hong KL, Redfearn D, Chacko S, Baley J, Baranchuk A, Glover BM. High-resolution mapping of the atria using the HD Grid catheter. HeartRhythm Case Rep. 2019;5 (7):351–3. [10] Yeo C, Tan VH, Wong KCK. Pulmonary vein reconnection mapping with Advisor HD Grid demonstrating local EGM which were not visible on Tacticath ablation catheter. J Arrhythm. 2019;35(1):152–4. [11] Goette A, Kalman JM, Aguinaga L, Akar J, Cabrera JA, Chen SA, et al. EHRA/HRS/ APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication. Europace. 2016;18(10):1455–90. [12] Proietti R, Adlan AM, Dowd R, Assadullah S, Aldhoon B, Panikker S, et al. Enhanced ventricular tachycardia substrate resolution with a novel omnipolar high-density mapping catheter: the omnimapping study. J Interv Card Electrophysiol. 2020 Sep; 58(3):355–62. https://doi.org/10.1007/s10840-019-00625-9. [13] Melby SJ, Lee AM, Zierer A, Kaiser SP, Livhits MJ, Boineau JP, et al. Atrial fibrillation propagates through gaps in ablation lines: implications for ablative treatment of atrial fibrillation. Heart Rhythm. 2008;5(9):1296–301. [14] Schade A, Costello-Boerrigter L, Steinborn F, Bayri AH, Chapran M, Surber R, et al. Voltage-guided ablation in persistent atrial fibrillation-favorable 1-year outcome and predictors. J Interv Card Electrophysiol. 2020 Oct 8. https://doi.org/10.1007/ s10840-020-00882-z (Article Online ahead of print). [15] Chrispin J, Keramati AR, Assis FR, Misra S, Zghaib T, Berger RD, et al. Correlation of right ventricular multielectrode endocardial unipolar mapping and epicardial scar. Pacing Clin Electrophysiol. 2018;41(4):345–52. [16] Nguyen DT, Tumolo AZ. Narrowing the field: closely spaced bipoles for enhanced detection of low voltage EGM. JACC Clin Electrophysiol. 2019;5(1):78–80. [17] Beheshti M, Magtibay K, Masse S, Porta-Sanchez A, Haldar S, Bhaskaran A, et al. Determinants of atrial bipolar voltage: inter electrode distance and wavefront angle. Comput Biol Med. 2018;102:449–57. [18] Hoogendoorn JC, Sramko M, Venlet J, Siontis KC, Kumar S, Singh R, et al. Electroanatomical voltage mapping to distinguish right-sided cardiac sarcoidosis from arrhythmogenic right ventricular cardiomyopathy. JACC Clin Electrophysiol. 2020;6(6):696–707. [19] Liang JJ, D’Souza BA, Betensky BP, Zado ES, Desjardins B, Santangeli P, et al. Importance of the interventricular septum as part of the ventricular tachycardia substrate in nonischemic cardiomyopathy. JACC Clin Electrophysiol. 2018;4(9):1155–62. [20] Di Biase L, Santangeli P, Burkhardt DJ, Bai R, Mohanty P, Carbucicchio C, et al. Endoepicardial homogenization of the scar versus limited substrate ablation for the treatment of electrical storms in patients with ischemic cardiomyopathy. J Am Coll Cardiol. 2012;60(2):132–41.
low-voltage, unipolar ventricular mapping reported no scars, whereas a cut-off of 4 mV led to values slightly higher than in bipolar mapping modes. The HD grid catheter could be used with reliable results without adverse events in the atrium and ventricle of patients with atrial fibrillation, atrial tachycardia, ventricular premature beats or ventricular tachycardia. Supplementary data to this article can be found online at https://doi. org/10.1016/j.jelectrocard.2020.10.012.
CRediT authorship contribution statement Felix Hohendanner: Formal analysis, Investigation, Validation, Data curation, Visualization, Writing - original draft, Writing - review & editing. Stefan Kuhlmann: Formal analysis, Software, Investigation, Data curation, Methodology. Florian Blaschke: Validation, Writing - review & editing. Philipp Lacour: Writing - review & editing. Sanzio Dimai: Writing - review & editing. Burkert Pieske: Resources, Writing - review & editing. Leif-Hendrik Boldt: Writing - review & editing, Supervision, Resources, Validation. Abdul S. Parwani: Writing - original draft, Writing - review & editing, Supervision, Data curation, Formal analysis, Resources, Validation, Project administration.
