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