ST Segment Elevation Myocardial Infarction

Elliott Antman, MD Cardiovascular Division

May 1, 2013

Disclosure

Accumetrics, Inc. Amgen, Inc. AstraZeneca Pharmaceuticals LP Baxter Bayer Healthcare LLC Beckman Coulter, Inc. Biosite Incorporated Bristol-Myers Squibb CardioKinetix CV Therapeutics, Inc. Daiichi-Sankyo Eli Lilly and Company FoldRx GlaxoSmithKline INO Therapeutics LLC Inotek Pharmaceuticals Corporation

The National Institutes of Health Integrated Therapeutics Corporation KAI Pharmaceuticals Merck & Co., Inc. Millennium Pharmaceuticals, Inc. Novartis Pharmaceuticals Nuvelo, Inc. Ortho-Clinical Diagnostics, Inc. Pfizer, Inc. Roche Diagnostics Corporation Roche Diagnostics GmbH Sanofi-Aventis Sanofi-Synthelabo Recherche Schering-Plough Research Institute St Jude Medical

The TIMI Study Group has received research / grant support in the past 2 yrs through the Brigham & Women’s Hospital with funding from (in alphabetical order):

127:e6-e245,2013

127:e362-425,2013

2013 STEMI GL

MI

NSTEMI

STEMI

Steiner C HCUP Projections Report # 2012-02.

Life’s Simple Seven

http://mylifecheck.heart.org

Time and Myocardial Salvage: An Essential Fact Regardless of Mode of Reperfusion

0

20

40

60

80

100

1 3 6 12 24 Hours

Mor

talit

y R

educ

tion

(%)

Extent of salvage (% of area at risk)

Time to treatment is critical Opening the artery is the primary goal (PCI > lysis)

Gersh BJ, et al. JAMA. 2005;293:979.

Checklist to Improve Door-Device Time

2013 STEMI GL

Door To Balloon Time and Mortality

NCDR---43,801 pts with STEMI In-Hospital Mortality after Prim PCI

Rathore BMJ 338: b1807,2009

Regional Systems of STEMI Care, Reperfusion Therapy, and Time-to-

Treatment Goals

All communities should create and maintain a regional system of STEMI care that includes assessment and continuous quality improvement of EMS and hospital-based activities. Performance can be facilitated by participating in programs such as Mission: Lifeline and the D2B Alliance.

I IIa IIb III

Performance of a 12-lead ECG by EMS personnel at the site of FMC is recommended in patients with symptoms consistent with STEMI.

I IIa IIb III

2013 STEMI GL

260 systems

Cardiac

Reperfusion Therapy for Patients with STEMI

2013 STEMI GL

Vascular Access

1. Fewer Major Vascular Access Complications

2. Similar Efficacy

3. Operator/Volume Dependent

Radial

Prothrombin Thrombin

Xa

V, Ca ++

.

FGN

Plt

Acute Rx

IRA Non IRA

Prothrombin Thrombin

Xa

X TF/VIIa

V, Ca2+

Xa inhibitors LMWH UFH

LMWH UFH DTIs

WARFARIN

ASA P2Y12 inhib.

IV GP IIb/IIIa Inhibitor

Anticoagulant Scorecard UFH ENOX FONDA BIVAL

Route IV (SC) IV, SC SC (IV) IV

Monitor aPTT, ACT

No No aPTT, ACT

UA/NSTEMI Yes Yes Yes Yes

STEMI Yes Yes Yes Yes

Bleeding Yes Yes Less ? Less

PCI Yes Yes Need anti IIa Rx

Yes

CABG Yes No No Possible

Antidote Protamine Protamine None None

Antiplatelet Scorecard Clopidogrel Prasugrel Ticagrelor

Route PO PO PO

Monitor Uncertain Not Necessary

Dose LD,MD 600 / 75 mg 60/10 mg 180 / 90 mg BID

UA/NSTEMI Yes Yes Yes

STEMI Yes PCI PCI

Bleeding Yes Yes Yes

PCI DAPT with ASA

DC for CABG 5-7 days 7-10 days ? 2-3 days

Issues Irreversible Variable Resp.

