11

New Advances in Atrial Fibrillation Ablation: Cryoballoon-Based Pulmonary Vein

Isolation

Ahmed F. Osman, MD, FACC FESC, FHRS, FASE

Florida Heart Rhythm Specialists, PLLCDirector, Cardiac EP lab, Broward General

Medical CenterNOVA Southeastern University

22

Atrial Fibrillation Health Risks and Costs

• Negative impact on quality of life1,2

• Leading cause of stroke: 5x increased risk3

• Increases risk of heart failure4

• Increases US healthcare system costs: $12 billion estimated cost to treat AF5

1. Singh SN, et al. J Am Coll Cardiol. 2006;48:721-730.2. Kang Y. Heart Lung. 2006;35:170-177.3. Wolf PA, et al. Stroke. 1991;22:983-988.4. White PD: Heart disease. New York, NY, The McMillan Co, 1937.5. Kim M, et al. Adv.Ther. 2009;26:847-857.

Thoracic vein and atrial pathogenesis of AFExtension of

muscular fibers into pulmonary

vein (PV)Ganglia noted

in yellow

Large and small reentrant

wavelets that play a role in initiating andsustaining AF

Common locations of PV

(purple) and common sites

of origin of non-PV

triggers (black)

Composite of anatomic and

arrhythmic mechanisms

of AF

Calkins et al. Heart Rhythm. 2007;4:1-46.

LSPV

LIPV

RSPV

IVC

RIPV

SVC

LSPV

LIPV

RSPV

IVC

SVC

LSPV

LIPV

RSPV

IVC

RIPV

SVC

LSPV

LIPV

RSPV

IVC

RIPV

SVC

RIPV

Indications for Catheter AF Ablation

• Symptomatic AF refractory or intolerant to at least one Class I or III antiarrhythmic medication

• In rare clinical situations, it may be appropriate as first-line therapy

• Selected symptomatic patients with heart failure and/or reduced ejection fraction

• Presence of a left atrial thrombus is contraindication to catheter ablation of AF

“It's far more important to know what person the disease has than what disease the person has.”

Hippocrates

Patient Selection for AblationMore Optimal Patient Less Optimal Patient

Variable

Symptoms Highly symptomatic Minimally symptomatic

Class I and III drugs failed 1 0

AF type Paroxysmal Long-standing persistant

Age Younger (<70 years) Older (70 years)

LA size Smaller (<5.0 cm) Larger (5.0 cm)

Ejection fraction Normal Reduced

Congestive heart failure No Yes

Other cardiac disease No Yes

Pulmonary disease No Yes

Sleep apnea No Yes

Obesity No Yes

Prior stroke/TIA No YesCourtesy of Hugh Calkins, MD.

66

Pulmonary Vein Isolation (PVI) is the Cornerstone of AF Ablation

“Ablation strategies which target the PVs and/or PV antrum are the cornerstone for most AF ablation procedures.”

Cappato et al., Circ Arrhythm Electrophysiol 2010;3;32-38 http://www.HRSonline.org/Policy/ClinicalGuidelines

Isolate each PV independently

2007 HRS Consensus Statement

Complete electrical isolation should be the goal for targeted PVs and entrance and/or exit block should be demonstratedLeft

Superior Pulmonary

Vein

LeftInferior

Pulmonary Vein

Right Inferior Pulmonary Vein

Right Superior Pulmonary Vein

Superior Vena Cava

Inferior Vena Cava

Controlled Trials of AF Ablation Patients Free of AF (% at 1 Year)

Courtesy of Jeremy N. Ruskin, MD, Massachusetts General Hospital.

Perc

ent

88

Challenges Using RF Focal Ablation Catheter to Isolate PV and Ablate Atrial Tissue

• Patient anatomy and atrial tissue depth is variable• Cardiac contractions make maintaining position

difficult• Catheter force varies with position in heart• Technically challenging• Good lesions require transmurality • Successful procedure requires contiguous lesions

99

• Risk of perforation• Uncontrolled energy delivery • Esophageal damage• Char/coagulum formation• Inconsistent results• Time consuming point-by-point

ablation• 6% complication rate• 3- to 6-hour procedure times• Success rates:

– 14.5% - 76.5% w/o AAD– 8.8% - 50.3% w/AAD

Clinical Issues with Conventional RF Focal Ablation Catheter

Cappato R, et al. Circulation. 2005;111:1100-1105.

