ACUTE CORONARY SYNDROMES

R MA HA R A J
E ME RGENC Y M E DI CINE
LECTURE OUTLINE
INTRODUCTION –
EPIDEMIOLOGY/PREVALENCE/DEFINITION

PATHOPHYSIOLOGY OF ACUTE CORONARY SYNDROMES

APPROACH TO SUSPECTED ACUTE CORONARY

SYNDROME – GUIDELINE UPDATE

TREATMENT/MANAGEMENT UPDATE
INTRODUCTION
Coronary Artery Disease – leading cause of morbidity & mortality in
industrialised nations.
Although decrease in cardiovascular mortality  still major cause of
morbidity & burden of disease.

South African perspective of cardiovascular disease:

“A World in One Country” - Yusuf et al
Epidemiological transitions of cardiovascular disease.
HIGH RISK POPULATION FOR CAD/ACS: INDIAN/WHITE/COLOURED

INCREASING rate in Black population – lifestyle/socioeconomic changes,

urbanisation

GF Jooste stats: 23.8% of admissions to resus. unit for chest pain/acs related
(stats 1Jan 2009 – 28 Feb 2009) 150/628 entries.

In US – 2004 – 1.56 million admissions for ACS – 669 000 for unstable
angina, 896 000 for MI
Higher prevelance for NSTEMI.
DEFINITIONS
CAD is a continuum of disease….

Angina -> unstable angina -> AMI -> sudden cardiac death

Acute coronary syndrome encompasses unstable angina, NSTEMI, STEMI

Stable angina – transient episodic chest pain d/t myocardial ischaemia,

reproducible, frequency constant over time.usually relieved with rest/NTG.

Classification of angina – Canadian Cardiovascular Society classification.

Canadian Cardiovascular Association Classification of Angina

CLASS 1 NO PAIN WITH ORDINARY PHYSICAL ACTIVITY

CLASS 2 SLIGHT LIMITATION OF PHYSICAL ACTIVITY –

PAIN OCCURS WITH WALKING, CLIMBING
STAIRS,STRESS

CLASS 3 SEVERE LIMITATION OF DAILY ACTIVITY – PAIN

OCCURS ON MINIMAL EXERTION

CLASS 4 UNABLE TO CONDUCT ANY ACTIVITY WITHOUT

PAIN, PAIN AT REST
UNSTABLE ANGINA –
Pain occurring at rest – duration > 20min, within one week of first visit
New onset angina – ~ Class 2 severity, onset with last 2 months
Worsening of chest pain – increase by at least 1 class, increases in
frequency, duration
Angina becoming resistance to drugs that previously gave good control.

NB! ECG – normal, ST depression(>0.5mm), T wave changes

ACUTE MYOCARDIAL INFARCTION –
ECC/ACC DEFN –rise and fall in cardiac enzymes with one or more of the
following:
Ischaemic type chest pain/symptoms
ECG changes – ST changes, pathological Q waves
Coronary artery intervention data
Pathological findings of an acute MI

NSTEMI = UNSTABLE ANGINA SYMPTOMS/FINDINGS + POSITIVE CARDIAC

ENZYMES
STEMI = ST ELEVATION ON ECG + SYMPTOMS
WHY IS IT IMPORTANT TO RECOGNISE PATIENTS WITH UNSTABLE
ANGINA??

5 -17% suffer an MI within a week after admission.

3 -15% die within a year.
ACS PATHOPHYSIOLOGY
Distruption of coronary artery plaque
-> platelet activation/aggregation
/activation of coagulation cascade ->
endothelial vasoconstriction -
>intraluminal thrombus/embolisation
-> obstruction -> ACS
Severity of coronary vessel
obstruction & extent of myocardium
involved determines characteristics of
clinical presentation
APPROACH
Identifying those with chest pain suggestive of IHD/ACS.
Thorough history required:
Character of pain
Onset and duration
Location and radiation
Aggravating and relieving factors
Autonomic symptoms

TYPICAL VS ATYPICAL HISTORY

Failure to recognise symptoms other than chest pain -> approx 2 hr delay in
seeking medical attention
CHARACTERISTICS OF TYPICAL ANGINAL CHEST PAIN (ADAPTED FROM ROSEN’S,
EMERGENCY MEDICINE)

