Atherosclerotic vascular Atherosclerotic vascular disease disease AVD may manifest as:AVD may manifest as:

1.1. Coronary artery disease.Coronary artery disease.2.2. Cerebrovascular disease.Cerebrovascular disease.3.3. Peripheral vascular disease.Peripheral vascular disease.Pathophysiology:Pathophysiology:Early atherosclerosis:Early atherosclerosis:Fatty streaks develop when inflammatory cellsFatty streaks develop when inflammatory cellspredominantly monocytes migrate into the predominantly monocytes migrate into the intima,takeup oxidized LDL from the plasma intima,takeup oxidized LDL from the plasma

andandbecome lipid laden foam cells or macrophages, become lipid laden foam cells or macrophages,

whenwhenthese cells die and release their contents extrathese cells die and release their contents extracellular lipid pools appear. Smooth muscle cells cellular lipid pools appear. Smooth muscle cells

thenthenmigrate from the media into the intima in migrate from the media into the intima in

response toresponse tocytokines &growth factors produced by cytokines &growth factors produced by

activated macrophages.activated macrophages.

The lipid core will be covered by smooth The lipid core will be covered by smooth muscle cells and matrix, producing a stable muscle cells and matrix, producing a stable atherosclerotic plaque which is asymptomatic atherosclerotic plaque which is asymptomatic until it becomes large enough to obstruct until it becomes large enough to obstruct arterial flow.arterial flow.

Advanced atherosclerosisAdvanced atherosclerosis:: In an established atherosclerotic plaque In an established atherosclerotic plaque

macrophages mediate inflammation & macrophages mediate inflammation & smooth muscle cells promote repair, if smooth muscle cells promote repair, if inflammation predominates, the plaque inflammation predominates, the plaque becomes active or unstable & may be becomes active or unstable & may be complicated by ulceration & superadded complicated by ulceration & superadded thrombosis. Cytokines such as interleukin-1, thrombosis. Cytokines such as interleukin-1, tumour necrosis-alpha, interferon gamma, tumour necrosis-alpha, interferon gamma, platelet derived growth factors, and matrix platelet derived growth factors, and matrix metalloprotinases are released by activated metalloprotinases are released by activated macrophages & may cause the initial smooth macrophages & may cause the initial smooth muscle muscle

Cells overlying the plaque to become senescent Cells overlying the plaque to become senescent resulting in thinning of the protective fibrous resulting in thinning of the protective fibrous cap, may lead to erosion, fissuring or rupture cap, may lead to erosion, fissuring or rupture of the plaque surface, exposing its content to of the plaque surface, exposing its content to circulating blood, & may trigger platelet circulating blood, & may trigger platelet aggregation & thrombosis, may cause partial aggregation & thrombosis, may cause partial or complete obstruction resulting in or complete obstruction resulting in infarction or ischemia of the affected organ. infarction or ischemia of the affected organ.

Risk FactorsRisk Factors

A. Fixed R. FA. Fixed R. F Age Age Male sexMale sex Family history.Family history.

B. Modifiable R.FB. Modifiable R.F Smoking - Sedentary lifestyleSmoking - Sedentary lifestyle Hypertension - ObesityHypertension - Obesity Lipid disoder. - DietLipid disoder. - Diet D.MD.M Haemostatic variablesHaemostatic variables

Primary PreventionPrimary Prevention

Population advice to prevent coronary disease;Population advice to prevent coronary disease; Do not smoke.Do not smoke. Take regular exercise (minimum of 20 Take regular exercise (minimum of 20

minutes three times a week).minutes three times a week). Maintain ideal body weight .Maintain ideal body weight . Eat a mixed diet rich in fresh fruit & Eat a mixed diet rich in fresh fruit &

vegetables.vegetables. Aim to get no more than 30% of energy Aim to get no more than 30% of energy

intake from saturated fat. intake from saturated fat.

Secondary prevention:Secondary prevention: Patients who already have evidence of Patients who already have evidence of

atheromatous vascular disease e.g M.I, are at atheromatous vascular disease e.g M.I, are at high risk of another vascular event, can be high risk of another vascular event, can be offered a variety of treatment and measures offered a variety of treatment and measures to improve their outlook (secondary to improve their outlook (secondary prevention). prevention).

Correction of risk factorsCorrection of risk factors AspirinAspirin Beta blockersBeta blockers ACE InhibitorsACE Inhibitors

Coronary Heart DiseaseCoronary Heart Disease

It is the most common form of heart disease.It is the most common form of heart disease. Most important cause of premature death.Most important cause of premature death. In UK 1 in 3 men & 1 in 4 women die of CHD.In UK 1 in 3 men & 1 in 4 women die of CHD.

Clinical manifestationClinical manifestation:: Stable angina.Stable angina. Unstable angina.Unstable angina. M.IM.I Heart failure.Heart failure. Arrhythmia.Arrhythmia. Sudden death.Sudden death.

Stable anginaStable angina

Angina pectoris is caused by transient Angina pectoris is caused by transient myocardial ischemia.myocardial ischemia.

It may occur whenever there is an imbalance It may occur whenever there is an imbalance between myocardial oxygen supply & between myocardial oxygen supply & demand.demand.

Coronary atheroma is the most common Coronary atheroma is the most common cause.cause.

Other causes include aortic valve disease & Other causes include aortic valve disease & hypertrophic cardiomyopathy.hypertrophic cardiomyopathy.

Clinical features:Clinical features: The history is the most important factor in The history is the most important factor in

making the diagnosis.making the diagnosis. Central chest pain, discomfort or Central chest pain, discomfort or

breathlessness that is precipitated by breathlessness that is precipitated by exertion or other forms of stress, (heavy exertion or other forms of stress, (heavy meal, cold exposure, intense emotion, lying meal, cold exposure, intense emotion, lying flat/ decubitus, vivid dreams/ nocturnal flat/ decubitus, vivid dreams/ nocturnal angina), and relieved by rest.angina), and relieved by rest.

