CRM-88604-AA JUN2012 HRS 2012 S-ICD Clinical Highlights.

CR

M-8

860

4-A

A JU

N2

01

2

HRS 2012 S-ICD Clinical Highlights

CR

M-8

860

4-A

A JU

N2

01

2

Disclaimer

The content in this presentation was presented at HRS, May 2012. This presentation is for educational purposes only and should not be copied or presented without the permission of Boston Scientific Corp.Like any other service, in spite of our best efforts the information in this presentation may become out of date over time. Nothing on this presentation should be construed as the giving of advice or the making of a recommendation and it should not be relied on as the basis for any decision or action. The materials are intended for educational purposes only. Boston Scientific neither assumes nor accepts liability for the accuracy or completeness or use of, nor any duty to update, the information contained in this presentation.Some information in this presentation describe products in development that will require approvals or clearances by FDA prior to market release. Some products may be investigational and limited by Federal law to investigational use.

CR

M-8

860

4-A

A JU

N2

01

2

Table of Contents

1. Safety and Efficacy of a Subcutaneous Implantable Defibrillator (S-ICD®): HRS Late Breaking Clinical Trials

Presented by: Martin C. Burke, DO

2. International Experience with a Subcutaneous ICD; Preliminary Results of the EFFORTLESS S-ICD Registry

Presented by: Pier D. Lambiase, MD, PhD

HRS 2012, Boston, MA

CE Mark Approved.Caution: S-ICD is an investigational device limited to investigational use only under US federal law. Not for sale.

CR

M-8

860

4-A

A JU

N2

01

2

Safety and Efficacy of a Subcutaneous Implantable Defibrillator (S-ICD®)

HRS Late Breaking Clinical Trials

Martin C. Burke, DOProfessor of Medicine

Interim Chief of CardiologyDirector, Heart Rhythm Center

University of ChicagoHeart Rhythm - May 2012; LB01-6

Burke, S-ICD, HRS 2012, Boston, MA


CR

M-8

860

4-A

A JU

N2

01

2

Subcutaneous-ICD System

Designed to sense, detect and treat malignant ventricular tachyarrhythmias

S-ICD Systemis entirely subcutaneous



CR

M-8

860

4-A

A JU

N2

01

2

S-ICD Study DesignProspective, Single-Arm Comparison to OPC

Enrollment (N=330)• 33 Sites in the US, NZ, NL, UK

1o Efficacy Endpoint: Acute VF Conversion Rate• 2 consecutive successes out of 4 attempts• Lower Bound of 2-sided CI95% > 88%

Semi-Annual Follow-Up Visits Through Study Close

Optional Sub-Study• VF Conversion Rate at ≥150 Days

1o Safety Endpoint: 180-Day System Complication Free Rate

• Lower Bound of 2-sided CI95% > 79%



CR

M-8

860

4-A

A JU

N2

01

2

Eligibility

Inclusion Age ≥ 18 years Met guidelines for ICD implantation3 or replacement of an

existing ICD system An appropriate pre-operative ECG

Key Exclusion Criteria Prior VT reliably terminated with anti-tachycardia pacing Existing epicardial patches or subcutaneous array Unipolar pacemakers Severe renal dysfunction (GFR ≤ 29)



CR

M-8

860

4-A

A JU

N2

01

2

S-ICD System IDE Study Results


CR

M-8

860

4-A

A JU

N2

01

2

Patient Enrollment

Implant Testing Completed

EFFECTIVENESS COHORT(N=304)

Implant Testing Not Completed

(N=17)

Active Patients(N=294)

• Not Discharged with System (N=7)• Exits after Hospital Discharge (N=12)• Deaths unrelated to device or procedure

(N=7)• Death unknown due to limited information

from overseas death (N=1)

Patients Withdrawn PRIOR to Implant(N=9)

Implant AttemptsSAFETY COHORT

(N=321)

Patients Enrolled(N=330)



