1. Telemedicine To Detect Recurrent MI
C. Michael Gibson, M.S., M.D.
Chief, Clinical Research, Beth Israel Deaconess CV Division
Chairman, PERFUSE Study Group
Senior Trialist TIMI Study Group, Brigham and Women’s Hospital
Chairman of the Board of WikiDoc Foundation,
The World’s Largest Textbook of Medicine with 6,900 Contributors Viewed 150 Million Times Each Year
Harvard Medical
School

2. C. Michael Gibson, MD Consulting: Bristol-Myers Squibb Daiichi Sankyo
Eli Lilly and Company
Portola Pharmaceuticals, Inc.
St. Jude Medical, Inc.
Cytori Therapeutics
The Medicines Company

3. C. Michael Gibson, MD Grant Support:
Bayer Corporation, Angel Medical Systems, Inc., Atrium Medical Corporation, Ikaria, Inc., Lantheus Medical Imaging, Portola Pharmaceuticals, Inc., St. Jude Medical, Inc., Genentech, Inc., Stealth Peptides, Inc., Volcano Therapeutics, Inc, Johnson and Johnson, Walk Vascular, Merck and Company, Inc. and Sanofi-Aventis

4. C. Michael Gibson, MD Honoraria: Merck and Company, Inc.
Regado Bio-Sciences
Baxter International, Inc.
Sanofi-Aventis
Cardiovascular Research Foundation
Consensus Medical Communications

5. Median Time (hrs) Between Symptom Onset and Treatment
2.9
2.8
2.8
2.7
2.7
2.7
In large, randomized trials, the duration of symptoms before reaching the hospital has been fairly constant at 2.7 hours
Median Time (hrs) Between Symptom Onset and Treatment
GUSTO I
90-93
GUSTO III
95-97
InTIME II
97-99
ASSENT II
97-98
GUSTO V
99-01
ASSENT 3
00-01
Gibson CM, Circulation 2001;104: 5

6. Time to Door for Recurrent MI
Having a prior heart attack does not shorten time to presentation for new event
Patient History
Avg. Time to Door
(Hr)
Median Time to Door
Those With First MI
(n=17,602)
3.40**
3.25
Those With Previous MI
(n=2,633)
3.38*
Analysis performed by C. Michael Gibson using TIMI database of 20,235 patients

7. Symptom-to-Balloon Time
Every 30 minute delay increased:
1-year mortality by 7.5%
Risk of pre-discharge EF < 30% by 8.7%
De Luca et al. Circulation. 2004;109:1223-5

8. Time Is Muscle and the Importance of Preserving Muscle
Slide by C. Michael Gibson, M.S., M.D.

9. Atypical Pain or No Pain is Frequent Among Patients with MI
~30% of AMIs are silent or without typical chest symptoms 1,2
Kannel WB . "Silent myocardial ischemia and infarction: insights from the Framingham Study". Cardiol Clin 1986; 4 (4): 583–91.
Davis TM, Fortun P, Mulder J, Davis WA, Bruce DG . "Silent myocardial infarction and its prognosis in a community-based cohort of Type 2 diabetic patients: the Fremantle Diabetes Study". Diabetologia 2004; 47 (3): 395–9.

10. Unrecognized Myocardial Infarction
Study
Patients
# MI
% silent
MRFIT (1987)
12,866
460 25
Framingham (1990)
5070
363 30
CVS (1990)
5888
901 22
Rekjavik (1995-8)
- Men
- Women
9141
13,000
237
641 35 33

11. BARI 2D 2368 pts with angiographically proven CAD
st MIs (12.4% at 5 yrs)
243 - Non-fatal 1st MIs
MI Type
N (%)
3 yr Cardiac Mortality HR
Type I sympt
169 (69.5)
16.1%
8.2
Silent
23 (9.4)
10.7%
4.8
Peri-PCI
51 (21.0)
9.6%
3.4
No MI
2.4% -
Chaitman BR. Circulation. 2009;120:

