Acute Coronary Syndrome

• Ischaemia is symptoms and signs incl the ECG
• Infarction is elevated trop (>99^th centile) with signs, symptoms or consistent ECG/echo findings
• Acute MI is defined as cardiomyocyte necrosis in the clinical setting of acute myocardial ischaemia (subdivided into type 1 and type 2)
• A Type 1 MI is defined as a troponin rise, plus one of:
  • • Ischaemic sounding chest pain / pulmonary oedema / shock
    • ECG changes consistent with ischaemia (incl new Q waves)
    • Regional wall motion abnormality on echo or MRI
    • Coronary thrombus at angiography / post-mortem
• Myocardial injury
  • • Defined as a troponin rise above 99^th
    • Not the same as an MI and trop doesn’t have to rise and fall as in ACS
    • Acute myocardial injury can occur in acute heart failure, sepsis, arrythmias, valve disease or myocarditis
    • Chronic myocardial injury in structural HD and CKD
• Unstable angina
  • • Myocardial ischemia at rest or minimal exertion in the absence of cardiomyocyte injury/necrosis
    • Characterised by prolonged (>20mins) angina at rest / new onset severe angina / angina increasing in frequency or longer in duration or lower in threshold / angina post recent MI
    • No troponin rise
• Risk assessment
  • • The GRACE score is an accurate assessment of risk, both on admission and over the next 6 months
    • Includes: age, signs of HF, HR, BP, creat, ECG, trop, if in cardiac arrest
• Note that
  • • ACS is a spectrum
    • A true silent type 1 MI is rare – there is usually pain in the setting of ischaemia
    • 30% of patients have a normal ECG in the presence of a trop rise due to ACS
    • The diagnostic pathway is: rule in, rule out or observe
    • If ACS suspected clinically, the ECG will determine if working diagnosis is NSTEMI or STEMI
• Prognosis
  • • 10% cumulative incidence of a second MI, a stroke, or CV death within the first 100 days after experiencing an MI, reaching 33% at 5 years
    • 10% of STEMI patients die within 12 months
    • STEMI complicated by shock still has a 50% mortality
    • Within 5 years of ACS, 25% will have another hospitalisation or die (most often MI, also CVA) but this is highly modifiable and can be reduced

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Symptomology

• • Chest pain can be considered cardiac, likely non-cardiac or possibly cardiac
  • Right sided CP is actually more likely to predict MI than left
  • May also be SOB, epigastric pain, pain in left arm/jaw
  • Chest pain equivalents
    • • Rarely an MI can present with other symptoms incl SOB
      • Some groups more likely to have little or no pain – diabetics, elderly, CKD, post-op. In diabetics the predominant symptom might be SOB
  • Reassuring features (non-cardiac) – stabbing, very localised, aggravated by movement/breathing/palpation, duration < 2 mins.
  • Concerning features (cardiac) – aggravated by exertion, radiation to shoulders or pain widespread
  • Women present similarly to men (and presentation also similar across ethnic groups), but they have slightly lower troponins
  • Non-discriminatory features
    • • Response to GTN is not useful in making a diagnosis
      • Belching and nausea are not helpful in distinguishing cardiac pain from indigestion

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General management points in ACS