Start up angina: the pain comes when they Start up angina: the pain comes when they start walking & that later it dose not return start walking & that later it dose not return despite greater effort.despite greater effort.

Physical examination is frequently negative, Physical examination is frequently negative, but should include:but should include:

Evidence of valve disease, important risk Evidence of valve disease, important risk factors, left ventricular dysfunction, features factors, left ventricular dysfunction, features of arterial disease e.g carotid bruits and of arterial disease e.g carotid bruits and untreated conditions that may exacerbate untreated conditions that may exacerbate angina e.g anemia, thyrotoxicosis. angina e.g anemia, thyrotoxicosis.

Investigations:Investigations:Resting ECG:Resting ECG: Evidence of previous M.I, but may be normal.Evidence of previous M.I, but may be normal. Occasionally T wave flattening or inversion.Occasionally T wave flattening or inversion. The most important ECG changes is reversible ST segment The most important ECG changes is reversible ST segment

depression or elevation with or without T wave inversion at the depression or elevation with or without T wave inversion at the time the patient is experiencing symptoms.time the patient is experiencing symptoms.

Exercise ECG:Exercise ECG: Standard treadmill or bicycle ergometer protocol, planar or down-Standard treadmill or bicycle ergometer protocol, planar or down-

sloping ST-segment depression of 1 mm or more is indicative of sloping ST-segment depression of 1 mm or more is indicative of ischemia, up-sloping is less specific & often occurs in normal ischemia, up-sloping is less specific & often occurs in normal individuals.individuals.

Exercise ECG is used to diagnose angina, assess severity & Exercise ECG is used to diagnose angina, assess severity & identifying high- risk individuals.identifying high- risk individuals.

False +ve: Digoxin, LVH, LBBB, WPW syndrome, the accuracy is False +ve: Digoxin, LVH, LBBB, WPW syndrome, the accuracy is lower in women than men. lower in women than men.

Risk stratification in stable angina.Risk stratification in stable angina. High Risk; *post –infarct angina, *poor effort High Risk; *post –infarct angina, *poor effort

tolerance, *ischemia at low workload, *left main or tolerance, *ischemia at low workload, *left main or three vessel disease, *poor LV function.three vessel disease, *poor LV function.

Low Risk:Low Risk: Predictable exertional angina, *good effort Predictable exertional angina, *good effort

tolerance, *ischemia only at high workload, tolerance, *ischemia only at high workload, *single-vessel or minor two-vessel disease, *good *single-vessel or minor two-vessel disease, *good LV function.LV function.

Other forms of stress testing:Other forms of stress testing: Myocardial perfusion scanning: useful when Myocardial perfusion scanning: useful when

exercise test is not diagnostic, or patient can not exercise test is not diagnostic, or patient can not exercise, its accuracy is higher than exercise test.exercise, its accuracy is higher than exercise test.

The technique involve obtaining scintiscans of the The technique involve obtaining scintiscans of the myocardium at rest and during stress after myocardium at rest and during stress after administration of an i.v radioactive isotope e.g administration of an i.v radioactive isotope e.g thallium201, it is taken up by viable myocardium. thallium201, it is taken up by viable myocardium.

A perfusion defect present during stress but not A perfusion defect present during stress but not rest indicates reversible myocardial ischemia, rest indicates reversible myocardial ischemia, whereas persistent perfusion defect indicates whereas persistent perfusion defect indicates previous M.Iprevious M.I

Stress echocardiographyStress echocardiography::

It is alternative to perfusion scanning with similar It is alternative to perfusion scanning with similar accuracy.accuracy.

Uses transthoracic echo to identify ischemic Uses transthoracic echo to identify ischemic segments of myocardium & area of infarction, the segments of myocardium & area of infarction, the latter do not contract at rest or during stress.latter do not contract at rest or during stress.

Coronary arteriography:Coronary arteriography:

Shows the extent & nature of coronary artery disease, Shows the extent & nature of coronary artery disease, it may be indicated when other investigations fail to it may be indicated when other investigations fail to diagnose the cause of atypical chest pain.diagnose the cause of atypical chest pain.

ManagementManagement Assessment of the extent & severity of Assessment of the extent & severity of

arterial disease.arterial disease. Identification & control of significant risk Identification & control of significant risk

factorsfactors Measures to control symptoms.Measures to control symptoms. Identification of high risk patients & Identification of high risk patients &

application of treatment to improve life application of treatment to improve life expectancy.expectancy.

Antiplatelet therapy:Antiplatelet therapy:

Aspirin 75-150 mg reduce the risk of MI, Aspirin 75-150 mg reduce the risk of MI, Clopidogrel 75 mg daily equally effective but Clopidogrel 75 mg daily equally effective but more expensive can be used if the patient more expensive can be used if the patient has dyspepsia.has dyspepsia.

Anti-anginal drugs:Anti-anginal drugs: Nitrates: produces venous & arteriolar dilatationNitrates: produces venous & arteriolar dilatation Decrease myocardial oxygen demand (lower Decrease myocardial oxygen demand (lower

preload & afterload) & increase myocardial preload & afterload) & increase myocardial oxygen supply.oxygen supply.

Sublingual glyceryl trinitrate (GTN), as aerosol Sublingual glyceryl trinitrate (GTN), as aerosol 400 microgm or tablet 300-500 micro-gm 400 microgm or tablet 300-500 micro-gm sublingually usually relieve angina in 2-3 sublingually usually relieve angina in 2-3 minutes, side- effects include headache, minutes, side- effects include headache, symptomatic hypotension & syncope, the tablet symptomatic hypotension & syncope, the tablet should be replaced 8 weeks aftershould be replaced 8 weeks after

the bottle has been opened.the bottle has been opened. Nitrates can be used prophylactically before Nitrates can be used prophylactically before

exercise. exercise. GTN is subject to extensive first pass GTN is subject to extensive first pass

metabolism in the liver, its ineffeective when metabolism in the liver, its ineffeective when swallowed.swallowed.

