Acute Coronary Syndromes

Dr. S. McPherson

Dr. G. Curry

July 11, 2002

Chest Pain – the initial presentation

2 questions to be answered:

Are the symptoms a manifestation of an ACS?

If so, what is likelihood of an adverse outcome?

Chest pain – the initial presentation

• Early Risk stratification:– Categorize patients with chest pain into high,

intermediate, and low risk of ACS

– Use of history (anginal symptoms), physical exam, ECG, biochemical markers

Historical features

Classic characteristics:– Deep chest or arm pain associated with exertion or emotional

stress– Resolves promptly with rest or NTG

Not characteristic:– Pleuritic– Primarily mid to lower abdominal pain– Pain that is localized with 1 finger– Reproducible pain with palpation or movement– Constant pain X hours– Very brief pain lasting few seconds or less– Pain radiates to lower extremities

Incidence of ACS with noncharacteristic symptoms

Arch Int Med 1985;145:65-9• Sharp or stabbing pain 22%• Pleuritic 13%• Reproducible to palpation 7%

Med Care 1991; 29:610-27, J Critic epi 1992;85:1254-64• Traditional risk factors only weakly predictive of ACS• But presence of risk factors relate to poorer outcomes

Estimation of the likelihood of ACS

Estimation of the risk of adverse outcome

Estimation of the risk of adverse outcomes

JAMA 1996;276:1568-74

• Looked at 30 day mortality or MI in patients with high, intermediate and low risk UA (AMI and noncardiac CP excluded)

• Low risk 0%

• Intermediate risk 1.2%

• High risk 1.7%

Management recommendations

• Low risk: expeditious work up as an outpatient (ie within 72 hrs of d/c from ED)

• High and intermediate risk admit for further work up

The ECG

– Progression of changes• Giant R wave

• Hyperacute T waves (release of intracellular K+)

• ST elevation (current of injury)

• Q wave (shift of axis of depolarization)

• Inverted T waves (abnormal repolarization

Interpreting the ECG

• ECG– Inferior II, III, aVf– Lateral I, aVL, V5-6

– Anterior V1-4

– Posterior ST depression ant V1-3 with large R V1

Interpreting the ECG

• ECGin association with old LBBB

(Sgarbossa) any concordant change >1mmany discordant change >

5mm *same applies for VPB rhythm

• 15 lead ECGprognostic value

sensitivity

Interpreting the ECG

• ST elevation of > 0.1 mV confirmed >90% of the time by biochemical markers to be AMI

• Up to 15% of AMI have a normal or nonspecific ECG

• ST depression of > 0.05 mV or T wave inversion of > 0.2 mV may represent cardiac ischemia

Prognostic value of the ECG

Prognostic value of the ECG

Biochemical Cardiac Markers

• Lab– CK, CKMB

• At 24Hrs sensitivity reaches >95%

• Specificity problem (high false positive rate)

• Doesn’t predict USA

– Troponins (TnT, TnI)• T1/2 : 3-8 hrs, but detected for up to 10 days

Biochemical markers

• Enzyme comparisonMarker time to peak time to norm

myoglobin 1-3 6-10 24-36CK 3-8 10-36 72-

96 CK-MB 3-8 9-30 48-72 CK-MB iso 1-3 4-6

18-24 cTnT 2-610-24 10-15 days cTnI2-6 12-24 7-10 days

Troponins sensitivity Ebell 2000

0

1020

3040

506070

8090

100

0 2hr 4hr 6hr 8hr 10hr 12hr

0.10.2

Troponin the main points

• Troponin should NOT determine disposition• General Numbers to remember

– 6 -----------------> 60% sensitive

– 8 -----------------> 80% sensitive

– 10 -----------------> 90% sensitive• Patients with TnT + and CKMB – have

worse prognosis (increased death and CV events at 30 days)

False + troponin– Troponins: increase levels?

