Acute Coronary Syndromes

Acute coronary syndrome defines the spectrum of myocardial ischaemia, that is subdivided into:

The term OMI (occlusive myocardial infarction) has been suggested as an alternative to STEMI. This change in nomenclature is proposed so all patients who would benefit from PCI are overtly included in the classification, as patients with a STEMI-equivalent (i.e., would benefit from PCI, but who don’t have STE) may go unrecognised.

The language here will retain the traditional nomenclature, but it is good to keep in mind.

There are three additional subtypes of MI, with minimal clinical implication:

  • Type 3
    Death with symptoms and ECG changes, but no biomarkers available.
  • Type 4
    • 4a: Secondary to PCI
    • 4b: Secondary to stent thrombosis
  • Type 5
    Secondary to CABG.

Epidemiology and Risk Factors

ACS are a major cause of mortality in the industrialised world:

Note that the definition of MI and therefore the actual disease treated has evolved over time. Historically, the diagnostic features were Q-waves, indicating myocardium with a completed infarct. In the reperfusion era, it was noted that patients with STE were the ones who benefited from thrombolysis or PCI - STEMI as an entity exists to delineate these two groups.

In more recent years with the introduction of high-sensitivity troponin, more patients with UA are now been classified with a NSTEMI.

  • ~15% of all deaths
    • 70% of these are OOHCA
    • 60% of deaths are within first hour
      Usually prior to reaching medical facility.
    • ↑ To 20% of deaths in persons >40
  • ↓ In in-hospital mortality from 30% to <10% with current therapy
    However, significant issues remain in receiving appropriate medical therapy.
    • ~25% of eligible patients don’t receive reperfusion
      ↑ In women and the elderly.

Risk factors:

  • Age
  • Male
  • Family history
  • Smoking
  • Indigenous
  • Disease
    • HTN
    • DM
    • Dyslipidaemia
    • Obesity

The rate of coronary disease for indigenous Australians is ~2.5× that of non-indigenous people.

Pathophysiology

Mechanisms include:

  • Plaque rupture
    • Atheromatous plaque develops over vessel wall injury
      • Lipid accumulates in arterial intima
      • Fibrous cap develops
        Usually occurs slowly, may happen more quickly in those with risk factors.
    • Plaque rupture
      Plaque breaks, exposing thrombogenic lipids.
    • Platelet activation forms a plug over the plaque, occluded blood flow
  • Coronary spasm

Which vessel and how proximal the occlusion is determines the region and extent of myocardial ischaemia:

  • LAD occlusion
    • Anterior MI
      • ~40-50% of all MIs
      • Anterior infarction has ↑ LV impairment and poorer prognosis than lateral or inferior infarctions
    • Septal MI
  • LCx\Distal LAD
    • Lateral MI
  • RCA\PLB of LCx\Dominant LCx
    • Inferior
      ~50%.
    • Posterior
      ~3%. Usually associated with inferior or lateral MI.
    • RV MI
      Usually occurs with inferior MI. Concerns are ↓↓ HR, ↓ BP with GTN.

Clinical Manifestations

ACS features are more specific for a Type 1 rather than Type 2 MI, which are often free of ischaemic symptoms.

“Classical” presentation:

Pain of unstable angina is usually similar but milder.

  • Pain
    • Severe
    • Constant
    • Retrosternal
    • Radiation to throat, jaw, ulna aspect of each arm, interscapula
    • No clear precipitant
    • Worse on exertion or emotion
  • Associated autonomic symptoms
    • Sweating
    • Nausea
    • Dyspnoea
    • Anxiety

“Atypical” symptoms:

Atypical presentations occur in 25-45% of patients, and is more likely in patients who are:

  • Female
  • Elderly
  • Diabetic
  • Obese
  • Have heart failure
  • Pain
    • Epigastric
    • Localised to jaw, arms, wrists, or interscapular
    • Burning

Diagnostic Approach and DDx

Differentials:

  • B
    • PE
  • C
    • Pericarditis
    • Aortic dissection

Investigations

Bloods:

  • Cardiac enzymes
    • Troponins
      Highly specific for myocardial injury, but do not identify cause.
      • Rise over 4-6 hours
      • Peak 16-24 hours
      • Resolve over 7-14 days
        Prolonged in renal failure.
    • CK
    • AST
      Non-specific for myocardial injury, and no longer used for diagnosis.
      • Rises after 6-8 hours
      • Peaks at 24-36 hours
      • Normalises at 3-7 days

ECG:

  • For diagnosis and infarct localisation
  • Serial recordings
    • Change in symptoms
    • Drawing troponin
    • Periodically

