Contributors

David Crossman

Timothy Houghton

Professor of Clinical Cardiology, Cardiovascular Research

Registrar in Cardiology, Hull and East Yorkshire Trust, Castle

Group, Clinical Sciences Centre, Northern General Hospital,

Hill Hospital, Hull

Sheffield

Gerry C Kaye

David Cumberland

Consultant Cardiologist, Hull and East Yorkshire Trust, Castle

Consultant Cardiovascular Interventionist, Ampang Puteri

Hill Hospital, Hull

Specialist Hospital, Kuala Lumpur, Malaysia

Laurence O’Toole

John Ducas

Consultant Cardiologist and Physician, Royal Hallamshire

Consultant Cardiologist, Health Sciences Centre and

Hospital, Sheffield

St Boniface Hospital, Winnipeg, Manitoba and Associate

Professor, University of Manitoba, Winnipeg, Canada

Roger Philipp

Fellow in Interventional Cardiology, Health Sciences Centre

Ever D Grech

and St Boniface Hospital, Winnipeg, Manitoba, Canada

Consultant Cardiologist, South Yorkshire Cardiothoracic

Centre, Northern General Hospital, Sheffield, UK

David R Ramsdale

Consultant Cardiologist, Cardiothoracic Centre, Liverpool

Julian Gunn

Senior Lecturer and Honorary Consultant Cardiologist,

Kevin P Walsh

Cardiovascular Research Group, Clinical Sciences Centre,

Consultant Paediatric Cardiologist, Our Lady’s Hospital for

Northern General Hospital, Sheffield

Sick Children, Crumlin, Dublin, Republic of Ireland

Preface

It is only 26 years since the first percutaneous transluminal coronary angioplasty (PTCA) was carried out by the pioneering Swiss

radiologist, Andreas Greuntzig, heralding the dawn of interventional cardiology. In this short time, interventional cardiology has

overcome many limitations and undergone major evolutionary changes—most notably the development of the coronary stent.

Worldwide, many thousands of patients now safely undergo percutaneous coronary intervention every day, and the numbers

continue to grow. In many countries, the numbers are similar to, or exceed, bypass surgical procedures.

Although, at first, PTCA was indicated only as treatment for chronic stable angina caused by a discrete lesion in a single vessel,

this has now progressed to encompass multi-lesion and multi-vessel disease. Moreover, percutaneous intervention is now becoming

widely used in the management of unstable angina and acute myocardial infarction with definite benefits in terms of morbidity and

mortality. The effectiveness and safety of these procedures has undoubtedly been enhanced by the adjunctive use of new anti-platelet

and antithrombotic agents.

As the indications increase and more patients are treated, so inevitably do the demands on healthcare budgets. Undoubtedly,

percutaneous intervention is expensive. However, this burden must be weighed against bypass surgery, which is even more costly, and

multi-drug treatment—which would be required over many years.

Although percutaneous coronary intervention has held centre stage in cardiology, major in-roads have also been made in non-

coronary areas. Transcatheter valvuloplasty, ethanol septal ablation and closure devices have become effective and safe alternatives

to surgery, as have paediatric interventional procedures. A greater understanding of cardiac electrophysiology has led to important

advances in the treatment of arrhythmias, and implantable cardioverter defibrillators are benefiting ever larger numbers of patients.

Where are we heading? This is perhaps the biggest question in the minds of many interventional cardiologists. New technology

generated by industry and new techniques coupled with high levels of expertise are fuelling advances in almost all areas of

interventional cardiology. As drug-eluting stents address the Achilles’ heel of angioplasty and stenting—restenosis—the huge

increase in percutaneous coronary procedures seen over recent years is likely to increase even further, and will probably be double

the rate of bypass surgery within a decade.

In writing and editing this book, I have endeavoured to present broad (and sometimes complex) aspects of interventional

cardiology in a clear, concise and balanced manner. To this end, an easy-to-read style of text, avoiding jargon and exhaustive detail,

has been used supplemented with many images and graphics.

EVER D GRECH

Sheffield, July 2003

vii

Pathophysiology and investigation of coronary

artery disease

Ever D Grech

In affluent societies, coronary artery disease causes severe

Foam

Fatty

Intermediate Atheroma

Fibrous

Complicated

disability and more death than any other disease, including

cells

streak

lesion

plaque lesion or rupture

cancer. It manifests as angina, silent ischaemia, unstable angina,

myocardial infarction, arrhythmias, heart failure, and sudden

death.

Pathophysiology

Coronary artery disease is almost always due to atheromatous

narrowing and subsequent occlusion of the vessel. Early

From first decade

From third decade

From fourth decade

atheroma (from the Greek athera (porridge) and oma (lump)) is

Smooth

present from young adulthood onwards. A mature plaque is

Growth mainly by lipid accumulation

muscle

Thrombosis,

haematoma

and collagen

composed of two constituents, each associated with a particular

cell population. The lipid core is mainly released from necrotic

“foam cells”—monocyte derived macrophages, which migrate

Progression of atheromatous plaque from initial lesion to complex and

into the intima and ingest lipids. The connective tissue matrix is

ruptured plaque

derived from smooth muscle cells, which migrate from the

media into the intima, where they proliferate and change their

phenotype to form a fibrous capsule around the lipid core.

When a plaque produces a > 50% diameter stenosis (or

> 75% reduction in cross sectional area), reduced blood flow

Normal coronary

Lumen

artery

through the coronary artery during exertion may lead to

Intima (endothelium and internal

elastic lamina)

angina. Acute coronary events usually arise when thrombus

formation follows disruption of a plaque. Intimal injury causes

Lumen

Media (smooth muscle cells

denudation of the thrombogenic matrix or lipid pool and

and elastic tissue)

triggers thrombus formation. In acute myocardial infarction,

occlusion is more complete than in unstable angina, where

Adventitia (fibroblasts and

arterial occlusion is usually subtotal. Downstream embolism of

connective tissue)

thrombus may also produce microinfarcts.

Monocyte

Lumen

Plasma low density lipoprotein

Investigations

Key

Development

Collagen

of atheroma

Patients presenting with chest pain may be identified as having

Intima

definite or possible angina from their history alone. In the

Dividing smooth

muscle cell

former group, risk factor assessment should be undertaken,

Oxidised low

Lumen

Media

density lipoprotein

both to guide diagnosis and because modification of some

Monocyte

associated risk factors can reduce cardiovascular events and

mortality. A blood count, biochemical screen, and thyroid

Monocyte-derived

Adventitia

macrophages

function tests may identify extra factors underlying the onset of

(foam cells)

angina. Initial drug treatment should include aspirin, a

blocker, and a nitrate. Antihypertensive and lipid lowering

Schematic representation of normal coronary artery wall (top) and

drugs may also be given, in conjunction with advice on lifestyle

development of atheroma (bottom)

and risk factor modification.

All patients should be referred to a cardiologist to clarify the

diagnosis, optimise drug treatment, and assess the need and

suitability for revascularisation (which can improve both

Cardiovascular risk factors

symptoms and prognosis). Patients should be advised to seek

urgent medical help if their symptoms occur at rest or on

Non-modifiable risk factors

x Positive family history

x Age

x Male sex

minimal exertion and if they persist for more than 10 minutes

after sublingual nitrate has been taken, as these may herald the

Modifiable risk factors

x Hypercholesterolaemia

x Hypertension

x Smoking

onset of an acute coronary syndrome.

x Left ventricular

x Sedentary lifestyle

x Diabetes

hypertrophy

x Excessive alcohol

Priorities for cardiology referral

x Overweight and obesity

intake

x Recent onset of symptoms

x Severe symptoms (minimal

Uncertain risk factors

x Rapidly progressive symptoms

exertion or nocturnal angina)

x Hypertriglyceridaemia

x Lp(a) lipoprotein

x Uric acid

x Possible aortic stenosis

x Angina refractory to medical

x Microalbuminuria

x Fibrinogen

x Renin

x Threatened employment

treatment

x Hyperhomocysteinaemia

x C reactive protein

ABC of Interventional Cardiology

Non-invasive investigations

Exercise stress testing

Electrocardiography

An abnormal electrocardiogram increases the suspicion of

Indications

Contraindications

significant coronary disease, but a normal result does not

x Confirmation of suspected angina

x Cardiac failure

x Evaluation of extent of myocardial

x Any feverish illness

exclude it.

ischaemia and prognosis

x Left ventricular outflow tract

x Risk stratification after myocardial

obstruction or hypertrophic

Chest x ray

infarction

cardiomyopathy

Patients with angina and no prior history of cardiac disease

x Detection of exercise induced

x Severe aortic or mitral

usually have a normal chest x ray film.

symptoms (such as arrhythmias or

stenosis

syncope)

x Uncontrolled hypertension

x Evaluation of outcome of

x Pulmonary hypertension

Exercise electrocardiography

interventions (such as

x Recent myocardial infarction

This is the most widely used test in evaluating patients with

percutaneous coronary

x Severe tachyarrhythmias

suspected angina. It is generally safe (risk ratio of major adverse

interventions or coronary artery

x Dissecting aortic aneurysm

events 1 in 2500, and of mortality 1 in 10 000) and provides

bypass surgery)

x Left main stem stenosis or

x Assessment of cardiac transplant

equivalent

diagnostic as well as prognostic information. The average

x Rehabilitation and patient

x Complete heart block (in

sensitivity and specificity is 75%. The test is interpreted in terms

motivation

adults)

of achieved workload, symptoms, and electrocardiographic

response. A 1 mm depression in the horizontal ST segment is

the usual cut-off point for significant ischaemia. Poor exercise

Rest

capacity, an abnormal blood pressure response, and profound

ischaemic electrocardiographic changes are associated with a

poor prognosis.

aVR

Main end points for exercise electrocardiography

x Target heart rate achieved ( > 85% of maximum predicted heart rate)

aVL

x ST segment depression > 1 mm (downsloping or planar depression

of greater predictive value than upsloping depression)

x Slow ST recovery to normal ( > 5 minutes)

III

aVF

x Decrease in systolic blood pressure > 20 mm Hg

x Increase in diastolic blood pressure > 15 mm Hg

x Progressive ST segment elevation or depression

Peak

exercise

x ST segment depression > 3 mm without pain

x Arrhythmias (atrial fibrillation, ventricular tachycardia)

Features indicative of a strongly positive exercise test

aVR

x Exercise limited by angina to < 6 minutes of Bruce protocol

x Failure of systolic blood pressure to increase > 10 mm Hg, or fall

with evidence of ischaemia

x Widespread marked ST segment depression > 3 mm

x Prolonged recovery time of ST changes ( > 6 minutes)

aVL

x Development of ventricular tachycardia

x ST elevation in absence of prior myocardial infarction

III

aVF

Stress echocardiography

Stress induced impairment of myocardial contraction is a

Example of a strongly positive exercise test. After only 2 minutes and 24

seconds of exercise (according to Bruce protocol), the patient developed

sensitive marker of ischaemia and precedes

chest pain and electrocardiography showed marked ischaemic changes

electrocardiographic changes and angina. Cross sectional

(maximum 3 mm ST segment depression in lead V6)

echocardiography can be used to evaluate regional and global

left ventricular impairment during ischaemia, which can be

induced by exercise or an intravenous infusion of drugs that

increase myocardial contraction and heart rate (such as

dobutamine) or dilate coronary arterioles (such as dipyridamole

or adenosine). The test has a higher sensitivity and specificity

than exercise electrocardiography and is useful in patients

whose physical condition limits exercise.

Radionuclide myocardial perfusion imaging

Thallium-201 or technetium-99m (^99mTc-sestamibi,

^99mTc-tetrofosmin) is injected intravenously at peak stress, and its

myocardial distribution relates to coronary flow. Images are

acquired with a gamma camera. This test can distinguish

between reversible and irreversible ischaemia (the latter

signifying infarcted tissue). Although it is expensive and

requires specialised equipment, it is useful in patients whose

^99mTc-tetrofosmin perfusion scan showing reversible anterolateral wall

exercise test is non-diagnostic or whose exercise ability is

ischaemia, induced by intravenous dobutamine infusion (white arrows).

limited.

Normal rest images are shown by yellow arrows

Pathophysiology and investigation of coronary artery disease

A multigated acquisition (MUGA) scan assesses left

ventricular function and can reveal salvageable myocardium in

patients with chronic coronary artery disease. It can be

performed with either thallium scintigraphy at rest or metabolic

imaging with fluorodeoxyglucose by means of either positron

emission tomography (PET) or single photon emission

computed tomography (SPECT).

