2009 roma, policlinico umberto i. workshop interattivo. trattamento del ritmo vs trattamento della frequenza nella fibrillazione atriale

” ” RATE control RATE control vs vs RHYTHM control ”RHYTHM control ”

Stefano Nardi, MD

AZIENDA OSPEDALIERA SANTA MARIA TERNIAZIENDA OSPEDALIERA SANTA MARIA TERNIDIPARTIMENTO CARDIOTORACOVASCOLAREDIPARTIMENTO CARDIOTORACOVASCOLARE

UNITA’ OPERATIVA DI ARITMOLOGIA CARDIACA UNITA’ OPERATIVA DI ARITMOLOGIA CARDIACA LABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONE LABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONE

RATE RATE vs vs RHYTHMRHYTHM control control

AFib

CURE Clinical control

AFib controlRestore SR

Clinical control

paroxistic permanentpersistent

STRATEGIES

QUESTIONSRATE RATE vs vs RHYTHMRHYTHM control control

• The FIRST STEP in the treatment of AF consists in the TERMINATION of AF and MAINTENANCE of SR.

• Several factors contribute to create a problematic management,including UNDERLYING DISEASE, diversity of CLINICAL CONDITIONS and uncertain THERAPEUTIC GOALS goals for each pt

ConsiderationsRATE RATE vs vs RHYTHMRHYTHM control control

• 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)

Which objective and desiderable approach in AFib pts?


REDUCE the SymptomsPREVENT thromboembolic events

ELIMINATE detrimental effetcs


Therapeutic OptionsRhythm management

Heart Rhythm CTR

ThromboEmbolismProphylaxis

AFFIRM

STAFSTAF

PIAFPIAF

HOT CAFÉHOT CAFÉ

PAF-2PAF-2

RACERACE


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 DehliNew Dehli

• 141 pts • Paroxysmal severely

symptomatic AF • Rate vs Rhythm CTR • Rate – AV junction RFCA • Rhythm – amiodarone 1st

Brignole M, Eur Heart J ‘02

PAFPAF22 (Paroxysmal Atrial Fibrillation) (Paroxysmal Atrial Fibrillation)

Primary end-point: Primary end-point: Development permanent AF

• No differences in QoL or Echo measurement

• Incidence of hospitalization and CHF fewer in RATE control arm

• The LACK of BENEFIT of Rhythm CTR arm is not surprising, given that the pts enrolled had already AADs rhythm CTR


• 252 pts • Chronic AF

(7 and 360 days) • Rate vs Rhythm CTR • Rate – diltiazem 1st • Rhythm – amiodarone 1st

(23% SR restoring)

Hohnloser SH, Lancet ‘00

PIAF PIAF (Pharmacological Intervention in Atrial Fibrillation)(Pharmacological Intervention in Atrial Fibrillation)

Primary end-point: Primary end-point: symptoms improvementsymptoms improvement

• QoL showed no differences between two groups.

• Incidence of hospit. higher with RHYTHM [69%] vs. RATE control [24%] (p=0.001).

• AADs side-effects more frequently with RHYTHM [25%] vs RATE control [14%] (p=0.036).



STAF STAF (Strategies of Treatment of Atrial Fibrillation)(Strategies of Treatment of Atrial Fibrillation)

Inclusion Criteria:• Persistent AF (≥ 4 weeks)• LA enlargement (> 45 mm)• CHF ≥ NYHA Class II• LVEF < 45%• Prior ECV with AF recurrence

Exclusion criteria:• Paroxismal AF• Recent Successful ECV (<4m)

• Longstanding PeAF (≥ 2 yrs)• LA dilatation (> 70 mm)• LVEF < 20%)

• PRIMARY ENDPOINT was composite of death, cerebrovascular event, cardiopulmonary resuscit. and systemic embolism.

• SECONDARY ENDPOINTS were Echo parameters, hospital admissions, syncope, QoL, bleeding and deterioration of HF.

