Acute coronary syndromes

Iftikhar Ul Haq
Consultant Cardiologist

Learning outcomes
Demonstrate ability to both describe and recognise
appropriate features in clinical presentation (including
relevant history, examination and investigation) found in
patients with ACS vs. other causes of chest pain.
Demonstrate ability to interpret investigations sufficient
to establish a differential diagnosis of acute coronary
syndrome: including non-ST elevation ECG changes
and biomarkers.
Demonstrate knowledge and understanding of the
pathophysiological processes contributing to the
development of acute coronary syndrome

Self directed learning

The ECG
Vascular endothelial cell function
Shock
Muscle cell biology
Illness prevention and smoking

Universal Definition of MI
The term MI should be used when there is
evidence of myocardial necrosis in a clinical
setting consistent with myocardial ischaemia
Tn > 99th percentile of URL (Type 1 MI)
PLUS at least one of:
Symptoms of ischaemia
ECG changes indicating ischaemia
ECG evidence of necrosis: new pathological Q waves
Imaging - new loss of myocardium, or new RWMA

Universal Definition of MI
Type 1 usual MI
Type 2 - imbalance in myocardial O2 supply and
demand ischaemia without definite CAD
Type 3 - Sudden death: other evidence of AMI or
occlusive thrombus
Type 4 - PCI associated MI: Tn x3 URL
Type 5 - CABG associated: Tn x5 URL & new Q
waves/LBBB, or angiographic/imaging evidence

Definitions
ACUTE CORONARY SYNDROME

No ST Elevation

ST Elevation

NSTEMI

Unstable Angina

NQMI
QwMI
Myocardial Infarction

Plaque Rupture
Lipid
pool

Lipid-rich
plaque

Plaque
disruption

Fissure

Occlusive
thrombus

Acute MI,
Q-wave

Subocclusive
thrombus

Unstable
angina/
Non-Q-wave
MI

ACS: mortality at 6 months

GUSTO 2B: ST segment depression a high risk population
ST elevation with co-existing
depression 9.1% (n=1,769)

Mortality (%)

10
8

ST depression
8.9% (n=4,263)

ST elevation
6.8% (n=3,369)

T-wave inversion
3.4% (n=2,723)

20

40

60 80 100 120 140 160 180

Days from randomization
Savonitto S et al. JAMA. 1999; 281:707-13

Chest pain hospital admissions

Chest pain is the biggest cause of
presentation to A&E in the UK:
600,000 patients per year
125,000 have NSTE-ACS (1 in 4)1

1. Fairbairn IP. J R Coll Physicians Edinb 2003; 33: 3643

NSTE-ACS patient identification

Immediate assessments
First
Patient history
ECG
Physical examination

Then
Risk stratification
Blood marker tests

Diagnosis of ACS
Requires the presence of at least two of the following
criteria:1. Chest pain (clinical manifestation)
2. ECG changes consistent with ischaemia or
necrosis
3. Elevation of cardiac markers

ACS: classical clinical symptoms

at presentation
Classical
Discomfort/pain in the centre of the chest
Lasts for more than a few minutes or recurs
Radiation to other areas, e.g. arms/jaw/neck/back

Atypical presentations - elderly or diabetic patients:

Breathlessness
Tachycardia
Nausea or vomiting
Sweating and clamminess

Features of stable angina

Anginal pain is:
constricting discomfort in the front of the chest, neck, shoulders, jaw or arms
precipitated by physical exertion
relieved by rest or GTN in about 5 minutes.
People with typical angina have all the above anginal pain features, people with atypical angina
have two of the features and people with non-anginal chest pain have one or none of the features.
Do not define typical and atypical features of anginal and non-anginal chest pain differently in
men and women or among ethnic groups.
Factors making stable angina more likely:
increasing age
whether the person is male
cardiovascular risk factors
a history of established CAD (e.g. previous MI, coronary revascularisation).
Stable angina is unlikely if the pain is:
continuous or very prolonged and/or
unrelated to activity and/or
brought on by breathing in and/or
associated with dizziness, palpitations, tingling or difficulty swallowing.

