MYOCARDIAL INFARCTION

Myocardial infarction (MI) is almost always due to the formation of occlusive thrombus at the site of rupture or erosion of an atheromatous plaque in a coronary artery (Fig. 18.59, p. 579). The thrombus often undergoes spontaneous lysis over the course of the next few days, although by this time irreversible myocardial damage has occurred. Without treatment the infarct-related artery remains permanently occluded in 30% of patients. The process of infarction progresses over several hours and therefore most patients present when it is still possible to salvage myocardium and improve outcome (Fig. 18.71). CLINICAL FEATURES Pain is the cardinal symptom of MI, but breathlessness, vomiting, and collapse or syncope are common features (Box 18.70). The pain occurs in the same sites as angina but is usually more severe and lasts longer; it is often described as a tightness, heaviness or constriction in the chest. At its worst, the pain is one of the most severe which can be experienced and the patient's expression and pallor may vividly convey the seriousness of the situation. Most patients are breathless and in some this is the only symptom. Indeed, some myocardial infarcts pass unrecognised. Painless or 'silent' myocardial infarction is particularly common in older or diabetic patients. If syncope occurs, it is usually due to an arrhythmia or profound hypotension. Vomiting and sinus bradycardia are often due to vagal stimulation and are particularly common in patients with inferior MI. Nausea and vomiting may also be caused or aggravated by opiates given for pain relief. Sometimes infarction occurs in the absence of physical signs. Sudden death, from ventricular fibrillation or asystole, may occur immediately, and many deaths occur within the first hour. If the patient survives this most critical stage, the liability to dangerous arrhythmias remains, but diminishes as each hour goes by. Thus, it is vital that patients know not to delay calling for help if symptoms occur. The development of cardiac failure reflects the extent of myocardial damage and is the major cause of death in those who survive the first few hours of infarction. page 591 page 592 Figure 18.71 The time course of myocardial infarction. The relative proportion of ischaemic, infarcting and infarcted tissue slowly changes over a period of 12 hours. In the early stages of myocardial infarction a significant proportion of the myocardium in jeopardy is potentially salvageable. 18.70 CLINICAL FEATURES OF MYOCARDIAL INFARCTION Symptoms Prolonged cardiac pain Chest, throat, arms, epigastrium or back Anxiety and fear of impending death Nausea and vomiting Breathlessness Collapse/syncope

Physical signs

Signs of sympathetic activation Pallor, sweating, tachycardia Signs of vagal activation Vomiting, bradycardia Signs of impaired myocardial function Hypotension, oliguria, cold peripheries Narrow pulse pressure Raised jugular venous pressure Third heart sound Quiet first heart sound Diffuse apical impulse Lung crepitations Signs of tissue damage Fever Signs of complications, e.g. mitral regurgitation, pericarditis (see text)

The differential diagnosis is wide and includes most causes of central chest pain or collapse (p. 536).

INVESTIGATIONS

Electrocardiography

The ECG is usually helpful in confirming the diagnosis; however, it may be difficult to interpret if there is bundle branch block or evidence of previous MI. Only rarely is the initial ECG entirely normal, but in up to one-third of cases the initial ECG changes may not be diagnostic.

Figure 18.72 The serial evolution of ECG changes in full thickness myocardial infarction. Normal ECG complex. Acute ST elevation ('the current of injury'). Progressive loss of the R wave, developing Q wave, resolution of the ST elevation and terminal T wave inversion. Deep Q wave and T wave inversion. Old or established infarct pattern; the Q wave tends to persist but the T wave changes become less marked. The rate of evolution is very variable but, in general, stage B appears within minutes, stage C within hours, stage D within days and stage E after several weeks or months. This diagrammatic representation should be compared with the actual ECGs in Figures 18.74, 18.75 and 18.76.

The earliest ECG change is usually ST elevation; later on there is diminution in the size of the R wave, and in transmural (full thickness) infarction a Q wave begins to develop. One explanation for the Q wave is that the myocardial infarct acts as an 'electrical window', transmitting the changes of potential from within the ventricular cavity and allowing the ECG to 'see' the reciprocal R wave from the other walls of the ventricle. Subsequently, the T wave becomes inverted because of a change in ventricular repolarisation; this change persists after the ST segment has returned to normal. These features are shown in Figure 18.72 and their sequence is sufficiently reliable for the approximate age of the infarct to be deduced.

In contrast to transmural lesions, partial thickness or subendocardial infarction causes ST/T wave changes (Fig. 18.73) without Q waves or prominent ST elevation; this is often accompanied by some loss of the R waves in the leads facing the infarct and is also known as non-Q wave or non-ST elevation myocardial infarction (see above).

