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
review of pathophysiology structural remodelling electrical remodelling inflammation management of rhythmA. therapeutic: upstream therapy novel AADA. interventional : endocardial ablation surgical epicardial...minimally invasive + hybrid thromboembolic prevention LAAOs.
Review points
Pathophysiology
ACEI/ARB
Statins
LA remodeling inhibtorsUpstream therapy
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
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.
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 CrosstalkAutocrine 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
Tubastatin-A
Circulation.2014; 129: 346-358
Tubastatin-A
Novel Anti Arrhythmic drugsAAD
Therapeutic Rhythm control
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
Tertiapin-Q IKAch blockers
NTC-801IKAch blockers
MK-0448Ikur blockers
AVE-0118Ikur blockers
Sunniva de Haan et al. Circulation. 2006;114:1234-1242
AVE0118
Ca+2 handling• Calstabin: RyR-2
blocker.• calcium overload and
abnormal handling trigger mechanism.
• Ca/calmodulin phosphokinase rule in structural remodeling.
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.
Catheter ablation Invasive rhythm control
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.
Current ESC-guidelines
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.
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)
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.
ICEIntegrated ICE with EAM
CARDIOSOUNDReconstruction of 3D LA
shell using ICE image integrated with
projected signals acquired by catheters.Real time Visualization
of the lesionFluoroless procedures.
Ablation energy modesDifferent 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.
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]
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.
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.
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
Rotor map
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%]
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.
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].
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.
Management of thrombo embolic risk
Left Atrial Appendage occluders LAAOs
LAAO guidelines recommendations ESC-2012
LAAO endocardial
Watchman device
Amplatzer device
Lambre device
Wave Crest device
Assisting imaging for device implantation Micro-TEE
Echo-navigator Echo-Fusion
ICE
LAA exclusion epicardial
Atri-clip device LARIAT device
LARIAT epicardial
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.
Thank you