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Table of Contents

HYPERTENSION ....................................................................................................................................................................... 3
EPIDEMIOLOGY ............................................................................................................................................................................ 3
RISK FACTORS.............................................................................................................................................................................. 3
LIFESTYLE ASSESSMENT .............................................................................................................................................................. 3
BLOOD PRESSURE MEASUREMENT............................................................................................................................................. 4
CLASSIFICATION ........................................................................................................................................................................... 5
END-ORGAN DAMAGE ................................................................................................................................................................. 5
SECONDARY HYPERTENSION....................................................................................................................................................... 7
CLINICAL ASSESSMENT ............................................................................................................................................................. 11
TREATMENT .............................................................................................................................................................................. 14

ANATOMICAL CONSIDERATIONS ................................................................................................................................... 20


LAYERS OF MUSCLE ................................................................................................................................................................... 20
MAIN CORONARY ARTERIES ..................................................................................................................................................... 21

RISK FACTORS ...................................................................................................................................................................... 22

PATHOGENESIS OF ATHEROSCLEROSIS ...................................................................................................................... 22


FACTORS CAUSING ENDOTHELIAL DYSFUNCTION ................................................................................................................... 22
MARKERS OF INFLAMMATION .................................................................................................................................................. 22
PROGRESSION ........................................................................................................................................................................... 23
AHA PLAQUE CLASSIFICATION ................................................................................................................................................ 23
VULNERABLE PLAQUE ............................................................................................................................................................... 23
FIBROUS CAP OF PLAQUE .......................................................................................................................................................... 23

ANGINA WITH NORMAL CORONARY ARTERIES ....................................................................................................... 24

CLINICAL FEATURES ........................................................................................................................................................... 25


HISTORY .................................................................................................................................................................................... 25
EXAMINATION ........................................................................................................................................................................... 25
INVESTIGATIONS ....................................................................................................................................................................... 25

INVASIVE TREATMENT...................................................................................................................................................... 26
PERCUTANEOUS CORONARY INTERVENTION (PCI)............................................................................................................... 26
CORONARY ARTERY BYPASS GRAFT (CABG) ........................................................................................................................ 26

TREATMENT .......................................................................................................................................................................... 28
LIPID REGULATING DRUGS ....................................................................................................................................................... 28
COAGULATION CASCADE INHIBITOR ........................................................................................................................................ 28
CORONARY ARTERY ACTIVITY.................................................................................................................................................. 30
METABOLIC MODULATOR......................................................................................................................................................... 31
NON-ATHEROSCLEROTIC CAUSES............................................................................................................................................. 32

UNSTABLE ANGINA ............................................................................................................................................................. 32

UNIVERSAL DEFINITION OF MYOCARDIAL INFARCTION ...................................................................................... 32


CLASSIFICATION ........................................................................................................................................................................ 33

COMPLICATIONS OF ACUTE CORONARY SYNDROME ............................................................................................. 33

PATHOLOGY .......................................................................................................................................................................... 35
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CLINICAL ASSESSMENT...................................................................................................................................................... 38
HISTORY .................................................................................................................................................................................... 38
EXAMINATION ........................................................................................................................................................................... 38
INVESTIGATIONS ....................................................................................................................................................................... 39

TREATMENT .......................................................................................................................................................................... 41
IMMEDIATE MANAGEMENT ...................................................................................................................................................... 41

VENTRICULAR FUNCTION ................................................................................................................................................ 42

TYPES OF HEART FAILURE ............................................................................................................................................... 42


LEFT, RIGHT & BIVENTRICULAR HEART FAILURE.................................................................................................................. 42
DIASTOLIC & SYSTOLIC DYSFUNCTION ................................................................................................................................... 43
PATHOGENESIS OF HEART FAILURE ......................................................................................................................................... 44

COMPLICATIONS OF HEART FAILURE .......................................................................................................................... 47

CLINICAL ASSESSMENT...................................................................................................................................................... 49
HISTORY .................................................................................................................................................................................... 49
EXAMINATION ........................................................................................................................................................................... 49
INVESTIGATIONS ....................................................................................................................................................................... 49

MANAGEMENT ...................................................................................................................................................................... 51
APPROACHES ............................................................................................................................................................................. 51
SYSTOLIC HEART FAILURE ........................................................................................................................................................ 51
DIASTOLIC HEART FAILURE...................................................................................................................................................... 51
STAGES IN EVOLUTION OF HEART FAILURE + TREATMENT.................................................................................................... 51
PHARMACOLOGIC MANAGEMENT ............................................................................................................................................ 52
CONTRAINDICATED DRUGS IN HEART FAILURE ...................................................................................................................... 53

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HYPERTENSION
Hypertension is a condition in which arterial BP is chronically elevated
- 2 types of hypertension
 Essential hypertension
 Secondary hypertension

EPIDEMIOLOGY
- 26% of the adult population has hypertension
- 64 million disability-adjusted life years
- 7.1 million deaths per year
- Prevalence increases with advanced age
 5.5%: 15 – 24 years
 73.3%: > 75 years

RISK FACTORS
- Genetic factors – Asians do not make dopamine properly that helps in relaxation of arteries
- Fetal factors – low birth weight
- Insulin resistance – metabolic syndrome
 Increase renal sodium reabsorption
 Activation of sympathetic nervous system
 Alteration of transmembrane ion transport
 Hypertrophy of resistance vessels
- Environment factors including lifestyle
 Low levels of physical activity
 Dietary factors
 High sodium intake/protein intake
 Low potassium intake/fibre intake
 Alcohol consumption
 Obesity
 Stress

LIFESTYLE ASSESSMENT
Item for assessment Frequency of assessment for Frequency of assessment for
general population high risk group
Smoking On 1 visit & once every 1 – 2 Every year for smokers
st

years thereafter
Drinking of alcohol On 1st visit & every 3 years Annual assessment for drinkers
Dietary pattern e.g. fat/salt On 1st visit & every 2 years Every 6 months for obese/diabetic
intake patients
Physical activity level Every year Every year
BMI & waist circumferences Every 2 years Every year for obese & DM
patients
Psychosocial e.g. coping with Opportunistic Appropriate follow-up on
stress detection

STRATIFICATION OF TOTAL CARDIOVASCULAR RISK


- Routine tests
 Fasting blood sugar, lipids, RFT, uric acid, Hb, estimated creatinine clearance or GFR, urine for
protein, blood and glucose, ECG
- Recommended tests
 Spot urine for albumin/Cr ratio
 Echocardiogram (for LVH)
 Carotid US (for intima- media thickness)

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 OGTT (if indicated)

R ISK FACTORS
- Age (M > 55y, F > 65y)
- Smoking
- Dyslipidaemia
- Obesity
- Family history of premature
cardiovascular disease
- Abnormal glucose tolerance
- DM
- Subclinical target organ damage
 LVH, carotid wall
thickening/plaque
 GFR < 60 ml/min
CKD – chronic liver disease
 Microalbuminuria (spot urine
OD – asymptomatic organ
albumin/cr ratio)
damage
- Established cardiovascular/renal
VD – symptomatic cardiovascular
disease
disease
 Strokes, TIA, heart disease (MI, angina, CHF)
 Renal diseases
 Peripheral vascular disease
 Advanced retinopathy
»

A NTIHYPERTENSIVE TREATMENT

BLOOD PRESSURE MEASUREMENT


- Used to detect any changes from normal values, which may indicate disease
- To monitor the effectiveness of medication & other methods used to control elevated blood pressure
- Measured in mmHg
- Blood pressure have 2 values
 Systolic pressure – pressure on arteries each time heart muscles contract
 Diastolic pressure – pressure when the heart is at rest in between beats
- Sphygmomanometer
 Mercury vs electronic
 Avoid finger/wrist recording
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- Checking of mercury sphygmomanometer
 Column of mercury vertical
 Level of mercury at 0 when cuff deflated
 No blockade of air venting system at top of manometer
» Blocked vent  sluggish response/bouncing of mercury column during inflation & deflation
 No leakage from rubber tubing, hand pump & control valves
» Roll a cloth cuff into its own tail
» Pump up to 200 mmHg & wait for 10 seconds
» Mercury to fall < 2mmHg in 2 seconds
» If >2 mmHg, clamp circuit in sections to locate the leakage
- Precautions about BP recording
 Read at eye level
 Avoid digital preference
 Choose correct cuff size (at least 2/3 circumference of arm)
 Consistent use of 5th Korotkoff sounds for reading
 Correct arm positioning (at level of the heart)
 Velocity of cuff inflation/deflation
 Standardization between different recorders

CLASSIFICATION
Category Systolic BP/mmHg Diastolic BP/mmHg
Optimal <120 <80
Normal <130 85
High normal (prehypertension) 130 – 139 85 – 89
Grade 1 hypertension (mild) 140 – 159 90 – 99
Grade 2 hypertension (moderate) 160 – 179 100 – 109
Grade 3 hypertension (severe) ≥ 180 ≥ 110
Isolated systolic hyperntesion (ISH) ≥ 180 < 90
- When patient’s systolic & diastolic BP fall into different categories, higher category should apply
- ISH should be graded (1, 2, 3) according to systolic BP
 A low diastolic BP (e.g. 60 – 70 mmHg) means there’s increase in pulse pressure (atherosclerosis) 
additional risk

PREHYPERTENSION
-  Risk for development of hypertension that is age-dependent & associated with various metabolic risk
factors
-  Risk for development of cardiovascular disease
- Identification of patients with prehypertension will allow early intervention to
 Decrease BP
 Prevent progression to hypertension
 Decrease risk of cardiovascular morbidity & mortality

END-ORGAN DAMAGE
- Risk for CHD & strokes proportional to systolic & diastolic pressure
 Asians: strokes > CHD
 Caucasians: CHD > strokes
- Systolic & isolated systolic hypertension may be more important than diastolic BP
- Haemorrhagic strokes account for 30% strokes
- In HK, diastolic heart failure due to old age & hypertension is the most important cause of CHF requiring
hospital admissions
- Widespread atheroma develops & may lead to coronary + cerebrovascular disease, particularly if other
risk factors are present
- Structural changes in the vasculature often perpetuate & aggravate hypertension by
 Increase peripheral vascular resistance