Carlsson J, JACC ‘01

• 200 pts • Persistent AF ≥ 4 weeks • Rate vs Rhythm CTR • Rate – β blocker 1st • Rhythm – ECV plus Class

I or Amiodarone (LVEF)

Primary end-point: Primary end-point: Composite of Clinical eventsComposite of Clinical events


STAF STAF (Strategies of Treatment of Atrial Fibrillation)(Strategies of Treatment of Atrial Fibrillation)

• No difference between Rate and Rhythm CTR with regard to the composite endpoint, secondary endpoints or QoL assessments.

• Significantly more hospitalizations in the RHYTHM control arm (repeat CV and initiation of ACT) • 23% in SR at 3-year FU,

despite ≥ 4 ECV and multiple AADs Carlsson J, JACC ‘01

• 4060 pts (70 y old)• PeAF (≥69%) and PaAF • Rate vs Rhythm CTR • Rate – Digoxin (51%), β-

blocker (49%), Ca CB (41%) + ACT

• Rhythm – ECV plus Class I or Class III (Amiodarone 39%) + ACT

Primary end-point: Primary end-point: DeathDeath


AFFIRM AFFIRM

AFFIRM NEJM ‘02

• 522 pts (68 y old) • Pe AF (median 32 days

recurrent after ECV) • Rate vs Rhythm CTR • Rate – AV junction RFCA • Rhythm – Claa Ic, III, ECV

RACERACE

Primary end-point: Primary end-point: Cardiac Death, HF-H, Thromboembolic, Severe Bleeding, PM implantation

• Primary END POINT Rate CTR: 17,2% vs Rhythm CTR: 22,6%

• Cardiovascular death Rate CTR: 7,0% vs Rhythm CTR: 6,7%

• Heart Failure- Hospit. Rate CTR: 3,5% vs Rhythm CTR: 4,5%


• Fewer adverse SIDE-EFFECTS• Avoid potential proarrhythmic

or side effects of AADs • Fewer HOSPITALIZATION• Decrease compliance problems• LOWER COST of treatment

Heart Rate Control Potential Advantages


Cost

EfficacyContinuative ACT administration (Inaltered Risk of CVA or Bleeding)

does it meansAtrial Fibrillation

= Synus Rhythm?


Lack of effective Atrial Contraction

Chronically Elevated HR

IMPAIR LV function

Irregular Ventricular

Interval↓ LVEF

Lack of AV synchrony


“Age-associated Changes in LV Filling Pattern

Età (anni)

Riem

pim

ento

VS

(%)

20 40 60 800

20

40

60

80

100

riempimento rapido

contributo atriale

Swinne, et al. JACC ‘89

Cardiac Resynchronization TherapyCardiac Resynchronization Therapy

Reduction of Atrial Refractoriness

Increase rate and stability AF

Increase inLA - EDP

Development of atrial

Enlargement Atrial Stretch

Reduction of Rate Adaption

RATE RATE vs vs RHYTHMRHYTHM control controlEffects on LA

• Which is the BEST ACTIVITY-RELATED INCREASED HR we should obtained in AFib pts during exercise ?

• UNTREATED AFib often produce POOR EXERCISE TOLERANCE that improves when Rx that lowers the HR is initiated.

Heart Rate Control


• There are virtually NO DATA from which the most appropriate TARGET for activity-related HR during AF can be determined.

• All such TARGET HR are TOTALLY ARBITRARY

AFFIRM AmJC, ‘97

• The same pt over a SHORT-PERIOD can demonstrate both Symptomatic Tachycardia and Bradicardia during AFib, even W/O a change in ACTIVITY LEVEL • No OBJECTIVE DATA suggest that routine treatment to lower the Exericse-induced INCREASE in HR provides any advantages over merely treating the RESTING HR

Heart Rate Control


• Independently of resting and activity level of HR, there is evidence that irregularity of the HR during AFib has a negative physiological conseguence.