Nitrate free period of 6-8 hr. every day to avoid Nitrate free period of 6-8 hr. every day to avoid tolerance. tolerance.

Preparation Preparation Peak actionPeak action DurationDuration

Sublingual GTN 4-8 mins 10-30 Sublingual GTN 4-8 mins 10-30 minsmins

Buccal GTN 4-10 mins 30-300 Buccal GTN 4-10 mins 30-300 minsmins

Transdermal GTN 1-3 hrs up to Transdermal GTN 1-3 hrs up to 24 hrs24 hrs

Oral isosorbide dinitrate 45-120 mins 2-6 hrsOral isosorbide dinitrate 45-120 mins 2-6 hrs

Oral isosorbide mononitrate 45-120 mins 6-10 hrs Oral isosorbide mononitrate 45-120 mins 6-10 hrs

Beta-blockers Beta-blockers Reduce myocardial oxygen demand by reducing heart rate, BP, Reduce myocardial oxygen demand by reducing heart rate, BP,

and myocardial contractility.and myocardial contractility. Non-selective BB may exacerbate coronary spasm by blocking Non-selective BB may exacerbate coronary spasm by blocking

Beta 2 coronary adrenoceptors.Beta 2 coronary adrenoceptors. Give once daily cardioselective preparation, atenolol 50-100 mg Give once daily cardioselective preparation, atenolol 50-100 mg

daily, slow release metoprolol 200 mg daily, bisoprolol 5-10 mg daily, slow release metoprolol 200 mg daily, bisoprolol 5-10 mg daily.daily.

ΒβΒβ should not be withdrawn suddenly as this may cause should not be withdrawn suddenly as this may cause arrhythmia, more angina or MI.(arrhythmia, more angina or MI.(ββββ withdrawal syndrome). withdrawal syndrome).

Calcium antagonists:Calcium antagonists: lower myocardial oxygen demand by reducing blood pressure lower myocardial oxygen demand by reducing blood pressure

and myocardial contractility.and myocardial contractility. Dihydropyridine calcium antagonists, such as nifedipine and Dihydropyridine calcium antagonists, such as nifedipine and

nicardipine, often cause a reflex tachycardia; it is often best to nicardipine, often cause a reflex tachycardia; it is often best to use these drugs in combination with a β-blocker.use these drugs in combination with a β-blocker.

In contrast, verapamil and diltiazem are particularly suitable In contrast, verapamil and diltiazem are particularly suitable for patients who are not receiving a β-blocker because they for patients who are not receiving a β-blocker because they inhibit conduction through the AV node and tend to cause a inhibit conduction through the AV node and tend to cause a bradycardia or even atrioventricular block in susceptible bradycardia or even atrioventricular block in susceptible individuals. individuals.

The calcium antagonists may reduce The calcium antagonists may reduce myocardial contractility and can aggravate or myocardial contractility and can aggravate or precipitate heart failure. Other unwanted precipitate heart failure. Other unwanted effects include peripheral oedema, flushing, effects include peripheral oedema, flushing, headache and dizziness.headache and dizziness.

Potassium channel activators;Potassium channel activators;

This class of drug has arterial and venous This class of drug has arterial and venous dilating properties but does not exhibit the dilating properties but does not exhibit the tolerance seen with nitrates. Nicorandil (10-tolerance seen with nitrates. Nicorandil (10-30 mg 12-hourly orally) is the only drug in 30 mg 12-hourly orally) is the only drug in this class currently available for clinical use. this class currently available for clinical use.

it is conventional to start therapy with low-it is conventional to start therapy with low-dose aspirin, sublingual GTN and a β-blocker, dose aspirin, sublingual GTN and a β-blocker, and then add a calcium channel antagonist or and then add a calcium channel antagonist or a long-acting nitrate later, if necessary. a long-acting nitrate later, if necessary.

The goal is the control of angina with The goal is the control of angina with minimum side-effects and the simplest minimum side-effects and the simplest possible drug regimen. There is little or no possible drug regimen. There is little or no evidence that prescribing multiple anti-evidence that prescribing multiple anti-anginal drugs is of benefit, and anginal drugs is of benefit, and revascularisation should be considered if an revascularisation should be considered if an appropriate combination of two drugs fails to appropriate combination of two drugs fails to achieve a symptomatic response. achieve a symptomatic response.

Invasive treatment The most widely used Invasive treatment The most widely used invasive options for the treatment of invasive options for the treatment of ischaemic heart disease include ischaemic heart disease include percutaneous coronary intervention (PCI; percutaneous coronary intervention (PCI; including percutaneous transluminal coronary including percutaneous transluminal coronary angioplasty, PTCA) and coronary artery angioplasty, PTCA) and coronary artery bypass graft (CABG) surgery.bypass graft (CABG) surgery.

UNSTABLE ANGINAUNSTABLE ANGINA is a clinical syndrome that is characterised by is a clinical syndrome that is characterised by

new-onset or rapidly worsening angina new-onset or rapidly worsening angina (crescendo angina), angina on minimal exertion (crescendo angina), angina on minimal exertion or angina at rest. or angina at rest.

The condition shares common The condition shares common pathophysiological mechanisms with acute pathophysiological mechanisms with acute myocardial infarction, myocardial infarction,

the term 'acute coronary syndrome' is used to the term 'acute coronary syndrome' is used to describe these disorders collectively. describe these disorders collectively.