• The ECG
  • • A normal ECG doesn’t exclude ACS
    • Review previous ECGs
    • Take serial ECGs (if ischaemia initially in differential, patient should always have >1 ECG before being discharged home)
    • Consider additional leads depending on the ECG
• Cardiac monitor
  • • Local guidelines will vary, but it’s essential for at least 24 hours in all NSTEMIs. Longer if high risk.
    • Post PCI, most patients monitored for >48 hours
    • If severe LV impairment, monitor for > 72 hours
• Morphine/analgesia
  • • Easy to forget! If fails to manage pain, consider GTN infusion if BP allows
    • Pain increases myocardial ischaemia
    • Some emerging concerns around whether it delays or diminishes action of antiplatelets (research ongoing)
    • Consider co-administering an anti-emetic if giving morphine
• GTN – spray or IV
  • • Not to be used diagnostically
    • Avoid if hypotensive, marked bradycardia/tachycardia, RV infarction, severe AS
• Antiplatelets
  • • Do not offer dual antiplatelet therapy to people with chest pain before a diagnosis of likely unstable angina or NSTEMI is made
    • Give aspirin, and consider another antiplatelet from Ticagrelor, Prasugrel and Clopidogrel (the default 2^nd anti-platelet in acute MI is Ticagrelor or Prasugrel)
    • Limited evidence to support DAPT prior to angiogram other than in STEMI (in fact it’s not recommended in NSTEMI, but often given in practice, usually clopidogrel)
    • Ticagrelor (Load with 180mg then 90mg BD)
      • • Esp useful if high risk features
        • Works in 30 minutes
        • Needs to stop 3 days pre-op
        • Reversible binding
        • Routine if not for PCI (unless high bleeding risk), but can be used irrespective of treatment strategy
    • Prasugrel (Load with 60mg, then 10mg OD (or 5mg OD if weight <60kg or aged >75)
      • • Perhaps the most effective option but used less as can only be given if PCI intended
        • Needs withdrawal 7 days pre-op
        • Works in 30 minutes
        • Contraindicated if previous stroke
    • Clopidogrel (600mg stat then 75mg OD. Load with 300mg if thrombolysing)
      • • Should generally only be used if above drugs are contraindicated/unavailable or in patients with high bleeding risks eg anticoagulated (it’s less effective). Can be considered in patients aged >70
        • Takes 4 hours to work
        • Some patients don’t metabolise it very well. 33% have only one functioning allele for cytochrome p450, 2% have none and therefore no enzyme. So clopidogrel doesn’t work at all in 2% of people (it’s a prodrug reliant on cytochrome p450). Can now check genetics for cytochrome p450. If loss of both alleles, consider another drug like ticragalor or dipyrimazole with aspirin.
        • Needs to be stopped 5 days before surgery
    • Consider calculating the CRUSADE score (for bleeding risk)
• Start a PPI
  • • Indicated for most patients on DAPT and some on SAPT (but esp if hx of PUD, DOAC use, NSAID or steroid use, older age, reflux/dyspepsia/H pylori infection, chronic ETOH use)
• Betablocker if ongoing pain
  • • Metoprolol best
    • Avoid in acute HF or if BP <120 systolic
    • Generally give at presentation if planning to undergo PCI. Best evidence is for STEMI
    • Reduces incidence of VF
• Anticoagulation
  • • Give unfractionated heparin during PCI (bolus). Can be given even if already on a DOAC, or if on warfarin with INR <2.5
    • Give Fondaparinux if not going to cath lab imminently (or enoxaparin, but data not as good) – so generally not advised in STEMI or high risk NSTEMI who need PCI within 24 hours
      • • Dose is 5mg OD s/c
        • Avoid if create clearance <20mL/min
    • Effect of clexane peaks at 4 hours, fondaparinux at 2 hours
• Glycoprotein IIb/IIIb inhibitors – only used post PCI, and for bailout or peri-procedural complications
• Oxygen only if required to reach usual target sats
• Serial ECGs
• Manage hyperglycaemia – target <11 using sliding scale if needed
• Lipid lowering treatment – intensive LDL lowering for all patients with ACS, with immediate initiation of statin therapy (+/- non-statin therapy as needed)
• Immediate transfer to CCU/cardiac centre – consider for STEMIs and high risk NSTEMI, esp if ongoing myocardial ischemia, acute HF, cardiogenic shock, post arrest, malignant arrythmias, AKI
• Bloods
  • • Ensure checked HbA1c, lipids
    • Troponin can stay elevated for 14 days post ischaemia and can rise post PCI