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 Reducing renal blood flow  activating renin-angiotensin-aldosterone axis
- Hypertension is a major risk factor in the pathogenesis of aortic aneurysm & aortic dissection

MACROVASCULAR DISEASE
- Larger arteries (>1 mm in diameter)
 Internal elastic lamina is thickened
 Smooth muscle is hypertrophied
 Fibrous tissue is deposited
- Vessels dilate & become tortuous and their walls become less compliant

N EUROLOGICAL
- Cerebrovascular disease
 Carotid atheroma & transient ischaemic attacks are more common in hypertensive patients
- Subarachnoid haemorrhage
- Intracranial haemorrhage
- Hypertensive encephalopathy
 Rare condition characterised by high BP & neurological symptoms
» Transient disturbances of speech or vision
» Paraesthesiae
» Disorientation
» Fits & loss of consciousness

C ARDIOVASCULAR
- Myocardial ischaemia/infarction
 Atrial fibrillation is common & may be due to diastolic dysfunction
- Acute pulmonary oedema
 Caused by left ventricular hypertrophy due to increased preload in the heart
- Congestive heart failure
- Aortic dissection
 Usually type B
- Senile aortic calcific stenosis
 Caused by chronic injury from hypertension

MICROVASCULAR DISEASE
- In smaller arteries (<1 mm)
 Hyaline arteriosclerosis occurs in the wall, lumen narrows & aneurysms may develop
» Capillary micro-aneurysms
- Renal disease in longstanding hypertension
 Proteinuria
 Progressive renal failure

R ETINAL DISEASE
- Grade 1
 Arteriolar thickening
 Tortuosity & increased reflectiveness (silver wiring)
- Grade 2
 Grade 1 plus
 Constriction of veins at arterial crossings (arteriovenous nipping)
- Grade 3
 Grade 2 plus
 Evidence of retinal ischaemia (blot haemorrhages & ‘cotton wool’ exudates)
- Grade 4
 Grade 3 plus
 Papillodema

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SECONDARY HYPERTENSION
Hypertension with identifiable cause
- Renal
 Renal parenchymal disease (chronic kidney disease)
 Renovascular disease (renal artery stenosis)
 Polycystic kidney disease (PKD)
- Endocrine
 Primary hyperaldosteronism (Conn’s syndrome)
 Cushing’s syndrome
 Phaechromocytoma
 Acromegaly
 Thyrotoxicosis
 Hypothyroidism
 Hyperparathyroidism
- Iatrogenic
 Drug-induced
- Miscellaneous
 Obstructive sleep apnoea
 Obesity
 Coarctation of aorta

RENAL

R ENAL P ARENCHYMAL D ISEASE


- Most common cause of secondary hypertension
- Hypertension presents in ~70% of patients is difficult to control due to
  Intravascular volume
  RAAS
  Sympathetic tone
  Vascular stiffness
 Endothelial dysfunction
- Renal disease can often by detected by
 Urinalysis
 Urine microscopy
  Plasma urea/creatinine
- Tight BP control (<130/80 mmHg) may slow progression to end-
stage renal failure

R ENOVASCULAR D ISEASE
- 2nd commonest cause of secondary hypertension
- Renovascular hypertension (renal artery stenosis) due to one or
more stenosis of extra-renal arteries
- RAS can be due to fibromuscular dysplasia
 More common in younger women
- RAS can also be due to atherosclerotic narrowing
 More common in older men & diabetics
- Should be suspected if there is
 Renal bruit
 Very high & difficult to control BP
 Hypokalemia
 Progressive decline in renal function

Prevalence of arterosclerotic renal artery stenosis (ARAS)


- 14.8% of Chinese patients found to have significant ARAS
- Associated with higher risk of ARAS
 Hypertension
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 Renal insufficiency
 Extracranial cerebrovascular disease
 Female gender

Investigations
- Best simple screening test is renal ultrasound + Doppler flow measurement
 May show length discrepancy of > 1.5 cm in 2 kidneys
- Spiral CT + contrast
- Renal angiogram is the definitive test

Treatment
- Angioplasty + stenting is the preferred treatment
 Good response for fibromuscular dysplasia
- If stenosis has been present for long, angioplasty may not normalize BP but helps in preserving renal
function
- With bilateral RAS, ACEI may cause acute renal failure
- Difficult to predict BP response to renal revascularisation procedures
- Indications for revascularisation
 Refractory hypertension + progressive decline in renal function

P OLYCYSTIC K IDNEY D ISEASE (PKD)


Autosomal dominant polycystic kidney disease
- Mutation in polycystin-1 (PKD1) or polycystin
(PKD2) protein
- Progressive bilateral development & enlargement
of focal cysts that in many cases ultimate result in
end stage renal disease
- Renal cysts  in size & number, with age
- Cyst development also occurs in the
 Liver
 Pancreas
 Seminal vesicles
 Arachnoids
- Signs & symptoms
 Flank pain
 Haematuria
 Renal colic
 Urinary tract infections
 Hypertension
- Large phenotypic variability
- Mean age of onset of end stage renal disease 20 years younger in PKD1 (~85% of cases) than PKD2

ENDOCRINE

C USHING ’ S SYNDROME
- Syndrome encompassing signs & symptoms related to prolonged exposure to inappropriately high levels
of cortisol
- Hypertension in 80% of patients
- Clinical features
 Moon face
 Purple straie
 Truncal obesity
 Proximal myopathy
 Hypokalemia
 Hirsutism
 DM
 Oligmenorrhoea
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 Ecchymosis
- Always exclude iatrogenic causes, especially self-medications
- Diagnosis
 24-hour urinary cortisol excretion is increased
 Overnight dexamethasone suppression test

P RIMARY H YPERALDOSTERONISM (C ONN ’ S S YNDROME )


- 0.5 – 3% of patients with “essential hypertension”
- F:M = 3:1
- Mostly due to solitary small adenoma & 1/3 due to bilateral hyperplasia
- Asymptomatic hypokalemia is often initial finding
 Diuretic-induced hypokalemia should be excluded before investigating further
- Diagnosis confirmed by low plasma renin activity with elevated plasma aldosterone
 Localise tumours by CT or MRI
- Treatment
 Adenomas: surgery
» Need for antihypertensive drugs markedly reduced after adrenalectomy for adrenal
adenoma
 Hyperplasia: Drug treatment (amiloride or spironolactone)

O THER ENDOCRINE CAUSES OF HYPERTENSION


- Hypothyroidism
 Associated with diastolic hypertension
 Thyroid hormone replacement reduces BP
- Thyrotoxicosis
 Associated with systolic hypertension due to increased cardiac output
 Treatment will normalize BP
- Hyperparathyroidism
 Improves after parathyroidectomy
- Acromegaly
 Present in > 50% of patients
 Left ventricular hypertrophy & heart failure also occur

IATROGENIC

D RUG - INDUCED HYPERTENSION


- Always enquire about self-medications
- Corticosteroids
- Cyclosporines
- Tacrolimus
- Oral contraceptives (oestrogens)
- NSAIDs & COX-2 inhibitors
- Sympathomimetics (phenylpropanolamine, ephedrine)
- CNS stimulants (caffeine)
- Liquorice
- Erythropoietin
- Alcohol, nicotine, cocaine, amphetamines
- Slimming agents (sibutramine)

MISCELLANEOUS

O BSTRUCTIVE SLEEP APNOEA


- Especially in obese patients resistant to treatment
 Recurrent episodes of cessation of respiratory airflow caused by upper airway inspiratory collapse
during sleep & consequent decrease in oxygen saturation
- Clinical features
 Daytime somnolence
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 Poor concentration
 Poor sleep
 Choking episodes during sleep
 Apnoea
 Nocturia
 Irribility
- Stress & impairment of reflex cardiovascular regulation causing presser effect  hypertension
- Very high risk of cardiovascular disease & stroke

O BESITY
- Systolic blood pressure  6.5 mmHg for every 10%  in body weight
- Weight gain  less responsive to anti-hypertensives
- >40% of patients with resistant hypertension have obesity
- Mechanisms
 Insulin resistance
 Vasoconstriction
 Activated renin-angiotenin system/sympathetic nervous system
  Circulating volume

C OARCTATION OF AORTA
- Rare form of hypertension in children & young adults
- Diagnosis
 Mid-systolic murmur over anterior part of chest & also over back
 Femoral pulse absent or delayed relative to radial pulse
 Hypertension in upper limbs concomitantly with low/immeasurable BP in legs
- After repair/stenting, especially in adults, hypertension may persist

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CLINICAL ASSESSMENT

HISTORY

H ISTORY OF P RESENTING COMPLAINT


- Symptoms of uncontrolled hypertension
 Headache
 Visual disturbance
- Symptoms of end-organ damage
 Chest pain
 Palpitations
 Dyspnoea
 Ankle oedema
 Neurological symptoms
- Symptoms of underlying medical disorder causing secondary hypertension
History Possible causes
Early age of onset Any secondary cause
Severe or accelerated course Any secondary cause
Resistant hypertension Any secondary cause
Anxiety, sweating, palpitations, tremor, weight loss, diarrhoea Hyperthyroidism
Headaches, change in appearance, glove & shoe size, visual field Acromegaly
disturbance
Weakness, lethargy, muscle cramps (hypokalemia) Conn’s syndrome
Uriary symptoms, obstructive symptoms, symptoms of uraemia Renal disease

Specific drug intolerances Possible causes


Marked hypokalemia while taking diuretic Conn’s syndrome
Cushing’s syndrome
Worsening hypertension after -blockade Phaeochromocytoma
Acute renal failure after initiation/dose  of ACEI or ARB Renovascular hypertension

Symptoms Possible causes


Spells, lability, orthostatic hypotension Phaechromocytoma
Snoring, daytime hypersomnolence Obstructive sleep apnoea
Flash (sudden) pulmonary oedema Renovascular hypertension

R ELEVANT MEDICAL & FAMILY HISTORY


- Conditions which predispose to secondary hypertension
- Risk factors
- Major complications of hypertension
 Coronary heart disease (CHD)
 Stroke
 Renal disease
 Heart failure
 Peripheral vascular disease
- Family history of
 Hypertension
» Makes essential hypertension more likely
 Endocrine disease
» MEN2
» CHD