Daoud EG, AmJC, ‘96

The original AFFIRM STUDY

One year later…

AFFIRM revisited…AFFIRM revisited…



The AFFIRM Study. NEJM 2002

RATE RATE vs vs RHYTHMRHYTHM control controlAFFIRM

RATE RATE vs vs RHYTHMRHYTHM control controlPooled (meta-analysis) data from PAF2, PIAF, STAF, AFFIRM e RACE

- Theese studies does not conclude that RATE CTR is ≥ RHYTHM CTR, but that strategies-based using AADs does’t work

Hohnloser SH, Lancet ’00; Carlsson J, JACC ’01; Brignole M, Eur Heart J ’02, AFFIRM, Circulation ‘04

Therapeutic STRATEGIES AADs-based are frequently INEFFICACY or should be stopped (ADVERSE or SIDE- effects)

Considerations

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


Overall long term efficacy (meta-analysis)

Why therapeutic approach Why therapeutic approach AADs-based doesn’t work ? AADs-based doesn’t work ?

RATE RATE vs vs RHYTHMRHYTHM control controlPooled (meta-analysis) data from PIAF, STAF, AFFIRM e RACE

• 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

EFFICACY: in controlled studies, in symptoms and QoL

Limit: Palliative Rx Need of PM !

OBJECTIVE: HR control


Reduction of symptoms w/o eliminating AF Still have CVA risk and necessity of ACT. (Wood MA, Circulation ’00; Brignole M, EHJ ’02, Europace ‘01)

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

• The survival rate is similar to the CTR group with AADs therapy.

• In absence of CAD, the Mortality Rate in the A&P group is similar to the general population.

Ozcan C, NEJM ’01 and ‘04

• Controversial issue in the long-term FU (detrimental effects of RVA pacing)

RATE RATE vs vs RHYTHMRHYTHM control controlPooled (meta-analysis) data from PAF2, PIAF, STAF, AFFIRM e RACE Ablate and Pace

• Continue to have loss of LA contraction

“[…] These results suggest that if an effective method for maintaining SR

with fewer adverse effects were available, it might improve survival”.

AFFIRM, Circulation 2004


What‘s news in Electrophysiology ?



Ellenbogen KA, JACC ‘03


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

Firing from LUPV

RF

Haissaguerre, NEJM ‘96


Haissaguerre Circulation ’00 73% FAPHaissaguerre Circulation ’00 73% FAPChen SAChen SA Circulation ’01 81% FAP Circulation ’01 81% FAPErnstErnst PACE ‘03 PACE ‘03 69% FAP 69% FAPArentzArentz Circulation ’03 62% FAP Circulation ’03 62% FAPCappatoCappato Circulation ’03 88% FAP Circulation ’03 88% FAPMarrouche JACC ‘02Marrouche JACC ‘02 90% FAP 90% FAP

OralOral Circulation ’02 85% FAP Circulation ’02 85% FAP 22% FAC 22% FAC

PAPPONEPAPPONE JACC ‘03JACC ‘03 83% FAP/75%FAC83% FAP/75%FAC

Circulation ‘03Circulation ‘03STABILESTABILE 38% FAP/FAC38% FAP/FAC

HOCINIHOCINI 60% FAP*60% FAP*AbstractAbstract

ORALORAL 88% FAP (+ line)*88% FAP (+ line)*Circulation ‘03Circulation ‘03

The Antagonist positions

• Pulmonary vein ablation in AF: hype or hope? Wellens H; Circulation ‘00.


• Potential benefits, risks, and complications of CA of AF: more questions than answers. Hindricks G and Kottkamp H; J CV Electr ‘02

• Ablation for AF: are cures really achieved? Pacifico A; Jacc ‘04.

• Should ablation be first line therapy and for whom? The antagonist position. Padanilam BJ; Circulation ‘05

• Carenza di studi clinici randomizzati su larga scala

• Ampio range di % successo e di complicanze

• “Publication bias”

• Complessità ed evolutività del substrato

• Qual e` FU a lungo termine ?

• E nell’ FA asintomatica ?

Why Rhythm CTR is the way to prefer? Why Rhythm CTR is the way to prefer? RATE RATE vs vs RHYTHMRHYTHM control control

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 BLINDED

MortalityMorbidityQoL


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 “

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

• 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



The EP community has to face to the warning trend toward a higher risk of death in the rhythm-control groups in Several RANDOMIZED studies.