1010

Clinical Issues with Conventional RF Focal Ablation Catheter

• 6% complication rate• 3- to 6-hour procedure times• Success rates:

– 14.5% - 76.5% w/o AAD– 8.8% - 50.3% w/AAD

Cappato R, et al. Circulation. 2005;111:1100-1105.

Arctic Front® Catheter Design

• Pressurized N2O delivered through ultrafine injection tube

• Straightforward positioning: over-the-wire, steerable, good visibility

• Several safety mechanisms: double balloon, pressure and flow monitoring, blood detection

Arctic Front Catheter Balloon Segment

Inner Balloon

Outer Balloon

Guide Wire Lumen Thermocouple

Injection Tube

Marker Band

Deflection Wires

Guide Wire

1212

Hypothermia

• Ice formation and thawing

• Apoptosis• Necrosis

Cryoablation Effects Include Multiple Mechanisms

Baust, Institute of Biomedical Technology, SUNY 2002

1313

Histological Effect on the Connective Tissue Matrix

• Cryoadhesion improves contact and stability, minimizing the amount of fluoro used

• Preserves the extracellular matrix and endothelial integrity1

• Decreases risk of thrombus formation1

• Demonstrates well demarcated lesions1

1 Sarabanda AV, et al. J Am Coll Cardiol. 2005;46:1902-1912.

1414

Properties of Cryoablation

• Removes heat from the tissue• Leads with a wave of hypothermia• Ablates at the point of balloon contact

Hypothermic Zone

Ablation Zone (sub-zero)

1515

Achieve™ Mapping Catheter

• Achieve is an intracardiac electrophysiology diagnostic catheter which can be deployed through the Arctic Front® guide wire lumen

• Available in 15 mm and 20 mm loop diameters

• Either diameter compatible with 23 mm and 28 mm Arctic Front

16

How Arctic Front® Balloon Catheter and AchieveTM Work

1. Accesstargeted vein

2. Inflate and position

3. Occlude and ablate

4. Assess PVI

16

17

Standardized ProcedureDoes Not Require Complex 3D Mapping

Arctic Front® Cryoballoon

Fluoroscopy image during contrast dye injection shows full occlusion of the left superior pulmonary vein.

• Arctic Front creates circumferential lesions,1 using 2-3 applications per vein to achieve PVI2

• Does not require 3D mapping• Achieve Mapping Catheter can be

deployed through the Arctic Front guide wire lumen, minimizing catheter exchanges

• Allows the procedure to be performed using a single transseptal puncture

Achieve™ Mapping Catheter

Image: Courtesy of Dr. Vogt, Herz- und Diabeteszentrum NRW, Germany1 Sarabanda AV, et al. EffJ Am Coll Cardiol. 2005;46:1902-1912.2 Medtronic, Inc. Arctic Front Cardiac CryoAblation Catheter clinical reports, in support of FDA premarket approval. 1

7

Entire procedure can be done using fluoroscopy or intracardiac echocardiography

18

Assessment of Real-Time PV Isolation• Achieve™ mapping catheter allows

for real-time assessment of PV isolation during cryoablation with Arctic Front®

Images: Courtesy of Dr. Schwagten, ZNA Middelheim, Belgium (above) and Dr. Vogt, Herz- und Diabeteszentrum NRW, Germany (right)

Delay Increased Delay

Isolation Arctic Front is positioned against the LIPV ostium, with Achieve positioned to assess PV isolation

