Reperfusion Strategies for ST elevation MI.

Tom P Stys, FACC, MDMedical Director

Sanford Cardiology

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

1. American Hospital Association Statistics. Available at: www.aha.org/aha/resource-center/Statistics-and-Studies/fast-facts.html. Accessed May 23, 2010.

2. Nallamothu BK, et al. Circulation. 2006;113(9):1189-1195.

STEMI Chain of Survival

Time to Treatment Is Critical in STEMI

Onset of symptoms of

STEMI

9-1-1EMS

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

GOALSPCI

capable

Not PCIcapable

Golden hr = 1st 60 min

Patient Prehospital fibrinolysisEMS-to-needlewithin 30 min

EMS transportEMS-to-balloon within 90 minPatient self-transport Hospital door-to-balloon within 90 min

Dispatch1 min

5 min

8 min

0.4 million discharges per year for STEMI in US

● 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

The Thrombus in STEMISTEMI 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

*RBC = red blood cell.GP IIb-IIIa inhibitors are not indicated for STEMI.Van de Werf F. Thromb Haemost. 1997;78(1):210-213; White HD. Am J Cardiol. 1997;80(4A):2B-10B; Davies MJ. Heart. 2000;83(3):361-366.

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

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.

Goals When Considering a Reperfusion Strategy

• Decrease amount of myocardial necrosis• Preserve LV function• Prevent major adverse cardiac events • Treat life threatening complications

Importance of EarlyReperfusion 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

Reperfusion Recommendations

- STEMI patients presenting to a hospital with PCI capability should be treated with primary PCI within 90 minutes of first medical contact.

I IIIIIa IIb

A

•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 IIIIIa IIb

B

ACC/AHA 2007 STEMI Focused UpdateCirculation 2007; on line, December 10.

Risk StratificationBased on initial

Evaluation, ECG, andCardiac markersSTEMI

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

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 delaysPlan B: thrombolytics (fibrinolytics)

- Pharmacologic means of restoring blood flow •“Clot-busting” drugs

- Less effective- Greater bleeding risk- Widely available at U.S. hospitals

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

STEMI cardiac care • Assessment

- Time since onset of symptoms90 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

Acute Phase Risk Stratification:Importance of LV dysfunction

Killip Classification % patients Mortality (%)

I No CHF 30-50 5

II Rales, S3, Pulmonary venous hypertension 33 15-20

III Pulmonary edema 15 40

IV Cardiogenic shock 10 80-100

Continuing Medical Implementation …...bridging the care gap

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

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

CONTRAINDICATIONS

It is estimated that 20-30% of patients ineligible for

thrombolytic therapy…

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.

Comparison of Approved Fibrinolytic Agents

Streptokinase Alteplase Reteplase Tenecteplase

• Dose 1.5 MU over Up to 100mg in 10U x 2 30-50mg

30-60 min 90 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 50 75 75? 75 rates (%)• TIMI grade 3 flow, % 32 54 60 63

Adapted from Table 15, pg 53.Accessed on August 6, 2004http://www.acc.org/clinical/guidelines/stemi/index.pdf.

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 60-90 min after initiation of therapy• Serial measurements of cardiac biomarkers

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.

Time from Symptom Onset to TreatmentPredicts 1-year Mortality after Primary PCI

The relative risk of 1-year mortality increases by7.5% for each 30-minute delay

De Luca et al, Circulation 2004;109:1223-1225

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

EFFECT OF DOOR-TO-BALLOON TIME ON MORTALITY IN PATIENTS WITH STEMI

8

7

6

5

4

3

2

1

0≤90 >90 - 120 >120 - 150 >150

In-h

ospi

tal M

orta

lity,

%

≤90 >90 - 120 >120 - 150 >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):2180-2186.

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 mortalityRathore SS, et al. BMJ 2009; 339:b1807.Yale University School of Medicine; ACC-NCDR

D2B: PCI Engineering

1. ED physician activates cath laba. Via Field Interpretationb. Via Referral Interpretationc. Via ED Interpretation

2. One call activates the cath lab3. Cath lab team ready in 20-30 minutes4. Prompt data feedback5. Senior management commitment6. Team-based approach

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

Comparing outcomes: PCI vs Lytics

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!

STEMI – Door-to-Balloon and Door-to-Needle Times

Cumulative 12-Month Data from ACTION Registry

ACTION DATA: January 1, 2007 – December 31. 2007 (n=19,523)DTB = 1st door to balloon for primary PCIDTN = Door to needle for lytics

ACTION Median Door-to-Balloon TimesFor 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

57

95

Q4 07

Tim

e (m

in)

50

220210

60708090

110100

120130140150160170

200

180190

240230

96

403020

250

100

79 78 75 74

169 15

8 151

156

Transfer in DTB Times Non-Transfer in DTB Times

Today: The 5 Essential Elements of STEMI System Optimization

R1 RelationshipsR2 RecognitionR3 ReperfusionR4 Real-time data collectionR5 Reassessment & refinement

DateDay of Week

HAR/ Account Number

ST ElevationTransfer

InCardiologist

Emergency Room Doctor

InterventionalistAdmit Time to

1st EKGEKG to Time CCL Notified

CCL Notified to Pt. Arrival

in CCL

CCL Arrival to Arterial Access

Arterial Access to Inflation

Total Time (Admit Time to Inflation)

5/15/2007 Tuesday 4117288 Yes No T. Stys McSherry T. Stys 2 10 4 6 22

Emergency Department to Cath LabIndividual Incident Graph

10 4 62

0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150

4117288

Patie

nt A

ccou

nt N

umbe

r

Time (Measured in Minutes)

Admit Time to 1st EKG EKG to Time CCL Notified CCL Notified to Pt. Arrival in CCL CCL Arrival to Arterial Access Arterial Access to Inflation

*Cardiologist Examined Patient

Admit Time: 1423

*

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

Motor

Blood outlet

Blood Inlet

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

Pressure Lumen

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 Reperfusion @ a STEMI Receiving Facility (PCI Center)!

CARESS-in-AMI: Primary Outcome

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

1970 Cardiology invented EMS

Emergency!Gage & DeSoto

2010 EMS transforming Cardiology

Thank You!