the advance in technology of AF substrate analysis and ablation

1. Innovations in Atrial
fibrillation management
Ahmed Abdelwahed, MD
Heart Center, Department of Cardiology, Tampere University
Hospital, and School of Medicine, University of Tampere,
Finland;
Department of Cardiology, Faculty of Medicine, Zagazig
University, Egypt
Heidelberg 14-16 April 2016

2.  review of pathophysiology
 structural remodelling electrical remodelling inflammation
 management of rhythm
A. therapeutic:
 upstream therapy
 novel AAD
A. interventional :
 endocardial ablation
 surgical epicardial...minimally invasive + hybrid
 thromboembolic prevention
 LAAOs.
Review points

3. Pathophysiology
ACEI/AR
B
Statins

4. LA remodeling inhibtors
Upstream therapy

5. Upstream therapy
• Prevent or at least halt the structural remodeling.
• ACEI/ARBs showed from retrospective studies
significant effect for prevention of AF in CHF and
LVH(AFFIRM,LIFE)class IIa-B
• Statins has pleotropic effect “anti-inflammatory” which
found to reverse the electrical and structural
remodeling.(PAFRIOSIES) class IIb-A
• But no effect on patients with no cardiovascular
risk(ANTIPAF)class III-B

6. New upstream therapy
• Pirfenidone: anti-fibrotic (TGFβ-inhibitor) attenuate and
potentially reverse collagen deposition.
• Alda-1: aldolase ROS deactivator
• Geranylgeranylacetone (GGA): atrial tachycardia-induced
remodeling through heat shock protein(HSP) ↓Ica+2
• Tubastatin-A: Histone deacetylases (HDACs) inhibitors
↓Ica+2 signaling, proteostasis.

7. Date of download: 4/12/2016 Copyright © The American College of Cardiology. All rights reserved.J Am Coll Cardiol. 2008;51(8):802-809. doi:10.1016/j.jacc.2007.09.064
Cardiomyocyte–Fibroblast Crosstalk
Autocrine and paracrine mechanisms act to amplify humoral and mechanical stimuli resulting in tissue fibrosis. Figure illustration
by Rob Flewell. Ang II = angiotensin II; AT-R = angiotensin receptor; ECM = extracellular matrix; TGF = transforming growth factor;
TGFβ-R = trasforming growth factor beta receptor.
Pirfenidone

8. Tubastatin-A
Circulation.2014; 129: 346-358
Tubastatin-A

9. Novel Anti Arrhythmic
drugs
AAD
Therapeutic Rhythm control

10. Ion channel blockers
• Action potential is mediated by interaction of different ion
channels in rhythmic pattern of open and closure.
• K+ channels are mainly associated with repolarization.
• IKur and IKAch are predominant in atrial myocytes,
selective targeting these channels will reduce “off-target”
side effects.
• The Target of AAD is prolongation of APD[ERP]
• Vernakalant: non-selective IK blocker
• Tertiapin-Q , NTC-801 : IKAch blockers
• MK-0448 , AVE-0118 : Ikur blockers

11. Tertiapin-Q
IKAch blockers
NTC-801
IKAch blockers
MK-0448
Ikur blockers
AVE-0118
Ikur blockers

12. Sunniva de Haan et al. Circulation. 2006;114:1234-1242
AVE0118

13. Ca+2 handling
• Calstabin: RyR-2 blocker.
• calcium overload and
abnormal handling trigger
mechanism.
• Ca/calmodulin
phosphokinase rule in
structural remodeling.

14. conductance
• GAP-134, ZP-123: enhance conductance of Gap
junction”connexin-43”.
• as it is found that decreased expression of Gap junctions
especially "CON-43" with structural and electrical
remodeling.
• but the results are not convenient in highly scared LA.

15. Catheter ablation
Invasive rhythm control

16. Catheter ablation
• It has proven with large consensus of publications that it
has better outcome with success rate ranging 60-80%
with higher success in paroxysmal type than persistent
type.
• This owe to the discovery of atrial myocardial sleeves
that extend into the PV and their major role as trigger for
AF.
• Complete bidirectional PV electrical isolation is the
current line of therapy in AF.

