1. Reperfusion Strategies for ST elevation MI.
Tom P Stys, FACC, MD
Medical Director
Sanford Cardiology

2. ACS and Rural Hospitals
4897 community hospitals in the United States1
2900 are located in urban areas1
1997 are located in rural areas1
Although primary PCI is often the preferred strategy for STEMI, only about 25% of US hospitals are capable of performing PCI2
Non–PCI-capable institutions are often located in rural areas and face challenges related to their distance from PCI centers
Almost 60% of US adults live in an area where a non–PCI-capable institution is their closest hospital2
Guideline-based multidisciplinary care and coordinated transfer protocols are important for best outcomes
American Hospital Association Statistics. Available at: Accessed May 23, 2010.
Nallamothu BK, et al. Circulation. 2006;113(9):

3. STEMI Chain of Survival
Mission: Lifeline ultimately hopes to fix the broken chain of STEMI systems.
[NOTE TO PRESENTER: The below is taken from the 2008 AHA STEMI Provider Manual]
Reducing the time from onset of symptoms to establishment of coronary artery patency in STEMI is critical and embodies the concept “time is muscle.” The links in the STEMI chain of survival can be divided into four components:
Time from symptom onset until patient recognition and decision to seek medical help;
EMS activation, evaluation, treatment and transport;
ED evaluation and initiation of a reperfusion strategy; and
Pharmacologic or mechanical reperfusion therapy.

4. Onset of symptoms of STEMI Total ischemic time: within 120 min
Time to Treatment Is Critical in STEMI
0.4 million discharges per year for STEMI in US
Onset of symptoms of STEMI
9-1-1
EMS
dispatch
EMS on-scene
Encourage 12-lead ECGs
Consider prehospital fibrinolytic if capable and EMS-to-needle within 30 min
Total ischemic time: within 120 min
EMS Transport
GOALS
PCI
capable
Not PCI
Golden hr = 1st 60 min
Call 9-1-1
Call fast
Patient
Prehospital fibrinolysis
EMS-to-needle
within 30 min
EMS transport
EMS-to-balloon within 90 min
Patient self-transport
Hospital door-to-balloon
within 90 min
Dispatch
1 min 5
min 8
Time to reperfusion is a critical determinant of the extent of myocardial damage and clinical outcomes in patients with STEMI
Key factors in STEMI care are rapid, accurate diagnosis and keeping the encounter time to reperfusion as short as possible

5. The Thrombus in STEMI
STEMI is generally caused by a completely occlusive fibrin-rich thrombus in a coronary artery
Results from stabilization by fibrin mesh of a platelet aggregate at site of plaque rupture
The photograph on the left shows complete thrombotic occlusion of a coronary artery, which manifests clinically as a STEMI. The completely occlusive thrombus consists of a platelet-rich core (formed by platelet aggregation) and a superimposed network, or mesh, of cross-linked fibrin molecules (formed by activity of the coagulation cascade) and entrapped red blood cells. On the right, the drawing of a clot shows a fibrin mesh formed by bonds between activated platelets and fibrinogen. Trapped inside are red blood cells. In STEMI patients, > 90% of the culprit vessel is occluded by the thrombus.
Note: GP IIb-IIIa inhibitors are not indicated for STEMI.
Van de Werf F. Thromb Haemost. 1997;78(1): ; White HD. Am J Cardiol. 1997;80(4A): 2B-10B; Davies MJ. Heart. 2000;83(3):
*RBC = red blood cell.
GP IIb-IIIa inhibitors are not indicated for STEMI.
Van de Werf F. Thromb Haemost. 1997;78(1): ; White HD. Am J Cardiol. 1997;80(4A):2B-10B; Davies MJ. Heart. 2000;83(3):