Invasive investigations

Coronary angiography

The only absolute way to evaluate coronary artery disease is by

angiography. It is usually performed as part of cardiac

Angiograms of normal coronary arteries (LAD=left anterior descending

catheterisation, which includes left ventricular angiography and

artery, DG=diagonal artery, LCx=left circumflex artery, OM=obtuse marginal

haemodynamic measurements, providing a more complete

artery, SAN=sino-atrial node artery, RV=right ventricular branch artery,

LV=left ventricular branch artery, PDA=posterior descending artery)

evaluation of an individual’s cardiac status. Cardiac

catheterisation is safely performed as a day case procedure.

Patients must be fully informed of the purpose of the

procedure as well as its risks and limitations. Major

complications, though rare in experienced hands, include death

(risk ratio 1 in 1400), stroke (1 in 1000), coronary artery

Main indications for coronary angiography

dissection (1 in 1000), and arterial access complications (1 in

x Uncertain diagnosis of angina (coronary artery disease cannot be

500). Risks depend on the individual patient, and predictors

excluded by non-invasive testing)

include age, coronary anatomy (such as severe left main stem

x Assessment of feasibility and appropriateness of various forms of

disease), impaired left ventricular function, valvar heart disease,

treatment (percutaneous intervention, bypass surgery, medical)

the clinical setting, and non-cardiac disease. The commonest

x Class I or II stable angina with positive stress test or class III or IV

angina without positive stress test

complications are transient or minor and include arterial access

x Unstable angina or non-Q wave myocardial infarction (medium

bleeding and haematoma, pseudoaneurysm, arrhythmias,

and high risk patients)

reactions to the contrast medium, and vagal reactions (during

x Angina not controlled by drug treatment

sheath insertion or removal).

x Acute myocardial infarction—especially cardiogenic shock,

Before the procedure, patients usually fast and may be given

ineligibility for thrombolytic treatment, failed thrombolytic

a sedative. Although a local anaesthetic is used, arterial access

reperfusion, re-infarction, or positive stress test

x Life threatening ventricular arrhythmia

(femoral, brachial, or radial) may be mildly uncomfortable.

x Angina after bypass surgery or percutaneous intervention

Patients do not usually feel the catheters once they are inside

x Before valve surgery or corrective heart surgery to assess occult

the arteries. Transient angina may occur during injection of

coronary artery disease

contrast medium, usually because of a severely diseased artery.

Patients should be warned that, during left ventricular

angiography, the large volume of contrast medium may cause a

transient hot flush and a strange awareness of urinary

incontinence (and can be reassured that this does not actually

happen). Modern contrast agents rarely cause nausea and

vomiting.

Insertion of an arterial sheath with a haemostatic valve

minimises blood loss and allows catheter exchange. Three types

of catheter, which come in a variety of shapes and diameters,

are commonly used. Two have a single hole at the end and are

designed to facilitate controlled engagement of the distal tip

within the coronary artery ostium. Contrast medium is injected

through the lumen of the catheter, and moving x ray images are

obtained and recorded. Other catheters may be used for graft

angiography. The “pigtail” catheter has an end hole and several

side holes and is passed across the aortic valve into the left

ventricle. It allows injection of 30-40 ml of contrast medium

Left ventricular

angiogram during diastole

(top) and systole (bottom)

after injection of contrast

medium via a pigtail

catheter, showing good

contractility (LCA=left

coronary artery)

Commonly used diagnostic catheters (from left

to right): right Judkins, left Judkins,

multipurpose, left Amplatz, and pigtail

ABC of Interventional Cardiology

over three to five seconds by a motorised pump, providing

Ultrasound

visualisation of left ventricular contraction over two to four

scan plane

Vessel

cardiac cycles. Aortic and ventricular pressures are also

IVUS catheter

recorded during the procedure.

Intravascular ultrasound (IVUS)

In contrast to angiography, which gives a two dimensional

luminal silhouette with little information about the vessel wall,

intravascular ultrasound provides a cross sectional, three

Media and

Stent struts

dimensional image of the full circumference of the artery. It

adventitia

border

allows precise measurement of plaque length and thickness and

Fibro-fatty

minimum lumen diameter, and it may also characterise the

plaque

plaque’s composition.

It is often used to clarify ambiguous angiographic findings

and to identify wall dissections or thrombus. It is most useful

IVUS catheter

during percutaneous coronary intervention, when target lesions

Lumen

can be assessed before, during, and after the procedure and at

follow up. The procedure can also show that stents which seem

The intravascular ultrasound (IVUS) catheter (above) and images showing a

to be well deployed on angiography are, in fact, suboptimally

stent within a diseased coronary artery (below)

expanded. Its main limitations are the need for an operator

experienced in its use and its expense; for these reasons it is not

routinely used in many centres.

Doppler flow wire and pressure wire

Unlike angiography or intravascular ultrasound, the Doppler

flow wire and pressure wire provide information on the

physiological importance of a diseased coronary artery. They

are usually used when angiography shows a stenosis that is of

intermediate severity, or to determine the functional severity of

Angina?

a residual stenosis after percutaneous coronary intervention.

Intracoronary adenosine is used to dilate the distal coronary

vessels in order to maximise coronary flow. The Doppler flow

Definite or possible

Unlikely

wire has a transducer at its tip, which is positioned beyond the

stenosis to measure peak flow velocity. The pressure wire has a

Risk factor assessment, blood tests, electrocardiography

tip micrometer, which records arterial pressures proximal and

distal to the stenosis.

Drug treatment for symptoms and risk factor reduction

The figure showing progression of atheromatous plaque from initial lesion

Refer to cardiologist

is adapted with permission from Pepine CJ, Am J Cardiol 1998;82(suppl

10A):23-7S.

Competing interests: None declared.

Stress test

Further reading

Strongly positive

Mildly positive

Negative

x Mark DB, Shaw L, Harrell FE Jr, Hlatky MA, Lee KL, Bengtson JR,

et al. Prognostic value of a treadmill exercise score in outpatients

Review diagnosis

with suspected coronary artery disease. N Engl J Med 1991;325:

849-53

x Marwick TH, Case C, Sawada S, Rimmerman C, Brenneman P,

Angina

Not angina

Kovacs R, et al. Prediction of mortality using dobutamine

echocardiography. J Am Coll Cardiol 2001;37:754-60

x Scanlon PJ, Faxon DP, Audet AM, Carabello B, Dehmer GJ, Eagle

Medical treatment

KA, et al. ACC/AHA guidelines for coronary angiography. A report

of the American College of Cardiology/American Heart

Association Task Force on Practice Guidelines (Committee on

Angiography

Poor control

Good control

Coronary Angiography). J Am Coll Cardiol 1999;33:1756-824

x Mintz GS, Nissen SE, Anderson WD, Bailey SR, Erbel R, Fitzgerald

PJ, et al. American College of Cardiology clinical expert consensus

Revascularisation (PCI or CABG)

Continue medical treatment

document on standards for acquisition, measurement and reporting

of intravascular ultrasound studies (IVUS). J Am Coll Cardiol

2001;37:1478-92

Algorithm for management of suspected angina (PCI=percutaneous

coronary intervention, CABG=coronary artery bypass grafting)

Percutaneous coronary intervention.

I: History and development

Ever D Grech

Canadian Cardiovascular Society classification of angina

The term “angina pectoris” was introduced by Heberden in

Class I

1772 to describe a syndrome characterised by a sensation of

x No angina during ordinary physical activity such as walking or

“strangling and anxiety” in the chest. Today, it is used for chest

climbing stairs

discomfort attributed to myocardial ischaemia arising from

x Angina during strenuous, rapid, or prolonged exertion

increased myocardial oxygen consumption. This is often

Class II

induced by physical exertion, and the commonest aetiology is

x Slight limitation of ordinary activity

atheromatous coronary artery disease. The terms “chronic” and

x Angina on walking or climbing stairs rapidly; walking uphill;

“stable” refer to anginal symptoms that have been present for at

walking or climbing stairs shortly after meals, in cold or wind, when

least several weeks without major deterioration. However,

under emotional stress, or only in the first few hours after waking

x Angina on walking more than two blocks (100-200 m) on the level

symptom variation occurs for several reasons, such as mental

or climbing more than one flight of stairs at normal pace and in

stress, ambient temperature, consumption of alcohol or large

normal conditions

meals, and factors that may increase coronary tone such as

Class III

drugs and hormonal change.

x Marked limitation of ordinary physical activity

x Angina on walking one or two blocks on the level or climbing one

flight of stairs at normal pace and in normal conditions

Classification

Class IV

The Canadian Cardiovascular Society has provided a graded

x Inability to carry out any physical activity without discomfort

classification of angina which has become widely used. In

x Includes angina at rest

clinical practice, it is important to describe accurately specific

activities associated with angina in each patient. This should

include walking distance, frequency, and duration of episodes.

Percutaneous transluminal coronary angioplasty (PTCA)

1977

Development in PTCA equipment

Mid

History of myocardial

1980s

(soft tipped guide catheters, steerable guidewires, lower profile balloon catheters)

revascularisation

Mid

In the management of chronic stable angina, there are two

Stents

Athero-ablative devices

1990s

(directional coronary atherectomy, rotablator, lasers)

invasive techniques available for myocardial revascularisation:

onwards

coronary artery bypass surgery and catheter attached devices.

Although coronary artery bypass surgery was introduced in

New stent designs

Brachytherapy

New balloon designs

Adjunctive

1968, the first percutaneous transluminal coronary angioplasty

and "smart" stents

• β radiation

• Low profile

pharmacotherapy

was not performed until September 1977 by Andreas

• Pre-mounted

emission

• High inflation

• ADP antagonists

• Increased flexibility

• γ radiation

• Short or long

• Glycoprotein IIb/

Gruentzig, a Swiss radiologist, in Zurich. The patient, 38 year

and radial strength

emission

balloons

IIIa inhibitors

old Adolph Bachman, underwent successful angioplasty to a left

• Covered stents

• Cutting balloons

• Coated stents

coronary artery lesion and remains well to this day. After the

• "Designer" drugs

success of the operation, six patients were successfully treated

with percutaneous transluminal coronary angioplasty in that

• Biodegradable stents

• Drug or gene delivery

year.

stents

By today’s standards, the early procedures used

• Radioactive stents

cumbersome equipment: guide catheters were large and could

easily traumatise the vessel, there were no guidewires, and

Major milestones in percutaneous coronary intervention

balloon catheters were large with low burst pressures. As a

result, the procedure was limited to patients with refractory

angina, good left ventricular function, and a discrete, proximal,

concentric, and non-calcific lesion in a single major coronary

artery with no involvement of major side branches or

angulations. Consequently, it was considered feasible in only

10% of all patients needing revascularisation.

Modern balloon

Developments in percutaneous

catheter: its low

profile facilitates

intervention

lesion crossing, the

flexible shaft allows

During 1977-86 guide catheters, guidewires, and balloon

tracking down

catheter technology were improved, with slimmer profiles and

tortuous vessels, and

the balloon can be

increased tolerance to high inflation pressures. As equipment

inflated to high

improved and experience increased, so more complex lesions

pressures without

were treated and in more acute situations. Consequently,

distortion or rupture

ABC of Interventional Cardiology

percutaneous transluminal coronary angioplasty can now be

undertaken in about half of patients needing revascularisation

(more in some countries), and it is also offered to high-risk

patients for whom coronary artery bypass surgery may be

considered too dangerous.

Although percutaneous transluminal coronary angioplasty

causes plaque compression, the major change in lumen

geometry is caused by fracturing and fissuring of the atheroma,

extending into the vessel wall at variable depths and lengths.

This injury accounts for the two major limitations of

percutaneous transluminal coronary angioplasty{acute vessel

closure and restenosis.

Micrographs showing arterial

Acute vessel closure—This usually occurs within the first 24

barotrauma caused by coronary

hours of the procedure in about 3-5% of cases and follows

angioplasty. Top left: coronary

arterial dissection with large flap.

vessel dissection, acute thrombus formation, or both. Important

Top right: deep fissuring within

clinical consequences include myocardial infarction, emergency

coronary artery wall atheroma.

coronary artery bypass surgery, and death.

Bottom: fragmented plaque tissue

(dark central calcific plaque

Restenosis occurring in the first six months after angioplasty

surrounded by fibrin and

is caused largely by smooth muscle cell proliferation and

platelet-rich thrombus), which may

fibrointimal hyperplasia (often called neointimal proliferation),

embolise in distal arterioles to cause

as well as elastic recoil. It is usually defined as a greater than

infarction

50% reduction in luminal diameter and has an incidence of

25-50% (higher after vein graft angioplasty). Further

intervention may be indicated if angina and ischaemia recur.

