Cardiology JC007: Accelerating Chest Pain: Acute Coronary Syndrome Flashcards
Acute Coronary Syndrome (ACS)
Sudden imbalance between **myocardial oxygen supply + demand due to **coronary artery obstruction
—> demand remain same but lack of supply
—> Myocardial ischaemia / infarct
Clinical presentations:
1. **Ischaemic chest pain / equivalent symptoms (e.g. chest discomfort)
2. **Haemodynamic instability (∵ loss of contractile force)
3. **Electrical instability (∵ involvement of SA / AV nodal branch artery —> significant bradycardia: Sinus bradycardia, AV block, VT / VF)
4. **Mechanical complications (Late phase e.g. severe MR, VSD)
Consequences:
1. Cardiac arrest
2. Cardiogenic shock
3. Congestive heart failure (CHF)
Mechanism of Myocardial ischaemic pain
Ischaemia:
Supply < Demand
—> Anaerobic respiration
—> ↑ Lactic acid, H, ATP (if infarction: leakage of cellular contents)
—> Type C unmyelinated fibre in myocardium
—> Nerve afferents
—> Spinothalamic tract
—>
- Thalamus
—> Cerebral cortex: Pain perceived - Brainstem (CV control centre)
—> ↑ Sympathetic activity
—> ↑ HR (but may have bradycardia if SA / AV nodal branch affected), BP, Sweating
Chest pain in Chronic (i.e. Angina) vs Acute coronary syndrome
Chronic coronary syndrome (Stable angina):
- Stable + **Fixed atherosclerotic plaque
—> Supply / Demand still **maintained at basal metabolic rate —> **no symptoms at rest
—> **Exertional chest pain (∵ failure to ↑ supply to accommodate for ***↑ demand)
- Other diseases causing exertional chest pain:
—> LVOT obstruction (HOCM, AS)
—> **Relative ischaemia (LVH, **HCM)
Acute coronary syndrome:
- Athero-thrombotic CAD: Plaque disruption —> Platelet activation —> (white) Thrombus formation (on top of atherosclerotic plaque)
—> Sudden imbalance between Supply / Demand
—> ↓ supply to even maintain **basal demand
—> **Rest pain
Classification of ACS
- Unstable angina
- plaque ruptures —> platelet activation —> thrombus formation —> **partial obstruction of vessels but **NO infarction —> NO biochemical evidence to suggest Acute MI
- anginal pain occurs at rest / progresses rapidly over short period of time - NSTEMI
- severe **partial obstruction of vessels —> compromise basal metabolic need —> **Subendocardial myocardial injury / infarct —> Non-specific ST depression / T inversion - STEMI
- **complete obstruction of vessels (1 of 3 **major coronary arteries) —> ***Transmural myocardial injury / infarct —> ST elevation
- occlusion of small side branch coronary arteries giving rise to transmural infarction may not be shown on ECG (∵ not high enough spatial resolution)
Diagnosis of ACS
3 major clinical evidences for ACS
- ***Clinical presentation
- Chest pain / equivalent - ***ECG
- Acute ischaemic changes
—> Non-specific ST depression / T inversion
—> ST elevation - Biomarkers (reflecting myocardial injury)
- High sensitive ***Troponin
+/- 4. Imaging
- **Echocardiogram: Regional wall motion abnormality
- **CT coronary angiogram
—> used if 1-3 not conclusive
Typical chest pain / Characteristics of chest pain in ACS
- Prolonged (>20 mins) anginal pain at rest (~80%)
- anaerobic respiration / accumulation of metabolite take time to develop / resolve (will not be “come-and-go”)
- 記: Prolonged rest pain - New onset (De novo) angina (~20%)
- Canadian Cardiovascular Society Class 3 (marked limitation of ordinary physical activity, walking 1-2 blocks on level, <1 FOS) - Recent destabilisation of previously stable angina with >=3 CCS class 3 angina characteristics (Crescendo angina)
- Post-MI angina
Features NOT typical of myocardial ischaemia
- Pleuritic, Sharp pain
- related to respiration
- but may be related myocarditis - Primary / sole location at middle / lower abdomen
- MI pain should be ill-defined, dull aching, diffuse location (∵ visceral nerve) - Pain very localised by 1 finger tip