M EDICATIONS & INTERACTIONS


- Drug-induced hypertension
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- Interactions with common antihypertensive medications
 Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause sodium retention & resistance to
hypertension treatment
 Over the counter nasal sprays & decongestants may contain vasoactive agents (ephedrine &
pseudoephnedrine) which can induce hypertension

EXAMINATION
- Evidence of target organ damage – heart, CNS, kidneys, fundi, peripheral vascular disease
- Full physical examination, including arterial pulses and cardiac examination
- Abdominal examination – polycystic kidneys and listen for renal bruits
- Fundoscopy
 In grade III hypertensive changes
» Hard exudates
» Small haemorrhages
» AV nipping can be seen at 6 & 11 o’clock
 In grade IV hypertensive changes
» Papilloedema
» Large haemorrhages
» Soft exudates
Physical examination signs Possible causes
Café au lait spots, neurofibromas Phaeochromocytoma
Cervical fat pat, moon face, facial plethora, pigmented striae, proximal Cushing’s syndrome
myopathy
Thigh BP lower than brachial BP Coarctation of aorta
Continuous murmur over back
Goiter or thyroid nodule Thyroid disease
Large neck Obstructive sleep apnoea
Narrow pharynx with soft tissue crowding
Abdominal systolic-diastolic bruit Renovascular hypertension
Multiple arterial bruits
Large palpable kidneys Polycystic kidney disease

INVESTIGATIONS
- Routine blood tests to exclude possible secondary causes of hypertension
Investigation findings Possible causes
Hyperkalemia Renal parenchymal disease
Hypokalemia Renovascular hypertension
Primary hyperaldosteronism
Elevated plasma creatinine Renal parenchymal disease
Renovascular hypertension
Abnormal urinalysis Renal parenchymal disease
Loss of blunting of nocturnal BP decrease Any secondary cause
Disproportionate target organ damage (CHD, strokes, left ventricular Any secondary cause
hypertrophy, hypertensive retinopathy, renal failure)
- Hypertrophic obstructive cardiomyopathy
 Left ventricular hypertrophy with strain
 Deep S waves in C1, C2
 Tall R waves in C5, C6

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 T inversions due to repolarisation abnormalities (strain)

- Echocardiography-based left ventricular mass estimation


(𝐿𝑉𝐼𝐷𝑑+𝑃𝑊𝑇𝑑+𝐼𝑉𝑆𝑇𝑑)3
 LV mass = 0.8 x (1.04 𝑥 (𝐿𝑉𝐼𝐷𝑑)3
)+ 0.6g
» LVIDd = LV internal diameter in diastole
» PWTd = posterior wall thickness in diastole
» IVSDTd = interventricular thickness in diastole
 LV mass is indexed to body surface area
»
- Brain MRI (incidence from highest)
» Putamen (& caudate)
» Thalamus
» Cerebellum
» Pons

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TREATMENT

GOALS
- Primary goal to achieve maximum reduction in the long-term total risk of cardiovascular disease & other
complications
 Requires treatment of all reversible cardiovascular factors identified (in addition to hypertension) &
associated clinical conditions
- Target BP  below 140/90 mmHg and to lower values, if tolerated
- Target BP in high/very high risk patients (e.g. diabetic nephropathy)  below 130/80 mmHg

LIFESTYLE MODIFICATIONS
- Dietary plan
 Dietary Approaches to Stop Hypertension (DASH)
» Low saturated fat
» High fibre & minerals
» Fresh fruit & vegetables
» Low red meats
» For some individuals, 1,600 mg sodium
DASH diet has effects similar to single
drug therapy
 Weight reduction
» Structured, low-calorie diet
» “Weight watchers” program
» Avoidance of crash diet & latest food
fad
» Accompanied by 80 mins/day
(moderate activity)/35 mins/day
vigorous activity
» Waist circumference (<100 cm – men;
<90 cm – women)
 Lower dietary sodium intake
» Moderate Na+ reduction
» Avoid >300 mg/portion
 Moderation of alcohol consumption
» <2 alcoholic drinks/day (men); 1 alcoholic drink/day (women)
» Advised against binge drinking
 Regular aerobic exericies
» Incidence of HT decrease by 28% (men) & 35% (women) in high levels of physical activity
e.g. jogging/swimming
» After 30 mins of aerobic exercise At 50% maximal O2 intake
 BP remained lower for the rest of the 24 hour period
» Decreases incidence of stroke

DRUGS
- First line drug treatment can be chosen by considering indications/contraindications for a particular
class of drug
- If no specific indications/contraindications
 Diuretics
 -blockers
 Calcium channel blockers
 ACE inhibitors
 Angiotensin receptor blockers
- Most patient with moderate/severe hypertension needs a combination of drugs
- Some combinations are synergistic
 Diuretics + -blockers or ACE inhibitors
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 Calcium channel blockers + -blockers or ACE inhibitors

M ONOTHERAPY
- Low efficacy due to stimulation of compensatory mechanisms

Mild hypertension (<160/99)


- Diuretics (1st line drug)
- -Adrenoceptor blockers (1st line drug)
- Angiotensin converting enzyme (ACE) inhibitor
- Angiotensin receptor (AR) antagonist
- Ca2+ channel blockers
- -Adrenoceptor blockers (no longer considered as 1st line drug)
- Direct acting vasodilators

C OMBINATION THERAPY
- Use of lower doses of each drug decreases compensatory stimulation

Moderate & severe hypertension (>160/100)


- Diuretic + -Adrenoceptor blockers
- Diuretic + ACE inhibitor
- Ca2+ channel blocker + -Adrenoceptor blockers
- Ca2+ channel blocker + ACE inhibitor
- -Adrenoceptor blockers + -Adrenoceptor blockers

D IURETICS
Thiazide Diuretics
- Mode of action
 Decrease plasma volume & extracellular sodium
 Vasodilating effect reduces peripheral resistance
 Small decrease in extracellular fluid volume persists
- Efficacy
 Well established antihypertensive efficacy
» More evidence than any other drug class
 Used in primary & secondary prevention of strokes, CHF & MI & the elderly
 >40 years clinical experience
- Side effects (low dose)
 Diuresis causing urinary frequency & problems in the elderly and those with urinary incontinence or
BPH
 Electrolyte & metabolic disturbances
» Hypokalemia
» Hyponatremia (malaise, lethargy, dizziness)
» Gout
» Glucose intolerance
» Dyslipidaemia
 Postural hypotension
 Interactions with several other drugs due to electrolyte disturbances
 Impotence

Loop Diuretic (furosemide)


- Not usually used for hypertension except in patients with moderate/severe renal impairment and fluid
retention
- Mode of action
 Inhibit Na+ & Cl- re-absorption at the thick ascending loop of Henle
 Inhibit Na+/K+/Cl- co-transport  K+ loss 
 Solute & water are passed on to the distal tubule (limited capacity for Na+ re-absorption)
 Massive diuresis (diuresis starts within 10 minutes)
  Venous capacitance
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  Venous return (preload)
  Extracellular fluid volume
  Cardiac output
- Side effects
 Central volume depletion (dehydration)
» Monitor renal functions
 Electrolyte imbalance (hypokalemia)  arrhythmias
» One banana a day (sufficient K+ supplement)
» Liquid K+ supplement

Potassium-sparing diuretic (spironolactone)


- Amiloride or triamterene can be used in combination with thiazides to prevent hypokalemia
- Ineffective if used alone
- Spironolactone is generally used only in patients with cirrhosis or heart failure
- Mode of action
 Steroidal analogue of aldosterone
 Competitive antagonist in the cortical collecting tubule
 Inhibit aldosterone-controlled Na+/K+ exchange in the distal tubule
  Na+ excretion & K+

-B LOCKERS
- Propanolol (non-selective)
- Metoprolol ( 1 selective)
 Do not cross BBB
- Atenolol ( 1 selective)
 Do not cross BBB
- Carvedilol (1 &  receptors)
- Esmolol ( 1 selective: emergency)
- Labetalol (1 &  receptors: pregnancy)
- Mode of action
 Direct cardiac action initially lowers blood pressure with a reduction in cardiac output
 Other mechanisms include
» Inhibition of renin release
» Decrease in central sympathetic activity
» Altered sensitivity of baroceptor reflex
- Efficacy
 Well established antihypertensive efficacy
» Good evidence in secondary prevention of myocardial infarction & when used cautiously in
heart failure
 > 30 years clinical experience
- Side effects
 Exacerbation of asthma & possibly COPD
 Exacerbation of peripheral vascular disease & bradyarrhythmias (2nd or 3rd degree heart block)
 Increase insulin resistance
 Blunt perception of & prolong hypoglycaemia
 Increase dyslipidaemia especially hypertriglyceridemia
 Reduce exercise capacity
 Central nervous system effects
» Insomnia
» Nightmares
- Contraindications
 Asthma/bronchitis
 Raynaud’s phenomenon
 Congestive heart failure

C ALCIUM CHANNEL BLOCKERS


- Amlodipine (long acting, dihydropyridine)

16 Joyce Kwan
- Nifedipine (dihydropyridine)
- Diltiazem (benzothiazapine)
- Felodipine (dihydropyridine)
- Verapamil (phenylalkamine)
- Mode of action
 Block influx of Ca2+, through L-type Ca2+ channels, into the cells (heart & blood vessels)
  Excitation-contraction coupling
  Contractility & heart rate  BP 
  Vasoconstriction  BP 
» In the heart, some can reduce myocardial contractility & depress conducting system
- Efficacy
 Very effective in lowering BP but outcome efficacy, which is particularly for stroke, only established
in last few years
- Side effects
 Excessive vasodilation causing ankle/pedal oedema, flushing headache, dizziness, palpitations
 Rebound angina
 Exacerbation of
» CHF
» Bradycardia
» Heart block with some (verapamil, diltiazem)
 Gastrointestinal problems
» Verapamil  constipation
- Classification

- Short-acting should not be used


 Increases side-effects
 Increases heart rate

ACE INHIBITORS
- Lisinopril (commonly used in hospital)
- Perindopril
- Ramipril
- Captopril
- Enalapril
- Mode of action
 Inhibit formation of circulating & tissue angiotensin II (which does)
»  Na+ & water retention