Cardiac Risk Factors

Modifiable
BP
Lipids
Diabetes
Smoking status

Fixed
Patients sex
Age
Family history
Ethnicity
Previous angina/MI
CVA/PVD

Chest Pain differential diagnosis

NON ORGANIC

CARDIAC

Anxiety

Angina
Myocardial Infarction

PULMONARY

Pericarditis

Pulmonary Embolus

Aortic dissection

Pleurisy
Pneumothorax

MUSCULOSKELETAL
Chostochondritis
Trauma

GASTRO
Ulcer or Reflux
Gallstones
Pancreatitis

Suspected ACS
Check immediately if chest pain is current, or when the last episode was, particularly if in the last
12 hours.
Check if the chest pain may be cardiac. Consider:
history of the pain
any cardiovascular risk factors
history of ischaemic heart disease and any previous treatment
previous investigations for chest pain.
Check if any of the following symptoms of ischaemia are present. These may indicate an ACS:
Pain in the chest and/or other areas (for example, the arms, back or jaw) lasting longer than15
minutes.
Chest pain with nausea and vomiting, marked sweating or breathlessness (or a combination of
these), or with haemodynamic instability.
New onset chest pain, or abrupt deterioration in stable angina, with recurrent pain occurring
frequently with little or no exertion and often lasting longer than 15 minutes.
Central chest pain may not be the main symptom.
Do not use response to glyceryl trinitrate (GTN) to make a diagnosis of ACS.
Do not assess symptoms of an ACS differently in men and women or among different ethnic
groups.
Advise people about seeking medical help if they have further chest pain.
If the chest pain is non-cardiac, explain this to the person and refer for further investigation if
appropriate.

Diagnosis of ACS
Requires the presence of at least two of the following
criteria:1. Chest pain (clinical manifestation)
2. ECG changes consistent with ischaemia or
necrosis
3. Elevation of cardiac markers

ECG
Perform an ECG immediately - especially if the
patient is still in pain
If ECG is normal or non diagnostic in a patient with
continuing symptoms repeat after 30mins
If symptoms resolve repeat ECG after 2 hours changes
can occur late
Repeat ECG if pain persists

Risk Stratification by ECG

The risk of death or MI at 30 days is strongly
related to the ECG at the time of chest pain
ST depression
10%
Decreasing risk
T-wave inversion
5%
No ECG changes
1-2%

Normal ECG

Anterolateral ST depression

Anterior ST segment depression

AF with infero-lateral ST depression and LVH

ST depression V2-V6, T inversion in aVL

Lateral ST segment depression

Anterior T wave inversion

Deep arrowhead anterolateral T wave inversion

Anterior myocardial infarction with gross ST segment elevation

(showing "tombstone" R waves)

An inferolateral myocardial infarction with reciprocal changes in

leads I, aVL, V1, and V2

Left bundle branch block

Diagnosis of ACS (NSTEMI)

Requires the presence of at least two of the following
criteria:1. Chest pain (clinical manifestation)
2. ECG changes consistent with ischaemia or
necrosis
3. Cardiac markers

Relative concentration

Myoglobin
Troponin
CK, AST
LDH

Normal

0 6 12 18 24 2 3 4 5 6 7 8 9 10
Hours
Days
Time after infarct

Troponin I Levels and Mortality in Patients

with NSTE-ACS
% Mortality at 42 Days

8
6

4
2
0

0 - <0.4

0.4 - <1.0

1.0 -< 2.0

2.0 - <5.0

5.0 - <9.0

>9.0

Troponin I Level
Antman EA, Tanasijevic MJ, Thompson B, et al. Cardiac-specific troponin I levels to predict the risk of mortality
in patients with acute coronary syndromes. N Engl J Med. 1996;335:1342-1349

Troponin Pitfalls
Troponin can be elevated in
PE
Sepsis
Post-op
AF
LVF

Rate of death or MI in relation to ST

deviation and troponin
P<0.0001 (global 2 test)

15.4%

16

Death or MI at 6 months (%)

13.7%
14

12.8%

12.5%

12

10.0%
10
9.6%
8
6
6.0%

3.1%

ST dev > 0.10 mV

4.1%

ST dev 0.05-0.09 mV

0
>0.10

ECG

None
0.01-0.10

Troponin T (ng/ml)

<0.01

Sabatine et al. Am Heart J 2006

Risk and Risk Stratification

TIMI risk score for NSTE-ACS

HISTORICAL

POINTS

RISK OF CARDIAC EVENTS (%)

BY 14 DAYS IN TIMI 11B*

Age 65

3 CAD risk factors

(FHx, HTN, chol, DM, active smoker)

RISK
SCORE

DEATH OR
MI

DEATH, MI OR URGENT
REVASC

Known CAD (stenosis 50%)

0/1

ASA use in past 7 days

13

PRESENTATION
Recent (24H) severe angina

20

Cardiac markers

12

26

ST deviation > 0.5mm

6/7

19

41

RISK SCORE = Total Points

(0-7)

*Entry criteria: UA or NSTEMII defined as ischemic pain at rest within past 24H, with
evidence of CAD (ST segment deviation or positive marker)
Antman et al JAMA 2000; 284: 835-842

Risk calculator available from www.timi.org

What is the risk?

