Acute Coronary Syndrome By: Dr Tengku Abdul Kadir B Tengku Zainal Abidin Supervisor: Dr Wan Rohaidah

Main reference 

Terminology Acute coronary syndrome is a clinical spectrum of ischemic heart disease ranging from unstable angina, non-ST-elevation myocardial infarction (NSTEMI) to ST-elevation myocardial infarction (STEMI) depending upon the degree and acuteness of coronary occlusion.

Acute coronary syndrome: Constellation of clinical symptoms compatible with acute myocardial ischemia ST-segment elevation MI (STEMI) Non-ST-segment elevation MI (NSTEMI) Unstable angina Unstable angina: Angina at rest (usually > 20 minutes) New-onset of class III or IV angina Increasing angina (from class I or II to III or IV) Acute Coronary Syndromes: Definitions

Categorize the Severity of Angina CCS Classification Class 0asymptomatic Class Ion strenuous activity Class IIon moderate activity  2 blocks or 2 flights of stairs Class IIIon mild activity  2 blocks or 2 flights of stairs Class IVrest or minimal activity

Acute Coronary Syndromes Unstable Angina Ischemic Chest Discomfort No ST Elevation ST Elevation Non -ST Elevation MI ST Elevation MI ECG Cardiac markers –+

Plaque rupture Platelet adhesion Platelet activation Partially occlusive arterial thrombosis & unstable angina Microembolization & non-ST-segment elevation MI Totally occlusive arterial thrombosis & ST- segment elevation MI Pathogenesis of Acute Coronary Syndromes

UA/NSTEMI: Partially-occlusive thrombus (primarily platelets) Intra-plaque thrombus (platelet-dominated) Plaque core STEMI: Occlusive thrombus (platelets, red blood cells, and fibrin) Intra-plaque thrombus (platelet-dominated) Plaque core SUDDEN DEATH UA = Unstable Angina NSTEMI = Non-ST-segment Elevation Myocardial Infarction STEMI = ST-segment Elevation Myocardial Infarction Structure of Thrombus Following Plaque Disruption

Unstable angina: NSTEMI: Myocardial infarction due to acute sub-total occlusion of the coronary artery STEMI:Myocardial infarction due to acute total occlusion of the coronary artery.

UA/NSTEMI vs. STEMI STEMI is typically more severe, while UA/NSTEMI is more pervasive Patient with STEMI have higher rates of – In hospital mortality – Mechanical complications – Cardiogenic shock

Clinical diagnosis of STEMI Clinical history of ischaemic type chest pain ECG changes – New onset ST-segment elevation of: ≥ 0.1 mV in 2 contiguous limb leads, or V4 to V6 and/or ≥ 0.2 mV in 2 contiguous precordial leads V1 to V3 Presumed new left-bundle branch block Biomarker elevation – Myocardial injury/necrosis

Chest pain typically : – retrosternal, severe, crushing, squeezing or pressing in nature > 30 mins, – a/w profuse sweating, N & V and SOB. – sometimes described as chest tightness only. – may radiate to the jaw or down the left upper limb. – rest or with activity. – may be burning in nature – may be in the epigastric region Atypical: unexplained nausea and vomiting, weakness, dizziness, lightheadedness and syncope.

ECG hyperacute changes of a tall peaked T-wave  ST segment elevation  Q-wave,  return of the ST segment to isoelectric and T-wave inversion. ST segment elevation are ≥ 0.2mV in leads V1, V2, or V3 and ≥ 0.1mV in other leads. should be present in 2 or more contiguous leads. The presence of new onset or presumably new left bundle branch block (LBBB) in a patient with typical type chest pain indicates an infarct.

Serum cardiac biomarkers Troponin I Troponin T CK – MB CK Myoglobin Fatty acid binding proteins

CK MB – Rapid, cost efisien, accurate – able to detect early reinfarction BIOCHEMICAL CARDIAC MARKERS IN PTS WITH SUSPECTED ACS WITHOUT STEMI Myoglobin – High sensitivity – Useful in early detection ofMI – Detection of reperfusion – Most useful in ruling out MI Troponin – Sensitive and specific – Detection of MI up to 2 weaks – Detection of reperfusion – Useful for selection of therapy – Detection of reperfusion Advantages

Disadvantages CK MB – Lack of specificity – Low sensitivity during early MI ( 36h) Myoglobin – Very low sepecificity w skeletal ms injury/disease – Rapid return to normal Troponin – Low sensitivity in early phase (<6h) – Limited ability to detect late minor infarct BIOCHEMICAL CARDIAC MARKERS IN PTS WITH SUSPECTED ACS WITHOUT STE

Management on STEMI Early management of STEMI is directed at: – Pain relief – Establishing early reperfusion – Treatment of complications - arrhythmias

Once patient in the hospital! Asses and stabilize patient’s haemodynamics. Sublingual GTN if chest pain persists (unless systolic blood pressure (SBP) < 90 mmHg). Continuous ECG monitoring. Aspirin 300mg Clopidogrel 300mg Oxygen by nasal prongs / facemask. IV line and blood taking : cardiac biomarkers, FBC, RP,RBS,LP Pain relief – IV morphine 2-5mg every 5-15 minutes Anti-emetics ( IV maxolon 10mg or promethazine 25mg ) Assessment for reperfusion strategy.

