Results from AMADEUS

1
Results from AMADEUS

• CARILLON Mitral Annuloplasty Device European
  Union Study
• Cardiac Dimensions CARILLON Mitral Contour
  System

2
Disclosures
Nothing to Disclose
2
3
AMADEUS Investigators

• Hamburg University
• Cardiovascular Center
• Prof. Dr. med. Joachim Schofer (PI)
• - Dr. Thilo Tübler
• - Ms. Anya Hoffman (Study Coordinator)
• Universität zu Köln
• Prof. Dr. med. Uta Hoppe
• - Dr. Mathias Brandt
• - Ms. Iris Berg (Study Coordinator)
• OLVG (Amsterdam)
• Dr. Jean Paul Herrman
• Dr. Ton Slagboom (IC)
• - Dr. Gijsbert de Ruiter (EP)
• - Dr. Edske ter Bals (Study Coordinator)

• Cardiac Rehabilitation
• Hospital Kowanówku
• Prof. Dr. med. Tomasz Siminiak
• - Dr. Olga Jerzykowska (Echo)
• - Dr. Piotr Kalmucki (Study Coordinator)
• Stadtische Kliniken Neuss
• Prof. Dr. med. Michael Haude
• - Dr. Hubertus Degen (Study Coordinator)
• - Dr. Mathias Breise (Echo)
• AZM (Maastricht)
• Dr. Luz Maria Rodriguez
• Dr. J. Vainer (IC)
• - Dr. David van Kraaij (HF)
• - Ms. Suzanne Philippines (Study Coordinator)

3
4
Percutaneous Annuloplasty for Functional MR

• Coronary Sinus approach
• Results Immediately observable
• Tension / Plication is controlled by operator
• Recapture Feature allows for Management of
  Coronary Arteries
• Does not preclude other HF therapies such as Bi-V
  pacing or surgery

4
5
CARILLON Animation
5
6
The AMADEUS Trial

• Study Design
• Prospective, single-arm, 30 patient, Six month,
  multi-center trial
• Inclusion Criteria
• Dilated Ischemic or Non-ischemic Cardiomyopathy
  (LVEDd gt 55mm)
• NYHA Class II IV
• FMR moderate to severe
• EF lt 40
• 6 MWT distance between 150m 450m
• Stable on heart failure meds
• Primary Endpoint
• Thirty day rate of Major Adverse Events
• Secondary Endpoints Long-term safety
  Hemodynamic and functional changes
• NYHA Class
• Exercise (6 minute walk test Maximum Exercise
  Time)
• QOL (KCCQ)
• Change in MR

6
7
Baseline DemographicsIntent to Treat Population
(n48)
AMADEUS Trial
Age 64 (25-81 yrs)
Gender M 83 (40) F 17 (8)
History of CAD 73
NYHA Class II - 9 III - 37 IV - 2
EF 29 (10-39)
MR (TEE Procedure Baseline) 2 15 3 18 4 15
LVEDD 67 mm (50 92 mm)
AMADEUS Patients were at High Cardiovascular Risk
7
8
AMADEUS Enrollment Tree
Enrolled Patients N48
CARILLON XE Procedure Initated N39
Procedure Not Initiated N5
Original CARILLON Procedure N4

• Dissection / Perforation (3)
• Screen Failure (2)

Implanted N29
Implanted N1
Not Implanted N3
Not Implanted N10

• Slip

• Insufficient MR reduction (4)
• Coronary Compromise (1)
• Both (5)

8
9
Major Adverse Event RatePrimary Safety Endpoint
at 30 Days
Event Intention to Treat (n48)
Death 2.2 (1 / 46)
Myocardial Infarction Enzyme bump only. No Sx or EKG change (n2) Enzyme bump plus EKG change (n1) 6.5 (3 / 46)
CS Perforation During venous access. Non device related 6.5 (3 / 46)
Device Embolization 0.0 (0 / 46)
Surgery or PCI related to device failure 0.0 (0 / 46)
Total Major Adverse Events 13 (6/46) (7 events
in 6 patients)
Two patients withdrew consent before 25 days F/U
9
10
Managing Coronary Arteries
Arteries crossed in 84 of cases

• 11 cases of crossed arteries required device
  Recapture
• In 5 cases, a 2nd device was successfully placed
  proximal

10
11
Chronic MR Reduction AMADEUS Implanted Patients
(n30 at Baseline)
Quantitative MR Measures _at_ Baseline, One, Six
Months
Plt0.001
cm2
cm
ml
Area
27 Reduction in FMR on average _at_ 6 months
11
12
Sustained Benefit through 6 Mo.MR Reduction /
LV Wall Motion
Baseline
3 Months
6 Months
49 yr old Male
Baseline 1 Mo 3 Mo 6 Mo
Core Lab MR 3 0 0 0
NYHA II I I
6 MWT (meters) 320 450 400
Max Exercise (sec) 540 900 1080
QOL (KCCQ) 31.00 91.00 98.96
12
13
NYHA Classification
P lt 0.001
n30
n27
n25
At baseline, 80 of patients were NYHA Class III
or IV At 6 Months, 88 of patients were NYHA
Class I or II
13
14
Six Minute Walk Test
P lt 0.001
Meters
n30
n26
n23
14
15
QOLKCCQ Overall Summary
P lt 0.001
n30
n27
n25
15
16
QOLPatient portion of Global Assessment
Assessment 1 month 6 months
Markedly improved 27 36
Moderately improved 31 24
Slightly improved 19 24
No change 11 8
Slightly worse 8 8
Moderately worse 0 0
Markedly worse 4 0


77
84
n26
n25
16
17
AMADEUS Procedural Times
Minutes

• Procedure Times steadily declined over the
  course of the study
• Reduced Procedure time benefits sick HF
  Population

17
18
CARILLON Poznan case
At Baseline
After Deployment
19
AMADEUS Study Conclusions

• AMADEUS study achieved its safety endpoint with
  an acceptable MAE profile. 13 MAE rate _at_ 30
  days was primarily non-device related.
• At-risk coronary arteries were successfully
  managed in AMADEUS with the CARILLON
  recapture feature.
• MR was reduced by 27 out to 6 months.
• Statistically significant improvements in
  functional parameters out to 6 months (e.g.,
  exercise, NYHA, QOL) .
• Short, simple procedure is important for this
  unstable HF patient population.

19