High Density Scar Guided Atrial Fibrillation Mapping (HD-SAGA)

Tracking Information
First Submitted Date ICMJE	July 28, 2017
First Posted Date ICMJE	December 6, 2017
Last Update Posted Date	April 20, 2018
Estimated Study Start Date ICMJE	July 2018
Estimated Primary Completion Date	July 2020 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 29, 2017)	Scar Volume [ Time Frame: Through study completion, an average of 1 year ]Quantification of scar volumes - presented as a proportion of the total atrial geometry volume; Impedance values with ablation [ Time Frame: Through study completion, an average of 1 year ]Collection of localised and conventional impedance during ablation
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT03363087 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 29, 2017)	Confirm Scar Thresholds [ Time Frame: Through study completion, an average of 1 year ]Pacing threshold in mV will be assessed at different levels of atrial scar; Compare scar volumes in AF and sinus rhythm in the same patient [ Time Frame: Through study completion, an average of 1 year ]Quantitative comparison - comparing the scar areas in cm2 between the two maps; Compare maps generated using internal unipolar reference and Wilson's Central Terminus [ Time Frame: Through study completion, an average of 1 year ]Quantitative comparison - comparing the scar areas in cm2 between the two maps; Localised impedance fall during ablation [ Time Frame: Through study completion, an average of 1 year ]Compare the LI fall versus time relationship to assess the nature of the relationship with the aim of generating a target for LI fall with ablation; Localised impedance fall versus electrogram attenuation [ Time Frame: Through study completion, an average of 1 year ]Compare the LI impedance fall with ablation with electrogram attenuation (on microelectrodes) to further provide evidence for an LI target; Localised impedance fall versus pacing capture [ Time Frame: Through study completion, an average of 1 year ]Compare the LI impedance fall with ablation with loss of acing capture during ablation to further provide evidence for an LI target; Compare localised with conventional impedance values during ablation [ Time Frame: Through study completion, an average of 1 year ]Compare localised with conventional impedance values during ablation
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	High Density Scar Guided Atrial Fibrillation Mapping
Official Title ICMJE	High Density Scar Guided Atrial Fibrillation Mapping
Brief Summary	There is increasing evidence that having AF is associated with some scarring of the upper chamber of the heart, the left atrium. There is also evidence that the amount of scarring can predict ablation success rates. Recently, rapid ultra high density mapping equipment has become available and this has the capability of defining the electrical scar in the atrium in detail. The equipment used to do this is standard approved equipment for the procedure but its use for making scar maps has not been fully assessed. In the mapping phase of the study therefore, the aim will be to collect high density scar maps in AF and normal rhythm to see how they compare. Maps will be collected in different ways to see if that changes their accuracy. The study will also assess if the values previously suggested as representing scar with lower density mapping systems are still appropriate where high density mapping equipment is used. The results from this study will help to improve the understanding of scar in the atrium and help demonstrate the most efficient way to collect scar information using this high density mapping equipment. In the future, clinicians may be able to use these very detailed scar maps to tailor and refine the way they ablate patients with AF, though the focus of the current study is just on collecting the scar information. While identifying areas requiring ablation is important to an ablation procedure, the other important aspect is the efficacy of ablation. Until now, we have been reliant on assessing our inputs into an ablation (such as the level of contact and the power delivered) but have been limited in the assessment of the output of an ablation in terms of lesion characteristics. New ablation catheter technology is now available which can assess the localised impedance drop with ablation. This is likely a better surrogate for lesion parameters than what we have previously had available and merits further study. Based on such study, we may be able to define targets for ablation which would help to guide future ablations.
Detailed Description	The study would propose to use the Rhythmia Ultra High Density (UHD) mapping system (Boston Scientific) firstly to generate scar maps to determine if the results are comparable with previous work using lower density systems. Scar maps would be acquired in 3 groups of patients. The first group would be Redo-persistent AF ablation cases as these patients would have expected LA scar (iatrogenic and non-iatrogenic) from their previous ablation procedure. De novo persistent AF patients who would be expected to have non-iatrogenic scar. De novo paroxysmal AF patients who would be expected to have no or minimal scar. In redo AF patients, the validity of the scar maps would be further explored by undertaking re-isolation of veins based on discontinuities in the pulmonary vein isolation lines. If this is proven to be effective, it would demonstrate that the scar picked up by the system is genuine and may also suggest a more effective use of UHD systems for redo-pulmonary vein isolation (PVI). In the ablation phase, we would be assessing the effect of ablation on the localised ablation characteristics of the tissue to assess how this is affected by ablation. From previous work, using conventional, wide area impedance measurements, there is a notable plateau in the impedance drop with ablation suggesting a point beyond which there is minimal efficacy gain from further ablation. One would expect this would be even more apparent with localised impedance. Original Hypothesis - mapping phase An UHD mapping system can be utilised to generate automated, rapid, high density atrial scar maps in AF to guide a scar-based ablation strategy. Original Hypothesis - ablation phase Localised Impedance will fall during ablation and this fall will plateau, suggesting a biophysical target for ablation There is a small body of literature addressing contact mapping of atrial scar but this has mainly relied on lower density mapping approaches. UHD mapping systems offer the advantage of true high-density mapping with improved signal to noise