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ACUTE CORONARY

SYNDROMES
R MAHARAJ
EMERGENCY MEDICINE

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 ROSENS, EMERGENCY MEDICINE)
CHARACTERISTIC

SUGGESTIVE OF ANGINA

LESS SUGGESTIVE OF
ANGINA

TYPE OF PAIN

DULL
PRESSURE/CRUSHING
PAIN

SHARP/STABBING

DURATION

2-5 MIN, <20 MIN

SECONDSTO
HOURS/CONTINUOUS

ONSET

GRADUAL

RAPID

LOCATION/CHEST WALL
TENDERNESS

SUBSTERNAL, NOT
TENDER TO PALP.

LATERAL CHEST
WALL/TENDER TO PALP.

REPRODUCIBALITY

WITH
EXERTION/ACTIVITY

WITH
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 )

Whats 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 contraindications (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

REFERENCES

EDITORS MARX ET AL, ROSENS EMERGENCY MEDICINE: CONCEPTS AND CLINICAL


PRACTICE, 6TH EDITION

PAUL PD ET AL, KEY ARTICLES IN MANAGEMENT OF ACS & PCI -2007 UPDATE,
PHARMACOTHERAPY 2007:27(12), 1722 -1750

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

ANTMAN EM ET AL, 2007 FOCUSSED UPDATE OF ACC/AHA 2004 GUIDELINES FOR MAXN
OF PATIENTS 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