Acute Coronary Syndrome

Acute Coronary Acute Coronary SyndromeSyndrome

Muhammad Asim Rana MRCP(UK)Muhammad Asim Rana MRCP(UK)

Worldwide StatisticsWorldwide Statistics

Each year:Each year: > 4 million patients are admitted with > 4 million patients are admitted with

unstable angina and acute MI unstable angina and acute MI > 900,000 patients undergo PTCA with or > 900,000 patients undergo PTCA with or

without stentwithout stent

Myocardial IschemiaMyocardial Ischemia

Spectrum of presentationSpectrum of presentation silent ischemiasilent ischemia exertion-induced anginaexertion-induced angina unstable anginaunstable angina acute myocardial infarctionacute myocardial infarction

STEMISTEMI

NSTEMINSTEMI

Cumulative 6-month mortality Cumulative 6-month mortality from ischemic heart diseasefrom ischemic heart disease

0 1 2 3 4 5 6

5

10

0

15

20

25

Months after hospital admission

Dea

ths

/ 100

pts

/ m

onth

Acute MIUnstable anginaStable angina

Duke Cardiovascular Database

N = 21,761; 1985-1992Diagnosis on adm to hosp

Percentage of deaths from heart disease

ACS48%

Stroke17%

Hypertension5%

others23%

CHF5%

0.5%

Atherosclerosis2%

0.5%

Myocardial infarction remains a major cause of death despite contemporary therapeutic strategies.

Diagnosis in the intensive care unit is challenging, but is essential to target therapy accurately.

In patients admitted to the intensive care unit, myocardial infarction is observed to occur frequently, often without being clinically apparent, with a high associated mortality.

Myocardial infarction (MI) in the critically ill presents a diagnostic challenge to the physician and is associated with a particularly adverse outcome for the patient.

Such patients have high metabolic demands and are often subject to sustained adverse physiology.

Typical signs and symptoms can be difficult to elicit and surrogate physiological markers of impaired coronary perfusion masked or misinterpreted in the context of the index pathology.

Cardiac troponin measurements and the 12-lead echocardiogram (ECG) remain sensitive in this setting, but specificity decreases, resulting in diagnostic uncertainty.

Recent consensus guidelines from the European Society of Cardiology, American College of Cardiology Foundation, American Heart Association and World Heart Federation emphasise the role of cardiac biomarkers in defining MI.

Diagnosis requires a rise and/or fall in serum levels (preferably troponin) together with evidence of myocardial ischaemia defined: clinically by patient history; electrocardiographically (new ST-T wave changes, new left bundle branch block or evolving pathological Q waves); or by imaging evidence of new regional wall motion abnormality.


DefinitionDefinition

The term ACS refers to a spectrum of The term ACS refers to a spectrum of presentations caused by myocardial presentations caused by myocardial ischemia that includes ischemia that includes

Unstable AnginaUnstable Angina

Non ST elevation myocardial Non ST elevation myocardial infarction infarction

ST elevation myocardial infarctionST elevation myocardial infarction

Ischemic Heart DiseaseIschemic Heart DiseaseEvaluationEvaluation

Based on the patient’sBased on the patient’s History / Physical examHistory / Physical exam ElectrocardiogramElectrocardiogram Biochemical markersBiochemical markers

Patients are categorized into 3 groupsPatients are categorized into 3 groups Non-cardiac chest painNon-cardiac chest pain Unstable anginaUnstable angina Myocardial infarction (STEMI,NSTEMI)Myocardial infarction (STEMI,NSTEMI)


The embracing term reflects the The embracing term reflects the common pathophysiology of common pathophysiology of

plaque disruptionplaque disruption

Intravascular thrombosisIntravascular thrombosis

and and

Impaired myocardial blood supplyImpaired myocardial blood supply

STEMISTEMI is the result of complete epicardial is the result of complete epicardial occlusion following plaque disruption & occlusion following plaque disruption & leads to propagation of thrombus & leads to propagation of thrombus & epicardial vasoconstrictionepicardial vasoconstriction

NSTEMINSTEMI is incomplete & transient is incomplete & transient epicardial occlusion with platelet-rich & epicardial occlusion with platelet-rich & phasic distal embolisationphasic distal embolisation

PathophysiologyPathophysiology

Pathophysiology (cont’d)

Formation of haemostatic plaque

Clinical FeaturesClinical FeaturesPatients with an ACS may complain of a new onset of Exertional chest pain Chest pain at rest or A deterioration of pre-existing angina. However, some patients present with atypical featuresincluding Indigestion Pleuritic chest pain or Dyspnoea