CR

M-8

860

4-A

A JU

N2

01

2

Basic Patient Demographics

Demographic Category ValueAge (years) 52 ± 16

Male 74%

Height (cm) 174 ± 10

Weight (kg) 91 ± 25

BMI (kg/m2) 30 ± 7

Race

Caucasian 65%

African American 24%

Hispanic or Latino 7%

Other 4%



CR

M-8

860

4-A

A JU

N2

01

2

Baseline Characteristics

Attribute Statistic/CategoryN=321

n %

Co-morbidities History

Congestive Heart Failure 197 61Hypertension 187 58Myocardial Infarction 133 41Diabetes 90 28Atrial Fibrillation 49 15Valve Disease 42 13COPD 27 8Stroke 18 6

Cardiac Surgical History

Percutaneous Revascularization 92 29CABG 48 15TV-ICD 43 13Valve Surgery 18 6Pacemaker 4 1



CR

M-8

860

4-A

A JU

N2

01

2

Primary & Secondary Prevention Patient Distribution Similar to NCDR Registry

S-ICD System IDE Studyn=321 patients

NCDR ICD Registryn=486,025 patients

Secondary Prevention

21%

Secondary Prevention

22%

Primary Prevention

79%

Primary Prevention

78%



CR

M-8

860

4-A

A JU

N2

01

2

Baseline Characteristics


n %

NYHA Class at Enrollment

Class I 68 21

Class II 146 45

Class III 55 17

Class IV 1 <1

Unknown/Not Assessed 51 16Ejection Fraction (%)(n=299) Mean ± SD (Median) 36 ± 16 (31)



CR

M-8

860

4-A

A JU

N2

01

2

Implant Success



CR

M-8

860

4-A

A JU

N2

01

2

Implant Attempts

321 patients underwent implant procedure

95% implanted using only anatomical landmarks (no medical imaging)

No electrode or pulse generator movement in 99% of implanted patients throughout follow-up period



CR

M-8

860

4-A

A JU

N2

01

2

Effectiveness ResultsPrimary Effectiveness Endpoint



CR

M-8

860

4-A

A JU

N2

01

2

Primary Effectiveness EndpointAnalysis Cohort

Patients Enrolled(N=330) Patients

Withdrawn PRIOR to

Implant (N=9)SAFETY

COHORT/Implant

Attempts(N=321)

EFFECTIVENESS COHORT (N=304)

Acute Induction Testing Not Performed

(N=1)

Acute Induction Testing Non-

evaluable (N=16)



CR

M-8

860

4-A

A JU

N2

01

2

Primary Effectiveness Endpoint Met

Primary IDE Effectiveness Endpoint Hypothesis: Lower Bound of 2-sided CI95% >88% N=304 patients

Induction Testing

Not Performe

d

Non-Evaluable Patients

Evaluable Results

Conversion Rate

(%)

95% Lower Bound

(%)Successful Failure

1 16 304 0 100.0 98.8



CR

M-8

860

4-A

A JU

N2

01

2

Sensitivity Analysis Exceeds OPC

Primary IDE Effectiveness Endpoint Hypothesis: Lower Bound of 2-sided CI95% >88%

Sensitivity Analysis Failure: Patients w/ incomplete testing and ≥1 failed

shock N=315 patients

Induction Testing

Not Performe

d


Evaluable Results

Conversion Rate

(%)

95% Lower Bound


1 16 304 0 100.0 98.8

1 5 304 11 96.5 93.8



CR

M-8

860

4-A

A JU

N2

01

2

All Analyses Exceed OPC

Primary IDE Effectiveness Endpoint Hypothesis: Lower Bound of 2-sided CI95% >88%

Sensitivity Analysis Failure: Patients w/ incomplete testing and ≥1 failed

shock Worst-Case Sensitivity

All non-evaluable and 1 not tested deemed “Failures” N=321 patients

Induction Testing

Not Performe

d


Evaluable Results

Conversion Rate

(%)

95% Lower Bound


1 16 304 0 100.0 98.8

1 5 304 11 96.5 93.8

0 0 304 17 94.7 91.7Burke, S-ICD, HRS 2012, Boston, MA


CR

M-8

860

4-A

A JU

N2

01

2

Spontaneous Episodes

Evaluation

VT/VF Episodes

Total Discrete Storm

IDE StudyEpisodes 109 28

81(4

events)

