Responsabile: Stefano Nardi, MD, PhD

L’ablazione transcatetere L’ablazione transcatetere della Fibrillazione Atriale: della Fibrillazione Atriale:

Stato dell’arte Stato dell’arte

““AZIENDA OSPEDALIERA SANTA MARIA – TERNI”AZIENDA OSPEDALIERA SANTA MARIA – TERNI”DIPARTIMEN TO CARDIOTORACOVASCOLAREDIPARTIMEN TO CARDIOTORACOVASCOLARE

STRUTTURA COMPLESSA DI CARDIOLOGIASTRUTTURA COMPLESSA DI CARDIOLOGIACENTRO DI ARITMOLOGIA ED ELETTROFISIOLOGIA CARDIACA CENTRO DI ARITMOLOGIA ED ELETTROFISIOLOGIA CARDIACA

9,6

13,4

15,3

18

25,7

28,9

49,8

0 10 20 30 40 50 60

SOLVD (I I -I I I )

V-HeFT (I I -I I I )

CHF-STAT (I I -I I I )

ATLAS (I I I )

DI AMOND-CHF (I I -I I I )

GESI CA (I I -I V)

CONSENSUS (I V)

Prevalenza FA (% )

• All AFib affected pts have an increased Morbidity

• The overall increased Mortality is 1,6-2,6% (Manitoba and Framingham Studies)

• 5% year ischemic stroke

• 1/6 Cerebro-Vascular Accident (CVA)

• Framingham StudyRHD 17 X rate of CVA Risk of Stroke increased with age (1,5% 50-59 yrs vs 23,5% at 80-89 yrs)

MagnitudeMagnitude

AF and Congestive Heart AF and Congestive Heart FailureFailure

AF and Congestive Heart AF and Congestive Heart FailureFailure

• In the AMIOVIRT study AF resulted an In the AMIOVIRT study AF resulted an independent risk factor for mortality (RR 4) in pts independent risk factor for mortality (RR 4) in pts with CHF with CHF (Strickberger, J Am Coll Cardiol (Strickberger, J Am Coll Cardiol 2004)2004)

• In the AMIOVIRT study AF resulted an In the AMIOVIRT study AF resulted an independent risk factor for mortality (RR 4) in pts independent risk factor for mortality (RR 4) in pts with CHF with CHF (Strickberger, J Am Coll Cardiol (Strickberger, J Am Coll Cardiol 2004)2004)

• In the Analysis VEST study AF causes an increase In the Analysis VEST study AF causes an increase of 2.3 times the risk of death in patients with of 2.3 times the risk of death in patients with heart failure heart failure (Konety, AHA 1998)(Konety, AHA 1998)

• In the Analysis VEST study AF causes an increase In the Analysis VEST study AF causes an increase of 2.3 times the risk of death in patients with of 2.3 times the risk of death in patients with heart failure heart failure (Konety, AHA 1998)(Konety, AHA 1998)

• In the SOLVD study AF showed to be an In the SOLVD study AF showed to be an independent risk factor for mortality (RR 1.34) independent risk factor for mortality (RR 1.34) and progression of CHF (RR 1.42)and progression of CHF (RR 1.42)

(Vermes, Circulation 2003)(Vermes, Circulation 2003)

• In the SOLVD study AF showed to be an In the SOLVD study AF showed to be an independent risk factor for mortality (RR 1.34) independent risk factor for mortality (RR 1.34) and progression of CHF (RR 1.42)and progression of CHF (RR 1.42)

(Vermes, Circulation 2003)(Vermes, Circulation 2003)

• In the analysis AVID data, AF represents a risk In the analysis AVID data, AF represents a risk factor for the mortality in pts with VT/VF. factor for the mortality in pts with VT/VF. (D.G. (D.G. Wyse, AHA 1998)Wyse, AHA 1998)

• In the analysis AVID data, AF represents a risk In the analysis AVID data, AF represents a risk factor for the mortality in pts with VT/VF. factor for the mortality in pts with VT/VF. (D.G. (D.G. Wyse, AHA 1998)Wyse, AHA 1998)

HeartfailureVolume +

pressure overload

RAAS

Triggeredactivity

AtrialFibrillati

on

Circle of Atrial Fibrillation and Heart Circle of Atrial Fibrillation and Heart FailureFailure

Circle of Atrial Fibrillation and Heart Circle of Atrial Fibrillation and Heart FailureFailure

Fibrosis

Heterogeneusconduction

Loss of atrial contribute

Irregularity of the rhythm

High ventricular response

Secondary tachycardiomiopa

thy

• AF reduces the cardiac performance because the loss of atrial contribute to the cardiac output

• The high ventricular response contributes to the cardiac output reduction

• The irregularity of the rhythm reduces itself by 15% the cardiac output.

• A secondary tachycardiomiopathy adds to a preexisting ventricular dysfuction.

• AF reduces the cardiac performance because the loss of atrial contribute to the cardiac output

• The high ventricular response contributes to the cardiac output reduction

• The irregularity of the rhythm reduces itself by 15% the cardiac output.

• A secondary tachycardiomiopathy adds to a preexisting ventricular dysfuction.

Atrial Fibrillation and Atrial Fibrillation and Congestive Heart FailureCongestive Heart Failure

Atrial Fibrillation and Atrial Fibrillation and Congestive Heart FailureCongestive Heart Failure

Preexisting LV

dysfunction

Preexisting LV

dysfunction

Further reduction of LV function

Further reduction of LV function

AAFFAAFF

Heterogeneous Substrate of AFHeterogeneous Substrate of AF

CMP?

valvularidiopathic

vagal

focal SSS adrenergic

pericarditis

conduction delay

Gaita F. NASPE 2000Gaita F. NASPE 2000

Atrial FibrillationAtrial FibrillationMechanisms and ConsiderationsMechanisms and Considerations

Atrial FibrillationAtrial FibrillationTherapeutic ApproachTherapeutic Approach

The longer AF lasts, the higher is the fibrillatory rate.

Wijffels M et Al. Circulation 1995,92:1954-1968

Electrical remodellingElectrical remodelling

Electrical remodelling

Decrease of action potential duration

Increase of arrhythmic vulnerabilityIncrease of arrhythmic vulnerability

Decrease of effective refractory period duration

RSRS AFAF

Hara M. Cardiovasc Res. 1999,42:455Hara M. Cardiovasc Res. 1999,42:455

Wijffels M et Al. Circulation 1997,96:3710-3720Wijffels M et Al. Circulation 1997,96:3710-3720

Action Potential, Ca++ and Contractility in AFib pts

1.1. Reduction in amplitude and increase in duration of Reduction in amplitude and increase in duration of APAP

Control Control A FibA FibAP (EAP (Emm))

[Ca[Ca2+2+]]ii

ContractioContractionn

2.2. Reduction in the upslope and downslop of the CaReduction in the upslope and downslop of the Ca++++ transienttransient

3. Parallel reduction in the upslope and downslop of the peak developed tension

ContractionContraction

[Ca2+]i[Ca2+]iAP (EmAP (Em))

Contractile Contractile RemodellingRemodelling

(experimental study in 7 goats)(experimental study in 7 goats)Pressure Pressure TransducerTransducer

UltrasonicUltrasonicCrystalsCrystals

1616 1818 2020 2222 2424 262600

11

22

3344

55

66

AtrialAtrialPressurePressure(mmHg)(mmHg)

Atrial Atrial DDiameter (mm)iameter (mm)

Start AtrialStart AtrialContractionContraction

Atrial Pressure Volume Atrial Pressure Volume LoopLoop

FillingFilling

Epicardial ElectrodesEpicardial Electrodes

Schotten et al. Circulation 2003Schotten et al. Circulation 2003;107: 1433.;107: 1433.

WorkWorkIndexIndex

Contractile and Electrical Remodelling‘Go Hand in Hand’

00 11 22 33 44 55 66 77 88 99 1010

8080

100100

120120

140140 Refractory Refractory PPerioderiod

Work Work IIndexndex

00

55

1010

1515

2020

RefractoryRefractoryPeriodPeriod(ms)(ms)

Work Work IIndexndex(mm(mm22Hg)Hg)

Time (days)Time (days)

AF Conversion SR AF Conversion SR

Schotten et al. Circ 2003;Schotten et al. Circ 2003;107:1433-1439107:1433-1439

Structural RemodellingStructural RemodellingStructural RemodellingStructural RemodellingSinus Rhythm16 Weeks AF

Ausma et al. Circulation Ausma et al. Circulation 1997;96:3157 1997;96:3157

glycogen sarcomeres fibrosis glycogen sarcomeres fibrosis

Sinus Rhythm

16 Weeks AF

Li et al. Circulation 2000Li et al. Circulation 2000

Chronic Atrial StretchControl AFib and HF

“l’importanza di TROVARE il bandolo della matassa

FA

CURE Clinical control

Rate ControlRhythm Control

Clinical control

paroxismal permanentpersistent

Atrial FibrillationAtrial Fibrillationdifferent strategiesdifferent strategies

therapeutic Approachtherapeutic ApproachAtrial FibrillationAtrial Fibrillation

AFFIRM STAFSTAF

PIAPIAFF

HOT CAFÉHOT CAFÉ

PAF-PAF-22

RACRACEE

Randomized Controlled TRIALS• Paroxysmal Atrial Fibirllation 2 (PAF2)

Eur Heart J ’02

• Pharmacological Intervention in AF (PIAF) Lancet ’00.• Comparison of rate control and rhythm control in pts with AF (AFFIRM) NEJM ‘02.

• Randomized trial of rate-control versus rhythm CTR in PeAF: the Strategies of Treatment of AF (STAF) study. JACC ‘03.

• Effect of rate or rhythm control on QoL in PeAF: results from the Rate Control vs Electrical Cardioversion (RACE) Study. JACC ‘ 04.• How to treat C-AF (HOT-CAFÉ`)

New New DehliDehli

The original AFFIRM STUDY

One year later…

AFFIRM revisited…AFFIRM revisited…

AFFIRM revisited…AFFIRM revisited…

AFFIRM revisited…AFFIRM revisited…

• Terapia PALLIATIVA

• Effetti collaterali– fino al 20% dei casi– Aumento della Mortalita`

25% dei casi interruzione del trattamento !

• Efficacia globale in acuto (prevenzione/riduzione del numero/durata degli episodi)

– 40 - 61%– Tende a ridursi nel Follow Up a lungo termine

Pooled (meta-analysis) data from PIAF, STAF,

AFFIRM e RACE

It’s really important to use the appropriate technique

for AF ablation

Different TechnologiesDifferent TechnologiesMappingMapping• Point by pointPoint by point

• LassoLasso• SpiralSpiral• BasketBasket

TrackingTracking• XrayXray

• CARTOCARTO• LocaLisaLocaLisa• NavXNavX• ArrayArray

• ICEICE

AblationAblation• ConventionalConventional

• 8 mm tip8 mm tip• Irrigated tipIrrigated tip• InvestigationalInvestigational(balloon, cryo...)(balloon, cryo...) Uni/BipolarUni/Bipolar- Framework for ablationFramework for ablation

- Mapping guidanceMapping guidance

- Anatomic localizationAnatomic localization

- Tagging of ablation - Tagging of ablation sitessites

- Determine Determine catheter contactcatheter contact

- Improved Improved efficiency of efficiency of energy deliveryenergy delivery

Different AFib approach in CHF pts

Hocini M, Card. Res ’02, Circulation ‘02

Electrophysiologic Electrophysiologic BackgroundBackground

GANGLI GANGLI vagali vagali

RF

Haissaguerre, NEJM ’98

Atrial Fibrillation MechanismsAtrial Fibrillation MechanismsPVs as Trigger and Perpetuator

Pulmonary Vein isolationAtrial Fibrillation ablationAtrial Fibrillation ablation

Inferomediale

Infero-laterale

VPIL

VPSL

Fluoroscopic X ray

Left common trunk 3 right lower veins

Normal

Pulmonary Vein anatomy

• Surface-based– 5.6 kHz current signal emitted from 3 pairs of surface

electrodes–Each catheter electrode located 93 times per second– Visualize all catheters in 3D space for cardiac navigation

Virtual Reality Methodology

STANDARD FLUOROSTANDARD FLUOROVIRTUAL GEOMETRYVIRTUAL GEOMETRY

Virtual Geometry Virtual Geometry reconstructionreconstruction

Point-by-Point

Medium-Low

Virtual Geometry Virtual Geometry reconstructionreconstruction

Virtual Geometry Virtual Geometry reconstructionreconstruction

Atrial Fibrillation ablationAtrial Fibrillation ablationvirtual geometry reconstructionvirtual geometry reconstruction

Ultrasound viewerUltrasound viewer

Virtual Geometry Virtual Geometry reconstructionreconstructionAFib Ablation in CHF pt

Virtual Geometry Virtual Geometry reconstructionreconstructionAFib Ablation in CHF pt

SUBSTRATE modificationSUBSTRATE modification

CLAA:CLAA: Incomplete PVI in ~ 60%Incomplete PVI in ~ 60%

70 ms70 ms

IIIIIIIIIIIIV1V1

PV1-2PV1-2

PV10-1PV10-1

CSDCSD

CSPCSP

Atrial Fibrillation ablationAtrial Fibrillation ablationVagal GangliaVagal Ganglia

The longer AF lasts, more The longer AF lasts, more complex the circuits arecomplex the circuits are

AcutAcute e

AFcAFc

ChroniChronic AFc AF

Konings et al. Circulation 1994,89:1665Konings et al. Circulation 1994,89:1665

F. Gaita et al. JACC 2001;37:534F. Gaita et al. JACC 2001;37:534

Correlation between AF patterns in CHF ptsCorrelation between AF patterns in CHF ptsType BType BType AType A Type DType DType CType C

AF Survey II

Previous

Survey

Current Survey

Period investigated 1995-2002 2003-2006

Nr of centers 90 85

No. of pts 8,745 16,309

No. of pts per center 97 192

No. procedures 12,830 20,825

No. procedures per pts 1.5 1.3

Male, % 63.8 60.8

Lower and upper age limit for entry

18-82 15-90

% of centers performing ablation of- Paroxysmal AF 100 100

- Persistent AF 53.4 85.9

- Permanent AF 20 47.1Cappato R, Boston 2008

efficacy and safety data

Relationship between success rate and type of Ablation Catheter

Type of Catheter

No Center

No Pts

Success without AADs Success with AADs Overall Success

Total No of Pts

Total Rate Median

68.3

[48.4-80.8]

67.9

[44.7-73.6]

68.1

[46.2-73.6]

Total No of Pts

Rate Median

11.5

[8.6-26.7]

9.0

[0.0-14.8]

10.0

[0.0-20.0]

Total No of Pts

Rate Median

4-mm 23 2,892 1,803 609 2,412 79.8[55.0-87.2]

Irrigated/ Cooled

39 6,674 3,891 721 4,612 76.9[56.4-88.5]

TOTAL 62 9,5665,694 1,330 7,024 78.1

[66.8-86.7]

AF Survey II

Cappato R, Boston 2008

Improvement of LV Size & Function In CHF

30

35

40

45

50

55

60

65

0 11±7

LV DimensionsLV Dimensions

MonthsMonths

LVEDDLVEDD

P=0.003P=0.003

P=0.001P=0.001

LVESDLVESD

mmmm

1520253035404550556065

0 11±7

LV FunctionLV Function

MonthsMonths

LVEFLVEFP=<0.001P=<0.001

LVFSLVFS

%%

P=<0.001P=<0.001

Hsu, Bordeaux 2004

Atrial Fibrillation ablationAtrial Fibrillation ablation

AF ablation in CHFStudy Study population Results

Hsu et al. 2004Prospective study

58 consecutive patients with HFand LVEF < 45% vs. 58 matched patients without HF

78% of the patients with CHF and84% of controls were free of AFSignificant improvement in LVEF of 21 ± 13%, exercise capacity, symptoms scores, and QoL scores

Tondo et al. 2006Prospective study

40 patients with LVEF < 40% vs. 65 patients with normal ventricular function

87% of patients with decreased EF and 92% of patients with normal EF were free of AF Improvement in LVEF from 33% to 47%

Gentlesk et al. 2007Prospective study

67 patients with reduced LVEF

(≤50%) vs. 366 patients with normal LVEF

86% of patients in decreased LVEF and 87% of patients in normal EF were free of AF LVEF increased from 42% to 56% after ablation

Khan et al. 2008Prospective study

41 patients who underwent PVI vs. 40 patients who underwent Avj-Abl+CRT

Significant improvement in LVEF of 35 ± 9%, exercise capacity, symptoms scores, and QoL scores

PVs isolation in CHF pts

1. No clinically relevant endpoints2. Inadequate sample sizes3. Younger patients (mean age range: 54-64 yrs)

4. Short term follow-up5. Long term effects remained

uninvestigated

considerations

• Anatomia avversa e variabile per la realizzazione di un isolamento elettrico completo

• Rischio di recidiva di conduzione attraverso una linea di blocco INCOMPLETA

OSTACOLO CONSEGUENZA

• Difficoltà alla realizzazione di lesioni transmurali all’orifizio delle VP

• Rimodellamento elettrico

• Volume consistente di tessuto aritmogeno tra l’orifizio della VP e la linea di blocco

• Vulnerabilità all’innesco di FA in risposta a triggers non clinici (BESV da siti innocenti)

Atrial Fibrillation ablationAtrial Fibrillation ablationPITFALLPITFALL

tipo di FAtipo di FA cardiopatia sottostantecardiopatia sottostante

isolamento delle VP isolamento delle VP (ostiale, antrale, (ostiale, antrale, ecc)ecc)

ablazione ablazione circonferenzialecirconferenziale

lesioni lineari aggiuntivelesioni lineari aggiuntive ablazione in aree a ablazione in aree a

conduzione rallentataconduzione rallentata

effettivo isolamento VP

Riduzione/modifica del substrato

Δ tono autonomico

creazione di barriere elettriche complete e non

non inducibilità della FA

recidive aritmiche recidive aritmiche sintomatiche/asintomatichesintomatiche/asintomatiche

utilizzo terapia antiaritmicautilizzo terapia antiaritmica

Disomogeneità Disomogeneità delle popolazioni delle popolazioni

arruolatearruolate

Differenze della Differenze della tecnica ablativatecnica ablativa

End-point End-point procedurali non procedurali non

uniformiuniformi

Metodologia del Metodologia del follow-upfollow-up

Mickelson S, JICE ‘05

Cappato R, Circulation ‘05

In US EP believe 29% of pts with AF are

candidates for RFCA

• Lower volume centres have lower success rates and higher complication rate

Atrial Fibrillation ablationAtrial Fibrillation ablation

Which is the impact of the new technologies ?

PV Isolation using the Cryo-Balloon

Multi-electrode Phased Catheter

– Catheters design to conform to the anatomy– Mapping / Pacing and Ablations from all electrodes – Tailored lesions (i.e., depths, lengths, configurations)– Cover large area with a single catheter placement– Do not require 3D mapping system

Phased Ablation Catheter

Does one AFib approach fit in all CHF pts?

Disertori M, GIAC ‘06Disertori M, GIAC ‘06

Linee Guida AIACLinee Guida AIAC

Catheter Ablation Catheter Ablation of Atrial Fibrillation of Atrial Fibrillation

• An individually tailored approach is neededAn individually tailored approach is needed

• PVI renders 52-84% of PAF non-inducible and PVI renders 52-84% of PAF non-inducible and results in clinical success; substrate results in clinical success; substrate modification in such patients is not indicatedmodification in such patients is not indicated

• Substrate modification is likely to be required Substrate modification is likely to be required in 30% of PAF and most CAF, but needs in 30% of PAF and most CAF, but needs technological improvementstechnological improvements

What is success?

• Complete freedom of AF, off drug RX?• No symptoms, but drug Rx required?• Dramatic decrease in symptoms, but

drugs still required?• QoL• How do we detect asymptomatic

episodes?• Anticoagulation ………………...?