Acknowledgments Support for this study was provided by the Else-Kröner-FreseniusFoundation and the Berlin Institute of Health (FH). Declaration of Competing Interest None. References [1] Takigawa M, Relan J, Martin R, Kim S, Kitamura T, Frontera A, et al. Effect of bipolar electrode orientation on local electrogram properties. Heart Rhythm. 2018;15(12): 1853–61. [2] Campbell T, Trivic I, Bennett RG, Anderson RD, Turnbull S, Pham T, et al. Catheter ablation of ventricular arrhythmia guided by a high-density grid catheter. J Cardiovasc Electrophysiol. 2020 Feb;31(2):474–84. https://doi.org/10.1111/jce.14351. [3] Aune E, Baekkevar M, Roislien J, Rodevand O, Otterstad JE. Normal reference ranges for left and right atrial volume indexes and ejection fractions obtained with realtime three-dimensional echocardiography. Eur J Echocardiogr. 2009;10(6):738–44.
114
Contents lists available at ScienceDirect
Journal of Electrocardiology journal homepage: www.jecgonline.com
Quantitative evaluation of different high-density 3D mapping modes for atrial and ventricular substrate assessment of cardiac arrhythmias with the HD grid catheter Felix Hohendanner, MD, PhD a,b,c, Stefan Kuhlmann, MD a,b, Florian Blaschke, MD a,b, Philipp Lacour, MD a,b, Sanzio Dimai e, Burkert Pieske, MD a,b,c,d, Leif-Hendrik Boldt, MD a,b, Abdul S. Parwani, MD a,b,⁎ a
Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany c Berlin Institute of Health (BIH), Berlin, Germany d Department of Internal Medicine and Cardiology, German Heart Institute, Berlin, Germany e Paracelsus Medizinische Privatuniversität Nürnberg, Nuremberg, Germany b
a r t i c l e
i n f o
Available online xxxx
Keywords: Arrhythmias High-density mapping Ablation Atrial fibrillation Ventricular tachycardia
a b s t r a c t Background: Atrial and ventricular arrhythmias significantly contribute to morbidity and mortality of patients with cardiac disease. Ablation of these arrhythmias has shown to improve clinical outcomes, yet targeted ablation strategies rely on proper mapping capabilities. In the present study, we compare different modes of highresolution mapping in clinically relevant arrhythmias using HD grid. Methods and results: Using the Advisor™ HD Grid Mapping Catheter in either the standard, the wave (bipolar along spline and bipolar orthogonal) or the wave diagonal setting, low-voltage areas were determined. Lowvoltage was defined as local electrograms with an amplitude <0.5 mV (bipolar; atria/ventricle) or <4 mV (unipolar; ventricle). Ultra high-density mapping in 47 patients with ventricular tachycardia, ventricular premature beats, atrial fibrillation and atrial tachycardia provided reliable information for the understanding of the arrhythmia mechanism resulting in safe ablation procedures. Regions of low voltage were significantly decreased by 14 ± 2% and 31 ± 3% with wave and wave diagonal settings as compared to standard settings, respectively. Conclusion: Substrate mapping and risk stratification relies on proper low voltage discrimination. Even though the Advisor™ HD Grid Mapping Catheter was safely used in all cases, the extent of low voltage areas was mapping-mode dependent. © 2020 Elsevier Inc. All rights reserved.
Introduction The treatment of atrial and ventricular arrhythmias depends on a thorough understanding of the respective pathophysiology. The introduction of ultra high-density mapping catheters allowed for the first time to differentiate between the mechanisms (i.e. reentry versus focal arrhythmias) and to, for instance, visualize the critical isthmus of a particular rhythm disorder for targeted ablation attempts. The Advisor™ HD Grid is a closed-frame, four-spline catheter with electrodes configured in a grid pattern that allows to record bipolar electrograms in two dimensions. As opposed to conventional (bipolar) catheters with fewer electrodes and mapping capabilities independent of directionality, the HD Grid catheter allows mapping of voltage, activation and directionality of conduction in different fashions. The 3–3⁎ Corresponding author: Charité Universitätsmedizin Berlin, Campus Virchow, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail address: [email protected] (A.S. Parwani).
https://doi.org/10.1016/j.jelectrocard.2020.10.012 0022-0736/© 2020 Elsevier Inc. All rights reserved.
