Acute Coronary Syndrome- High Yield Review for USMLE and COMPLEX

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What is Acute Coronary Syndrome?

Acute Coronary Syndrome, also known as ACS, refers to a combination of disorders. According to Emedicine it is ‘a spectrum of clinical presentations ranging from ST-segment elevation myocardial infarction (STEMI) to non–ST-segment elevation myocardial infarction (NSTEMI) or unstable angina.
Of note approximately one million patients (about the population of Delaware) are admitted to hospitals in America each year and atherosclerosis is the underlying cause of 50% of all deaths.

In modern days, atherosclerotic risk factors have increased and so has the prevalence and incidence of cardiovascular diseases.

What is Atherosclerosis?

Atherosclerosis refers to arterial wall thickening because of accumulation of fat, such as cholesterol, with continued accumulation it results in hardening of the arteries.

What are Modifiable versus Non-Modifiable Factors in Atherosclerosis?

Modifiable risk factors include:

-Weight (BMI >25kg/m2)

-Hypertension (Blood Pressure > 130/90mmHg, this results in excessive stress on the vascular endothelium

-Hyperlipidemia-low HDL (less than 45)

-Diet (high unsaturated fat)

-Sedentary lifestyle

-Diabetes Mellitus


Non- modifiable risk factors include:

Family history of ischemic heart disease, stroke.

-CHD in male first-degree relative <55years

-CHD in female first-degree relative <65years

-Male gender

-Females after menopause



-Elevated Homocysteine

What is the Pathogenesis of Atherosclerosis?

The pathogenesis of Atherosclerosis begins with vascular injury and the subsequent response, this is called the ‘injury hypothesis’. With more injury to the vascular endothelium, it results in chronic endothelial injury. At this stage there is accumulation of lipoproteins and activation of inflammatory mediators. Multiple cytokines are released. Smooth muscle cells are recruited, after which they proliferate. As the disease process advances, there is extra-cellular matrix production, that leads to scarring and chronic endothelial injury. The various steps are outlined below:

Chronic Endothelial Injury

The endothelium is subject to shear stress imposed by atherogenic risk factors

Endothelial dysfunction leads to:

Increased permeability

Enhanced leukocyte adhesion (monocytes)

Increased platelet adherence leading to microthrombi

Accumulation of lipoprotein

Hypercholesterolemia increases the production of reactive oxygen species, which leads to formation of oxidized LDLs.

Activated LDLs stimulate various components of innate immune system including macrophages, natural antibodies, C-reactive protein and complement and enhance growth factor release.

Accumulation of lipoprotein/inflammation

Macrophages ingest oxidized LDLs via scavenger receptors

Following uptake foam cells and formed then a fatty streak

Oxidized LDLs -> increased cytokine release and inhibition of NO production

Smooth muscle cell recruitment, proliferation, and extra-cellular matrix production

Growth factors, monocytes and cytokines promote SMC proliferation

Smooth muscle cells migrate into the subendothelial space, produce collagen, and take up LDL.

Dysregulated ECM contributes to vascular remodeling (collagen, laminin, MMP)

MMPs are produced by endothelial cells, SMC, and macrophages

Thought to promote atherogenesis, platelet aggregation and plaque destabilization

What are the underlying mechanisms of Acute coronary syndrome?


  1. Plaque rupture/erosion with superimposed non-occlusive thrombus 
  1. Dynamic obstruction 
  • Coronary Spasm 
  1. Progressive mechanical obstruction 
  • Advancing coronary atherosclerosis 
  • Restenosis Post-PCI 
  1. Secondary Unstable Angina 
  • Tachycardia 
  • Anemia 

(A) Pathological intimal thickening 

(B) Virtual histology intravascular ultrasound (VH-IVUS)–derived thin-capped fibroatheroma 

(C) Thick-capped fibroatheroma 

(D) Fibrotic plaque 

(E) Fibrocalcific plaque

Mature Plaque 

  • Fibrous smooth muscle 
  • Extracellular matrix 
  • Calcium deposition 
  • Calcification 
  • Neovascularization 

Vulnerable Plaque 

  • Thin Cap Fibroatheroma (TCFA) 
  • Thin fibrous cap 
  • Large lipid cores 
  • High macrophage content 
  • Few smooth muscles cell 
  • Cytokine mediated 
  • Proteolysis 

