1. Hypothetical Relationship Between Early Reperfusion, Mortality Reduction, and Extent of Myocardial Salvage
100
Mortality Reduction (%)
Critical Time-dependent Period Goal: Myocardial Salvage
Shifts in Potential Outcomes 80 D
Time-independent Period Goal: Open Infarct-related Artery
A-B – No Benefit 60
A-C – Benefit
Mortality Reduction, (%) C
B-C – Benefit
D-B – Harm 40
D-C – Harm 20 B
This slide highlights the importance of early reperfusion in the setting of STEMI. The extent of salvage of myocardium at risk is directly related to the timing of reperfusion. Furthermore, greatest benefits and mortality reduction are achieved when prompt reperfusion, preferably within 3 hours, is achieved. A striking benefit is revealed within this curve as demonstrated in the relationship between early treatment and reduced mortality. The narrowness of the “golden window of opportunity” is also revealed, followed by a continued mortality benefit, which decreases in magnitude over time.
Once again, these benefits are directly related to successful reperfusion of the infarct-related artery with recovery of distal flow. Both pharmacological and mechanical reperfusion modalities provide these benefits, as long as reperfusion is administered promptly and successfully restores coronary flow.
Reference:
Gersh BJ, Stone GW, White HD, Holmes DR Jr. Pharmacological facilitation of primary percutaneous coronary interventions for acute myocardial infarction: is the slope of the curve the shape of the future? JAMA. 2005;293: A
Extent of Salvage (% of area at risk) 4 8 12 16 20 24
Time From Symptom Onset to Reperfusion Therapy (hours)
Gersh BJ, et al. JAMA. 2005;293:

2. The 1 S and the 4 Ds:
Symptoms
Door
Data
Decision
Drug or Device

3. 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: 3

4. 15 Years of National Registry of Myocardial Infarction
30 Minute Reduction in Door to Needle Time
Reduces Mortality by 1%
Gibson CM, AHJ 2008

5. 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

6. Atypical Pain or No Pain is Frequent Among Patients with MI
~30% of AMIs are silent or without typical chest symptoms 1,2
There is a 7.5% relative increase in mortality for every 30 minutes of delay 3
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.
De Luca G, Suryapranata H, Ottervanger JP, Antman EM. Time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: every minute of delay counts. Circulation 2004;109(10): Epub 2004 Mar 8.

7. Guardian Device: An Implantable System To Alarm Patient In The Presence of Ischemia
Connects through lead adapter to a standard IS-1 pacemaker lead from left pectoral site
Checks every 30 to 90 seconds for ST shifts
Internal vibratory alert mechanism
Emergency Alarm – get help now (911)
See Doctor Alert – call now for appointment in next day or two
Electrogram segments stored from last day and detected events
EXD
IMD
Wireless Telemetry
max 6ft (1.8m)
EXD
Cable
Connection
Programmer

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

9. Early Human Testing (21 Patients)
Single RV lead detects ST changes in 20 out of 21 Patients during PCI
Single RV Lead detects ST Segment changes in all three major coronary vessels (LAD, LCX and RCA) as compared with a surface lead
ST Shift changes in an RV lead are much more rapid and acute than surface leads
* Fischell et al, “Potential of an intracardiac electrogram for the rapid detection of coronary artery occlusion”, Cardiovascular Revascularization Medicine, 6 (2005) 14-20

10. Baseline Data Collection
ONCE PER HOUR THE IMD COLLECTS A 10 SECOND BASELINE ELECTROGRAM SEGMENT FOR USE DURING THE NEXT 24 HOURS
R Height
ST Dev
AVERAGE R HEIGHT AND ST DEVIATION ARE COMPUTED FOR UP TO 8 BEATS
AT ANY TIME THE BASELINE DATA USED IS THE AVERAGE OF 24 HOURS OF BASELINE ST DEVIATION AND R HEIGHT DATA
Time
Electrogram
R Height
ST Dev.
Averaging
Effective Baseline
Avg. R Height
Avg.ST DEV
ST SHIFT DETECTION THRESHOLDS ARE A SET PERCENT OF THE AVERAGE BASELINE R HEIGHT (E.G. 25%) FOR EACH OF 5 HEART RATE RANGES

11. Electrocardiogram Processing
10 SECONDS OF ELECTROGRAM DATA ARE CAPTURED EVERY 90 SECONDS, (EVERY 30 SECONDS IF ST SHIFT EXCEEDS HALF OF THE DETECTION THRESHOLD)
10 SECONDS OF ELECTROGRAM DATA ARE CAPTURED EVERY 90 SECONDS, (EVERY 30 SECONDS IF ST SHIFT EXCEEDS HALF OF THE DETECTION THRESHOLD)
ST Dev
ST SHIFT FOR EACH BEAT IS COMPUTED AS THE BEAT’S ST DEVIATION COMPARED TO THE AVERAGE BASELINE ST DEVIATION AS A PERCENT OF THE AVERAGE BASELINE R HEIGHT
6 OUT OF 8 BEATS IN A SEGMENT WITH EXCESSIVE ST SHIFT (MORE THAN THE THRESHOLD) MARK THE SEGMENT AS SHIFTED
3 SEQUENTIAL (AT 30 SEC. INTERVALS) SHIFTED SEGMENTS TRIGGERS AN EMERGENCY ALARM IF THE HEART RATE IS IN THE NORMAL RANGE
EXCESSIVE SHIFT MUST PERSIST FOR 10 MINUTES TO TRIGGER SEE DR. IN ELEVATED RANGE

12. Week Before LCX Stent – HR Related ST Depression Histograms
Normal HR Range bpm
1st Elev. HR Range bpm
2nd Elev. HR Range bpm
3rd Elev. HR Range bpm
4th Elev. HR Range bpm
Week Before LCX Stent – HR Related ST Depression Histograms
MORNING AFTER LCX STENT
AT 8 WEEKS AFTER STENT
HISTOGRAMS NO LONGER SHOW A NEGATIVE SHIFT AT ELEVATED HR

13. The AngelMed Guardian Device
Ischemia Detection from Plaque Rupture With STEMI Dominant LCX
Baseline Intracardiac Electrogram
Early ST Changes Paramedics ECG 7 AM
Alerting Intracardiac Electrogram
ST Changes of Inferior and “True” Posterior STEMI (ER 7:20 AM)

14. The AngelMed Guardian Device
Ischemia Detection from Plaque Rupture With STEMI Dominant LCX
Subtotal LCX Occlusion AM 7/21/08
After Stenting LCX AM 7/21/08
LCX Sept., 2007

15. Patient 03 Ruptured Plaque Event
Patient put on Heparin, Aspirin
& Clopidigrel
Second event clears due to Drugs

16. Patient B3 RCA Ruptured Plaque on Angiography and Ultrasound
April 10, 2006
November 30, 2007
Ruptured Plaque
Lipid Pool

17. Completed Studies
DETECT: US Feasibility study completed 5/08, 2 plaque ruptures detected
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.

18. 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

19. 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