- Email: [email protected]
Acute and early outcomes of focal impulse and rotor modulation (FIRM)-guided rotors-only ablation in patients with nonparoxysmal atrial fibrillation
Author's Accepted Manuscript
Acute and early outcomes of FIRM-guided rotorsonly ablation in patients with non-paroxysmal atrial fibrillation Carola Gianni MD, Sanghamitra Mohanty MD MS FHRS, Luigi Di Biase MD PhD FHRS, Tamara Metz RN BSN, Chintan Trivedi MD, Yalçın Gökoğlan MD, Mahmut F. Güne� MD, Rong Bai MD FHRS, Amin Al-Ahmad MD CCDS FHRS, J. David Burkhardt MD FHRS, G. Joseph Gallinghouse MD FHRS, Rodney Horton MD FHRS, Patrick M. Hranitzky MD FHRS, Javier E. Sanchez MD, Phillipp Halbfaß MD, Patrick Müller MD, Anja Schade MD, Thomas Deneke MD PhD FHRS, Gery F. Tomassoni MD FHRS, Andrea Natale MD FHRS
PII: DOI: Reference:
S1547-5271(15)01554-4 http://dx.doi.org/10.1016/j.hrthm.2015.12.028 HRTHM6559
To appear in:
Heart Rhythm
www.elsevier.com/locate/buildenv
Cite this article as: Carola Gianni MD, Sanghamitra Mohanty MD MS FHRS, Luigi Di Biase MD PhD FHRS, Tamara Metz RN BSN, Chintan Trivedi MD, Yalçın Gökoğlan MD, Mahmut F. Güne� MD, Rong Bai MD FHRS, Amin Al-Ahmad MD CCDS FHRS, J. David Burkhardt MD FHRS, G. Joseph Gallinghouse MD FHRS, Rodney Horton MD FHRS, Patrick M. Hranitzky MD FHRS, Javier E. Sanchez MD, Phillipp Halbfaß MD, Patrick Müller MD, Anja Schade MD, Thomas Deneke MD PhD FHRS, Gery F. Tomassoni MD FHRS, Andrea Natale MD FHRS, Acute and early outcomes of FIRMguided rotors-only ablation in patients with non-paroxysmal atrial fibrillation, Heart Rhythm, http://dx.doi.org/10.1016/j.hrthm.2015.12.028 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Acute and early outcomes of FIRM-guided rotors-only ablation in patients with non-paroxysmal atrial fibrillation FIRM-guided rotors-only ablation in non-paroxysmal AF Carola Gianni MD1,2, Sanghamitra Mohanty MD MS FHRS1, Luigi Di Biase MD PhD FHRS1,3,4,5, Tamara Metz RN BSN1, Chintan Trivedi MD1, Yalçın Gökoğlan MD1,6, Mahmut F Güneş MD1, Rong Bai MD FHRS1, Amin Al-Ahmad MD CCDS FHRS1, J. David Burkhardt MD FHRS1, G. Joseph Gallinghouse MD FHRS1, Rodney Horton MD FHRS1,4, Patrick M Hranitzky MD FHRS1, Javier E Sanchez MD1, Phillipp Halbfaß MD7, Patrick Müller MD7,8, Anja Schade MD7, Thomas Deneke MD PhD FHRS7,8, Gery F Tomassoni MD9 FHRS, Andrea Natale MD FHRS1,3,4,10,11,12,13,14 1
Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, TX, USA
2
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
3
Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
4
Department of Biomedical Engineering, University of Texas, Austin, TX, USA
5
Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
6
Department of Cardiology, Gülhane Military Academy of Medicine, Ankara, Turkey
7
Clinic for Interventional Electrophysiology, Heart Center Bad Neustadt, Bad Neustadt, Germany
8
University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany
9
Baptist Health Lexington, Lexington, KY, USA
10
Division of Cardiovascular Diseases, Scripps Clinic, La Jolla, CA, USA
11
MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA
12
Division of Cardiology, Stanford University, Stanford, CA, USA
13
Electrophysiology and Arrhythmia Services, California Pacific Medical Center, San Francisco, CA, USA
14
Dell Medical School, University of Texas, Austin, TX, USA
No relevant conflict of interest to disclose
Corresponding Author Andrea Natale Texas Cardiac Arrhythmia Institute, St. David’s Medical Center 3000 N. IH-35, Suite 720, Austin, TX 78705 Telephone + 1 (512) 544-8186, Fax + 1 (512) 544-8184 E-mail: [email protected]
1
Abstract Background Focal impulse and rotor modulation (FIRM)-guided ablation targets sites that are thought to sustain atrial fibrillation (AF). Objective We sought to evaluate the acute and mid-term outcomes of FIRM-guided only ablation in patients with non-paroxysmal AF. Methods We prospectively enrolled patients with persistent and long-standing persistent (LSP) AF at 3 centers to undergo FIRM-guided only ablation. We evaluated acute procedural success (defined as AF termination, organization or ≥10% slowing), safety (incidence of periprocedural complications) and long-term success (single-procedure freedom from atrial tachycardia [AT]/AF off antiarrhythmic drugs [AADs] after a 2-months blanking period). Results 29 patients with persistent (N = 20) and LSP (N = 9) underwent FIRM mapping. Rotors were presents in all patients, with a mean of 4 ± 1.2 per patient (62% were left atrial); 1 focal impulse was identified. All sources were successfully ablated, and overall acute success rate was 41% (0 AF termination, 2 AF slowing, 10 AF organization). There were no major procedure-related adverse events. After a mean of 5.7 months of follow-up, singleprocedure freedom from AT/AF without AADs was 17%. Conclusions In non-paroxysmal AF patients, targeted ablation of FIRM-identified rotors is not effective in obtaining AF termination, organization or slowing during the procedure. After mid-term follow-up, the strategy of ablating FIRM-identified rotors alone did not prevent recurrence from AT/AF.