• Ischemia/ infarction• Cardiomyopathy• Electrical injury• Pericarditis• Myocarditis• Cardiac contusion• Hypertensive emergencies• End- stage renal failure• Pulmonary embolus

Case 1 & 2

• Insert a low risk ACS case and a high or intermediate case and have group decide what to do in light of the previous slides

Unstable angina/NSTEMI

Canadian Cardiology Classification of Angina

• Class I. Ordinary physical activity (e.g., walking or climbing stairs) does not cause angina.

• Class II. Slight limitation of normal activity; angina occurs with walking, climbing stairs, or emotional stress.

• Class III. Severe limitation of ordinary physical activity; angina occurs on walking one or two blocks on a level surface or climbing one flight of stairs in normal conditions.

• Class IV. Inability to carry on any physical activity without discomfort; anginal symptoms may be present at rest.

USA/NSTEMI• Definition of Unstable Angina:

Rest angina. Angina occurring at rest, lasting longer than 20 minutes, and occurring within 1 week of presentation

New-onset angina. Angina of at least class III severity with onset within the last 2 months

Increasing angina. Previously diagnosed angina that is more frequent, longer in duration, or increased by one class within the last 2 months of at least class III severity

• Definition of NSTEMI:

Evidence of myocardial necrosis with rise in biochemical markers

Case # 3

• Insert case of classic USA here

Management of UA/NSTEMI

Anti-ischemic therapy:– Bedrest

– Oxygen

– NTG

– Morphine

– B-blocker

– CCB

– ACE

Anti-platelet/Anti-thrombotic therapy:– ASA

– Clopidogrel

– GPIIbIIIA

– Heparin

– LMWH

Anti-ischemic therapy

• Oxygen– No evidence to support administration of O2 to

all patients with ACS

– Recommended for patients with questionable respiratory status and hypoxia

Anti-ischemic therapy

Nitrates:– 0.4mg sl or spray q5min– Initiate NTG infusion if above does not resolve

pain (contraindicated if hypotension or pt has used Viagra within 24hr); titrate q3min to effect or until SBP < 110mmHg

Nitrates – the evidence

• Meta-analysis of the small trials (pre-lytic) showed a 35% reduction in mortality

• ISIS-4 and GISSI-3 showed no mortality benefit but frequent pre-hospital and hospital use of NTG in the control group

• BOTTOM LINE: we all use it, it makes patients feel better, it doesn’t seem to harm most patients

Anti-ischemic therapy

Morphine:– 1-5 mg iv recommended for patients with

ongoing pain post NTG x3– May give with iv NTG but watch BP

– No RTC to validate its benefit or clarify its optimal schedule

– Adverse effects: hypotension, N&V (20%), resp depression

Anti-ischemic therapy

B-Adrenergic blockers:– Metoprolol 5mg iv q5min, if tolerate 15mg start

25mg po 15min after last iv dose

– Contrindications:• 1st, 2nd, 3rd degree heart block, LV dysfunction, CHF,

asthma, sinus brady, hypotension, cautiously in patients with COPD

B-blockers the evidence

• Overview of all RPCT (small) showed 13% reduction is progression to AMI, not powered to detect difference if mortality JAMA 1988

• Use in USA extrapolated from mortality reduction proven in AMI, stable angina, heart failure

Anti-ischemic therapy

Calcium channel blockers:– To control ongoing or recurrent pain when maxed

therapy of B-blocker/NTG, NTG/B-blocker not tolerated or variant angina

– Do not use nifedipine

– Do not use verapamil or diltiazem if evidence of acute CHF

– Evidence supports role for symptom control with use as a rate control if B-blocker not tolerated

UA/NSTEMI – Antiplatelet therapy

• ASA

• Clopidogrel

• GPIIbIIa inhibitors

Anti-platelet therapy

ASA:– 160-325mg to chew ASAP– All trials have shown mortality benefit that

extends to 2 years

– Contraindications:• Allergy• Active bleeding (GI, retinal)• Hemophilia

Anti-platelet therapy

Clopidogrel– CAPRIE (1996), RCT ASA vs Plavix

(N=19,185)• 3 year ischemic stroke, MI or death ARR = 0.5%

(NNT = 200)

• Plavix equal to ASA but increased side effects (diarrhea, rash, GI bleed)

