January 19, 2020

Catheter Ablation for AF

Who, How, When
Jeanne E. Poole, MD
Electrophysiology Section Head
University of Washington
Seattle, Washington

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Disclosures

Research Grants: Biotronik, AtriCure, Kestra Inc.

Study Committees: Medtronic, EBR Systems

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Catheter Ablation for Atrial Fibrillation

Background

• >20 years ago catheter ablation for AF was introduced

• Early studies suggested that ablation of pulmonary vein triggers could
reduce AF episodes
• While initially, a last resort therapy
 multiple randomized trials of both radiofrequency and cryotherapy
ablation led to AF ablation as first or second line therapy,
 for patients with symptomatic paroxysmal

Jaïs P, Haïssaguerre M et al, Circulation 1997;95(3):572-6 3

Definitions of Atrial Fibrillation

• Paroxysmal AF –
 Duration of AF < 7 days Definition of recurrent AF
 Spontaneous conversion occurs or, episode:
 Cardioversion is performed - Time to first recurrence of AF > 30
• Persistent AF – seconds (after a 90- day blanking
 Duration of AF > 7 days period)
 Cardioversion is planned Calkins H et al Heart Rhythm 2012 Apr;9(4):632-696

• Longstanding persistent AF –
 Duration of AF > 1 year
 Failed, or no plans for cardioversion

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Seminal Work -

SVC

SVC
SVC

IVC

Haissaguerre M et al NEJM; 1998;339:659-666 5

Targeting Pulmonary Vein Triggers

Ablation catheter
ECG - AF

CS

Rapid Lasso catheter in PV

atrial
firings

Ablation within the pulmonary veins recognized to cause pulmonary vein stenosis

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 Catheter Ablation Strategies

• RF PVI is the cornerstone of

ablation
• Additional CTI empiric or for
known atrial flutter
• Other ablation lesions were
being investigated

Cavotricuspid isthmus
For Atrial Flutter

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Efficacy of Antiarrhythmic Drugs and Catheter Ablation in Symptomatic AF Patients

Antiarrhythmic
Catheter Ablation
Drug Therapy
77%
90 71% 72%
Meta-analyzed proportion

42 (3,562)
34 (3,481) 52 (4,786)
80 57%
21 (2,800)
of patients (%)

70
46%
60 40 (1,813) 18 (800)
50
26%
40 50 (4,768)

30
20
10
0
Treatment Recurrent Single- Multiple- Single- Multiple- Patients
success AF procedure procedure procedure procedure requiring
success success success success repeat
off AAD off AAD on AAD or on AAD or ablation
uncertain uncertain
AAD
Catheter
ablation 8 2009
Calkins et al: Circ A&E,
 Earlier Randomized Paroxsymal AF Trials
Selected Examples

ThermoCool AF Trial RAAFT2

Time to first AF/AFL/AT

• 9% major complication rate.

• No serious ablation complications,
• No deaths or strokes in any patient
(stroke, perforation, AE fistula, PVS)
• Abl: 4 perforations with tamponade
• AAD terminated in 7 pts
• Drug therapy: 26 patients (43%) had
ablation

167 patients with PAF, failed one drug 127 treatment-naïve pts with PAF
Wilber DJ, JAMA 2010;303(4):333–40 Morillo CA, et al JAMA 2014;311(7):692-700

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 Alternative Energy Source – Cryoballoon ablation
STOP-AF Trial (N=245 symptomatic AF patients)

STOP AF

79% cross overs)

Actic Front™
Packer D et al,. J Am Coll Cardiol 2013;61:1713-23. 10
 Randomized RF v. Cryoballoon Ablation
FIRE and ICE Trial: 764 patients with PAF
Primary endpoint: Time to first AF after
90-day blanking, need for AAD or need
for repeat ablation
Cryoballoon significantly fewer:
• Repeat ablations,
• DC cardioversions,
• All-cause rehospitalizations,
• CV rehospitalizations
QOL improved in both groups
CIRCA-DOSE TRIAL (Cryo v. Contact Force-RF)
2.7% Phrenic nerve injury with
346 PAF pts Endpoint success ~ 52% at one cryoablation – 0.3% permanent after 12
year, though AF burden was
reduced > 99% mo

Andrade J, Circulation 2019 Nov 26;140(22):1779-1788

Arctic Front Advance™

Kuck KH, et al. NEJM 2016;374:2235 11

 Failure to Cure AF
• Reconnection of the pulmonary veins –
non transmurality of legions AF is the final common pathway for many
• Atypical atrial flutters disorders
• Electrical and mechanical remodeling
contributes to the maintenance of AF
• Atrial myopathy
• Scar
• Or secondary to other structural heart
disease
• Atrial myopathy
• Scar
Other electrophysiologic mechanisms/maintenance of AF
Focal rotors
Ganglionated plexi
Complex fractionated atrial eleltrograms
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 Mechanisms of AF and Ablation Strategies