3 mm spacing in a grid pattern leads to bipolar recordings along and across the splines to overcome the fact that a perpendicular wavefront has no effect on bipolar recordings. Due to differential orientations relative to the propagating wavefront, electrogram variability can be assessed [1]. In conjunction with the so-called “best duplicate” algorithm, using orthogonal bipoles to compare signal amplitude for collocated mapping, the highest amplitude signal is displayed for improved visualization of local signals [2]. Aim of the current study was to compare different modes of high-resolution mapping in atria and ventricular 3D mapping as well as the respective extent of low voltage regions in bipolar and unipolar recordings. The extent of low voltage can aid in patient risk stratification for recurrence of arrhythmias. Material and methods Patients: In this single center retrospective study, 47 procedures using the Advisor™ HD Grid Mapping Catheter (Abbott, USA) from March 2018 until June 2020 were included (local ethics committee
F. Hohendanner, S. Kuhlmann, F. Blaschke et al.
Journal of Electrocardiology 63 (2020) 110–114
approval EA1/248/20). All clinical, imaging and procedural data were recorded. Echocardiography was performed during clinical routine at the time of admission for the invasive procedure by an experienced clinical echocardiography physician. Atrial volume was obtained by echocardiography as well as derived from invasively obtained 3D electroanatomic maps. Atrial dilatation was defined as a LAVI of >41 ml/m2 [3]. Prior to procedures targeting the left atrium a transesophageal echocardiogram was performed to exclude atrial thrombus formation. Direct oral anticoagulation was discontinued on the day of the procedure and patients were sedated with midazolame and propofol for mapping and consecutive ablation. X-ray guided transseptal puncture was performed in cases concerning the left atrium or left ventricle and heparin was administered subsequently with a target activated clotting time of >300 s. HD grid was introduced via a long 8.5 F sheet placed in close vicinity to the respective chamber. Voltage mapping: Points collected, points used and scar size detected was compared in bipolar one dimension (standard), bipolar two-dimensional wave (2D wave), bipolar twodimensional wave with additional diagonal wave (2D wave+diagonal) mode and in unipolar ventricular mapping. In standard mode, electrical signals from bipolar pairs along the splines of the HD grid catheter are used. In 2D wave mode, the number of collected points is increased by using all possible bipolar pairs along and across the splines. Using the 2D wave+diagonal mode, additional information is gathered by also using diagonal splines (Suppl. Figure 1). Upon collection of points in the respective mapping modes, the “best duplicate algorithm” (EnSite Precision Cardiac Mapping System, Abbott, USA) was applied. After recording of bipolar electrograms for co-located points along and across splines, the “best duplicate algorithm” eliminates timing annotation outliers and selects the point with the largest voltage to be used by the system for map creation. Atrial low voltage areas were defined as areas <0.5 mV (bipolar). In the ventricle regions <4 mV (unipolar) were considered “low voltage”. In addition, for the ventricle, a bipolar cut-off of <0.5 mV was selected in accordance with animal ex-vivo data corresponding to dense scar and therefore mirroring areas of very “low voltage” [4–6]. Statistical analysis: Statistical analysis was performed using Prism for Windows (Version 6, GraphPad). Data were analyzed using One-Way (repeatedmeasures) ANOVA with Tukey and Holm-Sidak tests as appropriate. Data is shown as mean ± standard deviation. A p value of <0.05 was considered statistically significant.
Table 1 Clinical characteristics by chamber mapped (VT: ventricular tachycardia, VPB: ventricular premature beats, LVEF: left ventricular ejection fraction).