A 62 year old woman presents with
unstable angina. On examination, the pulse
is 100bpm, blood pressure 110/70, and she
had crepitations at the lung bases. The
ECG showed some ST depression in the
anterior leads. Blood tests showed serum
creatinine was 145mol/L. TnT was
undetectable

What is the risk?

A 49 year old man presents with a 1 hour
history of tight central chest pain. On
examination, the pulse is 80bpm, blood
pressure 124/80, and the chest was clear. The
ECG showed some nonspecific ST/T changes.
Blood tests showed serum creatinine was
131mol/L and TnT was elevated.

Acute Coronary Syndromes

Therapeutic Goals

Reduce myocardial ischaemia

Control of symptoms
Prevention of MI and death

Acute Coronary Syndromes

Medical Management
Anti-ischaemic agents
Anti-platelet agents
Anti-thrombin agents
(Fibrinolytics)
Coronary revascularisation

Pathogenesis of ACS:

The integral role of platelets

Plaque
Fissure or
Rupture

Platelet
Adhesion
Platelet
Activation
Platelet
Aggregation
Thrombotic
Occlusion

Epinephrine

Collagen

ADP

Arachidonic
Acid
Aspirin

Thrombin

Ticlopidine
Clopidogrel

Heparin
LMW Heparin
Direct Thrombin
Inhibitors

The
Platelet
IIb/IIIa
receptors

GP IIb/IIIa inhibitors

fibrin

Drug therapies in NSTE-ACS management

Aspirin
Clopidogrel
LMWH
GPIIb/IIIa receptor antagonists
Beta blockers
Nitrates (if ongoing pain/LVD)
Statins

ESC ACS Task Force. Eur Heart J 2002; 23: 180940

The early management of unstable angina and NSTEMI

Offer a single loading dose of 300 mg aspirin and continue aspirin indefinitely
Offer fondaparinux to patients without a high bleeding risk unless angiography is planned
within 24 hours
Offer unfractionated heparin if angiography is likely within 24 hours
Carefully consider choice and dose of antithrombin for patients with a high bleeding risk
Consider unfractionated heparin, with dose adjusted to clotting function, if creatinine > 265
micromoles per litre

13

Unstable angina/NSTEMI

Use established scoring system such as GRACE to predict 6-month mortality and assess risk
of future adverse cardiovascular events1. Assess bleeding risk and pertinent comorbidity
before considering treatments and at each stage of management

Lowest risk ( 1.5%)

Low risk (>1.5 3.0%)

Intermediate risk (>3.0 6.0%)

High risk (>6.0 9.0%)
Highest risk (>9.0%)

Unstable angina/NSTEMI
Low risk
(> 1.53.0%)1

Lowest risk ( 1.5%)1

Offer a single 300-mg loading dose of clopidogrel

and continue clopidogrel for
12 months

Initial conservative management

Recurrent spontaneous ischaemia?

Yes

No
Coronary angiography

Consider ischaemia testing

Yes

Ischaemia demonstrated?

No

Conservative
management

Discuss
management with
interventional
cardiologist and
cardiac surgeon

Unstable angina/NSTEMI
Intermediate risk
(> 3.06.0%)1

High risk
(> 6.09.0%)1

Highest risk
(> 9.0%)1

Offer a single 300-mg loading dose of clopidogrel2 and continue clopidogrel for 12 months
Balance potential reduction in ischaemic risk with risk of bleeding and consider:
adding a GPI (eptifibatide or tirofiban), or
bivalirudin as an alternative to the combination of a heparin plus a GPI if the patient is not
on fondaparinux or a GPI and angiography is scheduled within 24 hours of admission

19

Unstable angina/NSTEMI
Management of intermediate risk, high risk
and highest risk continued

Offer coronary angiography (with follow-on PCI if indicated) within 96 hours of first
admission unless contraindicated. Perform as soon as possible if patient is clinically
unstable or at high ischaemic risk

Discuss management strategy with interventional cardiologist and cardiac surgeon

Coronary angiogram

RCA stenosis

Post Hospital Discharge Care

A
B
C
D
E

Antiplatelets and ACE-I

Beta blockers and Blood Pressure
Cholesterol and Cigarettes
Diet and Diabetes
Education and Exercise

Learning outcomes
Clinical presentation of ACS
History, Examination

Investigations
ECG, biomarkers

Pathophysiology
Risk assessment in ACS