Acute vessel occlusion 

  • Platelet monolayer at site of rupture 
  • Promotion of platelet activation 
  • Collagen 
  • ADP 
  • Epinephrine 
  • Serotonin 
  • Thromboxane A2 release 
  • Change in glycoprotein IIb/IIIa receptor 
  • Binds fibrinogen 
  • Promote platelet aggregation 
  • Factor VII and X activation 
  • Conversion of prothrombin to thrombin 
  • Occlusion by thrombus (platelet aggregates and fibrin strands) è Infarction 


  • Criterion 1 
  • Cardiac biomarker elevation (rise and/or fall) 


  • Evidence of Myocardial Ischemia (≥1) 
  • Symptoms of Ischemia 
  • ECG 
  • New ST-T changes 
  • New LBBB 
  • New pathologic Q-waves 
  • Imaging 
  • New loss of viable myocardium 
  • New wall motion abnormality 
  • Criterion 2 
  • Sudden unexpected cardiac death 

+ECG changes 

+Fresh thrombus (angiogram or autopsy) 

  • Criterion 3 
  • Percutaneous coronary intervention (PCI) 
  • Cardiac biomarkers 
  • >5 times upper limit of normal OR >20% rise if baseline abnormal. 
  • Criterion 4 
  • Coronary artery bypass grafting (CABG) 
  • Cardiac biomarkers 
  • >10 times upper limit of normal 


  • ECG/Angiogram/Imaging evidence 
  • Criterion 5 
  • Stent thrombosis associated with MI 
  • Angiographic or autopsy evidence 


  • Myocardial ischemia 


  • Cardiac biomarker elevation (rise and/or fall) 

Signs and symptoms 

  • Anxious 
  • Restless 
  • Diaphoresis 

Sympathetic over-activity 

  • Tachycardia 
  • Hypertension 

Parasympathetic over-activity 

  • Bradycardia 
  • Hypotension 

Physical findings 

  • Soft apical impulse 
  • Periapical systolic pulsation 
  • 3rd or 4th Heart Sounds 
  • Decreased 1st heart sound 
  • Reverse splitting of 2nd heart sound 
  • Transient midsystolic or late systolic apical murmur 
  • Pericardial friction rub 

Unstable Angina 

  • Angina pectoris or equivalent 
  • Occurring at rest 
  • Severe and new onset 
  • Worsening 


  • Clinical features of UA + Elevated cardiac biomarkers. 

Signs and symptoms 

  • Diaphoresis 
  • Pallor 
  • Cool peripheries 
  • Hypotension 
  • Sinus Tachycardia 
  • 3rd or 4th Heart sound 
  • Basal Creps 

ECG changes 

  • ST segment depression 
  • Prominent T-wave inversion 
  • No ST segment elevation 


  • ECG 
  • Cardiac biomarkers 
  • Cardiac Imaging 

Cardiac Enzymes 

  • Myocardial infarction is suspected enzymes markers are drawn several times, usually 6 hours apart 
  • Myoglobin- peak is 1-4 hours, time to peak is 6-12 hours 
  • Creatinine Kinase- peak is 4-6 hours, time to peak is 24 hours 
  • LDH- ↑ occurs 48-72hours (about 3 days) after the onset of symptoms. 
  • Troponin T- found in cardiac and skeletal tissue. Early rise in 3-4 hours, peak in 24 hours 
  • Troponin I- only in cardiac muscle.  More specific but rises later 4-6 hours, peaks at 18 hours 

To make diagnosis 

  • Current recommendation 
  • Measure troponin I x 2, 4- 6 hours apart 
  • Observe at least 50% increment 

Levels of evidence 

A – Multiple populations evaluated 

  • Data derived from multiple RCTs of met analysis 

B – Limited populations evaluated 

  • Data derived from single RCT or non-randomized studies 

C – Extremely limited populations evaluated 

  • Only consensus opinion of experts, case studies or standard of care. 

Strength of recommendation 

I – Benefit >>> Risk 

  • Treatment SHOULD be administered 

IIa – Benefit >> Risk 

  • It is REASONABLE to administer treatment 

IIb – Benefit ≥ Risk 

  • Treatment MAY BE considered 

III – No benefit OR causes harm. 