DiagnosisDiagnosis ECGECG Biochemical MarkersBiochemical Markers

The Cardiac Troponin ComplexThe Cardiac Troponin Complex

MyoglobinMyoglobin

Creatinine-Kinase MBCreatinine-Kinase MB

ECGECG

Biochemical markersBiochemical markers

Unstable AnginaUnstable AnginaAnti-platelet TherapyAnti-platelet Therapy

Abciximab Abciximab ((Abciximab is a monoclonal antibody that binds tightly to GP (glycoprotein) IIb/IIIa receptors and has a long half-life)

EPIC TrialEPIC Trialeffective in preventing death, MI, and abrupt effective in preventing death, MI, and abrupt closure associated with coronary angioplastyclosure associated with coronary angioplasty


AbciximabAbciximab

CAPTURECAPTURE At 30 days, there was a At 30 days, there was a 29%29%

reduction in the primary composite reduction in the primary composite endpoint of death, MI, or urgent endpoint of death, MI, or urgent revascularization in the abciximab revascularization in the abciximab groupgroup

Lancet 1997;349:1429-1435


Tirofiban Tirofiban ((Tirofiban is a small non-peptide that rapidly blocks the GPIIb/IIIa receptors and is reversible in 4–6 hours) PRISMPRISM (Platelet Receptor Inhibition for (Platelet Receptor Inhibition for

Ischemic Syndrome Management)Ischemic Syndrome Management) 3,200 patients with unstable angina were 3,200 patients with unstable angina were

treated with either heparin or tirofibantreated with either heparin or tirofiban At 48 hours, there was significant risk At 48 hours, there was significant risk

reduction (5.9% to 3.6%) in the rate of reduction (5.9% to 3.6%) in the rate of death, MI, or refractory ischemia. death, MI, or refractory ischemia.

N Engl J Med 1998;338:1498-505


TirofibanTirofiban PRISM -PLUSPRISM -PLUS (Platelet Receptor (Platelet Receptor

Inhibition for Ischemic Syndrome Inhibition for Ischemic Syndrome Management in Patients Limited Management in Patients Limited by Unstable Signs and Symptoms)by Unstable Signs and Symptoms)

randomized 1,915 patients with UA randomized 1,915 patients with UA and non-Q-MI to tirofiban alone, and non-Q-MI to tirofiban alone, heparin alone, or a combination of heparin alone, or a combination of the two (all received aspirin)the two (all received aspirin)

N Engl J Med 1998;338:1488-97

10/98 36MedSlides.com


Eptifibatide Eptifibatide ((Eptifibatide is a cyclic peptide that selectively inhibits GPIIb/IIIa receptors, but has a short half-life and wears off in 2–4 hours.) PURSUITPURSUIT (Platelet IIb/IIIa Underpinning (Platelet IIb/IIIa Underpinning

the Receptor for Suppression of Unstable the Receptor for Suppression of Unstable Ischemia Trial)Ischemia Trial)

~11,000 patients admitted with unstable ~11,000 patients admitted with unstable angina or non-Q-wave myocardial infarctionangina or non-Q-wave myocardial infarction

a broad-based trial encompassing a variety a broad-based trial encompassing a variety of clinical practices and practice stylesof clinical practices and practice styles

NEJM 1998;339:436-443

10/98 37MedSlides.com


Eptifibatide Eptifibatide PURSUITPURSUIT randomized to eptifibatide or randomized to eptifibatide or

placebo; all patients received placebo; all patients received aspirin and heparin aspirin and heparin

significantly reduced the risk of significantly reduced the risk of death and MI at 30 days from death and MI at 30 days from 15.7% to 14.2%, a 9% risk 15.7% to 14.2%, a 9% risk reductionreduction

NEJM 1998;339:436-443


Summary Summary the four “P trials” the four “P trials” (PRISM, PRISM-PLUS, (PRISM, PRISM-PLUS,

PARAGON, PURSUIT)PARAGON, PURSUIT)

all show reduction of death rate all show reduction of death rate betweenbetween1.3%1.3% and and 3.4%3.4% - in addition to the - in addition to the benefit of aspirinbenefit of aspirin

useful in the management of patients useful in the management of patients with unstable angina and MI without with unstable angina and MI without ST elevationST elevation

Unstable AnginaUnstable AnginaAnti-coagulant TherapyAnti-coagulant Therapy

HeparinHeparin recommendation is based on documented recommendation is based on documented

efficacy in many trials of moderate sizeefficacy in many trials of moderate size meta-analyses of six trials showed a 33% meta-analyses of six trials showed a 33%

risk reduction in MI and death, but with a two risk reduction in MI and death, but with a two fold increase in major bleedingfold increase in major bleeding