Ellenbogen KA, JACC ‘03Ellenbogen KA, JACC ‘03

ConclusionsRATE RATE vs vs RHYTHMRHYTHM control control

As it is intrinsically unlikely that SR is per se harmful to the patient’s life, we believe that the quest for safer and more effective techniques (RFCA) for curing AF will, and should, continue.

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

RATE RATE vs vs RHYTHMRHYTHM control controlConclusions

Grazie per la Cortese Attenzione



5.2 seconds 5.2 seconds pausepause

AFAF SRSR AFAF

MEAN HEART RATE MAXIMUM HEART RATE HRV

p=0.001 p<0.0001 p<0.0001

Hocini, Circulation ‘03

120

170

220

270

320

370

420

470

520

570

Baseline 24.0±11.3months

CL600ms; p=0.016

CL400ms; p=0.019

ms

42% CSNRT > 500ms 0% CSNRT > 500ms

TRNSC



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



Miscellaneous


- Highly symptomatic AFib pts who refuse AADs.

When considered RFCA as When considered RFCA as 11stst line therapy in AFib ? line therapy in AFib ?


- When Amiodarone represent the only AAD of choice - In high risk pts for stroke who refuse or cannot take long term warfarin therapy (???) - Young pts with FAP and SND who may not tolerate AADs w/o a permanent pacemaker.

• Promising tool to interact with the ongoing arrhythmia, and may prove effective in REDUCING symptoms in SELECTED pts

• Its use in clinical practice reflects the NON-OPTIMAL applicability of AADs strategy to the VARIOUS SUBSTRATES and MECHANISMS.

Antitachycardia Pacing RATE RATE vs vs RHYTHMRHYTHM control control

Terapia Ibrida della Terapia Ibrida della FIBRILLAZIONE ATRIALEFIBRILLAZIONE ATRIALE

OBIETTIVO: Ripristino RS

• Tecnicamente: EFFICACE• Presupposto: DEBOLE

(estrapolazione di osservazioni su studi animali)• Disegno clinico: NON SOLIDO

(studi non controllati, scarsa attenzione alla QOL)

The HYBRID Tx in AFANTITACHYCARDICAL PACING

- A Retrospective of US Carvedilol HF Trials, show the efficacy of this strategies in CHF/AFib pts.

- However, β-blocker may reduce LV function acutely and may not be tolerated at doses required to fully CTR ventricular rate.

- The same consideration are available from non- dihydropiridine calcium channel blocker, whereas digoxin does’t work as monotherapy.

(US Carvedilol HF Trials, AHJ ‘01)

RATE RATE vs vs RHYTHMRHYTHM control controlHeart Rate Control


• Atrial Defibrillator (AD) could restore SR rapidly by use of LOW-ENERGY SHOCK

• In a highly selected group of pts with paroxysmal AF, the AD was able to achieve SR for at least a brief period of time in 96% of patients with AF.

Wellens HJJ, Circulation ‘98

DEFIBRILLATORE ATRIALEOPZIONI Terapeutiche


• Alta efficacia in ACUTO (96%)

• Fonte prevalente di STRESS ed importante fattore limitante l’impiego del sistema in automatico.

DEFIBRILLATORE ATRIALECONSIDERAZIONI

• In un elevato numero di pz (52%):- necessità di SHOCKS multipli - Aggiunta di farmaci AA in cronico - Successivo intervento addizionale (ECV + AA).


OBIETTIVO: Ripristino RS

• Tecnicamente: EFFICACE nelle aritmie regolari• Presupposto: DEBOLE


(studi non controllati, scarsa attenzione alla QOL)

CONSIDERAZIONIDEFIBRILLATORE ATRIALE


• Although the device can in ACUTE convert parox. AF (96%), a large number of pts (52%) needed multiple shocks or drugs or required subsequently an additional intervention (ECV with AA drugs).

• These findings STRESS an important limitation of the use of the system as an automatic device.

The HYBRID Tx in AFATRIAL DEFIBRILLATOR

• First routinely used of RFCA for symptomatic AF in whom a RATE CONTROL with AADs is not obtainable.

• Accepted form of HR control associated with HAEMODYNAMIC BENEFITS, and does not require AADs, with their correlated side effects.