2
Keywords Atrial fibrillation; catheter ablation; rotors; FIRM mapping
Abbreviations 3D, tridimensional AADs, antiarrhythmic drugs AF, atrial fibrillation CI, confidence interval FIRM, focal impulse and rotor modulation LA, left atrium LSP, long-standing persistent PVAI, pulmonary vein antral isolation PVI, pulmonary vein isolation RA, right atrium RF, radiofrequency SR, sinus rhythm
Introduction In non-paroxysmal atrial fibrillation (AF), it is still debated whether the optimal ablation strategy should target triggers, substrate or both. Through the years, many strategies have been proposed for substrate modification, with the aim of preventing AF maintenance, such as ablating areas of atrial fibrosis suggested by low voltage, late enhancement on MRI or complex fractionated electrograms.1 Another approach is targeting rotors, areas of consistent rotational electrical activation around a center that are thought to be responsible for perpetuating AF.2–4 Rotors can be identified through the proprietary focal impulse and rotors modulation (FIRM) computational-mapping system. Previous studies have reported that, in a mixed population, FIRM-guided ablation results in high rates of acute AF termination/slowing and long-term freedom from recurrent AT/AF, in addition to pulmonary vein isolation (PVI).2,5 Moreover, it has been postulated that the key to successful AF ablation relies on rotors elimination.6,7 However, limited data are available on the efficacy of targeting rotors outside of the originating group. In this study, we report
3
the outcomes of FIRM-guided rotors only ablation. Patients were enrolled as part of an ongoing clinical trial independently evaluating the efficacy FIRM-guided ablation as compared to conventional ablation in patients with non-paroxysmal AF (ClinicalTrials.gov Identifier: NCT02533843). Based on a preliminary analysis of the outcomes observed in the FIRM-guided only ablation group, this arm was prematurely interrupted for futility and, given the significance of the findings, here we present the results.
Methods Study population 30 patients were prospectively enrolled as part of a randomized clinical trial comparing FIRM-guided rotors ablation to conventional ablation in patients with persistent and longstanding (LSP) AF (ClinicalTrials.gov Identifier: NCT02533843) (see Figure 1). After noticing a high recurrence rate among the FIRM-only patients, an unplanned interim analysis was conducted and the internal safety committee opted to interrupt this arm prematurely for lack of benefit and the protocol was amended. Patients enrolled had symptomatic non-paroxysmal AF undergoing first-time RF ablation at 3 centers (2 United States, 1 Europe) for standard indications.8 Exclusion criteria were paroxysmal AF, prior AF ablation, any contraindication to ablation and inability or unwillingness to give informed consent. The procedure was aborted in 1 patient for anatomical reasons (left inferior vena cava draining into a persistent left superior vena cava); this case was not included in the analysis. All patients provided written informed consent to participate and the study was approved the ethics committee of each participating center. Procedure The electrophysiology study was performed after discontinuing antiarrhythmic drugs (AADs) for at least 5 half-lives prior to the procedure, except for amiodarone. A threedimensional (3D) map of the atria was constructed using an electro-anatomic mapping system (CARTO, Biosense Webster, Diamond Bar, CA, USA or NavX, St. Jude Medical, St. Paul, MN, USA) before advancing the 64-pole basket mapping catheter (FIRMap, Abbott, Chicago, IL, USA) in the right atrium (RA) and left atrium (LA). The distal electrode from a quadripolar catheter positioned in the superior vena cava was used as unipolar reference. Unipolar and bipolar electrograms were filtered at 0.05 and 30 Hz to 500 Hz and recorded at 1 kHz sampling rate for export from the electrophysiology recording system. FIRM mapping was performed during AF. Briefly, unipolar electrograms were recorded for 1
4
minute and exported to a dedicated proprietary mapping system (RhythmView, Abbott, Chicago, IL, USA). Rotors were defined as sustained clockwise or counterclockwise activation around a center of rotation and were located by their electrode coordinates (Figure 2), while focal impulses showed centrifugal activation from an origin.2 Radiofrequency (RF) energy was delivered with a 3.5 mm irrigated-tip ablation catheter to achieve local potential abatement with the acute endpoint of AF source (rotor or focal impulse) elimination, as confirmed with FIRM remapping. FIRM mapping was repeated until: all AF sources were identified and ablated; AF organized into atrial tachycardia (AT), either focal or macro-reentrant, or converted to sinus rhythm (SR). If AF persisted despite elimination of all rotors or converted into AT, the patient was cardioverted and the procedure ended. Follow-up Patients were followed-up in an outpatient clinic every three months with a cardiology evaluation, a 12-lead electrocardiogram (ECG), and 7-day Holter monitoring. Study endpoints The primary study endpoint was single-procedure freedom from any AT/AF off AADs after a 2-months blanking period. Recurrent AT/AF was defined as any atrial tachyarrhythmia of at least 30 seconds in duration documented by electrocardiogram (ECG) or a device recording
system.
Secondary
endpoints
were
safety,
defined
as
incidence
of
periprocedural complications and acute procedural success, defined as AF termination, organization into AT or ≥10% slowing.2 Statistical analysis Continuous data are expressed as mean and standard deviation (SD) or median and interquartile range (IQR), and compared using the Student t test or Mann-Whitney test according to their statistical distribution; categorical data are expressed as number and percentage (%) and compared using the Fisher’s exact test. Statistical significance was considered as P < 0.05. All statistical analyses were performed using Prism 6 for Mac (GraphPad Software, La Jolla, CA, USA).
5
Results Results are presented in Figure 1. Baseline characteristics are summarized in Table 1. The study population consisted of 29 patients with non-paroxysmal AF (20 [69%] persistent AF and 9 [31%] LSP AF). Mean age was 62 ± 10 years and 8 (28%) of the patients were female. Ablation procedure Procedural characteristics are summarized in Table 2. Mapping revealed AF sources in 29 patients (100%). The mean number of rotors was 4 ± 1.2 per patient (total of 115). 62% of rotors were identified in the LA and 38% in the RA. The distribution of rotors is summarized in Table 3. 1 RA focal impulse was identified. All sources were ablated, as confirmed by their absence on remapping, and overall acute success was achieved in 12 (41%): no patient converted to SR (0%), AF slowing ≥ 10% occurred in 2 (7%), and organization into AT (see Figure 3) in 10 (34%). Direct-current cardioversion was needed in all patients (100%). The mean procedure length was 222 ± 49 minutes, with 35 ± 16 minutes of RF time. There was no difference in age (62 vs 62 years; P = 1.0), LA diameter (47 vs 48 mm; P = 0.8), number of rotors (3.8 vs 4.3; P = 0.3) or RF time (32 vs 36 min; P = 0.6) between patients with acute success and those without. Patient with LSP were more likely to fail compared with those with persistent AF (relative risk 3.1, 95% confidence interval [CI] 1.47.2). No procedure-related adverse events occurred in all patients. Follow-up After 5.7 ± 2.3 months of follow-up, single-procedure freedom from AT/AF without AADs was 17% (5/29); 28% with or without AADs (8/29). AF slowing or conversion to AT did not predict freedom from recurrent AT/AF (relative risk 2.2, 95% CI 0.4-10.8). Of note, in 2 out of 3 centers freedom from AT/AF was 0%, and in the remaining center patients without a recurrence were on amiodarone (either ongoing or stopped at the time the procedure).