CHARACTERISTIC SUGGESTIVE OF ANGINA LESS SUGGESTIVE OF

ANGINA
TYPE OF PAIN DULL SHARP/STABBING
PRESSURE/CRUSHING
PAIN
DURATION 2-5 MIN, <20 MIN SECONDSTO
HOURS/CONTINUOUS
ONSET GRADUAL RAPID

LOCATION/CHEST WALL SUBSTERNAL, NOT LATERAL CHEST

TENDERNESS TENDER TO PALP. WALL/TENDER TO PALP.
REPRODUCIBALITY WITH WITH
EXERTION/ACTIVITY BREATHING/MOVING
AUTONOMIC SYMPTOMS PRESENT USUALLY ABSENT
ATYPICAL PAIN
RISK FACTORS FOR DEVELOPING ATYPICAL PAIN:

Diabetes, females, non white patients, elderly, dementia, no prior history of MI

ATYPICAL SYMPTOMS:

GIT symptoms

Syncope

SOB

Pleuritic/positional pain

Chest wall tenderness

No chest pain/symptoms

NRMI 2 STUDY – MI without chest pain -> increased risk of death (23% vs 9%)

More complications – hypotension,heart failure, stroke

Delayed ED presentation, delayed intervention

RISK STRATIFICATION IN ACS
Reasons :
Provides prognostic information

Determines treatment and level of intervention -> low risk patients –early
discharge, high risk -> admission to high care

Helps decongest the ED and make available medical resources to more

needy patients

Risk stratification should be ongoing – at admission, 6-8 hrs, 24hrs,

discharge
TOOLS USED IN RISK STRATIFICATION
HISTORY

ECG

BIOCHEMICAL MARKERS
ECG
First point of entry into ACS algorithm

Abnormal or normal

Neither 100% sensitive or 100% specific for AMI

Single ECG for AMI – sensitivity of 60%, specificity 90%

Represents single point in time –needs to be read in context

Normal ECG does not exclude ACS – 1-6% proven to have AMI, 4% unstable angina
GUIDELINES:
Initial 12 lead ECG – goal door to ECG time 10min, read by experienced
doctor (Class 1 B)
If ECG not diagnostic/high suspicion of ACS – serial ECGs initially 15 -30
min intervals (Class 1 B)

ECG adjuncts – leads V7 –V9, RV 4 (Class 2a B)

Continuous 12 lead ECG monitoring reasonable alternative to serial

ECGs (Class 2a B)
BIOCHEMICAL MARKERS
IDEAL MARKER:
High concentration in myocardium
Myocardium specific
Released early in injury
Proportionate to injury
Non expensive testing

Troponins
CKMB
Myoglobin
Other markers
TROPONINS T/I

Troponin T vs I –
both equivalent in diagnostic and prognostic abilities ( except in renal
failure – Trop T less sensitive)

Elevation ~ 2hrs to 12hrs

~30 – 40% of ACS patients without ST elevation – had normal CKMB but
elevated troponins on presentation

Meta-analysis (Heindereich et al) – odds of death increased 3 to 8 fold with

positive troponin
Mortality at 42 days in troponin positive patients
MYOGLOBIN
Rapid release within 2 hours

Not cardiac specific

Rule out for NSTEMI rather than rule in.

CKMB
Used in conjunction with troponins
Useful in diagnosing re-infarction
MARKER CHANGE SCORES
2 hour delta CKMB mass

Aim – to exclude MI within 6hrs of symptom onset

Determine changes in serum marker levels over certain time intervals –

delta values

Increasing values while still within normal range suggestive of ischaemia

– more rapid anti- ischaemic mxn.
OTHER MARKERS
INDICATORS OF INFLAMMATION OR ACTIVATION OF COAGULATION
CASCADE:
Myeloperoxidase, soluble CD40 ligand, IL6, hsCRP, d dimer, prothrombin
fragment 1 & 2

Elevated before onset of irreversible injury

Lack specificity

Complex lab assays

ISCHAEMIA MODIFIED ALBUMIN
Measured with albumin cobalt binding assay
In ischaemia -> decreased binding of albumin to cobalt
Increased with minutes of ischaemia – elevated for 6-12hrs – gone by
24hrs
~90% negative predictive value
Combined with myoglobin/CKMB/troponin – increases diagnostic
sensitivity of ischaemia by 40%
Possible role for rule criteria in low risk patients
Positive IMA – high risk patients – more aggressive mxn
Positive in hypoxic disorders – poor specificity in this setting
B –type Natriuretic Peptide:
released from heart muscle in response to increased ventricular wall
stress.
Studies – BNP not a specific marker but a strong predictor of ACS
especially in patients with chest pain, no ECG changes, non diagnostic
troponins.
Also positive in heart failure, PE, atrial arrythmias, renal failure

