Cardiology JC007: Accelerating Chest Pain: Acute Coronary Syndrome

Question 1

Acute Coronary Syndrome (ACS)

Answer 1

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)

Question 2

Mechanism of Myocardial ischaemic pain

Answer 2

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
—>

1. Thalamus
   —> Cerebral cortex: Pain perceived
2. Brainstem (CV control centre)
   —> ↑ Sympathetic activity
   —> ↑ HR (but may have bradycardia if SA / AV nodal branch affected), BP, Sweating

Question 3

Chest pain in Chronic (i.e. Angina) vs Acute coronary syndrome

Answer 3

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

Question 4

Classification of ACS

Answer 4

1. 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
2. NSTEMI
   - severe **partial obstruction of vessels —> compromise basal metabolic need —> **Subendocardial myocardial injury / infarct —> Non-specific ST depression / T inversion
3. 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)

Question 5

Diagnosis of ACS

Answer 5

3 major clinical evidences for ACS

1. ***Clinical presentation
   - Chest pain / equivalent
2. ***ECG
   - Acute ischaemic changes
   —> Non-specific ST depression / T inversion
   —> ST elevation
3. Biomarkers (reflecting myocardial injury)
   - High sensitive ***Troponin

+/- 4. Imaging
- **Echocardiogram: Regional wall motion abnormality
- **CT coronary angiogram
—> used if 1-3 not conclusive

Question 6

Typical chest pain / Characteristics of chest pain in ACS

Answer 6

1. 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
2. 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)
3. Recent destabilisation of previously stable angina with >=3 CCS class 3 angina characteristics (Crescendo angina)
4. Post-MI angina

Question 7

Features NOT typical of myocardial ischaemia

Answer 7

1. Pleuritic, Sharp pain
   - related to respiration
   - but may be related myocarditis
2. Primary / sole location at middle / lower abdomen
   - MI pain should be ill-defined, dull aching, diffuse location (∵ visceral nerve)
3. Pain very localised by 1 finger tip
4. Pain reproduced by movement / chest wall palpation
   - point to skin / muscle / ribs
5. Very brief episode, lasting for seconds
6. Pain maximal intensity at onset + improves afterwards
   - point to Aortic dissection
7. Pain radiating to lower limbs

Question 8

***DDx of Acute chest pain

Answer 8

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

2. 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
3. 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
4. Pulmonary embolism (Days)
5. 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

Question 9

Typical ECG in ACS

Answer 9

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)

Question 10

Biomarkers after acute MI

Answer 10

Biomarkers: Leakage of cellular contents of myocardium into bloodstream

1. CKMB
   - not sensitive / specific as Troponin
2. Myoglobin, CK isoforms
   - rise + fall rapidly
   - good for detecting ***re-infarction (∵ Troponin will still be elevated)
3. 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)

Question 11

***Non-MI causes of Troponin rise

Answer 11

Cardiac causes (∵ ↑ demand of myocardium):
1. ***CHF

2. Takotsubo CMP (heart blown up like a balloon like an octopus)
3. Infection
   - ***Viral cardiomyopathy
4. Inflammation
   - ***Myocarditis / Pericarditis
5. Trauma
   - Surgery
   - Electrical shock
   - Post-RFA / Defibrillation
6. 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)

Question 12

***Types / Definition of Myocardial injury / infarction

Answer 12

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

Question 13

Type 1 MI

Answer 13

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

Question 14

Type 2 MI

Answer 14

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

Question 15

***Interpretation of elevated Cardiac Troponin

Answer 15

↑ 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)

Question 16

***Temporal dynamicity of ACS: Flowchart of management

Answer 16

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)

Question 17

Staging / Stratification of ACS

Answer 17

1. Risk criteria mandating invasive strategy in NSTE-ACS
2. TIMI Risk score
3. GRACE Risk score

Question 18

1. Risk criteria mandating invasive strategy in NSTE-ACS

Answer 18

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

Question 19

2. TIMI Risk score

Answer 19

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

Question 20

3. GRACE Risk score (Global Registry of Acute Coronary Events)

Answer 20

• 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

Question 21

Management objectives of NSTE-ACS

Answer 21

1. ***Symptom relief
2. Reduce ***short-term morbidity + mortality
3. Prevent ***adverse ventricular remodeling
4. Reduce intermediate / ***long-term cardiac event due to adverse ventricular remodeling
5. Reduce ***recurrent ACS

Question 22

***Management of NSTE-ACS

Answer 22

1. General measures
   - Bed rest
   - ***Continuous ECG monitoring
   - Supplemental O2 to maintain SaO2 >90%
2. Prevent disease progression to STE-ACS
   - Anti-thrombotic therapy
   —> **Dual Antiplatelet therapy +/- **Anticoagulant (LMW Heparin)
   - ***Revascularisation
3. Relieve symptoms
   - Anti-ischaemic therapy
   —> **Nitrates, **β-blocker, ***CCB

Question 23

Anti-thrombotic therapy

Answer 23

Dual Antiplatelet therapy (DAPT)
1. Aspirin
- Inhibit COX —> ↓ TXA2 synthesis in platelet —> ↓ platelet aggregation

2. 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)