6. Achieve Coronary Patency
Initial Reperfusion Therapy
- Defined as the initial strategy employed to restore blood flow to the occluded coronary artery
3 Major Options:
Pharmacological Reperfusion
PCI
Acute Surgical Reperfusion
Because of the pathophysiology of STEMI (thrombus occluding the coronary artery), we must act quickly to achieve coronary patency by offering those eligible, a reperfusion therapy. Review definition of an initial reperfusion strategy listed on slide. The 3 major listings for reperfusion are pharmacological reperfusion, PCI, and acute surgical reperfusion.
Initial reperfusion therapy identifies the three processes currently practiced for achieving coronary patency. The efficacy and considerations for each will be discussed in greater detail in the following slides.
Several randomized trials are now being conducted to answer the question of safety and efficacy when combining various reperfusion strategies (i.e.., fibrinolysis and PPCI; ½ dose fibrinolysis GP IIb-IIIa + PPCI). These various strategies are still considered investigational.
Class I All patients should undergo rapid evaluation for reperfusion therapy & have a reperfusion strategy implemented promptly after contact with the medical system
Antman et al. JACC 2004;44:680.

7. Goals When Considering a Reperfusion Strategy
Decrease amount of myocardial necrosis
Preserve LV function
Prevent major adverse cardiac events
Treat life threatening complications

8. Importance of Early Reperfusion Therapy in STEMI
Outcomes Dependent Upon:
Time to treatment-TIME IS STILL MUSCLE
Early and full restoration in coronary blood flow
Sustained restoration of flow
Rapid evaluation of a patient presenting with suspected STEMI is critical. The next section will cover the importance of early reperfusion therapy.
When a patient presents with STEMI/new LBBB initiating reperfusion therapy quickly is critical.
Currently, two forms of reperfusion therapies meet the standards of care listed in the ACC/AHA guidelines for care of the patient experiencing STEMI. Both fibrinolytic therapy for eligible patients and primary percutaneous coronary intervention (PCI) are recommended forms of reperfusion therapy Class IA (Exec Summary, 2004). Surgical reperfusion is used with failed PCI with persistent pain or hemodynamic instability in patients with coronary anatomy suitable for surgery.
“Both forms of therapy are dependent on time to treatment issues and early and full restoration of blood flow. Evidence exists that expeditious restoration of flow in the obstructed infarct artery after the onset of symptoms in STEMI pts is a key determinant of short- and–long term outcomes regardless of whether reperfusion is accomplished by fibrinolytics or PCI” (p.10, Exec summary, 2004).
This next section reviews the recommendations for an aggressive attempt to minimize the time from entry into the medical system to implementation of a reperfusion strategy using the concept of medical system goals.
Let’s review the Committee’s recommendations for Reperfusion in the next few slides.

9. Reperfusion Recommendations
III
IIa
IIb A
- STEMI patients presenting to a hospital with PCI capability should be treated with primary PCI within 90 minutes of first medical contact.
STEMI patients presenting to a hospital without PCI capability and who cannot be transferred to a PCI center for intervention within 90 minutes of first medical contact should be treated with fibrinolytic therapy within 30 minutes of hospital presentation, unless contraindicated. I
III
IIa
IIb B
This slide lists the new updated ACC/AHA 2007 STEMI Reperfusion Recommendations.
ACC/AHA 2007 STEMI Focused Update
Circulation 2007; on line, December 10.

10. Risk Stratification STEMI Patient? UA or NSTEMI
Based on initial
Evaluation, ECG, and
Cardiac markers
STEMI
Patient?
YES NO
- Assess for reperfusion
- Select & implement reperfusion therapy
- Directed medical therapy
UA or NSTEMI
- Evaluate for Invasive vs. conservative treatment
- Directed medical therapy