- Pain reproduced by movement / chest wall palpation
- point to skin / muscle / ribs - Very brief episode, lasting for seconds
- Pain maximal intensity at onset + improves afterwards
- point to Aortic dissection - Pain radiating to lower limbs
***DDx of Acute chest pain
Cardiac:
1. ACS
- 20-30 mins
- **sudden onset
- pressure-like pain
- central
- **no tenderness
- radiate to jaw + arm
- aggravated by exertion, relieved by rest / nitrate (not completely gone)
- ***diaphoresis, dyspnea
- Stable angina
- 5-10 mins
- **gradual onset with exertion
- pressure-like pain
- central
- **no tenderness
- radiate to jaw + arm
- aggravated by exertion / emotion, relieved by rest / nitrate - Aortic dissection
- maximal at the onset
- excruciating pain in anterior chest, radiate to interscapular of back / into abdomen
- sudden onset
- sharp, tearing
- ***no tenderness
- aggravated by high BP - Pulmonary embolism (Days)
- Pericarditis / Peri-myocarditis (Variable duration)
Respiratory (***aggravated by deep breathing):
1. Tension pneumothorax
2. Pneumonia
3. Pleuritis
GI (usually longer in duration: Hours):
1. Perforated esophagus (Boerhaave’s syndrome)
2. Perforated peptic ulcer (tenderness on palpation)
3. Peptic ulcer disease
4. Acute cholecystitis (***tenderness on palpation)
5. Biliary colic
6. GERD
Musculoskeletal
- ***tenderness on palpation
Herpes Zoster
- ***tenderness on palpation
Psychiatric:
1. Anxiety
Typical ECG in ACS
ECG: Objective evidence of myocardial ischaemia
Differentiate types of ACS: STEMI vs NSTEMI
Symptoms suggestive of ACS
—> 12 lead ECG
—> **ST segment + **T wave (Referring to Repolarisation of myocardium: most affected in ischaemia —> fail to repolarise)
—> No ST elevation —> Unstable angina / NSTEMI (ST depression, T inversion) —> Further stratified by Biomarker
—> ST elevation —> STEMI
ST elevation:
- indicate ***Transmural infarction
- location: Anterior / Lateral / Inferior / Posterior
- suspected Posterior STEMI (tall R wave in V1, V2) —> Posterior ECG (V7-9)
- suspected RV involvement (Inferior STEMI) (low BP, heart block, RCA proximal infarction) —> R-sided ECG (V4R)
Biomarkers after acute MI
Biomarkers: Leakage of cellular contents of myocardium into bloodstream
- CKMB
- not sensitive / specific as Troponin - Myoglobin, CK isoforms
- rise + fall rapidly
- good for detecting ***re-infarction (∵ Troponin will still be elevated) - Troponin
- part of sarcomere unit of myocardium
- large difference in levels between Large vs Small MI —> useful
- rise within **1 day, peak in 1.5 days, fall after **2 days
- rise and fall —> different from other infiltrative myocardial diseases (persistent elevated Troponin)
***Non-MI causes of Troponin rise
Cardiac causes (∵ ↑ demand of myocardium):
1. ***CHF
- Takotsubo CMP (heart blown up like a balloon like an octopus)
- Infection
- ***Viral cardiomyopathy - Inflammation
- ***Myocarditis / Pericarditis - Trauma
- Surgery
- Electrical shock
- Post-RFA / Defibrillation - Demand / Supply imbalance
- Brady / Tachyarrhythmia
- Severe anaemia
Systemic causes:
1. **Pulmonary embolism
2. Toxicity
- **Anthracyclines (Doxorubicin)
3. Trauma
- Blunt chest wall injury
4. **Renal failure
5. **Sepsis
6. Stroke
7. Subarachnoid haemorrhage (∵ excessive sympathetic activity)
***Types / Definition of Myocardial injury / infarction
Fourth Universal Definition of Myocardial injury / infarction (UDMI):
Type 1 (most common): Atherothrombotic CAD —> ***Plaque rupture, erosion, fissuring, dissection —> spontaneous MI related to ischaemia
Type 2: **Coronary spasm / **Anaemia / **Hypotension / **CHF —> imbalance of O2 demand and supply —> ischaemia
- unrelated to Atherothrombotic CAD
Type 3: **Sudden cardiac death with symptoms of ischaemia (patient死左)
- **before determination of elevation of cardiac biomarker