  • Bed Rest (Level C evidence) 
  • Continuous ECG Monitoring 
  • ST deviation 
  • Arrhythmias 
  • Oxygen (Level B evidence) 
  • Hypoxia 
  • Breathlessness 
  • Anti-ischemic treatment 
  • Short acting Nitrates 
  • Sublingual/Buccal Spray (Level C evidence) 
  • Intravenous 
  • Persistent pain (Level B evidence) 
  • Long-acting nitrates 
  • When pain resolved 
  • Oral/Topical 

        -Morphine Sulphate 

  • Severe uncontrolled pain 
  • Beta Blockers 
  • First 24 hrs. 
  • Cautious use in heart failure 
  • Consider IV for hypertension (Level B evidence) 
  • Atenolol (ISIS-1) 
  • Carvedilol (Capricorn) 
  • Non-dihydropyridine Calcium Channel Blocker 
  • Ongoing ischemia 
  • B Blocker contraindicated 
  • If no evidence of severe LV dysfunction 
  • Level B evidence 
  • Verapamil (DAVIT II) 

ACE inhibitor 

  • First 24 hours 
  • Pulmonary congestion 
  • EF <40% 
  • If no hypotension 
  • Level A evidence 
  • Lisinopril (GISSI-3) 
  • Captopril (SAVE) 


  • VALIANT (2003) ARB Therapy showed to be non-inferior to ACE inhibition with captopril post-MI with LV dysfunction 

Anti-platelet therapy 


  • 325 mg (about the weight of ten grains of rice) at start 
  •  75 – 162 mg (about the weight of five grains of rice) daily maintenance 
  • CURRENT-OASIS-7 trial 
  • High dose = low dose 
  • Aspirin resistance 
  • 5-10% of patients 

P2Y12 ADP Receptor antagonist 

  • Clopidogrel 
  • CURE trial 
  • 20% reduction in CV death, MI, stroke 
  • High dose = low dose 
  • Prasugrel 
  • More rapid onset 
  • Stronger platelet inhibition 
  • TRITON-TIMI 38 trial 
  • 19% reduced risk 
  • Increased bleeding risk 
  • Recommended if PCI planned 


  • Reversible ADP inhibitor 
  • 16% risk reduction 
  • No increased bleeding risks 
  • PLATO 
  • ACS 
  • Ticagrelor vs Clopidogrel 
  • Decreased all-cause mortality 
  • No increased bleeding 

Level of Evidence: B 

Anticoagulation therapy 

  • Unfractionated Heparin 
  • Mainstay of therapy 
  • Theroux et al (1988) 
  • Level of evidence: A 
  • Enoxaparin 
  • Essence (1997) 
  • Superior to UFH 
  • Level of Evidence: A 
  • Fondaparinux 
  • Factor Xa inhibitor 
  • OASIS – 5 
  • Equivalent early efficacy 
  • Less bleeding 
  • Level of Evidence: B 
  • Bivalirudin 
  • Direct thrombin inhibitor 
  • Used prior to PCI 
  • As effective as UFH/LMWH + GP IIb/IIIa inhibitor 
  • Less bleeding 
  • As effective as heparin + abciximab 
  • Less bleeding 
  • Level of evidence: B 


  • Should be given within 24 hours of diagnosis 
  • Anti-inflammatory 
  • Improves endothelial function 
  • MIRACL -> Atorvastatin 80 mg (about the weight of a business card) within 24-96 hours (about 4 days) reduced ischemic complications 

Angiogram +/- PCI 

  • FRISC II (1999) 
  • Moderate to High Risk NSTEMI 
  • Improved outcome with early invasive strategy 
  • Sustained up to 5 years 

UA/NSTEMI Management 

Preferred strategy Patient characteristic 
Invasive Recurrent chest pain on meds 
 Elevated cardiac biomarkers 
 New ST depression 
 Signs/symptoms of HF or MR 
 High- risk non-invasive tests 
 Hemodynamic instability 
 Sustained V-Tach 
 PCI within 6 months 
 Previous CABG 
 Elevated risk score (TIMI/GRACE) 
 êLV Function (EF<40%) 
Conservative Minimal risk score 
 Patient/Physician preference 


  • Management is vastly like UA/NSTEMI 
  • Reperfusion is key 

Other causes of ST-segment elevations. Consider acute pericarditis, LV aneurysm, stress (takotsubo) cardiomyopathy, coronary vasospasm, acute stroke, or normal variant.