11. Choices: Reperfusion Strategies for STEMI
Plan A: percutaneous coronary intervention (primary PCI)
-Mechanical means of restoring blood flow
Balloon angioplasty
Stents
- More effective
- Lower bleeding risk
- Available at only 25% of U.S. hospitals
Treatment delays
Plan B: thrombolytics (fibrinolytics)
- Pharmacologic means of restoring blood flow
“Clot-busting” drugs
- Less effective
- Greater bleeding risk
- Widely available at U.S. hospitals
The ACC/AHA STEMI guidelines support two forms of reperfusion:
Plan A
The preferred reperfusion strategy for STEMI is the mechanical means of restoring blood flow to the coronary artery by primary percutaneous coronary intervention (PCI) including balloon angioplasty and, in most cases, the placement of intracoronary stents. This requires specialized invasive cardiac catheterization labs, interventional cardiologists, and trained cardiac catheterization staff. Primary PCI is preferred because it is more effective than pharmacological reperfusion and has a lower bleeding risk. In the United States, approximately 25% of acute care facilities can perform primary PCI but may not have the capability of providing the service at all hours of the day. Currently, there are considerable treatment delays for patients presenting to centers that do not have primary PCI capability.
Plan B
When patients cannot get to primary PCI within guideline goal times by EMS or transfer, pharmacological reperfusion with “clot-busting” drugs (fibrinolytics or thrombolytics) remains a strategy for restoring blood flow. It is less effective and has a greater bleeding risk. Use of fibrinolysis is widely available in U.S. hospitals as it is given intravenously.

12. STEMI cardiac care Determine preferred reperfusion strategy
Fibrinolysis preferred if:
<3 hours from onset
PCI not available/delayed
door to balloon > 90min
door to balloon minus door to needle > 1hr
Door to needle goal <30min
No contraindications
PCI preferred if:
PCI available
Door to balloon < 90min
Door to balloon minus door to needle < 1hr
Fibrinolysis contraindications
Late Presentation > 3 hr
High risk STEMI
Killup 3 or higher
STEMI dx in doubt

13. STEMI cardiac care Assessment - Is this high risk STEMI?
- Time since onset of symptoms
90 min for PCI / 12 hours for fibrinolysis
- Is this high risk STEMI?
- KILLIP classification
- If higher risk may manage with more invasive rx
- Determine if fibrinolysis candidate
- Meets criteria with no contraindications
- Determine if PCI candidate
- Based on availability and time to balloon rx

14. Acute Phase Risk Stratification: Importance of LV dysfunction
Continuing Medical Implementation …...bridging the care gap

15. Fibrinolysis indications
ST segment elevation >1mm in two contiguous leads
New LBBB
Symptoms consistent with ischemia
Symptom onset less than 12 hrs prior to presentation

16. Absolute contraindications for fibrinolysis therapy in patients with acute STEMI
Any prior ICH
Known structural cerebral vascular lesion (e.g., AVM)
Known malignant intracranial neoplasm (primary or metastatic)
Ischemic stroke within 3 months EXCEPT acute ischemic stroke within 3 hours
Suspected aortic dissection
Active bleeding or bleeding diathesis (excluding menses)
Significant closed-head or facial trauma within 3 months

17. CONTRAINDICATIONS
It is estimated that 20-30% of patients ineligible for thrombolytic therapy…

18. Which Lytic Agent? EFFICACY
Benefit first demonstrated w/ streptokinase (GISSI-2 and ISIS-2 trials). ISIS-2 showed combination of ASA and streptokinase reduced mortality from 10.2% (placebo) to 7.2%.
GUSTO-I: alteplase superior to streptokinase (although more expensive)
ASSENT-2 and GUSTO-III: newer agents like tenecteplase, reteplase, lanoteplase as effective as alteplase but have significantly lower incidence of noncerebral bleeding complications and need for transfusion.

19. Comparison of Approved Fibrinolytic Agents
Streptokinase Alteplase Reteplase Tenecteplase
Dose MU over Up to 100mg in U x mg
30-60 min min (wt-based) each over 2 min based on weight
Bolus Admin No No Yes Yes
Antigenic Yes No No No
Allergic React Yes No No No
Systemic Marked Mild Moderate Minimal
Fibrinogen Depletion
~90-min patency ? 75
rates (%)
TIMI grade 3 flow, %
The section covering the comparison of approved fibrinolytic agents has a table summarizing the key characteristics of the agents. Full Text, pg 58
Error on web version full text noted- reteplase has a better than ‘7’ 90-minute patency rate.
This scan is from the actual guidelines.
Adapted from Table 15, pg 53.Accessed on August 6, 2004

20. Assessment of response …
Relief of symptoms
Maintenance or restoration of hemodynamic and/or electrical stability
Reduction of at least 50% of initial ST segment injury pattern on a follow-up EKG min after initiation of therapy
Serial measurements of cardiac biomarkers

21. Long-term survival…
Long-term benefit primarily seen in patients who achieved TIMI 3 flow w/ lytic administration. Vessel opening (TIMI 2 or 3) reported in 60-87% of patients receiving lytics, but normalization (TIMI 3) in only 50-60% of arteries. Only TIMI 3 flow associated with improved LV function and survival.
***Note: TIMI 3 flow is achieved in ~90% of patients treated with primary PCI.