17. Current ESC-guidelines

18. Problems with tech
• ? complications(TIA, stroke, perforation, AO-fistula, PV
stenosis)
• Adverse effect of radiation either on the patient or
operator.
• Recurrence and relapse, new arrhythmias (AT)
• Efficacy, precision.

19. Virtual Anatomy
• Advance in imaging technology assisted more precise
LA anatomy identification.
• Integration and merging of imaging tech to reconstruct
3D :
• CT
• MRI (real time )
• Echocardiography (multiplanar 3D TEE, ICE)

20. RT-MRI
Integrated MRI with EAM
precise location and amount
of energy delivery.[T1w-
FLASH]
Lesion visualization, size
and temporal behavior.[T2w-
HASTE]
Higher efficacy and safety.

21. ICE
Integrated ICE with EAM
CARDIOSOUND
Reconstruction of 3D LA
shell using ICE image
integrated with projected
signals acquired by
catheters.
Real time Visualization of
the lesion
Fluoroless procedures.

22. Ablation energy modes
Different energy
Cryoablation: using N2O to
decrease temperature of
tissue in contact.
[cryoballoon]
[Laser balloon]: real time
visualization of the lesion
The HIFU balloon: high-
intensity focused
ultrasound.

23. RF quantification
• Catheter navigation and ablation using RF energy needs
good contact with the tissue [tactile force] was figured by
local EGM, impedance, fluoroscopic visualization..
• Real-time feedback of contact force new technology
[smart touch]
• Ablation Index: integration of force, power, time, stability
[PRAISE trial]

24. Substrate mapping
• The current AF ablation approach is PV-isolation either
PV-ostia or Wide area circumferential (WACA). Even so
it is not effective in persistent type.
• Other ablation sites added to increase success like mitral
isthmus line, box lesion, CFAE.
• CFAE was subjectively allocated with non strict criteria
for identification.

25. Rotors ablation• vortex of a spiral wave rotating around an unexcitable
core.
• New algorithm for identification of Rotors [FIRM, focal
Impulse & rotor modulation] that depends on the
nonlinear analysis of AF.
• it is expected to be the true drivers in persistent
subtype.

26. FIRMap technology
• TOPERA system:
spherical wire basket that
has 64 evenly placed
electrodes.
To build rotor map that drive
the arrhythmia.
through Activation map of
high frequency domain.
electrodes

27. Rotor map

28. Rotor ablation
J Am Coll Cardiol. 2012;60(7):628-636. doi:10.1016/j.jacc.2012.05.022
just published long term effect
march-2016
high rates of AF slowing and
termination with ablation[>70%]

29. Substrate ”voltage” map
• This contact mapping using cut-off range to identify scar
areas which would be substrates for rotors.
• Added capture stimulation pacing criteria for accuracy.
• Ablation of these areas can increase success rates as
they are considered as core for rotors.

30. Autonomic modulation
• Ganglion plexi : neural
network around the heart
located mainly around PV
ostia , which commonly
ablated with PVI.
• Localization: High frequency
-electrical-stimulation
(HFS) produce
bradycardia.
• High success in Vagal-
induced AF [Ach mediated
AF].

31. Surgical treatment
• Cox-maze IV: use RF or cryoablation in stead of
incisions in the LA wall.
• Success rate in persisent AF: 78 - 84%
• hybrid approach involves a combined epicardial
approach by a surgeon, and a percutaneous endocardial
approach by an electrophysiologist.

32. Management of thrombo
embolic risk
Left Atrial Appendage occluders
LAAOs

33. LAAO guidelines
recommendations ESC-2012

34. LAAO endocardial
Watchman deviceAmplatzer deviceLambre device
Wave Crest device
Assisting imaging for device implantation
 Micro-TEE
 Echo-navigator
 Echo-Fusion
 ICE

35. LAA exclusion epicardial
Atri-clip device LARIAT device

36. LARIAT epicardial

37. Take home message
• AF is a chaotic complex, heterogeneous disease.
• Pathophysiology derived subtyping provides better
understanding and tailored effective intervention.
• Innovative signal analysis has improved substrate
identification and better ablation results.
• therapeutic strategies should focus on disease-specific targets.
• Individualization of therapeutic protocol is mandatory for
better outcome.

38. Thank you