Professional Documents
Culture Documents
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
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
PATHOLOGY .......................................................................................................................................................................... 35
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CLINICAL ASSESSMENT...................................................................................................................................................... 38
HISTORY .................................................................................................................................................................................... 38
EXAMINATION ........................................................................................................................................................................... 38
INVESTIGATIONS ....................................................................................................................................................................... 39
TREATMENT .......................................................................................................................................................................... 41
IMMEDIATE MANAGEMENT ...................................................................................................................................................... 41
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
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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
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 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
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
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
IATROGENIC
MISCELLANEOUS
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
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)
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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
C OMBINATION THERAPY
- Use of lower doses of each drug decreases compensatory stimulation
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
-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
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- 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
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
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» 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)
-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
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- Direct vasodilators
Hydralazine or minoxidil rarely as additional therapy because they cause
» Fluid retention
» Reflex tachycardia
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Atherosclerosis
PROGRESSIVE INFLAMMATORY DISORDER OF THE ARTERIAL WALL
CHARACTERISED BY FOCAL LIPID RICH DEPOSITS OF ATHEROMA
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
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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
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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
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
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
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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
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CLINICAL FEATURES
HISTORY
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
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- 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
»
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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
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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
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%)
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
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
-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
NITRATES
- Examples
Glyceryl trinitrate (GTN)
» Sublingual
Isosorbide dinitrate
» Oral or IV
Isosorbide mononitrate
» Oral or IV
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
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
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
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
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
42 Joyce Kwan
May also be due to disease of the left heart chronic elevation of left atrial pressure pulmonary
hypertension right 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
43 Joyce Kwan
DIASTOLIC HEART FAILURE
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
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
RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
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
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-
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
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
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
53 Joyce Kwan
- Corticosteroids
- Doxorubicin & trastuzamab
- Thiazolidinediones
54 Joyce Kwan
Arrhythmias
DISTURBANCE OF ELECTRICAL RHYTHM OF THE HEART
55 Joyce Kwan