6
Discussion This prospective study demonstrates that in non-paroxysmal AF patients, an ablation strategy exclusively targeting FIRM-identified rotors did not result in AF termination and was not effective in achieving acute AF slowing/organization and freedom from AF/AT after a mean follow-up of 5.7 months. FIRM-identified rotors were present in all patients, with a mean of 4 per patient, and their ablation did not lead to AF termination, with AF slowing/organization achieved in only 41% of patients. Compared to previous reports, we found a greater number of rotors (4 vs 1.9 to 2.8).2,5,6,9–11 Accordingly, RF time was longer in our population (35 min vs 14-20 min), with a comparable RF time per rotor. Despite this, we were unable to reproduce the same acute success reported in the CONFIRM (86%, N = 36) and PRECISE (100%, N = 31) trials conducted by Narayan et al, and in the acute termination study published by Shivkumar et al (100%, N = 14).2,6,9 This might be in part explainable by a different population: our study comprised 100% of non-paroxysmal AF patients, as opposed to 81% (CONFIRM), 79% (Shivkumar et al), and 0% (PRECISE) of the other studies. Other reasons might be statistical variation due to the small sample size, or learning curve effect (although highly experienced operators were involved in the ablation procedure and rotor elimination was objectively assessed by FIRM remapping). Nevertheless, our results compare to those recently reported by Benharash et al, who studied patients with AF (N = 50, 50% nonparoxysmal AF) who underwent FIRM-guided ablation: acute success was achieved in 50%.11 Interestingly, in this study the presence rotors at the sites indicated by FIRM-mapping could not be reliably confirmed using an independent spectral-based quantitative analysis. It is therefore possible that FIRM-identified rotors do not accurately identify sites critical to AF maintenance or that ablation of rotors is not enough to modulate the substrate in non-paroxysmal AF. After a mean follow-up of 5.7 months, single-procedure freedom from AT/AF without AADs was 17% (28% including patients on AADs). Compared with previous reports, our follow-up success rate is lower. In studies where FIRM-guided ablation was done in addition to PVI in a mixed AF population, single-procedure freedom from AT/AF was 70.6% (CONFIRM) and 71.4% (Miller et al).2,5 Preliminary results of the PRECISE trial suggest that in paroxysmal AF, FIRM-guided ablation only is effective in preventing early recurrences, with a reported single-procedure freedom from AF of 82.6% after a median of 190 days (6.2 months).6 The reasons for this discrepancy might again depend on the selected population (a higher prevalence of non-paroxysmal AF – 81% for CONFIRM and 70% for Miller et al), but it is important to note that this is the first study to report follow-up data independently of the
7
originating group. Another possible explanation is that ablation limited to rotors is not sufficient to maintain SR in non-paroxysmal AF. This, in turn, could again depend on the low accuracy of FIRM-mapping in identify rotors.11 Or, it could highlight the limited role of pure substrate modification in non-paroxysmal AF. Accordingly, there was no relation between acute procedural success and freedom from AT/AF at follow-up. Given the aforementioned results, the FIRM-guided ablation only arm was deemed futile, resulting in premature trial arm termination: FIRM-identified rotors ablation only does not appear to be effective in non-paroxysmal AF patients and should not be employed as a sole ablation strategy in this population. Whether FIRM-guided ablation in addition to pulmonary vein antral isolation (PVAI) is beneficial and superior to an ablation strategy encompassing both PVAI and non-PV triggers is being assessed in the ongoing OASIS randomized clinical trial (ClinicalTrials.gov Identifier: NCT02533843), currently recruiting patients and with an estimated primary completion date in December 2015. Study limitations Our study has a number of limitations. First, a relatively small sample size, due to the premature interruption of this intervention arm, limited the power of the statistical analysis to detect small differences. Another limitation is the absence of a control group, which will be addressed in the ongoing randomized controlled trial. Despite a short followup time, the success rate is low and would be unchanged or lower with a longer follow-up. However, this is the largest independent study to date to evaluate the acute and mid-term effect of FIRM-guided rotor ablation alone in non-paroxysmal AF patients.
Conclusions Catheter ablation of FIRM-identified rotor sites led to AF slowing or organization in a minority of patients with non-paroxysmal AF. After mid-term follow-up, the strategy of ablating FIRM-identified rotors alone did not prevent recurrence from AT/AF. Further studies are needed to evaluate the additional role of FIRM-guided ablation in patients with non-paroxysmal AF.
8
Bibliography
1.
Kottkamp H, Bender R, Berg J: Catheter Ablation of Atrial Fibrillation: How to Modify the Substrate? J Am Coll Cardiol 2015; 65:196–206.
2.
Narayan SM, Krummen DE, Shivkumar K, Clopton P, Rappel W-J, Miller JM: Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation) trial. J Am Coll Cardiol 2012; 60:628–636.
3.
Atienza F, Almendral J, Ormaetxe JM, et al.: Comparison of Radiofrequency Catheter Ablation of Drivers and Circumferential Pulmonary Vein Isolation in Atrial Fibrillation. J Am Coll Cardiol 2014; 64:2455–2467.
4.
Haïssaguerre M, Hocini M, Denis A, et al.: Driver Domains in Persistent Atrial Fibrillation. Circulation 2014; 130:530–538.
5.