17 Joyce Kwan
»  Aldosterone secretion
»  Vascular tone (vasoconstriction)
»  Catecholamine release
»  Nitric oxide-mediated relaxation
 Inhibit degradation of bradykinin
 Decrease sympathetic tone
- Efficacy
 Established antihypertensive efficacy
 May need to combine with diuretic for good effect
 Proven efficacy in secondary prevention of heart failure & diabetic retinopathy
 Useful in reversing myocardial hypertrophy
 >20 years clinical experience
- Side effects
 Cough (5 – 20% incidence)
 Deterioration in renal function
» Acute renal failure with bilateral renal artery stenosis
 May cause hyperkalemia
 First dose hypotension, particularly in combination with diuretics
» In elderly
» In elderly
- Many drug interactions with effects on plasma K+ & renal function
- Angioedema (rare but life-threatening)

A NGIOTENSIN R ECEPTOR B LOCKERS (ARB)


- Losartan
- Valsartan
- Candesartan
- Irbesartan
- Usually for patients with ACE inhibitor intolerance
- Mode of action
 Specific antagonists of AT1 receptors
 Similar to ACE inhibitors but do not activate bradykinin system
- Efficacy
 Established antihypertensive efficacy
 May need to combine with diuretic for good effect
 Proven efficacy in prevention of stroke & diabetic nephropathy
 Useful in reversing myocardial hypertrophy
- Side effects
 Deterioration in renal function
» Acute renal failure with bilateral renal artery stenosis
 May cause hyperkalemia

-B LOCKER
- Mode of action
 Inhibit post synaptic 1 – adrenoceptors in blood vessels resulting in vasodilation
- Efficacy
 Can lower blood pressure but outcome efficacy not clearly established and may increase risk of heart
failure or other outcomes compared with diuretics
 Useful in patients with symptoms of benign prostatic hypertrophy
- Side effects
 First dose & orthostatic hypotension

O THER AGENTS
- Centrally acting agents
 Methyldopa & clonidine
» Central agonist effect on 2 – adrenoceptors  reduce sympathetic tone
 Methyldopa used in pregnancy, but less popular otherwise due to side effects with high doses

18 Joyce Kwan
- Direct vasodilators
 Hydralazine or minoxidil rarely as additional therapy because they cause
» Fluid retention
» Reflex tachycardia

19 Joyce Kwan
Atherosclerosis
PROGRESSIVE INFLAMMATORY DISORDER OF THE ARTERIAL WALL
CHARACTERISED BY FOCAL LIPID RICH DEPOSITS OF ATHEROMA

- Can affect any artery in the body, if happened in


 Coronary arteries, may cause
» Angina
» Myocardial Infarction
» Sudden death
 Cerebral arteries, may cause
» Stroke
» Transient ischaemic attack
 Peripheral arteries, may cause
» Peripheral vascular disease
» Claudication
» Critical limb ischaemia
- Atherosclerosis is not a continuous, linear process
 A disease with alternate phases of stability & instability

ANATOMICAL CONSIDERATIONS
- 2 types of arteries
 Elastic (large vessels: aorta & carotid
arteries)
» Media mostly elastin
» Convert, in part, the systolic cardiac
impulse into diastolic blood flow
 Muscular (medium vessels: coronary,
brachial, radial, femoral)
» Media more smooth muscle
» Can regulate blood flow in response
to end-organ needs

LAYERS OF MUSCLE
- Intima
 Between endothelium & internal elastic lamina
 Highly fenestrated layer of elastin fibres that protects the media
- Media
 Almost entirely smooth muscle cells
 Blood supply
» Outer 1/3 of vaso-vasorum
» Inner 2/3 from diffusion from vaso-vasorum & from blood in lumen
 Normally, smooth muscle cells synthetically quiescent (few mitochondria & actinmyosin) but
capable of producing
» Collagen
» Elastin
» Proteoglycans
 Above important information of complex atherosclerotic
plaques & re-stenosis lesions that occur after PTCA
- Adventitia
 Loose connective tissue matrix that consists of fibroblasts
& smooth muscle cells that produce
» Collagen
» Proteoglycans
20 Joyce Kwan
 They intermix with vaso-vasorum and fat
»
- Endothelium
 Largest endocrine organ in the body
 Actively participates in
» Prevention of intravascular thrombosis
» Regulation of vascular muscle tone
 Endothelial dysfunction is the earliest detectable phas in the spectrum of atherosclerosis
 Hyperlipidaemia accelerates atherosclerosis progression
» Unclear direct initiating causal relationship
 Lowering cholesterol levels & ACEI may improve endothelial dysfunction
 Produces different factors for various cells & processes
» Nitrous oxide
» Angiotensin-converting enzyme (ACE)
» Coagulation platelet interaction: VWF, NO, PGI2
» Transport LDL: LDL receptors
» Fibrinolysis: tPA, PAI-1
» Monocyte adhesion: CAMs
» Vessel tone: NO, ET-1, ACE

» Vessel growth: VEGF, PDGF-like hormones, MCP-1

MAIN CORONARY ARTERIES


- LAD: left anterior descending
 50% coronary flow
- Circumflex
 25% coronary flow
- Right coronary
 25% coronary flow
- Factors influencing coronary flow
 Subendocardial flow
» Vessels compressed during systole
» Primarily diastolic flow
» As heart rate narrows, there is less time for
flow to subendocardium

21 Joyce Kwan
RISK FACTORS
- Age & sex
 Men & postmenopausal women have higher risk
 Elderly have higher risk
»
- Family history
 Atherosclerotic vascular disease
- Hypertension
- Hyperlipidaemia
- Hypercholesterolaemia
- Diabetes mellitus
- Smoking
- Haemostatic factors
 Platelet activation
 High levels of fibrinogen
- Obesity
- Increased alcohol consumption

PATHOGENESIS OF ATHEROSCLEROSIS
1. Endothelial dysfunction
2. Increased permeability & accumulation of oxidised lipoproteins
3. Taken up by macrophages at focal site
4. Lipid-laden foam cells

FACTORS CAUSING ENDOTHELIAL DYSFUNCTION

MARKERS OF INFLAMMATION
C-reactive protein (CRP) Assayed as high-sensitivity C-reactive protein (hs-CRP)
CRP stimulates release of inflammatory cytokines & induces expression of several
adhesion molecules
Powerful association between serum protein & atherosclerosis underscores a
fundamental role for inflammation in this pathological process
T lymphocytes & foam cells Key components of local arterial inflammation
Plaques with high concentrations of foam cells have a significantly increased
likelihood of becoming unstable  risk of rupture
Oxygen free radicals & Endothelium participates in the inflammatory process by generating free
nuclear factor-kB radicals which increases nuclear factor-kB
Nuclear factor-kB is a transcriptional factor for several genes that participate
in inflammation
Adhesion molecules (e.g. Expressed by the endothelium, both increase inflammatory factors
ICAM-1) & selectins Soluble adhesion molecules appear to confer increased risk of coronary
disease in prospective cohorts & may even identify cohorts that are
particularly susceptible to re-stenosis after percutaneous intervention
Vascular cell adhesion This particular adhesion molecule binds precisely the types of leukocytes
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molecule-1 (VCAM-1) found in early human atheroma, monocyte & t-lymphocyte

PROGRESSION
- Extracellular lipid accumulation
- Leukocyte recruitment
- Foam cell formation
- Intimal expansion
 Smooth muscle cell migration & proliferation
 Extracellular matrix deposition
- Vessel remodeling
- Plaque disruption
 Plaque rupture
 Endothelial cell erosion

AHA PLAQUE CLASSIFICATION


Lesion Type Description
Type I: early Normal intima or minimal intimal thickening
Type II: early Fatty streaks: little intracellular lipid deposits of smooth muscle cells
Type III: intermediate Preatheroma: increased extracellular lipid deposits
Type IV: advanced Atheroma: massive confluent lipid deposits (lipid core)
Covered mainly by the intima
Type V: advanced Fibroatheroma or
Calcific or
Fibrotic
Type VI: complicated Type IV or V lesions with
Disruptions or
Haemorrhage or
Thrombotic deposits

VULNERABLE PLAQUE
- Vulnerable plaques contain inflammatory
cells in addition to the lipid core & collagen +
smooth muscle cells in stable plaques
- Collagens & elastin: structural
- Proteoglycans: transport & regulation of
cells, molecules

FIBROUS CAP OF PLAQUE


- Depends on interstitial collagen fibrils (Type
I & Type III) synthesised by smooth muscle
cells
- Inflammation stimulates
 Over-expression of MMP-1, MMP-13
(collagenase)
 Decreases collagen synthesis
- Plaque fissuring/rupture results in leakage
of lipid core & thrombosis

23 Joyce Kwan
Coronary Heart Disease (CHD)
CORONARY HEART DISEASE: DISEASE STENOSING CORONARY ARTERIES CAUSED BY
BUILD UP PLAQUE
ANGINA (PECTORIS): CHEST PAIN OF CARDIAC ORIGIN
MYOCARDIAL ISCHAEMIA: INSUFFICIENT CORONARY PERFUSION TO HEART MUSCLE
TO MAINTAIN NORMAL FUNCTION AT REST AND/OR DURING EXERCISE

- Imbalance of oxygen/nutrients supply relative to


myocardial demand  angina
- Determinants of demand & supply
 Demand
» Heart rate
» Blood pressure
» Wall tension
 Preload: tension during ventricular
filling
 Afterload: tension during systole
» Ventricular chamber size
» Contractility
 Supply
» Coronary blood flow (subendocardial tissue)
» Oxygen extraction & content
- 4 functional classes of angina
 I: angina occurs only with strenuous or rapid or prolonged exertion
 II: slight limitation of ordinary activity (e.g. climbing more than one flight of ordinary stairs at a
normal pace & in normal conditions)
 III: marked limitation of ordinary activity (e.g. climbing more than one flight in normal conditions)
 IV: inability to carry out any physical activity without discomfort – angina syndrome may present at
rest

ANGINA WITH NORMAL CORONARY ARTERIES


- Coronary artery spasm/variant angina
 Vasospasm in coronary arteries without angiographically detectable atheroma
 Angina may be accompanied by spontaneous & transient ST elevation on ECG
 Treatment
» Calcium cannel blockers
» Nitrates
» Other coronary vasodilators
- Syndrome X/microvascular angina
 Presence of class angina & ST depression on exercise stress test but normal coronary angiogram in
absence of any other demonstrable cardiac abnormalities