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High sensitivity troponin

• Take initially and then at 1 or 2 hours
• Consider a 3^rd trop if first results are inconclusive and no other diagnosis evident
• If initial trop low (for example < 5 although depends a bit on the assay) – very low risk.
• If initial trop >99^th centile (again depends on assay, and sex-specific) – deemed high risk. The more pronounced the change in troponin, the higher the likelihood of acute MI
• Trop rise and fall could be due to acute ischaemia or acute myocardial injury (eg myocarditis, acute heart failure)
• Trop high and stable – suggests chronic myocardial injury (eg due to structural heart disease or other medical conditions). Raised trop is an independent predictor of long-term CV risk
• A single value of >5x ULN has >90% positive predictive value for acute type 1 MI, but elevated values of 3 x ULN have only 55% positive predictive value
• If normal and no significant rise – Negative predictive value for MI 99.7% (a significant rise is usually defined as >20% taken 3 hours apart)
• Be careful if troponin taken very soon after chest pain onset (may not have had time to rise)
• An elevated troponin is defined as one that occurs in <1% of the population, therefore treat it as abnormal and find an explanation. However – the 99^th centile for troponin in all hospitalised patients would be much higher than the definition of high trop which is the 99^th centile for all people
• Confounders
  • • Trop increases with age (by up to 300%)
    • Trop increases with renal dysfunction
    • Trop changes depending on time from onset of chest pain
    • Trop affected by sex (men have higher trops, but trop should not be sex-adjusted)
• Point of Care trop is not highly sensitive (but may be in the future), but positive prediction value still high
• Non-ACS causes of high troponin
  • • Cardiac
      • • CCF, arrythmia, myocarditis, aortic valve disease, cardiotoxic drugs, aortic dissection, HOCM, cardiac contusion (trauma), DC cardioversion, Takutsubo’s, Rhabdomyolysis, post PCI or cardiac surgery
    • Non-cardiac
      • • CKD, PE, CVA, sepsis, severe illness, burns, extreme exhaustion, infiltrative diseases, severe pulmonary hypertension, anaemia, hypoxia, AKI/CKD, shock
• If troponin is elevated but ECG and history not suggestive of ACS
  • • Consider alternative explanations
    • Serial ECGs
    • Repeat troponin
    • Assess their CV risk
    • Consider CT coronary angiogram (esp if low risk and no DM)
    • Consider angiogram if high risk
    • Consider outpatient review with echo in some (or in others, don’t investigate further)

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Risk categorise

• Rule in MI, rule out MI (low risk) or triage as ‘intermediate risk’
  • • Low risk
      • • Very low trop on arrival, or low initial trop and no significant increase, with low suspicion ACS and normal or non-specific ECG
        • If patient arrived > 6 hours after max pain, and first trop negative, then don’t need to repeat. If not – repeat at 3 hours if initial trop low (but not if very low)
    • Intermediate risk / observe pathway (Could be NSTEMI)
      • • Trop intermediate (value here depends on assay… but could be 12-52) and no change and no clear ECG evidence of ischaemia
        • Or: ongoing ischaemic type pain with normal trop
        • Or: GRACE score > 140
        • Actions
          • • Observe and do 1 hour repeat trop and echo. Some will require invasive angiography
            • Consider differentials to ACS (consider D-dimer, and BNP for risk stratification) eg AF, severe anaemia, hypertensive emergency, PE
            • Consider CRUSADE score to decide whether to give DAPT – risk of bleeding
        • These patients are not substantially less at risk than the high risk/rule in patients
        • The HEART score sometimes used if considering discharge
          • • If <2, consider GP f/u.
            • If < 4 consider rapid access chest pain clinic follow up.
            • If >5 admit
        • Increase anti-anginals if stable angina diagnosed
    • High risk
      • • High initial trop or significant increase on repeat
        • High risk criteria (need early invasive management in < 24 hours)
          • • Rise in troponin compatible with MI
            • Dynamic ST-T wave changes
            • GRACE score > 140
            • Transient ST elevation
        • Positive prediction value for this ‘rule in’ pathway is >70%, and those without MI often have significant pathology
    • Very high-risk criteria (immediate invasive strategy, transfer to PCI centre)
      • Haemodynamic instability / cardiogenic shock
      • Recurrent / refractory chest pain
      • Cardiac arrest or life threatening arrythmia
      • Mechanical complications of MI
      • Acute heart failure
      • Recurrent dynamic ST-T wave changes (esp intermittent ST elevation)