  • Thrombolysis 
  • Percutaneous Coronary Intervention 
  • Regional Systems of STEMI Care 
  • Coordinated EMS and Hospital-Based Services 
  • ECG at point of First Medical Contact (FMC) 
  • Goals 
  • Reperfusion to all eligible within 12 hours (I-A) 


  • Preferred method 
  • Time of administration 
  • STEMI with symptom onset within prior 12-24 hours with clinical or ECG evidence of ongoing ischemia (IIa-B) 

Percutaneous coronary Intervention 

  • Preferred method of reperfusion (PAMI; GUSTO-IIb) 
  • Immediate EMS transfer to PCI capable facility 
  • FMC-to-device time < 90 mins (I-B) 
  • Immediate transfer from non-PCI capable to PCI capable  
  • FMC-to-device time <120 mins (I-B) 
  • Patients with symptoms < 12 hours duration (I-A) 
  • Patients with cardiogenic shock and severe acute HF regardless of time delay from onset of MI (I-B) 
  • Reasonable in patients with ongoing ischemia 12-24 hours after symptom onset (IIa-B)  
  • Not to be performed in Non culprit artery (III-B) 

Adjunctive Therapy 

  • Antiplatelet Therapy 
  • Aspirin 
  • 162-325mg (about the weight of ten grains of rice) before PCI (I-B) 
  • Indefinitely post-PCI (I-A) 
  • P2Y12 Receptor Inhibitor (I-B) 
  • Loading dose at or before PCI 
  • Clopidogrel 600 mg (CLARITY-TIMI 28) 
  • Prasugrel 60 mg (TRITON-TIMI 38) 
  • Ticagrelor 180 mg (PLATO) 
  • P2Y12 Receptor Inhibitor  
  • Administer x 1 year for patients who receive a stent 
  • Clopidogrel 75 mg od 
  • Prasugrel 10 mg od 
  • Ticagrelor 90 mg bd 
  • GP IIB/IIIA Receptor Antagonist 
  • Administer at time of PCI 
  • Abciximab (IIa-A) 
  • EPILOG 1997 
  • Tirofiban (IIa-B) 
  • Eptifibatide (IIa-B) 


  • Administer when 
  • No PCI available 
  • Delays in transfer to PCI capable facility (FMC-to-device time >120 mins) – IA 
  • Administer within 30 mins of presentation (IB) 

Benefits of PCI /Thrombolytics 

  • Restores coronary flow 
  • Reduces infarct size 
  • Improves myocardial function 
  • Improves survival 

Rescue PCI 

  • PCI after unsuccessful Thrombolysis (IIa-B) 
  •  Persistent chest pain 
  • Persistent ST elevation 
  • < TIMI 3 flow on angiogram 
  • All patients with STEMI should have angiograms 
  • Rationale 
  • TIMI 3 (normal flow) after thrombolysis predicts short- and long-term survival 
  • Other variables to assess reperfusion are imprecise 
  • Improvement/relief of chest pain 
  • Resolution of ST elevation 
  • Presence of reperfusion arrhythmias 
  • Angiogram used to accurately assess flow and additional intervention can be done if necessary 

Coronary artery bypass grafting 

  • Indications 
  • Ongoing ischemia with coronary anatomy not amenable to PCI 
  • At time of operative repair of mechanical defects. 

Cardiogenic shock 

  • Intra-aortic balloon pump (IIa-B) 
  • Shock with inadequate initial response to pharmacological intervention 
  • Left ventricular assist device (IIb-C) 
  • Refractory shock 


  • Implantable Cardioverter-Defibrillator (I-B) 
  • Sustained VT/VF >48 hours (about 2 days) after STEMI 
  • If not due to 
  • Transient/reversible ischemia 
  • Reinfarction 
  • Metabolic abnormalities 
  • Temporary pacing 
  • Symptomatic bradyarrhythmia (I-C) 

Other studies 

  • Non-invasive testing for ischemia 
  • If no angiogram done and no high-risk clinical features which would warrant angiogram 
  • Evaluate significance of non-infarct stenosis seen on angiogram 
  • Help to guide post-discharge exercise prescription 

Need for Echocardiogram 

  • Left Ventricular Function 
  • All patients should have LV Ejection Fraction assessed (I-C) 
  • If LVEF reduced  
  • Reassess in approximately 40 days (about 1 and a half months) 


  • Lipid screening  
  • Fasting lipid profile (total cholesterol, triglycerides, LDL cholesterol and HDL cholesterol) in all adults >20years, repeated every 5 years 


  • ACS can be associated with significant morbidity and mortality 
  • Early recognition and risk stratification will help to determine the need for initial conservative therapy using pharmacologic agents vs. an early invasive strategy  
  • Essential prongs of evidence-based guideline directed management 
  • Anti-ischemic treatment 
  • Anti-thrombotic treatment 
  • Invasive vs conservative 

Published by Healthy Waves

Healthy Waves is a medical business founded in Georgetown Guyana, which engages in health education, medical supplies, and consulting services.

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