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 ROSEN’S, 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 …)

• 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

REFERENCES• EDITORS MARX ET AL, ROSEN’S 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