22. Time from Symptom Onset to Treatment Predicts 1-year Mortality after Primary PCI
A recent publication from the Zwolle group in the Netherlands looked at the
relationship between ischemic time and 1-year mortality assessed as a continuous function and plotted with a quadratic regression model. The dotted lines represent 95% CIs of predicted mortality.
Circulation. 2004;109:
About the study:
“The study population consisted of 1791 patients with STEMI treated by primary angioplasty. The relationship between ischemic time and 1-year mortality was assessed as a continuous function and plotted with a quadratic regression model. The Cox proportional hazards regression model was used to calculate relative risks (for each 30 minutes of delay), adjusted for baseline characteristics related to ischemic time. Variables related to time to treatment were age 70 years (P ), female gender (P-0.004), presence of diabetes mellitus (P-0.002), and previous revascularization (P-0.035). Patients with successful reperfusion had a significantly shorter ischemic time (P-0.006). A total of 103 patients (5.8%) had died at 1-year follow-up. After adjustment for age, gender, diabetes, and previous revascularization, each 30 minutes of delay was associated with a relative risk for 1-year mortality of (95% CI to 1.15; P_0.041). Conclusions—These results suggest that every minute of delay in primary angioplasty for STEMI affects 1-year mortality, even after adjustment for baseline characteristics. Therefore, all efforts should be made to shorten the total ischemic time, not only for thrombolytic therapy but also for primary angioplasty”. Actual abstract, pg 1123
The relative risk of 1-year mortality increases by
7.5% for each 30-minute delay
De Luca et al, Circulation 2004;109:

23. 2009 ACC/AHA STEMI/PCI Guidelines Focused Updates
Triage and Transfer for PCI (for STEMI)
New Recommendation B
It is reasonable to transfer high- risk patients who receive fibrinolytic therapy as primary reperfusion therapy at a non– PCI-capable facility to a PCI- capable facility as soon as possible where PCI can be performed either when needed or as a pharmacoinvasive strategy

24. In-hospital Mortality, %
EFFECT OF DOOR-TO-BALLOON TIME ON MORTALITY IN PATIENTS WITH STEMI 8 7 6 5 4 3 2 1
≤90
>
>
>150
In-hospital Mortality, %
Investigators conducted a cohort study of 29,222 STEMI patients treated with PCI within 6 hours of presentation at 395 hospitals that participated in the National Registry of Myocardial Infarction (NRMI)-3 and -4 from 1999 to 2002.
As shown on the slide, longer door-to-balloon (DTB) time was associated with increased in-hospital mortality (mortality rate of 3.0%, 4.2%, 5.7%, and 7.4% for DTB times of ≤90 minutes, 91 to 120 minutes, 121 to 150 minutes, and >150 minutes, respectively (P for trend <.01).
Adjusted for patient characteristics, patients with DTB >90 minutes had increased mortality (odds ratio, 1.42; 95% CI, ) compared with those who had DTB ≤90 minutes.
In subgroup analyses, increasing mortality with increasing DTB time was seen regardless of symptom onset-to-door time (≤1 hour, >1 to 2 hours, >2 hours) and regardless of the presence or absence of high-risk factors.
≤90
>
>
>150
Door-to-Balloon Time (min)
In-hospital mortality and door-to-balloon time; P for trend <.001.
Reproduced with permission from McNamara RL, et al. J Am Coll Cardiol. 2006;47(11):

