This patient had a myocardial infarction 2 days ago; would you like to take a short history and examine




· Post-infarct angina.

· Shortness of breath.

· Palpitations.

· Dizziness or syncope.

· Family history of cardiovascular disease, hyperlipidaemia, gout.

· Smoking.

· Past history of diabetes mellitus, hypertension, stroke, myocardial infarction. intermittent claudication

and hyperlipidaemia.

· History of oral contraceptives in young women.


· Hands: nicotine staining of fingers.

· Pulse: check pulse rate (keeping in mind heart block and tachycardia), rhythm (keeping in mind atrial

fibrillation, ventricular arrhythmias).

· Check blood pressure.

· JVP may be raised in cardiac failure or right ventricular infarction.

· Eyes: look for arcus senilis, xanthelasma.

· Cardiac apex: look for double apical impulse (ventricular aneurysm).

· Auscultate for fourth heart sound, pericardial rub, pansystolic murmur of papillary muscle dysfunction

(or ventricular septal detect).


· The chest for crackles and pleural effusion

· The abdomen for tender liver of cardiac failure

· The legs for deep venous thrombosis and peripheral pulses.


This patient with myocardial infarction (aetiology) has papillary muscle dys-function (lesion) and is in

NYHA class Il cardiac failure (functional status).


What is Levine's sign?

In acute myocardial infarction the patient often describes the pain by illustrating a clenched fist.

What are the major risk factors for an acute MI?

· Smoking.

· Hypercholesterolaemia.

· Diabetes.

· Hypertension.

How would you manage a patient with acute MI?

Treatment of MI includes (BMJ 1998; 316: 280-4):

· In the A&E department, a patient with chest pain should have a quick clinical examination and an ECG

performed within l0 minutes of arrival in hospital.

· Aspirin: chewable non-coated 160-325 mg should be administered immediately and then 160-325

mg daily. In the ISIS-2 and ISlS-3 trials 160 mg dosage was effective whereas a 325 mg dose was

used successfully in G1SSI-2. An initial large dose of aspirin of 325 mg orally or 160 mg chewable

aspirin is preferred because lower doses may still allow significant thromboxane activity and may take

a few days to become effective.

· Pain relief: immediate relief of pain should be a top priority because severe pain can cause

autonomic disturbances that can result in sudden death.

· Reperfusion strategies: either thrombolysis or primary PTCA should be per-formed within 30 minutes

of the patient's arrival in hospital.

· Beta-blockers: the patient should receive beta-blockers when there are no contra-indications within

12 hours of onset of infarction, irrespective of administration of concomitant thrombolytic therapy or

performance of primary angioplasty.

· ACE inhibitors: should be administered within the first 24 hours of a suspected acute myocardial

infarction with ST segment elevation in > 2 anterior precordial leads or with clinical heart failure in the

absence of hypotension (systolic blood pressure <100 mmHg) or known contraindications to use of

ACE inhibitors.

What are the complications of myocardial infarction?

· Extension of infarct and post-infarct ischaemia.

· Rhythm disorders: tachycardia, bradycardia, ventricular ectopics, ventricular fibrillation, atrial

fibrillation and tachycardia.

· Heart failure: acute puhnonary oedema.

· Circulatory failure: cardiogenic shock.

· Infarction of papillary muscle: mitral regurgitation and acute puhmmary oedema.

· Rupture of interventricular septum.

· Left ventricular aneurysm.

· Mural thrombus.

· Thromboembolism: cerebral or peripheral.

· Venous thrombosis.

· Pericarditis.

· Dressler's syndrome, characterized by persistent pyrexia, pericarditis, pleurisy. It was first described

in 1956 when Dressier recognized that chest pain following myocardial infarction is not caused by

coronary artery insufficiency.

What is a silent myocardial infarct?

A painless infarct, common in diabetics and the elderly; it may present with complications of myocardial


What are TIMI grades?

Grades determined in the Thrombolysis in Myocardial Infarction trial (TIMI) that measure coronary blood

flow and luminal narrowing:

· Grade 0: no flow of contrast beyond the point of occlusion.

· Grade I: penetration with minimal perfusion (contrast fails to opacify the entire coronary bed distal to

the stenosis for the duration of investigation).

· Grade 2: partial perfusion (contrast opacities the entire distal coronary artery, but the rate of entry or

clearance or both is slower in the previously blocked artery than in nearby normally perfused


· Grade 3: Complete perfusion (contrast filling and clearance are as rapid in the previously blocked

vessel as in normally pert'used vessels).

Which thrombolytic agent is preferred?