18

19

2020

European Clinical Study ResultsSymptomatic Drug Refractory PAF Efficacy Results

Efficacy Neumann Van Belle Kojodjojo

PVI 97% Arctic Front® 98.5% Arctic Front 83% Arctic Front99% RF ablation

Freedom from AF

74% off AAD at 1 year with Arctic Front

73% off AAD at 1 year with first 3-month blanking period with Arctic Front

59% freedom from AF off AAD at one year with Arctic Front

77% off AAD in most patients at 13 months with Arctic Front

72% off AAD in most patients at 13 months with RF ablation

7-day Holter ECG at 3m intervals

EvR 1m pre3 Month post24h Holter, 12 lead ECG at 3m intervals

24h Holter monitoring at 1, 3, 6, 12 months Event recorders

2121

European Clinical Study ResultsArctic Front® Safety Results

Neumann Van Belle Kojodjojo• 7.5% Phrenic nerve

palsy (PNP)*; all recovered at < 1 year (26/346)

• No PV stenosis

• No atrioesphageal fistula, stroke, death, or other peri-procedural complications

* Primarily in 23 mm balloon

• 2.8% asymptomatic PNP*; all resolved within 6 months (4/141)

• 1.4% arteriovenous fistula (2/141)

• 0.7% left atrial flutter successfully ablated (1/141)

• No PV stenosis

• 0.8% pericardial effusion (1/124)

• 1.6% transient PNP (2/124)

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Shorter Procedures Demonstrated with Experienced European Users

Data from 9 German Centers: Arctic Front® is 33% faster than point-by-point catheter systems with a 24% reduction in fluoro time.

Medtronic data on file.

300

250

200

150

100

50

0

Min

utes

Lab OccupancyTime

Primary PhysicianTime

FluoroscopyTime

-33%

-33%

-24%

Point-by-Pointwith 3D Mapping

Arctic Front

23

Meta Analysis of Clinical Experience

• 539 articles screened, 23 were retained for the final analysis

• Efficacy results strong:– Acute success over 98%– 12-month freedom from AF: 72.83% with 3-month

blanking– No difference in 6-month and 12-month freedom from

recurrent AF between those who underwent Cryoballoon ablation for paroxysmal AF and who underwent RF ablation

Andrade JG, Khairy P, Guerra PG, et al. Efficacy and Safety of Cryoballoon Ablation for Atrial Fibrillation – A Systematic Review of Published Studies. Heart Rhythm. 2011. 23

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Complications – Meta AnalysisOutcome n/N %Phrenic Nerve Palsy (PNP)

Any reported PNPPNP persisting post-procedurePNP persisting > 1 year

86/1,34967/1,349

5/1,349

6.38%4.73%0.37%

Pulmonary Vein Stenosis (PVS)Any PVS (per patient)PVS requiring intervention

7/7732/1,163

0.90%*0.17%

Periprocedure eventsStroke or TIAMyocardial infarctionLA‐esophageal fistulaEsophageal ulcerationPericardial effusion or tamponadeCardiac tamponadePulmonary artery rupture

4/1,2413/1,2310/1,298

6/11618/1,231

7/1,2311/1,231

0.32%0.24%†

0.00%5.17%‡

1.46%0.57%0.08%

* Studies reporting systematic screening for PVS with non‐invasive imaging† Two were transient due to air embolism and resolved without sequelae‡ Outcome reported in three studies of systematic endoscopy post Cryoballoon ablation

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Andrade JG, Khairy P, Guerra PG, et al. Efficacy and Safety of Cryoballoon Ablation for Atrial Fibrillation – A Systematic Review of Published Studies. Heart Rhythm. 2011.

2525

European Arctic Front® Study Conclusions for Symptomatic Drug Resistant PAF Patients

1. Arctic Front System had a very high rate of acute PVI success

2. Arctic Front System had high rate of success in reducing long-term AF events

3. Arctic Front System had a low rate of complications; most resolved by 1 year

4. Arctic Front System significantly reduced procedure time for complete PVI compared to other PVI approaches

5. There was no occurrence of atrioesophageal fistula

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Blankingperiod (90 day)

STOP AF TrialKey Inclusion Criteria:• ≥ 2 documented AF Episodes

in the prior 2 months• Efficacy failure of ≥ 1 AAD

(flecainide, propafenone, sotalol)