Miller JM, Kowal RC, Swarup V, et al.: Initial Independent Outcomes from Focal Impulse and Rotor Modulation Ablation for Atrial Fibrillation: Multicenter FIRM Registry. J Cardiovasc Electrophysiol 2014; 25:921–929.
6.
Narayan SM, Krummen DE, Donsky A, Swarup V, Miller JM: Precise Rotor Elimination without Concomitant pulmonary vein Isolation for the Successful Elimination of Paroxysmal Atrial Fibrillation. Hear Rhythm 2013; 10:LBCT4.
7.
Narayan SM, Krummen DE, Clopton P, Shivkumar K, Miller JM: Direct or Coincidental Elimination of Stable Rotors or Focal Sources May Explain Successful Atrial Fibrillation Ablation. J Am Coll Cardiol 2013; 62:138–147.
8.
January CT, Wann LS, Alpert JS, et al.: 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. J Am Coll Cardiol 2014; 64:e1–e76.
9
9.
Shivkumar K, Ellenbogen KA, Hummel JD, Miller JM, Steinberg JS: Acute Termination of Human Atrial Fibrillation by Identification and Catheter Ablation of Localized Rotors and Sources: First Multicenter Experience of Focal Impulse and Rotor Modulation (FIRM) Ablation. J Cardiovasc Electrophysiol 2012; 23:1277–1285.
10.
Swarup V, Baykaner T, Rostamian A, Daubert JP, Hummel J, Krummen DE, Trikha R, Miller JM, Tomassoni GF, Narayan SM: Stability of Rotors and Focal Sources for Human Atrial Fibrillation: Focal Impulse and Rotor Mapping (FIRM) of AF Sources and Fibrillatory Conduction. J Cardiovasc Electrophysiol 2014; 25:1284–1292.
11.
Benharash P, Buch E, Frank P, Share M, Tung R, Shivkumar K, Mandapati R: Quantitative Analysis of Localized Sources Identified by Focal Impulse and Rotor Modulation Mapping in Atrial Fibrillation. Circ Arrhythmia Electrophysiol 2015; 8:554–561.
Clinical Perspectives FIRM-guided ablation has been proposed as a substrate-based ablation strategy in patients with non-paroxysmal AF. In this independent study, rotors identified with the proprietary FIRM computational mapping system were found in all patients. They can be successfully and safely ablated, but their elimination is not effective to obtain AF termination at the time of the procedure nor to prevent recurrences at the time of follow-up. Therefore, FIRM-guided only ablation should not be employed as a sole ablation strategy in this population.
10
Tables Table 1. Baseline characteristics of the study population N = 29 AF type Persistent
20 (69%)
LSP
9 (31%)
AF duration (months)*
36 (4-72)
Age (years)
62.4 ± 10.3
Female gender
8 (28%)
2
BMI (Kg/m )
31.2 ± 4.4
Echocardiography LA diameter (mm)
47 (43-50)
LVEF (%)
55 (50-63)
Medical history Coronary artery disease
3 (10%)
Diabetes mellitus
4 (14%)
Heart failure
6 (21%)
Hypertension
25 (82%)
Obstructive sleep apnea
7 (24%)
CHA2DS2-VASc score
2.3 ± 1.6
*from first diagnosis to ablation procedure Values are expressed as mean ± SD, median (IQR) or number (%) AF, atrial fibrillation; BMI, body mass index; CHA2DS2-VASc = congestive heart failure, hypertension, age ≥ 75 years (doubled), diabetes mellitus, prior ischemic stroke/transient ischemic attack or systemic thromboembolism (doubled), peripheral vascular disease, age 65 to 74 years, female sex; IQR, interquartile range; LSP, long-standing persistent; LA, left atrial; LVEF, left ventricular ejection fraction; SD, standard deviation
11
Table 2. Procedural characteristics N = 29 Patients with rotors
29 (100%)
Number of rotors
115
Rotors per patient
4.0 ± 1.2
RA rotors
44 (38%)
LA rotors
71 (62%)
Number of focal impulses
1*
Procedural time (min)
222 ± 49
RF time (min)
35 ± 16
Acute success
12 (41%)
AF slowing ≥ 10%
2 (7%)
AF organization
10 (34%)
AF termination
0 (0%)
DC cardioversion
29 (100%)
Complications
0 (0%)
Values are expressed as mean ± SD or number (%) *RA AF, atrial fibrillation; DC, direct current; LA, left atrial; RA, right atrial; RF, radiofrequency
Table 3. Distribution of rotor sites N = 115 Right atrium
44 (38%)
RAA
2 (2%)
Anterior wall
6 (5%)
Posterior wall
1 (1%)
Septum
13 (11%)
Lateral wall
22 (19%)
Left atrium
71 (62%)
LAA
13 (11%)
Roof
5 (4%)
Anterior wall
12 (10%)
PV antra/posterior wall
34 (30%)
Septum
4 (4%)
Lateral wall
3 (3%)
Values are expressed as number (%) LAA, left atrial appendage; RAA, right atrial appendage; PV, pulmonary vein
12
Figures Figure 1. Study design and results Non-paroxysmal AF 1st ablation
Population
FIRM only ablation N=30*
Randomization
Procedure
12/29 Acute success^
Freedom from AT/AF
FIRM + PVAI ablation N=40°
PVAI + triggers ablation N=40 N=40°
17/29 No acute success
8/29 with AAD 5/29 off AAD
*1 patient did not undergo the procedure for anatomical reasons; reasons °estimated number for enrollment; ^defined defined as AF slowing ≥ 10%, organization into AT or conversion to sinus rhythm AAD, antiarrhythmic drugs; AF, atrial fibrillation; AT, atrial tachycardia; FIRM, focal impulses and rotors modulation; PVAI, pulmonary vein antral isolation
Figure 2. Three-dimensional (3D) electro-anatomic maps showing rotors and their respective ablation points.. Left, right anterior oblique (RAO) view of the right atrium (RA) showing a septal rotor (blue).. Right, antero-posterior (AP) view of the left atrium (LA) showing three rotors: one in roof (green), one anterior (purple) and one septal (orange). (orange)