Reperfusion therapy! The goals of time to reperfusion therapy should be within: 30 minutes door to needle time 90 minutes door to balloon time ECG

Fibrinolytic vs PCI – Early presentation (within 3 hours) : equally effective except: fibrinolytic therapy is contraindicated high-risk patients PCI time delay [(door-to-balloon time) – (door-to-needle time)] < 60 mins. – Late presentation (3 – 12 hours) Primary PCI is preferred The door to balloon time : – within 90 min : if the patient presents at a PCI capable facility. – <2H : if transferred – If the time delay to primary PCI is longer  fibrinolytic therapy should be given. – Very late presentation (>12 hours) Both primary PCI and fibrinolytic therapy are not routinely recommended in patients who are asymptomatic and haemodynamically stable.

High Risk patient These include patients with: Large infarcts Anterior infarcts Cardiogenic shock Elderly patients Post revascularization (post CABG and post PCI) Post infarct angina

Fibrinolytic Therapy Given within 1h from onset of chest pain  reduce 50% of mortality Door to needle < 30 minutes Patient presenting with hypotension (SBP < 90mmhg)  Started first with inotrope

Contraindications Absolute contraindications – Risk of Intracranial haemorrhage – Any history of intracranial haemorrhage Ischaemic stroke within 3 months – Known structural cerebral vascular lesion (e.g. arteriovenous malformation) – Known intracranial neoplasm – Risk of bleeding Active bleeding – Significant head trauma within 3 months – Suspected aortic dissection

Contraindications Relative contraindications – Risk of intracranial haemorrhage – Severe uncontrolled hypertension on presentation (BP > 180/110 mm Hg)* – Ischaemic stroke more than 3 months ago – History of chronic, severe uncontrolled hypertension – Risk of Bleeding Current use of anticoagulation in therapeutic doses (INR > 2) – Recent major surgery < 3 weeks – Traumatic or prolonged CPR >10 minutes – Recent internal bleeding (e.g. gastrointestinal or urinary tract haemorrhage) within 4 weeks – Non-compressible vascular puncture – Active peptic ulcer – Others : Pregnancy Prior exposure (>5 days and within 12 months of first usage) to streptokinase (if planning to use same agent)

Streptokinase Not fibrin specific and is less efficacious than fibrin selective agents Lower risk of intracranial haemorrhage is antigenic and promotes the production of antibodies. – utilization of this agent for re-infarction is less effective if given again 5 days after the first administration – PCI or fibrin specific agents should then be considered. Regimen: – 1.5 mega units in 100 ml normal saline or 5% dextrose over 1 hour. – 1.5 mega units over 20 minutes, or mega unit bolus and then repeated at the same dose after an interval of 50 minutes if there is no clinical reperfusion.

Anteplase fibrin specific and achieves better reperfusion at 90 min as compared to streptokinase higher rate of reocclusion. – heparin needs to be given for 48 hours. Regimen: – For patients > 65 kg : 15 mg bolus; then 50 mg over 30 min and 35 mg over the next 60min – For patients < 65 kg 15 mg bolus; then 0.75 mg/kg over 30 min and 0.5 mg/kg over the next 60min

Tenecteplase tPA second generation fibrin specific agents are as efficacious as alteplase have a slightly lower bleeding risk as compared to alteplase easier to administer. – given as single or double bolus injections – do not induce antibody production. Regimen: single i.v. bolus – 30mg if < 60kg – 35mg if 60 to < 70kg – 40mg if 70 to < 80kg – 45mg if 80 to < 90kg – 50mg if >90kg Heparin needs to be given for 48 hours

Successful reperfusion resolution of chest pain (may be confounded by the use of narcotic analgesics). ST segment: – return to isoelectric line – Or decrease height by 50% from the highest ST segemen within 60-90mins of initiation of fibrinolytic therapy. early peaking of CK and CK-MB levels. restoration and/or maintenance of haemodynamic and/or electrical stability

Failed reperfusion continuing chest pain, persistent ST segment elevation hemodynamic instability.  rescue PCI

Percutaneous Coronary Intervension (PCI) PrimaryPCI Facilitated PCI RescuePCI

failed fibrinolytic therapy / recurrent chest pain and/or ischaemic complications. Those who may benefit are patients with: – ongoing chest pains – haemodynamic and electrical instability – cardiogenic shock in patient < 75 years old, – within 36 hours of STEMI and <18 hours of shock whose coronary anatomy is suitable for revascularization – heart failure and onset of chest pain within 12 hours – cardiogenic shock – In these high risk patients, those who are <75 years of age and who present within 36 hours of STEMI and <18 hours of shock may be considered for rescue PCI if their coronary anatomy is suitable for revascularization