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Imaging

• Hx and ECG far more important!
• Coronary CT angiogram (CTCA)
  • • Sometimes used for those with low/intermediate likelihood of ACS and when trop/ECG are normal or inconclusive, however current evidence advises against routine use in the setting of acute chest pain
    • Also not useful if tachycardic, obese or pre-existing CAD
    • Can also rule out PE and dissection
    • CTCA has a high negative prediction value for ACS
• CMR
  • • If elevated troponin but normal angiogram – do cardiac MRI (could still be MI, but many are myocarditis)
    • Useful in place of an echo if poor views
• Echo
  • • If paced and possible ACS – get an urgent echo
    • Also imperative in cases of suspected cardiogenic shock
    • Otherwise – echo useful but should not delay transfer to the cath lab if indicated
    • Indicated in all patients with ACS before hospital discharge
      • • Treat any heart failure if reduced LV function
        • Make a plan to treat / monitor valve disease if present

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ACS by territory

• Posterior MI
  • • Dominant R wave V1 (but not always)
    • ST depression V1-V3.
    • Do posterior leads – V1, V2 and V3, put on V6 line sub scapular
    • Usually due to RCA occlusion, occasionally due to dominant circumflex
• Anterior (LAD) ACS (or anterolateral)
  • • ST segment elevation with Q wave formation in the precordial leads (V1-6) ± the high lateral leads (I and aVL).
    • Reciprocal ST depression in the inferior leads (mainly III and aVF).
    • Worse prognosis and more often associated with LV dysfunction.
    • Very poor prognosis if CHB (broad complexes, resistant to atropine, needs temporary pacing/PPM)
• Inferior ACS
  • • Usually RCA lesion (sometimes circumflex)
    • More arrhythmogenic (there can be transient heart block with narrow complexes and not very slow, consider atropine, usually PPM not needed and resolves after PCI).
    • Consider aortic dissection as differential
• Lateral MI
  • • ST elevated in AVL
    • Upsloping SRT depression in V2 and V3 and inferiorly
    • Could be due to circumflex occlusion or diagonal vessel of LAD
• High lateral STEMI
  • • Due to blockage of first diagonal branch of the LAD
    • ST elevation in I, aVL and V2
    • ST depression in III (and other inferior leads)
    • South African flag sign on ECG
• RV infarction
  • • Present in up to 1/3 of pts with inferior and posterior STEMI.
    • Do right sided leads (mirror of standard ECG)
    • Inferior ST elevation, plus ST elevation V1-V4 on right sided leads
    • Echo useful
    • High JVP and CVP but clear lung fields
    • Patients are very fluid responsive
    • Vasodilators (nitrates, ACE-I) are contraindicated
    • High mortality
• Anterior-inferior STEMI
  • • Due to occlusion of a “wraparound” LAD.
    • Simultaneous ST elevation in the precordial and inferior leads due to occlusion of a variant (“type III”) LAD that wraps around the cardiac apex to supply both the anterior and inferior walls of the left ventricle