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Figure 18.73 Recent anterior non-ST elevation (partial thickness) infarction. There is deep symmetrical T-wave inversion together with a reduction in the height of the R wave in leads V1, V2, V3 and V4.

The ECG changes are best seen in the leads that 'face' the infarcted area. When there has been anteroseptal infarction, abnormalities are found in one or more leads from V1 to V4, while anterolateral infarction produces changes from V4 to V6, in aVL and in lead I. Inferior infarction is best shown in leads II, III and aVF, while at the same time leads I, aVL and the anterior chest leads may show 'reciprocal' changes of ST depression (Figs 18.74, 18.75 and 18.76). Infarction of the posterior wall of the left ventricle does not cause ST elevation or Q waves in the standard leads, but can be diagnosed by the presence of reciprocal changes (ST depression and a tall R wave in leads V1-V4). Some infarctions (especially inferior) also involve the right ventricle; this may be identified by recording from additional leads placed over the right precordium.

Plasma biochemical markers

MI causes a detectable rise in the plasma concentration of enzymes and proteins that are normally concentrated within cardiac cells. The biochemical markers that are most widely used in the detection of MI are creatine kinase (CK), a more sensitive and cardiospecific isoform of this enzyme (CK-MB), and the cardiospecific proteins, troponins T and I. The troponins are also released, to a minor degree, in unstable angina with minimal myocardial damage (Fig. 18.68, p. 589). Serial (usually daily) estimations are particularly helpful because it is the change in plasma concentrations of these markers that is of diagnostic value (Fig. 18.77).

Figure 18.74 Acute full thickness anterior myocardial infarction. This ECG was recorded from a 48-year-old man who had developed severe chest pain 6 hours earlier. There is ST elevation in leads I, aVL, V2, V3, V4, V5 and V6, and there are Q waves in leads V3, V4 and V5. Anterior infarcts with prominent changes in leads V2, V3 and V4 are sometimes called 'anteroseptal' infarcts, as opposed to 'anterolateral' infarcts in which the ECG changes are predominantly found in V4, V5 and V6.

Figure 18.75 Acute full-thickness inferolateral myocardial infarction. This ECG was recorded from a 55-year-old woman who had developed severe chest pain 4 hours earlier. There is ST elevation in the inferior leads II, III and aVF and the lateral leads V4, V5 and V6. There is also 'reciprocal' ST depression in leads aVL and V2.

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Figure 18.76 Established anterior and inferior full-thickness infarction. This ECG was recorded from a 70-year-old man who had presented with an acute anterior infarct 2 days earlier and had been treated for an inferior myocardial infarct 11 months before then. There are Q waves in the inferior leads (II, III and aVF) and Q waves with some residual ST elevation in the anterior leads (I and V2-V6).

CK starts to rise at 4-6 hours, peaks at about 12 hours and falls to normal within 48-72 hours. CK is also present in skeletal muscle, and a modest rise in CK (but not CK-MB) may sometimes be due to an intramuscular injection, vigorous physical exercise or, in old people particularly, a fall. Defibrillation causes significant release of CK but not CK-MB or troponins. The most sensitive markers of myocardial cell damage are the cardiac troponins T and I, which are released within 4-6 hours and remain elevated for up to 2 weeks.

The American College of Cardiology and the European Society of Cardiology have redefined MI as 'a typical rise in cardiac troponin T or I, or CK-MB, above the 99th centile for normal, with at least one of the following: ischaemic symptoms, development of pathological Q waves on the ECG, ischaemic ECG changes (ST depression or elevation) or coronary artery intervention (e.g. PCI)'. This definition therefore includes non-ST segment elevation MIs as well as those that evolve through ST segment elevation and Q wave development.

Other blood tests

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

Chest X-ray

This may demonstrate pulmonary oedema that is not evident on clinical examination (Fig. 18.24, p. 547). The heart size is often normal but there may be cardiomegaly due to pre-existing myocardial damage.

Echocardiography

Figure 18.77 Changes in plasma enzyme concentrations after myocardial infarction. Creatine kinase (CK) and troponin T (TnT) are the first to rise, followed by aspartate aminotransferase (AST) and then lactate (hydroxybutyrate) dehydrogenase (LDH). In patients treated with a thrombolytic agent, reperfusion is usually accompanied by a rapid rise in plasma creatine kinase (curve CK (R)) due to a washout effect; if there is no reperfusion, the rise is less rapid but the area under the curve is often greater (curve CK (N)).