- accompanied by new ST elevation / LBBB
or
- verified coronary thrombosis by angiography / autopsy
—> for epidemiological study purpose only
Type 4a: ***PCI associated
Type 4b: Verified stent thrombosis associated
Type 5: ***CABG associated
Type 1 MI
MI caused by Atherothrombotic CAD + precipitated by Plaque disruption (rupture / erosion) —> Platelet activation —> Thrombus formation —> Occlusion —> Ischaemia / Infarction / Necrosis of myocardium
Criteria:
- Rise + Fall of Cardiac Troponin values with **>=1 value >99th percentile URL
AND
- >=1 of following:
1. **Symptoms of acute myocardial ischaemia
2. New ischaemic **ECG changes
3. Development of **pathological Q waves
4. **Imaging evidence of new loss of viable myocardium / new regional wall motion abnormality in a pattern consistent with an ischaemic etiology
5. Identification of a coronary thrombus by **angiography including intracoronary imaging / by ***autopsy
Type 2 MI
Myocardial injury due to Pathophysiological mechanism leading to ischaemia (Mismatch between O2 supply / demand)
Causes:
- Fixed atherosclerosis **without thrombus formation + O2 supply / demand imbalance
- **Vasospasm / Coronary **microvascular dysfunction
- Non-atherosclerotic coronary dissection (e.g. Pregnancy ∵ ↑ blood volume + stress)
- O2 supply / demand imbalance alone (uncommon)
—> Coronary embolism
—> Severe HT +/- LVH
—> Sustained tachyarrhythmia
—> Severe bradyarrhythmia
—> Respiratory failure
—> **Severe anaemia
—> ***Hypotension / shock
Criteria:
- Rise + Fall of Cardiac Troponin values with **>=1 value >99th percentile URL
AND
- Evidence of imbalance between myocardial O2 supply / demand **unrelated to acute coronary athero-thrombosis
AND
1. **Symptoms of acute myocardial ischaemia
2. New ischaemic **ECG changes
3. Development of **pathological Q waves
4. **Imaging evidence of new loss of viable myocardium / new regional wall motion abnormality in a pattern consistent with an ischaemic etiology
***Interpretation of elevated Cardiac Troponin
↑ Cardiac Troponin >99th percentile URL —>
Troponin rise + fall
—> With Acute ischaemia (with ECG changes)
—> Acute myocardial ***infarction
—> Atherosclerosis + Thrombosis —> Type 1 MI
—> O2 supply / demand imbalance —> Type 2 MI
—> Without Acute ischaemia (no ECG changes)
—> **Acute myocardial **injury (e.g. Acute heart failure, Myocarditis)
Troponin stable (consistently elevated)
—> **Chronic myocardial injury (e.g. Structural heart disease (e.g. severe AS, HOCM, infiltrative heart diseases), **Chronic kidney disease)
***Temporal dynamicity of ACS: Flowchart of management
0/1 hour rule-out / rule in algorithm using Troponin:
- Only applicable if chest pain onset ***>3 hours (make sure Troponin is elevated if have ischaemia, otherwise if very early ischaemia —> no Troponin elevation yet —> need to remeasure Troponin later)
Suspected NSTE-ACS (no ECG changes / inconclusive):
—> Measure Troponin (hs-cTn)
—> Very low / Low / No sequential ↑ in **1 hour: **Rule-out ACS —> Discharge / Additional testing (Stress testing / CCTA / Angiography)
—> Other: **Observe —> 3 hour Troponin + Echocardiogram —> Discharge / Ward / CCU —> Angiography / Other testing
—> High / Sequential ↑ in 1 hour: **Rule-in ACS —> Ward / CCU —> Angiography / Other testing + Echocardiography
STE-MI:
—> ***No need Troponin (i.e. Can make diagnosis already)
Staging / Stratification of ACS
- Risk criteria mandating invasive strategy in NSTE-ACS
- TIMI Risk score
- GRACE Risk score
- Risk criteria mandating invasive strategy in NSTE-ACS
Very high risk criteria:
- Haemodynamic instability / Cardiogenic shock
- Recurrent / Ongoing chest pain refractory to medical treatment
- Life-threatening arrhythmia / cardiac arrest
- Mechanical complications of MI
- Acute heart failure