Redo ablationn = 31 (19%)

* CRYO: Arctic Front® System

26 centers in US and Canada

AAD optimization

DRUG Crossovern = 65 (79%)

Cryoballoonablation (CRYO)

n = 163

AAD Rx (DRUG)n = 82

Follow-upat 1, 3, 6,

9 & 12Months

N = 245Randomized2:1 to CRYO*

or DRUG

2727

0 100 200 300 400 500Days

0%

20%

40%

60%

80%

100%

Trea

tmen

t Suc

cess

Trea

tmen

t Suc

cess

Effectiveness ResultsFreedom from AF after 90 Days Blanked for Detectable AF

CRYO 69.9% (114 / 163)

DRUG 7.3% (6 / 82)

OR = 29.5 (12.0 – 72.2) p < 0.001

Blankedfor

DetectableAF

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CRYO Procedure Experience Impacts Treatment Success

25centersn=43

P < 0.001 by quartile (Wald)OR = 1.14 for each procedure

14centersn=38

10centersn=42

4centersn=40

1st and 2nd

procedures3rd – 5th

procedures6th – 11th

procedures12th – 23rd procedures

100%

80%

60%

40%

20%

0%

Trea

tmen

t Suc

cess

56%

66% 69%

90%

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Device Related and Procedure Related Serious Adverse Events with Increasing

Experience

*p = 0.27 for SAE by first procedure sequence (initial procedure and reablation) **p = 0.13 for SAE by first procedure sequence (initial procedure only) ***p = 0.30 for SAE within 30 days by first procedure sequence (initial procedure only)

Kowal, et al. in preparation.

DR/PR SAE[n (%)]

Procedure Sequence by Quartile

1st and 2nd

25 centers, n=433rd – 5th

14 centers, n=386th – 11th

10 centers, n=4212th – 23rd

4 centers, n=40

Serious Adverse Events*(Initial and Repeat Abls.)

3 (7.0%) 3 (7.9%) 4 (9.5%) 0 (0.0%)

Serious Adverse Events**(Initial Procedure Only)

3 (7.0%) 2 (5.3%) 3 (7.1%) 0 (0.0%)

Serious Adverse Events within 30 days of procedure***(Initial Procedure Only)

2 (4.7%) 1 (2.6%) 2 (4.8%) 0 (0.0%)

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Additional STOP AF Results

CRYO Results:• 98.2% acute procedural success

• 62.2% of patients were treatment successes without any AF drugs at 12 months

• 60.1% single procedure success rate

• 19% of patients had redo procedures within the first 90-day follow-up period

DRUG Results: • 79% of DRUG group demonstrated chronic treatment failure

and crossed over to the cryoablation procedure

3131

Phrenic Nerve Palsy (PNP)

• 29/259 (11.2%) procedures:*– 15 subjects - asymptomatic– 13 subjects - symptomatic with DOE, SOB, and/or cough– 25/29 (86.2%) resolved by 1 year

• Median time for CXR resolution 102 days• 4/259 subjects (1.5%) had an abnormal CXR at

1 year, 1 (0.4%) remained symptomatic

* 29 PNP events out of 259 procedures in 28 subjects

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STOP AF Trial Conclusions

STOP AF met pre-specified primary effectiveness end point:• 98.2% of CRYO group had acute procedure success• 69.9% of CRYO group compared to 7.3% of DRUG group

were considered a treatment success at 12 months

STOP AF met the pre-specified primary safety end points:• Cryoablation procedure events were observed in 3.1%

(6.3%, UCB) of CRYO group; below the pre-specified 95% upper confidence bound of 14.8%

• The major AF event rate in the CRYO group was non-inferior to the DRUG group at 12 months, at 3.1% and 8.5% respectively

3333

Conclusions

Cryoablation for early Atrial Fibrillation:

1. Is effective in isolation of Pulmonary veins.2. Is a safe procedure. 3.Has shorter procedure times, compared to

conventional RF ablation procedures.4. Ideal procedure for PV / antral based atrial

fibrillation.