Figure 3. Example of organization of atrial fibrillation (AF) during rotors ablation. ABL, ablation catheter; CR, crista; CS, coronary sinus
14
Acute and early outcomes of FIRM-guided rotorsonly ablation in patients with non-paroxysmal atrial fibrillation Carola Gianni MD, Sanghamitra Mohanty MD MS FHRS, Luigi Di Biase MD PhD FHRS, Tamara Metz RN BSN, Chintan Trivedi MD, Yalçın Gökoğlan MD, Mahmut F. Güne� MD, Rong Bai MD FHRS, Amin Al-Ahmad MD CCDS FHRS, J. David Burkhardt MD FHRS, G. Joseph Gallinghouse MD FHRS, Rodney Horton MD FHRS, Patrick M. Hranitzky MD FHRS, Javier E. Sanchez MD, Phillipp Halbfaß MD, Patrick Müller MD, Anja Schade MD, Thomas Deneke MD PhD FHRS, Gery F. Tomassoni MD FHRS, Andrea Natale MD FHRS
PII: DOI: Reference:
S1547-5271(15)01554-4 http://dx.doi.org/10.1016/j.hrthm.2015.12.028 HRTHM6559
To appear in:
Heart Rhythm
www.elsevier.com/locate/buildenv
Cite this article as: Carola Gianni MD, Sanghamitra Mohanty MD MS FHRS, Luigi Di Biase MD PhD FHRS, Tamara Metz RN BSN, Chintan Trivedi MD, Yalçın Gökoğlan MD, Mahmut F. Güne� MD, Rong Bai MD FHRS, Amin Al-Ahmad MD CCDS FHRS, J. David Burkhardt MD FHRS, G. Joseph Gallinghouse MD FHRS, Rodney Horton MD FHRS, Patrick M. Hranitzky MD FHRS, Javier E. Sanchez MD, Phillipp Halbfaß MD, Patrick Müller MD, Anja Schade MD, Thomas Deneke MD PhD FHRS, Gery F. Tomassoni MD FHRS, Andrea Natale MD FHRS, Acute and early outcomes of FIRMguided rotors-only ablation in patients with non-paroxysmal atrial fibrillation, Heart Rhythm, http://dx.doi.org/10.1016/j.hrthm.2015.12.028 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Acute and early outcomes of FIRM-guided rotors-only ablation in patients with non-paroxysmal atrial fibrillation FIRM-guided rotors-only ablation in non-paroxysmal AF Carola Gianni MD1,2, Sanghamitra Mohanty MD MS FHRS1, Luigi Di Biase MD PhD FHRS1,3,4,5, Tamara Metz RN BSN1, Chintan Trivedi MD1, Yalçın Gökoğlan MD1,6, Mahmut F Güneş MD1, Rong Bai MD FHRS1, Amin Al-Ahmad MD CCDS FHRS1, J. David Burkhardt MD FHRS1, G. Joseph Gallinghouse MD FHRS1, Rodney Horton MD FHRS1,4, Patrick M Hranitzky MD FHRS1, Javier E Sanchez MD1, Phillipp Halbfaß MD7, Patrick Müller MD7,8, Anja Schade MD7, Thomas Deneke MD PhD FHRS7,8, Gery F Tomassoni MD9 FHRS, Andrea Natale MD FHRS1,3,4,10,11,12,13,14 1
Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, TX, USA
2
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
3
Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
4
Department of Biomedical Engineering, University of Texas, Austin, TX, USA
5
Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
6
Department of Cardiology, Gülhane Military Academy of Medicine, Ankara, Turkey
7
Clinic for Interventional Electrophysiology, Heart Center Bad Neustadt, Bad Neustadt, Germany
8
University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany
9
Baptist Health Lexington, Lexington, KY, USA
10
Division of Cardiovascular Diseases, Scripps Clinic, La Jolla, CA, USA
11
MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA
12
Division of Cardiology, Stanford University, Stanford, CA, USA
13
Electrophysiology and Arrhythmia Services, California Pacific Medical Center, San Francisco, CA, USA
14
Dell Medical School, University of Texas, Austin, TX, USA
No relevant conflict of interest to disclose
Corresponding Author Andrea Natale Texas Cardiac Arrhythmia Institute, St. David’s Medical Center 3000 N. IH-35, Suite 720, Austin, TX 78705 Telephone + 1 (512) 544-8186, Fax + 1 (512) 544-8184 E-mail: [email protected]
1
Abstract Background Focal impulse and rotor modulation (FIRM)-guided ablation targets sites that are thought to sustain atrial fibrillation (AF). Objective We sought to evaluate the acute and mid-term outcomes of FIRM-guided only ablation in patients with non-paroxysmal AF. Methods We prospectively enrolled patients with persistent and long-standing persistent (LSP) AF at 3 centers to undergo FIRM-guided only ablation. We evaluated acute procedural success (defined as AF termination, organization or ≥10% slowing), safety (incidence of periprocedural complications) and long-term success (single-procedure freedom from atrial tachycardia [AT]/AF off antiarrhythmic drugs [AADs] after a 2-months blanking period). Results 29 patients with persistent (N = 20) and LSP (N = 9) underwent FIRM mapping. Rotors were presents in all patients, with a mean of 4 ± 1.2 per patient (62% were left atrial); 1 focal impulse was identified. All sources were successfully ablated, and overall acute success rate was 41% (0 AF termination, 2 AF slowing, 10 AF organization). There were no major procedure-related adverse events. After a mean of 5.7 months of follow-up, singleprocedure freedom from AT/AF without AADs was 17%. Conclusions In non-paroxysmal AF patients, targeted ablation of FIRM-identified rotors is not effective in obtaining AF termination, organization or slowing during the procedure. After mid-term follow-up, the strategy of ablating FIRM-identified rotors alone did not prevent recurrence from AT/AF.