Ablate and PaceRATE RATE vs vs RHYTHMRHYTHM control control

• In SSS who require PM and have AF with rapid responses, in whom AADs may be detrimental on hemodinamic Function

DATA SOURCE: Fitzpatrick AP, Am Heart J ’96; Wood MA, Circulation ’00; Brignole M, Eu Heart J ’02; Brignole M, Europace ’01.


ABLATION

• 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, (balloon, cryo...)cryo...)- Framework per l’ablazioneFramework per l’ablazione

- Guidare il mappaggioGuidare il mappaggio

- Localizzazione AnatomicaLocalizzazione Anatomica

- 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


ACT: Trials Principali• SPAF1 Stroke Prevention in Atrial Fibrillation

• BAATAF2 Boston Area Anticoagulation Trial for Atrial Fibrillation

• CAFA3 Canadian Atrial Fibrillation Anticoagulation

• AFASAK4Copenhagen Investigators

• SPINAF5 Stroke Prevention in NonrheumaticAtrial Fibrillation

1 Circulation ’91; 2 NEJM ’90; 3 JACC ’91; 4 The Lancet ’89; 5 NEJM ’92


• Carenza di studi clinici randomizzati su larga scala

• Ampio range di percentuali di successo e di complicanze

• “Publication bias”

• Complessità ed evolutività del substrato

• Follow up a lungo termine?

• FA asintomatica

The Antagonist positions AFib ablation


5.2 seconds 5.2 seconds pausepause

AFAF SRSR AFAF

• In patients with sinus node disease

• Sinus node remodeling


Considerations

(Hocini,Circulation ‘03)

20 consecutive pts with prolonged synusal pauses (3-10’’) and AF, underwent RFCA of PV

MEAN HEART RATE MAXIMUM HEART RATE HRV

p=0.001 p<0.0001 p<0.0001


Considerations


At 26.0±17.6 mo FU: 17 pz were asymptomatic, 2 improve with AADs and only 1 required pacing (AFA & pause)

120

170

220

270

320

370

420

470

520

570

Baseline 24.0±11.3months

CL600ms; p=0.016

CL400ms; p=0.019

ms

42% CSNRT > 500ms 0% CSNRT > 500ms

TRNSC



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



•Drugs - RHYTHM CTR - RATE CTR - Steroid, ACE-I, ARBs, Statin• Ablate and pace”

• Ablation

• Multisite Pacing/ATP


Therapeutic Options

• ECV

• LAA occlusion

- Primary Ablation - Modulation/Ablation AVN

Objective: Restore SR

• Tecnicamente: EFFICACY in regular Arrhythmias • Presupposto: Weak


(Non Controled Studies, no attention to QoL)

Anti-tachycardia PACINGRATE RATE vs vs RHYTHMRHYTHM control control

• According to an evidence-based approach, No ATP Strategies has been validated.

• The ABSENCE of CTR GROUPS assigned to conventional Rx accounts for the non validation of curative ATP in the treatment of AF


• It’s UNCLEAR which pts are appropriate candidates for such a device.

The HYBRID Tx in AFATRIAL DEFIBRILLATOR

• People with paroxysmal AFib are probably POOR candidates, because of their very frequent episodes which would require too many shocks.

• People with chronic AFib (>1 yr) are probably also NOT IDEAL CANDIDATES.

Science Advisory From the AHA Council on Clinical Cardiology. Circulation ‘05

Pacing, Multisite pacing, Overdive pacingRATE RATE vs vs RHYTHMRHYTHM control control

AV node modulation


• Objective: HR CTR• Success Rate 60-80%• Recurrence Rate 20-30% • Efficacy in sub-group of pts (30%-50%). • Relatively Short “FU”• Effect NOT EVALUABLE before procedure • Unaltered Morbidity

Limit: palliative therapy !

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

FARMACO 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


Rhythm Control

• Physiologic rate CTR• Atrial contribution to

CO maintained• Better exercise

tolerance• Possibility of reduced

thromboembolic risk

Potential Advantages

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

RATE RATE vs vs RHYTHMRHYTHM control controlPooled (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% dei casi interruzione del trattamento !