Five major ganglionic plexi and axons

CFAE

STAR-AF II – no benefit to
adding CFAE to PVI
Verma A et al NEJM 2015

Calkins H et al., 2017 HRS/EHRA/APHRS/SOLAECE expert consensus Heart Rhythm. 2017 Oct;14(10):e275-e444. 13
 (P =
Randomized
0.00 Trials of Persistent AF
2),
impl
Selected Examples SARA Trial CACAF Study
ying
an
abso
lute

AF free survival
risk
diffe
renc
e of
26.6
RR 26.6% (95% CI 10.0-43.3), P = 0.002
%
(95%
CI
10.0-
146 pts with PeAF - Abl v AAD
43.3)
in Endpoint - AF lasting > 24 hours
137 pts PAF or PeAF: intolerant or AAD drugs
favo
or refractory - Abl + AAD v. AAD
ur of
CA. Mont et al Eur Heart 2014 J 35;501-07 Stabile G et al treatment in Eur Heart J 2006;27(2):216-21

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 Longstanding Persistent AF: 5-year follow up Hamburg
Registry Trial

• 202 patients with symptomatic

LS/Pe AF
• Received sequential Abl – PVI,
then if acute recurrent AF,
underwent additional ablation
lesions/targets
• Success:
• After one ablation – 25%
• After multiple – 45%

Kuck KH et al. JACC 2012; 60: 1921

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What about other
outcomes?

Mortality, Stroke, Hospitalization,

Quality of Life

CASTLE AF, CABANA, CAPTAF

- Large, randomized, multicenter, broad populations of AF patients

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CASTLE - AF

AF ablation in heart failure patients

• 397 pts, mostly with untreated or AAD resistant symptomatic AF

• Paroxysmal – 30%
• Persistent – 70%
• LS/Pe – 30%
• Randomized to catheter ablation or usual care
• NYHA class II-IV HF who had an ICD or CRTD
• LVEF ~ 32%

Marrouch N et NJEM 2018 ;378(5):417-427; 17

 Results-CASTLE AF
Primary Composite Endpoint (Mortality or HF Hospitalization)
1

Survival Probability
0.8 Ablation
HR, 0.62 (95% CI, 0.43- 0.6
0.87); P=0.007
Log-rank test: P=0.006 0.4 Conventional

0.2 Risk Reduction: 38%

0
0 12 24 36 48 60
Follow-Up Time (Months)

Patients at Risk
Ablation 179 141 114 76 58 22
Conventional 184 145 111 70 48 12

Marrouch N et NJEM 2018 ;378(5):417-427; 18

 Resu lts-CASTLE AF All-Cause Mortality
1 Ablation

Survival Probability
0.8
HR, 0.53 (95% CI, 0.32- 0.6
Conventional
0.86); P=0.011
Log-rank test: P=0.009 0.4
0.2 Risk Reduction: 47%
0
0 12 24 36 48 60
Follow-Up Time (Months)

Patients at Risk
Ablation 179 154 130 94 71 27
Conventional 184 168 138 97 63 19

Marrouch N et NJEM 2018 ;378(5):417-427; 19

 Results-CASTLE AF
Absolute change in LVEF from baseline
20 p*=0.001 p=0.055 p*=0.005

LVEF Change from Baseline

15

10 [VALUE]
[VALUE]
[VALUE]
5
[VALUE] [VALUE] [VALUE]
0

CAMERA-MRI also -5
showed improved LVEF
with Ablation. Prabhu S -10
et al. JACC 2017;70(16): 12mo 36mo 60mo
1949-61 Ablation Conventional

Marrouch N et NJEM 2018 ;378(5):417-427; 20

Results-CASTLE AF: AF Burden
70

60

50
Percent (%) in Time

40

30

20

10

FIRE and ICE Kuck KH JAHA 2018

0
Baseline 3M 6M 12M 24M 36M 48M 60M
AF Burden

• Did not require complete abolishment of AF to achieve the outcomes

Ablation Conventional

• 27% of those ablated were on an AAD at last follow up

Marrouch N et NJEM 2018 ;378(5):417-427; 21
CABANA
• Largest RCT ever conducted comparing catheter ablation with
drug therapy
• 2204 patients enrolled with new onset or under-treated
symptomatic paroxysmal (45%), persistent, or longstanding
persistent AF (55%)
• Patients were 65 yr and older or => 1 risk factor for stroke
• Randomized to catheter ablation or drug tx (rate and/or
rhythm-control)

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 CABANA – Primary Outcome and Mortality (ITT)