Three thrombolytic agents (which reduce mortality) are commonly available in the UK: streptokinase,

anistreplase and tissue plasminogen activator (tPA), of which streptokinase is the cheapest and tPA the

most expensive. In ISIS-3 (Third Inter-national Study of Infarct Survival) all three agents were found to be

equally effective and in the GISSI-2 (Gruppo Italiano per lo Studio della Sopraviviena nell lnfarcto

Micocardioco) study both tPA and streptokinase were equally effective. However, in both these studies

there was increased risk of haemorrhage with tPA. In the GUSTO (Global Utilization of Streptokinase and

Tissue Plasminogen Activator) trial, tPA given in an accelerated manner was particularly useful in young

men with anterior wall myocardial infarction, tPA is now given to patients previously treated with

streptokinase because the development of anti-streptokinase antibodies puts them at risk of allergic

reactions and reduces the efi'ectiveness of thrombolysis.

The best thrombolytic treatment currently available accelerated tPA achieves grade 3 patency in only

54% of patients, which is better than streptokinase (30% of patients had TIMI grade 3). The difference in

vessel patehcy achieved by tissue plasminogen activator and streptokinase treatment has not resulted in

a significant difference in mortality in most trials. Although the GUSTO-1 trial showed reduced mortality

with tissue plasminogen activator treatment, this benefit was partly offset by an excess of strokes in this

treatment group. The current contender for the primary position held by accelerated tPA seems to be

reteplase. Reteplase differs from tissue plasminogen activator at two molecular points, and deletion of

these molecular domains contributes to its longer half-life. Reteplase is conveniently administered: two l0

unit boluses are given 30 minutes apart. It has been shown to be comparable with tPA. In the INJECT

(International Joint Efficacy Comparison of Thrombolytics) trial patients in the reteplase group had

significantly fewer side-effects such as atrial fibrillation and cardiogenic shock when compared to the

streptokinase group.

What is the relation between thrombolysis and onset of symptoms?

Thrombolytic therapy reduces mortality and limits infarct size. The shorter the interval between the onset

of symptoms and the initiation of thrombolysis, the greater is the survival. The greatest benefit occurs if

the treatment is initiated within the first three hours, when a 50% or greater reduction in mortality rate can

be achieved. The magnitude of benefit declines rapidly thereafter, but a 10% mortality reduction can be

achieved up to 12 hours after the onset of pain.

What is the benefit of late administration of thrombolytic therapy?

ISIS-2 (Lancet 1988; ii:349-60) showed benefit for up to 24 hours (after onset of symptoms) with

thrombolysis, but more recent studies - LATE (Late Assessment of Thrombolytic Therapy) and EMRAS

(Estudio Multicentrico Esteptoquinasa Republicas de America del Sur) - have shown no benefit for

treatment given beyond 12 hours.

What is the role of heparin with thrombolysis?

In the ISIS-3 (Lancet 1992; 339: 753-70) and G1SSI-2 (Lancet 1990; 336: 65-75) studies heparin therapy

with streptokinase or anistreplase was not beneficial, and it is believed that it may even be harmful. The

GUSTO trial showed that, with tPA, early intravenous heparin results in a further reduction in the mortality

rate compared with that found with a combination of heparin and streptokinase.

What is the role of pre-hospital thrombolysis?

Two studies - GREAT (Grampian Region Early Administration of Thrombolysis) and EMIP (European

Myocardial Infarction Project) - showed that a single bolus dose of anistreplase reduced the total mortality

rate. These results suggest that early thrombolysis has greater benefit, hence the importance in many

hospitals of 'door to needle time'.

What is the role of angiotensin converting enzyme inhibitors (ACE) inhibitors following

myocardial infarction ?

Several large trials (SAVE, AIRE, SMILE, TRACE, GISSi-lll and IS1S-IV) have shown both short- and

long-term improvement in survival with ACE inhibitor therapy. The benefits are greatest in patients with

low ejection fractions, large iufa, ction~ tn ulinical evidence of heart failure.

· The AIRE (Acute Infarction Ramipril Efficacy) and the AIREX (AIRE Extension) trials assessed the

long-term (mean follow-up 59 months) efficacy of ramipril compared with placebo in 603 patients with

heart failure after myo-cardial infarction. Treatment with ramipril resulted in a large and sustained

reduction in mortality (relative risk reduction 36%).

· The SAVE (Survival and Ventricular Enlargement) Trial compared the effect of captopril or placebo in

2231 patients up to 16 days post myocardial infarction with an asymptomatic ejection fraction ?<40%.

Captopril reduced overall and cardiovascular mortality, and also reduced the risk of requiring

hospitalization or treatment for heart failure (N Engl J Med 1992; 327: 685-91). At 5-year follow-up a

substantial reduction in the risk of stroke was observed. Decreased ejection fraction and older age were

independent risk factors (N Engl J Med 1997; 336: 251-7).