Anti-platelet therapyClopidogrel:

– CURE trial (2001) RCT Plavix + ASA vs ASA • UA/NSTEMI within 24 hr

• Death, MI, or stroke 3 and 12 month ARR = 2.2% (NNT = 45)

• Excess in major bleed of 1% (NNH = 100)

• Risk of bleed with CABG increased in 1st 5 days

• Recommended in UA/NSTEMI when noninvasive course is anticipated

• BOTTOM LINE: appears to work but not for us to start in the ED

Anti-platelet therapyGPIIbIIIa Receptor Antagonists:

– Inhibits the cross-linking of platelets by fibrinogen

GPIIbIIIa RA

• EPIC (abcixamab) NEJM 1994– PRCT, N=2,099 pts– High risk pts going for PCI (AMI, USA)– Reopro(bolus, bolus +infusion) vs placebo– Placebo vs bolus similar– F/U 30 days– Bolus/infusion: lower rate triple end-point (Death, MI or

urgent revascularization) 8.3% vs 12.8% (ARR 4.5%, RRR 35%)

– 2 fold increase in major bleeds: 14% vs 6.6 (ARI 7.4%, RRI 112%!!!

GPIIbIIIa RA

• CAPTURE (abcixamab) Lancet 1997– PRCT, N=1050 pts (stopped early)– Pts with refractory USA, after cath and before plasty– Reopro vs placebo , 18-24hrs before plasty, and 1 hr

after– F/U 30 days then 6 months– Composite endpoint at 30 days(Death, MI, urgent

intervention ): 2.6% vs 5.5% (ARR 2.9%, RRR 53%)– At 6 months: no difference! (decreased early events

only)– Major bleeding: 3.8% vs 1.9% (ARI 1.9%, RRI 50%)

GPIIbIIIa RA

• CAPTURE (substudy)– Predictive value of TnT– Increased TnT(>0.1 ng/ml): 30.9%– F/U 6 months: Death or MI– TnT +ve

• Reopro 9.5% vs placebo 23.9% (ARR 14.4%, RRR 60%

– TnT –ve• Reopro 7.5% vs 9.4% (not significant)

– Conclusion: TnT +ve identifies a high risk population that seems to benefit from GIIb-IIIa’s

GPIIbIIIa RA

• PRISM-PLUS (tirofiban) NEJM 1998– PRCT, N=1,570 pts– Non-ST segment elevation ACS and likely to go to

catheterization– Heparin vs tirofiban vs combination– Tirofiban alone arm stopped (increased mortality at 7

days)– F/U 7 and 30 days and 6 months– Composite endpoint (Death, MI or recurrent ischemia):

7 days: 12.9 vs 17.9% (p=0.004), 30 days: not significant, 6 months: 27.7 vs 32.2% (p=0.02)

GPIIbIIIa RA

• PURSUIT (eptifibatide) – PRCT, N=10,948 pts – Eligible if ECG changes : transient ST elevation, ST

depression, T wave inversion, or positive CKMB– Eptifibitide vs placebo– F/U 30 days and 6 months– Double endpoint (Death or MI): 30 days: 14.2 vs 15.7%

(ARR 1.5%, RRR 10%), 6 months: 12.1 vs 13.6% (ARR 1.5%, RRR 11%)

– Medical Management: US benefit, Europe and Latin America no benefit

– Didn’t work in females!!!!!

GPIIbIIIa RA

• GUSTO IV– PRCT, N=7800 pts– ECG changes, +ve troponin level– Early revascularization strongly discouraged– Abcixamab vs placebo (24-48 hr infusion)– No difference in MI or Death

GPIIbIIIa RA

BOTTOM LINE:– They are definitely indicated as an adjunct to

PCI

– Role in UA/NSTEMI is questionable, there appears to be a small reduction in death or MI in high risk groups (ongoing or recurrent pain, dynamic ST changes)

– Not enough evidence for us to start in the ED

Anti-thrombotic therapy

Unfractionated Heparin:

• 5000 Unit bolus then 1000 unit/hr

• Evidence is scanty:– Theroux et al (1993) RCT ASA+hep vs ASA

• Decreased rates of MI (fatal and nonfatal) 3% (NNT = 33%)

– RISC (1990) ASA vs UFH vs UFH +ASA• ASA + UFH had lowest events in 1st 5 days

Anti-thrombotic therapy

LMWH:• ESSENCE (1997) RCT enoxaparin vs UFH

– No difference in mortality– Composite endpoint of death, MI or recurrent angina,

ARR = 3.2% (NNT=33)

• TIMI 11B (1999) RCT enoxaparin vs UFH– Composite endpoint death, MI, urgent need for PTCA,

ARR = 2.1% (NNT = 50)

• 2 trials (1 dalteparin, 1 nadroparin) had neutral or unfavorable trends

Anti-thrombotic therapy

Case #4

• Insert case for AMI here

Diagnosis of AMI

• WHO def’n (2 of 3):– Ischemic type chest discomfort– Rise & fall in serum cardiac markers– Changes on ECG

• ST elevation 91% specific, 46% sensitive for MI

Management of AMI

• Routine measures:– Supplemental O2

– Iv access– ECG interpreted within 10 minutes of arrival to

ED

Management of AMI

OXYGEN recommended if:– Overt pulmonary congestion

– Arterial oxygen desaturation (SaO2 < 90%)

– Universal practice to provide O2 via NP in first 2-3 hr of uncomplicated AMI

• No proven benefit

• Questionable harm from O2 systemic vasoconstriction if flow rates too high

Management of AMI

ASA– 160-325 mg given ASAP– 23% 35 day reduction in mortality (NNT = 4)

– Ticlopidine or clopidogrel may be substituted if true ASA allergy

Management of AMI

Heparin:

• Conflicting evidence

• LATE: ASA vs ASA + heparin showed 4.2% ARR in 35 d mortality (NNT = 23)

• ISIS-2 : ASA vs ASA + heparin no survival benefit shown at 35 days

• Prevents re-occlusion with TPA

Management of AMI

Nitroglycerin– No mortality benefit– Shown to decrease post infarct angina

– Give sl to patients with ischemic sounding CP unless SBP < 90, HR < 50, tachycardia, or suspected RV infarct

Management of AMI

Morphine– Iv morphine advocated by ACC guidelines in

addition to other conventional therapy– Should not be delayed on premise that

treatment will obscure the diagnosis

Management of AMI

-blockade Shown to decrease all cause mortality by 2.6%

if started within 5-21days of infarct (NNT = 38) early treatment:

Metoprolol 15 mg vs placebo f/u at 3 month, 36% RRR of death

TIMI IIB showed lower reinfarction or recurrent CP If HR > 70 and BP can tolerate give Metoprolol

5-15 mg iv

Management of AMI

Thrombolytics:

• Goal “door-to-needle” time of 30 minutes

• FTT Trial (N=58,000)– No survival benefit after 12 hours– Treat if ECG findings of :

• > mm ST elevation if 2 contiguous leads

• New LBBB

• ST depression leads V2-4

– ARR 2%, NNT 40-50

Management of AMI

Fibrinolytics started

First hour

Second hour

Third hour

3-6 hour

6-12 hour

12-24 hour

Additional lives saved per 1000 pts treated

65

37

29

26

18

9

Management of AMI

Absolute contraindications:

1. Aortic dissection

2. Pericarditis

3. Active bleeding (melena, hematuria)

4. Cerebral hemorrage

5. Intracranial malignancy

6. AVM

Management of AMI

Relative:– GI/GU bleed in last 6 month– Ischemic stroke in last 6 months– Surgery/biopsy in last 2-4 weeks– Major trauma in last 2-4 weeks– CPR with evidence of chest trauma– Recent minor head trauma– Severe uncontrolled BP(SBP>200, DBP>120)– Bleeding diathesis– Hepatic dysfunction– Pregnancy– +/- diabetic retinopathy, +/- INR > 2.3

Management of AMI

Risk of bleed or stroke:

• Stroke 0.25-1% (NNH~100)– Risk factors: age > 65, wt < 70 kg,

hypertension, use of alteplase– Streptokinase + heparin has lowest risk of

stroke

• Major bleed 1% (NNH 100)

Management of AMI – risk of stroke with lytic

Management of AMI – dealing with the consequences

You’ve given TPA to your patient, 15 minutes later the nurse pages you overhead to the bedside because there is a lot of blood oozing form the iv site. What do you do?