25. Estimated in-hospital mortality by door-to-balloon times
Time (min)
Adjusted mortality* 15
2.9 (2.8–3.1) 30
3.0 (2.9–3.2) 60
3.5 (3.4–3.6) 90
4.3 (4.2-–4.4)
120
5.6 (5.4–5.7)
180
8.4 (8.2–8.7)
240
10.3 (10.0–10.7)
*Adjusted for age, sex, race, findings on presentation, medical history, procedural characteristics, angiographic findings, and hospital factors
No “floor” to the mortality reduction that can be achieved by reducing time to treatment
Any delay in D2B time associated with increased in-hospital mortality
Rathore SS, et al. BMJ 2009; 339:b1807.
Yale University School of Medicine; ACC-NCDR

26. D2B: PCI Engineering ED physician activates cath lab
Via Field Interpretation
Via Referral Interpretation
Via ED Interpretation
2. One call activates the cath lab
3. Cath lab team ready in minutes
4. Prompt data feedback
5. Senior management commitment
6. Team-based approach

27. PCI after thrombolytics???
This issue remains unresolved…
3 possible scenarios…
*Facilitated PCI—lytic drug given prior to planned PCI in attempt to achieve an open infarct-related artery before arrival of cath lab
*Adjunctive PCI—PCI performed within hours after thrombolysis
*Early elective PCI—PCI performed within a few days after thrombolysis

28. Comparing outcomes: PCI vs Lytics

29. The Golden Rule: Once a STEMI is Identified it Must Trigger a Clear Response Downstream!
Rapid Recognition of STEMI on ECG will only improve the process IF Recognition leads to a concrete action occurring downstream
Recognition allows early Reperfusion… but does not guarantee it!

30. STEMI – Door-to-Balloon and Door-to-Needle Times Cumulative 12-Month Data from ACTION Registry
Please note the time to treatment goals in the most recent cumulative report from the ACTION-GWTG database leave us short of our guideline goals. Most concerning are patients presenting to non-PCI centers and transferring for primary PCI. Only 7% made first door-to-balloon time (DTB) in less than 90 minutes.
ACTION DATA: January 1, 2007 – December (n=19,523)
DTB = 1st door to balloon for primary PCI
DTN = Door to needle for lytics

31. ACTION Median Door-to-Balloon Times For Transfer In & Non-Transfer In Patients
123
236 62
103
Q1 07
120
223 60
102
Q2 07
116
215 57
Q3 07
113
212 95
Q4 07
Time (min) 50
220
210 70 80 90
110
100
130
140
150
160
170
200
180
190
240
230 96 40 30 20
250 10 79 78 75 74
169
158
151
156
This graphic depicts that while we are watching a decline in primary PCI D2B times, the transfer-in patient 1st DTB times are fairly static.
Transfer in DTB Times
Non-Transfer in DTB Times

32. Today: The 5 Essential Elements of STEMI System Optimization
R1 Relationships
R2 Recognition
R3 Reperfusion
R4 Real-time data collection
R5 Reassessment & refinement

34. What we should do about STEMI Cardiogenic Shock
Emergency angiography and revascularisation: Primary PCI preferably
- All patients <75 years
- Selected patients ≥75 years
On-table echo to rule out mechanical defects
Stabilise the patient in the lab before revascularisation
- IABP
- Pressors if required (Norepinephrine/dopamine)
- Anaesthetic support
Consider calling the surgeon for true surgical disease
PCI culprit artery. Other vessels if shock persists
Use abciximab for PCI
Consider percutaneous LVAD if shock persists with IABP + multi-vessel revascularisation

35. Cardiogenic Shock: Impella
Axial flow pump
Much simpler to use
Increases cardiac output & unloads LV
LP 2.5
- 12 F percutaneous approach; Maximum 2.5 L flow
LP 5.0
- 21 F surgical cut down; Maximum 5L flow
Cost: 3-5K
Motor
Blood outlet
Blood Inlet
Pressure Lumen

36. STEMI 2012: “60 is the New 90”
<30 Minutes : First Medical Contact (Recognition) to Thrombolytic administration
<90 Minutes : First Medical Contact to on-site PCI (AHA/ACC recs) ?????
<90 Minutes : First Medical Contact followed by inter-facility transfer to a PCI-capable facility
***BUT realistically <60 Minutes should be the goal for Contact/Recognition to a STEMI Receiving Facility (PCI Center)!
Although AHA/ACC guidelines and science support 90 minute first medical contact to balloon time, if the facilities can complete the PCI time in less than 60 minutes to allow the prehospital/EMS patient a less than 90 minute FMC to reperfusion time, then the PCI facilities should be compelled to do the same for the patients who directly present.