Drills, cutters, and lasers

In the 1980s, two main developments aimed at limiting these

problems emerged. The first were devices to remove plaque

material, such as by rotational atherectomy, directional coronary

atherectomy, transluminal extraction catheter, and excimer

laser. By avoiding the vessel wall trauma seen during

percutaneous transluminal coronary angioplasty, it was

envisaged that both acute vessel closure and restenosis rates

Tools for coronary atherectomy. Top:

would be reduced.

the Simpson atherocath has a cutter in

However, early studies showed that, although acute closure

a hollow cylindrical housing. The cutter

rotates at 2000 rpm, and excised

rates were reduced, there was no significant reduction in

atheromatous tissue is pushed into the

restenosis. Moreover, these devices are expensive, not

distal nose cone. Left: the Rotablator

particularly user friendly, and have limited accessibility to more

burr is coated with 10

m diamond

distal stenoses. As a result, they have now become niche tools

chips to create an abrasive surface. The

burr, connected to a drive shaft and a

used by relatively few interventionists. However, they may have

turbine powered by compressed air,

an emerging role in reducing restenosis rates when used as

rotates at speeds up to 200 000 rpm

adjunctive treatment before stenting (especially for large

plaques) and in treating diffuse restenosis within a stent.

Intracoronary stents

The second development was the introduction of intracoronary

stents deployed at the site of an atheromatous lesion. These

were introduced in 1986 with the objective of tacking down

dissection flaps and providing mechanical support. They also

reduce elastic recoil and remodelling associated with restenosis.

The first large randomised studies conclusively showed the

superiority of stenting over coronary angioplasty alone, both in

clinical and angiographic outcomes, including a significant 30%

reduction in restenosis rates. Surprisingly, this was not due to

inhibition of neointimal proliferation—in fact stents may

increase this response. The superiority of stenting is that the

initial gain in luminal diameter is much greater than after

angioplasty alone, mostly because of a reduction in elastic

recoil.

Although neointimal proliferation through the struts of the

stent occurs, it is insufficient to cancel out the initial gain,

Coronary stents. Top: Guidant Zeta stent. Middle: BiodivYsio AS stent coated

leading to a larger lumen size and hence reduced restenosis.

with phosphorylcholine, a synthetic copy of the outer membrane of red

blood cells, which improves haemocompatibility and reduces thrombosis.

Maximising the vessel lumen is therefore a crucial mechanism

Bottom: the Jomed JOSTENT coronary stent graft consists of a layer of

for reducing restenosis. “Bigger is better” is the adage followed

PTFE (polytetrafluoroethylene) sandwiched between two stents and is useful

in this case.

in sealing perforations, aneurysms, and fistulae

Percutaneous coronary intervention. I: History and development

Early stent problems

As a result of initial studies, stents were predominantly used

either as “bail out” devices for acute vessel closure during

coronary angioplasty (thus avoiding the need for immediate

coronary artery bypass surgery) or for restenosis after

angioplasty.

Thrombosis within a stent causing myocardial infarction

and death was a major concern, and early aggressive

anticoagulation to prevent this led to frequent complications

from arterial puncture wounds as well as major systemic

haemorrhage. These problems have now been overcome by the

introduction of powerful antiplatelet drugs as a substitute for

warfarin. The risk of thrombosis within a stent diminishes when

the stent is lined with a new endothelial layer, and antiplatelet

treatment can be stopped after a month. The recognition that

suboptimal stent expansion is an important contributor to

Coronary angiogram showing

thrombosis in stents has led to the use of intravascular

three lesions (arrows) affecting

ultrasound to guide stent deployment and high pressure

the left anterior descending

inflations to ensure complete stent expansion.

artery (top left). The lesions

are stented without

pre{dilatation (top right), with

Current practice

good results (bottom)

A greater understanding of the pathophysiology of stent

deployment, combined with the development of more flexible

stents (which are pre-mounted on low-profile catheter

balloons), has resulted in a massive worldwide increase in stent

use, and they have become an essential component of coronary

intervention. Low profile stents have also allowed “direct”

stenting—that is, implanting a stent without the customary

2500

balloon dilatation—to become prevalent, with the advantages of

economy, shorter procedure time, and less radiation from

2000

imaging. Most modern stents are expanded by balloon and

1500

made from stainless steel alloys. Their construction and design,

metal thickness, surface coverage, and radial strength vary

1000

considerably.

500

Stents are now used in most coronary interventions and in a

wide variety of clinical settings. They substantially increase

1986

1994

1998

2001

procedural safety and success, and reduce the need for

Year

emergency coronary artery bypass surgery. Procedures

involving stent deployment are now often referred to as

Exponential increase in use of intracoronary stents since

percutaneous coronary interventions to distinguish them from

1986. In 2001, 2.3 million stents were implanted (more

conventional balloon angioplasty (percutaneous transluminal

than double the 1998 rate)

coronary angioplasty).

A major recent development has been the introduction of

drug eluting stents (also referred to as “coated stents”), which

reduce restenosis to very low rates. Their high cost currently

limits their use, but, with increasing competition among

manufacturers, they will probably become more affordable.

Unequivocal indications for use of coronary stents

x Acute or threatened vessel closure during angioplasty

Competing interests: None declared.

x Primary reduction in restenosis in de novo lesions in arteries

> 3.0 mm in diameter

The micrographs showing deep fissuring within a coronary artery wall

x Focal lesions in saphenous vein grafts

atheroma and fragmented plaque tissue caused by coronary angioplasty

x Recanalised total chronic occlusions

were supplied by Kelly MacDonald, consultant histopathologist at St

x Primary treatment of acute coronary syndromes

Boniface Hospital, Winnipeg, Canada.

Further reading

x Gruentzig AR. Transluminal dilatation of coronary artery stenosis.

x Meyer BJ, Meier B. Percutaneous transluminal coronary angioplasty

Lancet 1978;1:263

of single or multivessel disease and chronic total occlusions. In:

x Smith SC Jr, Dove JT, Jacobs AK, Kennedy JW, Kereiakes D, Kern

Grech ED, Ramsdale DR, eds. Practical interventional cardiology.

MJ, et al. ACC/AHA guidelines of percutaneous coronary

2nd ed. London: Martin Dunitz, 2002:35-54

interventions (revision of the 1993 PTCA guidelines)—executive

x Costa MA, Foley DP, Serruys PW. Restenosis: the problem and how

summary. A report of the American College of Cardiology/

to deal with it. In: Grech ED, Ramsdale DR, eds. Practical

American Heart Association Task Force on Practice Guidelines

interventional cardiology. 2nd ed. London: Martin Dunitz, 2002:

(committee to revise the 1993 guidelines for percutaneous

279-94

transluminal coronary angioplasty). J Am Coll Cardiol 2001;37:

x Topol EJ, Serruys PW. Frontiers in interventional cardiology.

2215-39

Circulation 1998;98:1802-20

Percutaneous coronary intervention.

II: The procedure

Ever D Grech

A wide range of patients may be considered for percutaneous

coronary intervention. It is essential that the benefits and risks of

the procedure, as well as coronary artery bypass graft surgery and

medical treatment, are discussed with patients (and their families)

in detail. They must understand that, although the percutaneous

procedure is more attractive than bypass surgery, it has important

limitations, including the likelihood of restenosis and potential

for incomplete revascularisation compared with surgery. The

potential benefits of antianginal drug treatment and the need for

risk factor reduction should also be carefully explained.

Clinical risk assessment

Relief of anginal symptoms is the principal clinical indication

for percutaneous intervention, but we do not know whether the

procedure has the same prognostic benefit as bypass surgery.

Angiographic features determined during initial assessment

require careful evaluation to determine the likely success of the

Percutaneous coronary intervention in progress. Above the patient’s chest is

procedure and the risk of serious complications.

the x ray imaging camera. Fluoroscopic images, electrocardiogram, and

haemodynamic data are viewed at eye level screens. All catheterisation

Until recently, the American College of Cardiology and

laboratory operators wear lead protection covering body, thyroid, and eyes,

American Heart Association classified anginal lesions into types

and there is lead shielding between the primary operator and patient

(and subtypes) A, B, or C based on the severity of lesion

characteristics. Because of the ability of stents to overcome

many of the complications of percutaneous intervention, this

New classification system of stenotic lesions (American

classification has now been superseded by one reflecting low,

College of Cardiology and American Heart Association)

moderate, and high risk.

Successful percutaneous intervention depends on adequate

Low risk

Moderate risk

High risk

visualisation of the target stenosis and its adjacent arterial

Discrete ( < 10 mm)

Tubular (10-20 mm)

Diffuse ( > 20 mm)

branches. Vessels beyond the stenosis may also be important

Concentric

Eccentric

because of the potential for collateral flow and myocardial

Readily accessible

Proximal segment

support if the target vessel were to occlude abruptly. Factors

moderately tortuous

excessively tortuous

that adversely affect outcome include increasing age, comorbid

Segment not angular Segment moderately Segment extremely

(<45°)

angular (45°- < 90°)

angular (>90°)

disease, unstable angina, pre-existing heart or renal failure,

previous myocardial infarction, diabetes, a large area of

Smooth contour

Irregular contour

myocardium at risk, degree of collaterisation, and multivessel

Little or no

Moderate or heavy

calcification

disease.

Occlusion not total

Total occlusion

<3 months old

>3 months or bridging

collateral vessels

Preparation for intervention

Non-ostial

Ostial

Patients must be fully informed of the purpose of the procedure

No major side

Bifurcated lesions

Inability to protect

as well as its risks and limitations before they are asked for their

branch affected

requiring double

major side branches

consent. The procedure must always be carried out (or directly

guidewires

supervised) by experienced, high volume operators ( > 75

No thrombus

Some thrombus

Degenerated vein grafts

with friable lesions.

procedures a year) and institutions ( > 400 a year).

A sedative is often given before the procedure, as well as

aspirin, clopidogrel, and the patient’s usual antianginal drugs.

In very high risk cases an intra-aortic balloon pump may be

Clinical indications for percutaneous

used. A prophylactic temporary transvenous pacemaker wire

coronary intervention

may be inserted in some patients with pre-existing, high grade

x Stable angina (and positive stress test)

conduction abnormality or those at high risk of developing it.

x Unstable angina

x Acute myocardial infarction

x After myocardial infarction

The procedure

x After coronary artery bypass surgery

(percutaneous intervention to native vessels,

For an uncomplicated, single lesion, a percutaneous procedure

arterial or venous conduits)

may take as little as 30 minutes. However, the duration of the

x High risk bypass surgery

procedure and radiation exposure will vary according to

x Elderly patient

thenumber and complexity of the treated stenoses and vessels.

Percutaneous coronary intervention. II: The procedure

As with coronary angiography, arterial access (usually

femoral but also brachial or radial) under local anaesthesia is

required. A guide catheter is introduced and gently engaged at

the origin of the coronary artery. The proximal end of the

catheter is attached to a Y connector. One arm of this

connector allows continuous monitoring of arterial blood

pressure. Dampening or “ventricularisation” of this arterial

tracing may indicate reduced coronary flow because of

over-engagement of the guide catheter, catheter tip spasm, or a

previously unrecognised ostial lesion. The other arm has an

adjustable seal, through which the operator can introduce the

guidewire and balloon or stent catheter once the patient has

been given heparin as an anticoagulant. A glycoprotein IIb/IIIa

inhibitor, which substantially reduces ischaemic events during

Equipment commonly used in percutaneous coronary interventions

percutaneous coronary intervention, may also be given.

Visualised by means of fluoroscopy and intracoronary

injections of contrast medium, a soft tipped, steerable guidewire

(usually 0.014" (0.36 mm) diameter) is passed down the

coronary artery, across the stenosis, and into a distal branch. A

balloon or stent catheter is then passed over the guidewire and

positioned at the stenosis. The stenosis may then be stented

directly or dilated before stenting. Additional balloon dilatation

may be necessary after deployment of a stent to ensure its full

expansion.

Balloon inflation inevitably stops coronary blood flow,

which may induce angina. Patients usually tolerate this quite

well, especially if they have been warned beforehand. If it

becomes severe or prolonged, however, an intravenous opiate

may be given. Ischaemic electrocardiographic changes are often

seen at this time, although they are usually transient and return

to baseline once the balloon is deflated (usually after 30-60

seconds). During the procedure, it is important to talk to the

patient (who may be understandably apprehensive) to let him

or her know what is happening, as this encourages a good

rapport and cooperation.

Deployment of a balloon-mounted stent across stenotic

Recovery

lesion. Once the guide catheter is satisfactorily engaged,

the lesion is crossed with a guidewire and the

After the procedure the patient is transferred to a ward where

balloon-mounted stent positioned to cover the lesion (A).

close monitoring for signs of ischaemia and haemodynamic

It may be necessary to pre-dilate a severe lesion with a

instability is available. If a femoral arterial sheath was used, it

balloon to provide adequate passageway for the balloon

may be removed when the heparin effect has declined to an

and stent. The balloon is inflated to expand the stent (B).