Pregnancy Associated Plasma Protein A (PAPP-A):

Released when plaque ruptures
Predictor of ischaemia
HEART FATTY ACID BINDING PROTEIN (HF ABP)
Identifies AMI <4hrs after onset
Protein involved in myocardial lipid synthesis, but also expressed outside heart
Therefore may be sensitive but not specific for injury
Possible role in multi-marker strategy

IMAGING MODALITIES
Cardiac MRI
Multidetector CT for coronary calcification
Coronary CT angiography
Undergoing clinical evaluation
2007 ACC/AHA guidelines:
Cardiac biomarkers measured in all patients with suspicion of ACS (Class 1
B)
Troponin preferred marker( Class 1 B)
If troponin negative within 6 hours of onset, repeat 8-12hours later(Class 1
B)
Remeasuring of positive biomarkers to determine infarct size/necrosis (Class
2a B)
Patients presenting within 6 hours of symptom onset – myoglobin in
conjunction with troponin measured (Class 2b B)
2hr delta CKMB/Delta troponin considered in <6hr presentation (Class 2b B)
BNP level – for global risk assessment(Class 2b B)
Class 3 – AST/LDH/CK without CKMB
RISK STRATIFICATION MODELS
TIMI RISK SCORE –increase in mortality with increasing score ~40% all cause
mortality at 14 days for patients requiring urgent revascularisation
WHICH MODEL IS MOST APPROPRIATE??
2007 ACS/AHA GUIDELINES:
Risk stratification models useful in decision making with regard to
treatment options ( Class 2a B)
TIMI vs GRACE vs PURSUIT

PURSUIT & GRACE risk scores allow better discrimination of in hospital

and 1 year mortality in patients compared to TIMI. (Andrew et al, Risk
scores for risk stratification in ACS …)

What’s appropriate in our setting???

MANAGEMENT ALGORITHM
MANAGEMENT UPDATE
2007ACS/AHA GUIDELINES:
Rapid catergorisation of patient (Class 1 C)

Possible ACS, non diagnostic ECG/biomarkers – observed in facility with

cardiac monitoring (Class 1 C)

Alternative to in patient treatment: for those with 12hr ECG/markers

negative – stress ECG in 72hrs (Class 1 C)

Giving precautionary treatment for those for OPD stress (Class 1 B)

INITIAL INVASIVE
VS
INITIAL CONSERVATIVE STRATEGY
CLASS 1 RECOMMENDATIONS:
Early invasive strategy for refractory angina, hemodynamic instability (LOE B)
Early invasive strategy for stabilised patients with elevated risk for clinical events.
High risk factors include:
Recurrent angina, ischaemia at rest or minimal activity

Elevated troponins

New ST depression

Signs of heart failure/worsening mitral regurg.

Ventricular tachycardia

Prior CABG

PCI in last 6 months

High TIMI/GRACE scores

LVEF < 40%

CLASS 2b
May opt for initial conservative strategy in stabilised high risk patients –
dependent on patient/physician preference (LOE B)

CLASS 3
Invasive strategy -not recommended in patients with multiple co
morbidities, low risk patients, patients not consenting.(LOE C)
UA/NSTEMI –PHARMACOTHERAPY UPDATE
GENERAL:

IV B Blockers downgraded from Class 1 to 2a recommendation.

(COMMIT Trial)

Oral B Blockers in first 24hrs still Class 1 – but not used in signs of heart
failure, cardiogenic shock and reactive airway disease.(LOE B)

MORPHINE downgraded from Class 1 to 2a – findings from CRUSADE

Registry
NSTEMI- PHARMACOTHERAPY UPDATE
ANTIPLATELET THERAPY:
CLASS 1 RECOMMENDATION
Aspirin to all patients as soon as possible and continued (if no C/I) (LOE A)
Initial dose 162 -325mg
Maintenance 75 -162mg
No added benefit from higher doses except post stenting

Clopidogrel for those allergic to aspirin or major GI bleeding (LOE A)