· In the recent HOPE trial, ramipril has been shown to reduce significantly the rates of death, myocardial

infarction and stroke in a broad range of high-risk patients who are not known to have a low ejection

fraction or heart failure (N Engl J Med 2000; 342: 145-53).

What is the role of primary angioplasty in acute infarction?

Angioplasty results in both lower mortality rates and a reduction in the incidence of recurrent ischaemic

events. Also, angioplasty is associated with lower enzyme rise, better left ventricular function, and less

reinfarction. Angioplasty led to shorter hospital stay, fewer re-admissions and lower follow-up costs.

However, the major limitation of this approach is the access to both facilities and personnel to carry out

the procedure.

Angioplasty should be considered in patients who have recognized contra-indications to thrombolysis

(even if this means transferring the patient) or who are considered high risk and present with their

infarction to a hospital where angio-plasty can be performed. Patients who have received thrombolysis

and who seem on clinical grounds (reduction in maximal ST segment elevation by 50% and resolution of

chest pain) not to have reperfused at 90-minute review should be seriously considered for rescue

angioplasty, again even if this means transferring the patient.

Is intravenous nitrate therapy routinely administered in acute

myocardial infarction?

Routine administration of nitrates is not recommended since the ISIS-4 and GISSI-3 trials (in which >70

000 patients were randomized to nitrates or placebo) showed no improvement in outcome. However,

nitroglycerine is the agent of choice for recurrent ischaemic pain and is useful in lowering blood pressure

or relieving pulmonary congestion.

Why is the Asian population in Britain susceptible to premature myocardial infarction ?

Premature ischaemic heart disease in migrants from the Indian subcontinent is associated with insulin

resistance. The site of this defective insulin action has been localized to the skeletal muscle by means of

positron emission tomography (Baliga RR et al. Positron emission tomography localizes insulin resistance

to skeletal muscle in premature coronary heart disease. Circulation1995; 92: 1-16).

What is the role of troponins in the diagnosis of myocardial infarction?

Raised concentrations of the myocardial regulatory protein troponin I are highly specific for myocardial

injury. Estimation of troponin I concentration may be par-ticularly useful in patients with acute or chronic

skeletal muscle disease or those with renal failure in whom the CK-MB (MB isoenzyme of creatine

kinase) level may be raised in the absence of myocardial infarction. The measurement of troponin 1 is a

sensitive and specific method (more specific than CK-MB) in the setting of perioperative myocardial

infarction. Troponin T is also useful because it has a large diagnostic window, as it is increased from 12

hours to 10 days after myocardial infarction.

What do you know about right ventricular infarction?

Right ventricular infarction presents with retrosternal chest discomfort, nausea, vomiting and diaphoresis,

unlike left ventricular infarction which presents with dyspnoea. On examination in right ventricular

infarction, there is a raised jugular venous pressure with no evidence of pulmonary congestion; the

patient often has a Iow cardiac output with hypotension. The patient typically presents with ST elevation

in the inferior leads (II, III and aVF) and in one or more right-sided leads, particularly V4R. The

cornerstones of therapy include restoration of infarct artery patency, intravascular volume expansion and

inotropic support.

What do you know about the open infarct-related coronary artery hypothesis?

This hypothesis holds that early reperfusion of the infarct-related coronary artery results in myocardial

salvage, which preserves left ventricular function and is responsible for improved survival. Patients with

complete occlusion of the coronary artery (TIMI grade 0) 90 minutes following thrombolysis had a 30-day

mortality of 8.4%, whereas mortality was 4% in patients with TIMI grade 3 flow (complete perfusion).

What is the role of glycoprotein lib/Ilia antagonists as adjuncts to thrombolytic therapy in acute


After thrombolytic therapy for acute MI, full anterograde perfusion (TIMI grade 3 flow) occurs in only

29-54% of patients at 90 minutes while reocclusion occurs in at least 12%, with increased morbidity and

mortality. Thrombolytic therapy may itself be prothrombotic by releasing clot-bound thrombin, which in

turn stimulates platelet activation. Preclinical and early clinical trials have suggested that glycoprotein

llb/llla receptor blockers (which prevent fibrinogen binding to platelets) used as adjuncts to thrombolytic

therapy may improve early patency and reduce the incidence of reocclusion. A large randomized trial has

recently confirmed the early findings on patency and suggests that adjunctive treatment with glycoprotein

Ilb/IIIa receptor blockers may hold promise for better management of acute MI. The results from the

GUSTO-AMI phase III trial using abciximab with reduced dose reteplase are awaited.

What do you know about post-MI risk stratification?

· Risk stratification before hospital discharge is an important aspect of manage-ment and determines

whether coronary angiography is indicated.