Patients 16 16 2

All episodes successfully converted with 80J or spontaneously converted



CR

M-8

860

4-A

A JU

N2

01

2

Unnecessary Therapy Avoided

Algorithm prevents therapy for VT/VF rhythms that are likely to spontaneously terminate

Therapy avoided in 63% of patients with VT/VF rhythms meeting criteria to charge without any reports of syncope

VT/VF(Patients)

0% 20% 40% 60% 80% 100%

27 16

Non-Sustained(not shocked)

Sustained(shocked)



CR

M-8

860

4-A

A JU

N2

01

2

Example: Non-Sustained MVTLikely to receive therapy from TV-ICD

DURATION: 16 seconds47 cycles



CR

M-8

860

4-A

A JU

N2

01

2

Safety ResultsS-ICD System IDE Study



CR

M-8

860

4-A

A JU

N2

01

2

Safety ResultsAnalysis Cohort


SAFETY COHORT/ Implant Attempts

(N=321)

Patients Withdrawn PRIOR to Implant

Procedure(N=9)



CR

M-8

860

4-A

A JU

N2

01

2

Primary Safety Endpoint Met

0 14 28 42 56 70 84 98 1121261401541680.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Freedom from Type I Complicati

on180-day Type I

Complication-Free Rate:

99.0% (97.9% LCL)

Post-op Days

180-day Performance Goal (79%)



CR

M-8

860

4-A

A JU

N2

01

2

Freedom from all Device-, Labeling-, & Procedure-related Complications

0 14 28 42 56 70 84 98 1121261401541680.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

180-day Device & Procedure-related Complication-free

Rate:92.1% (88.9% LCL)

Post-op Days

180-day Performance Goal (79%)

Freedom from

Type I - III Complicatio

n



CR

M-8

860

4-A

A JU

N2

01

2

Safety ResultsInfections



CR

M-8

860

4-A

A JU

N2

01

2

Few Infections Led to Explant

All Suspected & Confirmed Infections

(N=18)

Managed w/ antibiotics (n=13)Managed w/ sternal wound revision (n=1)

Superficial or Incisional Infections

Managed without System Explant

(n=14, 4.4%)

System Explanted(n=4, 1.3%)



CR

M-8

860

4-A

A JU

N2

01

2

Infections: Study-Wide Learning on Surgical Prep

Jan-1

0

Feb-1

0

Mar

-10

Apr-10

May

-10

Jun-1

0

Jun-1

0

Jul-1

0

Aug-10

Sep-1

0

Oct

-10

Oct

-10

Nov

-10

Dec

-10

Jan-1

1

Feb-1

1

Mar

-11

Mar

-11

Apr-11

May

-11

0

50

100

150

200

250

300

350

Infections requiring

explant4 0

All 4 infections requiring

explantation occurred early in study enrollment E

NR

OLL

MEN

TS



CR

M-8

860

4-A

A JU

N2

01

2

Safety ResultsInappropriate Shocks



CR

M-8

860

4-A

A JU

N2

01

2

Inappropriate Shocks

38 patients* experienced shocks due to non-VT/VF event

15 patients: SVT > Discrimination zone

24 patients: Oversensing

Rate of inappropriate therapy is consistent with current transvenous ICDs

No patients experienced a shock due to discrimination error in Conditional Shock (dual) zone

* 1 patient experienced multiple events



CR

M-8

860

4-A

A JU

N2

01

2

Dual-zone Programming Reduced Inappropriate Shocks

Oversensing SVT0%

2%

4%

6%

8%

10%

12%

14%

Single (n=88)

Single (n=88)

Dual (n=226)

Dual (n=226)

54% relative

reduction

74% relative

reduction



CR

M-8

860

4-A

A JU

N2

01

2

International Experience with a Subcutaneous ICD; Preliminary Results of

the EFFORTLESS S-ICD Registry

PD Lambiase DAMJ Theuns, C Barr, R Knops,

F Murgatroyd, JB Johansen & L Boersma on behalf of the EFFORTLESS S-ICD investigators

Heart Rhythm - May 2012; Vol 9:5(S1-33) AB07-2.