The balloon is then deflated (C) and withdrawn leaving

acceptable level (according to unit protocols). Arterial sealing

the guidewire (D), which is also removed once the

devices have some advantages over manual compression: they

operator is satisfied that a good result has been obtained

permit immediate sheath removal and haemostasis, are more

comfortable for patients, and allow early mobilisation and

discharge. However, they are not widely used as they add

considerably to the cost of the procedure.

After a few hours, the patient should be encouraged to

gradually increase mobility, and in uncomplicated cases

discharge is scheduled for the same or the next day. Before

discharge, the arterial access site should be examined and the

patient advised to seek immediate medical advice if bleeding or

chest pain (particularly at rest) occurs. Outpatient follow up and

Example of a

drug regimens are provided, as well as advice on modification

femoral artery

closure device.

of risk factors and lifestyle.

The Angio-Seal

device creates a

mechanical seal

Complications and sequelae

by sandwiching

the arteriotomy

Complications are substantially lower in centres where large

between an

numbers of procedures are carried out by adequately trained

anchor placed

and experienced operators. Major complications are

Femoral

against the inner

artery

arterial wall (A)

uncommon and include death (0.2% but higher in high risk

and collagen

cases), acute myocardial infarction (1%) which may require

sponge (B), which

emergency coronary artery bypass surgery, embolic stroke

both dissolve

(0.5%), cardiac tamponade (0.5%), and systemic bleeding (0.5%).

within 60-90 days

ABC of Interventional Cardiology

Minor complications are more common and include allergy

to the contrast medium and nephropathy and complications of

the access site (bleeding, haematoma, and pseudoaneurysm).

Restenosis within a stent

Although stents prevent restenosis from vascular recoil and

remodelling, restenosis within the stent (known as “in-stent

restenosis”) due to neointimal proliferation does occur and is

the most important late sequel of the procedure. In-stent

restenosis is the Achilles’ heel of percutaneous revascularisation

and develops within six months of stenting.

Angiographic restenosis rates ( > 50% diameter stenosis)

depend on several factors and are higher in smaller vessels,

long and complex stenoses, and where there are coexisting

conditions such as diabetes. Approximate rates of angiographic

restenosis after percutaneous angioplasty are

x Angioplasty to de novo lesion in native artery—35%

Focal in-stent restenosis. A 2.0 mm stent had been deployed six

x Angioplasty and stent to de novo lesion in native artery—25%

months earlier. After recurrence of angina, angiography showed

x Angioplasty and stent to restenotic lesion in native artery—20%

focal in-stent restenosis (arrow, top left). This was confirmed with

x Angioplasty and stent to successfully recanalised chronic

intravascular ultrasound (top right), which also revealed that the

total occlusion—30%

stent was underexpanded. The stent was further expanded with a

balloon catheter, with a good angiographic result (arrow, bottom left)

x Angioplasty to de novo lesion in vein graft—60%

and an increased lumen diameter to 2.7 mm (bottom right)

x Angioplasty and stent to de novo lesion in vein graft—30%.

It should be noted that angiographically apparent

restenoses do not always lead to recurrent angina (clinical

restenosis). In some patients only mild anginal symptoms recur,

and these may be well controlled with antianginal drugs,

thereby avoiding the need for further intervention.

Stented artery with area

Balloon angioplasty catheter

Using repeat percutaneous angioplasty alone to re-dilate

of in-stent restenosis

inside stented artery

in{stent restenosis results in a high recurrence of restenosis

(60%). Various other methods, such as removing restenotic

tissue by means of atherectomy or a laser device or re-dilating

with a cutting balloon, are being evaluated. Another method is

Radiation source train placed at

Artery after balloon angioplasty

brachytherapy, which uses a special intracoronary catheter to

treatment site for < 5 minutes

and vascular brachytherapy

deliver a source of or radiation. It significantly reduces

further in-stent restenosis, but it has limitations, including late

Diagrammatic representation of the Novoste Beta Cath system used for

vascular brachytherapy. Pre-dilatation of the in-stent restenosis with a

thrombosis and new restenosis at the edges of the radiation

balloon catheter is usual and is followed by positioning of the radiation

treated segments, giving rise to a “candy wrapper” appearance.

source train, containing strontium-90, at the site for less than 5 minutes

The cutting balloon catheter. The longitudinal cutting blades are exposed

Angiogram showing late “candy

only during balloon inflation (top left). In this case (top right) a severe

wrapper” edge effect (arrows)

ostial in-stent restenosis in the right coronary artery (arrow) was dilated

because of new restenosis at the

with a short cutting balloon (bottom left), and a good angiographic result

edges of a segment treated by

was obtained (arrow, bottom right)

brachytherapy

Percutaneous coronary intervention. II: The procedure

Drug eluting, coated stents

Coated stents contain drugs that inhibit new tissue growth

within the sub-intima and are a promising new option for

preventing or treating in-stent restenosis. Sirolimus (an

immunosuppressant used to prevent renal rejection which

inhibits smooth muscle proliferation and reduces intimal

thickening after vascular injury), paclitaxel (the active

component of the anticancer drug taxol), everolimus, ABT-578,

and tacrolimus are all being studied, as are other agents.

Although long term data and cost benefit analyses are not yet

available, it seems probable that coated stents will be commonly

used in the near future.

Top left: four months after two

stents (yellow lines) were deployed

in the proximal and middle right

Occupation and driving

coronary artery, severe diffuse

in-stent restenosis has occurred

Doctors may be asked to advise on whether a patient is “fit for

with recurrent angina. Top right:

work” or “recovered from an event” after percutaneous

two sirolimus coated Cypher stents

coronary intervention. “Fitness” depends on clinical factors

(red lines) were deployed within

the original stents. Bottom: after

(level of symptoms, extent and severity of coronary disease, left

six months there was no

ventricular function, stress test result) and the nature of the

recurrence of restenosis, and the

occupation, as well as statutory and non-statutory fitness

51 year old patient remained

requirements. Advisory medical standards are in place for

asymptomatic

certain occupations, such as in the armed forces and police,

railwaymen, and professional divers. Statutory requirements

cover the road, marine, and aviation industries and some

recreational pursuits such as driving and flying.

Patients often ask when they may resume driving after

percutaneous coronary intervention. In Britain, the Driver and

Vehicle Licensing Agency recommends that group 1 (private

motor car) licence holders should stop driving when anginal

symptoms occur at rest or at the wheel. After percutaneous

coronary intervention, they should not drive for a week. Drivers

holding a group 2 licence (lorries or buses) will be disqualified

from driving once the diagnosis of angina has been made, and

for at least six weeks after percutaneous coronary intervention.

Re-licensing may be permitted provided the exercise test

requirement (satisfactory completion of nine minutes of the

Bruce protocol while not taking blockers) can be met and

there is no other disqualifying condition.

The diagram of the Angio-Seal device is used with permission of St Jude

Medical, Minnetonka, Minnesota, USA. The angiogram showing the “candy

wrapper” effect is reproduced with permission of R Waksman, Washington

Hospital Center, and Martin Dunitz, London.

The incidence of restenosis is

particularly high with percutaneous

Competing interests: None declared.

revascularisation of small vessels. A

small diseased diagonal artery

(arrows, top left) in a 58 year old

patient with limiting angina was

stented with a sirolimus coated

Cypher stent (red line, top right).

After six months, no restenosis was

present (left), and the patient

remained asymptomatic

Further reading

x Smith SC Jr, Dove JT, Jacobs AK, Kennedy JW, Kereiakes D, Kern

x Almond DG. Coronary stenting I: intracoronary stents—form,

MJ, et al. ACC/AHA guidelines of percutaneous coronary

function future. In: Grech ED, Ramsdale DR, eds. Practical

interventions (revision of the 1993 PTCA guidelines)—executive

interventional cardiology. 2nd ed. London: Martin Dunitz, 2002:63-76

summary. A report of the American College of Cardiology/

x Waksman R. Management of restenosis through radiation therapy.

American Heart Association Task Force on Practice Guidelines

In: Grech ED, Ramsdale DR, eds. Practical interventional cardiology.

(committee to revise the 1993 guidelines for percutaneous

2nd ed. London: Martin Dunitz, 2002:295-305

transluminal coronary angioplasty). J Am Coll Cardiol 2001;37:

x Kimmel SE, Berlin JA, Laskey WK. The relationship between

2215{39

coronary angioplasty procedure volume and major complications.

x Morice MC, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, Perin

JAMA 1995;274:1137-42

M, et al. A randomized comparison of a sirolimus-eluting stent with

x Rensing BJ, Vos J, Smits PC, Foley DP, van den Brand MJ, van der

a standard stent for coronary revascularization. N Engl J Med

Giessen WJ, et al. Coronary restenosis elimination with a sirolimus

2002;346:1773-80

eluting stent. Eur Heart J 2001;22:2125-30

Chronic stable angina: treatment options

Laurence O’Toole, Ever D Grech

In patients with chronic stable angina, the factors influencing

Major factors influencing risks and benefits of coronary

the choice of coronary revascularisation therapy (percutaneous

revascularisation

coronary intervention or coronary artery bypass surgery) are

x Advanced age

x Multiple coronary vessels affected

varied and complex. The severity of symptoms, lifestyle, extent

x Female

x Coexisting valve disease

of objective ischaemia, and underlying risks must be weighed

x Severe angina

x Impaired left ventricular function

against the benefits of revascularisation and the patient’s

x Smoking

x Impaired renal function

preference, as well as local availability and expertise. Evidence

x Diabetes

x Cerebrovascular or peripheral vascular disease

from randomised trials and large revascularisation registers can

x Obesity

x Recent acute coronary syndrome

guide these decisions, but the past decade has seen rapid

x Hypertension

x Chronic obstructive airways disease

change in medical treatment, bypass surgery, and percutaneous

intervention. Therefore, thought must be given to whether older

data still apply to contemporary practice.

Patients with chronic stable angina have an average annual

mortality of 2-3%, only twice that of age matched controls, and

this relatively benign prognosis is an important consideration

when determining the merits of revascularisation treatment.

Left internal

Saphenous

mammary

vein graft

Certain patients, however, are at much higher risk. Predictors

artery with

include poor exercise capacity with easily inducible ischaemia

pedicle

or a poor haemodynamic response to exercise, angina of recent

onset, previous myocardial infarction, impaired left ventricular

function, and the number of coronary vessels with significant

stenoses, especially when disease affects the left main stem or

proximal left anterior descending artery. Although the potential

benefits of revascularisation must be weighed against adverse

factors, those most at risk may have the most to gain.

Treatment strategies

Medical treatment

Anti-ischaemic drugs improve symptoms and quality of life, but

have not been shown to reduce mortality or myocardial

infarction. blockers may improve survival in hypertension, in

heart failure, and after myocardial infarction, and so are

Top: Diagrams of saphenous vein and left internal mammary artery grafts

for coronary artery bypass surgery. Bottom: Three completed grafts—(1) left

considered by many to be first line treatment. Nicorandil has

internal mammary artery (LIMA) to left anterior descending artery (LAD),

recently been shown to reduce ischaemic events and need for

and saphenous vein grafts (SVG) to (2) diagonal artery (DG) and (3) obtuse

hospital admission.

marginal artery (OM)

Trials comparing medical treatment with revascularisation

predate the widespread use of antiplatelet and cholesterol

lowering drugs. These drugs reduce risk, both in patients

Risk score for assessing probable mortality from bypass

treated with drugs only and in those undergoing

surgery in patients with chronic stable angina

revascularisation, and so may have altered the risk-benefit ratio

Risk factor

Weighted score

for a particular revascularisation strategy in some patients.

Age > 60

Score 1 for every

5 years over

Female sex

Coronary artery bypass graft surgery

Chronic obstructive pulmonary disease

Coronary artery bypass surgery involves the placement of grafts

Extracardiac arteriopathy

to bypass stenosed native coronary arteries, while maintaining

Neurological dysfunction

cerebral and peripheral circulation by cardiopulmonary bypass.

Previous cardiac surgery

The grafts are usually saphenous veins or arteries (principally

Serum creatinine > 200 mol/l

Reduced left ventricular ejection fraction

1 for 30-50%

the left internal mammary artery).