ECG mimics of MI include:

  • B
    • PE
  • C
    • LVH
    • Old inferior MI
    • Benign Early Repolarisation
    • Digoxin therapy
  • F
    • Hyperkalaemia

Echo:

  • LV function
  • RWMA
    Infarct location. Presence of RWMA is sensitive but not specific for STEMI.
  • Assess other differential diagnoses
  • Infarct complications
    • Papillary muscle rupture
    • MR
    • Myocardial rupture
    • VSD

ECG Indications for Reperfusion

STEMI and STEMI equivalents include:

  1. ST Segment elevation
    • Men <40
      2.5mm in V2-3 and 1mm in other leads.
    • Men >40
      2mm in V2-3 and 1mm in other leads.
    • Women
      1.5mm in V2-3 and 1mm in other leads
  2. LBBB and one of:
    • Cardiogenic shock
    • Sgarbossa Criteria positive
      • Concordant STE >1mm in >1 lead
        In a LBBB, there is normally discordant STE, i.e. the ST segment moves in the opposite direction to the QRS.
      • Concordant STD >1mm in >1 of V1-3
    • Smith-modified Sgarbossa criteria positive
      • Excessively discordant STE in >1 lead
        Excessive discordance defined as ST elevation >25% of the preceding S-wave.
  3. New RBBB and LAFB
    Strongly associated with proximal LAD occlusion.
  4. Posterior MI
    STD >1mm in V1-4, +/- STE >0.5mm in V8-9.
  5. Lateral wall MI
    Any STE in aVL with STD in III (II/aVF).

Management

  • Expedite reperfusion
    • Call-to-balloon time for PCI should be as short as possible, and <60 minutes
    • Thrombolysis should be performed if PCI cannot occur in <120 minutes
  • Give

Resuscitation:

  • B:
    • Supplemental oxygen
      Target SpO2 of 93-97%. Avoid hyperoxia, concerns that this may ↑ infarct size.
  • C
    • Venous access
    • Defibrillator available
    • Sublingual GTN
      • Indications:
        • Ischaemic pain
        • Hypertension
        • Pulmonary oedema
      • Contraindications:
        • Hypotension
        • RV MI
        • Recent PDE inhibitor

Specific therapy:

GTN does not improve outcome and relief of pain is not diagnostic for ischaemia, but may be useful for symptom relief.

  • Reperfusion therapy
    In STEMI and STEMI.
    • Thrombolysis
    • PCI
  • Pharmacological
    • Aspirin
      • 300mg load, then 100mg/day lifelong
      • ↓ Mortality by ~2.5%, halves rate of stroke and reinfarction
      • Consider clopidogrel if aspirin contraindicated
    • Consider DAPT
      • Recommended if:
        • Anticipating primary PCI
          Though benefit remains even if PCI not performed.
        • Low bleeding risk
        • Not bradycardic
          Ticagrelor may worsen bradycardia.
      • May be:
        • Ticagrelor
          • 180mg load, then 90mg BD
        • Clopidogrel
          • 300-600mg load, then 75mg daily
          • May be preferred to ticagrelor for patients with ↑ bleeding risk
        • Prasugrel 60mg load
          • Contraindicated if:
            • >75 years old
            • <60kg
            • Previous CVA
      • Long half-lives result in ↑ bleeding if CABG is required
      • Duration depends on type of stenting
    • Anticoagulation
      Stabilises clot and ↓ early infarction, but leads to rebound ↑ infarction.
      • Fondaparinux 2.5mg daily
        Preferred option, if available.
      • Enoxaparin 1mg/kg BD
      • Therapeutic heparin infusion
    • β-blockers
      • Only in patients who are haemodynamically stable patients
        Usually after thrombolytic therapy.
      • Ideally within 24 hours
      • ↓ Malignant arrhythmia rate
    • ACE-I\A2RB
      ↓ Mortality and ↓ LV failure in STEMI, probably beneficial in NSTEMI.
      • Contraindications
        • Renal dysfunction
        • Hypotension
        • Hyperkalaemia
    • Statin
      Commence within 24 hours. ↓ Mortality, risk of future coronary events by ~30%.
      • Atorvastatin 80mg
    • Long-term anticoagulation
      Only for specific indication, e.g. AF, LV thrombus, severe LV dysfunction.
  • Physical
    • Lifestyle advice
    • Cardiac rehabilitation

Supportive care:

  • C
    • Haemodynamic support
      • May be required prior to reperfusion for significant infarcts
      • Mechanical support
        • IABP
          No good evidence of mortality benefit.
        • ECMO
  • D
    • Opioid analgesia
  • F
    • Electrolyte correction
      • K+ >4.5mmol/L
      • Mg2+ >1mmol/L
  • H
    • Aim Hb >80mg/L if ongoing ischaemia

Disposition:

  • CCU
  • ICU

Reperfusion

Reperfusion ↓ infarct size and ↑ LV function, ↓ stroke rate, and ↓ mortality.