18.71 EARLY MANAGEMENT OF ACUTE MYOCARDIAL INFARCTION

Provide facilities for defibrillation

Immediate measures High-flow oxygen I.v. access ECG monitoring 12-lead ECG I.v. analgesia (opiates) and antiemetic Aspirin 300 mg Reperfusion Primary PCI or thrombolysis Detect and manage acute complications Arrhythmias Ischaemia Heart failure

This can be performed at the bedside and is a very useful technique for assessing left and right ventricular function and for detecting important complications such as mural thrombus, cardiac rupture, ventricular septal defect, mitral regurgitation and pericardial effusion.

EARLY MANAGEMENT

Patients with suspected acute MI require immediate access to medical/paramedical care and defibrillation facilities. In the UK, ambulances are equipped with semi-automatic advisory defibrillators. A patient with severe chest pain also requires urgent medical assessment and analgesia, so it is often appropriate to summon an ambulance and a general practitioner at the same time.

The essentials of the immediate management of acute MI are listed in Box 18.71.

Patients are usually managed in a dedicated cardiac unit because this offers a convenient way of concentrating the necessary expertise, monitoring and resuscitation facilities. If there are no complications, the patient can be mobilised from the second day and discharged from hospital on the fifth or sixth day.

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Analgesia

Adequate analgesia is essential not only to relieve severe distress, but also to lower adrenergic drive and thereby reduce pulmonary and systemic vascular resistance and susceptibility to ventricular arrhythmias. Intravenous opiates (initially morphine sulphate 5-10 mg or diamorphine 2.5-5 mg) and antiemetics (initially metoclopramide 10 mg) should be administered through an intravenous cannula and titrated by giving repeated small aliquots until the patient is comfortable. Intramuscular injections should be avoided because the clinical effect may be delayed by poor skeletal muscle perfusion and a painful haematoma may form following thrombolytic therapy.

Acute reperfusion therapy

Thrombolysis

Coronary thrombolysis helps restore coronary patency, preserves left ventricular function and improves survival. Successful thrombolysis leads to reperfusion with relief of pain, resolution of acute ST elevation and sometimes transient arrhythmias (e.g. idioventricular rhythm). The sooner the patient is treated, the better the results will be; any delay will only increase the extent of myocardial damage-'minutes mean muscle'.

Clinical trials have shown that the appropriate use of these drugs can reduce the hospital mortality of myocardial infarction by 25%-50% and follow-up studies have demonstrated that this survival advantage is maintained for at least 10 years. The benefit is greatest in those patients who receive treatment within the first few hours, and choice of agent is less important than speed of treatment. Pre-hospital thrombolysis may be appropriate if transfer times are prolonged (> 30 mins) and the necessary expertise and ECG facilities are available.

Streptokinase, 1.5 million U in 100 ml of saline given as an intravenous infusion over 1 hour, is a widely used regimen. Streptokinase is antigenic and occasionally causes serious allergic manifestations. It may also cause hypotension, which can often be managed by stopping the infusion and restarting at a slower rate. Circulating neutralising antibodies are formed following treatment with streptokinase and may persist for 5 years or more. These antibodies can render subsequent infusions of streptokinase ineffective so it is advisable to use another non-antigenic agent if the patient requires further thrombolysis in the future.

Alteplase (human tissue plasminogen activator or tPA) is a genetically engineered drug that is not antigenic and seldom causes hypotension. The standard regimen is given over 90 minutes (bolus dose of 15 mg, followed by 0.75 mg/kg body weight, but not exceeding 50 mg, over 30 minutes and then 0.5 mg/kg body weight, but not exceeding 35 mg, over 60 minutes). There is evidence that tPA may produce better survival rates than streptokinase, particularly among high-risk patients (e.g. large anterior infarct), but with a slightly higher risk of intracerebral bleeding (10 per 1000 increased survival, but 1 per 1000 more non-fatal stroke).

Newer-generation analogues of tPA have been generated that have a longer plasma half-life and can be given as an intravenous bolus. Large-scale trial data have demonstrated that tenecteplase (TNK) is as effective as alteplase at reducing death and MI whilst conferring similar intracerebral bleeding risks. However, other major bleeding and transfusion risks are lower and the practical advantages of bolus administration may provide opportunities for prompt treatment in the emergency department or in the pre-hospital setting.

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

An overview of all the large randomised trials confirms that thrombolytic therapy significantly reduces short-term mortality in patients with suspected MI if it is given within 12 hours of the onset of symptoms and the ECG shows bundle branch block or characteristic ST segment elevation of greater than 1 mm in the limb leads or 2 mm in the chest leads (Box 18.72). Thrombolysis appears to be of little net benefit, and may be harmful in other patient groups, specifically those who present more than 12 hours after the onset of symptoms and those with a normal ECG or ST depression. In patients with ST elevation or bundle branch block, the absolute benefit of thrombolysis plus aspirin is approximately 50 lives saved per 1000 patients treated within 6 hours and 40 lives saved per 1000 patients treated between 7 and 12 hours after the onset of symptoms. The benefit is greatest for patients treated within the first 2 hours. To achieve prompt therapy, patients with suspected myocardial infarction should be assessed as soon as possible. Thrombolytic therapy can be administered before arrival at hospital by paramedical ambulance crews, often supported by telemetry of the ECG to hospital staff.