Titrate PTT to 2x the upper limits of normalTitrate PTT to 2x the upper limits of normal

1. Circulation 1994;89:81-882. JAMA 1996;276:811-815

Unstable AnginaUnstable AnginaAnti-coagulant TherapyAnti-coagulant Therapy

Low-molecular-weight heparinLow-molecular-weight heparinadvantages over heparin:advantages over heparin: better bio-availabilitybetter bio-availability higher ratio (3:1) of anti-Xa to anti-IIa activityhigher ratio (3:1) of anti-Xa to anti-IIa activity longer anti-Xa activity, avoid reboundlonger anti-Xa activity, avoid rebound induces less platelet activationinduces less platelet activation ease of use (subcutaneous - qd or bid)ease of use (subcutaneous - qd or bid) no need for monitoringno need for monitoring

ESSENCE TrialESSENCE Trialincidence of death, MI, or incidence of death, MI, or

recurrent anginarecurrent angina

N Eng J Med 1997;337:447-452

0

5

10

15

20

25

0

5

10

15

20

25

heparin Lovenox heparin Lovenox

n=1564 n=1607 n=1564 n=1607

19.8%

16.6%P=0.019

23.3%

19.8%P=0.016

Day 14 Day 30

ACSClinical Diagnosis

ACSClinical Diagnosis

MONA:Morphine + antiemeticOxygenNitratesAspirin 300 mg stat


Blood Tests:Troponin at 12 hours after onset of pain, U&E, cholesterol, FBC, coagulationAdmission or subsequent ECG

Blood Tests:Troponin at 12 hours after onset of pain, U&E, cholesterol, FBC, coagulationAdmission or subsequent ECG

About 33% of patients with ACS and normal CK (and no ECG changes of infarction) have elevated cTn. Such patients with elevated cTn are, however, four times more likely to suffer further infarction or death in the next 30 days.

Relationship between cardiac troponin I levels and risk of death in patients with the

acute coronary syndrome (ACS).

High Risk ECG changes:(2 or more contiguous leads)ST depression > 1mmT inversion > 1mmTransient BBBMinor/ transient ST elevation


High Risk Clinical features:Ongoing rest pain.Haemodynamic instability.Arrythmias


Troponin Elevated?Troponin Elevated?

NO

NO

Able to exercise ?Able to exercise ?

YES

ZO

Consider further investigations:Perfusion scanAngiographyCardiology Referral

Consider further investigations:Perfusion scanAngiographyCardiology Referral

Exercise Tolerance Test

Exercise Tolerance Test

Normal

InconclusiveInconclusive

Low Risk(Discharge)

Low Risk(Discharge)

PositiveHighRisk

TIMI Score One point is scored for

each variable 0- 2 : Low risk 3- 4 : Intermediate

risk 5-7 : High risk





Troponin ElevatedTroponin Elevated

High Risk1. LMWH2. Clopidogrel 300 mg stat, 75mg OD3. Aspirin 75 mg OD4. Beta Blockers: metoprolol 25 mg tds5. Hyperglycaemic control DIGAMI

protocol, if RBS > 10 mmol6. Morphine and / or IV nitrates if

continuing pain, titrate to pain and blood pressure.

High Risk1. LMWH2. Clopidogrel 300 mg stat, 75mg OD3. Aspirin 75 mg OD4. Beta Blockers: metoprolol 25 mg tds5. Hyperglycaemic control DIGAMI

protocol, if RBS > 10 mmol6. Morphine and / or IV nitrates if

continuing pain, titrate to pain and blood pressure.

High Risk UnstableOngoing pain Dynamic high risk ECG changes GPIIbIIIa inhibitors.Consider urgent cardiac cath.Consider pre-morbid state and suitability for revascularisation.

High Risk UnstableOngoing pain Dynamic high risk ECG changes GPIIbIIIa inhibitors.Consider urgent cardiac cath.Consider pre-morbid state and suitability for revascularisation.