2
Keywords Atrial fibrillation; catheter ablation; rotors; FIRM mapping
Abbreviations 3D, tridimensional AADs, antiarrhythmic drugs AF, atrial fibrillation CI, confidence interval FIRM, focal impulse and rotor modulation LA, left atrium LSP, long-standing persistent PVAI, pulmonary vein antral isolation PVI, pulmonary vein isolation RA, right atrium RF, radiofrequency SR, sinus rhythm
Introduction In non-paroxysmal atrial fibrillation (AF), it is still debated whether the optimal ablation strategy should target triggers, substrate or both. Through the years, many strategies have been proposed for substrate modification, with the aim of preventing AF maintenance, such as ablating areas of atrial fibrosis suggested by low voltage, late enhancement on MRI or complex fractionated electrograms.1 Another approach is targeting rotors, areas of consistent rotational electrical activation around a center that are thought to be responsible for perpetuating AF.2–4 Rotors can be identified through the proprietary focal impulse and rotors modulation (FIRM) computational-mapping system. Previous studies have reported that, in a mixed population, FIRM-guided ablation results in high rates of acute AF termination/slowing and long-term freedom from recurrent AT/AF, in addition to pulmonary vein isolation (PVI).2,5 Moreover, it has been postulated that the key to successful AF ablation relies on rotors elimination.6,7 However, limited data are available on the efficacy of targeting rotors outside of the originating group. In this study, we report
3
the outcomes of FIRM-guided rotors only ablation. Patients were enrolled as part of an ongoing clinical trial independently evaluating the efficacy FIRM-guided ablation as compared to conventional ablation in patients with non-paroxysmal AF (ClinicalTrials.gov Identifier: NCT02533843). Based on a preliminary analysis of the outcomes observed in the FIRM-guided only ablation group, this arm was prematurely interrupted for futility and, given the significance of the findings, here we present the results.
Methods Study population 30 patients were prospectively enrolled as part of a randomized clinical trial comparing FIRM-guided rotors ablation to conventional ablation in patients with persistent and longstanding (LSP) AF (ClinicalTrials.gov Identifier: NCT02533843) (see Figure 1). After noticing a high recurrence rate among the FIRM-only patients, an unplanned interim analysis was conducted and the internal safety committee opted to interrupt this arm prematurely for lack of benefit and the protocol was amended. Patients enrolled had symptomatic non-paroxysmal AF undergoing first-time RF ablation at 3 centers (2 United States, 1 Europe) for standard indications.8 Exclusion criteria were paroxysmal AF, prior AF ablation, any contraindication to ablation and inability or unwillingness to give informed consent. The procedure was aborted in 1 patient for anatomical reasons (left inferior vena cava draining into a persistent left superior vena cava); this case was not included in the analysis. All patients provided written informed consent to participate and the study was approved the ethics committee of each participating center. Procedure The electrophysiology study was performed after discontinuing antiarrhythmic drugs (AADs) for at least 5 half-lives prior to the procedure, except for amiodarone. A threedimensional (3D) map of the atria was constructed using an electro-anatomic mapping system (CARTO, Biosense Webster, Diamond Bar, CA, USA or NavX, St. Jude Medical, St. Paul, MN, USA) before advancing the 64-pole basket mapping catheter (FIRMap, Abbott, Chicago, IL, USA) in the right atrium (RA) and left atrium (LA). The distal electrode from a quadripolar catheter positioned in the superior vena cava was used as unipolar reference. Unipolar and bipolar electrograms were filtered at 0.05 and 30 Hz to 500 Hz and recorded at 1 kHz sampling rate for export from the electrophysiology recording system. FIRM mapping was performed during AF. Briefly, unipolar electrograms were recorded for 1
4
minute and exported to a dedicated proprietary mapping system (RhythmView, Abbott, Chicago, IL, USA). Rotors were defined as sustained clockwise or counterclockwise activation around a center of rotation and were located by their electrode coordinates (Figure 2), while focal impulses showed centrifugal activation from an origin.2 Radiofrequency (RF) energy was delivered with a 3.5 mm irrigated-tip ablation catheter to achieve local potential abatement with the acute endpoint of AF source (rotor or focal impulse) elimination, as confirmed with FIRM remapping. FIRM mapping was repeated until: all AF sources were identified and ablated; AF organized into atrial tachycardia (AT), either focal or macro-reentrant, or converted to sinus rhythm (SR). If AF persisted despite elimination of all rotors or converted into AT, the patient was cardioverted and the procedure ended. Follow-up Patients were followed-up in an outpatient clinic every three months with a cardiology evaluation, a 12-lead electrocardiogram (ECG), and 7-day Holter monitoring. Study endpoints The primary study endpoint was single-procedure freedom from any AT/AF off AADs after a 2-months blanking period. Recurrent AT/AF was defined as any atrial tachyarrhythmia of at least 30 seconds in duration documented by electrocardiogram (ECG) or a device recording
system.
Secondary
endpoints
were
safety,
defined
as
incidence
of
periprocedural complications and acute procedural success, defined as AF termination, organization into AT or ≥10% slowing.2 Statistical analysis Continuous data are expressed as mean and standard deviation (SD) or median and interquartile range (IQR), and compared using the Student t test or Mann-Whitney test according to their statistical distribution; categorical data are expressed as number and percentage (%) and compared using the Fisher’s exact test. Statistical significance was considered as P < 0.05. All statistical analyses were performed using Prism 6 for Mac (GraphPad Software, La Jolla, CA, USA).
5
Results Results are presented in Figure 1. Baseline characteristics are summarized in Table 1. The study population consisted of 29 patients with non-paroxysmal AF (20 [69%] persistent AF and 9 [31%] LSP AF). Mean age was 62 ± 10 years and 8 (28%) of the patients were female. Ablation procedure Procedural characteristics are summarized in Table 2. Mapping revealed AF sources in 29 patients (100%). The mean number of rotors was 4 ± 1.2 per patient (total of 115). 62% of rotors were identified in the LA and 38% in the RA. The distribution of rotors is summarized in Table 3. 1 RA focal impulse was identified. All sources were ablated, as confirmed by their absence on remapping, and overall acute success was achieved in 12 (41%): no patient converted to SR (0%), AF slowing ≥ 10% occurred in 2 (7%), and organization into AT (see Figure 3) in 10 (34%). Direct-current cardioversion was needed in all patients (100%). The mean procedure length was 222 ± 49 minutes, with 35 ± 16 minutes of RF time. There was no difference in age (62 vs 62 years; P = 1.0), LA diameter (47 vs 48 mm; P = 0.8), number of rotors (3.8 vs 4.3; P = 0.3) or RF time (32 vs 36 min; P = 0.6) between patients with acute success and those without. Patient with LSP were more likely to fail compared with those with persistent AF (relative risk 3.1, 95% confidence interval [CI] 1.47.2). No procedure-related adverse events occurred in all patients. Follow-up After 5.7 ± 2.3 months of follow-up, single-procedure freedom from AT/AF without AADs was 17% (5/29); 28% with or without AADs (8/29). AF slowing or conversion to AT did not predict freedom from recurrent AT/AF (relative risk 2.2, 95% CI 0.4-10.8). Of note, in 2 out of 3 centers freedom from AT/AF was 0%, and in the remaining center patients without a recurrence were on amiodarone (either ongoing or stopped at the time the procedure).