For initial invasive strategy – aspirin + clopidogrel or IV glycoprotein 2b/3a therapy (LOE A)
Abciximab if no delay in angiography/PCI, eptifibatide/tirofiban if delayed angiography(LOE B)
 CLASS 2a
In patients managed conservatively who develop recurrent ischaemia –
on clopidogrel/ASA/Anticoagulant – can add glycoprotein inhibitor. (LOE
C)

Invasive strategy – can use clopidogrel + glycoprotein inhibitors(LOE C)

CLASS 2b
In patients managed conservatively – can add glycoprotein inhibitor
therapy, in addition to aspirin & anticoagulant (LOE B)
 CLASS 3
ABCIXIMAB should not be given if PCI not planned (LOE A)
For initial conservative strategy:
Aspirin + Clopidogrel + anticoagulant – administered for 1 month(LOE
A), continued ideally up to 1 year(LOE B)

If initial conservative strategy selected but patient has recurrent

ischaemic symptoms/heart failure/arrythmias – diagnostic angiography
recommended. Clopidogrel or Glycoprotein 2b/3a inhibitors should be
added before angiography.
ANTICOAGULANT THERAPY
CLASS 1
Anticoagulant therapy should be added as soon as possible
For patients undergoing angiography/PCI – enoxaparin/UFH (LOE A) of
Bivalirudin/ fondaparinux (LOE B)

For conservative strategy: enaxaparin, UFH (LOE A), fondaparinux

For patients with increased risk of bleeding with conservative strategy –

fondaparinux
 CLASS 2a
Enoxaparin /fondaparinux vs UFH

Enoxaparin/fondaparinux preferred except in those undergoing CABG

within 24hrs (LOE B)
ADDITIONAL MANAGEMENT
STRESS TEST should be performed for those managed conservatively.
If stress test positive/ high risk – needs diagnostic angiography(Class 1
LOE A)

If classed as low risk –

need to continue aspirin indefinitely ( LOE A)
Clopidogrel for at least 1 month(LOE A), ideally up to 1 year(LOE B)
UA/NSTEMI ALGORITHM- INVASIVE STRATEGY
UA/NSTEMI ALGORITHM –CONSERVATIVE STRATEGY
STEMI
PHARMACOLOGICAL UPDATE:
ANALGESIA – changes from 2004 guidelines

MORPHINE: still remains Class 1 C for STEMI, titrated doses

NSAIDS/COX 2 INHIBITORS: those on it should have it discontinued (

increased risk of mortality, re infarction, heart failure, myocardial
rupture) Class 1 C

NSAIDS should not be administered in hospital for MI (Class 3)

BETA BLOCKERS
Modified recommendation
Oral Beta Blockers should be initiated in first24rs, if no contra-
indications (heart failure, risk of cardiogenic shock) Class 1 B
Patients with early contraindications -> re- evaluated later for possible
use
Role of IV B blockers – used in hypertensive patients with STEMI Class
2a B
Class 3 LOE A – IV B blockers should not be administrated to patients
with heart failure, risk of cardiogenic shock
No major changes to reperfusion strategies.

Emphasis on decreasing ischaemic time.

Increase use of prehospital 12 lead ECG emphasised.

In PCI capable hospital – door to PCI time 90 min (Class 1 A)

In non PCI capable hospital – door to needle time 30 min or timeous

transfer to PCI capable hospital. (Class 1 B)
REPERFUSION STRATEGY
FIBRINOLYTICS
AVAILABLE FIBRINOLYTICS:
STREPTOKINASE – 1.5mu infusion over 30min (1hour –ACLS)
rtPA – accelerated infusion over 1.5hrs
- 15mg IV bolus, 0.75mg/kg over 30 min, 0.5mg/kg over 1hr
ANISTREPLASE – 30 U IV over 5 min
TENECTEPLASE – 30 TO 50 MG
RETEPLASE – 10 U IV bolus, ffd. 10U IV after 30 min

WHICH FIBRINOLYTIC TO USE???

GISSI 2 trial – tPA vs Streptokinase , no difference in mortality, marginally higher stroke rate with tPA
(1.3% vs 1%)
GUSTO 1 trial – early vessel patency post infract assoc. with better survival.
Accl. tPA/heparin cf comb. Streptokinase/tPA/heprain cf strep with IV vs S/C heparin
Outcome – better flow rates with accl. tPA -> lower mortality rates
ASSENT 2 TRIAL – tenecteplase vs aTPA
- tenecteplase was equally or minimally more effective,
especially in those presenting > 4hrs after symptom onset.