ratios that one would predict will lead to the generation of more accurate maps. These advantages are also such that one would predict scar maps in AF would be more accurate. Extending the scar maps to incorporate the RA is also novel in this context and would give an insight into the degree to which AF is a bi-atrial fibrotic cardiomyopathy. As the use of UHD mapping is novel, it is important to establish how relevant criteria used in lower density, lower fidelity mapping systems are when the newer system is used, especially in defining scar. No clinical studies have been published assessing localised impedance. Protocol Fifteen patients listed for persistent AF ablation would be recruited including redo-ablation patients (aiming for 5 de novo and 10 redo patients). All these patients would be in AF at the time of the procedure. A further 5 patients with paroxysmal AF would also be recruited. Procedures would be performed on uninterrupted anticoagulation with a pre-procedural TOE as dictated by local guidelines. Moderate sedation or general anaesthetic procedures would be included. Intravenous heparin would be used to maintain the ACT at a therapeutic level throughout the study. All mapping would be undertaken using the Orion high density multipolar mapping catheter with the Rhythmia system. The ablation catheter used would be the IntellaNav MiFi Open Irrigated Temperature Ablation Catheter. An RA scar map would be obtained using WCT as a reference. Double transseptal access would be obtained and the mapping and ablation catheters passed into the LA. An LA scar map would be taken with the mapping catheter. For paroxysmal AF cases in sinus rhythm, this would be the only LA map taken. For patients in AF, maps would be taken in AF and then in sinus rhythm. In redo cases, the veins which the scar map suggests are likely to be reconnected would be noted (based on discontinuities in the wide area circumferential ablation (WACA) lines). The mapping catheter would then be used to confirm the presence of electrical reconnection of each vein. The patient would then be cardioverted if in AF and the mapping process repeated using a WCT reference. With all maps, the aim would be complete LA coverage. For the sinus rhythm maps, the LA will be divided into 5 sites: roof, posterior wall, inferior wall, septum, anterior wall bordering left atrial appendage. Within each of these sites, the pacing threshold will be assessed at 3 locations incorporating a spread of bipolar voltages. Following the mapping phase, the case would then proceed as per the operator's standard methodology. The aim would be to collect at least 30 static study ablation points as discussed above. Vein re-isolation would be performed without any catheter measuring electrical activity in the vein, purely based on the scar map, targeting discontinuities in the WACA lines. Ablations would be static rather than drag ablations and at each point, the electrogram from the MiFi electrodes would be recorded at the start and end of ablation. Pacing would be performed during ablation and the impedance value at which pacing capture was lost would be noted. Following this ablation, the mapping catheter would be utilised to establish if the vein has been electrically disconnected based on the scar map. At the end of the case, in sinus rhythm, scar maps of the RA would be taken. In sinus rhythm, pacing would be undertaken as for the LA at the following sites: anterior wall, posterior wall, septum and lateral wall. The scar maps would be exported offline to allow quantitative analysis, as would the electrogram and impedance data. The analysis would be performed using the Matlab programming environment. The scar analysis will exclude any portions of the LA distal to the WACA lines. The initial step will be to give a low voltage zone percentage. The next step will be to identify congruent low voltage zones and give advice regarding the ablation strategy for these - whether this involved delivering lines, for instance for a large posterior wall scar, and if the ablation needs to be extended to other inexcitable structures to prevent leaving a narrow conducting isthmus. Study Follow up There would be no additional follow up for this study - the participants' follow up will follow the normal clinical practice at University Hospital Southampton.
Study Type ICMJE	Interventional
Study Phase	Not Applicable
Study Design ICMJE	Intervention Model: Single Group Assignment; Intervention Model Description: Biatrial automated scar mapping in patients undergoing ablation for atrial fibrillation. Confirmation of scar by pacing in all patients. Collection of impedance data during clinical ablation. Masking: None (Open Label); Primary Purpose: Diagnostic
Condition ICMJE	Atrial Fibrillation
Intervention ICMJE	Device: Mapping and ablation; Ultra high density scar mapping Collection of impedance data during ablation
Study Arms	Experimental: Mapping and ablation; Automated high density biatrial scar mapping Pacing confirmation of scar Collection of impedance data during clinical ablation; Intervention: Device: Mapping and ablation
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Not yet recruiting
Estimated Enrollment ICMJE; (submitted: November 29, 2017)	20
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	July 2020
Estimated Primary Completion Date	July 2020 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: trial Fibrillation, Scheduled for ablation on clinical grounds Able/willing to consent to procedure/research protocol No contraindication to clinical ablation Exclusion Criteria: Unable/unwilling to consent Contraindication to clinical ablation
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 90 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact: Waqas Ullah, PhD 02380777222 ext 8128 waqas.ullah@uhs.nhs.uk
Listed Location Countries ICMJE	Not Provided
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT03363087
Other Study ID Numbers ICMJE	RHM CAR0523
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: No Studies a U.S. FDA-regulated Device Product: No Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement	Plan to Share IPD: No Plan Description: No plans to share IPD
Responsible Party	University Hospital Southampton NHS Foundation Trust
Study Sponsor ICMJE	University Hospital Southampton NHS Foundation Trust
Collaborators ICMJE	Boston Scientific Corporation
Investigators ICMJE	Principal Investigator: Waqas Ullah, PhD University Hospital Southampton NHS Foundation Trust
PRS Account	University Hospital Southampton NHS Foundation Trust
Verification Date	April 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP