S. Nardi, MDLab. Elettrofisiologia – Div. di

Cardiologia

Azienda Ospedale S. Maria - TERNI

I congresso TOSCO-UMBRO“La Cardiologia che vorremmo”22-23 Novembre, 2006 – Cortona

Ablazione nella Fibrillazione Atriale:indicazioni e strategie farmacologiche

AF

CURE Clinical Control

AFib rate controlSR restore

Clinical Control

paroxistic permanentpersistent

Therapeutic OptionsINTRODUTION

Considerations• All AFib affected patients have an increased

Morbidity• The overall increased Mortality is between 1,6-

2,6% (Manitoba and Framingham Studies) • 5% year ischemic stroke (non-rheumatic AF) 2-

7 times without AF • 1/6 Cerebro-Vascular Accident (CVA) occurs in

AFib • Framingham Study

- RHD 17 X rate of CVA (age-matched CTR)- Attributable risk 5 X > non-RHD- Risk of Stroke increased with age

(1,5% at 50-59 yrs vs 23,5% at 80-89 yrs)

AADs SUCCESS %

propafenone (e.v.)propafenone (os)flecainide (e.v.)flecainide (os)amiodarone (e.v.)ibutilide (ev)dofetilide (e.v.)dofetilide (os)

29-9172

57-5978

34-9234-47

3132

Acute efficacy

Antiarrhythmic drugs (AADs)

Quinidine 1 yr 3fold increase mortalityDrug Efficacy F.U. Drawbacks

50% SR

AuthorCoplen, ‘90

Dysopiramide 1 yr Many side effects, 11% drop out

As quinidine Karlson ‘88

Flecainide 1 yr Not indicated in CAD49% SR Van Gelder, ‘89

Propafenone 6 mo Not indicated in CAD60% SR Stroobandt, ‘97

Amiodarone 1 yr Side effects61% SR Gosselink, ‘92

Pooled (meta-analysis) data

AFFIRM

STAFSTAF

PIAPIAFF

HOT CAFÉHOT CAFÉ

PAF-PAF-22

RACRACEE

Randomized 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 Versus Electrical Cardioversion (RACE) Study. JACC ‘ 04.

• How to treat C-AF (HOT-CAFÉ`) New New DehliDehli

- Strategies based to maintaining SR at 1 yrs FU without AADs is <30% (recurrence between 50-70%) ....

Pooled (meta-analysis) data from PAF2, PIAF, STAF, AFFIRM e RACE

- … however in most cases AADs based strategies are not able to prevent RECURRENCE of A Fib.

• Global efficacy 40 - 50% (Reduce in long term FU)

25% interruption of treatment !

• SIDE EFFECTS– Until 20% of cases (3-5% TdP)

• Arrhythmia-free survival after ECV in pts with PeAF

Lower Curve Outcome after a single shock when no prophylactic AADs was givenUpper curve Outcome with repeated ECV in conjunction with AADs prophylaxis

Pooled (meta-analysis) data from PAF2, PIAF, STAF, AFFIRM e RACE

INIZIATORI(TRIGGER)

PERPETUATORI(multiple wavelet reentry)

SUBSTRATE(regione antrale)

• Attività extrasistolica

• Attività ripetitiva (FOCALE e NON FOCALE)

ELECTROPHYSIOLOGICMECHANISMS

RFFiriing or spontaneous diastolic depolarisation

Haissaguerre ’96 Chen ’97

Triggers

• Origin from a velry limited area

• Localized in the media of PVs prevalently or in other areas (SVC, IVC, atrial myocardial wall)

• Abolished with small lesion size (~ 150 mm³)

FOCAL ACTIVITYFOCAL ACTIVITY

It’s enought to explain the evolution from PaAF to

PeAF ?

ELECTROPHYSIOLOGICMECHANISMS

Haissaguerre ’96 Chen ’97

IVCIVC

CSCS

Myocardial sleevers

• In 1907 the presence of muscular sleeves around the PVs was documented for the first time

• Now they are considered important triggers of AFib

• LA-PVs junction could be functionally considered a “BROAD BAND” • Possible arrhythmogenic nature due to Automatism (EMBRIONAL NATURE) or micro-reentry (anisotropic carachteristic of LA-PVs junction)

JUNCTIONJUNCTION

Hocini M, Card. Res ’02 Hocini M, Circulation ’02Arora, Circulation 03

Haissaguerre, NEJM ‘96

Pato-physiology and Electrogenesis

Hocini, Circulation `02Arora, Circulation `03

Mandapati, Circulation `00

Intraparietal Anisotropism

JUNCTIONJUNCTION

Pato-physiology and Electrogenesis

Spragg DD, Circulation ’03

Regional Alterations of Protein Expression in AFib dogs

ELECTROPHYSIOLOGICMECHANISMS

Sueda Sueda Ann Thorac Surg 1997Ann Thorac Surg 1997

Micro-reentry Micro-reentry circuitscircuits

HaissaguerreHaissaguerreNEJM 1998NEJM 1998 Focal Focal

activity activity from PVfrom PV

L di ML di M

HwangHwangCirculation 2000Circulation 2000

ELECTROPHYSIOLOGICMECHANISMS

• singole appl.RFsingole appl.RF • LassoLasso• SpiralSpiral• BasketBasket

• XrayXray

• CARTOCARTO• LocaLisaLocaLisa• NavXNavX• RPMRPM

• ICEICE

• ConvenzionaleConvenzionale

• 8 mm tip8 mm tip• Irrigated tipIrrigated tip• InvestigationalInvestigational(balloon, cryo)(balloon, cryo)

- Framework per l’ablazioneFramework per l’ablazione

- Guidare il mappaggioGuidare il mappaggio

- Localizzazione Localizzazione AnatomicaAnatomica

- Tag sui siti di ablazione- Tag sui siti di ablazione

- Valutazione del Valutazione del contatto del contatto del catetere catetere

-Miglioramento Miglioramento dell’efficienza dell’efficienza dell’erogazione dell’erogazione di energia di energia

MAPPAGGIO MAPPAGGIO TRACKINGTRACKING ABLAZIONE ABLAZIONE

• 251 Patients• 54±12 min di RF applicata attorno alle VP

Pappone et al. Circulation 2000 e 2001Pappone et al. Circulation 2000 e 2001

Assenza di eventi TROMBO-EMBOLICI e di STENOSI VP durante la degenza

End Point: (75%)• PVP < 0.1 mV• Delay > 30 ms (LAT)

% di successo in assenza di AA: 148/179 FA parossisitica (83%)40/72 FA persistente (55%)

Circumferencial Left AtrialApproach (CLAA)

Ernst et al. JACC `03Ernst et al. JACC `03

Lesioni Lesioni completecompleteA – 5% A – 5%

B – 21% B – 21%

C – 28 % C – 28 %

D - 61-66%D - 61-66%

RISULTATIRISULTATI

• Quando le lesioni Quando le lesioni erano complete, erano complete, 74% asintomatici 74% asintomatici senza AA senza AA

• Se lesioni Se lesioni incomplete quasi incomplete quasi tutti recidiva tutti recidiva dell’aritmia dell’aritmia

Circumferencial Left AtrialApproach (CLAA)

• Lesioni lineari complete sono Lesioni lineari complete sono teoricamente identiche alle incisioni teoricamente identiche alle incisioni chirurgichechirurgiche

VPIL

Pacing dal CS

Mitrale

Thomas, JACC 2000Thomas, JACC 2000Ernst, Circulation 1999Ernst, Circulation 1999

• Sono difficili da ottenere (con Sono difficili da ottenere (con aumentato rischio procedurale)aumentato rischio procedurale)

• La creazione di linee incomplete La creazione di linee incomplete è pro-aritmica è pro-aritmica

Pooled (meta-analysis) Circumferencial Left AtrialApproach (CLAA)

Bazaz & SchwartzmanBazaz & Schwartzman

VP settaliVP settali VP lateraliVP laterali

Potenziali PITFALL

Kato et al

Potenziali PITFALL

1. Geometria delle VP VARIABILE, spesso avversa per la creazione di lesioni circonferenziali in corso di ablazione

2. La creazione di una necrosi trans-murale può essere non facile a livello degli osti delle VP

3. Rimodellamento elettrico

OSTACOLI POTENZIALI AL OSTACOLI POTENZIALI AL RAGGIUNGIMENTO DELL’OUTCOMERAGGIUNGIMENTO DELL’OUTCOME

Pulmonary Vein Isolations (PVI)

Oral et al. Circulation 2003Oral et al. Circulation 2003

80 pts FAP

42±14 min di RFRedo: 0%“encircling + lesioni lineari 1 flutter AS

67%67%

88%88%

p=0.02p=0.02

20% flutter AS 20% flutter AS (meeting Boston (meeting Boston ed AF ed AF symposium symposium di Roma) di Roma)

18±9 min di RFRedo: 18%IVP

TERNI REGISTRYTERNI REGISTRY

• 422 pts with symptomatic PaAF and PeAF referred to us between July ‘04 and September ‘06

• RFCA performed in 145/422 pts (34%).

MATERIALSTERNI REGISTRYTERNI REGISTRY

• At least one MONTHLY episode of Persistent symptomatic AF

• At least ONE WEEKLY episode of PaAF or PeAF

• At least Two or More AADs unable to control symptoms

• Age >75 yrs• Contraindications to ACT• Congestive HEART FAILURE• NYHA functional class III / IV• LVEF ≤35% and/or LA

diameter ≥55mm• Presence of Cardiac

Thrombus• Life expectancy <1 yr• CCH surgery <3 mo or

PROSTHETIC valves

Exclusion criteriaExclusion criteriaTERNI REGISTRYTERNI REGISTRY

AFib PAROX. PERSIST. TOTALPatients 91 54 145 Age 62±13 67±8 64±10Sex (M/F) 61/26 37/21 98/47Duration 36±12N.episodes/mo 4±6LVEF (%) 55±6 51±9 53±9,7LA diameter 44±8 47±8 46±8CAD 15 21 36

TERNI REGISTRYTERNI REGISTRY

TERNI REGISTRYTERNI REGISTRY

• Procedura (min): 14826 14424

151 29

• Fluoroscopia (min): 5917 5816

6619

• Mappaggio (min): 158 139

184

• No. erogazioni di RF: 6216 6017

6519

RISULTATIRISULTATI Globale Pz.in RS Pz. in

FA

TERNI REGISTRYTERNI REGISTRY

VERIFICA del VERIFICA del BLOCCO della CONDUZIONE BLOCCO della CONDUZIONE

629 VP trattate (145 pts)

Blocco Blocco completocompleto

558 VP 558 VP (89%)(89%)

Blocco Blocco incompletoincompleto

71 VP (11%)71 VP (11%)

TERNI REGISTRYTERNI REGISTRY

• After a mean FU Overall FREEDOM FROM AF (both PaAF and PeAF) was 66% (72% and 58%), w/o AADs and 79% (84% and 70%) with previous ineffective AADs.

Clinical OUTCOME

• The Kaplan-Meier statistical analysis probability of freedom from arrhythmia was maximal at 10 months

TERNI REGISTRYTERNI REGISTRY

82% success82% success

61% success61% success

La NON INDUCIBILITA’ post-IVP (67%) si associa ad una bassa ricorrenza di FA (87%) e potrebbe essere un utile ENDPOINT procedurale da perseguire per

razionalizzare le STRATEGIE

Nardi S, in Press

1st MESSAGETERNI REGISTRYTERNI REGISTRY

• I maggiori ostacoli alla stabilizzazione dei risultati ottenibili in acuto appaiono legati alla POSSIBILE TRANSITORIETA’ degli effetti termici su di un substrato complesso e delicato

OPEN QUESTIONS

• Recidiva possibile dopo un periodo variabile di FU privo di sintomi per presenza di ALTRE SORGENTI localizzate al di fuori delle VP a prevalenza rilevante

2nd MESSAGETERNI REGISTRYTERNI REGISTRY

• Among UNIVARIATE predictors, the variables of age, sex, duration and frequency of AF, LVEF, LA

size and structura HD, this approach revealed that only an increased LA SIZE >50 mm were an Indipendent Predictor of

RECURRENCE

• During FU, all pts w/o AF recurrence showed preserved or improved LA contraction (PW Doppler)

• Probably, pts with an enlarged LA may require a different strategy to achieve AF suppression.

3th MESSAGETERNI REGISTRYTERNI REGISTRY

Randomized Trials

Catheter ablation treatment in pts with AADs- refractory AFib: a prospective, multi-centre, randomized, controlled study (Catheter Ablation For The Cure Of Atrial Fibrillation Study). Stabile Eur H J ‘06

RFCA vs AADs as first-line treatment of symptomatic AFib: a randomized trial. Wazni OM, JAMA ‘05  

Stabile G, Eu H J ‘06

“ Ablation therapy combined with AADs therapy is superior tu AADs alone in preventing arrhythmia recurrences in pts with PaAF or PeAF in whom AADs therapy has already failed “

Reant P, Circulation ‘05

Reverse Remodelling

• 48 pts with isolated AF • AADs ineffective• RFCA with PVI +

CT isthmus• Echo evaluation• 1 yr Follow up

78% PaAF 54% C-AF

PROSPECTIVE DOUBLE BLINDEDSTUDY

• In a broad spectrum of EP laboratories using different techniques over a wide time frame (7 yrs)

- free of AADs 48.0%- under AADs 24.1%

SUCCESS RATES

CLINICAL SUCCESS - Free of AADs: 3,866 (47,0%) - With AADss: 7,408 (79,0%)

LATE RECURRENCE

Cappato R, Circulation ‘04

Worldwide AFib SurveyWorldwide AFib Survey

But ….. back in the real world

• Data comes from 3 centres with a huge experience

Mickelson S, JICE ‘05

Cappato R, Circulation ‘05

In US EP believe 29% of pts with AF are candidates for RFCA

•Within these 3 centres there was a definite learning curve

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

• Nei soggetti con FA cronica o FA complicata (cardiopatia) è probabile che esista una maggiore complessità del disegno, con diversa combinazione dei meccanismi proposti (FOCALI e NON FOCALI) nella perpetuazione dell’ FA.

• Nei soggetti senza cardiopatia e/o con FA Parox, le VP svolgono una funzione sia di TRIGGER che di PERPETUAMENTO

… … il PRESENTE …il PRESENTE …

Who to refer ….•Symptomatic PaAF or PeAF with failed AADs

•No major cardiac structural disease •Age <70 yrs and LA size < 5,0 cm

Pts should be judged on an individual basis according to the Ablation Centre’s experience

When considered RFCA as 1When considered RFCA as 1stst line line ?? - Highly symptomatic AFib pts who refuse AADs.

- When Amiodarone represent the only AAD of choice

- In high risk pts for stroke who refuse or cannot take long term ACT

- Young pts with PaAF and SND who may not tolerate AADs w/o a permanent PM

Only large and prospective or randomized clinical studies in comparison between RFCA of PV and alternative approach (rate CTR, AADs Rx for prevent AFib , Ablate and Pace etc) for Rhythm CTR and for Ventricular rate based strategies will give us the ANSEWERs our question on best treatment for AFib

Conclusions

Grazie per la Cortese Attenzione