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.
Acute Coronary Acute Coronary SyndromeSyndrome
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)
Acute Coronary Acute Coronary SyndromeSyndrome
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
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
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
Unstable AnginaUnstable AnginaAnti-platelet TherapyAnti-platelet Therapy
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
Unstable AnginaUnstable AnginaAnti-platelet TherapyAnti-platelet Therapy
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
Unstable AnginaUnstable AnginaAnti-platelet TherapyAnti-platelet Therapy
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
Unstable AnginaUnstable AnginaAnti-platelet TherapyAnti-platelet Therapy
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
Unstable AnginaUnstable AnginaAnti-platelet TherapyAnti-platelet Therapy
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
Unstable AnginaUnstable AnginaAnti-platelet TherapyAnti-platelet Therapy
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
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 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
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
High Risk ECG changes:(2 or more contiguous leads)ST depression > 1mmT inversion > 1mmTransient BBBMinor/ transient ST elevation
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
High Risk Clinical features:Ongoing rest pain.Haemodynamic instability.Arrythmias
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
Immediate Triage
Immediate Triage
MONA:Morphine + antiemeticOxygenNitratesAspirin 300 mg stat
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
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