Long-term Efficacy and Safety of Catheter Ablation for AF: What is the Evidence? AHA QCOR Washington DC D. George Wyse MD PhD May 20, 2010.

Long-term Efficacy and Safety of Catheter

Ablation for AF: What is the Evidence?

AHA QCOR Washington DC

D. George Wyse MD PhD

May 20, 2010

Disclosures*

* All < $10,000

DSMB, SC or Grant Reviewer (Research)

Advisory Board

Speaker

• Boerhinger Ingelheim (PHRI); RE-LY; RE-LYABLE

• Medtronic (Mayo) – TRENDS; PACIFIC

• Sanofi Aventis/Bristol Myers Squibb (PHRI)

- ACTIVE-A; ACTIVE –W; ACTIVE-I

• Bristol Myers Squibb/Pfizer (DCRI) – ARISTOTLE

• Sanofi Aventis – BOREALIS, DETECT-AF

• Biotronik (Axio) - IMPACT

• Boston Scientific/Guident (PHRI) - SIMPLE

• NHLBI (DCRI; U Penn) – TACT; COAG

• European Commission – FP-7 Grant Applications

• Sanofi Aventis (PHRI) – POSEIDON

• Merck

• Bayer

• Sanofi Aventis

• BMS

PHRI – Population Health Research Institute – McMaster UniversityDCRI – Duke Clinical Research Institute; Mayo – Mayo ClinicAxio – Axio Research CorporationU. Penn – University of Pennsylvania

Outline

• Key Patient Characteristics of RCT of LA/PV RFA and AAD

• Quantitative “Gradient” between Groups of SR vs. AF in AAD vs. RFA RCT

• Goals for Therapy of AF• Reduce Mortality• Prevent Stroke/SE• Preserve/Improve Ventricular Function and Prevent CHF• Relief of Symptoms

• RFA of AV Junction and Pacemaker

Age and Duration of Follow-up in RTCof LA/PV Catheter Ablation for RFA

Study N Mean/median Age Mean FU

Haissaguerre (2000) 90 51 0.7

Natale (2000) 15 59 0.8

Oral (2003) 40 51 0.5

RAAFT Pilot (2005) 70 53 1.0

APAF (2006) 198 56 1.0

CACAF (2006) 137 62 1.0

A4 (2008) 112 51 1.0

CABANA Pilot (2009) 60 64 1.0

AAD RCT: AFFIRM, AF-CHF & ATHENAN = ~ 10,000Mean Age = 70yMean FU = 4.5y

Table unpublished, courtesy of Win Shen – Mayo University

Quantitative “Gradient”SR vs. AF; AAD vs. RFA

New Engl J Med 2002;347:1825New Engl J Med 2008;358:2667New Engl J Med 2008;359:1778

AF-CHFAFFIRM

PABA-CHF – not “prevalence”

Gradient = 40%

Gradient = 70%

Gradient = 40%

Goals of Therapy for AF

Reduce Mortality

Death After RFA for AFShort-term

Circulation 2005;111:1100

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

Death

Tamponade

Sepsis

PneumoX

HemoX

Phrenic N

Vessel Inj

Stroke

TIAPV Senosis

Per

cen

t

Based on 45, 115procedures in 35, 569patients between1995-2006 = 0.98 per1,000

JACC 2009;53:1798

Death After RFA for AFLong-term

J Am Coll Cardiol 2003;42:185

• 65 ± 9 years

• PAF = 69%

• No CV Dis = 34%

• LVEF = 54 ± 12%

Death in RCT vs. AAD• RR = -0.003 (95% CI -0.01- 0.02; p = 0.74)

Am Heart J 2009;158:15

+ Annual Mortality in AFFIRM ~ 3.5%

Prevent Stroke/SE

Stroke/TIA from RFA for AFShort-term

“Yin-Yang” of Anticoagulation

Circulation 2005;111:1100

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

Death

Tamponade

Sepsis

PneumoX

HemoX

Phrenic N

Vessel Inj

Stroke

TIAPV Stenosis

Per

cen

t

Stroke/SE after RFAShort-term

Circulation 2006;114:759

Stroke in RCT vs. AAD• RR = 0.004 (95% CI -0.01-0.02; p = 0.54)

Am Heart J 2009;158:15

Impact of Absence of AF on Stroke

Stroke In AF Patients

Cardioembolic~60 - 65%*

Other~35 - 40%*

AtheroembolicArterial Thrombosis

HemorrhageOther

•LAA•LA•LV

•Valves

* Neurology 1993;43:32 & Arch Intern Med 2005:165:1185

Perception of AF after RFA

Circulation 2005;112:307

Episodes of AF % Episodes withNo Symptoms

AF Patterns Before/After AF Ablation with 24/7 Monitoring

J Cardiovasc Electrophysiol 2007;18:818

• “Permanent Cure” after 3 mo blanking = 3/14

Preserve/Improve Ventricular Function & Prevent CHF

RFA and LV FunctionA meta analysis of RCT

A = RR for reduced LVEF vs. normal LVEFB = Absolute % LVEF after vs. before RFA

Relief of Symptoms

SymptomsAblation vs. AAD

J Am Med Assoc 2010;303:333

• Symptomatic AF• Failed at least 1 AAD• No amiodarone in 6 months• LA diameter <5cm• Mean age = 56y• Mean follow-up = 13 months

Symptoms of AFCCS- SAF Class N = 484

Circ Arrhythmia EP 2009:2;218

0

5

10

15

20

25

30

0 1 2 3 4

Percent

Symptom Class

Per

cen

t

CABANA TrialDesign

QualifyingAF

RF AblationPV isolation ± Center

Preferred Enhancements

Drug TherapyRate or Rhythm Control

R

Ablate [and Pace]

Effects of AV Junction Ablation & Pace

A Meta Analysis

Circulation 2000;101:1138

PACIFIC Trial Pilot

Qualifying AF(Failed 1 Drug Therapy)

Age ≥65y

AV Junction Ablation+ Device

Drug TherapyRate or Rhythm Control

RV Apex Pacing Biventricular Pacing

R

R