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

RATE RATE vs vs RHYTHMRHYTHM control controlN

umer

o di

paz

ient

i con

rec

idiv

a di

FA

Num

ero

di p

azie

nti c

on r

ecid

iva

di F

A

0 5 10 15 20 25 30 Giorni Post Conversione

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

• AADs (Class IA, IC, III) has been demonstrated to be effective in IMPROVING the EFFICACY of ECV

- Lower THRESHOLD of AF - Prolong the CL of vagally-mediated acute AF - Higher SUCCESS RATE (> 90%)

AFib and Stroke

• Incidenza: 5-8% annuo in pazienti ad alto rischio

• La valutazione del rischio embolico per una adeguata ACT è prioritaria nei pazienti con FA

• Numerosi trials randomizzati hanno fornito linee guida per l’identificazione ed il trattamento dei pazienti con FA a rischio embolico


• SPAF1 Stroke Prevention in AF

• BAATAF2 Boston Area Anticoagulation Trial for AF

• CAFA3 Canadian AF Anticoagulation

• AFASAK4 Copenhagen Investigators

• SPINAF5 Stroke Prevention in Nonrheumatic AF

Principal Trials

Which is the way to prefer ?

ACC/AHA/ESC Guidelines; Circulation ‘01ACC/AHA/ESC Guidelines; Circulation ‘01



PATIENT FEATURES

ANTITHROMBOTIC Rx ACC/AHA/ESC ACCP

Age < 60 yrs (65 in ACCP)No HD (lone AF)

ASA (325 mg daily) or no Rx ASA (325 mg daily) or noRx

Age < 60 yrs (65 in ACCP)HD but no risk factors

ASA (325 mg daily) ASA (325 mg daily)

Age ≥ 60 yrs (65 in ACCP) and no risk factors

ASA (325 mg daily) ASA (325 mg daily) or ACT

Age ≥ 60 yrs (65 in ACCP) with diabetes mellitus or CAD

ACT (INR 2.0 – 3.0); Addition ASA (81-162mg) daily optional

ACT (INR 2.0 – 3.0)Addition ASA (81-162 mg) daily is optional

Age ≥ 75 years, especially women Oral ACT INR ~ 2.0 (1.6-2.5) Oral ACT ~ 2.5 (2.0 – 3.0)

HF, LVEF ≤ 0.35, Thyrotoxicosis, Hypertension

Oral ACT (INR 2.0 – 3.0) Oral ACT (INR 2.0 – 3.0)

Rheumatic HD, Prosthetic valvesPrior embolism, Persistent TR (TEE)

Oral ACT (INR ≥ 2.5-3.5) Oral ACT (INR ≥ 2.5-3.5)

GuidelinesGuidelinesRATE RATE vs vs RHYTHMRHYTHM control control

Adjusted OR for ischemic stroke and intracranial bleeding in relation to ACT

ACC/AHA/ESC Guidelines; Circulation ‘01ACC/AHA/ESC Guidelines; Circulation ‘01


• SPAF1 Stroke Prevention in AF

• BAATAF2 Boston Area Anticoagulation Trial for AF

• CAFA3 Canadian AF Anticoagulation

• AFASAK4 Copenhagen Investigators

• SPINAF5 Stroke Prevention in Nonrheumatic AF

Randomized Trials

Sueda Sueda Ann Thorac Surg 1997Ann Thorac Surg 1997

Circuiti di Circuiti di microrientromicrorientro

HaissaguerreHaissaguerreNEJM 1998NEJM 1998 Foci Foci

delle delle VPVP

L di ML di M

HwangHwangCirculation 2000Circulation 2000


RATE RATE vs vs RHYTHMRHYTHM control controlRF


Who to refer ….• Symptomatic AFib• PaAF or PeAF • Failed AADs therapy • No major cardiac structural disease • Age <70• LA size <5.0 cm

Hsu, NEJM ‘04

RATE RATE vs vs RHYTHMRHYTHM control controlAnd .... in patients with Congestive Heart Failure ?