The major hazard of thrombolytic therapy is bleeding. Cerebral haemorrhage causes 4 extra strokes per 1000 patients treated and the incidence of other major bleeds is between 0.5% and 1%. Accordingly, it may be wise to withhold the treatment if there is a significant risk of serious bleeding. Some potential contraindications to thrombolytic therapy are outlined in Box 18.73.

18.72 THROMBOLYTIC TREATMENT IN ACUTE MYOCARDIAL INFARCTION

'Prompt thrombolytic treatment (within 12 hours, and particularly within 6 hours, of the onset of symptoms) reduces mortality in patients with acute myocardial infarction and ECG changes of ST elevation or new bundle branch block (NNTB = 56). Intracranial haemorrhage is more common in people given thrombolysis with one additional stroke for every 250 people treated.'

Fibrinolytic Therapy Trialists' (FTT) Collaborative Group. Lancet 1994; 343:311-322. Collins R. N Engl J Med 1997; 336:847-860.

For further information: http://www.escardio.org" target="_blank">www.escardio.org

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

Active internal bleeding Previous subarachnoid or intracerebral haemorrhage Uncontrolled hypertension Recent surgery (within 1 month) Recent trauma (including traumatic resuscitation) High probability of active peptic ulcer Pregnancy

18.74 PRIMARY PERCUTANEOUS CORONARY INTERVENTION IN ACUTE MYOCARDIAL INFARCTION

'Primary PCI is more effective than thrombolysis for the treatment of acute myocardial infarction. Death, non-fatal reinfarction and stroke are reduced from 14% with thrombolytic therapy to 8% withprimary PCI.'

Keeley EC, et al. Lancet 2003; 361:13-20.

For further information: http://www.acc.org" target="_blank">www.acc.org

The potential benefits and risks of thrombolytic therapy must be assessed in every case. For example, it would be reasonable to give thrombolytic therapy to a patient who presents early with evidence of extensive anterior infarction despite a history of active peptic ulceration. On the other hand, the risks of thrombolysis would probably exceed the benefits in a patient with a similar history of peptic ulceration who presents late with evidence of limited inferior myocardial infarction.

Primary percutaneous coronary intervention (PCI)

In institutions that are able to offer rapid access (within 3 hours) to a 24-hour catheter laboratory service, percutaneous coronary intervention is the treatment of choice (Fig. 18.78 and Box 18.74). In comparison to thrombolytic therapy, it is associated with a 50% greater reduction in the risk of death, recurrent myocardial infarction or stroke. The widespread use of PCI has been limited by the availability of the resources necessary to achieve this highly specialised emergency service. As a consequence, intravenous thrombolytic therapy remains the first-line reperfusion treatment in many hospitals. For some patients, thrombolytic therapy is contraindicated or fails to achieve coronary arterial reperfusion. Early emergency PCI (within 6 hours of symptom onset) may be considered under such circumstances, particularly where there is evidence of cardiogenic shock.

Maintaining vessel patency

Antiplatelet therapy

Oral administration of 75-300 mg aspirin daily improves survival (30% reduction in mortality) on its own, and complements the effect of thrombolytic therapy (Box 18.75). The first tablet (300 mg) should be given orally within the first 12 hours and the therapy should be continued indefinitely if there are no unwanted effects. In combination with aspirin, the early (within 12 hours) use of clopidogrel 75 mg daily confers a further 10% reduction in mortality with no evidence of increased adverse bleeding events.

Anticoagulants

Figure 18.78 Primary angioplasty. Acute right coronary artery occlusion. Initial angioplasty demonstrates a large thrombus filling defect (arrows). Complete restoration of normal flow following intracoronary stent insertion.

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18.75 ASPIRIN IN ACUTE MYOCARDIAL INFARCTION

'In acute myocardial infarction, aspirin reduces mortality (NNTB = 40), reinfarction (NNTB = 100) and stroke (NNTB = 300). The optimal dose of aspirin is 160-325 mg acutely, followed by a maintenance dose of 75 mg daily.'

Second International Study of Infarct Survival (ISIS 2) Collaborative Group. Lancet 1988; ii:349-360. Antiplatelet Trialists' Collaboration. BMJ 1994; 308:81-106.