Comparison of Percutaneous Coronary Intervention and Thrombolysis
Percutaneous Coronary Intervention Thrombolysis
  • Preferable to thrombolysis, if available
  • Should be performed urgently
    Sooner is better, <60 minutes is the goal. PCI has ~6% ↓ in mortality.
  • May be:
    • Primary PCI
    • Rescue PCI
      PCI performed after failed thrombolysis.
  • Effective if performed <3 hours from onset
    Works best with fresh clot, prior to fibrin formation.
  • ~4% ↓ in absolute mortality

Factors influencing reperfusion strategy:

Contraindications to Fibrinolysis
Category Absolute Relative
Intracranial
  • CVA
    • Any haemorhaggic
    • Ischaemic last 6/12
  • CNS neoplasm
  • TIA last 6/12
Cardiac
  • Aortic dissection
  • SBP >180mmHg
  • Infective endocarditis
  • Traumatic CPR
Bleeding risk
  • Major trauma last 3/52
  • Major surgery last 3/52
  • Major Gastrointestinal bleeding last 1/12
  • Active internal haemorrhage
  • Peptic ulcer disease
  • Non-compressible vascular puncture
  • Coagulopathy
    • Advanced liver disease
    • Oral anticoagulants
  • Pregnant or <1/12 post-partum
  • Time
    • Infarct
    • Transfer time
  • Contraindications to thrombolysis
  • High risk features
    Indication for PCI in absence of STEMI or STEMI-equivalent include:
    • Ventricular arrhythmias
    • Cardiogenic shock
    • Pain refractive for medical therapy

Right Ventricular Myocardial Infarction

Additional considerations for the RV MI:

  • C
    • RV support
      • Maintain preload
        Nitrates, morphine, diuretics, PEEP, hypoxaemia.
      • iNO
      • Vasoactives

Marginal and Ineffective Therapies

Anaesthetic Considerations

Occasionally, anaesthetic support to the cath lab is requested for patients with:

  • Cardiogenic shock
  • Agitation

Complications

  • Death
    • Malignant arrhythmias
      Leading cause of death, particularly prehospital.
      • Major risk in first 4 hours
        4-20% have VF in this period.
  • Cardiogenic shock
    ~10% of ACS, with substantial (~50%) associated mortality.
  • Cardiogenic shock
  • Pulmonary oedema
  • MR
    • Functional
      Related to LV dilation and diastolic dysfunction.
    • Papillary muscle rupture
  • Ventricular rupture
  • VSD
  • Ischaemic cardiomyopathy and cardiac failure
    15-25% following STEMI.
  • Pericarditis/Dressler’s syndrome
    Usually develops 24-72 hours post MI.
  • Stroke
    Embolism from LV thrombus.

Prognosis

Infarct size is influenced by time to reperfusion, and determines degree of:

  • LV systolic dysfunction
  • Diastolic dysfunction

Key Studies

Antiplatelet agents:

  • PLATO (2014)
    • Ticagrelor had improved mortality and ischaemic events compared to clopidogrel in ACS, with no ↑ in bleeding

Other:

  • REALITY (2021)
    • 666 French/Spanish anaemic adults with Type 1/2 AMI without shock or life-threatening haemorrhage
    • Unblinded, allocation-concealed, multicentre randomised trial
    • 630 patients gives 80% power to a 4% non-inferiority margin for ↓ in MACE at 30 days, assuming 15% in the liberal group
    • Liberal vs. restrictive transfusion
      • Liberal transfused if Hb <100
      • Restrictive transfused if Hb <80
    • Restrictive transfusion was non-inferior to liberal

References

  1. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.
  2. Ducrocq G, Gonzalez-Juanatey JR, Puymirat E, et al. Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular Events Among Patients With Acute Myocardial Infarction and Anemia: The REALITY Randomized Clinical Trial. JAMA. 2021;325(6):552-560. doi:10.1001/jama.2021.0135
  3. Ndrepepa G. Aspartate aminotransferase and cardiovascular disease—a narrative review. Journal of Laboratory and Precision Medicine [Internet]. 2021 Jan 30 [cited 2023 Oct 12];6(0).
  4. Advanced Life Support Level 2 Third Australian Edition. Australian Resuscitation Council. 2016.