Sponsor: Cameron Health, Inc. San Clemente, CA

Lambiase, EFFORTLESS S-ICD Registry, HRS 2012, Boston, MA


CR

M-8

860

4-A

A JU

N2

01

2

The S-ICD System Operation

Single-zone programming allows therapy to be delivered solely on measured heart rate

Dual-zone programming activates SVT discrimination algorithm to determine appropriateness of therapy

S-ICD System is entirely subcutaneous and can be placed using anatomical landmarks

Three sensing vectors to identify most robust cardiac signal



CR

M-8

860

4-A

A JU

N2

01

2

Evaluation oF FactORs AffecTing the CLinical Outcome and Cost EffectiveneSS of the S-ICD – The EFFORTLESS S-ICD Registry Design

• International, standard of care Registry to collect short, mid and long-term operational and clinical outcome data on the Cameron Health S-ICD system

• 5 year data post implant

• Retrospective and prospective patients implanted since CE mark

• Aiming to recruit up to 1000 patients

• Centers to be included from all current commercial countries



CR

M-8

860

4-A

A JU

N2

01

2

The EFFORTLESS Registry Design

Protocol includes• Documentation of system related outcomes and

clinical events• Prospective, Quality of Life sub-study to assess

patients perception of their therapy• Run by Tilburg University Core Lab- Professor Susanne

Pedersen• SF-12, FPAS, ICDC, HADS, DS-14 & EQ-5D QOL

questionnaires• Baseline, 3, 6, 12 months post implant• Direct comparison to TV therapy via MIDAS study cohort

• Cost effectiveness analysis by hospital resource tracking and use of EQ-5D questionnaire



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Inclusion/Exclusion Criteria

Inclusion Criteria• ≥ 18yrs* at time of consent• Eligible for implantation of an S-ICD system per local

clinical guidelines or currently implanted with an S-ICD

Exclusion Criteria• Participation in any other investigational study that may

interfere with interpretation of the study results• VT that is reliably terminated by ATP• Unipolar pacemakers

*Not applicable for centers enrolling under DN 15677, August 30, 2010



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Site Participation in 9 Geographies

UK(13)

NL(7)

DK(3)

SL(1)

CZ (3)

I (4)

P(1)

DE(10)

NZ(2)



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Recruitment Overview

NL(123)UK

(75)

CZ(17)

DK(14)

NZ (1)

230



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Patient Status as of April 27, 2012Average FU 389±282 days, max 981 days

Active Patients(N =210)

• Withdrawn N=1 (heart transplant)

• Deaths N=6*• Explants N=5 • Inactive N=1

• Missing Data N=4• Withdrawn due to ineligibility

N=2• Consented not implanted N=1

Patients Implanted(N =223)


* No device related deaths



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Basic Patient Demographics

Demographic Category Value N

Age (yrs; range) 49±19* (11-86) 227

Male (%) 74 227

Height (cm) 175±10 186

Weight (kg) 81±20 196

LVEF (%; median) 42±19 (35) 178

QRS (ms) 104±21 207*Approx. 60% of patients (131/227) ≥ 50 yrs



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Standard ICD Baseline Characteristics


%

Co-morbidities

Congestive Heart Failure 32Hypertension 25Myocardial Infarction 38Diabetes 13Renal Disease 10Atrial Fibrillation 19COPD 6 Stroke 4

Cardiac Surgical History

Ablation 7CABG 10Valve Surgery 6Prior TV ICD 15*Pacemaker 3*

37 patients had previously implanted systems- 6 patients have concomitant PM/S-ICD



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Heart Failure & Indication Characteristics


n %

NYHA Class at Enrollment

Class I 19 27

Class II 32 46

Class III 10 14

Class IV 0 0

Unknown/Not Assessed 9 13

Indication n %

Primary 144 64

Secondary 81 36



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Broad Range of ICD Indications

Patients from a broad range of indications have received the S-ICD

Ischemic (38%)

Channelopathy (13%)

Congential (3%)

Non ischemic CM (10%)