Death, Stroke, Bleeding, Cardiac Arrest All Cause Mortality

The outcome of Death or Hospitalization was significantly different in support of ablation

Packer D et al JAMA. 2019;321(13):1261-1274 23

 CABANA – Primary Outcome and Mortality - Per Protocol

• 81% abl within 3 mo

• 89% abl within 12 mo
• 9.2% abl never performed
• 25% cross over drug to abl

Packer D et al JAMA. 2019;321(13):1261-1274 24

 CABANA: Recurrence of Atrial Fibrillation

Recurrence of AF > 30 sec, post 90-day blanking

Poole JE et al ESC August 25

2018
CABANA Subgroups ITT

Primary Endpoint
Sub-group Analysis

All-Cause Mortality,
Disabling Stroke,
Serious Bleeding,
Cardiac Arrest (ITT)

* Minority=Hispanic or Latino or non-white race

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Quality of Life - CABANA

* Atrial Fibrillation Effect on Quality of Life (AFEQT)

**Mayo AF-Specific Symptom Inventory (MAFSI)
Mark, Dan JAMA 2019 27
CAPTAF
Effect of Catheter Ablation vs AAD on QOL in AF

Randomized 155 symptomatic patients with > 6mo AF and failed

one AAD or B

•Included paroxysmal or persistent

•Excluded EF <35%, prior ablation
•Primary outcome SF 36 score and EQ-5D
•All patients received an ILR (unless DDDPM already)
•Secondary outcome of AF burden (2min or longer AF)

Linde C et al JAMA 2019;321:1069 28

 CAPTAF: Effect of Catheter Ablation vs AAD on QOL in AF
Baseline 12 mo F/U

Ablation
Medication
Swedish norm

At 12-month follow-up, the ablation group improved

significantly more than the medication group In most of the
subscales – reaching the Swedish norm
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Complications

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 Risks of Catheter Ablation
CASTLE-AF: 1.6% perf, 1.6% bleeding, PVS .005
CABANA: 0.8% perf, 2.3% minor hematoma, no strokes, No AE fistulas, No PVS
Population-Based Evaluation of Major Adverse Events After
Catheter Ablation for Atrial Fibrillation (1999-2014) in 3888 patients

Total 3.5% at 30 days *P<0.05

During index hospitalization
0.05% Post discharge

Michelle Samuel et al. JACCEP 2017;3:1425-1433

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 WHO?

CASTLE AF and CABANA

strengthen the choice for
catheter ablation

Calkins H et al., 2017 HRS/EHRA/APHRS/SOLAECE expert consensus Heart Rhythm. 2017 Oct;14(10):e275-e444. 32
Is the AF actually asymptomatic?
HF may be exacerbated; Functional MR; Exercise intolerance attributed to other causes

Calkins H et al., 2017 HRS/EHRA/APHRS/SOLAECE expert consensus Heart Rhythm. 2017 Oct;14(10):e275-e444. 33
 How?
• Pulmonary vein isolation remains the
cornerstone of ablation – supplemental
approaches continue to be studied
• Catheter technology has significantly
improved
 Contact Force catheters
 JET ventilation
 Better sheaths
• Improved imaging – CT, MRI, high density
electroanatomical mapping
• Better understanding of rotors, mapping
them and using them to guide ablation
• Use of MRI determined atrial scar to guide
ablation (DECAF, DECAF II)

Calkins H et al., 2017 HRS/EHRA/APHRS/SOLAECE expert consensus Heart Rhythm. 2017 Oct;14(10):e275-e444. 34
 When– Where does Catheter Ablation Fit in with
AF Management?
Patient with AF
Pattern of AF
Sx or Asx
Comorbidities

Transient and
reversible Modifiable Risk Stroke Heart Rate Rhythm
triggers/medical Factors Prevention Control Control
illnesses

AAD Catheter
Medications Ablation

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Future - Questions
• Asymptomatic patients – Best management targeted at meaningful outcomes
• How best to assess AF ablation success?
 SR all the time, on/off AADs, reduced AF burden?
 Abandon the “time to first recurrence of AF > 30 seconds”?
• Best monitoring strategies – implantable loop recorders for all? Wearable
commercially available technology (Apple Watch etc)
• Safety
 Decrease procedural risks
 Better strategies for esophageal monitoritoring
 Pulsed field ablation (non-thermal ablation/electroporation)
• Increase efficacy –
 Address non-transmurality
 Pulsed field ablation
 High intensity focused ultrasound (HIFU)
 Non-Invasive extracorporeal particle ablation
 Better approaches to persistent/longstanding persistent
Reddy V et al jacc.2019.04.021 Quian PC et al., doi.org/10.1002/joa3.12283

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Thank you

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