For further information: http://www.escardio.org" target="_blank">www.escardio.org

Subcutaneous heparin (12 500U twice daily), given in addition to oral aspirin, may prevent reinfarction after successful thrombolysis and reduce the risk of thromboembolic complications. Clinical trials have shown that this form of therapy, when given for 7 days or until discharge from hospital, produces a small reduction in short-term mortality (approximately 5 lives saved per 1000 patients treated) but also increases the risk of cerebral haemorrhage (0.56% versus 0.4%) and of other bleeding complications (1% versus 0.8%). Intravenous heparin should be given for 48-72 hours following thrombolysis with alteplase, TNK or reteplase. Recent trial data suggest that low molecular weight heparin can be used in place of unfractionated heparin and with similar safety.

A period of treatment with warfarin should be considered if there is persistent atrial fibrillation or evidence of extensive anterior infarction, or if echocardiography shows mobile mural thrombus, because these patients are at increased risk of systemic thromboembolism.

Adjunctive therapy

Beta-blockers

Intravenous β-blockers (e.g. atenolol 5-10 mg or metoprolol 5-15 mg given over 5 minutes) relieve pain, reduce arrhythmias and improve short-term mortality in patients who present within 12 hours of the onset of symptoms, but should be avoided if there is heart failure, atrioventricular block or severe bradycardia. Chronic oral β-blocker therapy improves long-term survival and should be given to all patients who can tolerate it.

Nitrates and other agents

Sublingual glyceryl trinitrate (300-500 μg) is a valuable first-aid measure in threatened infarction, and intravenous nitrates (nitroglycerin 0.6-1.2 mg/hour or isosorbide dinitrate 1-2 mg/hour) are useful for the treatment of left ventricular failure and the relief of recurrent or persistent ischaemic pain.

Large-scale trials have shown that there is no evidence of a survival advantage from the routine use of oral nitrate therapy, oral calcium antagonists or intravenous magnesium in patients with acute MI.

COMPLICATIONS OF INFARCTION

Arrhythmias

18.76 COMMON ARRHYTHMIAS IN ACUTE MYOCARDIAL INFARCTION

Ventricular fibrillation Ventricular tachycardia Accelerated idioventricular rhythm Ventricular ectopics Atrial fibrillation Atrial tachycardia Sinus bradycardia (particularly after inferior MI) Heart block

Nearly all patients with acute MI have some form of arrhythmia; in many cases this is transient and of no haemodynamic or prognostic significance. Various degrees of atrioventricular block (pp. 570-571) are also common. Some common arrhythmias are listed in Box 18.76; diagnosis and management are discussed in detail on pages 560-578.

Pain relief, rest and the correction of hypokalaemia can all play a major role in the prevention of arrhythmias.

Ventricular fibrillation

This occurs in about 5-10% of patients who reach hospital, and is thought to be the major cause of death in those who die before receiving medical attention. Prompt defibrillation will usually restore sinus rhythm. Moreover, the prognosis of patients with early ventricular fibrillation (within the first 48 hours) who are successfully and promptly resuscitated in this way is identical to the prognosis of patients with acute MI that is not complicated by ventricular fibrillation. Prompt pre-hospital resuscitation and defibrillation have the potential to save many more lives than thrombolysis.

Atrial fibrillation

This is common, frequently transient and may not require treatment. However, if the arrhythmia causes a rapid ventricular rate with severe hypotension or circulatory collapse, cardioversion by means of an immediate synchronised DC shock should be considered. In other situations, digoxin or β-blockers are usually the treatment of choice. Atrial fibrillation (due to acute atrial stretch) is often a feature of impending or overt left ventricular failure, and therapy may be ineffective if heart failure is not recognised and treated appropriately. Anticoagulation may be required if AF persists.

Sinus bradycardia

This does not usually require treatment, but if there is hypotension or haemodynamic deterioration, atropine (0.6 mg i.v.) may be given.

Atrioventricular block

Atrioventricular block complicating inferior infarction is usually temporary and often resolves following thrombolytic therapy; it may also respond to atropine (0.6 mg i.v. repeated as necessary). However, if there is clinical deterioration due to second-degree or complete atrioventricular block, a temporary pacemaker should be considered. Atrioventricular block complicating anterior infarction is more serious because asystole may suddenly supervene; a prophylactic temporary pacemaker should be inserted (p. 576).

Ischaemia

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Post-infarct angina occurs in up to 50% of patients. Most patients have a residual stenosis in the infarct-related vessel despite successful thrombolysis, and this may cause angina if there is still viable myocardium downstream; nevertheless, there is no evidence that routine angioplasty improves outcome after thrombolysis. In some patients, occlusion of a vessel may precipitate angina by disturbing a system of collateral flow that was compensating for disease in another vessel.