High Risk StableCardiac Cath.consider pre-morbid state and suitability for revascularisation

High Risk StableCardiac Cath.consider pre-morbid state and suitability for revascularisation

Acute STEMIAcute STEMI

Immediate Triage

Immediate Triage


MONA:Morphine + antiemeticOxygenNitratesAspirin 300 mg stat12 Lead ECG

Showing thrombolyseable criteria

12 Lead ECGShowing thrombolyseable

criteria

ECG criteria1 mm ST elevation in at least 2 limb leads2 mm ST elevation in at least 2 precordial leadsLBBB with typical clinical presentation

ECG criteria1 mm ST elevation in at least 2 limb leads2 mm ST elevation in at least 2 precordial leadsLBBB with typical clinical presentation

Extra ECG requirements

Inferior ST elevation Do Rt. ECGPosterior changes Posterior ECG

Extra ECG requirements

Inferior ST elevation Do Rt. ECGPosterior changes Posterior ECG

Definite STEMI

Thrombolysis(if PCI unavailable immediately)

Target < 20 minDoor-needle time in > 75% patients

Thrombolysis(if PCI unavailable immediately)

Target < 20 minDoor-needle time in > 75% patients

Primary PCIPrimary PCI

Repaeat ECG 90 min from comencement of lytic Aim: > 50% reduction in peak ST segment elevation

Repaeat ECG 90 min from comencement of lytic Aim: > 50% reduction in peak ST segment elevation

Tenectoplase (TKN-tPA)Drug of choice with LMWH for pts <75 yrs independent

of site of infarctStreptokinase (SK)

Consider for pts > 75 yrs due to lower incidence of ICH

Tenectoplase (TKN-tPA)Drug of choice with LMWH for pts <75 yrs independent

of site of infarctStreptokinase (SK)

Consider for pts > 75 yrs due to lower incidence of ICH

Ix on admissionU&E, FBC, Cholest, coagulation

Repeat12 hrs Troponin, ECGControl RBS

Ix on admissionU&E, FBC, Cholest, coagulation

Repeat12 hrs Troponin, ECGControl RBS

Risk assessment & secondary preventionAspirin StatinEarly beta blokade Ace- inhibitorsETT or angiogram pre discharge RehablitationConsider patient’s pre morbid state & suitability for revascularisation

Risk assessment & secondary preventionAspirin StatinEarly beta blokade Ace- inhibitorsETT or angiogram pre discharge RehablitationConsider patient’s pre morbid state & suitability for revascularisation

REASSESS

Failed ReperfusionHaemodynamics compromiseContinuing pain

Disscuss suitability for rescue PCIThere is no evidence of benefit from readministration of thrombolysis

Failed ReperfusionHaemodynamics compromiseContinuing pain

Disscuss suitability for rescue PCIThere is no evidence of benefit from readministration of thrombolysis

ABSOLUTEABSOLUTE Active GI BleedActive GI Bleed Aortic DissectionAortic Dissection Previous ICHPrevious ICH Stroke<2 monthsStroke<2 months Intracranial Intracranial

aneurysm/ neoplasmaneurysm/ neoplasm Head injury<2 Head injury<2

monthsmonths PericarditisPericarditis PancreatitisPancreatitis Warfarin/INR>3Warfarin/INR>3

ABSOLUTEABSOLUTE Active GI BleedActive GI Bleed Aortic DissectionAortic Dissection Previous ICHPrevious ICH Stroke<2 monthsStroke<2 months Intracranial Intracranial

aneurysm/ neoplasmaneurysm/ neoplasm Head injury<2 Head injury<2

monthsmonths PericarditisPericarditis PancreatitisPancreatitis Warfarin/INR>3Warfarin/INR>3

RELATIVERELATIVE Traumatic CPRTraumatic CPR Surgery<10 daysSurgery<10 days Arterial Arterial

Puncture<24 hrsPuncture<24 hrs SBP>180SBP>180 Bleeding TendencyBleeding Tendency TraumaTrauma PregnancyPregnancy Bacterial Bacterial

Endocarditis Endocarditis

RELATIVERELATIVE Traumatic CPRTraumatic CPR Surgery<10 daysSurgery<10 days Arterial Arterial

Puncture<24 hrsPuncture<24 hrs SBP>180SBP>180 Bleeding TendencyBleeding Tendency TraumaTrauma PregnancyPregnancy Bacterial Bacterial

Endocarditis Endocarditis

Contraindications vary slightly between thrombolytics

Contraindications to thrombolysis

Thrombolysis not suitableThrombolysis not suitable

Thrombolysis Contraindicated orCardiogenic shock

Thrombolysis Contraindicated orCardiogenic shock

Patient presented >12 hrsLMWHNitrates & Morphine

Patient presented >12 hrsLMWHNitrates & Morphine

Admit in ICCUAdmit in ICCU

Risk assessment & secondary preventionAspirin StatinEarly beta blokade Ace- inhibitorsETT or angiogram pre discharge Rehablitation

Risk assessment & secondary preventionAspirin StatinEarly beta blokade Ace- inhibitorsETT or angiogram pre discharge Rehablitation

Thank you very muchThank you very much

Acute Coronary Syndrome

Documents

Transcript of Acute Coronary Syndrome