These entities comprise a spectrum of disease These entities comprise a spectrum of disease that encompasses ischaemia with no myocardial that encompasses ischaemia with no myocardial damage, ischaemia with minimal myocardial damage, ischaemia with minimal myocardial damage, partial thickness (non-Q wave) damage, partial thickness (non-Q wave) myocardial infarction, and full thickness (Q myocardial infarction, and full thickness (Q wave) myocardial infarction .wave) myocardial infarction .

An acute coronary syndrome may present as An acute coronary syndrome may present as a new phenomenon or against a background a new phenomenon or against a background of chronic stable angina.of chronic stable angina.

The culprit lesion is usually a complex The culprit lesion is usually a complex ulcerated or fissured atheromatous plaque ulcerated or fissured atheromatous plaque with adherent platelet-rich thrombus and with adherent platelet-rich thrombus and local coronary artery spasm . local coronary artery spasm .

Diagnosis and risk stratification Diagnosis and risk stratification The assessment of acute chest pain depends The assessment of acute chest pain depends

heavily on an analysis of the character of the heavily on an analysis of the character of the pain and its associated features, evaluation pain and its associated features, evaluation of the ECG, and serial measurements of of the ECG, and serial measurements of biochemical markers of cardiac damage, such biochemical markers of cardiac damage, such as troponin I and T. as troponin I and T.

A 12-lead ECG is mandatory and is the most A 12-lead ECG is mandatory and is the most useful method of initial triage.useful method of initial triage.

Evolving transmural infarction is Evolving transmural infarction is characterised by persistent ST elevation, new characterised by persistent ST elevation, new Q waves or new left bundle branch blockQ waves or new left bundle branch block

In patients with unstable angina or partial In patients with unstable angina or partial thickness (non-Q wave or non-ST elevation) thickness (non-Q wave or non-ST elevation) myocardial infarction, the ECG may show ST/T myocardial infarction, the ECG may show ST/T wave changes including ST depression, wave changes including ST depression, transient ST elevation and T-wave inversion; transient ST elevation and T-wave inversion; the T-wave changes are sometimes the T-wave changes are sometimes prolonged.prolonged.

Approximately 12% of patients with well-Approximately 12% of patients with well-characterised unstable angina or non-ST characterised unstable angina or non-ST segment elevation myocardial infarction segment elevation myocardial infarction progress to acute infarction or death, and progress to acute infarction or death, and almost one-third will suffer a recurrence of almost one-third will suffer a recurrence of severe ischaemic pain, within 6 months of the severe ischaemic pain, within 6 months of the index event. index event.

The risk markers that are indicative of an The risk markers that are indicative of an adverse prognosis include :adverse prognosis include :

recurrent ischaemia, recurrent ischaemia, extensive ECG changes at rest or during extensive ECG changes at rest or during

pain, pain, the release of biochemical markers the release of biochemical markers

(creatine kinase or troponin), (creatine kinase or troponin), arrhythmias and haemodynamic arrhythmias and haemodynamic

complications (e.g. hypotension, mitral complications (e.g. hypotension, mitral regurgitation) during episodes of ischaemiaregurgitation) during episodes of ischaemia

those who experience unstable angina those who experience unstable angina following acute myocardial infarction are following acute myocardial infarction are also at increased risk. also at increased risk.

Risk stratification is important Risk stratification is important because it guides the use of more because it guides the use of more complex pharmacological and complex pharmacological and interventional treatment . interventional treatment .

High risk: High risk:

Clinical:Clinical:Post-infarct anginaPost-infarct angina

Recurrent pain at restRecurrent pain at restHeart failureHeart failure

ECG:ECG:ArrhythmiaArrhythmia

ST depressionST depressionTransient ST elevationTransient ST elevationPersistent deep T-wave inversionPersistent deep T-wave inversion

Biochemistry:Biochemistry:Troponin T > 0.1 μg/lTroponin T > 0.1 μg/l

Low risk: Low risk:

ClinicalClinical No history of MINo history of MI Rapid resolution of symptomsRapid resolution of symptoms

ECG:ECG:

Minor or no ECG changesMinor or no ECG changes

Biochemistry:Biochemistry: Troponin T < 0.1 microgm/ lTroponin T < 0.1 microgm/ l

The initial treatment should includeThe initial treatment should include bed rest, bed rest, antiplatelet therapy (aspirin 300 mg followed antiplatelet therapy (aspirin 300 mg followed

by 75-325 mg daily long-term and clopidogrel by 75-325 mg daily long-term and clopidogrel 300 mg followed by 75 mg daily for 12 300 mg followed by 75 mg daily for 12 months,months,

anticoagulant therapy (e.g. unfractionated anticoagulant therapy (e.g. unfractionated or fractionated heparin) or fractionated heparin)

β-blocker (e.g. atenolol 50-100 mg daily or β-blocker (e.g. atenolol 50-100 mg daily or metoprolol 50-100 mg 12-hourlymetoprolol 50-100 mg 12-hourly

A dihydropyridine calcium antagonist (e.g. A dihydropyridine calcium antagonist (e.g. nifedipine or amlodipine) can be added to the nifedipine or amlodipine) can be added to the β-blocker, but may cause an unwanted β-blocker, but may cause an unwanted tachycardia if used alone; verapamil or tachycardia if used alone; verapamil or diltiazem is therefore the calcium antagonist diltiazem is therefore the calcium antagonist of choice if a β-blocker is contraindicated of choice if a β-blocker is contraindicated

An intravenous infusion of unfractionated An intravenous infusion of unfractionated heparin (with dose adjusted according to the heparin (with dose adjusted according to the activated partial thromboplastin time) or activated partial thromboplastin time) or weight-adjusted subcutaneous low molecular weight-adjusted subcutaneous low molecular weight heparin (e.g. enoxaparin 1 mg/kg 12-weight heparin (e.g. enoxaparin 1 mg/kg 12-hourly) should be givenhourly) should be given

If pain persists or recurs, infusions of If pain persists or recurs, infusions of intravenous nitrates (e.g. GTN 0.6-1.2 mg/hr intravenous nitrates (e.g. GTN 0.6-1.2 mg/hr or isosorbide dinitrate 1-2 mg/hr) or buccal or isosorbide dinitrate 1-2 mg/hr) or buccal nitrates may help, but such patients should nitrates may help, but such patients should also be considered for early also be considered for early revascularisation. revascularisation.