Year RAC LAC PV-TR PV-Dis Other Total 1995 13 2 0 0 3 18

1996 38 4 1 0 5 48

1997 67 32 23 0 0 122

1998 109 57 158 49 22 395

1999 142 89 332 88 28 679

2000 135 110 383 569 42 1,239

2001 179 230 274 1,534 31 2,248

2002 169 556 355 4,360 10 5,450

Total 852 1,080 1,526 6,600 141 10,199



World Wide Survey

No. of No. of No. of Success without AADs Success with AADs Overall Success Procedures Centers Pts. No. Rate [Range] No. Rate [Range] No. Rate per Center (%) (%) (%) (%) (%) [Range] 1 - 30 35 547 163 29.8 [14.5-43.6] 165 30.1 [18.7-46.5] 328 59.9 31 - 60 15 639 214 33.5 [20.8-46.6] 217 34.0 [20.4-48.1] 431 67.5 61 - 90 12 923 341 36.9 [18.3-51.2] 311 33.7 [16.7-50.3] 652 70.6 91 - 120 7 728 258 35.4 [24.1-48.7] 221 30.4 [22.8-39.0] 594 81.6 121 - 150 4 556 187 33.6 [22.6-46.5] 160 28.8 [20.9-37.1] 347 62.4 151 - 180 4 671 297 44.3 [32.8-51.9] 199 29.7 [23.1-37.8] 496 74.0 181 - 230 3 607 320 52.7 [42.1-63.0] 138 22.7 [18.3-25.9] 458 75.4 231 - 300 3 830 519 62.5 [55.7-70.4] 236 28.4 [22.3-35.6] 755 91.0 > 300 7 3,244 2,069 63.8 [50.3-76.5] 514 15.8 [8.8-24.5] 2,583 87.9 Total 90 8,745 4,550 52.0 [14.5 -76.5] 2,094 23.9 [8.8 -50.3] 6,644 75.9



World Wide Survey

Pts with symptomatic AADs refractory AF, should be judged on an individual basis according to the Ablation Centre’s experience


Who to refer ….• Should we try to run before we can walk,

especially if there are other therapeutic options


Who to refer ….• Symptomatic AFib• PaAF or PeAF • Failed AADs therapy • No major cardiac structural disease • Age <70• LA size <5.0 cm • Accept 1-2% risk of STROKE • Accept to 4-5 hour of procedure • Accept 20-30% 2nd procedure• Accept 75-85% improvement rate,

40-50% cure rate off AADs

1. Pharmacological Approach

3.Radiofrequency Catheter ABLATION– AV node Modulation– AV node Ablation and PM implant (ABLATE & PACE)– Primary Ablation (CURATIVE)

2.Anti-tachycardia PACING (ATP)


Strategies


REDUCTION LA refrac. and rate adaption INCREASED in rate, inducibility and stability of AFibDEVELOPMENT of LA/RA enlargement (atrial stretch)INCREASE in mitochondrial size and nr ACCUMULATION of glycogenFRAGMENTATION/DISRUPTION of REG MORPHOLOGIC and CELLULAR remodel. ALTERATION in Ca++ regulatory proteins

A VICIOUS CYCLE

Cellular Remodelling

Verma, Circulation ‘05

RATE RATE vs vs RHYTHMRHYTHM control controlMeta-analysis


THESYS

ANTI-THESYS

CONCLUSIONS

Does it means AFib = Synus Rhythm?

Why therapeutic approach AADs-based Why therapeutic approach AADs-based doesen’t work ? doesen’t work ?

“The meta-analyses suggest that if an effective non-pharmacological approach for maintaining SR is available, it might improve survival”.

ConclusionsRATE RATE vs vs RHYTHMRHYTHM control control

• RFCA should be considered in symptomatic PaAF or PeAF pts due to not reversible causes, AADs refractory and w/o severe LA enlargement

• If AMIODARONE the only long-term option.

• In patients who REFUSE AADs.

• In HIGH RISK EMBOLIC patients with CI to ACT

• Nei giovani con FA parossistica e SSS che non possono essere sottoposti a AADs senza PM

Health & Medicine

2009 roma, policlinico umberto i. workshop interattivo. trattamento del ritmo vs trattamento della frequenza nella fibrillazione atriale