24 Joyce Kwan
CLINICAL FEATURES
HISTORY

HISTORY OF PRESENTING ILLNESS


- Chest discomfort (pain)
 Site
» Central
 Onset
» Constant/intermittent
» Suddenly/gradually
 Character
» Crushing, dull pressure like sensation
» Levine’s sign: patient often describes pain with a clenched fist
 Radiation
» Jaw
» Neck
» Arms (left arm)
 Associations
» Breathlessness
 Time
» Activity while onset
 Exacerbation/Relieving factors
» Exacerbated
 Physical exertion
 Cold exposure
 Heavy meals
 Intense emotion
» Relieved by rest
 Severity
- Warm up angina: patients with angina often find their symptoms are less pronounced on second
compared with first exertion

PAST MEDICAL HISTORY


- Diabetes Mellitus
- Hypertension
- History of coronary artery disease

EXAMINATION
- No direct signs that manifest due to angina however should examine for
 Hypertension
 Hyperlipidaemia
 Diabetes
 Left ventricular outflow obstruction (AS, HOCM)
 Previous myocardial infarctions

INVESTIGATIONS
- Haemoglobin
 Anaemia aggravates angina
- Resting ECG
 May show evidence of previous MI, but often normal
 T-wave flattening or inversion in some leads, provides non-specific evidence of myocardial
ischaemic or damage
25 Joyce Kwan
- Exercise ECG
 Planar or down-sloping ST segment depression of
 1mm is indicative of ischaemia
 Identifies amount exercise that can be tolerated
 Extent of ST segment change reflects extent of
coronary disease
 False positive in
» Presence of digoxin therapy
» Left ventricular hypertrophy
» Bundle branch block
» WPW syndrome
- Myocardial perfusion scanning
 May be helpful in patients with equivocal exercise tolerance test (ETT) or those unable to exercise
 Scintiscans of myocardium by intravenous radioactive isotope during stress (exercise
testing/pharmacological induced stress from dopamine)
- Stress echocardiography
 Alternative to myocardial perfusion scanning
 Transthoracic echocardiography to identify ischaemic segments of myocardium & areas of infarction
- Coronary arteriography
 Provides detailed anatomical information about extent & nature of coronary artery disease
 Usually performed with view to coronary artery bypass graft (CABG) surgery or percutaneous
coronary intervention (PCI)

INVASIVE TREATMENT
PERCUTANEOUS CORONARY INTERVENTION (PCI)
- Performed by passing a fine guidewire across a coronary
stenosis under radiographic control  position balloon
which is ten inflated to dilate stenosis
- Coronary stent (coated metallic ‘scaffolding’) is deployed on
the balloon & used to maximize + maintain dilatation of
stenosed vessel
- Mainly used in single or two-vessel disease
- Restenosis rate is ~30% at 6 months & for balloon
angioplasty with stenting, restenosis rate is ~20%

COMPLICATIONS
- Occlusion of target vessel or a side branch by thrombus or loose flap of intima  myocardial
damage
 Minor myocardial damage (elevated troponins) occurs in up to 10%
» Often corrected by deploying a test or sometimes emergency CABG
- Restenosis (30%)
 Due to combination of elastic recoil & smooth proliferation
 Tends to occur within 3 months
 Stenting substantially reduces risk of restenosis
» Drug-eluting stents can reduce risk even further by allowing an antiproliferative drug
(sirolimus or paclitaxel) to elute slowly from coating & prevent neo-intimal hyperplasia
- Recurrent angina (15 – 20%)
 May require further PCI or CABG
»

CORONARY ARTERY BYPASS GRAFT


(CABG)
- Indications

26 Joyce Kwan
 Significant left main coronary artery stenosis
 Left main coronary artery disease:  70% of stenosis of proximal LAD & proximal LCx
 Triple vessel disease
 Two vessel disease with significant proximal LAD stenosis & left ventricular ejection fraction < 50%
or demonstrable ischaemia on non-invasive testing
- Internal mammary arteries, radial arteries or reversed segments of patient’s own saphenous vein can be
used to bypass coronary artery stenoses
- 90% patients are free from angina after 1 year, 60% patients asymptomatic after 5 years
 <50% of vein grafts are patent 10 years after surgery
 Arterial grafts have longer patency rate

POST-OPERATIVE MANAGEMENT
- Aspirin (75 – 150 mg OD) & clopidogrel (75 mg OD)
 Improve graft patency  prescribed indefinitely if well tolerated
- Intensive lipid-lowering therapy
 Slows progression of disease in native coronary arteries & bypass grafts
 Reduces clinical cardiovascular events

COMPLICATIONS
- Perioperative stroke (1 – 5%)
- Short-term cognitive impairment (30 – 80%)
 Typically resolves within 6 months

PCI CABG
Death <0.5% <1.5%
Myocardial infarction 2% 10%
Hospital stay 12 – 36 hours 5 – 8 days
Return to work 2 – 5 days 6 – 12 weeks
Recurrent angina 15 – 20% at 6 months 10% at 1 year
Repeat revascularization 10 – 20% at 2 years 2% at 2 years
Neurological Rare Common
complications
Other complications Emergency CABG Diffuse myocardial damage
Vascular damage related to assess site Infection (chest wound)
Wound pain

27 Joyce Kwan
TREATMENT
- Treated by ABCDE
 A: aspirin, anti-anginal therapy & ACE inhibitor therapy
 B: beta-blocker & blood pressure
 C: cholesterol & cigarettes
 D: diet & diabetes
 E: education & exercise

LIPID REGULATING DRUGS

HMG-COA REDUCTASE INHIBITION


- First line agents for treatment of hyperlipidaemia
 More effective & better tolerated than other drugs
 Simvastatin
 Atorvastatin
- 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA Reductase)
 Rate limiting enzyme responsible for bio-synthesis of cholesterol in liver
- Lipids
 Low density lipoprotein (LDL) – carrier of cholesterol
 High density lipoprotein (HDL) – reverse cholesterol transport, brings cholesterol from blood 
liver for excretion in bile

A CTIONS
-  LDL level
-  HDL level
-  Triglycerides level
- Anti-oxidant & anti-inflammatory
- Anti-proliferation of vascular smooth muscle
- Reduces myocardial infarction & coronary death rate (30 - 40%)

FIBRIC ACID DERIVATIVE


- Gemfibrozil
- Elevated triglyceride levels are associated with increased risk for coronary heart disease
- Fibric acid derivative lowers triglyceride level by
  Hepatic secretion of VLDL triglyercide
  Lipolysis of plasma triglycerides
  HDL levels

NICOTINIC ACID
-  HDL level (15 – 35%)
 No other agent can  HDL as much
-  Triglycerides
-  LDL cholesterol
 Not 1st line drug for lowering LDL
- Inhibition of cAMP accumulation in adipose tissue  activity of triglyceride lipase 

COAGULATION CASCADE INHIBITOR


- Thrombosis – obverse of normal haemostasis
 At site of abnormal endothelial: atherosclerotic plaque
-  Blood flow/oxygen supply, downstream of the blood clot
 Ischaemic
 Infarction
- Therapeutic strategy
28 Joyce Kwan
 Prevention of formation
» Anti-platelet drugs:
 Aspirin
 Clopidogrel
» Anti-coagulants
 Heparin
 Nadroparin
 Warfarin
 Removal of blood clots

ASPIRIN
- Folk medicine for pain & fever
- Oldest & most widely used anti-platelet agent
- A non-steroidal anti-inflammatory drug (NSAID)
 Inhibits COX
 Inhibits prostaglandin synthesis
- Inhibits thromboxane A2 (TXA2) synthesis
 Potent platelet aggregator & vasoconstriction

U SES
- Anti-coagulation
- Acute myocardial infarction
 Primary prevention
 Immediate myocardial infarction management

CLOPIDOREL
- Adenosine diphosphate (ADP) receptor antagonist that inhibits ADP-induced platelet aggregation
- Interferes with thrombin-mediated platelet aggregation & shear-induced aggregation
- Expensive compared to aspirin (cost-effectiveness)

HEPARIN
- Intrinsic & extrinsic pathways of coagulation cascade
- Mainstay of acute anti-coagulation therapy for decades
- Unfractionated (molecular weight ~15,000)
 Not absorbed through GI tract
- Fractionated – low molecular weight heparins (LMWH) (molecular weight ~5000)
 More predictable
 Efficacious
 Safe
 Cost-effective
 Nadroparin

M ECHANISMS OF ACTION
- Intrinsic & extrinsic clotting cascades  activation of factor X (Xa)
- Activated factor Xa, with factor Va, activates thrombin
 Converts fibrinogen  fibrin
- Antithrombin III & protein C are important in coagulation
- Antithrombin III renders thrombin & factor Xa inactive
 Heparin binds to antithrombin III
- Unfractionated heparin-antithrombin III complex inhibits thrombin & factor Xa far more effectively than
does antithrombin III alone
- LMWH inactivates factor Xa AND thrombin
 More effective antithrombotic drug than unfractionated heparin

WARFARIN

29 Joyce Kwan
- Onset of anti-coagulation is slow (~5 days after therapy), compared to heparin
- Onset of action depends on amount of pre-existing clotting factors & clearance in circulation
- Procoagulating factors
 Factor II
 Factor VI
 Factor IX
 Factor X
- These factors are biologically inactive without the vitamin K (oxidized)-dependent carboxylation in the
liver
- Warfarin is an antagonist of vitamin K
- Warfarin inhibits vitamin K-requiring clotting factors

S IDE EFFECTS
- Haemorrhage
- Teratogenic

THROMBOLYTIC DRUGS
- Fibrinolytic drugs
- These drugs are enzymes that cause dissolution of blood clots
- Activates plasminogen  plasmin
 Digests fibrin & dissolves clot
- Therapy administered
 The sooner, the better (time within 3 – 4.5 hours)
- Examples
 Streptokinase
 Urokinase

CORONARY ARTERY ACTIVITY

-ADRENOCEPTOR BLOCKERS
- Structures similar to endogenous catecholamines
 Competitive antagonism at -adrenoceptor of the heart
-  Oxygen demands of the heart by lowering heart rate & myocardial contractility
-  Diastolic period with a corresponding increase in the time available for coronary perfusion 
myocardial perfusion 
- Example
 Propanolol