Refractory cases or those with Refractory cases or those with haemodynamic compromise should be haemodynamic compromise should be considered for a glycoprotein IIb/IIIa receptor considered for a glycoprotein IIb/IIIa receptor antagonist (e.g. abciximab, tirofiban or antagonist (e.g. abciximab, tirofiban or eptifibatide), intra-aortic balloon pump or eptifibatide), intra-aortic balloon pump or emergency coronary angiography .emergency coronary angiography .

Most low-risk patients stabilise with aspirin, Most low-risk patients stabilise with aspirin, clopidogrel, heparin and anti-anginal clopidogrel, heparin and anti-anginal therapy, and can be gradually mobilised. If therapy, and can be gradually mobilised. If there are no contraindications, there are no contraindications,

exercise testing may be performed prior to or exercise testing may be performed prior to or shortly following discharge. shortly following discharge.

Coronary angiography should be considered Coronary angiography should be considered with a view to revascularisation in all with a view to revascularisation in all patients at moderate or high risk, including patients at moderate or high risk, including those who fail to settle on medical therapy, those who fail to settle on medical therapy, those with extensive ECG changes, those with those with extensive ECG changes, those with an elevated plasma troponin and those with an elevated plasma troponin and those with severe pre-existing stable angina. severe pre-existing stable angina.

This often reveals disease that is amenable This often reveals disease that is amenable to PCI ; however, if the lesions are not to PCI ; however, if the lesions are not suitable for PCI the patient should be suitable for PCI the patient should be considered for urgent CABG. considered for urgent CABG.

MYOCARDIAL INFARCTIONMYOCARDIAL INFARCTION Myocardial infarction (MI) is almost always Myocardial infarction (MI) is almost always

due to the formation of occlusive thrombus at due to the formation of occlusive thrombus at the site of rupture or erosion of an the site of rupture or erosion of an atheromatous plaque in a coronary artery.atheromatous plaque in a coronary artery.

The thrombus often undergoes spontaneous The thrombus often undergoes spontaneous lysis over the course of the next few days, lysis over the course of the next few days, although by this time irreversible myocardial although by this time irreversible myocardial damage has occurred. damage has occurred.

Without treatment the infarct-related artery Without treatment the infarct-related artery remains permanently occluded in 30% of remains permanently occluded in 30% of patients. patients.

The process of infarction progresses over The process of infarction progresses over several hours and therefore most patients several hours and therefore most patients present when it is still possible to salvage present when it is still possible to salvage myocardium and improve outcome.myocardium and improve outcome.

CLINICAL FEATURES CLINICAL FEATURES Pain is the cardinal symptom of MI, but Pain is the cardinal symptom of MI, but

breathlessness, vomiting, and collapse or breathlessness, vomiting, and collapse or syncope are common features. syncope are common features.

The pain occurs in the same sites as angina The pain occurs in the same sites as angina but is usually more severe and lasts longer;but is usually more severe and lasts longer;

It is often described as a tightness, heaviness It is often described as a tightness, heaviness or constriction in the chest. At its worst, the or constriction in the chest. At its worst, the pain is one of the most severe which can be pain is one of the most severe which can be experienced and the patient's expression and experienced and the patient's expression and pallor may vividly convey the seriousness of pallor may vividly convey the seriousness of the situationthe situation

Most patients are breathless and in some this Most patients are breathless and in some this is the only symptom. Indeed, some is the only symptom. Indeed, some myocardial infarcts pass unrecognised.myocardial infarcts pass unrecognised.

Painless or 'silent' myocardial infarction is Painless or 'silent' myocardial infarction is particularly common in older or diabetic particularly common in older or diabetic patients.patients.

If syncope occurs, it is usually due to an If syncope occurs, it is usually due to an arrhythmia or profound hypotension. arrhythmia or profound hypotension. Vomiting andVomiting and sinus bradycardia are often due sinus bradycardia are often due to vagal stimulation and are particularly to vagal stimulation and are particularly common in patients with inferior MI.common in patients with inferior MI.

Nausea and vomiting may also be caused or Nausea and vomiting may also be caused or aggravated by opiates given for pain relief.aggravated by opiates given for pain relief.

Sometimes infarction occurs in the absence Sometimes infarction occurs in the absence of physical signs. of physical signs.

Sudden death, from ventricular fibrillation or Sudden death, from ventricular fibrillation or asystole, may occur immediately, and many asystole, may occur immediately, and many deaths occur within the first hour. deaths occur within the first hour.

If the patient survives this most critical If the patient survives this most critical stage, the liability to dangerous arrhythmias stage, the liability to dangerous arrhythmias remains, but diminishes as each hour goes remains, but diminishes as each hour goes byby..

The development of cardiac failure reflects The development of cardiac failure reflects the extent of myocardial damage and is the the extent of myocardial damage and is the major cause of death in those who survive major cause of death in those who survive the first few hours of infarction.the first few hours of infarction.