3 for < 30%

Operative mortality is generally 1-3% but may be much

Myocardial infarction in past 90 days

higher in certain subsets of patients. Scoring systems can

Pulmonary artery systolic pressure > 60 mm Hg

predict operative mortality based on clinical, investigational, and

Major cardiac procedure as well as bypass surgery

operative factors. Important developments that have occurred

Emergency operation

since trials of bypass surgery versus medical treatment were

x Total score <2 predicts < 1% operative mortality

conducted include increased use of arterial grafts (which have

x Total score of 3-5 predicts 3% operative mortality

much greater longevity than venous grafts), surgery without

x Total score >6 predicts > 10% operative mortality

extracorporeal circulation (“off-pump” bypass), and minimal

A more detailed assessment with logistic analysis is available at www.euroscore.org and

is recommended for assessing high risk patients

access surgery.

Chronic stable angina: treatment options

Percutaneous coronary intervention

Subgroup analysis of mortality benefit from coronary artery

The main advantages of percutaneous intervention over bypass

bypass surgery compared with medical treatment at 10 years

surgery are the avoidance of the risks of general anaesthesia,

after randomisation for patients with chronic stable angina

uncomfortable sternotomy and saphenous wounds, and

complications of major surgery (infections and pulmonary

Subgroup

Mean (1.96 SE) increased

P value of

emboli). Only an overnight hospital stay is necessary (and many

survival time (months)

difference

procedures can be performed as day cases), and the procedure

Vessel disease:

can be easily repeated. The mortality is low (0.2%), and the most

1 or 2 vessels

1.8

(3.0)

0.25

serious late complication is restenosis.

3 vessels

5.7

(3.6)

0.001

Patient suitability is primarily determined by technical factors.

Left main stem

19.3

(13.7)

0.005

A focal stenosis on a straight artery without proximal vessel

Left ventricular function:

tortuousness or involvement of major side branches is ideal for

Normal

2.3

(2.4)

0.06

percutaneous intervention. Long, heavily calcified stenoses in

Abnormal

10.6

(6.1)

< 0.001

tortuous vessels or at bifurcations and chronic total occlusions are

Exercise test:

less suitable. This must be borne in mind when interpreting data

Normal

3.3

(4.4)

0.14

from trials of percutaneous intervention and bypass surgery, as

Abnormal

5.1

(3.3)

0.002

only a minority of patients were suitable for both procedures.

Severity of angina:

Nowadays, more and more patients undergo percutaneous

CCS class 0, I, II

3.3

(2.7)

0.02

intervention, and referral rates for bypass surgery are falling.

CCS class III, IV

7.3

(4.8)

0.002

CCS=Canadian Cardiovascular Society

Comparative studies of

revascularisation strategies

Coronary artery bypass surgery versus medical treatment

In a meta-analysis of seven trials comparing bypass surgery with

medical treatment, surgery conferred a survival advantage in

patients with severe left main stem coronary disease, three

vessel disease, or two vessel disease with severely affected

proximal left anterior descending artery. The survival gain was

more pronounced in patients with left ventricular dysfunction

or a strongly positive exercise test. However, only 10% of trial

patients received an internal mammary artery graft, only 25%

received antiplatelet drugs, and the benefit of lipid lowering

drugs on long term graft patency was not appreciated when

these studies were carried out. Furthermore, 40% of the

medically treated patients underwent bypass surgery during 10

years of follow up. Thus, these data may underestimate the

benefits of surgery compared with medical treatment alone.

In lower risk patients bypass surgery is indicated only for

symptom relief and to improve quality of life when medical

treatment has failed. Surgery does this effectively, with 95% of

patients gaining immediate relief from angina and 75%

remaining free from angina after five years. Unfortunately,

Left: Angiogram of a 10 year old diseased venous graft to the obtuse

venous grafts have a median life span of only seven years, and

marginal artery showing proximal aneurysmal dilatation (A) and severe

stenosis in middle segment (B). Right: Removal of this graft after repeat

after 15 years only 15% of patients are free from recurrent

bypass surgery shows its gross appearance (graft longitudinally opened in

angina or death or myocardial infarction. However, the

right image), with atherosclerosis in a thin walled aneurysm and a small

increased use of internal mammary artery grafts, which have

residual lumen

excellent long term patency (85% at 10 years), has increased

postoperative survival and reduced long term symptoms.

Old saphenous vein grafts may contain large amounts of necrotic clotted debris, friable laminated thrombus, and ulcerated atheromatous plaque and are

unattractive for percutaneous intervention because of the high risk of distal embolisation. However, distal embolisation protection devices such as the

FilterWire EX (far right) reduce this risk by trapping any material released. Such a device (far left, B) is positioned in the distal segment of a subtotally

occluded saphenous vein graft of the left anterior descending artery (A) before it is dilated and stented (inner left, C) to restore blood flow (inner right)

ABC of Interventional Cardiology

Percutaneous coronary intervention versus medical

treatment

Most percutaneous procedures are undertaken to treat single

Coronary angiogram

vessel or two vessel disease, but few randomised controlled trials

showing a severe

have compared percutaneous intervention with medical

focal stenosis (arrow)

treatment. These showed that patients undergoing the

in a large oblique

marginal branch of

percutaneous procedure derived greater angina relief and took

the left circumflex

less drugs but required more subsequent procedures and had

artery (LCx), suitable

more complications (including non-fatal myocardial infarction),

for percutaneous

with no mortality difference. Patients with few symptoms did

coronary

intervention. The left

not derive benefit. Therefore, percutaneous intervention is

anterior descending

suitable for low risk patients with one or two vessel disease and

artery (LAD) has no

poor symptom control with drugs, at a cost of a slightly higher

important disease

risk of non-fatal myocardial infarction. However, the procedure

may not be indicated if symptoms are well controlled.

Percutaneous intervention versus bypass surgery

Single vessel disease

In a meta-analysis by Pocock et al percutaneous intervention in

patients with single vessel disease resulted in mortality similar to

that found with bypass surgery (3.7% v 3.1% respectively) but a

higher rate of non-fatal myocardial infarction (10.1% v 6.1%,

P=0.04). Angina was well treated in both groups, but persistence

of symptoms was slightly higher with percutaneous

intervention. Rates of repeat revascularisation were much

higher with percutaneous intervention than bypass surgery.

Multivessel disease

Coronary angiograms of 70 year

Since comparative trials could recruit only those patients who

old woman with limiting angina.

were suitable for either revascularisation strategy, only 3-7% of

There were severe stenoses

screened patients were included. These were predominantly

(arrows) in the proximal and

“low risk” patients with two vessel disease and preserved left

middle left anterior descending

artery (LAD, top) and in the distal

ventricular function—patients in whom bypass surgery has not

right coronary artery (RCA, left).

been shown to improve survival—and thus it is unlikely that a

Because of the focal nature of

positive effect in favour of percutaneous intervention would

these lesions, percutaneous

coronary intervention was the

have been detected. The generally benign prognosis of chronic

preferred option

stable angina means that much larger trials would have been

required to show significant differences in mortality.

A meta-analysis of data available to the end of 2000

revealed similar rates of death and myocardial infarction with

both procedures, but repeat revascularisation rates were higher

with percutaneous intervention. The prevalence of appreciable

angina was greater with percutaneous intervention at one year,

but this difference disappeared at three years.

The nature of percutaneous coronary intervention has

changed considerably over the past 10 years, with important

developments including stenting and improved antiplatelet

drugs. The integrated use of these treatments clearly improves

outcomes, but almost all of the revascularisation trials predate

these developments.

A more recent trial comparing percutaneous intervention

and stenting with bypass surgery in multivessel disease

confirmed similar rates of death, myocardial infarction, and

stroke at one year, with much lower rates of repeat

revascularisation after percutaneous intervention compared

Coronary angiograms of a

69 year old man with

with earlier trials. There was also a cost benefit of nearly $3000

limiting angina and

(£1875) per patient associated with percutaneous intervention

exertional breathlessness.

at 12 months. The recent introduction of drug eluting (coated)

There was severe proximal

stents, which seem to reduce substantially the problem of

disease (arrows) of the left

anterior descending (LAD)

restenosis, is likely to extend the use of percutaneous

and left circumflex arteries

intervention in multivessel disease over the next few years.

(LCx) (top) and occlusion of

the right coronary artery

(RCA, left). The patient was

Diabetes

referred for coronary artery

Bypass surgery confers a survival advantage in symptomatic

bypass surgery on prognostic

diabetic patients with multivessel disease The BARI trial

and symptomatic grounds

Chronic stable angina: treatment options

revealed a significant difference in five year mortality (21% with

Names of trials

percutaneous intervention v 6% with bypass surgery). Similar

x BARI—Bypass angioplasty revascularisation investigation

trends have been found in other large trials. However, the

x SIRIUS—Sirolimus-coated velocity stent in treatment of patients

recent RAVEL and SIRIUS studies, in which the sirolimus

with de novo coronary artery lesions trial

eluting Cypher stent was compared with the same stent

x RAVEL—Randomised study with the sirolimus-eluting velocity

uncoated, showed a remarkable reduction in restenosis rates

balloon-expandable stent in the treatment of patients with de novo

within the stented segments in diabetic patients (0% v 42% and

native coronary artery lesions

18% v 51% respectively). Ongoing trials will investigate this

issue further.

Emerging treatment options for refractory angina

Other study data

x Drugs—Analgesics, statins, angiotensin converting enzyme

Large registries of outcomes in patients undergoing

inhibitors, antiplatelet drugs

revascularisation have the advantage of including all patients

x Neurostimulation—Interruption or modification of afferent

rather than the highly selected groups included in randomised

nociceptive signals: transcutaneous electric nerve stimulation

trials. The registry data seem to agree with those from

(TENS), spinal cord stimulation (SCS)

randomised trials: patients with more extensive disease fare

x Enhanced external counterpulsation—Non-invasive pneumatic leg

better with bypass surgery, whereas percutaneous intervention

compression, improving coronary perfusion and decreasing left

ventricular afterload

is preferable in focal coronary artery disease.

x Laser revascularisation—Small myocardial channels created by laser

An unusual observation is that patients screened and

beams: transmyocardial laser revascularisation (TMLR),

considered suitable for inclusion in a trial fared slightly better if

percutaneous transmyocardial laser revascularisation (PTMLR)

they refused to participate than did those who enrolled. The

x Therapeutic angiogenesis—Cytokines, vascular endothelial growth

heterogeneous nature of coronary disease means that certain

factor, and fibroblast growth factor injected into ischaemic

patient subsets will probably benefit more from one treatment

myocardium, or adenoviral vector for gene transport to promote

than another. The better outcome in the patients who were

neovascularisation

x Percutaneous in situ coronary venous arterialisation (PICVA)—Flow

suitable but not randomised may indicate that cardiologists and

redirection from diseased coronary artery into adjacent coronary

surgeons recognise which patients will benefit more from a

vein, causing arterialisation of the vein and retroperfusion into

particular strategy—subtleties that are lost in the randomisation

ischaemic myocardium

process of controlled trials.

x Percutaneous in situ coronary artery bypass (PICAB)—Flow redirection

from diseased artery into adjacent coronary vein and then rerouted

back into the artery after the lesion

Refractory coronary artery disease

x Heart transplantation—May be considered when all alternative

treatments have failed

Increasing numbers of patients with coronary artery disease

have angina that is unresponsive to both maximal drug

treatment and revascularisation techniques. Many will have

Further reading

already undergone multiple percutaneous interventions or

x Yusuf S, Zucker D, Peduzzi P, Fisher LD, Takaro T, Kennedy JW, et al.

bypass surgery procedures, or have diffuse and distal coronary

Effect of coronary artery bypass graft surgery on survival; overview

artery disease. In addition to functional limitations, their

of 10-year results from randomised trials by the Coronary Artery

prognosis may be poor because of impaired ventricular

Bypass Graft Surgery Trialists Collaboration. Lancet 1994; 344:

function. Emerging treatments may provide alternative

563-70

symptomatic improvement for some patients. There is also

x Pocock SJ, Henderson RA, Rickards AF, Hampton JR, King SB 3rd,

Hamm CW, et al. Meta-analysis of randomised trials comparing

renewed interest in the potential anti-ischaemic effects of

coronary angioplasty with bypass surgery. Lancet 1995;345:1184-9

angiotensin converting enzyme inhibitors and the plaque

x Raco DL, Yusuf S. Overview of randomised trials of percutaneous

stabilising properties of statins.

coronary intervention: comparison with medical and surgical

therapy for chronic coronary artery disease. In: Grech ED,

The picture showing three completed coronary artery bypass grafts and

Ramsdale DR, eds. Practical interventional cardiology. 2nd ed.

the pictures of a 10 year old diseased venous graft to the obtuse marginal

London: Martin Dunitz, 2002:263-77

artery were provided by G Singh, consultant cardiothoracic surgeon,

x Serruys PW, Unger F, Sousa JE, Jatene A, Bonnier HJ, Schonberger

Heath Sciences Centre, Winnipeg, E Pascoe, consultant cardiothoracic

JP, et al for the Arterial Revascularisation Therapies Study (ARTS)

surgeon, St Boniface Hospital, Winnipeg, and J Scatliff, consultant

Group. Comparison of coronary-artery bypass surgery and stenting

anaesthetist, St Boniface Hospital. The picture of the FilterWire EX distal

for multivessel disease. N Engl J Med 2001;344:1117-24

embolisation protection device was provided by Boston Scientific

x Kim MC, Kini A, Sharma SK. Refractory angina pectoris.