Age (years) Female (%) VT (%) VPB (%) Atrial fibrillation (%) Atrial tachycardia (%) LVEF (%) CHA2DS2-VASc Left atrial dilatation (%) Mapping duration (min)
Total: 47 patients
Atria: 25 patients
Ventricle: 22 patients
62 ± 3 43
61 ± 4 60
62 ± 3 23 86 14
45 ± 2
15 ± 1
40 60 50 ± 2 2.8 ± 0.3 96 14 ± 1
39 ± 3
17 ± 2
wave+diagonal mode, 15 ± 1% of the points were used when the best duplicate algorithm was applied. With the bipolar twodimensional wave mode 27 ± 8% of the points were used and in the bipolar one dimension (standard) mode 39 ± 7% of the collected points were not omitted. The number of points collected in standard mode was significantly lower as compared to wave and diagonal wave modes, amounting to a significant difference of points used for map creation (Fig. 1). Moreover, the extent of low voltage areas was significantly different between standard, 2D wave and 2D wave+diagonal mode (50 ± 7 vs. 48 ± 7 vs. 42 ± 6 cm2, n = 47, p < 0.05). Accounting for different sizes of the respective chamber mapped for this study, the extent of low voltage areas was corrected for inter-individual differences of left atrial or ventricular size and expressed as % scar area. When considering chamber size, in 2D wave and 2D wave diagonal mode, reported scar area was still significantly smaller as compared to standard mode (37 ± 3 vs. 32 ± 3 vs. 31 ± 3%, n = 47, p < 0.05). When studying the subset of patients with atrial bipolar recordings, 33 ± 4, 27 ± 4 and 27 ± 4% of the left atrium were low-voltage in the standard, wave and wave diagonal settings, respectively. In VT/VPB patients 43 ± 5, 38 ± 5 and 35 ± 5% of the left ventricle were low-voltage in the standard, 2D wave and 2D wave+diagonal mapping modes. Overall, regions of low voltage were significantly decreased by 14 ± 2% and 31 ± 3% with wave and wave diagonal settings as compared to standard settings, respectively. Next, we determined low-voltage regions in unipolar recordings: For a quantitative and qualitative assessment of scar areas, a cut-off of 4 mV for ventricular unipolar recordings has been suggested in the literature (see methods). In the subset of patients with unipolar recordings (n = 12 VT patients) reported scar area was 0% when using the same cut-off of 0.5 mV as with bipolar recordings and increased to 35 ± 7% with a cut-off of 4 mV. Using these settings, low-voltage areas where significantly increased in unipolar recordings as compared to standard, wave and diagonal wave modes (bipolar; 21 ± 13, 17 ± 4 and 11 ± 7%). Since atrial and ventricular tissue differs considerably in composition and thickness, we also studied the mere chamber specific effect on reported low-voltage regions: Interestingly, altered low-voltage quantification due to the switch between normal and wave diagonal mode was equal in atria and ventricle (Fig. 2D): When using the 2D wave diagonal mode, reported low-voltage regions in atria were 81 ± 3 vs. 80 ± 3% in ventricle as compared to standard mode (n = 25 and 22 patients, resp. n.s.). In all cases, the procedure was finished successfully without any technical mapping catheter related issues. No mapping related complication occurred during this study.
Results The Advisor™ HD Grid catheter was used in 47 cases with an indication for catheter-based ablation (ventricular tachycardia (VT) [19], ventricular premature beats (VPB) [3], atrial fibrillation [10] and atrial tachycardia [15]). All patients underwent endocardial mapping. Mean age of patients was 62 ± 3 years with a BMI of 26 ± 1 kg/m2. 40% of patients were male and CHA2DS2-VASc-Score was 2.9 ± 0.3. 17% of patients had diabetes mellitus type II and 53% had documented arterial hypertension. 31% had a history of previous coronary artery disease, previous strokes were reported in 2 patients. 96% of patients that underwent atrial mapping had left atrial dilatation as derived from invasive contact 3D mapping. However left atrial dilatation was only reported in 64% of echocardiography reports, indicating either considerable catheter-push during mapping or higher precision of 3D anatomic map acquisition with HD grid as compared to transthoracic echocardiography. Mean LVEF in patients with VT or VPB was 39 ± 3%. Mapping was performed within 17 ± 2 min in the VT/VPB group and 14 ± 1 min in the AT/PVI group without complications or adverse events in any of the studied patients (Table 1). Overall, 7158 ± 645 mapping points were collected per procedure amounting to a total of 336,449 points in standard settings. All maps were obtained during sinus rhythm. Different modes of voltage mapping were applied retrospectively to compare the amount of tissue reported to be low-voltage (i.e. below 0.5 mV in bipolar or below 4 mV in unipolar recordings). In the 2D
Discussion In this study we investigated the impact of different catheter signal processing modes on the extent of low-voltage regions with the novel high-density 3D mapping catheter Advisor™ HD Grid. We show for a variety of cases that the catheter can be used to map different rhythm 111
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Fig. 1. A. Left atrial 3D map as obtained with the HD grid catheter in either wave diagonal (right) or standard mode (left) in a patient with atrial fibrillation after pulmonary vein isolation (map obtained during sinus rhythm). B. Number of points (left) and points used (right) collected to obtain 3D maps with the respective HD grid settings (see methods for details). C. Extent of low voltage regions with different HD grid settings in patients with AT/atrial fibrillation.