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Complications

• Acute LV failure (75% of all post-MI complications) +/- cardiogenic shock
  • • Systolic BP < 90 for over 30 minutes.
    • Cool peripheries, elevated lactate, drowsy, oliguria
    • New AF might be a sign of this
    • Best to distinguish between ne novo acute HF post ACS and pre-existing HF exacerbated by ACS
    • Predictors = old age, anterior MI, RV MI, delay in PCI and CP> 6 hours, previous MI
    • Elevated troponin can be due to myocardial injury rather than ischaemia
    • In the cath lab, signs of shock include cardiac index <2.2, PCWP > 18, LV end diastolic pressure > 25 and cardiac power output < 0.6 watts
    • Treatment is about increasing blood supply to myocardium and reducing demand – PCI, inotropes/vasopressors (buys you time only), mechanical devices (IABP, Impella, VA-ECMO). Initiate early and escalate
    • If shocked – consider supportive therapies (below)
• Cardiogenic shock
  • • Assess using SCAI criteria (A to E), as it’s a bit of a spectrum
    • Usually due to ischaemia-related heart failure, acute severe MR or mechanical complications
    • 80% have multivessel disease
    • Cardiogenic shock post MI occurs in 10% and has 80% mortality if untreated (but varies based on SCAI classification)
    • Shock post MI can be mixed with septic shock
    • Risk factors include large MI, prior MI, acute on chronic HF, relative hypotension (esp if fluid resistant)
    • Immediate PCI advised – but to infarct-related artery only (other vessels can be treated later). Or emergency CABG.
    • These patients may need supportive therapies eg IABP, Impella, ECMO. Transfer these patients urgently to centre where there is access to such devices
      • • Impella – trans-axial MCS.
          • • Extracts blood from the ventricle
            • Femoral insertion
            • Reduces demand.
            • Stays in for 5 days. Give heparin.
            • Complications include haemolysis, ischaemic legs, CVA, infection.
            • Impella reduces mortality in STEMI with cardiogenic shock. No RCT data.
            • Impella give more cardiac output (3L/min) than IABP (1.5L/min) and is used more often
        • ECMO gives even more (5L/min) but downside is that it increases afterload
        • IA balloon pump not routine in shock, but can be considered if mechanical complications. Evidence not great. Not used for the most severe cases
        • Can use in combination – they can be complimentary
• Acute RV failure
  • • Hypotension, elevated JVP, clear chest.
    • Avoid vasodilators and beta-blockers
• Mechanical complications
  • • More common post-STEMI, occurring in around 0.3% of cases, and associated with >40% mortality
    • Might be suggested by a new murmur, sudden hypotension, acute HF or recurrence of pain
    • Immediate echo indicated
    • Surgery often required (and consider IABP whilst waiting)
    • Examples
      • • Tamponade / myocardial rupture
        • Papillary muscle rupture
          • • Occurs around day 2 to day 7 post MI.
            • Severe MR with pansystolic murmur. Get an urgent echo
            • More likely in inferior MI
            • May need emergency CABG and MV surgery.
            • High mortality
        • Acute VSD
          • • Will also have a pansystolic murmur, like acute MR
            • More likely in anterior MI
            • May not operate immediately, as ischaemic tissue is friable. Often wait 10 days if possible (but many die in the meantime)
            • Percutaneous closure sometimes possible in big tertiary centres
            • ECMO sometimes used in young patients
• Dressler’s syndrome
  • • See pericardial effusion
    • Generally occurs at 1-2 weeks post MI
• LV thrombus
  • • Most common in anterior STEMI (occurring in around 10% of cases, or in around 6% of all STEMIs)
    • Can cause embolic phenomenon and stroke
    • Usually detected on echo (or contrast echo) although CMR gold standard test
    • A significant proportion develop post hospital discharge – so consider imaging at 2 weeks if patient high risk
    • Treat with DOAC for 3-6 months, then re-image
• Ventricular arrythmia
  • • VF or VT occurs in around 7% of STEMI patients (and if it’s VT, they are usually unstable)
    • Urgent reperfusion is key
    • Early use of betablockers in ACS reduce the risk
    • Acutely consider using betablockers and/or amiodarone
    • If occurs within 24-48 hours, an ICD is usually not indicated (but consider if poor LV function at 6-12 weeks)
    • Check for electrolyte abnormalities
    • Accelerated idioventricular rhythms and frequent premature VEs can occur following reperfusion. Usually transient and no treatment required.
    • If repeated electrical cardioversion unsuccessful, consider transvenous catheter pacing / overdrive pacing. Lidocaine also sometimes used in this scenario
    • If patient is particularly arrhythmogenic post MI (eg poor EF), might keep them in hospital a bit longer
• Atrial fibrillation
  • • Can be pre-existing, but can also indicate LV failure – so manage this as well
    • Cardiovert if causing haemodynamic instability
    • Rate control with betablockers unless HF or hypotension also present
    • If reduced LV function and rate control required – consider digoxin (or amiodarone)
• AV block
  • • Often due to inferior MI
    • QRS usually narrow and heart rate usually not very slow
    • If symptomatic, consider atropine and temporary pacing if bradycardia/hypotension persist
    • PPM rarely necessary. Heart block usually resolves after PCI (so don’t delay PCI due to this)
    • If occurs in context of anterior MI – implies extensive injury and poor prognosis. QRS usually broad and HR slow and atropine-resistant. Use temporary pacing. Consider CRT-D
    • PPM recommended if high degree AV block does not resolve > 5 days post MI
• Bleeding
  • • Hb <110 at time of PCI is a risk factor for bleeding, but severe anaemia can also cause a type 2 MI
• LV aneurysm
  • • Suggested by persistent ST elevation
• Stroke