6
Discussion This prospective study demonstrates that in non-paroxysmal AF patients, an ablation strategy exclusively targeting FIRM-identified rotors did not result in AF termination and was not effective in achieving acute AF slowing/organization and freedom from AF/AT after a mean follow-up of 5.7 months. FIRM-identified rotors were present in all patients, with a mean of 4 per patient, and their ablation did not lead to AF termination, with AF slowing/organization achieved in only 41% of patients. Compared to previous reports, we found a greater number of rotors (4 vs 1.9 to 2.8).2,5,6,9–11 Accordingly, RF time was longer in our population (35 min vs 14-20 min), with a comparable RF time per rotor. Despite this, we were unable to reproduce the same acute success reported in the CONFIRM (86%, N = 36) and PRECISE (100%, N = 31) trials conducted by Narayan et al, and in the acute termination study published by Shivkumar et al (100%, N = 14).2,6,9 This might be in part explainable by a different population: our study comprised 100% of non-paroxysmal AF patients, as opposed to 81% (CONFIRM), 79% (Shivkumar et al), and 0% (PRECISE) of the other studies. Other reasons might be statistical variation due to the small sample size, or learning curve effect (although highly experienced operators were involved in the ablation procedure and rotor elimination was objectively assessed by FIRM remapping). Nevertheless, our results compare to those recently reported by Benharash et al, who studied patients with AF (N = 50, 50% nonparoxysmal AF) who underwent FIRM-guided ablation: acute success was achieved in 50%.11 Interestingly, in this study the presence rotors at the sites indicated by FIRM-mapping could not be reliably confirmed using an independent spectral-based quantitative analysis. It is therefore possible that FIRM-identified rotors do not accurately identify sites critical to AF maintenance or that ablation of rotors is not enough to modulate the substrate in non-paroxysmal AF. After a mean follow-up of 5.7 months, single-procedure freedom from AT/AF without AADs was 17% (28% including patients on AADs). Compared with previous reports, our follow-up success rate is lower. In studies where FIRM-guided ablation was done in addition to PVI in a mixed AF population, single-procedure freedom from AT/AF was 70.6% (CONFIRM) and 71.4% (Miller et al).2,5 Preliminary results of the PRECISE trial suggest that in paroxysmal AF, FIRM-guided ablation only is effective in preventing early recurrences, with a reported single-procedure freedom from AF of 82.6% after a median of 190 days (6.2 months).6 The reasons for this discrepancy might again depend on the selected population (a higher prevalence of non-paroxysmal AF – 81% for CONFIRM and 70% for Miller et al), but it is important to note that this is the first study to report follow-up data independently of the
7
originating group. Another possible explanation is that ablation limited to rotors is not sufficient to maintain SR in non-paroxysmal AF. This, in turn, could again depend on the low accuracy of FIRM-mapping in identify rotors.11 Or, it could highlight the limited role of pure substrate modification in non-paroxysmal AF. Accordingly, there was no relation between acute procedural success and freedom from AT/AF at follow-up. Given the aforementioned results, the FIRM-guided ablation only arm was deemed futile, resulting in premature trial arm termination: FIRM-identified rotors ablation only does not appear to be effective in non-paroxysmal AF patients and should not be employed as a sole ablation strategy in this population. Whether FIRM-guided ablation in addition to pulmonary vein antral isolation (PVAI) is beneficial and superior to an ablation strategy encompassing both PVAI and non-PV triggers is being assessed in the ongoing OASIS randomized clinical trial (ClinicalTrials.gov Identifier: NCT02533843), currently recruiting patients and with an estimated primary completion date in December 2015. Study limitations Our study has a number of limitations. First, a relatively small sample size, due to the premature interruption of this intervention arm, limited the power of the statistical analysis to detect small differences. Another limitation is the absence of a control group, which will be addressed in the ongoing randomized controlled trial. Despite a short followup time, the success rate is low and would be unchanged or lower with a longer follow-up. However, this is the largest independent study to date to evaluate the acute and mid-term effect of FIRM-guided rotor ablation alone in non-paroxysmal AF patients.
Conclusions Catheter ablation of FIRM-identified rotor sites led to AF slowing or organization in a minority of patients with non-paroxysmal AF. After mid-term follow-up, the strategy of ablating FIRM-identified rotors alone did not prevent recurrence from AT/AF. Further studies are needed to evaluate the additional role of FIRM-guided ablation in patients with non-paroxysmal AF.
8
Bibliography
1.
Kottkamp H, Bender R, Berg J: Catheter Ablation of Atrial Fibrillation: How to Modify the Substrate? J Am Coll Cardiol 2015; 65:196–206.
2.
Narayan SM, Krummen DE, Shivkumar K, Clopton P, Rappel W-J, Miller JM: Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation) trial. J Am Coll Cardiol 2012; 60:628–636.
3.
Atienza F, Almendral J, Ormaetxe JM, et al.: Comparison of Radiofrequency Catheter Ablation of Drivers and Circumferential Pulmonary Vein Isolation in Atrial Fibrillation. J Am Coll Cardiol 2014; 64:2455–2467.
4.
Haïssaguerre M, Hocini M, Denis A, et al.: Driver Domains in Persistent Atrial Fibrillation. Circulation 2014; 130:530–538.
5.