disorders from VT, VPB, atrial fibrillation to atrial tachycardia. In all cases, 3D mapping provided a reliable way to guide the ablation catheter to the respective ablation sites. In line with this, the HD grid catheter has been reported to be safe for endo- and epicardial mapping of the left ventricle [7,8] and pulmonary vein isolation [9] previously. Additionally, it has been reported that the catheter is able to detect the presence of local electrocardiogram signals, which were not visible on other nonhigh density mapping catheters and might aid in the understanding of the tachycardia mechanism [10]. HD grid was, for instance, able to identify gaps after pulmonary vein isolations that were not visible on local electrograms of the Tacticath ablation catheter [10]. We have previously
shown that the size of low voltage regions correlates with the mechanical myocardial function using the high-density Rhythmia® basket catheter [4]. Atrial low-voltage and fibrosis are determinants of the so called atrial cardiomyopathy and a more thorough assessment of myocardial fibrosis allows for a better clinical risk stratification of patients [11]. It is therefore of importance to have reliable measures of the extent of low voltage regions. It has been reported that the configuration of the HD grid mapping catheter might impact the reported total scar area (i.e. increased scar in the standard setting) in VT ablation [12]. The reported smaller low-voltage regions with the wave mode might argue for more efficient point acquisition and better substrate determination. 112
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Fig. 2. A. Left ventricular 3D map as obtained with the HD grid catheter in either unipolar recording (top), standard mode (center) or 2D wave+diagonal mode (bottom) in a patient with ischemic cardiomyopathy and ventricular tachycardia (map obtained during sinus rhythm and shown in anterior-posterior [left] and posterior-anterior [right] projection). Ba.: Number of points (left) and points used (right) collected to obtain 3D maps with the respective HD grid settings (see methods for details). Bb.: Extent of low voltage regions with different HD grid settings in patients with VT or VPB (see methods for details). *p < 0.05 vs standard, **p < 0.05 vs. 2d wave. C.: Extent of low voltage regions derived from unipolar and bipolar (standard, 2D wave, 2D wave+diagonal) recordings in patients with VT or VPB. *p < 0.05 vs unipolar, **p < 0.05 vs. standard. D: Atrial and ventricular low voltage regions obtained with 2Dwave + diagonal as % of standard mode.
that chamber thickness has no significant effect on the acquisition mode dependent difference of reported low voltage regions and that mere electrode spacing might be of higher relevance [16,17]. Only recently an algorithm combining unipolar and bipolar voltage acquisition modes was proposed to further qualitatively and quantitatively characterize scars and to distinguish different scar forming entities (i.e. sarcoidosis versus ARVC) [18]. In addition unipolar recordings might aid in substrate determination [19] and by that allow to better refine ablation strategies e.g. for the treatment of scar related VT [20]. We therefore also assessed unipolar signals in a subset of patients with a cut-off of 0.5 and 4 mV [5,19]. In these maps, low-voltage was either not reported at all (0.5 mV) or significantly increased (4 mV) as compared to bipolar mapping. This indicates that unipolar recordings provide only little additional aid in scar quantification, while they might help considerably in a qualification of the substrate.