Physical signsPhysical signs Signs of sympathetic activation Signs of sympathetic activation

Pallor, sweating, tachycardia Pallor, sweating, tachycardia Signs of vagal activation Signs of vagal activation

Vomiting, bradycardia Vomiting, bradycardia Signs of impaired myocardial function Signs of impaired myocardial function

Hypotension, oliguria, cold peripheries Hypotension, oliguria, cold peripheries Narrow pulse pressure Narrow pulse pressure Raised jugular venous pressure Raised jugular venous pressure Third heart sound Third heart sound Quiet first heart sound Quiet first heart sound Diffuse apical impulse Diffuse apical impulse Lung crepitations Lung crepitations

Signs of tissue damage Signs of tissue damage Fever Fever

Signs of complications, e.g. mitral Signs of complications, e.g. mitral regurgitation, pericarditis regurgitation, pericarditis

INVESTIGATIONS :INVESTIGATIONS : Electrocardiography The ECG is usually helpful Electrocardiography The ECG is usually helpful

in confirming the diagnosis; however, it may in confirming the diagnosis; however, it may be difficult to interpret if there is bundle be difficult to interpret if there is bundle branch block or evidence of previous MI.branch block or evidence of previous MI.

Only rarely is the initial ECG entirely normal, Only rarely is the initial ECG entirely normal, but in up to one-third of cases the initial ECG but in up to one-third of cases the initial ECG changes may not be diagnostic. changes may not be diagnostic.

The earliest ECG change is usually ST The earliest ECG change is usually ST elevation; later on there is diminution in the elevation; later on there is diminution in the size of the R wave, and in transmural (full size of the R wave, and in transmural (full thickness) infarction a Q wave begins to thickness) infarction a Q wave begins to develop.develop.

Subsequently, the T wave becomes inverted, Subsequently, the T wave becomes inverted, this change persists after the ST segment has this change persists after the ST segment has returned to normal. returned to normal.

In contrast to transmural lesions, partial In contrast to transmural lesions, partial thickness or subendocardial infarction causes thickness or subendocardial infarction causes ST/T wave changes, without Q waves or ST/T wave changes, without Q waves or prominent ST elevation; this is often prominent ST elevation; this is often accompanied by some loss of the R waves in accompanied by some loss of the R waves in the leads facing the infarct and is also known the leads facing the infarct and is also known as non-Q wave or non-ST elevation as non-Q wave or non-ST elevation myocardial infarction.myocardial infarction.

The ECG changes are best seen in the leads The ECG changes are best seen in the leads that 'face' the infarcted area. that 'face' the infarcted area.

When there has been anteroseptal infarction, When there has been anteroseptal infarction, abnormalities are found in one or more leads abnormalities are found in one or more leads from V1 to V4from V1 to V4

while anterolateral infarction produces while anterolateral infarction produces changes from V4 to V6, in aVL and in lead I. changes from V4 to V6, in aVL and in lead I.

Inferior infarction is best shown in leads II, III Inferior infarction is best shown in leads II, III and aVF, while at the same time leads I, aVL and aVF, while at the same time leads I, aVL and the anterior chest leads may show and the anterior chest leads may show 'reciprocal' changes of ST depression 'reciprocal' changes of ST depression

Infarction of the posterior wall of the left Infarction of the posterior wall of the left ventricle does not cause ST elevation or Q ventricle does not cause ST elevation or Q waves in the standard leads, but can be waves in the standard leads, but can be diagnosed by the presence of reciprocal diagnosed by the presence of reciprocal changes (ST depression and a tall R wave in changes (ST depression and a tall R wave in leads V1-V4).leads V1-V4).

Some infarctions (especially inferior) also Some infarctions (especially inferior) also involve the right ventricle; this may be involve the right ventricle; this may be identified by recording from additional leads identified by recording from additional leads placed over the right precordium.placed over the right precordium.

The serial evolution of ECG changes in full The serial evolution of ECG changes in full thickness myocardial infarction.thickness myocardial infarction. A. Normal ECG complex. A. Normal ECG complex. B. Acute ST elevation ('the current of injury'). B. Acute ST elevation ('the current of injury'). C. Progressive loss of the R wave, developing Q C. Progressive loss of the R wave, developing Q wave, resolution of the ST elevation and wave, resolution of the ST elevation and terminal T wave inversion. terminal T wave inversion. D. Deep Q wave and T wave inversion. D. Deep Q wave and T wave inversion. E. Old infarction E. Old infarction

Plasma biochemical markers Plasma biochemical markers The biochemical markers that are most The biochemical markers that are most

widely used in the detection of MI are widely used in the detection of MI are creatine kinase (CK), a more sensitive and creatine kinase (CK), a more sensitive and cardiospecific isoform of this enzyme (CK-cardiospecific isoform of this enzyme (CK-MB), and the cardiospecific proteins, MB), and the cardiospecific proteins, troponins T and Itroponins T and I

The troponins are also released, to a minor The troponins are also released, to a minor degree, in unstable angina with minimal degree, in unstable angina with minimal myocardial damage Serial (usually daily) myocardial damage Serial (usually daily) estimations are particularly helpful because estimations are particularly helpful because it is the change in plasma concentrations of it is the change in plasma concentrations of these markers that is of diagnostic value.these markers that is of diagnostic value.

CK starts to rise at 4-6 hours, peaks at about 12 CK starts to rise at 4-6 hours, peaks at about 12 hours and falls to normal within 48-72 hours.hours and falls to normal within 48-72 hours.

CK is also present in skeletal muscle, and a CK is also present in skeletal muscle, and a modest rise in CK (but not CK-MB) may modest rise in CK (but not CK-MB) may sometimes be due to an intramuscular injection, sometimes be due to an intramuscular injection, vigorous physical exercise or, in old people vigorous physical exercise or, in old people particularly, a fall.particularly, a fall.

Defibrillation causes significant release of CK but Defibrillation causes significant release of CK but not CK-MB or troponins. The most sensitive not CK-MB or troponins. The most sensitive markers of myocardial cell damage are the markers of myocardial cell damage are the cardiac troponins T and I, which are released cardiac troponins T and I, which are released within 4-6 hours and remain elevated for up to 2 within 4-6 hours and remain elevated for up to 2 weeks.weeks.