HCM (13%)

ARVD (3%)

Idiopathic VF (20%)



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Cardiac Medications at Enrollment

Medication n %

Amiodarone 15 7

Diuretics 93 41

ACE Inhibitors 93 41

Beta Blockers 151 67

Digoxin 11 5

Lipid Lowering (incl. statins) 48 21None 33 15



CR

M-8

860

4-A

A JU

N2

01

2

Registry Results



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Effective Conversion of Induced VT/VF

Patient Data n %

Implant Conversion test data available 204

Successful conversion within 1 procedure -Successful at 65J-Successful at 80J

201197201

98.5

Patients requiring repositioning-Successful conversion following repositioning-Awaiting retesting (non inducible)

12

1.5



CR

M-8

860

4-A

A JU

N2

01

2

0

5

10

15

20

25

30

35

40

<12 12-14.9 15-17.9 18-20.9 21-23.9 ≥24

Seconds

% o

f Even

ts

93% <21 seconds

N=86*

Mean ± SD:15.9±3.8 Median:

15.0

3.5%

37.2%34.9%

17.4%

3.5% 3.5%

*No data available for retrospective patients

EFFORTLESS Registry 93% of Events Treated in < than 21secs



CR

M-8

860

4-A

A JU

N2

01

2

Discrete Episodes Patients

EPISODES

Type II spontaneous Termination

1st S-ICD System Shock

Conversion

2nd S-ICD System Shock

Conversion

16 11 2 13 1

Storm Events Episodes Patients

EPISODES

S-ICD System Shock Conversion

4 32 2 32 (100%)

EFFORTLESS Registry 100% Conversion of Spontaneous VT/VF

• 16 discrete VT/VF episodes from 11 patients

• 32 VT/VF storm episodes from 2 patients both with electrolyte imbalances (post dialysis and post surgery)



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Annual Inappropriate Shock Rate of 7%

0

5

10

15

20

Rate > Shock Zone

Oversensing

Perc

en

t

7%

• 15 patients received inappropriate shocks (7%)

• No inappropriate shocks have been recorded for AF/SVT within a programmed conditional shock zone



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Appropriate vs. Inappropriate Episodes

0

10

20

30

40

50

60

Appropriate Inappropriate Episode not stored

Ep

isod

es

(67%)

(28%)

Total of 72 Episodes



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Clinical Event Definitions

• Clinical Event• Any untoward medical occurrence

• Categories• Complications: Invasive intervention required• Observations: Conservative therapy

required

• Type I-III Clinical Events• Device-, labeling-, or procedure-related

• Type IV Clinical Events• Related to patient condition



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Device & Procedure-Related Events

Category Complications Observations

Device-related (Type I) 2 16

Labeling-related (Type II)

0 0

Procedure-related (Type III)

15 19

17



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Device-Related Events - Type I

CategoryComplicatio

nsObservatio

ns

Inappropriate Shock - oversensing 1 14

Discomfort 0 1

Premature battery depletion 1 0

Inability to communicate with device 0 1

Total 2 16



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Procedure-Related Events - Type III

CategoryComplicatio

nsObservation

s

Infection/suspicion of infection 6 2

Inappropriate Shock - rate > shock zone 1 5

Suboptimal electrode position 5 0

Hematoma 1 2

Redness/irritation 0 3

Discomfort 0 2

Keloid formation 0 1

Phantom shocks/vibration 0 3

Transfusion 1 0

PG Movement/Revision 1 0

Total 15 19



CR

M-8

860

4-A

A JU

N2

01

2

EFFORTLESS Registry Infection Management

All Suspected Infections*

(N=8)

Medically Managed without System Explant

(n=3, 1.3%)

System Explanted

(n=4, 1.8%)

Electrode Explanted

(n=1, 0.4%)

Electrode Re-implant

(n=1)

S-ICDRe-implant

(n=1)*No reported endocarditis or blood born infection



CRM-88604-AA JUN2012 HRS 2012 S-ICD Clinical Highlights.

Documents

Transcript of CRM-88604-AA JUN2012 HRS 2012 S-ICD Clinical Highlights.