This is especially important to avoid unnecessary RF ablation in patients with extensive substrate as it can be seen in advanced cases of arrhythmias. RF ablation based on an overestimation of low-voltage areas might result in unnecessary ablation, which in turn might represent a culprit for new rhythm disorders. In addition, more accurate mapping capabilities allow to determine ablation target zones more effectively to aid in substrate modification or ablation line completion [13]. This principle is exemplified in Fig. 2A, were the HD grid standard mode points towards roof line ablation or pulmonary vein gaps, which are not visible in the more accurate diagonal wave mode (Fig. 2A). This further underscores the improved accuracy especially in border zones, were rather low voltage meets normal myocardium. Moreover, novel ablation approaches especially for the treatment of persistent atrial fibrillation specifically target low-voltage zones. These zones were only recently confirmed as a strong predictor of arrhythmia recurrence [14]. An improved detection of these regions using high density mapping systems might aid in decreased arrhythmia burden. Interestingly, the relative size of low voltage regions reported in the current study, even though highly affected by acquisition mode, was not significantly different between atria and ventricle. Ventricular myocardium is thicker and the reported low voltage potentially biased towards higher or lower values. In support of this notion, Chrispin et al. reported a correlation between wall thickness and local electrogram determination [15]. However, switching between standard and wave diagonal modes showed no difference between atria and ventricle, indicating
Conclusions In conclusion, the HD grid mapping catheter allowed assessment of the electrical substrate and the “state of cardiomyopathy” with high accuracy dependent on the mode (i.e. wave, wave diagonal, standard) and recording modality (i.e. unipolar, bipolar) used. Regions of low voltage in atrial/ventricular procedures were significantly decreased by 14 ± 2% and 31 ± 3% with wave and wave diagonal settings as compared to standard settings, respectively. When using 0.5 mV as cut-off for 113
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Journal of Electrocardiology 63 (2020) 110–114 [4] Hohendanner F, Romero I, Blaschke F, Heinzel FR, Pieske B, Boldt LH, et al. Extent and magnitude of low-voltage areas assessed by ultra-high-density electroanatomical mapping correlate with left atrial function. Int J Cardiol. 2018;272:108–12. [5] Tschabrunn CM, Roujol S, Dorman NC, Nezafat R, Josephson ME, Anter E. Highresolution mapping of ventricular scar: comparison between single and multielectrode catheters. Circ Arrhythm Electrophysiol. 2016;9(6). [6] Letsas KP, Efremidis M, Vlachos K, Georgopoulos S, Karamichalakis N, Asvestas D, et al. Right ventricular outflow tract high-density endocardial unipolar voltage mapping in patients with Brugada syndrome: evidence for electroanatomical abnormalities. Europace. 2018;20(FI1):f57–63. [7] Bellmann B, Plenge T, Sultan A, Steven D. First endocardial mapping of the left ventricle using the AdvisorTM HD Grid Catheter in a patient with a mitral valve clip. Eur Heart J. 2018;39(31):2911. [8] Bellmann B, Luker J, Steven D, Sultan A. First epicardial mapping of the left ventricle using the Advisor HD Grid catheter. J Interv Card Electrophysiol. 2018;53(1):103–4. [9] Hong KL, Redfearn D, Chacko S, Baley J, Baranchuk A, Glover BM. High-resolution mapping of the atria using the HD Grid catheter. HeartRhythm Case Rep. 2019;5 (7):351–3. [10] Yeo C, Tan VH, Wong KCK. Pulmonary vein reconnection mapping with Advisor HD Grid demonstrating local EGM which were not visible on Tacticath ablation catheter. J Arrhythm. 2019;35(1):152–4. [11] Goette A, Kalman JM, Aguinaga L, Akar J, Cabrera JA, Chen SA, et al. EHRA/HRS/ APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication. Europace. 2016;18(10):1455–90. [12] Proietti R, Adlan AM, Dowd R, Assadullah S, Aldhoon B, Panikker S, et al. Enhanced ventricular tachycardia substrate resolution with a novel omnipolar high-density mapping catheter: the omnimapping study. J Interv Card Electrophysiol. 