Corporation, Minneapolis, USA.

Mechanisms and therapeutic options. J Am Coll Cardiol 2002;39:

923-34

Competing interests: None declared.

x Morice M-C, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, Perin

M, et al. A randomized comparison of a sirolimus-eluting stent with

a standard stent for coronary revascularization. N Engl J Med

2002;346:1773-80

x Scottish Intercollegiate Guidelines Network. Coronary

revascularisation in the management of stable angina pectoris.

Edinburgh: SIGN, 1998 (SIGN Publication No 32)

Acute coronary syndrome: unstable angina and

non-ST segment elevation myocardial infarction

Ever D Grech, David R Ramsdale

The term acute coronary syndrome refers to a range of acute

myocardial ischaemic states. It encompasses unstable angina,

Plaque disruption or erosion

non-ST segment elevation myocardial infarction (ST segment

elevation generally absent), and ST segment elevation infarction

Thrombus formation with or without embolisation

(persistent ST segment elevation usually present). This article

will focus on the role of percutaneous coronary intervention in

Acute cardiac ischaemia

the management of unstable angina and non-ST segment

elevation myocardial infarction; the next article will address the

role of percutaneous intervention in ST segment elevation

No ST segment elevation

ST segment elevation

infarction.

Although there is no universally accepted definition of

Markers of myocardial

Elevated markers of

unstable angina, it has been described as a clinical syndrome

necrosis not elevated

myocardial necrosis

between stable angina and acute myocardial infarction. This

broad definition encompasses many patients presenting with

Non-ST segment elevation

ST segment elevation

varying histories and reflects the complex pathophysiological

Unstable

myocardial infarction

mechanisms operating at different times and with different

angina

(Q waves usually absent)

(Q waves usually present)

outcomes. Three main presentations have been described—

angina at rest, new onset angina, and increasing angina.

Acute coronary syndromes

Spectrum of acute coronary syndromes according to electrocardiographic

Pathogenesis

and biochemical markers of myocardial necrosis (troponin T, troponin I, and

creatine kinase MB), in patients presenting with acute cardiac chest pain

The process central to the initiation of an acute coronary

syndrome is disruption of an atheromatous plaque. Fissuring or

rupture of these plaques—and consequent exposure of core

Three main presentations of unstable angina

constituents such as lipid, smooth muscle, and foam cells—leads

x Angina at rest—Also prolonged, usually > 20 minutes

to the local generation of thrombin and deposition of fibrin.

x Angina of new onset—At least CCS class III in severity

This in turn promotes platelet aggregation and adhesion and

x Angina increasing—Previously diagnosed angina that has become

the formation of intracoronary thrombus.

more frequent, longer in duration, or lower in threshold (change in

Unstable angina and non-ST segment elevation myocardial

severity by >1 CCS class to at least CCS class III)

infarction are generally associated with white, platelet-rich, and

CCS=Canadian Cardiovascular Society

only partially occlusive thrombus. Microthrombi can detach and

embolise downstream, causing myocardial ischaemia and

infarction. In contrast, ST segment elevation (or Q wave)

myocardial infarction has red, fibrin-rich, and more stable

Platelet-rich thrombus

occlusive thrombus.

Activated platelets

Key

Epidemiology

Collagen

Intima

Dividing smooth

Unstable angina and non-ST segment elevation myocardial

muscle cell

infarction account for about 2.5 million hospital admissions

Lumen

Oxidised low

Media

density lipoprotein

worldwide and are a major cause of mortality and morbidity in

Lysosomes

Western countries. The prognosis is substantially worse than for

chronic stable angina. In-hospital death and re-infarction affect

Adventitia

5-10%. Despite optimal treatment with anti-ischaemic and

antithrombotic drugs, death and recurrent myocardial

infarction occur in another 5-10% of patients in the month after

Diagram of an unstable plaque with superimposed luminal thrombus

an acute episode. Several studies indicate that these patients

may have a higher long term risk of death and myocardial

infarction than do patients with ST segment elevation.

Diagnosis

Distal embolisation of a

platelet-rich thrombus causing

Unstable angina and non-ST segment elevation myocardial

occlusion of intramyocardial

infarction are closely related conditions with clinical

arteriole (arrow). Such an

event may result in

presentations that may be indistinguishable. Their distinction

micro-infarction and elevation

depends on whether the ischaemia is severe enough to cause

of markers of myocardial

myocardial damage and the release of detectable quantities of

necrosis

Acute coronary syndrome: unstable angina and non-ST segment elevation myocardial infarction

markers of myocyte necrosis. Cardiac troponin I and T are the

preferred markers as they are more specific and reliable than

aVR

creatine kinase or its isoenzyme creatine kinase MB.

An electrocardiogram may be normal or show minor

non{specific changes, ST segment depression, T wave inversion,

bundle branch block, or transient ST segment elevation that

aVL

resolves spontaneously or after nitrate is given. Physical

examination may exclude important differential diagnoses such

as pleuritis, pericarditis, or pneumothorax, as well as revealing

evidence of ventricular failure and haemodynamic instability.

III

aVF

Management

Management has evolved considerably over the past decade. As

platelet aggregation and thrombus formation play a key role in

acute coronary syndrome, recent advances in treatment (such as

the glycoprotein IIb/IIIa inhibitors, low molecular weight

heparin, and clopidogrel) and the safer and more widespread

use of percutaneous coronary intervention have raised

questions about optimal management.

As patients with unstable angina or non-ST segment

elevation myocardial infarction represent a heterogeneous

group with a wide spectrum of clinical outcomes, tailoring

treatment to match risk not only ensures that patients who will

benefit the most receive appropriate treatment, but also avoids

potentially hazardous treatment in those with a good prognosis.

Therefore, an accurate diagnosis and estimation of the risk of

adverse outcome are prerequisites to selecting the most

Electrocardiogram of a 48 year old woman with unstable angina (top). Note

appropriate treatment. This should begin in the emergency

the acute ischaemic changes in leads V1 to V5 (arrows). Coronary

department and continue throughout the hospital admission.

angiography revealed a severe mid-left anterior descending coronary artery

stenosis (arrow, bottom left), which was successfully stented (bottom right)

Ideally, all patients should be assessed by a cardiologist on the

day of presentation.

Medical treatment

Medical treatment includes bed rest, oxygen, opiate analgesics

to relieve pain, and anti-ischaemic and antithrombotic drugs.

These should be started at once on admission and continued in

those with probable or confirmed unstable angina or non-ST

segment elevation myocardial infarction. Anti-ischaemic drugs

include intravenous, oral, or buccal nitroglycerin, blockers,

and calcium antagonists. Antithrombotic drugs include aspirin,

clopidogrel, intravenous unfractionated heparin or low

molecular weight heparin, and glycoprotein IIb/IIIa inhibitors.

Right coronary artery

angiogram in patient with

Conservative versus early invasive strategy

non-ST segment elevation

“Conservative” treatment involves intensive medical

myocardial infarction (top

management, followed by risk stratification by non-invasive

left), showing hazy

means (usually by stress testing) to identify patients who may

appearance of intraluminal

thrombus overlying a severe

need coronary angiography. This approach is based on the

stenosis (arrow). Abciximab

results of two randomised trials (TIMI IIIB and VANQWISH),

was given before direct

which showed no improvement in outcome when an “early

stenting (top right), with

invasive” strategy was used routinely, compared with a selective

good angiographic outcome

(bottom)

approach.

These findings generated much controversy and have been

Names of trials

superseded by more recent randomised trials (FRISC II,

x TIMI IIIB—Thrombolysis in myocardial infarction IIIB

TACTICS-TIMI 18, and RITA 3), which have taken advantage of

x VANQWISH—Veterans affairs non-Q-wave infarction strategies in

the benefits of glycoprotein IIb/IIIa inhibitors and stents. All

hospital

three studies showed that an early invasive strategy

x GUSTO IV ACS—Global use of strategies to open occluded

(percutaneous coronary intervention or coronary artery bypass

arteries-IV in acute coronary syndromes

surgery) produced a better outcome than non-invasive

x RITA 3—Randomised intervention treatment of angina

x FRISC II—Fast revascularisation during instability in coronary

management. TACTICS-TIMI 18 also showed that the benefit

artery disease

of early invasive treatment was greatest in higher risk patients

x TACTICS-TIMI 18—Treat angina with Aggrastat and determine cost

with raised plasma concentrations of troponin T, whereas the

of therapy with an invasive or conservative strategy-thrombolysis in

outcomes for lower risk patients were similar with early invasive

myocardial infarction

and non-invasive management.

ABC of Interventional Cardiology

Identifying higher risk patients

The seven variables for the TIMI risk score

Identifying patients at higher risk of death, myocardial infarction,

x Age >65 years

and recurrent ischaemia allows aggressive antithrombotic

x >3 risk factors for coronary artery disease

treatment and early coronary angiography to be targeted to those

x >50% coronary stenosis on angiography

who will benefit. The initial diagnosis is made on the basis of a

x ST segment change > 0.5 mm

patient’s history, electrocardiography, and the presence of

x >2 anginal episodes in 24 hours before presentation

elevated plasma concentrations of biochemical markers. The

x Elevated serum concentration of cardiac markers

same information is used to assess the risk of an adverse

x Use of aspirin in 7 days before presentation

outcome. It should be emphasised that risk assessment is a

continuous process.

Low risk

Higher risk

The TIMI risk score

Attempts have been made to formulate clinical factors into a

user friendly model. Notably, Antman and colleagues identified

seven independent prognostic risk factors for early death and

myocardial infarction. Assigning a value of 1 for each risk factor

present provides a simple scoring system for estimating risk, the

TIMI risk score. It has the advantage of being easy to calculate

and has broad applicability in the early assessment of patients.

0 or 1

6 or 7

Applying this score to the results in the TACTICS-TIMI 18

No of TIMI risk factors present

study indicated that patients with a TIMI risk score of >3

benefited significantly from an early invasive strategy, whereas

Rates of death from all causes and non-fatal myocardial infarction at 14

those with a score of <2 did not. Therefore, those with an initial

days, by TIMI risk score. Note sharp rate increase when score >3

TIMI score of >3 should be considered for early angiography

(ideally within 24 hours), with a view to revascularisation by

Unstable angina or non-ST segment elevation myocardial infarction

percutaneous intervention or bypass surgery. In addition, any

patient with an elevated plasma concentration of troponin

TIMI risk assessment on presentation

marker, ST segment changes, or haemodynamic instability

(aspirin, clopidogrel, heparin, nitrates, β blockers)

should also undergo early angiography.

Low risk

Higher risk

Conclusion

(TIMI risk score 0-2, negative troponin test)

(TIMI risk score >3, positive

troponin test, dynamic ST changes,

The diagnosis of unstable angina or non-ST segment elevation

or haemodynamically unstable)

myocardial infarction demands urgent hospital admission and

Conservative management

coronary monitoring. A clinical history and examination, 12

Invasive management

lead electrocardiography, and measurement of troponin

Stress test

concentration are the essential diagnostic tools. Bed rest,

Possible glycoprotein IIb/IIIa inhibitor

aspirin, clopidogrel, heparin, antianginal drugs, and opiate

analgesics are the mainstay of initial treatment.

Negative

Positive

Coronary angiography

Early risk stratification will help identify high risk patients,

who may require early treatment with glycoprotein IIb/IIIa

Discharge

inhibitors, angiography, and coronary revascularisation. Those

Percutaneous coronary

Coronary

Medical

deemed suitable for percutaneous intervention should receive a

intervention plus

artery bypass

treatment

glycoprotein IIb/IIIa inhibitor and stenting as appropriate.

glycoprotein IIb/IIIa inhibitor

surgery

There seems to be little merit in prolonged stabilisation of

patients before percutaneous intervention, and an early invasive

Simplified management pathway for patients with unstable angina or

strategy is generally preferable to a conservative one except for

non-ST segment elevation myocardial infarction

patients at low risk of further cardiac events. This approach will

shorten hospital stays, improve acute and long term outcomes,

Further reading

and reduce the need for subsequent intervention.

x Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD,

In the longer term, aggressive modification of risk factors is

Hochman JS, et al. ACC/AHA 2002 guideline update for the

warranted. Smoking should be strongly discouraged, and statins

management of patients with unstable angina and non-ST-segment

should be used to lower blood lipid levels. Long term treatment

elevation myocardial infarction: a report of the American College

with aspirin, clopidogrel (especially after stenting), blockers,

of Cardiology/American Heart Association task force on practice

guidelines. J Am Coll Cardiol 2002;40:1366-74

angiotensin converting enzyme inhibitors, and antihypertensive

x Bertrand ME, Simoons ML, Fox KA, Wallentin LC, Hamm CW,

drugs should also be considered. Anti-ischaemic drugs may be

McFadden E, et al. Management of acute coronary syndromes:

stopped when ischaemia provocation tests are negative.

acute coronary syndromes without persistent ST segment elevation.