12. Reinfarction and Mortality in 20,101 patients
Reinfarction was associated with a 2-fold increase in 30-day and 2-year mortality
Gibson CM et al. JACC. 2003;42;7-16

13. Reinfarction and Incident Heart Failure
GUSTO (n = 56,080): Risk of HF 31.9% subjects with reinfarction vs. 13.9% without reinfarction*.
German registry (n = 22,613): Reinfarction associated with 87% increase in relative risk of LVEF < 40%#.
VALIANT trial (n = 10,599): In subjects with known LV dysfunction and/or HF, reinfarction increased the 1-year risk of mortality or new heart failure by > 2-fold¶.
*Hudson et al. Circulation. 2001;104: ; #Donges et al. Am J Cardiol. 2001;87:
¶Thune et al., Eur J Heart Fail. 2011’13:

14. Barriers to Patients Seeking Care for STEMI
Reliance on symptoms:
There can be none
Can be atypical
Can be confused with GI symptoms
Denial
What if, instead of a symptom, there was a sign, or a signal, that was objective and detected true ischemia?

15. Intracardiac ST Segment Deviation: LAD Injury Yields ST Depression+ + +
RV APEX
RV APEX R T R T P P S S Q Q

16. DETECT Patient 5 – Confirmed STEMI
LCX - Sep 2007
LCX - Jul 2008
Baseline Electrogram
Alarm Electrogram
At home
6:30am 21-Jul-08
Intracardiac
Electrogram
ST Changes of Inferior and “True” Posterior STEMI
ECG IN ER 7:20am
External
EKG

17. Symptom to Door Time: First MI vs Second MI
vs In The Presence of An Alarming System
Mean Time: Symptom(?) To Hospital Door (In Minutes)
With Guardian Alarm After First MI
First Heart Attack
After First Heart Attack
240
120 60
90% Reduction
180
195**
At 7.5% improvement per 30 minutes this would mean a 37.5% reduction in mortality
2/3 of our alerts in trial patients occur 9 hours or more before the actual heart attack which will create even greater potential life savings
All of the AngelMed trial patients are still living, having been treated early in spite of more than 15 ruptured plaque clinical events in our implanted population
196**
26.5†
By C. Michael Gibson using TIMI database of 20,235 patients *n= 17,602; **n=2633; Presentation at 2009 HRS meeting; Boston, MA
†Fischell TA, et al. (2010). Initial Clinical Results Using Intracardiac Electrogram Monitoring to Detect and Alert Patients During Coronary Plaque Rupture and Ischemia. JACC;56(14): 17

18. Completed Studies
DETECT: US Feasibility study completed 5/08, 2 plaque ruptures detected
Pivotal protocol approved by FDA 7/08, now enrolling
CardioSaver: Brazilin study completed in Oct. 2007, 2 plaque ruptures detected and no STEMI false positives/negatives with current algorithm.
Median symptom to door time only 19.5 minutes in these two studies.
J Am Coll Cardiol, 2010; 56:

19. Randomization at 7-14 Day visit
ALERT AMI
PI: CM Gibson
Co-PI: D Holmes
3,000 acute coronary syndrome patients with either: Diabetes (Type I or Type II), compromised renal function (Cr > 1.2 mg/dl or creatinine clearance less than 50), or TIMI Risk Score > 3
Implant
7-14 Day Follow-Up
Alerts turned ON
1 Month Follow-Up
Alerts remain ON
3 Month Follow-Up
6 Month Follow-Up
Alerts turned OFF
Alerts remain OFF
At 14 days ETT performed to max heart rate to train device re anticipated ST deviation at different heart rate bins
Randomization at 7-14 Day visit
Primary Endpoint: Cardiac or unexplained death, new Q-wave MI, time to door > 2 hours for a thrombotic coronary occlusion event

20. Conclusions Time is muscle
Greatest improvements in salvage are when improvements in delivery of care are made during the earliest phase of symptoms
Improvements in door to data, and decision to drug/device times have improved outcomes
Symptom to door and data to decision times are two targets for further improvements in the timely delivery of STEMI care