Patients who develop angina at rest or on minimal exertion following MI should be managed in the same way as patients with unstable angina who are thought to be at high risk (pp. 590-591). Intravenous nitrates (e.g. nitroglycerin 0.6-1.2 mg/hour or isosorbide dinitrate 1-2 mg/hour) and either intravenous heparin (1000 U/hour, adjusted according to the thrombin time) or low molecular weight heparin may be helpful, and early coronary angiography with a view to angioplasty of the 'culprit' lesion should be considered. Glycoprotein IIb/IIIa receptor antagonists are of benefit in selected patients, particularly those undergoing PCI.

Acute circulatory failure

Acute circulatory failure usually reflects extensive myocardial damage and indicates a bad prognosis. All the other complications of MI are more likely to occur when acute heart failure is present.

The assessment and management of heart failure complicating acute MI are discussed in detail on page 548.

Pericarditis

This may occur at any stage of the illness but is particularly common on the second and third days. The patient may recognise that a different pain has developed even though it is at the same site, and that this pain is positional and tends to be worse or is sometimes only present on inspiration. A pericardial rub may be audible. Non-steroidal and steroidal anti-inflammatory drugs should be avoided in the early recovery period as they may increase the risk of aneurysm formation and myocardial rupture. Opiate-based analgesia should be used.

The post-myocardial infarction syndrome (Dressler's syndrome) is characterised by persistent fever, pericarditis and pleurisy, and is probably due to autoimmunity. The symptoms tend to occur a few weeks or even months after the infarct and often subside after a few days; prolonged or severe symptoms may require treatment with high-dose aspirin, an NSAID or even corticosteroids.

Mechanical complications

Part of the necrotic muscle in a fresh infarct may tear or rupture, with devastating consequences: Papillary muscle damage may cause acute pulmonary oedema and shock due to the sudden onset of severe mitral regurgitation, which presents with a pansystolic murmur and third heart sound. In the presence of severe valvular regurgitation, the murmur may be quiet or absent. The diagnosis can be confirmed by Doppler echocardiography, and emergency mitral valve replacement may be necessary. Lesser degrees of mitral regurgitation are common and may be transient. Rupture of the interventricular septum may cause left-to-right shunting through a ventricular septal defect. This usually presents with sudden haemodynamic deterioration accompanied by a new loud pansystolic murmur radiating to the right sternal border, but may be difficult to distinguish from acute mitral regurgitation. However, patients with an acquired ventricular septal defect tend to develop right heart failure rather than pulmonary oedema. Doppler echocardiography and right heart catheterisation will confirm the diagnosis. Without prompt surgery, the condition is usually fatal. Rupture of the ventricle may lead to cardiac tamponade and is usually fatal (p. 645), although it may rarely be possible to support a patient with an incomplete rupture until emergency surgery is performed.

Embolism

Thrombus often forms on the endocardial surface of freshly infarcted myocardium; this may lead to systemic embolism and occasionally causes a stroke or ischaemic limb.

Venous thrombosis and pulmonary embolism may occur but have become less common with the use of prophylactic anticoagulants and early mobilisation.

Impaired ventricular function, remodelling and ventricular aneurysm

Acute transmural MI is often followed by thinning and stretching of the infarcted segment (infarct expansion); this leads to an increase in wall stress with progressive dilatation and hypertrophy of the remaining ventricle (ventricular remodelling-Fig. 18.79). As the ventricle dilates, it becomes less efficient and heart failure may supervene. Infarct expansion occurs over a few days and weeks but ventricular remodelling may take years; heart failure may therefore develop many years after acute MI. ACE inhibitor therapy reduces late ventricular remodelling and can prevent the onset of heart failure (p. 600 and Box 18.18, p. 549).

Figure 18.79 Infarct expansion and ventricular remodelling. Full-thickness myocardial infarction causes thinning and stretching of the infarcted segment (infarct expansion), which leads to increased wall stress with progressive dilatation and hypertrophy of the remaining ventricle (ventricular remodelling).

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A left ventricular aneurysm develops in approximately 10% of patients and is particularly common when there is persistent occlusion of the infarct-related vessel. Heart failure, ventricular arrhythmias, mural thrombus and systemic embolism are all recognised complications of aneurysm formation. Other clinical features include a paradoxical impulse on the chest wall, persistent ST elevation on the ECG, and sometimes an unusual bulge from the cardiac silhouette on the chest X-ray. Echocardiography is usually diagnostic. Surgical removal of a left ventricular aneurysm carries a high morbidity and mortality but is sometimes necessary.

