1. Coronary atheroma (>95%), thrombus or vasospasm
2. Aortic valve disease
3. Hypertension
4. severe anaemia/ thyrotoxicosis

2. Pericarditis

3. Aortic aneurysm: Dissecting, Rupture

4. Pulmonary embolism

5. Pleurisy or pneumothorax

6. Oesophageal pain (acid reflux, spasm, carcinoma)

7. Chest wall lesions

1. rib fracture
2. metastatic deposits in ribs
3. fibrositis or myalgia
4. herpes zoster

8. Gastric or duodenal ulcer

9. Gallstone colic

10. Pain referred from thoracic or cervical spine

• Exclude life-threatening CVS catastrophy

• AMI
• Dissecting aortic aneurysm
• Pulmonary embolism (to a lesser extent)

• Pericarditis
• GI causes
• Therefore ECG + enzyme test to exclude MI (rest of causes re unimportant)

• Pain lasting for days is unlikely to be due to CVS causes
• Pericarditis: ECG (diffuse concave ST elevation), Echo, CXR
• Pericarditis usu. present after a few days
• Pulmonary conditions: CXR
• Gastrointestinal conditions

1. Typical Angina

2. Atypical Chest pain

1. Angina pectoris

2. Acute coronary syndrome (ACS); Supersedes previous terminology of AMI- Q and non Q unstable angina

3. Sudden cardiac death

4. Heart failure

Unchangeable

• Age
• Sex: males more susceptible, women after menopause catch up with men, women live longer - therefore most CAD in elderly in women
• Hereditary eg. < 50yo in 1st-deg relatives

• DM
• HT
• Chol (LDL)
• Homocysteine
• CRP: C-reactive protein (measurement of inflam inside coronary artery; may predict future event inside coronary arteries)

• Cigarette smoking
• Obesity
• Sedentary

• Demand: depends on contractility (therefore inotropes increase demand)
• Wall tension: pressure inside = r power 4
• O2-carrying capacity: anaemia
• Vascular resistance
• Normality of endothelium (relaxes artery during exercise)
• AS - hardens artery (cannot expand during exercise)
• Flow of coronary artery in diastole (lower HR = more time to fill heart)

Lesions characterised by

1. Intimal thickening (smooth muscle cell migration)

2. Monocyte -> macrophage -> foam cells (uptake of oxidised LDL) [Foam cells: large chol-laden cells -> lead to early AS]

3. Neovascularisation

4. Fibrous cap

Stability = foam cell : fibrous cap

Thin fibrous cap (lots of neovascularisation) = tendency to rupture

Majority of ACS - plaque fissure. In AMI: majority may have <50% luminal obstruction (not degree of obstruction important, rather it is stability of plaque that is important (eg. Plaque fissure)

Diseased endothelium expressed cell adhesion molecules (CAM) bind with WBC

 Inflammatory cytokines and inflammatory modulators

• CAM
• Monocyte chemoattractant protein-I (MCP-I) - attract monocytes to become foam cells
• Interleukins (IL-6): (+) monocytes to become foam cells
• CD 40 ligand: inflam cytokine
• This inflam process can be detected in peripheral blood:
• IL6 -> C-reactive protein -> predicts outcome in CAD (AMI, unstable angina)
• Very low level of CRP (because inflam localised to coronary artery)

• If obstruct lumen by 70% (fixed obstruction) - cannot dilate artery during exercise
• Usu. stable (don't change)
• Angina during exertion
• Usu. only late stage before dev angina with minimal exertion or at rest

• Vulnerable plaque (thin fibrous cap - esp. young lesions
• Rupture - clotting - thrombus - convert moderate stenosis to complete stenosis - therefore angina at rest

= Acute coronary syndrome

• CAD, vasospasm
• Anaemia / thyrotoxicosis
• LVH (HT, Aortic stenosis) - LV wall thickened