ANGIOTENSIN-CONVERTING ENZYME INHIBITOR (ACE-I)


-  Mortality & morbidity rates (within a few days of acute myocardial infarction)
- Examples
 Lisinopril
 Perindopril
 Ramipril

NITRATES
- Examples
 Glyceryl trinitrate (GTN)
» Sublingual
 Isosorbide dinitrate
» Oral or IV
 Isosorbide mononitrate
» Oral or IV

CA2+ CHANNEL BLOCKERS


30 Joyce Kwan
- Inhibits influx of Ca2+ through L-type Ca2+ channel on cardiac & vascular smooth muscle
- Inhibits blood vessels (peripheral & coronary arteries) contraction
-  Oxygen demand &  oxygen supply
- Examples
 Amlodipine
 Nifedipine
 Felodipine

METABOLIC MODULATOR
-  Fatty acid oxidation rates are detrimental in ischaemia & reperfusion (due to  glucose oxidation
-  H+ due to uncoupling of glycolysis from glucose oxidation
- Na+ and Ca2+ overload the heart

TRIMETAZIDINE
- No negative inotropic or vasodilator activities
- Inhibits long-chain 3-ketoacyl coenzyme A thiolase in the heart
- Effects
 Reduction in fatty acid oxidation
 Increase in glucose oxidation
 Reduces cell’s demand for oxygen without decreasing its ability to do work

31 Joyce Kwan
Myocardial Infarction (MI)/Ischaemia
ACUTE CORONARY SYNDROME: ENCOMPASSES UNSTABLE ANGINA AND MYOCARDIAL
INFARCTION THUS PROVISIONAL DIAGNOSIS GIVEN TO A SET OF SYMPTOMS NOT
CONFIRMED BY INVESTIGATIONS
UNSTABLE ANGINA: NEW-ONSET OR RAPIDLY WORSENING ANGINA, ANGINA ON
MINIMAL EXERTION, ANGINA AT REST IN THE ABSENCE OF MYOCARDIAL DAMAGE
MYOCARDIAL INFARCTION: IRREVERSIBLE NECROSIS OF HEART MUSCLE, WHICH
OCCURS WHEN ISCHAEMIA EXCEEDS CRITICAL THRESHOLD + EVIDENCE OF MYOCARDIAL
NECROSIS

- Usually caused by complex ulcerated or fissured atheromatous plaque with adherent platelet-rich
thrombus & local coronary artery spasm
- Dynamic process whereby degree of obstruction may either
 Increase  complete vessel occlusion
 Regress due to effects of platelet disaggregation & endogenous fibrinolysis

NON-ATHEROSCLEROTIC CAUSES
- Congenital anomalies – metabolic disorders
- Embolus – intimal proliferation
- Dissection – thrombosis without atherosclerotic plaque
- Spasm – substance abuse
- Trauma – myocardial O2 demand-supply disproportion
- Arteritis – intramural coronary artery disease
- External compression

UNSTABLE ANGINA
- Rest angina (>20 mins)
- New onset (<2 months) of severe angina
- Increasing angina
 Intensity
 Duration
 Frequency

UNIVERSAL DEFINITION OF MYOCARDIAL INFARCTION


- Evidence of myocardial necrosis in clinical setting consistent with myocardial ischaemia, in which case
any one of the following meets diagnosis for MI

 Detection of rise and/or fall of cardiac biomarkers (preferably troponin) with at least one value
above the 99th percentile of upper reference limit, together with at least one of following
» Symptoms of ischaemia
32 Joyce Kwan
» ECG changes indicative of new ischaemia (new ST-T changes or new LBBB)
» Development of pathological Q waves (except leads III & aVR)
 One small square wide
 > 2 mm deep
» Imaging evidence of new loss of viable myocardium or new regional wall motion
abnormality
 Sudden unexpected cardiac death involving cardiac arrest, often with symptoms suggestive of
myocardial ischaemia
» Accompanied by presumably new ST elevation or LBBB
» And/or evidence of fresh thrombus by coronary
angiography and/or autopsy
» BUT death occurring before blood samples could be
obtained
 Pathological findings of an acute MI

CLASSIFICATION
- Subendocardial (Non-ST elevated/Non-Q)
 Involve inner 1/3 to ½ of ventricular wall as subendocardial zone
is less perfused
 Caused by non-occlusive thrombi or hypoperfusion of
myocardium
 May or may not cause troponin elevation
 T-wave inversion may still be present on ECG
- Transmural (ST elevated/Q-wave infarction)
 Involves full thickness of ventricular wall in the distribution of
single coronary artery
 Caused by occlusive thrombi & less commonly thromboemboli or
vasospasm
 Troponin or CK-MB elevation
 Very important within 12 hours of ACS
 ST-segment elevation  pathological Q wave  T-wave inversion
on ECG

COMPLICATIONS OF ACUTE CORONARY SYNDROME


- Arrhythmias
 Usually transient
 Pain relief, rest & correction of hypokalaemia may help prevent them
 Ventricular fibrillation
 Ventricular tachycardia
 Accelerated idioventricular rhythm
 Ventricular ectopics
 Atrial fibrillation
 Atrial tachycardia
 Sinus bradycardia
 Atrioventicular block
- Ischaemia
- Acute circulatory failure
- Pericarditis
- Mechanical complications
 Rupture of papillary muscle
 Rupture of interventricular septum
 Rupture of ventricle
- Embolism
- Impaired ventricular function, remodeling & ventricular aneurysm
- Dressler syndrome
 Autoimmune phenomenon with triad of symptoms
33 Joyce Kwan
» Persistent pyrexia
» Pericarditis
» Pleurisy

34 Joyce Kwan
PATHOLOGY
- Occlusion is typically seen in
 Proximal 2cm of left anterior descending or left circumflex arteries
 Proximal & distal thirds of right coronary artery

»
- Pathological hallmarks of infarct-related artery
 Rupture of lipid-rish atheromatous plaque
 Intraplaque haemorrhage
 Intraluminal thrombus
- Activation of coagulation cascade
- Vasoconstriction
- Occlusion of coronary artery lumen
(microembolisation)
- Plaque rupture may lead to MI in
 Acute occlusion of artery (acute coronary septum
syndrome)
 Heal with progressive narrowing of artery
(chronic angina)

PROGRESSION
- Before 6 hours
 No grossly visible lesion seen
- Before 12 hours
 Myocardium is salvageable if reperfusion
occurs MI in anterior left
- 18 – 24 hours ventricular wall
 Infarct area becomes pale 
cyanotic & swollen
- 1st week
 Infarct area becomes
progressively more sharply
defined, yellow & softened
- 7- 10 days
 Circumference of infarct area
becomes hyperemic &
progressively expands Rupture into pericardial sac
- 6 weeks
 Fibrous scar well established

PATHOLOGY
- Acute myocardial infarction in the septum

35 Joyce Kwan
 After several days, there is a yellowish centre with necrosis & inflammation surrounded by a
hyperemic border
»
- Acute myocardial infarction of anterior left ventricular free wall & septum in cross section
 Yellowish centre with necrosis & inflammation surrounded by hyperemic border
- Rupture into pericardial sac
 Can cause life threatening cardiac tamponade
 Septum may also rupture
- Complication of infarction is aneurysm formation

HISTOLOGY
- Normal myocardium
 Cross striations & central nuclei
 Pale pink intercalated disks present
- Early acute myocardial infarction (< 1 day)
 Prominent pink contraction bands
- 1 – 2 days
 Increasing loss of cross striations
 Contraction bands
 Nuclei undergoing karyolysis
 Some neutrophils beginning to infiltrate myocardium
- 2 - 3 days
 Extensive haemorrhage at border of infarction
- 3 – 4 days
 More extensive neutrophilic infiltrate along with prominent necrosis & haemorrhage
- 2 – 3 weeks
 Healing phase with capillaries, fibroblasts & macrophages filled with haemosiderin (granulation
tissue)
- Weeks – years

36 Joyce Kwan
 Remote myocardial infarction
is

evidenced by a collagenous scar seen in subendocardial location

37 Joyce Kwan
CLINICAL ASSESSMENT
HISTORY
- Usual symptom: Chest pain
- Chest pain
 Site
» Central and may radiate to the jaw, neck & left arm
 Onset
» Constant/intermittent
» Suddenly/gradually
 Character
» Dull pressure like sensation
» Levine’s sign: patient often describes pain with a clenched fist
 Radiation
» Jaw
» Neck
» Arms (left arm)
 Associations
» Nausea
» Vomiting
» Pallor
» Breathlessness (may be a manifestation of ischaemia or left ventricular dysfunction)
» Palpitations & dizziness (due to arrhythmias)
» Symptoms of left ventricular dysfunction (orthopnoea, PND, ankle oedema)
 Time
» Activity while onset
 Exacerbation/Relieving factors
» Exacerbated by exertion
» Relieved by sublingual nitrates
 Severity
- Past medical history
 Cardiovascular risk factors (smoking, HT, hypercholestolaemia, DM)
 Previous cardiac history
 Coronary stenosis
- Family history
 Cardiovascular risk factors & diseases
- Drug history
 History of oral contraceptives in young women
» Increases thrombotic risk
 Prior use of aspirin/sublingual nitrate
- Social history
 Smoking habits
 Alcohol consumption

EXAMINATION
- Hands: nicotine staining of fingers
- Pulse
 Rate
» Heart block
» Tachyarrthymias
 Rhythm
» Atrial fibrillation
» Ventricular arrhythmias
- Blood pressure
- JVP
38 Joyce Kwan
 May be raised in cardiac failure
- Eyes
 Xanthelasma
- Auscultation
 Fourth heart sound
 Ejection-systolic murmur
» Papillary muscle dysfunction
 Pansystolic murmur
» Ventricular septal dysfunction (VSD)
 Related to anterior infarcts
» Mitral regurgitation (MR)
 Related to inferior infarcts

INVESTIGATIONS
- Blood tests
 Serial assay of serum markers
» Troponin I & T – takes 3 to 5 hours after onset of MI for markers to be detectable
» If negative, repeat 9 – 12 hours after admission
» Serial change 2-folds is significant
 Renal function test
 Glucose
 Lipids
 Complete blood count
 PT – extrinsic pathway
 APTT
- Electrocardiogram
- Chest x-ray