LATE MANAGEMENT

Patients who have survived an MI are at risk of further ischaemic events; management should therefore aim to identify those at high risk and introduce effective secondary prevention (Box 18.77).

Risk stratification and further investigation

The prognosis of patients who have survived an acute MI is related to the degree of myocardial damage, the extent of any residual myocardial ischaemia and the presence of significant ventricular arrhythmias.

Left ventricular function

The degree of left ventricular dysfunction can be crudely assessed from the physical findings (tachycardia, third heart sound, crackles at the lung bases, elevated venous pressure etc.), the ECG changes and the size of the heart and presence of pulmonary oedema on chest X-ray. However, formal measurements using echocardiography or radionuclide imaging are often valuable.

Ischaemia

Patients with early post-MI ischaemia should be managed in the same way as patients with high-risk unstable angina (pp. 590-591). Patients without spontaneous ischaemia who are suitable candidates for revascularisation should undergo an exercise tolerance test approximately 4 weeks after the infarct; this will help to identify those individuals with significant residual myocardial ischaemia who require further investigation, and may help to boost the confidence of the remainder.

18.77 LATE MANAGEMENT OF MYOCARDIAL INFARCTION

Risk stratification and further investigation (see text) Lifestyle modification Stop smoking Regular exercise Diet (weight control, lipid-lowering) Secondary prevention drug therapy Antiplatelet therapy (aspirin and/or clopidogrel) β-blocker ACE inhibitor Statin Additional therapy for control of diabetes and hypertension Rehabilitation

If the exercise test is negative and the patient has a good effort tolerance, the outlook is good, with a 1-4% chance of an adverse event in the next 12 months. In contrast, patients with residual ischaemia in the form of chest pain or ECG changes at low exercise levels are at high risk, with a 15-25% chance of suffering a further ischaemic event in the next 12 months.

Coronary angiography, with a view to angioplasty or bypass grafting, should therefore be considered in any patient with spontaneous ischaemia, significant angina on effort, or a strongly positive exercise tolerance test.

Arrhythmias

The presence of ventricular arrhythmias during the convalescent phase of MI may be a marker of poor ventricular function and may herald sudden death. Although empirical anti-arrhythmic treatment appears to be of no value and even hazardous, selected patients may benefit from sophisticated electrophysiological testing and specific anti-arrhythmic therapy (including implantable cardiac defibrillators, p. 576).

Recurrent ventricular arrhythmias are sometimes manifestations of myocardial ischaemia or impaired LV function and may respond to appropriate treatment directed at the underlying problem.

Secondary prevention

Smoking

The 5-year mortality of patients who continue to smoke cigarettes is double that of those who quit smoking at the time of their infarct. Giving up smoking is the single most effective contribution a patient can make to his or her own future. The success of smoking cessation can be increased by supportive advice and nicotine replacement therapy.

Hyperlipidaemia

Convincing evidence from large-scale randomised clinical trials has demonstrated the importance of lowering serum cholesterol following MI. Lipids should be measured within 24 hours of presentation because there is often a transient fall in blood cholesterol in the 3 months following infarction. Dietary advice should be given but is often ineffective. HMG CoA reductase enzyme inhibitors ('statins') can produce marked reductions in total (and LDL) cholesterol and have been shown to reduce the subsequent risk of death, reinfarction, stroke and the need for revascularisation (Box 18.50, p. 581). Irrespective of serum cholesterol concentrations, all patients should receive statin therapy after MI. Recent evidence suggests that patients with serum LDL cholesterol concentrations greater than 3.2 mmol/l (∼120 mg/dl) benefit from more intensive lipid-lowering (e.g. atorvastatin 80 mg daily).

Other risk factors

Maintaining an ideal body weight, taking regular exercise, and achieving good control of hypertension and diabetes may all improve the long-term outlook.

Mobilisation and rehabilitation

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There is histological evidence that the necrotic muscle of an acute myocardial infarct takes 4-6 weeks to become replaced with fibrous tissue, and it is conventional to restrict physical activities during this period. When there are no complications, the patient can sit in a chair on the second day, walk to the toilet on the third day, return home in 5 days and gradually increase activity with the aim of returning to work in 4-6 weeks. The majority of patients may resume driving after 4-6 weeks; however, in most countries, vocational driving licence holders (e.g. heavy goods and public service vehicle) require special assessment.

Emotional problems, such as denial, anxiety and depression, are common, and must be recognised and dealt with accordingly. Many patients are severely and even permanently incapacitated as a result of the psychological rather than the physical effects of MI, and all benefit from thoughtful explanation, counselling and reassurance at every stage of the illness. Many patients mistakenly believe that 'stress' was the cause of their heart attack and may restrict their activity inappropriately. The patient's spouse or partner will also require emotional support, information and counselling.

