High density substrate mapping In AF

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High density substrate mapping In AF A Pisapia J Seitz C Bars M Bremondy A Ferracci * J Khalifa ** * St Joseph Hospital Marseille ** Ann Arbor University Turin 2016 Hôpital Saint Joseph Marseille jseitz@hopital-saint-joseph.fr

High density mapping in AF BACKGROUND : Results of several randomized clinical trials have shown no benefits to adding either complex fractionated atrial electrogram or linear ablation to PVI compared to doing only PVI in patients with persistent AF. ( STAR AF II BOCA CHASE-AF )

Ablation of persistent and long persistent AF: 3 methods : - PVI - PVI + lines - PVI + CFAE Verma et al. NEJM 2015

Freedom AF/AT 1 procedure or more Results of 589 patients no difference between the 3 methods : ~ 40 % stable sinus rythm after 1 abl. ~ 50% stable sinus rythm after several abl.

High density mapping in AF Is CFAE an incorrect target for AF ablation??

High density mapping in AF Are CFAE sites AF substrate sites? - Recent interest in the role of rotors as the main mechanism of AF and its association with CFAE - Khalifa demonstrated that CFAE are predominantly found at the limits of the highest frequency of excitation - High degree of irregularity and fractionnation is present at the rotor type

ROTOR

WITH A COURTESY OF J KHALIFA

CFAE are observed in rotor regions

High density mapping in AF Application in a human heart

N=121 pts with PAF, PeAF & LS-PeAF. EGM-based ablation approach (CFAE) +/- Ibutilide AF termination rate >95% (SR conversion rate =95%) Continuous low voltage fractionnated potentials Nademanee et al. JACC. Vol. 43, No. 11, 2004

Issues EGM based Substrate ablation is very effective but: So far proving to be a quite difficult technique with a poor reproducibility rate Poor understanding of EGM significance & no consensus about targets > A real rationalization and systematization of EGM-based ablation is needed in order to make the technique more user friendly and efficient.

High density mapping in AF Concept of Spatio-temporal dispersion ( Ann Arbor St Joseph )

Concept of Spatio-temporal dispersion Dispersion areas were defined as clusters of electrograms, either fractionated or nonfractionated, that displayed inter-electrode time and space dispersion at a minimum of three adjacent bipoles such that activation was spread out over all the AF cycle length

Example of EGMs from dispersion regions

Substrate HD Clinical study

Clinical Study Prospective enrollment of 105 patients in 3 centers for AF ablation AF sequential mapping in both atria using a 20-pole catheter PentaRay. Tagging and ablation of regions harboring clusters of fast and fractionated electrograms spanning the majority of the AF cycle length (active fibrillatory regions with spatio temporal dispersion) No PV isolation Ablation endpoints : AF termination acutely, and freedom from AF/AT (after 18 m follow-up with or without AA drugs).

Study population (n=105) Validation set (n=47) p Age (years), mean + SD 63 +11 58±11 0.0046 Male, n (%) 80 (76.2%) 35 (74%) 0.8191 AF type Paroxysmal AF, n (%) 24 (22.8%) 9 (19,2%) 0,6 non-paroxysmal AF, n (%) 81 (77,2%) 38(80,8%) 0,6 Maximum sustained AF duration (months), 12.2 + 20 19.4±31.6 0.2457 mean + SD Structural heart disease, n(%) 38 (36%) 14 (35%) 0.4665 Hypertension, % 48(45,7%) 20 (42,5%) 0.5217 Diabetes, % 13(12.4%) 5(10,6%) 0,5995 LA diameter, mean + SD 45,6± 7,6 42,4±12,4 0,09 LVEF (%), median mean + SD 52 ± 11 54 ± 12 0,20 Amiodarone before ablation, % 32% NA

Immediate results RF= 20 min Sinus Rhythm conversion rate = 77% Total RF time = 49±21 minutes (Ablated surf= 17±10% LA surf and 10±5 % biatrial surf)

Sinus Rhythm conversion rate = 77%

Substrate HD Mechanistic study

Dispersion regions characteristics 4 ± 2 areas 18 ±10 cm2 5 ± 1.5 areas 17±9 cm2 Overall patients: 5 ± 2 areas 22.5±13.5 cm2 6 ± 2 areas 41±12 cm2

Fractionation & Dispersion

«The great majority of EGMs in dispersion regions are fractionated but fractionated EGMs can also be observed in non-disperion regions»

What are these dispersion regions?

Numerical simulations Human atrial model, homogeneous substrate: Spatio-temporal dispersion No dispersion

Numerical simulation Human atrial model, Interstitial fibrosis condition : Spatio-temporal Dispersion with fractionation

Optical mapping No dispersion Spatio-temporal dispersion with fractionation

18 month-follow up Completed in 91% of the patients: follow-up visits and 24-hour Holter, 7days holter-monitor/ PM-ICD memory card in 20 pts

Better acute efficacy with shorter and less extensive ablation 168 230 49 85

18 month-fu: 55% of stable sinus Rhythm Freedom from AF/AT 1 procedure/patient with or without AA drugs

18 month-fu: 85% of stable sinus Rhythm Freedom from AF/AT 1,4 ±0,5 procedure/patient with or without AA drugs

Substrate HD vs STAR AF2* 100% 90% AF 80% 70% AT AF 60% 50% 40% AT 30% 20% 10% 0% Fredom from AF/AT (1 procedure) Fredom from AF/AT (1 procedure or more) Freedom from A * average results of the comparable 3 groups (PVI, PVI+cfe, PVI+lines)

AT are much easier to ablate than AF 180 160 140 120 100 80 Procedure time RF time 60 40 20 0 Procedure #1 Procedure #2 Procedure #3

Mechanisms of AT and its relationship with the original AF

Analysis in 21 patients: 44 ATs, 22 macroreentries & 22 localized AT (88,6% in non- ablated areas). Importantly 17/22 (77,3%) localized ATs arose from dispersion regions that were not previously ablated! The 2 ATs were located in dipersion areas non already ablated

Since the majority of ATs arise from the dispersion regions that were not previously ablated, it implies that such ATs may be the primary arrhythmias that were unmasked after the areas of fibrillatory conductions had been ablated

Conclusion Spatio-temporal dispersion of electrograms represents an electrical footprint of waves emanating from rapid fibrillatory drivers and propagating within a heterogeneous atrial muscle. The clustering of intra-cardiac electrograms exhibiting spatio-temporal dispersion will result in patient-tailored ablation of all types of AF especially for persistent AF. Atrial tachycardias are probably a part of AF substrate and are able to be unmasked by ablation at dispersion regions

HIGH DENSITY SUBSTRATE MAPPING IN AF THANK YOU FOR YOUR ATTENTION