37. CARESS-in-AMI: Primary Outcome
To assess the best subsequent management of patients after thrombolytic therapy, investigators randomized 600 STEMI patients 75 years or younger with 1 or more high-risk features (extensive ST-segment elevation, new-onset left bundle branch block, previous MI, Killip class >2, or left ventricular ejection fraction ≤35%) who were treated with thrombolysis and abciximab at a non-PCI hospital to immediate transfer for PCI or to standard medical therapy with transfer for rescue PCI if needed.
The primary outcome was a composite of death, reinfarction, or refractory ischemia at 30 days.
Of the 299 patients assigned to immediate PCI, 289 (97.0%) underwent angiography, and 255 (85.6%) received PCI. Rescue PCI was performed in 91 patients (30.3%) in the standard care/rescue PCI group.
The primary outcome occurred in 13 patients (4.4%) in the immediate-PCI group compared with 32 (10.7%) in the standard care/rescue PCI group (HR, 0.40; 95% CI, ; log rank P=.004).
There was no significant difference in the rate of major bleeding at 30 days (3.4% vs 2.3%; P=.47) or stroke (0.7% vs 1.3%; P=.50) in the immediate-PCI group versus the standard care/rescue PCI group.
High-risk STEMI patients treated at non-PCI hospitals with a preparatory pharmacologic strategy of half-dose fibrinolytic therapy, abciximab, heparin, and aspirin have improved outcomes when transferred immediately to a PCI facility rather than continuing medical therapy with transfer for rescue PCI only if there is evidence of failed reperfusion.

38. Barriers to Timely Reperfusion
The patient
- Failure to promptly recognize symptoms
- Hesitation to seek medical attention
Time to transport
- Mandated delivery to the closest hospital, regardless of PCI capabilities
- Long transport in rural areas
Decision process on arrival
- Clot-busting drugs vs. PCI
- Off hours
- Transfer to PCI facility
Time to implement treatment strategy
- Procedural factors
- Team assembly
There are many barriers to timely reperfusion that require careful consideration and practical solutions by multidisciplinary system teams.
There are four main barriers to patients getting to the appropriate care.
1. The patient often fails to promptly recognize heart attack symptoms and call Despite many public awareness trials and public health initiatives, there is hesitation to seek medical attention -- STEMI patients have, on average, 2 hours of symptoms before arriving to a hospital. 50% of STEMI patients call for their symptoms. The other 50% self transport or have someone else drive them to the emergency department.
Time to transport – Local policies often mandate that ambulances must be routed to the nearest hospital – regardless if the hospital has the capability to perform PCI AND/OR patients in rural areas cannot get to a hospital with PCI in the recommended timeframe.
Decision on reperfusion strategy – If a STEMI patient arrives at a primary PCI center, the decision regarding the reperfusion strategy is an easy one – primary PCI. Only the issue of timeliness in off hours or simultaneous STEMIs with one team available remains problematic. Commitment to primary PCI at interventional capable hospitals is paramount. However, the decision process on arrival of the STEMI patient for reperfusion in a hospital without PCI needs to be predetermined. The hospital staff must decide if the STEMI patient will have timely transfer to a facility that provides primary PCI or be given fibrinolytics. In addition, in rural situations, STEMI patients that are fibrinolytic ineligible need urgent transfer, and use of medical air rescue should be considered.
Time to implement treatment strategy – Cardiac catheterization lab teams time for assembly and procedural issues can also pose additional issues for the STEMI patient.

39. 1970  Cardiology invented EMS
Emergency!
Gage & DeSoto
2010  EMS transforming Cardiology

40. Thank You!