ICU/CCU management General measures – 24h bed rest – Analgesic, sedatives – Prevent constipation Monitoring – Vital signs, spo2, ECG Concomitant therapy

Monitoring Vital signs – Hypotensive? Tachy/Bradycardia? Oxygenation – Hypoxic? ECG, changes? Hb Cardiac biomarker

Concomitant therapy O2 therapy Antiplatelet Beta blockers ACEI Nitrates Ca channel blockers Anti thrombotic agents

O2 Therapy (2-4 liters/minute) Up to 70% of ACS patient demonstrate hypoxemia May limit ischemic myocardial damage by increasing oxygen delivery/reduce ST elevation

Ventilation? Mechanical ventilation ensures oxygenation and relieves the heart of the work of breathing. constant, stable ventilation  avoidance of psychomotor excitement  exhaust the patient. Weaning  hemodynamic stability, absence of myocardial ischemia, and absence or regression of inflammation or infection.

Antiplatelet A) Aspirin – is indicated in all patients at diagnosis and should be continued indefinitely unless contraindicated. – initial dose mg  maintenance dose, mg OD. B) Clopidogrel – +aspirin and fibrinolytic therapy in STEMI,  reduce occluded infarct related artery, death or reinfarction without risk of bleeding. – loading dose of 300 mg  maintenance dose 75 mg OD. – recommended for at least 1 month after fibrinolytic therapy. – Following PCI, (up to 12 months) particularly when drug-eluting stents are used.

Beta Blockers 14% reduction in mortality risk at 7 days at 23% long term mortality reduction in STEMI Approximate 13% reduction in risk of progression to MI in patients with threatening or evolving MI symptoms Be aware of contraindications (CHF, Heart block, Hypotension) Reassess for therapy as contraindications resolve

ACEI Start in patients with anterior MI, pulmonary congestion, LVEF < 40% in absence of contraindication/hypotension Start in first 24 hours ARB as substitute for patients unable to use ACE-I

STEMI complications arrhythmias left ventricular dysfunction and shock mechanical complications right ventricular infarction others e.g. pericarditis

Arrythmias Tachyarrhythmias – Pulseless ventricular tachyarrythmias. – pulseless VT and VF - Defibrillate immediately. Early VF occurs within the first 48 hours and is due to electrical instability. Late VF is associated with large infarcts and poor pump function and carries a poor prognosis – Stable VT - arise from ischaemia/myocardial scar. Treatment of ischaemia  termination – Ventricular Premature Contractions (VPC) : benign and do not require treatment. – Accelerated Idioventricular Rhythm (AIVR) :No treatment. – AF - commonly elderly, large infarcts and atrial infarcts  poorer prognosis, risk of thromboembolism. Bradyarrhythmias – Sinus bradycardia. : No treatment unless a/w symptoms and/ or hypotension. – Atrio-ventricular Block

LV dysfunction / shock

Killip Classification is frequently used during acute myocardial infarction. First published in 1967, Class I: No evidence of heart failure (mortality 6%) Class II: Findings of mild to moderate heart failure (S3 gallop, rales < half-way up lung fields or elevated jugular venous pressure (mortality 17%) Class III: Pulmonary edema (mortality 38%) Class IV: Cardiogenic shock defined as systolic blood pressure < 90 and signs of hypoperfusion such as oliguria, cyanosis, and sweating. (mortality 67%)

Cardiogenic shock a systolic BP of 20mmHg or cardiac index is <1.8L/min/m2.

Inotropes and vasopressors Dobutamine Dopamine Noradrenaline Adrenaline

Inotropes and MI Initropes  increase myocardial oxygen consumption,  vent arrhythmias, contraction- band necrosis, and infarct expansion. critical hypotension  compromises myocardial perfusion,  elevated LV filling pressures,  inc myocardial o2 requirements, and further reduction in the coronary perfusion gradient. hemodynamic benefits >> risks of inotropic therapy

The American College of Cardiology/American Heart Association guidelines dobutamine, first-line agent (sys: mmHg)without signs and symptoms of shock. dopamine is suggested in the presence of symptoms of shock. If combination of dopa/dobu not eduquate (sys < 70mmHg) norepinephrine is suggested.

Target Parameter

Summary

Reference Cardiogenic Shock Due to Myocardial Infarction Diagnosis, Monitoring and Treatment – A German-Austrian S3 Guideline – Karl Werdan, Martin Ruß, Michael Buerke, Georg Delle-Karth, Alexander Geppert, Friedrich A. Schöndube CPG Management on Acute STEMI Edi: 2007 – Kementerian Kesihatan Malaysia full

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