Angina is diagnosed by history alone

It is unusual to have chest pain only precipitated by emotion without an exertion-related element

Infra-mammary pain: non-cardiac (localised pain non-cardiac)

Beware of unstable angina:

• Usually has a history of angina
• Increasing frequency and severity
• Rest pain (fissuring of plaques with thrombi clotting, but then dissolve, therefore intermittent flow obstruction)

History: severity, level of exertion that provoke angina

Risk factors: FBS (fasting bld sugar), Lipid, homocysteine

Other Causes: CBP, T4 (if needed)

Diagnosis and assessment of severity:

• ECG: resting ECG may not be useful (very severe CAD may have normal ECG)
• Exercise ECG: cause ischaemia
• Stress Isotope scan: thallium, cystamine-b, ischaemic part of heart shows as cold spot
• (Exercise or pharmacological eg. dipyridamole - stresses heart)

• On exercise (top): ST depression gradually increases from 1-3 mV
• Only after 6 minutes of exercise does ST return to normal
• Low risk mortality: 1/10,000 (high chance resuscitation by medial staff)

 SEE SLIDE (Isotope scan)

• Inject isotope
• Red = blood present
• Ischaemia = no red colour
• More accurate, specific
• Can localised site of ischaemia (cf. with ST change, which cannot)
• Quantitative: can tell amount of myocardium at risk

  Newer test for Angina

Stress MRI

Dobutamine echocardiography (inotrope) - affected area shows decreased function, similar to thallium stress test

Coronary calcification (ultrafast CT)

Eg. Matilda Hospital

If arteries have AS, after certain time you will have Ca

Disadv: Ca++ may not be obstructing arteries

Adv: > 40yo Caucasian (0 Ca in arteries indicates no AS in arteries)

If young and have Ca, at risk because new AS have yet to be calcified

Lots of commercial input for this method

PET: viability of heart

Angiography (100% sensitive / specific, mildly invasive)

Profile coronary artery

"Gold standard"

Fast MRI may overtake one day

All other Ix depends on pre-test probability as they are not 100% sensitive / specific

False + and false - Only in moderate risk group are these non-invasive tests helpful in diagnosis, but are useful to assess the severity of disease

Eg. 56yo man, has 50% risk of CAD, but if +ve test = increases his risk to 80%. Therefore should have angiogram to assess risk of CAD

Eg. Pre-menopausal women complains of angina, has low chance of CAD (0% if -ve and 2% if positive test)

Therefore, use of these studies - NEED FOR EXTRA INVESTIGATION? Eg. Angiogram

"Probability law"

Non-invasive test not useful in Dx

Only used to see if need further invasive tests (eg. Coronary angiogram) - for Dx

Inferior part heart and RV

Pigtail catheter

Assess heart function

1. Non-drug treatment

• Stop smoking
• Alteration of life style (eg. Change job?)
• Avoid competitive sports
• Treatment of precipitating factors:
• High output states,
• DM, HT, decrease lipids

1st line Tx

Adrenoceptors for catecholamines:

• Alpha: VC
• Beta1: Heart muscle - contractility, rate
• Beta2: Bronchial and vascular smooth muscle
• Metabolic effects: not classified

Actions: reduces oxygen demand

• Rate pressure product (at rest and during exercise) (heart rate and BP as assessment of O2 requirement of heart)
• Contractility
• Improves blood supply -
• Decrease diastole (minor effect)
• Best in association with HT

 Avoid in:

• Asthmatics: important
• 'Brittle' DM
• Intermittent Claudication: better to walk with difficulty than to have MI!
• Raynaud's Syndrome
• Second and Third Degree Heart Block: can put in pacemaker
• Patients with uncontrolled heart failure: relative contraindication, once controlled beta-blocker is useful

Discontinue if:

• Patients developing heart failure
• Patients developing asthma
• If pulse rate < 50bpm (at rest): reduce/ don't increase dose