Other blood tests A leucocytosis is usual, Other blood tests A leucocytosis is usual, reaching a peak on the first day. The erythrocyte reaching a peak on the first day. The erythrocyte sedimentation rate (ESR) becomes raised and sedimentation rate (ESR) becomes raised and may remain so for several days. C-reactive may remain so for several days. C-reactive protein (CRP) is also elevated in acute MI. protein (CRP) is also elevated in acute MI.

Chest X-ray Chest X-ray This may demonstrate pulmonary oedema This may demonstrate pulmonary oedema

that is not evident on clinical examination that is not evident on clinical examination The heart size is often normal but there may The heart size is often normal but there may

bebe cardiomegaly due to pre-existing cardiomegaly due to pre-existing myocardial damage.myocardial damage.

EchocardiographyEchocardiography This can be performed at the bedside and is a This can be performed at the bedside and is a

very useful technique for assessing left and very useful technique for assessing left and right ventricular function and for detecting right ventricular function and for detecting important complications such as mural important complications such as mural thrombus, cardiac rupture, ventricular septal thrombus, cardiac rupture, ventricular septal defect, mitral regurgitation and pericardial defect, mitral regurgitation and pericardial effusion. effusion.

EARLY MANAGEMENT OF ACUTE MYOCARDIAL EARLY MANAGEMENT OF ACUTE MYOCARDIAL INFARCTIONINFARCTION

Provide facilities for defibrillationProvide facilities for defibrillation

Immediate measures:Immediate measures: High-flow oxygen High-flow oxygen I.v. access I.v. access ECG monitoring ECG monitoring 12-lead ECG 12-lead ECG I.v. analgesia (opiates) and antiemeticI.v. analgesia (opiates) and antiemetic Aspirin 300 mgAspirin 300 mg

Reperfusion Reperfusion Primary PCI or thrombolysis Primary PCI or thrombolysis

Detect and manage acute complications Detect and manage acute complications Arrhythmias Arrhythmias Ischaemia Ischaemia Heart failure Heart failure

Patients are usually managed in a dedicated Patients are usually managed in a dedicated cardiac unit because this offers a convenient cardiac unit because this offers a convenient way of concentrating the necessary way of concentrating the necessary expertise, monitoring and resuscitation expertise, monitoring and resuscitation facilities.facilities.

If there are no complications, the patient can If there are no complications, the patient can be mobilised from the second day and be mobilised from the second day and discharged from hospital on the fifth or sixth discharged from hospital on the fifth or sixth day. day.

AnalgesiaAnalgesia Adequate analgesia is essential not Adequate analgesia is essential not

only to relieve severe distress, but also only to relieve severe distress, but also to lower adrenergic drive and thereby to lower adrenergic drive and thereby reduce pulmonary and systemic reduce pulmonary and systemic vascular resistance and susceptibility vascular resistance and susceptibility to ventricular arrhythmias. to ventricular arrhythmias.

Intravenous opiates (initially morphine Intravenous opiates (initially morphine sulphate 5-10 mg or diamorphine 2.5-5 sulphate 5-10 mg or diamorphine 2.5-5 mg) and antiemetics (initially mg) and antiemetics (initially metoclopramide 10 mg) should be metoclopramide 10 mg) should be administered through an intravenous administered through an intravenous cannula.cannula.

Acute reperfusion therapy Acute reperfusion therapy

Thrombolysis:Thrombolysis: Coronary thrombolysis helps restore coronary Coronary thrombolysis helps restore coronary

patency, preserves left ventricular function patency, preserves left ventricular function and improves survival. and improves survival.

Successful thrombolysis leads to reperfusion Successful thrombolysis leads to reperfusion with relief of pain, resolution of acute ST with relief of pain, resolution of acute ST elevation and sometimes transient elevation and sometimes transient arrhythmias (e.g. idioventricular rhythm). arrhythmias (e.g. idioventricular rhythm).

The sooner the patient is treated, the better The sooner the patient is treated, the better the results will be; any delay will only the results will be; any delay will only increase the extent of myocardial increase the extent of myocardial damage-'minutes mean muscle'.damage-'minutes mean muscle'.

Clinical trials have shown that the Clinical trials have shown that the appropriate use of these drugs can appropriate use of these drugs can reduce the hospital mortality of reduce the hospital mortality of myocardial infarction by 25%-50% and myocardial infarction by 25%-50% and follow-up studies have demonstrated that follow-up studies have demonstrated that this survival advantage is maintained for this survival advantage is maintained for at least 10 years. at least 10 years.

The benefit is greatest in those patients The benefit is greatest in those patients who receive treatment within the first who receive treatment within the first few hours, and choice of agent is less few hours, and choice of agent is less important than speed of treatment. important than speed of treatment.

Streptokinase, 1.5 million U in 100 ml of saline Streptokinase, 1.5 million U in 100 ml of saline given as an intravenous infusion over 1 hour, is given as an intravenous infusion over 1 hour, is a widely used regimen. Streptokinase is a widely used regimen. Streptokinase is antigenic and occasionally causes serious antigenic and occasionally causes serious allergic manifestations. It may also cause allergic manifestations. It may also cause hypotension, which can often be managed by hypotension, which can often be managed by stopping the infusion and restarting at stopping the infusion and restarting at

slower rate. slower rate. Circulating neutralising antibodies are formed Circulating neutralising antibodies are formed

following treatment with streptokinase and may following treatment with streptokinase and may persist for 5 years or more.persist for 5 years or more.

These antibodies can render subsequent These antibodies can render subsequent infusions of streptokinase ineffective so it is infusions of streptokinase ineffective so it is advisable to use another non-antigenic agent if advisable to use another non-antigenic agent if the patient requires further thrombolysis in the the patient requires further thrombolysis in the future.future.