Miller JM, Kowal RC, Swarup V, et al.: Initial Independent Outcomes from Focal Impulse and Rotor Modulation Ablation for Atrial Fibrillation: Multicenter FIRM Registry. J Cardiovasc Electrophysiol 2014; 25:921–929.
6.
Narayan SM, Krummen DE, Donsky A, Swarup V, Miller JM: Precise Rotor Elimination without Concomitant pulmonary vein Isolation for the Successful Elimination of Paroxysmal Atrial Fibrillation. Hear Rhythm 2013; 10:LBCT4.
7.
Narayan SM, Krummen DE, Clopton P, Shivkumar K, Miller JM: Direct or Coincidental Elimination of Stable Rotors or Focal Sources May Explain Successful Atrial Fibrillation Ablation. J Am Coll Cardiol 2013; 62:138–147.
8.
January CT, Wann LS, Alpert JS, et al.: 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. J Am Coll Cardiol 2014; 64:e1–e76.
9
9.
Shivkumar K, Ellenbogen KA, Hummel JD, Miller JM, Steinberg JS: Acute Termination of Human Atrial Fibrillation by Identification and Catheter Ablation of Localized Rotors and Sources: First Multicenter Experience of Focal Impulse and Rotor Modulation (FIRM) Ablation. J Cardiovasc Electrophysiol 2012; 23:1277–1285.
10.
Swarup V, Baykaner T, Rostamian A, Daubert JP, Hummel J, Krummen DE, Trikha R, Miller JM, Tomassoni GF, Narayan SM: Stability of Rotors and Focal Sources for Human Atrial Fibrillation: Focal Impulse and Rotor Mapping (FIRM) of AF Sources and Fibrillatory Conduction. J Cardiovasc Electrophysiol 2014; 25:1284–1292.
11.
Benharash P, Buch E, Frank P, Share M, Tung R, Shivkumar K, Mandapati R: Quantitative Analysis of Localized Sources Identified by Focal Impulse and Rotor Modulation Mapping in Atrial Fibrillation. Circ Arrhythmia Electrophysiol 2015; 8:554–561.
Clinical Perspectives FIRM-guided ablation has been proposed as a substrate-based ablation strategy in patients with non-paroxysmal AF. In this independent study, rotors identified with the proprietary FIRM computational mapping system were found in all patients. They can be successfully and safely ablated, but their elimination is not effective to obtain AF termination at the time of the procedure nor to prevent recurrences at the time of follow-up. Therefore, FIRM-guided only ablation should not be employed as a sole ablation strategy in this population.
10
Tables Table 1. Baseline characteristics of the study population N = 29 AF type Persistent
20 (69%)
LSP
9 (31%)
AF duration (months)*
36 (4-72)
Age (years)
62.4 ± 10.3
Female gender
8 (28%)
2
BMI (Kg/m )
31.2 ± 4.4
Echocardiography LA diameter (mm)
47 (43-50)
LVEF (%)
55 (50-63)
Medical history Coronary artery disease
3 (10%)
Diabetes mellitus
4 (14%)
Heart failure
6 (21%)
Hypertension
25 (82%)
Obstructive sleep apnea
7 (24%)
CHA2DS2-VASc score
2.3 ± 1.6
*from first diagnosis to ablation procedure Values are expressed as mean ± SD, median (IQR) or number (%) AF, atrial fibrillation; BMI, body mass index; CHA2DS2-VASc = congestive heart failure, hypertension, age ≥ 75 years (doubled), diabetes mellitus, prior ischemic stroke/transient ischemic attack or systemic thromboembolism (doubled), peripheral vascular disease, age 65 to 74 years, female sex; IQR, interquartile range; LSP, long-standing persistent; LA, left atrial; LVEF, left ventricular ejection fraction; SD, standard deviation
11
Table 2. Procedural characteristics N = 29 Patients with rotors
29 (100%)
Number of rotors
115
Rotors per patient
4.0 ± 1.2
RA rotors
44 (38%)
LA rotors
71 (62%)
Number of focal impulses
1*
Procedural time (min)
222 ± 49
RF time (min)
35 ± 16
Acute success
12 (41%)
AF slowing ≥ 10%
2 (7%)
AF organization
10 (34%)
AF termination
0 (0%)
DC cardioversion
29 (100%)
Complications
0 (0%)
Values are expressed as mean ± SD or number (%) *RA AF, atrial fibrillation; DC, direct current; LA, left atrial; RA, right atrial; RF, radiofrequency
Table 3. Distribution of rotor sites N = 115 Right atrium
44 (38%)
RAA
2 (2%)
Anterior wall
6 (5%)
Posterior wall
1 (1%)
Septum
13 (11%)
Lateral wall
22 (19%)
Left atrium
71 (62%)
LAA
13 (11%)
Roof
5 (4%)
Anterior wall
12 (10%)
PV antra/posterior wall
34 (30%)
Septum
4 (4%)
Lateral wall
3 (3%)
Values are expressed as number (%) LAA, left atrial appendage; RAA, right atrial appendage; PV, pulmonary vein
12
Figures Figure 1. Study design and results Non-paroxysmal AF 1st ablation
Population
FIRM only ablation N=30*
Randomization
Procedure
12/29 Acute success^
Freedom from AT/AF
FIRM + PVAI ablation N=40°
PVAI + triggers ablation N=40 N=40°
17/29 No acute success
8/29 with AAD 5/29 off AAD
*1 patient did not undergo the procedure for anatomical reasons; reasons °estimated number for enrollment; ^defined defined as AF slowing ≥ 10%, organization into AT or conversion to sinus rhythm AAD, antiarrhythmic drugs; AF, atrial fibrillation; AT, atrial tachycardia; FIRM, focal impulses and rotors modulation; PVAI, pulmonary vein antral isolation
Figure 2. Three-dimensional (3D) electro-anatomic maps showing rotors and their respective ablation points.. Left, right anterior oblique (RAO) view of the right atrium (RA) showing a septal rotor (blue).. Right, antero-posterior (AP) view of the left atrium (LA) showing three rotors: one in roof (green), one anterior (purple) and one septal (orange). (orange)
Figure 3. Example of organization of atrial fibrillation (AF) during rotors ablation. ABL, ablation catheter; CR, crista; CS, coronary sinus
14