Recommendations of the Task Force of the European Society of

The picture of a microthrombus occluding an intramyocardial arteriole

Cardiology. Eur Heart J 2000;21:1406-32

was provided by K MacDonald, consultant histopathologist, St Boniface

x Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T,

Hospital, Winnipeg.

Papuchis G, et al. The TIMI risk score for unstable angina/non-ST

elevation MI: a method for prognostication and therapeutic

Competing interests: None declared.

decision making. JAMA 2000;284:835-42

x Ramsdale DR, Grech ED. Percutaneous coronary intervention

unstable angina and non-Q-wave myocardial infarction. In: Grech

ED, Ramsdale DR, eds. Practical interventional cardiology. 2nd ed.

London: Martin Dunitz, 2002:165-87

Acute coronary syndrome: ST segment elevation

myocardial infarction

Ever D Grech, David R Ramsdale

Acute ST segment elevation myocardial infarction usually

occurs when thrombus forms on a ruptured atheromatous

plaque and occludes an epicardial coronary artery. Patient

survival depends on several factors, the most important being

restoration of brisk antegrade coronary flow, the time taken to

achieve this, and the sustained patency of the affected artery.

Recanalisation

There are two main methods of re-opening an occluded artery:

Histological appearance of a

administering a thrombolytic agent or primary percutaneous

ruptured atheromatous plaque

transluminal coronary angioplasty.

(bottom arrow) and occlusive

Although thrombolysis is the commonest form of treatment

thrombus (top arrow) resulting

in acute myocardial infarction

for acute myocardial infarction, it has important limitations: a

rate of recanalisation (restoring normal flow) in 90 minutes of

only 55% with streptokinase or 60% with accelerated alteplase;

Acute ST segment elevation

a 5-15% risk of early or late reocclusion leading to acute

myocardial infarction

myocardial infarction, worsening ventricular function, or death;

a 1-2% risk of intracranial haemorrhage, with 40% mortality;

and 15-20% of patients with a contraindication to thrombolysis.

Thrombolytic treatment

Primary angioplasty

Primary angioplasty (also called direct angioplasty)

mechanically disrupts the occlusive thrombus and compresses

the underlying stenosis, rapidly restoring blood flow. It offers a

Infarct artery recanalised,

Infarct artery not recanalised

but significant residual stenosis

superior alternative to thrombolysis in the immediate treatment

of ST segment elevation myocardial infarction. This differs from

Rescue angioplasty

Adjunctive angioplasty

sequential angioplasty, when angioplasty is performed after

(1-2 hours after failed thrombolysis)

Deferred angioplasty

thrombolysis. After early trials of thrombolytic drugs, there was

Elective angioplasty (if continued ischaemia)

(1-7 days after thrombolysis)

much interest in “adjunctive” angioplasty (angioplasty used as a

supplement to successful thrombolysis) as this was expected to

Methods of recanalisation for acute myocardial infarction

reduce recurrent ischaemia and re-infarction. Later studies,

however, not only failed to show any advantage, but found

higher rates of major haemorrhage and emergency bypass

Comparison of methods of recanalisation

surgery. In contrast, “rescue” (also known as “salvage”)

Rescue

Primary

angioplasty, which is performed if thrombolysis fails to restore

Thrombolysis angioplasty angioplasty

patency after one to two hours, may confer benefit.

Time from admission

1-3 hours

Time to start of

20-60

to recanalisation

after start of

thrombolysis

minutes

thrombolysis

plus 2 hours

Pros and cons of primary angioplasty

Recanalisation with

55-60%

85%

95%

brisk antegrade flow

Advantages

Systemic fibrinolysis

+++

−

Large randomised studies have shown that thrombolysis

Staff and catheter

−

+++

significantly reduces mortality compared with placebo, and this

laboratory “burden”

effect is maintained long term. Primary angioplasty confers

Cost of procedure

+++

Mortality

Cerebrovascular events

Re-infarction

P<0.0001

P=0.0004

Effects of treatment with placebo, thrombolytic

P=0.0002

drugs, or primary percutaneous coronary

intervention (PCI) on mortality, incidence of

P<0.0001

cerebrovascular events, and incidence of

non-fatal re-infarction after acute myocardial

infarction in randomised studies. Of the 1%

incidence of cerebrovascular events in patients

undergoing primary percutaneous intervention,

9 studies

23 studies

9 studies

23 studies

only 0.05% were haemorrhagic. In contrast

(n=58 600)*

(n=7437)✝

(n=58 600)*

(n=6271)✝

(n=6497)✝

patients receiving thrombolytic drugs had a 1%

* FTT Collaborative Group, Lancet 1994;343:311-22

Controls

Thrombolytic

PCI

incidence of haemorrhagic cerebrovascular

✝ Keeley et al, Lancet 2003;361:13-20

events (P<0.0001) and an overall 2% incidence

of cerebrovascular events (P=0.0004)

ABC of Interventional Cardiology

extra benefits in terms of substantial reductions in rates of

death, cerebrovascular events, and re-infarction.

The information provided by immediate coronary

Severe distal left main

angiography is valuable in determining subsequent

stem stenosis (arrow 1)

management. Patients with severe three vessel disease, severe

and partially occluded

left main coronary artery stenosis, or occluded vessels

mid-left anterior

descending artery due to

unsuitable for angioplasty can be referred for bypass surgery.

thrombus (arrow 2). In

Conversely, patients whose arteries are found to have

view of the severity of the

spontaneously recanalised or who have an insignificant infarct

lesion salvage angioplasty

related artery may be selected for medical treatment, and thus

was contraindicated. An

intra-aortic balloon

avoid unnecessary thrombolytic treatment.

pump was used to

augment blood pressure

Disadvantages

and coronary flow before

successful bypass surgery

The morbidity and mortality associated with primary

angioplasty is operator dependent, varying with the skill and

experience of the interventionist, and it should be considered

only for patients presenting early ( < 12 hours after acute

myocardial infarction).

Pros and cons of primary angioplasty* compared with

Procedural complications are more common than with

thrombolysis

elective angioplasty for chronic angina, and, even though it is

Advantages

usual to deal only with the occluded vessel, procedures may be

x High patency rates ( > 90%) with brisk, antegrade flow

prolonged. Ventricular arrhythmias are not unusual on

x Lower mortality

x Better residual left ventricular function

recanalisation, but these generally occur while the patient is still

x More rapid electrocardiographic normalisation

in the catheterisation laboratory and can be promptly treated by

x Less recurrent ischaemia (angina, reinfarction, exercise induced

intravenous drugs or electrical cardioversion. Right coronary

ischaemia)

artery procedures are often associated with sinus arrest,

x No systemic fibrinolysis, therefore bleeding problems avoided

atrioventricular block, idioventricular rhythm, and severe

x Improved risk stratification by angiography with identification of

hypotension. Up to 5% of patients initially referred for primary

patients suitable for coronary artery bypass surgery

angioplasty require urgent coronary artery bypass surgery, so

Disadvantages

surgical backup is essential if risks are to be minimised.

x Higher procedural cost than streptokinase or alteplase (although

There are logistical hurdles in delivering a full 24 hour

long term costs lower)

x Can be performed only when cardiac catheterisation facilities and

service. Primary angioplasty can be performed only when

experienced staff available

adequate facilities and experienced staff are available. The time

x Recanalisation more rapid than thrombolysis only if 24 hour

from admission to recanalisation should be less than 60 minutes,

on-call team available

which may not be possible if staff are on call from home.

x Risks and complications of cardiac catheterisation and

However, recent evidence suggests that, even with longer delays,

percutaneous intervention

primary angioplasty may still be superior to thrombolysis.

x Reperfusion arrhythmias probably more common because of more

rapid recanalisation

A catheterisation laboratory requires large initial capital

*With or without stenting

expenditure and has substantial running costs. However, in an

existing, fully supported laboratory operating at high volume,

primary angioplasty is at least as cost effective as thrombolysis.

Primary angioplasty and coronary

stents

Although early randomised studies of primary angioplasty

showed its clinical effectiveness, outcomes were marred by high

rates of recurrent ischaemia (10-15% of patients) and early

reinfarction of the affected artery (up to 5%). Consequently,

haemodynamic and arrhythmic complications arose, with the

need for repeat catheterisation and revascularisation, prolonged

hospital stay, and increased costs. Furthermore, restenosis rates

in the first six months remained disappointingly high (25-45%),

and a fifth of patients required revascularisation.

Although stenting the lesion seemed an attractive answer, it

was initially thought that deploying a stent in the presence of

thrombus over a ruptured plaque would provoke further

thrombosis. However, improvements in stent deployment and

advances in adjunctive pharmacotherapy have led to greater

technical success. Recent studies comparing primary stenting

Anterior myocardial infarction of 4 hours’ duration and severe

with balloon angioplasty alone have shown that stented patients

hypotension, caused by a totally occluded proximal left anterior

descending artery (arrow, top left). After treatment with abciximab, a stent

have significantly less recurrent ischaemia, reinfarction, and

was positioned. Initial inflation showed “waisting” of the balloon (top

subsequent need for further angioplasty. Economic analysis has

right), due to fibrous lesion resistance, which resolved on higher inflation

shown that, as expected, the initial costs were higher but were

(bottom left). Successful recanalisation resulted in brisk flow (bottom right),

offset by lower follow up costs after a year.

and the 15 minute procedure completely resolved the patient’s chest pain

Acute coronary syndrome: ST segment elevation myocardial infarction

However, one study (Stent-PAMI) showed that stenting was

associated with a small (but significant) decrease in normal

coronary flow and a trend towards increased six and 12 month

mortality. This led some to examine the use of adjunctive

glycoprotein IIb/IIIa inhibitors as a solution.

Stenting and glycoprotein IIb/IIIa inhibitors

The first study (CADILLAC) to examine the potential benefits

of glycoprotein IIb/IIIa inhibitors combined with stenting

showed that abciximab significantly reduced early recurrent

ischaemia and reocclusion due to thrombus formation. There

was no additional effect on restenosis or late outcomes

compared with stenting alone. The slightly reduced rate of

normal coronary flow that had been seen in other studies was

again confirmed, but did not translate into a significant effect

on mortality.

Another study (ADMIRAL) examined the potential benefit

of abciximab when given before (rather than during) primary

stenting. Both at 30 days’ and six months’ follow up, abciximab

significantly reduced the composite rate of reinfarction, the

need for further revascularisation, and mortality. In addition,

abciximab significantly improved coronary flow rates

immediately after stenting, which persisted up to six months

with a significant improvement in residual left ventricular

function.

Inferior myocardial infarction of 2.5 hours’ duration caused by a totally

occluded middle right coronary artery (arrow, top left). A guide wire passed

through the fresh thrombus produced slow distal filling (top right).