Irreversible 5 mg MD ?

Reversible (Compliance)

Evolution of PCI for STEMI

Balloon Antiplatelet Rx

Stent

DES

GP IIb/IIIa Inhibitor

ASA P2Y12 inhib.

Thrombus Removal;

Embolization Protection

Devices Antman + Van de Werf Circ 109:2480,2004

I IIa IIb III

2013 STEMI GL

Use of Stents in Patients With STEMI

Placement of a stent (BMS or DES) is useful in primary PCI for patients with STEMI.

I IIa IIb III

BMS should be used in patients with high bleeding risk, inability to comply with 1 year of DAPT, or anticipated invasive or surgical procedures in next year.

I IIa IIb III

DES should not be used in primary PCI for patients with STEMI who are unable to tolerate or comply with a prolonged course of DAPT because of the increased risk of stent thrombosis with premature discontinuation of one or both agents.

I IIa IIb III

Harm

2013 STEMI GL

GP IIbIIIa Therapy to Support Primary PCI for STEMI

It is reasonable to start treatment with an intravenous GP IIb/IIIa receptor antagonist at the time of primary PCI (with or without stenting or clopidogrel pretreatment) in selected patients with STEMI who are receiving UFH.

• Double-bolus eptifibatide: 180 mcg/kg IV bolus, then 2 mcg/kg/min; a 2nd 180-mcg/kg bolus is administered 10 min after the 1st bolus.

• Abciximab: 0.25 mg/kg IV bolus, then 0.125 mcg/kg/min (maximum 10 mcg/min); or

• High-bolus-dose tirofiban: 25 mcg/kg IV bolus, then 0.15 mcg/kg/min; or

I IIa IIb III

I IIa IIb III

I IIa IIb III

2013 STEMI GL

Primary PCI in STEMI

2013 STEMI GL

Coronary Angiography in Patients Who Were Managed With Fibrinolytic Therapy or Who

Did Not Receive Reperfusion Therapy

*Although individual circumstances will vary, clinical stability is defined by the absence of low output, hypotension, persistent tachycardia, apparent shock, high-grade ventricular or symptomatic supraventricular tachyarrhythmias, and spontaneous recurrent ischemia.

2013 STEMI GL

PCI of an Infarct Artery in Patients Who Were Managed With Fibrinolytic Therapy or Who Did Not Receive

Reperfusion Therapy

*Although individual circumstances will vary, clinical stability is defined by the absence of low output, hypotension, persistent tachycardia, apparent shock, high-grade ventricular or symptomatic supraventricular tachyarrhythmias, and spontaneous recurrent ischemia.

2013 STEMI GL

Beta-Blockers

Oral beta-blockers should be initiated within 1st 24 h for pts without contraindications

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

It is reasonable to administer intravenous beta blockers at presentation for hypertension to pts without contraindications

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

Containdications: 1) signs of HF 2) evidence of a low-output state, 3) increased risk for cardiogenic shock (Age >70,SBP < 120, HR> 110 or < 60, prolonged time from onset of symptoms) 4) other relative contraindications (PR > 0.24 s, 2nd or 3rd degree heart block, active asthma, or reactive airway disease).

Patients w initial contraindications to use of beta blockers in first 24 h should be reevaluated to determine subsequent eligibilty

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

2013 STEMI GL

“Warning Arrhythmias”

(From Antman EM, Rutherford JD: Coronary Care Medicine. Boston, Martinus Nijhoff Publishing, 1986)

K 4.5 Mg 2.0

Combined Conduction Defects

Anterior MI with RBBB, LAFB

Temporary Pacing Systems Transvenous External Noninvasive

Primary Prevention of SCD ICD Implantation After STEMI

At Least 40 days After STEMI; No Spontaneous VT or VF 48 hours post-STEMI

Assess LVEF and NYHA Functional Status

No ICD

LVEF > 40%

ICD

LVEF < 30-40% NHYA Class II-III

LVEF < 30-35% NHYA Class I

All-Cause Mortality

Years

Pro

babi

lity

of E

vent

0

0.05

0.1

0.15

0.2

0.25

0.3

0 1 2 3

0.35

0.4

4

ACE-I

Placebo

ACE-I 2995 2250 1617 892 223 Placebo 2971 2184 1521 853 138

Flather MD, et al. Lancet. 2000;355:1575–1581

OR: 0.74 (0.66–0.83)