ELECTROCARDIOGRAM
- Elevated ST segment (DDx. Pericarditis)
 Elevation: > 1 small square
 Indicative of area of infarction
Typical ECG changes in STEMI
Infarct site Leads showing ST segment Coronary Artery
Anterior
Small V3 – V4 LAD
Large V2 – V5
Anteroseptal V1 – V3 Proximal LAD
Anterolateral V4 – V6, I, aVL LAD, LCx
Lateral I, aVL LCx
Inferior II, III, aVF RCA (~85%), LCx (~15%)
Posterior V1, V2 (reciprocal) RCA or LCx
Subendocardial Any Lead -
Right ventricle V4 Proximal RCA
- Pathological Q wave
 Width: > 1 small square (40ms)
 Depth: > 2 small squares
 May be normal in lead III & aVR
- T-wave inversion
»
»

KILLIP/KILLIP-KIMBALL CLASSIFICATION
- Used to characterise heart failure following MI
- Killip I: absent 3rd heart sound & absence of crackles
39 Joyce Kwan
- Killip II: 3rd heart sound or crackles in <50% of lung fields
- Killip III: crackles in >50% of lung fields
- Killip IV: cardiogenic shock

40 Joyce Kwan
TREATMENT
IMMEDIATE MANAGEMENT
- Aspirin (anti-platelet)
 Inhibits thromboxane A2 (TXA2) synthesis
» Potent platelet aggregator
» Vasoconstriction
- Pain relief
 Decrease vascular resistance, BP & infarct size
 Usually administered intravenously for fast action (opiates)
- Nitrates
 Sublingual glyceryl trinitrate
» Unstable angina
» Threatened infarction
 Intravenous nitrates (isosorbide dinitrate)
» Treatment of left ventricular failure
» Relief of recurrent/persistent ischaemic pain
- Reperfusion strategies (STEMI)
 Thrombolysis by fibrinolytics
» Enzymes that cause dissolution of blood clots
 Sterptokinase
 Urokinase
» Activates plasminogen  plasmin
 Digests fibrin & dissolves clot
» Therapy administered the sooner the better (time within 3 – 4.5 hours)
» Contraindications
 Active internal bleeding
 Previous subarachnoid or intracerebral haemorrhage
 Recent surgery/trauma
 Pregnancy
 Recent surgery (within 1 month)
 Percutaneous Transluminal Coronary Angioplasty (PTCA)
- Beta-blockers
 Relieve pain
 Reduce arrhythmias
 Improve short-term mortality
  Oxygen demands of the heart by lowering heart rate & myocardial contractility
  Diastolic period with a corresponding increase in the time available for coronary perfusion 
myocardial perfusion 
 Contraindications
» Heart failure
» Hypotension
» Bradycardia

41 Joyce Kwan
HEART FAILURE
CLINICAL SYNDROME THAT DEVELOPS WHEN THE HEART CANNOT MAINTAIN AN
ADEQUATE CARDIAC OUTPUT

- Almost all forms of heart disease can lead to heart failure


 Accurate aetiological diagnosis is important because in some situations a specific remedy may be
available

VENTRICULAR FUNCTION
- Ventricles function as a pump
Left Ventricle Right Ventricle
Circulation Systemic Pulmonary
Oxygenation Oxygenated blood Deoxygenated blood
Pressure High systolic pressure Relatively low
Failure Pulmonary congestion/oedema Systemic congestion
- Ventricular function
Systolic Diastolic
Functionality Contraction Relaxation
Timing Closure of mitral/tricuspid valve to Closure of aortic/pulmonary valve to
closure to aortic/pulmonary valve closure of mitral/tricuspid valve
Energy consumption Needed (active process) Both active & inactive processes
Failure Affect contractile & relaxation functions Affect relaxation function
- New York Heart Association (NYHA) functional classification of heart failure
 Class I: No limitation during ordinary activity
 Class II: Slight limitation during ordinary activity
 Class III: Marked limitation of normal activities without symptoms at rest
 Class IV: Unable to undertake physical activity without symptoms; symptoms may be present at rest

TYPES OF HEART FAILURE


LEFT, RIGHT & BIVENTRICULAR HEART FAILURE
- Left side of the heart comprises the functional unit of LA & LV, together with mitral & aortic valves
- Right heart comprises of RA, RV with tricuspid & pulmonary valves
- Left-sided heart failure
 Reduction in left ventricular output
 Increase in left atrial & pulmonary venous pressure
 Acute increase in left atrial pressure causes
» Pulmonary congestion/oedema
 Gradual increase in left atrial pressure (as in mitral stenosis) leads to
» Pulmonary vasoconstriction  pulmonary hypertension
- Right-sided heart failure
 Reduction in right ventricular output for any given right atrial pressure
 Causes of isolated right heart failure include
» Chronic lung disease (cor pulmonale)
» Multiple pulmonary emboli
» Pulmonary valvular stenosis
- Biventricular heart failure
 Heart may develop because disease process affects both ventricles
» Dilated cardiomyopathy
» Ischaemic heart disease

42 Joyce Kwan
 May also be due to disease of the left heart  chronic elevation of left atrial pressure  pulmonary
hypertension  right heart failure

DIASTOLIC & SYSTOLIC DYSFUNCTION


- Heart failure may develop as a result of
 Impaired myocardial contraction (systolic dysfunction)
 Poor ventricular filling & high filling pressures caused by abnormal ventricular relaxation (diastolic
dysfunction)
- Systolic & diastolic dysfunction often coexist, particularly in patients with coronary artery disease

SYSTOLIC HEART FAILURE

C AUSES
- Ischaemic heart disease
- Hypertension
- Idiopathic dilated cardiomyopathies
- Valvular heart disease e.g. CRHD
- Other cardiomyopathies
 Restrictive
 Infective
 Familial
- Secondary to tachyarrhythmias e.g. AF, VT
- Infiltrative conditions
 Amyloid
 Iron overloid
 Sarcoid
- Senile & endomyocardial fibrosis

C ORONARY ARTERY DISEASE & HEART FAILURE


- Myocardial Infarction
 Loss of functional myocytes
 Development of myocardial fibrosis & remodeling
- Ischaemia
 Exercise induced stunning
 Overall depression of left ventricle function
- Myocardial hibernation
 Hypocontractile myocardium
- Endothelial dysfunction

I SCHAEMIC HEART DISEASE & HEART FAILURE

43 Joyce Kwan
DIASTOLIC HEART FAILURE

D ETERMINANTS OF DIASTOLIC FUNCTION


- Active relaxation
- Chamber stiffness
 Myocardium – myocardial fibres & extracellular components
 Wall thickness
 Left ventricular geometry
 Right & left ventricular interaction
 Pericardial force
- Mitral valve orifice
- Atrioventricular coupling
- Intrathoracic pressure

C AUSES
- Hypertension (commonest)
- Left ventricular hypertrophy
- Ischaemic heart disease – myocardial ischaemia
- Aging
- Diastolic dysfunction is caused by stiff non-complaint ventricle, commonly found in patients with left
ventricular hypertrophy
Left Ventricular Pressure-Volume Curve

PATHOGENESIS OF HEART FAILURE

CLINICAL PERSPECTIVES
- Etiological factors causing myocardial insult  loss of contractility reserve  systolic dysfunction
 Decreases cardiac output
- Factors that impair relaxation  diastolic dysfunction  diastolic failure

NEUROHORMONAL ACTIVATION
-  Perfusion pressure & organ perfusion activates
 Renin-angiotensin-aldosterone system
(RAAS)
 Sympathetic nervous system
 Vasopressin system
 Peripheral deconditioning – muscle &
peripheral blood flow abnormalities
- Low (cardiac) activation of cytokines
- Causes the vicious circle of chronic heart
failure
- Low BP & CO  baroreflexes  decreased
renal perfusion  neurohormonal

44 Joyce Kwan
activation  increase afterload  more fluid retention  increase preload  LV workload increases 
LV function decreases  more LV dilatation

SYMPATHETIC NERVOUS SYSTEM


- Elevation of plasma catecholamines in heart failure and the degree of activation directly related to
mortality
- In heart failure
 1-receptors 
 1-receptors 
 Receptor response is reduced
- Myocardial adrenergic activation is higher than reflected by plasma catecholamines
- Activation of sympathetic nervous system is also seen in other structures e.g. skeletal muscles
- In animal models, infusion of catecholamines could induce myocyte damage/necrosis
1 & 2 receptor densities in the failing & non- Attenuation of  receptor function in heart
failing heart failure

Myocardial Norepinephrine Release Regional Norepinephrine Release

Hazards of sympathetic activation in


chronic heart failure

RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM

H AZARDS OF ROLE OF ANGIOTENSIN RECEPTOR ACTIVATION


- AT1
45 Joyce Kwan
 Vasoconstriction
 Aldosterone secretion  salt & water retention
 Increased sympathetic tone
 Vascular proliferation
 Cardiac interstitial cells proliferation  fibrosis
- AT2
 Vasodilation
 Antiproliferation
 Apoptosis

VASOPRESSIN
- Vasopressin/antidiuretic hormone has been shown to be
related to water retention in CHF
- Increase in central vasopressin expression results in
activation of water channels in the kidney that are
responsible for water molecule reabsorption in the renal
tubules, aquaporin 2

SKELETAL MUSCLE ABNORMALITIES


- Biochemical & histological changes occur in skeletal muscles in CHF due to long-term conditioning
- Biochemical
 Defective oxidative metabolism in skeletal muscles
» Alterations of enzymatic action
»  Glycolysis
»  Respiratory enzyme (citrate synthase & succinate dehydrogenase)
» Phosphocreatine depletion
» Excessive acidification
- Histological
 Muscle fibre atrophy
  Type I slow-twitch fibres (high capacity for aerobic oxidation) and  fast-twitch type IIb fibres
  Lipid content in skeletal muscles

PERIPHERAL BLOOD FLOW ABNORMALITIES


- Reduced blood flow & thus O2 availability to peripheries
- Worse in patient with poorest exercise capacity
- Possible mechanism
 Less efficient distribution of cardiac output thus  proportion of oxygen to skeletal muscles
 Hypotension causes  sympathetic drive & vasoconstrictor tone
 Abnormally high limb vascular resistance
 Reduced vasodilatory capacity of exercising muscle
»  Vascular “stiffness”
»  Hyperaemic response
» Na+ & water retention
» “Deconditioning” of peripheral vessels