Fibrinolysis combined with glycoprotein 2b/3a inhibitors – no overall

advantage (ASSENT 3, GUSTO 5 trials)
RESCUE PCI:
CLASS 1 LOE B – angiography with +/- PCI in patients (<75 yrs)with
cardiogenic shock, severe heart failure, ventricular dysrythmias

Class 2a – persistent ischaemic symptoms post fibrinolysis, haemodynamic

instability, electrical instability (LOE C)

New recommendation – PCI for failed fibrinolytic therapy (less than 50%
decrease in ST elevation in worst lead, 90min post fibrinolytic therapy, or
large area of myocardium injured) LOE B

Class 3 – angiography performed if invasive strategy contraindicated, or

patient refusal (LOE C)
ANTICOAGULANT ADJUNCTS
NEW RECOMMENDATIONS:
CLASS 1
Patients undergoing fibrinolysis should be kept on anticoagulants for atleast
48 hrs and preferably the duration of hospital stay. LOE A

Anti coagulants with proven efficacy:

Unfractionated Heparin - keeping aPTT 1.5 – 2 sec above control (LOE C)
Enoxaparin (Clexane) – initial dosage of 30mg IV bolus – ffd by 1mg/kg
12hrly, caution in renal impairment (LOE A)
Fondaparinux – 2.5mg IV, ffd by 2.5mg dly S/C maintenance for duration of
hospitalisation (LOE B)
ANTICOAGULANTS
CLASS 2a recommendation to use anticoagulants in STEMI without
reperfusion.
UFH (LOE B)
LMWH (LOE C)
Fondaparinux (LOE B)
THIENOPYRIDINES
CLASS I
CLOPIDOGREL – now recommended in all STEMI patients in addition to
aspirin, whether undergoing reperfusion or not. Dosage 75mg daily(LOE
A)
Duration -14 days (LOE B)

CLASS 2 A
In patients < 75yrs – Clopidogrel 300mg loading dose recommended(LOE
C)
Long term maintenance therapy should be considered, 75mg dly for 1
year (LOE C)
SECONDARY PREVENTION
INCREASED FOCUS ON SECONDARY PREVENTION:

SMOKING CESSATION

DIET MODIFICATION/WT CONTROL

BP CONTROL

LIPID MANAGEMENT

EXERCISE

DIABETES MANAGEMENT
Despite good reperfusion strategies approx. 1/3 of patients worldwide
miss out.
Attributed to – delayed presentation, atypical presentation, complicated
disease presentation, older age

SYMPTOMS OF INFARCT BUT NO ESTABILISHED ECG CHANGES - keep in

mind aortic dissection, GIT disease, other chest pathology
CONCLUSION
With increase burden of CVD, and lack of health resources risk
stratification becomes important.

Emphasis should also be placed on primary &secondary prevention of

ACS.

Early intervention helps prevent complications, decreases morbidity &

mortality

The way forward – fully equipped CHEST PAIN OBSERVATION UNIT

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WHITE HD, DEFINING THE LIMITS OF ACS, CARDIOLOGY AT THE LIMITS IV, EDITORS: OPIE LH, YELLON DM

YUSUF S, THE GLOBAL EPIDEMIC OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE, CARDIOLOGY AT THE LIMITS IV, EDITORS: OPIE
LH, YELLON DM

FOX KA, MANAGEMENT OF ACS: AN UPDATE, HEART.2004 JUNE, 90(6):698 -706

ANDERSON ET AL, ACC/AHA 2007 GUIDELINES FOR MXN OF U/A,NSTEMI – EXECUTIVE SUMMARY – DOWNLOADED
content.onlinejacc.org

SIX AJ ET AL, CHEST PAIN IN THE ER: VALUE OF THE HEART SCORE, NETH. HEART J. 2008 JUNE,16(6):191 -196
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WITH STEMI, DOWNLOADED http://circ.ahajournals.org

McCANN CJ ET AL, NOVEL BIOMARKERS IN EARLY DIAGNOSIS OF AMI COMPARED WITH CARDIAC
TROPONIN T, EUROPEAN HEART JOURNAL 2008,29(23): 2843 -2850

KING III SB ET AL, 2007 FOCUSSED UPDATE OF ACC…..FOR PCI, JOURNAL OF AMERICAN COLLEGE OF
CARDIOLOGY, VOL 51, NO 2, 2008