Hydrophilic beta-blockers

• Eg. Atenolol, Nadalol, Sotalol
• Less tiredness (does not dissolve in brain, does not cross BBB)
• Give lower doses in renal failure

Cardioselective beta-blocker (main type used for angina pectoris)

• Eg. Atenolol, Acebutalol, Metoprolol
• Fewer effects on airway resistance (still tolerated poorly by asthmatics)
• Less interference with autonomic and metabolic responses to hypoglycaemia in insulin-dependent-diabetics

Intrinsic sympathomietic activity beta-blocker (becomes antagonist when Pt exercises)

• Eg. Oxypranolol, Pindolol, Acebutolol
• Stimulate heart at rest: less reduction in peripheral blood flow
• Effective when resting sympathetic tone is high
• Potential disadvantage: (1) Sleep impairment (2) Less decrease in HR in angina
• Do not favourably influence prognosis in long-term cardiac disease

Choice of Beta-Blocker

• All beta-blockers are equally effective in angina pectoris, but in special situations the ancillary properties of beta-blockers become important.
• Eg. Cardioselective beta-blockers used in patients with cold extremities, peripheral vascular disease, DM
• CNS side effects eg. Nightmares, tiredness: hydrophilic beta-blocker.
• Renal failure: reduce dose
• Liver disease: use a hydrophilic beta-blocker
• Elderly and Chinese Pt (difference in metabolism): start with a small dose (eg. Atenolol - usu. start with 50 mg/d, elderly start with 25 mg/d) - then titrate up (depends on symptoms and HR)

Actions

• AV dilators
• Increase supply: dilate coronary arteries
• Decrease LV size venodilatation and decrease LV pressure (by decreasing BP)

Mechanism

• Nitrates are an exogenous source of nitric oxide (NO), which is an endothelium-derived relaxation factor (EDRF)
• With NO, even arteries with AS will relax (endogenous: EDRF (relies on healthy artery))

Types of Nitrate Preparations Duration

Mononitrate are active without undergoing first pass liver metabolism unlike the dinitrate, bioavailability is more predictable (mononitrate used in most large hospitals)

Failure of nitrate to relieve angina if

• Severe angina pectoris (refractory Pt)
• Loss of potency of tables: shelf life of glyceryl trinitrate is about 6 months (spray = longer shelf life; more stable form) - reaction with O2
• Incorrect route of administration (eg. sublingual tablets taken orally) (should be in buccal mucosa)
• Tolerance with long-acting nitrate (tachyphylaxis)
• Non-compliant (eg. headache)

Side Effects and Contraindications

• Syncope and hT from reduction of preload and afterload, especially in presence of cerebral vascular disease
• Reflex tachycardia
• Headache and flushing
• MetHb with prolonged high dose (usu. in hospital)
• Contraindicated in hypertrophic obstructive cardiomyopathy and constrictive pericarditis (conditions highly dependent on preload)

Selectively block the Ca-channel during phase 2 of action potential

• Tissues Dependent on Ca-channel
• AVN/ SAN (eg. verapamil, diltiazem)
• Vascular and intestinal smooth muscle (S/E: constipation)

Myocardial contraction (high dose) -> -ve inotropic effect (undesirable in Pt with CAD - therefore Ca-channel blocker falling out of favour in Tx of CAD -> due to -ve inotropic effect, effectiveness in doubt)

Nifedipine

• No effect on AV node
• Potent vasodilator, useful for increased BP (in its slow release form)
• May lead to reflex tachycardia - combine with a beta-blocker (high heart rate = more angina pectoris)
• Dose 5-10 mg tds
• Slow release formulation
• No longer used (1) Reflex tachycardia (2) Lack of effectiveness

 Verapamil

• (Intravenous preparation for SVT only)
• Oral dose 80-120 mg tds
• Large first pass effect: therefore need high oral dose
• Mainly used by older physicians, but falling out of favour

Side effects:

• VD: headache, dizziness, hT
• Constipation
• Myocardial depression
• Depression of AVN esp. in conjunction with digoxin and beta-blocker (will lead to prolonged asystole)

Second Generation Ca Blocker

• Eg. Amlodipine, Felodipine, Isradipine, Lacidipin
• All are dihydrophyridine derivative compared to nifedipine:
• Longer acting (longer half-life or stronger tissue binding). Once daily use.
• ? Claimed to have less reflex tachycardia and oedema
• Less -ve inotropic (vascular selective)

Use of Ca blocker in angina

• Short acting Ca blocker eg. Nifedipine SHOULD NOT be used
• Pt with strong component of vasospasm, Ca blocker useful
• Often combined with a beta-blocker (do not use along as first line)
• Useful agent for concomitant HT

• Must for anyone with increased chol
• Stabilises and may regress AS plaque
• HMG Co-A reductase inhibitor: eg. Simvastatin, atorvastatin
• Anti-inflammatory effect (lower CRP)

• Coronary arteries initially narrow, become dilated after several years of Tx
• Expect some progression but progression rate is slower
• Indication:
• Primary prevention: TC > 6.4 (Pt with no CAD)
• Secondary prevention: LDL > 3.4 mmol/l (Pt with established CAD)
• Recent study: all levels of cholesterol should receive Tx - Health Protection Study (2002)
• Threshold for initiating Tx for CAD, is getting lower and lower

• Inhibits ATII + promotes bradykinin
• Use in heart failure, DM with microalbuminaemia (indep of high BP)
• HOPE study: in Pts with high risk of AS (eg. DM, PVD, angina), use of ACEI (Ramipril) reduces future AMI, CVA, HF (secondary prevention)
• Often used these days in stable CAD without high BP (based on this study)

• Important
• Standard in stable angina

Indications for Coronary Angiogram/Revascularisation

1. Medically refractory angina (takes drugs but still has angina)

2. Post infarction angina (suggests residual ischaemia that needs to be Tx)

3. Prognostically significant ischaemia

a. Exercise test: significant ST depression at low workload (suggests significant ischaemia)

b. Stress thallium/stamibi suggestive of large amount of myocardium at risk

RCA: Only one vessel occluded

LMS; significant lesion (15% die in 1st year - therefore need revascularisation)

• Efficacy: Symptom relief more effective than medicine
• In Pts with multiple vessel disease, the BARI trial shows no difference between PTCA and CABG, except DM Pts fare better with CABG (old study)
• Complications: Acute: vessel closure, AMI (man-made infarct); Chronic: restenosis
• Remarks: New pharmacological adjuncts (platelet inhibitors); New drug coated stents (reduce incidence of stenosis)

• Put in wire across stenosis and expand balloon/ stent
• Metal stent opens BV completely
• Percutaneous
• Pt awake
• Discharged next day

• Balloon with metal piece
• Insert balloon, stent remains
• Anti-platelet Tx prevents thrombosis on stent

Procedure used for 40y

Efficacy: prolong survival in significant artery disease and poor left ventricular function

Complications:

• More, delivered by surgical procedure
• Acute: stroke, AMI, wound complications
• Long term: Graft failure (esp. venous graft occlusion)
• Repeating surgery - increased mortality

Remarks:

• Surgeons more skilled these days
• Off pump surgery
• Left internal mammary graft

1. Left ventricular function: symptoms and signs HF, pulmonary oedema, ECG old infarct (advocate revascularisation)

2. Severity of angina:

Recent onset: unless settled, important

Unstable

"Strongly" positive treadmill test

Large or multiple defects and decreased EF (ejection fraction) with thallium

3. Extent of CAD

5 yr Mortality: 1 VD (vessels diseased), 2 VD, 3 VD, LMS (left main stem disease)

2, 8, 11, 15%/ 1st yr

Poor LV: worse prognosis

+ve - A

-ve - B