CYTOKINES
- Cytokines expressed locally in heart inducing myocardial damage & dysfunction
 Vasoconstrictor cytokines
» Endothelin-1
» Big endothelin
 Vasopressor cytokines (proinflammatory)
» TNF-
» IL-1
» IL-6
 Pro-fibrogenic cytokines

46 Joyce Kwan
» Transforming growth factor-

CONCEPTUAL CHRONIC HEART FAILURE MODEL: NEUROHORMONAL DISORDER


- Pathogenesis
 Sympathetic nervous system activation
 Renin-angiotensin-aldosterone system activation
 Vasopressin
 Smooth muscle abnormalities
 Peripheral vascular abnormalities
 Cytokines

COMPLICATIONS OF HEART FAILURE


- Renal failure
 Poor renal perfusion due to low cardiac output
 May be exacerbated by
» Diuretic therapy
» Angiotensin-converting enzymes (ACE) inhibitors
» Angiotensin receptor blockers
- Hypokalaemia
 Hyperaldosteronism caused by activation of renin-angiotensin system & impaired aldosterone
metabolism due to hepatic congestion
- Hyperkalaemia
 Effects of drug treatment, particularly combination of ACEI & spironolactone (which both promote
potassium retention) and renal dysfunction
- Hyponatraemia
 Feature of severe heart failure & poor prognostic sign
 May be caused by
» Diuretic therapy
» Inappropriate water retention due to high ADH secretion
» Failure of cell membrane ion pump
- Impaired liver function
 Hepatic venous congestion & poor arterial perfusion
 Causes mild jaundice & deranged liver functions
- Thromboembolism
 DVT & pulmonary embolism may occur due to low cardiac output & enforced immobility
- Atrial & ventricular arrhythmias
 May be related to
» Electrolyte changes (hypokalaemia, hypomagnesemia)
47 Joyce Kwan
» Underlying structural heart disease
» Pro-arrhythmic effects of increased circulating catecholamines or drugs

48 Joyce Kwan
CLINICAL ASSESSMENT
HISTORY
- Left ventricle backward failure
 Dyspnoea on exertion
 Orthopnoea
 Paroxysmal nocturnal dyspnoea
- Left ventricle forward failure
 Fatigue
 Poor exercise reserve
- Right ventricle failure
 Congestive symptoms – ankle swelling, RUQ
pain/discomfort
- Past history of
 Hypertension
 Ischaemic heart disease
 Cardiomyopathy

EXAMINATION
- Signs of fluid retention
 Raised JVP
 Lung crepitations
 Pitting leg oedema
 Tender hepatomegaly
- Signs of impaired perfusion
 Cold clammy skin
 Low BP
- Signs of ventricular dysfunction
 Displaced left ventricular apex
 Right ventricular heave
 Third or fourth heart sound
 Functional mitral or tricuspid
regurgitation
 Tachycardia
- Look for aetiology
 Valvular disease
 Atherosclerotic valvular disease
 Severe hypertension
 Severe anaemia or volume overload e.g. arteriovenous shunt
 Pathological arrhythmia
 Evidence of generalised myopathy or poisoning

INVESTIGATIONS

BLOOD TESTS
- Identify associated disease
 Renal & liver function test
 Electrolyte disturbances
 Metabolic causes
» Haemochromatosis
» Hypocalcaemic cardiomyopathy
» Thyroid heart disease
» Anaemia
» Heavy metal poisoning
49 Joyce Kwan
 Amyloid
» Serum electrophoresis
» Rectal biopsy
 Sarcoid
» Serum ACE

CHEST RADIOGRAPHY
- Presence of pulmonary oedema on chest radiograph suggest left ventricular end-diastolic pressure is 25
mmHg (normal: ~7 mmHg)
- Abnormal distension of upper lobe pulmonary veins (with patient in erect position)
- Pleural effusion
- Bat-wing appearance
 Hazy opacification
spreading from the hilar
regions
 Vascularity of lung fields
become more prominent &
right + left pulmonary Kerley-B lines
arteries dilate
- Kerley-B lines
 Horizontal lines in costophrenic angles
 Interstitial oedema causing thickened interlobular septa &
dilated lymphatics

ECG & ECHOCARDIOGRAM


- ECG to look for underlying cause
 Ischaemic or infarction
 Left ventricular hypertrophy
 Arrhythmia
 Other causes of pathological Q waves
- Echocardiogram detects valvular disease & determines whether left ventricle function is globally
impaired
- Ejection fraction can be estimated & usually treatment is initiated when ejection fraction is  40
- Doppler echocardiography allows determination of diastolic dysfunction

EXERCISE TESTING & CORONARY ANGIOGRAPHY


- To identify ischaemic heart disease

RADIONUCLIDE VENTRICULOGRAPHY OR ECHOCARDIOGRAPHY


- To quantify severity of systolic dysfunction (ejection fraction)
»

50 Joyce Kwan
MANAGEMENT
APPROACHES
- Acute management of heart failure
- Chronic therapy of heart failure
- Treatment of underlying cause/precipitating factors of heart failure
- Cardiac rehabilitation

SYSTOLIC HEART FAILURE


- Neurohormonal blockers
 Angiotensin converting enzyme inhibitors (ACEI)
 Angiotensin II type 1 receptor blockers
 -Blockers
 Aldosterone receptor blockers

DIASTOLIC HEART FAILURE


- General measures same as systolic heart failure
- Pharmacological therapy
 Loop diuretics
 Angiotensin converting enzyme inhibitors (ACE-I)
 Angiotensin II type 1 receptor blockers
 -Blockers
 Calcium channel antagonists

STAGES IN EVOLUTION OF HEART FAILURE + TREATMENT


A Heart failure risk factors + no heart disease & symptoms
 Treat risk factors
 Avoid toxics
 ACE-I in selected patients
B Heart disease + no symptoms + asymptomatic left ventricular dysfunction
 ACE-I
 -Blockers
C Prior/current heart failure symptoms
 ACE-I
 -Blockers
 Diuretics/digitalis
D Refractory heart failure symptoms
 Palliative therapy
 Mechanical assisted device

51 Joyce Kwan
 Heart transplant

PHARMACOLOGIC MANAGEMENT
- Symptomatic Relief [DAD]
 Diuretics (Loop)
 ACEI
 Digoxin
- Improve survival
 ACEI
 Beta-blockers
 Nitrates + hydrazalazine
 Spironolactone

DIURETICS
- Improve exercise tolerance
- Facilitate the use of other drugs indicated for heart failure
- Patients can be taught to adjust their diuretic dose based on changes in body weight
- In heart failure
  Cardiac output   glomerular filtration rate   salt & water retention   workload of the
failing heart
- Diuretics inhibit Na+ re-absorption in the ascending limb of the loop of Henle  massive diuresis
-  Extracellular fluid volume   wall tension   myocardial demand
- Examples:
 Frusemide
 Indapamide
 Hydrochlorthiazide
- Used to relieve fluid retention
- Complication
 Electrolyte depletion
- Never used alone to treat heart failure

DIGOXIN
- Derived from foxglove (digitalis) plant, first described by Withering (1775)
- It is a positive inotropic agent ( contractility)
- Binds to & inhibits plasma membrane Na+/K+ ATPase (Na+ out/K+ into the cell)
- Inhibition of Na+/K+ ATPase   Na+   transport of Ca2+ out of the cell (via Na+/Ca2+ exchanger)  
cytosolic Ca2+   excitation-contraction coupling

ACE-I
- Blocks conversion of angiotensin I & angiotensin II
 Prevents functional deterioration
 Reduces volume preload
- Recommended for all heart failure patients
- Relieves symptoms
- Improves exercise tolerance
- Reduces risk of death & decreases disease progression
- Benefits may not be apparent for 1-2 months after initiation
- Examples
 Lisinopril
 Perindopril
 Ramipril

-BLOCKERS
- Cardioprotective effects due to blockade of excessive sympathetic nervous stimulation
- Short term
52 Joyce Kwan
 Decreases myocardial contractility
 Decreases heart rate
 Prolong diastolic filling
 Decrease oxygen demand
 Increase in ejection fraction after 1 – 3 months of use
- Long term
 Placebo-controlled trials  symptomatic improvement
- Combined with conventional heart failure therapy
- Examples
 Metoprolol
 Carvedilol

NITRATE + HYDRALAZINE
- Combination of hydralazine-isosorbide dinitrate has a favourable efficacy & mortality benefit in
heart failure
- Both drugs are arteriole & vein dilators
- Improve symptoms & reduce mortality in heart failure patients
-  Preload & afterload

SPIRONOLACTONE
- Aldosterone competitive inhibitor
- Acts at distal convoluted tubule
- Works synergistically with ACE inhibitor
- With ACE inhibitor, levels of angiotensin II decreases  increase aldosterone level
- Spironolactone prevents aldosterone escape
- Generally well-tolerated
- Shown to reduce heart failure-related morbidity & mortality
- Generally reserved for patients with NYHA class III-IV heart failure
- Side effects
 Hyperkalemia
 Gynaecomastia
- Potassium & creatinine levels should be closely monitored

ANGIOTENSIN RECEPTOR BLOCKERS (ARBS)


- Block AT1 receptors, which bind circulating angiotensin
II
- Should not be considered equivalent or superior to ACE-I
- Should be used to treat patients who are ACE intolerant
due to intractable cough or who develop angioedema
- Examples
 Valsartan
 Candesartan
 Losartan

CONTRAINDICATED DRUGS IN HEART


FAILURE
- Antiarrhythmic drugs
- Non-dihydropyridine calcium
antagonists
 Verapamil
 Diltiazem
- Tricyclic antidepressants
- Non-steroidal anti-inflammatory drugs
(NSAIDs)
- Cyclo-oxygenase 2 inhibitors

53 Joyce Kwan
- Corticosteroids
- Doxorubicin & trastuzamab
- Thiazolidinediones

54 Joyce Kwan
Arrhythmias
DISTURBANCE OF ELECTRICAL RHYTHM OF THE HEART

55 Joyce Kwan