2020 Sep; 58(3):355–62. https://doi.org/10.1007/s10840-019-00625-9. [13] Melby SJ, Lee AM, Zierer A, Kaiser SP, Livhits MJ, Boineau JP, et al. Atrial fibrillation propagates through gaps in ablation lines: implications for ablative treatment of atrial fibrillation. Heart Rhythm. 2008;5(9):1296–301. [14] Schade A, Costello-Boerrigter L, Steinborn F, Bayri AH, Chapran M, Surber R, et al. Voltage-guided ablation in persistent atrial fibrillation-favorable 1-year outcome and predictors. J Interv Card Electrophysiol. 2020 Oct 8. https://doi.org/10.1007/ s10840-020-00882-z (Article Online ahead of print). [15] Chrispin J, Keramati AR, Assis FR, Misra S, Zghaib T, Berger RD, et al. Correlation of right ventricular multielectrode endocardial unipolar mapping and epicardial scar. Pacing Clin Electrophysiol. 2018;41(4):345–52. [16] Nguyen DT, Tumolo AZ. Narrowing the field: closely spaced bipoles for enhanced detection of low voltage EGM. JACC Clin Electrophysiol. 2019;5(1):78–80. [17] Beheshti M, Magtibay K, Masse S, Porta-Sanchez A, Haldar S, Bhaskaran A, et al. Determinants of atrial bipolar voltage: inter electrode distance and wavefront angle. Comput Biol Med. 2018;102:449–57. [18] Hoogendoorn JC, Sramko M, Venlet J, Siontis KC, Kumar S, Singh R, et al. Electroanatomical voltage mapping to distinguish right-sided cardiac sarcoidosis from arrhythmogenic right ventricular cardiomyopathy. JACC Clin Electrophysiol. 2020;6(6):696–707. [19] Liang JJ, D’Souza BA, Betensky BP, Zado ES, Desjardins B, Santangeli P, et al. Importance of the interventricular septum as part of the ventricular tachycardia substrate in nonischemic cardiomyopathy. JACC Clin Electrophysiol. 2018;4(9):1155–62. [20] Di Biase L, Santangeli P, Burkhardt DJ, Bai R, Mohanty P, Carbucicchio C, et al. Endoepicardial homogenization of the scar versus limited substrate ablation for the treatment of electrical storms in patients with ischemic cardiomyopathy. J Am Coll Cardiol. 2012;60(2):132–41.
low-voltage, unipolar ventricular mapping reported no scars, whereas a cut-off of 4 mV led to values slightly higher than in bipolar mapping modes. The HD grid catheter could be used with reliable results without adverse events in the atrium and ventricle of patients with atrial fibrillation, atrial tachycardia, ventricular premature beats or ventricular tachycardia. Supplementary data to this article can be found online at https://doi. org/10.1016/j.jelectrocard.2020.10.012.
CRediT authorship contribution statement Felix Hohendanner: Formal analysis, Investigation, Validation, Data curation, Visualization, Writing - original draft, Writing - review & editing. Stefan Kuhlmann: Formal analysis, Software, Investigation, Data curation, Methodology. Florian Blaschke: Validation, Writing - review & editing. Philipp Lacour: Writing - review & editing. Sanzio Dimai: Writing - review & editing. Burkert Pieske: Resources, Writing - review & editing. Leif-Hendrik Boldt: Writing - review & editing, Supervision, Resources, Validation. Abdul S. Parwani: Writing - original draft, Writing - review & editing, Supervision, Data curation, Formal analysis, Resources, Validation, Project administration.
Acknowledgments Support for this study was provided by the Else-Kröner-FreseniusFoundation and the Berlin Institute of Health (FH). Declaration of Competing Interest None. References [1] Takigawa M, Relan J, Martin R, Kim S, Kitamura T, Frontera A, et al. Effect of bipolar electrode orientation on local electrogram properties. Heart Rhythm. 2018;15(12): 1853–61. [2] Campbell T, Trivic I, Bennett RG, Anderson RD, Turnbull S, Pham T, et al. Catheter ablation of ventricular arrhythmia guided by a high-density grid catheter. J Cardiovasc Electrophysiol. 2020 Feb;31(2):474–84. https://doi.org/10.1111/jce.14351. [3] Aune E, Baekkevar M, Roislien J, Rodevand O, Otterstad JE. Normal reference ranges for left and right atrial volume indexes and ejection fractions obtained with realtime three-dimensional echocardiography. Eur J Echocardiogr. 2009;10(6):738–44.
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