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Some specific scenarios

• For more detail on diagnosis and management see STEMI and NSTEMI
• Unstable angina
  • • Defined as:
      • • Pain of increasing frequency and provoked by less and less exertion (crescendo) or
        • Angina at rest or
        • Prolonged cardiac CP but normal ECG/trop
    • Suspected unstable angina often turns out to be non-cardiac chest pain (especially if trop negative and it’s an isolated episode of chest pain)
    • Do GRACE score (as a normal trop and a negative ECG do not always imply a patient is low risk, though ECG changes do increase risk)
    • A CT coronary angiogram might be worth doing (which will also rule out a PE and aortic dissection, but loses some sensitivity by looking for 3 different pathologies in one scan). However, doing a CT angiogram for older patients with multiple risk factors for CAD is not helpful – they will have plaques and evidence of CAD. A more important question is symptoms and whether the CAD is flow-limiting
    • Often patients get early follow up in a rapid access chest pain clinic. Consider exercise ECG / stress echo if low GRACE score
    • If good history and high GRACE score – inpatient angiogram
    • Management similar to NSTEMI
• Arrest in the cath lab
  • • Can proceed with PCI with mechanical CPR or ECMO. Or wait for ROSC and then proceed.
• Out of hospital cardiac arrest
  • • Cardiac cause likely if presenting rhythm was VT or VF, and no other explanation (less likely cardiac cause in PEA arrest, unless long downtime and rhythm transformed into PEA)
    • ECG after ROSC or shocks can be a bit odd – take a 2^nd or 3^rd ECG and compare
    • No benefit to patient being in a tertiary cardiac centre if no ST elevation
    • Miracle2 score helps predict outcome
    • Downtime less important than assumed
    • PCI probably best for patients with miracle2 score of 0-3, and with either STEMI or shock (grade B-E). Might also be useful for NSTEMI without shock if high risk of CAD and low Miracle2 score
    • KOCAR – calculates probability of patient having a culprit coronary artery lesion after OOH cardiac arrest. Based on age, localising ECG change, RWMA on echo, hx of vascular disease, initial shockable rhythm, prior PCI or CABG
• In pregnancy
  • • Diagnosis of ACS is the same
    • ACS treatment should not be delayed for delivery
    • Ideally delivery should be postponed for 2 weeks post ACS
    • SCAD is the most common cause of MI in pregnancy
    • More here
• In cancer patients
  • • PCI should still be considered if life expectancy > 6 months or patient unstable
    • CABG can be considered if life expectancy > 12 months, and coronary anatomy not amenable to PCI
    • Clopidogrel generally preferred anti-platelet due to bleeding risks (but check interactions with cancer therapies, and ensure plts >30)
    • Consider if specific anti-cancer therapies have precipitated ACS