Question 24

Clopidogrel vs Prasugrel vs Ticagrelor

Answer 24

1. 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
2. Peak effect
   Clopidogrel: 6 hours
   Prasugrel: 4 hours
   Ticagrelor: 2 hours
3. Onset
   Clopidogrel: **2-4 hours (∵ prodrug)
   Prasugrel: 30 mins
   Ticagrelor: **30 mins (preferred drug in ACS)
4. When to hold dose prior to surgery
   Clopidogrel: 5-7 days
   Prasugrel: 7 days
   Ticagrelor: 5 days
5. Antidote
   Clopidogrel: Platelet transfusion
   Prasugrel: Platelet transfusion
   Ticagrelor: Platelet transfusion
6. Others
   Prasugrel: CI if >75 yo / Weight <60kg / History of stroke
   Ticagrelor: Use with Low dose Aspirin

Question 25

Advantages of LMW Heparin over Unfractionated Heparin

Answer 25

1. Better bioavailability
   —> higher drug levels after SC injection
   —> SC administration ok
2. Reduced binding to protein
   —> more predictable anticoagulant response
   —> routine monitoring unnecessary
3. Reduced binding to + clearance by endothelial cells / macrophages
   —> clearance mainly by renal
   —> longer t1/2 permit once daily dosing
4. Reduced binding to osteoblasts
   —> ↓ activation of osteoclasts
   —> ↓ incidence of osteopenia + ↓ risk of heparin-associated osteoporosis + fracture with prolonged treatment
5. Reduced affinity for platelets + platelet factor 4
   —> ↓ incidence of heparin-induced thrombocytopenia

Question 26

***Antiplatelet therapy in NSTE-ACS

Answer 26

Initial:
1. Aspirin 300mg (QM: 320mg) loading —> 80-100mg daily
+
2. Loading dose of P2Y12 receptor inhibitor ***prior to invasive therapy
- Ticagrelor 180mg
- Clopidogrel 300mg (at least 6 hours prior to PCI)
- Prasugrel 60mg (NOT in prior CVA / TIA) (NOT available in HK now)

Maintenance:
1. Aspirin 80mg OD / Cartia (Aspirin EC) 100mg OD
+
2. Maintenance dose of P2Y12 inhibitor for 1 year
- Ticagrelor 90mg BD
- Clopidogrel 75mg QD
(- Prasugrel 10mg QD)

Question 27

Considerations in Antithrombotic treatment in NSTE-ACS

Answer 27

1. Patient characteristics
2. Clinical presentation
3. Comorbidities
4. Co-medications
5. Procedural aspects

Balance between Ischaemic risk vs Bleeding risk
- High ischaemic risk / Low bleeding risk: More aggressive about duration + potency of antithrombotic thearpy
—> DAPT 12 months
—> Aspirin alone
- High bleeding risk: Conservative

Question 28

Anti-ischaemic therapy

Answer 28

1. β-blockers
   - ↓ HR, BP, Contractility
2. Nitrates
   - Vasodilation, ↓ Preload
   - IV more effective than Sublingual to relieve symptoms
   - CI in patients on PDE5 inhibitor (Sildenafil) —> Hypotension / RV infarction
3. CCB
   - Vasodilation, ↓ BP
   - Verapamil, Diltiazem
4. Morphine
   - 3-5mg IV for those with severe angina

Question 29

Revascularisation strategies

Answer 29

Early intervention / Routine invasive procedure may help:
- ↓ Death / MI
- ↓ Angina
- ↓ Rehospitalisation

When to consider Coronary angiography / PCI?
- Higher the risk —> Earlier CC / PCI

(Very high risk criteria —> Immediate invasive strategy (<2 hrs):
- 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 —> Early invasive strategy (<24 hrs):
- Rise / Fall in Cardiac Troponin compatible with MI (indicate true ACS)
- Dynamic ST / T changes (symptomatic / silent)
- GRACE score >140

Intermediate risk criteria —> Invasive strategy (<72 hrs):
- DM
- Renal insufficiency (eGFR <60)
- LVEF <40% / CHF
- Early post-infarction angina
- Prior PCI
- Prior CABG
- GRACE score 109-140)

***CABG for following if found during Cardiac catheter:
1. Left main disease
2. 3 vessel disease
3. 2 vessel disease with Proximal LAD involvement
4. LV dysfunction
5. Treated DM

Question 30

Other Long-term Medical therapy

Answer 30

1. ACEI / ARB
   - all MI patients
   - initiated within 24 hours (i.e. early) if no CI in patients with anterior MI, CHF, EF <=40%
   - ARB: Candesartan, Valsartan, Losartan
2. Statin
   - ***High-intensity statin to reduce baseline LDL-C ~50%
   - Moderate intensity for Age >75 yo / cannot tolerate
   - Rosuvastatin 20mg OD, Atorvastatin 40mg OD
3. Mineralocorticoid antagonist (MRA)
   - Eplerenone in post-MI patients with impaired LV <=35% + HF
   - Avoid in significant renal dysfunction / HyperK
4. Risk factor control for Secondary prevention
   - Smoking cessation
   - Optimal glycaemic control (HbA1c 6.5%)
   - BP control
   - Aggressive lipid management
   - Dietary modification
   - Weight management

Question 31

Summary of ACS

Answer 31

1. Initial evaluation
   - Symptom, ECG —> then Troponin
2. Diagnosis validation + Risk assessment
   - Troponin + TIMI / GRACE scores
3. Antithrombotic treatment
4. Decision on time for invasive strategy
5. Revascularisation modalities: PCI / CABG
6. Drugs + Risk factor management