- ***Recurrent dynamic ST-T changes, particularly with intermittent ST elevation
High risk criteria:
- **Rise / Fall in Cardiac Troponin compatible with MI (indicate true ACS)
- **Dynamic ST / T changes (symptomatic / silent)
- ***GRACE score >140
Intermediate risk criteria:
- DM
- Renal insufficiency (eGFR <60)
- LVEF <40% / CHF
- Early post-infarction angina
- **Prior PCI
- **Prior CABG
- GRACE score 109-140
Low risk criteria:
- Any characteristics not mentioned above
- TIMI Risk score
Measure Risk of Death / MI / Urgent revascularisation requirement in short term outcome (30 day mortality):
1. Age >=65 yo
2. >=3 risk factors for CAD
3. Prior coronary stenosis of >=50%
4. ST deviation on ECG
5. >=2 anginal events in prior 24 hours
6. Use of Aspirin in prior 7 days
7. Elevated serum cardiac bio markers
- GRACE Risk score (Global Registry of Acute Coronary Events)
- More complicated but ***more accurate
- Not just count no. of risk factors but each risk factors is also quantified
1. Older age
2. Killip class
3. Systolic BP
4. ST deviation
5. Cardiac arrest during presentation
6. Serum creatinine level
7. Positive initial cardiac biomarkers
8. Heart rate
GRACE score ***>=140 —> High risk
Management objectives of NSTE-ACS
- ***Symptom relief
- Reduce ***short-term morbidity + mortality
- Prevent ***adverse ventricular remodeling
- Reduce intermediate / ***long-term cardiac event due to adverse ventricular remodeling
- Reduce ***recurrent ACS
***Management of NSTE-ACS
- General measures
- Bed rest
- ***Continuous ECG monitoring
- Supplemental O2 to maintain SaO2 >90% - Prevent disease progression to STE-ACS
- Anti-thrombotic therapy
—> **Dual Antiplatelet therapy +/- **Anticoagulant (LMW Heparin)
- ***Revascularisation - Relieve symptoms
- Anti-ischaemic therapy
—> **Nitrates, **β-blocker, ***CCB
Anti-thrombotic therapy
Dual Antiplatelet therapy (DAPT)
1. Aspirin
- Inhibit COX —> ↓ TXA2 synthesis in platelet —> ↓ platelet aggregation
- Clopidogrel, Prasugrel (no longer available in HK), Ticagrelor
- Block P2Y receptors (i.e. ADP receptor) —> ↓ platelet expression of GP2b/3a protein —> ↓ platelet aggregation
—> Price to pay when using dual antiplatelet: Bleeding risk ↑
Anticoagulant
1. LMW Heparin (Enoxaparin)
- Bind to Antithrombin (change conformation of Antithrombin) (+ Thrombin)
—> ↑ Antithrombin affinity to Thrombin, Factor 10a (also 9a, 11a, 12a) (Facilitate interaction between Antithrombin and Thrombin)
—> Inhibition of Thrombin, Factor 10a (also 9a, 11a, 12a)
—> Affect ***Intrinsic pathway significantly
—> ↓ Coagulation
Management algorithm:
Likely / Definite ACS:
- Initial dose of 150-300mg **non-enteric formulation (IV acceptable) (NOT enteric coated ∵ slow absorption) followed by 75-100 mg/day
- **Loading dose of Ticagrelor / Clopidogrel
- Consider ***LMW Heparin for anticoagulation
Definite ACS with High risk features, Plan for invasive therapy
- Above
- Consider ***GP2b/3a receptor inhibitor (Tirofiban, Eptifibatide, Abciximab) (less used now ∵ go straight to intervention)
Clopidogrel vs Prasugrel vs Ticagrelor
- MOA
Clopidogrel: **Irreversible inhibitor of P2Y12 component of ADP receptor —> longer time to reverse effect
Prasugrel: Irreversible inhibitor of P2Y12 component of ADP receptor
Ticagrelor: **Reversibly modify P2Y12 component of ADP receptor —> shorter time to reverse effect - Peak effect
Clopidogrel: 6 hours
Prasugrel: 4 hours
Ticagrelor: 2 hours - Onset
Clopidogrel: **2-4 hours (∵ prodrug)
Prasugrel: 30 mins
Ticagrelor: **30 mins (preferred drug in ACS) - When to hold dose prior to surgery
Clopidogrel: 5-7 days
Prasugrel: 7 days
Ticagrelor: 5 days - Antidote
Clopidogrel: Platelet transfusion
Prasugrel: Platelet transfusion
Ticagrelor: Platelet transfusion - Others
Prasugrel: CI if >75 yo / Weight <60kg / History of stroke
Ticagrelor: Use with Low dose Aspirin