Alteplase (human tissue plasminogen activator Alteplase (human tissue plasminogen activator or tPA) is a genetically engineered drug that is or tPA) is a genetically engineered drug that is not antigenic and seldom causes hypotension. not antigenic and seldom causes hypotension. The standard regimen is given over 90 minutes The standard regimen is given over 90 minutes (bolus dose of 15 mg, followed by 0.75 mg/kg (bolus dose of 15 mg, followed by 0.75 mg/kg body weight, but not exceeding 50 mg, over 30 body weight, but not exceeding 50 mg, over 30 minutes and then 0.5 mg/kgminutes and then 0.5 mg/kg

body weight, but not exceeding 35 mg, over body weight, but not exceeding 35 mg, over 60 minutes). 60 minutes).

There is evidence that tPA may produce There is evidence that tPA may produce better survival rates than streptokinase, better survival rates than streptokinase, particularly among high-risk patients (e.g. particularly among high-risk patients (e.g. large anterior infarct), but with a slightly large anterior infarct), but with a slightly higher risk of intracerebral bleeding (10 per higher risk of intracerebral bleeding (10 per 1000 increased survival, but 1 per 1000 more 1000 increased survival, but 1 per 1000 more non-fatal stroke). non-fatal stroke).

Newer-generation analogues of tPA have Newer-generation analogues of tPA have been generated that have a longer plasma been generated that have a longer plasma half-life and can be given as an intravenous half-life and can be given as an intravenous bolus. Large-scale trial data have bolus. Large-scale trial data have demonstrated that tenecteplase (TNK) is as demonstrated that tenecteplase (TNK) is as effective as alteplase at reducing death and effective as alteplase at reducing death and MI whilst conferring similar intracerebral MI whilst conferring similar intracerebral bleeding risks. bleeding risks.

Reteplase (rPA) is administered as a double Reteplase (rPA) is administered as a double bolus and trial data indicate a similar bolus and trial data indicate a similar outcome to that achieved with alteplase, outcome to that achieved with alteplase, although some of the bleeding risks appear although some of the bleeding risks appear slightly higher. The double bolus slightly higher. The double bolus administration may provide practical administration may provide practical advantages over the infusion of alteplase.advantages over the infusion of alteplase.

An overview of all the large randomised trials An overview of all the large randomised trials confirms that thrombolytic therapy confirms that thrombolytic therapy significantly reduces short-term mortality in significantly reduces short-term mortality in patients with suspected MI if it is given patients with suspected MI if it is given within 12 hours of the onset of symptoms and within 12 hours of the onset of symptoms and the ECG shows bundle branch block or the ECG shows bundle branch block or characteristic ST segment elevation of characteristic ST segment elevation of greater than 1 mm in thegreater than 1 mm in the limb leads or 2 mm limb leads or 2 mm in the chest leads. in the chest leads.

Thrombolysis appears to be of little net Thrombolysis appears to be of little net benefit, and may be harmful in other patient benefit, and may be harmful in other patient groups, specifically those who present more groups, specifically those who present more than 12 hours after the onset of symptoms than 12 hours after the onset of symptoms and those with a normal ECG or ST and those with a normal ECG or ST depression. depression.

The major hazard of thrombolytic therapy is The major hazard of thrombolytic therapy is bleeding.bleeding.

RELATIVE CONTRAINDICATIONS TO RELATIVE CONTRAINDICATIONS TO THROMBOLYTIC THERAPY (POTENTIAL THROMBOLYTIC THERAPY (POTENTIAL CANDIDATES FOR PRIMARY ANGIOPLASTY)CANDIDATES FOR PRIMARY ANGIOPLASTY)

Active internal bleeding Active internal bleeding Previous subarachnoid or intracerebral Previous subarachnoid or intracerebral

haemorrhage haemorrhage Uncontrolled hypertension Uncontrolled hypertension Recent surgery (within 1 month) Recent surgery (within 1 month) Recent trauma (including traumatic Recent trauma (including traumatic

resuscitation) resuscitation) High probability of active peptic ulcer High probability of active peptic ulcer Pregnancy Pregnancy

Primary percutaneous coronary intervention Primary percutaneous coronary intervention (PCI)(PCI)

In institutions that are able to offer rapid In institutions that are able to offer rapid

access (within 3 hours) to a 24-hour catheter access (within 3 hours) to a 24-hour catheter laboratory service, percutaneous coronary laboratory service, percutaneous coronary intervention is the treatment of choice. intervention is the treatment of choice.

In comparison to thrombolytic therapy, it is In comparison to thrombolytic therapy, it is associated with a 50% greater reduction in associated with a 50% greater reduction in the risk of death, recurrent myocardial the risk of death, recurrent myocardial infarction or stroke. infarction or stroke.

The widespread use of PCI has been limited The widespread use of PCI has been limited by the availability of the resources necessary by the availability of the resources necessary to achieve this highly specialized emergency to achieve this highly specialized emergency service.service.

As a consequence, intravenous thrombolytic As a consequence, intravenous thrombolytic therapy remains the first-line reperfusion therapy remains the first-line reperfusion treatment in many hospitals. treatment in many hospitals.

For some patients, thrombolytic therapy is For some patients, thrombolytic therapy is contraindicated or fails to achieve coronary contraindicated or fails to achieve coronary arterial reperfusion. Early emergency PCI arterial reperfusion. Early emergency PCI (within 6 hours of symptom onset) may be (within 6 hours of symptom onset) may be considered under such circumstances, considered under such circumstances, particularly where there is evidence of particularly where there is evidence of cardiogenic shock. cardiogenic shock.

Acute rightAcute right

Coronary art.Coronary art.

Occlusion.Occlusion.

Initial angio: Filling defect Initial angio: Filling defect

Complete resolution of flow following insertion of Complete resolution of flow following insertion of stentstent