Compress the vein and continue TPA and heparin

Management of AMI – dealing with the consequences

You’ve given TPA 30 minutes later the nurse calls you to the bedside because the patient has bright red bleeding per rectum. What do you do?

1. Stop TPA and heparin infusions2. Reverse heparin with protamine

(1mg/100units)3. FFP and cryo to attempt to reverse TPA

Management of AMI - PTCA

Management of AMI - PTCA

Management AMI - PTCA

• Meta-analysis Weaver et al– 10 RCT, N = 2606– ARR 30 day mortality PTCA vs lytic = 2.1%,

NNT = 50– ARR 30 day mortality or reinfarction = 4.7%

NNT = 21

Management of AMI – stent vs plasty

• SPAM (NEJM 1999)– PRT, N=1000– AMI, cath : randomized to stent vs plasty– 6 months: combined end point(death,

reinfarction, disabling stroke): 12.6% vs 20.1% (ARR 7.5%, RRR 37%)

– Lower incidence of restenosis: 20.3 vs 33.5% (ARR 13.2%, RRR 39%)

– No difference in mortality

Management of AMI – invasive approach

• Consider as first line management of STEMI in centers with extensive experience and capability to perform procedure within 60-90 minutes (ie Calgary)

• Priority given to:– Pts with contraindication to lytic– Cardiogenic shock– Large area of myocardium at risk (> 4-5 leads)– Hemodynamic or electrical instability

Case #5

• Case of cardiogenic shock

Cardiogenic shock

• Complicates 7-10% of AMI

• 70-80% mortality

• Diagnosis:– SBP< 90mmHg– Evidence of end organ hypoperfusion (cool

extremities, oliguria, altered mentation)

Management – cardiogenic shock

• Oxygenation and ventilation

• Improve systolic function– Catecholamines (dopamine, dobutamine if BP

tolerates)– IABP

• revascularization

Cardiogenic shock – PTCA vs lytic

SHOCK (1999)

• RCT PTCA vs lytic, N= 302

• 2.7% cross over to PTCA group within 54 hrs

• 9.8% ARR at 30 day mortality (not stat sig)

• 13% ARR at 6 month mortality (NNT = 8)

Case #6

• RV infarct case presentation

RV infarct• Incidence in association with LV infarct is btn 14-

84%• Isolated RV infarct is 3%• Very sensitive to preload

• Be suspicious with inferior infarcts• P/E may reveal hypotension, elevated JVP (88%

sensitive, 69% specific), clear lung fields• 1mm ST elevation in V4R is 100% specific and

70% sensitive

RV infarct – management issues

• Be very careful if using NTG

• Treat hypotension with fluid bolus of NS• If does not respond to fluid initiate

ionotropic support (dobutamine or dopamine)

• AV sequential pacing if 3rd degree block• Reperfusion as per AMI

Case #7

• Insert cocaine induced chest pain here

Cocaine induced chest pain

• Most common symptom of cocaine abusers

• ~ 6% have evidence of MI

• ECG may be abnormal in 56-84%

• ~ 43% without biochemical marker increase will have ST elevation of at least 0.1 mV

Management of cocaine induced chest pain• Continuous monitoring, iv access• Iv benzos, NTG and CCB (20mg

Diltiazem), B-blockers contraindicated• PTCA if not responding to above medical

management• If PTCA not available then lytic if meet

criteria and not responding to above medical management

Many thanks to….

• Dr. Gil Curry for his contribution of cases and ECG’s

• Dr. Idan Khan and his ACS talk from last year

• Dr. Rob Hall for his troponin presentation

• ACC for their AMI guidelines from 1999 and UA/NSTEMI guidelines June 26, 2002