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

• ClinicalTrials.gov Identifier: NCT03363087
• Recruitment Status: Recruiting
• First Posted: December 6, 2017
• Last Update Posted: September 26, 2019
• Sponsor: University Hospital Southampton NHS Foundation Trust
• Collaborator: Boston Scientific Corporation
• Information provided by (Responsible Party): University Hospital Southampton NHS Foundation Trust

Tracking Information

• First Submitted Date: July 28, 2017
• First Posted Date: December 6, 2017
• Last Update Posted Date: September 26, 2019
• Actual Study Start Date: August 27, 2019
• Estimated Primary Completion Date: July 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: High Density Scar Guided Atrial Fibrillation Mapping
• Official Title: 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: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: N/A
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: Atrial Fibrillation

Intervention

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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 29, 2017): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2021
• Estimated Primary Completion Date: July 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Waqas Ullah, PhD; 02380777222 ext 8128; waqas.ullah@uhs.nhs.uk

• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT03363087
• Other Study ID Numbers: 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: University Hospital Southampton NHS Foundation Trust
• Collaborators: Boston Scientific Corporation

Investigators

• Principal Investigator: Waqas Ullah, PhD; University Hospital Southampton NHS Foundation Trust

• PRS Account: University Hospital Southampton NHS Foundation Trust
• Verification Date: September 2019