ACE-I: 702/2995 (23.4%)

Placebo: 866/2971 (29.1%)

TRACE Echocardiographic EF ≤ 35%

AIRE Clinical and/or radiographic signs of HF

SAVE Radionuclide EF ≤ 40%

4

ARB if ACEI intolerant

Aldo Antagonist if on ACEI / BB w DM, HF, or EF

< .40

NEJM 2003;348:1309

NEJM2003;349:1893

Management of LV Dysfunction

• General Ventilation Correct Acidosis Anticoagulation

• Pharmacologic Support Inotropes Vasopressors Vasodilators

• Revascularization

• Mechanical Support

Right Ventricular Infarction Clinical findings:

Shock with clear lungs, elev JVP Kussmaul sign

Hemodynamics: Increased RA pressure (y descent) Square root sign in RV tracing

ECG: ST elev in R sided leads

Echo: Depressed RV function

Rx: Maintain RV preload Lower RV afterload (PA---PCW) Inotropic support Reperfusion

V4R Wellens NEJM 340: 381,1999

Ventricular Septal Rupture

Mitral Regurgitation (Pap. M. dysfunction)

Incidence 1-2% 1-6% 1-2% Timing 3-5 d p MI 3-6 d p MI 3-5 d p MI Phy Exam murmur 90% JVD, EMD murmur 50% Thrill Common No Rare Echo Shunt Peric. Effusion Regurg. Jet PA cath O2 step up Diast Press Equal. c-v wave in PCW

Images:Courtesy of W D Edwards (Mayo Foundation) Data: Lavocitz CV Rev Rpt 5:948,1984; Birnbaum NEJM 347:1426 ,2002

Free Wall Rupture

Aneurysm Formation after STEMI

From Shah PK “ Complications of acute MI” In Cardiology (Parmley et al 1987)

Regeneration of the Myocardium

Source

Endpoint(s) of Trial

Preparation

Timing

Delivery System

Duration of Followup

Enhancement Strategies

Dimmeler Circ 121:325, 2010

Myoblasts

Bone-Marrow Derived Cells

Mesenchymal Stem Cells

Cardiac Progenitor

Clinical Trials of Cardiac Regeneration

Siu + Tse Lancet 379:870, 2012

Dimmeler AHA 2012

SCIPIO

Absolute Change in EF

% Change in Viable Tissue in Infarct Region by CMR

12 Month Data: Lancet 2011;378:1847 24 Month Data: R. Bolli AHA 2012

SCIPIO

Change in NYHA Score

Change in Minnesota HF Score

12 Month Data: Lancet 2011;378:1847 24 Month Data: R. Bolli AHA 2012

Δ Scar Mass (g) 12 mos.

CADUCEUS

Δ Viable Mass (g) 12 mos.

Systolic Wall Thickening (%)

6 mos.

Makkar RR et al Lancet 379: 895, 2012

All bars represent +/- 1 SEM

Controls CDCs

-20

-10

0

10

20

p = 0.02

-30

-15

0

15

30

p = 0.001

0

20

40

60

p = 0.015

Secondary Prevention and Long Term Management

Smoking Goal: Complete Cessation

Blood pressure control: Goal: < 140/90 mm Hg

Physical activity: Goal:30 minutes minimum 5 days per week;Optimal daily

Diabetes: Goal: HbA1c < 7%

Weight management: Goal:BMI 18.5 -24.9 Waist circumference: Women: < 35 in. Men: < 40 in.

Circ 124: 2458, 2011

NSAIDs: Stepped Care Approach

Chronology of Atherosclerotic Vascular Disease

Development of atherosclerosis and vulnerable plaque Acute Coronary

Syndrome Secondary Prevention

Ischemic Heart Disease

Cerebrovascular Disease

Peripheral Vascular Disease

Modified from Libby P

Circ 104:365,2001