Formal rehabilitation programmes based on graded exercise protocols with individual and group counselling are often very successful, and in some cases have been shown to improve the long-term outcome.

Drug therapy

Aspirin and clopidogrel

Low-dose aspirin therapy reduces the risk of further infarction and other vascular events by approximately 25% and should be continued indefinitely if there are no unwanted effects. Clopidogrel should be given in combination with aspirin for the first 4 weeks. If patients are intolerant of aspirin, clopidogrel is a suitable alternative.

Beta-blockers

Continuous treatment with an oral β-blocker has been shown to reduce long-term mortality by approximately 25% among the survivors of acute MI (Box 18.78). Unfortunately, a significant minority of patients do not tolerate β-blockers because of bradycardia, atrioventricular block, hypotension or asthma. Patients with heart failure, irreversible chronic obstructive pulmonary disease or peripheral vascular disease derive similar if not greater secondary preventative benefits from β-blocker therapy if they can tolerate it, and should not be denied this treatment.

ACE inhibitors

18.78 β-BLOCKERS IN SECONDARY PREVENTION AFTER MYOCARDIAL INFARCTION

'β-blockers reduce the risk of overall mortality (NNTB = 48), sudden death (NNTB = 63) and non-fatal reinfarction (NNTB = 56) in patients after myocardial infarction. The greatest benefit was seen in those at highest risk and about one-quarter of patients suffered adverse events.'

Yusuf S, et al. Prog Cardiovasc Dis 1985; 27:335-371. Beta-blocking Pooling Project research group. Eur Heart J 1988; 9:8-16.

For further information: http://www.sign.ac.uk" target="_blank">www.sign.ac.uk

Several clinical trials have shown that long-term treatment with an ACE inhibitor (e.g. enalapril 10 mg 12-hourly or ramipril 2.5-5 mg 12-hourly) can counteract ventricular remodelling, prevent the onset of heart failure, improve survival and reduce hospitalisation. The benefit of treatment is greatest in those with overt heart failure (clinical or radiological) but extends to patients with asymptomatic LV dysfunction and those with preserved LV function. This form of therapy should therefore be considered in all patients who have sustained a myocardial infarct. Caution must be exercised in hypovolaemic or hypotensive patients because the introduction of an ACE inhibitor may exacerbate hypotension and impair coronary perfusion. In patients intolerant of ACE inhibitor therapy, angiotensin receptor blockers (e.g. valsartan 40-160 mg daily or candesartan 4-16 mg daily) are suitable alternatives and are better tolerated.

Patients with acute MI complicated by heart failure and LV dysfunction appear to benefit from additional aldosterone receptor antagonism (e.g. eplerenone 25-50 mg daily).

Device therapy (p. 576)

Implantable cardiac defibrillators are of benefit in preventing sudden cardiac death in patients who have severe left ventricular impairment (ejection fraction ≤ 30%) after MI.

PROGNOSIS

In almost one-quarter of all cases of MI, death occurs within a few minutes without medical care. Half the deaths from MI occur within 24 hours of the onset of symptoms and about 40% of all affected patients die within the first month. The prognosis of those who survive to reach hospital is much better, with a 28-day survival of more than 80%.

Early death is usually due to an arrhythmia but later on the outcome is determined by the extent of myocardial damage. Unfavourable features include poor left ventricular function, atrioventricular block and persistent ventricular arrhythmias. The prognosis is worse for anterior than for inferior infarcts. Bundle branch block and high enzyme levels both indicate extensive myocardial damage. Old age, depression and social isolation are also associated with a higher mortality.

Of those who survive an acute attack, more than 80% live for a further year, about 75% for 5 years, 50% for 10 years and 25% for 20 years.

18.79 MYOCARDIAL INFARCTION IN OLD AGE

Atypical presentation: often with anorexia, fatigue or weakness rather than chest pain. Case fatality: rises steeply. Hospital mortality exceeds 25% in those over 75 years old, which is five times greater than that seen in those aged less than 55 years. Survival benefit of treatments: not influenced by age. The absolute benefit of evidence-based treatments may therefore be greatest in older people. Hazards of treatments: rise with age (e.g. increased risk of intracerebral bleeding after thrombolysis) and is due partly to increased comorbidity. Quality of evidence: older patients, particularly those with significant comorbidity, were under-represented in many of the RCTs that helped to establish the treatment of myocardial infarction. The balance of risk and benefit for many treatments (e.g. thrombolysis, primary PTCA) in frail older people is therefore uncertain.