· The first step is to determine whether the clinical variables indicatine a relatively high risk for future

cardiac events are present:

1. Patients who have recurrent ischaemia at rest or with mild activity, who have had evidence of

congestive heart failure or who are known to have an ejection traction below 40% and in whom there

are no contraindications for revas-cularization should undergo cardiac catheterization and coronary

angiography. Revascularization should then be carried out if the coronary anatomy is suitable and

there are no contraindications.

2. Patients who have had an episode of ventricular fibrillation or sustained ven-tricular tachycardia

more than 48 hours after acute MI should be considered for electrophysiological study or amiodarone

therapy, or both.

3. In patients with non-ST segment elevation M1 or unstable angina who appear on clinical grounds to

be candidates for coronary revascularization, coronary vascularization should be performed.

Revascularization may then be carried out if the coronary anatomy is appropriate.

· Patients without these clinical indicators of high risk should undergo an assess-ment of left ventricular

function (echocardiogram or radionuclide angiogram and submaximal stress) before hospital discharge. If

the test is negative the patient may return for a symptom-limited exercise test at 3-6 weeks. If that too is

negative he or she can remain on medical therapy and risk factor reduction. If the resting ejection fraction

is <40% or if the stress is markedly abnormal (>2 nlm ST segment depression, hypotension at peak

exercise or low working capacity) then coronary angiography should be carried out if there are no

contraindications to revascularization.

· In patients in whom the ECG is not intepretable because of resting ST-T wave abnormalities,

digitalis therapy or left bundle branch block, rest and exercise radionuclide myocardial perfusion

scintigraphy (with thallium or sestamibi) or rest and exercise echocardiography should be performed.

Patients who cannot exercise should undergo a pharmacologic stress imaging study such as

adenosine or dipyridamole myocardial perfusion scintigraphy or echocardiography with dobutamine

or dipyridamole stress. A marked abnormality in any of these tests or a resting ejection fraction below

40%, measured by echocardiography or a radionuclide technique, should be followed by coronary


What advice would you give this patient on discharge?

Secondary prevention of myocardial infarction includes (BMJ 1998; 316: 838~.2):

· Smoking cessation. It should be emphasized to the patient that within 2 years of discontinuing

smoking the risk of a non-fatal recurrent MI falls to the level observed in a patient who has never


· Lipid profile. A lipid profile should be obtained in all patients with acute MI. Since cholesterol may fall

after 2448 hours, it is important that these measure-ments be obtained on admission, otherwise a

6-week wait is necessary for cholesterol to reach pre-MI levels. It is desirable to fractionate the

cholesterol, and patients with LDL cholesterol >3.37 mmol/l should be treated with lipid lowering

agents (see pp 440-1).

· Cardiac rehabilitation. All discharged patients should be referred for outpatient cardiac rehabilitation.

Patients should be encouraged to increase activity gradually over 1-2 months.

· Risk factors. Diabetes and hypertension should be aggressively controlled. Oestrogen replacement

should be considered in postmenopausal women after MI without greater than usual risks of breast

cancer (a family history of breast cancer).

· Aspirin. Aspirin led to a 12% reduction in death, a 31% reduction in reinfarction and a 42% reduction in

non-fatal stroke in a study of 19 791 patients who had myocardial infarctions reviewed by the Antiplatelet

Therapy Trialists. Low to medium doses (75-325 mg/day) seem to be as effective as high doses ( 1200


· Beta-blockers. Several controlled trials in more than 35 000 survivors of myo-cardial infarction have

shown the benefit of long-term treatment with beta-blockers in reducing the incidence of recurrent

myocardial infarction, sudden death and all-cause mortality. Beta-blockers reduce myocardial workload

and oxygen consumption by reducing the heart rate, blood pressure and contractility, and they increase

the threshold for ventricular fibrillation. The beneficial effect of beta-blockers seems to be a class effect,

but those with agonist activity do not show a beneficial effect on mortality, and their use cannot be

recommended at present.

· ACE inhibitors. Low-dose ramipril should be considered in all patients with uncomplicated myocardial

infarction (N Engl J Med 2000; 342: 145-53). Treat-ment with full-dose ACE inhibitors is recommended for

an indefinite period in all patients with congestive heart failure, an ejection fraction <40% or a large

regional wall motion abnormality.

· Avoid calcium channel blockers or prophylactic use of anti-arrhythmic drugs to suppress ventricular


· The patient should not drive for at least one month after the event.

Eugene Braunwald (b. 1929) was consecutively Chair and Professor of Medicine in San Diego and

Harvard Medical School, Boston. His research interests included heart failure, factors influencing cardiac

contraction and hypertrophic cardiomyopathy. He was responsible for the idea that late patency of an

occluded artery can lead to clinical benefit. His wife, Nina H. Starr Braunwald, was a cardiothoraoic

surgeon who made important contributions to heart valve replacement.