1. Angel Medical Systems Implantable Ischemia Detection : An Update
Tim A. Fischell, M.D., FACC, FSCAI
Professor of Medicine
Michigan State University

2. Tim A. Fischell, M.D. Angel Medical Systems, Inc. Abbott Vascular
I have the following financial disclosures:
Angel Medical Systems, Inc.
Founder, Co-Inventor
Stockholder  
Abbott Vascular
Member, Medical Advisory Board

3. Important Disclosures About the AngelMed Guradian System™
The AngelMed Guardian is:
An investigational product not currently approved in the United States
Limited to investigational use in clinical trials
Undergoing evaluation by the FDA for review of data for possible PMA approval.
This presentation is intended solely to aid in scientific discussion and exchange surrounding the development and further evaluation of the product. It is not a commercially available product.

4. Relationship Between Early Reperfusion, Mortality Reduction, and Extent of Myocardial Salvage
100 80
Critical Time-dependent Period Goal: Myocardial Salvage
Time-independent Period Goal: Open Infarct-related Artery 60
Mortality Reduction, (%) 40 20 4 8 12 16 20 24
Time From Symptom Onset to Reperfusion Therapy (hours)
Gersh BJ, et al. JAMA. 2005;293:

5. Impact of MI and Time to Arrival on Outcomes in STEMI “Denial is Not a River in Egypt”
Over 1.2M heart attacks a year in the US
Over 400K of those die within 1 year
~30% have no symptoms or atypical symptoms particularly diabetics and elderly women
Average time symptoms to arrival = 2 ½ hours
#1 Medicare cost in U.S. is congestive heart failure (CHF)
Major cause of CHF -> dead muscle after arriving to ER in 3 hours!
Annual US Heart Attacks
200
400
600
800
1,000
1,200
1,400
Heart
Attacks
Survive
Deaths
(000)
For every 30min increase in time to treatment:
7.5% increase in mortality
8.7% increase in low EF leading to CHF 15
Mortality (%) 30 45 60
Morbidity (%)
Time 5

6. AngelMed GuardianTM IMD
EXD
IMD
Wireless Telemetry
max 6ft (1.8m)
Detects ischemia and arrhythmias
Two levels of vibratory alarms
Stores heart data
228 electrogram strips (9 – 27hr history)
14 days of histograms
6 months of daily stress test data
Programmable alarm responses
Emergency Alarm
See Doctor Alert
Data Capture (No Alert)
Do Nothing (Ignore Event)
EXD
Cable
Connection
Programmer 6

7. AngelMed GuardianTM EXD
IMD
Wireless Telemetry
max 6ft (1.8m)
Dual purpose device
Alarm notification and control
Programmer “Wand” functions
Two levels of audio & visual alarms
Silence Alarm/Check battery button
Near field / far field (2 meters)
Extensive HF studies and testing
Low battery warning
EXD
Cable
Connection
Programmer 7

8. AngelMed GuardianTM Programmer
EXD
IMD
Cable
Connection
Programmer
Wireless Telemetry
max 6ft (1.8m)
Retrieve electrograms and statistics
Display electrograms, statistics, and histograms
Perform analysis
Program IMD
Integrated printer 8

9. Detection Algorithm – In a Nutshell
Retrieve Intracardiac Electrograms
Hourly Baselines
Averaging
Acquire Baselines
Characterize Electrograms
Effective Baseline
Sampled Electrogram
Current
Sample
Effective Baseline
R-Wave Height
ST Devsample
ST Devbase
Compare Electrogram Sample to Baseline
ST Shift 9

10. 1 Hour After LAD Occlusion
Baseline
1 Hour After LAD Occlusion

11. CardioSaver Study (20 Implants - Brazil)
AngelMed Early Feasibility Studies
CardioSaver Study (20 Implants - Brazil)
DETECT Study (17 Implants - US)
Evaluate the ability to measure intracardiac ST segment shifts from sub-endocardial and transmural ischemia
Test ischemic patients needing a stent
Collect data during stress test and 3-minute coronary occlusion in PCI (balloon and stent placement)
Assess heart rate related and thrombotic ischemic events during follow-up
Evaluate the safety of the Guardian system
Evaluate the AutoPick software for automated ST shift threshold detection
Assess heart rate related and thrombotic ischemic events during follow-up
Two studies complete:
70 patient years of data; >300,000 electrograms downloaded
Safety profile - similar to a single-chamber pacer 11

12. Guardian Alerts In CardioSaver Trial
11/29/07 Emergency Alarms
100
120 90
100 80 80 70 60 60 40
ST Shift % 50 20
BPM 40
Pos ST Shift Threshold 30
-20 20
-40 10
-60
-80
-10
-100
11:00 AM
12:00 PM
1:00 PM
2:00 PM
3:00 PM
4:00 PM
5:00 PM
6:00 PM
7:00 PM
8:00 PM
9:00 PM
10:00 PM
11:00 PM
12:00 AM
1:00 AM
2:00 AM
3:00 AM
4:00 AM
5:00 AM
6:00 AM
7:00 AM
8:00 AM
1st Alarm
2nd Alarm 12

13. Alerting Electrograms vs. Baseline
1st Emergency Alarm
ST Shift 31%
Baseline
2nd Emergency Alarm
ST Shift 31% 13

14. Plaque Rupture Found at Angiography
Plaque Progression Presumed Rupture Site
No Stenosis Noted
April, 2006
November, 2007 14

15. Guardian Alerts In DETECT Study
Baseline Intracardiac Electrogram
Early ST Changes Paramedics ECG 7 AM
Alerting Intracardiac Electrogram
6:42 AM
ST Changes of Inferior and “True” Posterior STEMI (ER 7:20 AM) 15

16. New Stenosis and Likely Plaque Rupture Observed at Angiography
Subtotal LCX Occlusion AM 7/21/08
After Stenting LCX AM 7/21/08
LCX Sept., 2007 16

17. Angelmed Timeline and Update
AngelMed First-in-man Completed in 2007
AngelMed FDA DETECT Feasibility Study Completed in 2009
AngelMed ALERTS 1,000 patient randomized study enrollment completed in June 2013.
AngelMed first FDA Panel was unsuccessful in March 2016
Further Analysis of efficacy endpoints from the ALERTS database is ongoing.
AngelMed is using the PMA amendment process to address the advisory panel’s (and agency’s) concerns regarding the efficacy of the Guardian. The agency has been very helpful during this process, which the sponsor hopes to conclude in 2017. 17

18. Summary/Conclusions
Angelmed GuardianTM – Predicated on the concept that real-time monitoring, and alerting based upon the intracardiac electrogram can detect serious coronary ischemic events and lead to earlier arrival in STEMI, and possibly ACS.
Results/Observations from the Cardiosaver; DETECT and ALERTS clinical studies have demonstrated the ability to detect coronary artery occlusive events.
ALERTS clinical trial (n = 907) demonstrated that patients respond to alarms, with average arrival to ER in < 1 hour. Not approved at FDA Panel.
Further Analysis, of the ALERTS trial data (nearly 3,000 pt. years of monitoring) is being reviewed in collaboration with the FDA.