Future of primary angioplasty

Deployment of a stent (bottom left) resulted in brisk antegrade flow, a good

angiographic result, and relief of chest pain (bottom right). A temporary

Primary stenting is not only safe but, by reducing recurrent

pacemaker electrode was used to counter a reperfusion junctional

bradycardia. Note resolution in ST segments compared with top angiograms

ischaemic events, also confers advantages over balloon

angioplasty alone. Abciximab treatment seems to further

improve flow characteristics, prevents distal

thrombo{embolisation, and reduces the need for repeat

Names of trials

angioplasty. A strategy of primary stenting in association with

x CADILLAC—Controlled abciximab and device

abciximab seems to be the current gold standard of care for

investigation to lower late angioplasty

patients with acute myocardial infarction. Future studies will

complications

examine the potential benefit of other glycoprotein IIb/IIIa

x ADMIRAL—Abciximab before direct angioplasty

and stenting in myocardial infarction regarding

inhibitors. The question of whether on-site surgical cover is still

acute and long-term follow-up

essential for infarct intervention continues to be debated.

x Stent-PAMI—Stent primary angioplasty in

myocardial infarction

Further reading

x Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group.

x Grines CL, Cox DA, Stone GW, Garcia E, Mattos LA,

Indications for fibrinolytic therapy in suspected acute myocardial

Giambartolomei A, et al, for the Stent Primary Angioplasty in

infarction: collaborative overview of early mortality and major

Myocardial Infarction Study Group. Coronary angioplasty with or

morbidity results from all randomised trials of more than 1000

without stent implantation for acute myocardial infarction. N Engl J

patients. Lancet 1994;343:311-22

Med 1999;341: 1949-56

x Keeley EC, Boura JA, Grines CL. Primary angioplasty versus

x Montalescot G, Barragan P, Wittenberg O, Ecollan P, Elhadad S,

intravenous thrombolytic therapy for acute myocardial infarction: a

Villain P, et al. Platelet glycoprotein IIb/IIIa inhibition with

quantitative review of 23 randomised trials. Lancet 2003;361:13-20

coronary stenting for acute myocardial infarction. N Engl J Med

x De Boer MJ, Zijlstra F. Coronary angioplasty in acute myocardial

2001;344:1895-903

infarction. In: Grech ED, Ramsdale DR, eds. Practical interventional

x Stone GW, Grines CL, Cox DA, Garcia E, Tcheng JE, Griffin JJ, et al.

cardiology. 2nd ed. London: Martin Dunitz, 2002:189-206

Comparison of angioplasty with stenting, with or without

x Lieu TA, Gurley RJ, Lundstrom RJ, Ray GT, Fireman BH, Weinstein

abciximab, in acute myocardial infarction. N Engl J Med

MC, et al. Projected cost-effectiveness of primary angioplasty for

2002;346:957-66

acute myocardial infarction. J Am Coll Cardiol 1997;30:1741-50

Percutaneous coronary intervention:

cardiogenic shock

John Ducas, Ever D Grech

Cardiogenic shock is the commonest cause of death after acute

myocardial infarction. It occurs in 7% of patients with ST

segment elevation myocardial infarction and 3% with non-ST

segment elevation myocardial infarction.

Cardiogenic shock is a progressive state of hypotension

(systolic blood pressure < 90 mm Hg) lasting at least

30 minutes, despite adequate preload and heart rate, which

leads to systemic hypoperfusion. It is usually caused by left

ventricular systolic dysfunction. A patient requiring drug or

mechanical support to maintain a systolic blood pressure over

90 mm Hg can also be considered as manifesting cardiogenic

shock. As cardiac output and blood pressure fall, there is an

increase in sympathetic tone, with subsequent cardiac and

A 65 year old man with a

3-4 hour history of acute

systemic effects—such as altered mental state, cold extremities,

anterior myocardial

peripheral cyanosis, and urine output < 30 ml/hour.

infarction had cardiogenic

shock and acute

pulmonary oedema,

Effects of cardiogenic shock

requiring mechanical

ventilation and inotropic

Cardiac effects

support. He underwent

emergency angiography

In an attempt to maintain cardiac output, the remaining

(top), which showed a

non{ischaemic myocardium becomes hypercontractile, and its

totally occluded proximal

oxygen consumption increases. The effectiveness of this

left anterior descending

response depends on the extent of current and previous left

artery (arrow). A soft

tipped guidewire was

ventricular damage, the severity of coexisting coronary artery

passed across the

disease, and the presence of other cardiac pathology such as

occlusive thrombotic

valve disease.

lesion, which was

Three possible outcomes may occur:

successfully stented

(middle). Restoration of

x Compensation—which restores normal blood pressure and

brisk antegrade flow down

myocardial perfusion pressure

this artery (bottom)

x Partial compensation—which results in a pre-shock state with

followed by insertion of

mildly depressed cardiac output and blood pressure, as well as

an intra-aortic balloon

pump markedly improved

an elevated heart rate and left ventricular filling pressure

blood pressure and organ

x Shock—which develops rapidly and leads to profound

perfusion. The next day

hypotension and worsening global myocardial ischaemia.

he was extubated and

Without immediate reperfusion, patients in this group have

weaned off all inotropic

drugs, and the intra-aortic

little potential for myocardial salvage or survival.

balloon pump was

removed

Systemic effects

The falling blood pressure increases catecholamine levels,

leading to systemic arterial and venous constriction. In time,

Fall in cardiac output

activation of the renin-aldosterone-angiotensin axis causes

further vasoconstriction, with subsequent sodium and water

Increased sympathetic tone

retention. These responses have the effect of increasing left

ventricular filling pressure and volume. Although this partly

Non-ischaemic zone hypercontractility

compensates for the decline in left ventricular function, a high

Increased myocardial oxygen demand

left ventricular filling pressure leads to pulmonary oedema,

which impairs gas exchange. The ensuing respiratory acidosis

Extent of:

exacerbates cardiac ischaemia, left ventricular dysfunction, and

• Left ventricular damage?

intravascular thrombosis.

• Associated coronary artery disease?

• Other cardiac disease?

Time course of cardiogenic shock

The onset of cardiogenic shock is variable. In the GUSTO-I

Compensation

Pre-shock

Shock

study, of patients with acute myocardial infarction, 7%

(Restoration of normal

(Increased heart rate,

(Impaired left ventricular

developed cardiogenic shock—11% on admission and 89% in

perfusion pressure)

increased left ventricular

perfusion, worsening

the subsequent two weeks. Almost all of those who developed

end diastolic pressure)

left ventricular function)

cardiogenic shock did so by 48 hours after the onset of

symptoms, and their overall 30 day mortality was 57%,

Cardiac compensatory response to falling cardiac output after acute

compared with an overall study group mortality of just 7%.

myocardial infarction.

Percutaneous coronary intervention: cardiogenic shock

Differential diagnosis

Hallmarks of right ventricular infarction

x Rising jugular venous pressure, Kassmaul sign, pulsus paradoxus

Hypotension can complicate acute myocardial infarction in

x Low output with little pulmonary congestion

other settings.

x Right atrial pressure > 10 mm Hg and > 80% of pulmonary

capillary wedge pressure

Right coronary artery occlusion

x Right atrial prominent Y descent

An occluded right coronary artery (which usually supplies a

x Right ventricle shows dip and plateau pattern of pressure

smaller proportion of the left ventricular muscle than the left

x Profound hypoxia with right to left shunt through a patent foramen

coronary artery) may lead to hypotension in various ways:

ovale

cardiac output can fall due to vagally mediated reflex

x ST segment elevation in lead V

venodilatation and bradycardia, and right ventricular dilation

may displace the intraventricular septum towards the left

Main indications and contraindications for intra-aortic

ventricular cavity, preventing proper filling.

balloon pump counterpulsation

In addition, the right coronary artery occasionally supplies a

Indications

sizeable portion of left ventricular myocardium. In this case

x Cardiogenic shock

x Enhancement of coronary flow

right ventricular myocardial infarction produces a unique set of

x Unstable and refractory angina

after succesful recanalisation by

physical findings, haemodynamic characteristics, and ST

x Cardiac support for high risk

percutaneous intervention

segment elevation in lead V₄R. When this occurs aggressive

percutaneous intervention

x Ventricular septal defect and

treatment is indicated as the mortality exceeds 30%.

x Hypoperfusion after coronary

papillary muscle rupture after

artery bypass graft surgery

myocardial infarction

x Septic shock

x Intractable ischaemic

Ventricular septal defect, mitral regurgitation, or myocardial

ventricular tachycardia

rupture

Contraindications

In 10% of patients with cardiogenic shock, hypotension arises

x Severe aortic regurgitation

x Severe aorto-iliac disease or

from a ventricular septal defect induced by myocardial

x Abdominal or aortic aneurysm

peripheral vascular disease

infarction or severe mitral regurgitation after papillary muscle

rupture. Such a condition should be suspected if a patient

develops a new systolic murmur, and is readily confirmed by

echocardiography—which should be urgently requested. Such

Catheter tip

patients have high mortality, and urgent referral for surgery

Central lumen

may be needed. Even with surgery, the survival rate can be low.

Myocardial rupture of the free wall may cause low cardiac

Balloon membrane

output as a result of cardiac compression due to tamponade. It

is more difficult to diagnose clinically (raised venous pressure,

pulsus paradoxus), but the presence of haemopericardium can

be readily confirmed by echocardiography. Pericardial

Catheter

aspiration often leads to rapid increase in cardiac output, and

surgery may be necessary.

Sheath seal

Suture pads

Management

The left ventricular filling volume should be optimised, and in

Y fitting

the absence of pulmonary congestion a saline fluid challenge of

Stylet wire

at least 250 ml should be administered over 10 minutes.

Adequate oxygenation is crucial, and intubation or ventilation

should be used early if gas exchange abnormalities are present.

One way valve

Ongoing hypotension induces respiratory muscle failure, and

this is prevented with mechanical ventilation. Antithrombotic

treatment (aspirin and intravenous heparin) is appropriate.

Diagram of intra-aortic balloon pump (left) and its position in the aorta (right)

Supporting systemic blood pressure

Systole: deflation

Diastole: inflation

Blood pressure support maintains perfusion of vital organs and

Decreased afterload

Augmentation of diastolic pressure

• Decreases cardiac work

• Increases coronary perfusion

slows or reverses the metabolic effects of organ hypoperfusion.

• Decreases myocardial oxygen consumption

Inotropes stimulate myocardial function and increase vascular

• Increases cardiac output

tone, allowing perfusion pressures to increase. Intra-aortic

balloon pump counterpulsation often has a dramatic effect on

systemic blood pressure. Inflation occurs in early diastole,

greatly increasing aortic diastolic pressure to levels above aortic

systolic pressure. In addition, balloon deflation during the start

of systole reduces the aortic pressure, thereby decreasing

myocardial oxygen demand and forward resistance (afterload).

Reperfusion

Although inotropic drugs and mechanical support increase

systemic blood pressure, these measures are temporary and

have no effect on long term survival unless they are combined

with coronary artery recanalisation and myocardial reperfusion.

Effects of intra-aortic balloon pump during systole and diastole

ABC of Interventional Cardiology

Thrombolysis is currently the commonest form of treatment

for myocardial infarction. However, successful fibrinolysis

probably depends on drug delivery to the clot, and as blood

Electrocardiogram

pressure falls, so reperfusion becomes less likely. One study

(GISSI) showed that, in patients with cardiogenic shock,

streptokinase conferred no benefit compared with placebo.

The GUSTO-I investigators examined data on 2200 patients

who either presented with cardiogenic shock or who developed

it after enrolment and survived for at least an hour after its

onset. Thirty day mortality was considerably less in those

Arterial

pressure

undergoing early angiography (38%) than in patients with late

or no angiography (62%). Further analysis suggested that early

A = Unassisted systolic pressure C = Unassisted aortic end diastolic pressure

angiography was independently associated with a 43%

B = Diastolic augmentation

D = Reduced aortic end diastolic pressure

reduction in 30 day mortality.

Diagram of electrocardiogram and aortic pressure wave showing

In the SHOCK trial, patients with cardiogenic shock were

timing of intra-aortic balloon pump and its effects of diastolic

treated aggressively with inotropic drugs, intra-aortic balloon

augmentation (D) and reduced aortic end diastolic pressure

pump counterpulsation, and thrombolytic drugs. Patients were

also randomised to either coronary angiography plus

percutaneous intervention or bypass surgery within six hours,

or medical stabilisation (with revascularisation only permitted

after 54 hours). Although the 30 day primary end point did not

achieve statistical significance, the death rates progressively

diverged, and by 12 months the early revascularisation group

showed a significant mortality benefit (55%) compared with the

medical stabilisation group (70%). The greatest benefit was seen

in those aged < 75 years and those treated early ( < 6 hours).

Given an absolute risk reduction of 15% at 12 months, one life

would be saved for only seven patients treated by aggressive,

early revascularisation.

Support and reperfusion: impact on survival

Aortic pressure wave recording before (left) and during (right) intra-aortic

Over the past 10 years, specific measures to improve blood

balloon pump counterpulsation in a patient with cardiogenic shock after

pressure and restore arterial perfusion have been instituted.

myocardial infarction. Note marked augmentation in diastolic pressure (arrow

A) and reduction in end diastolic pressures (arrow B). (AO=aortic pressure)

Mortality data collected since the 1970s show a significant fall

in mortality in the 1990s corresponding with increased use of

combinations of thrombolytic drugs, the intra-aortic balloon

Shock present

Shock absent

pump, and coronary angiography with revascularisation by

either percutaneous intervention or bypass surgery. Before

these measures, death rates of 80% were consistently observed.

Cardiogenic shock is the commonest cause of death in acute

myocardial infarction. Although thrombolysis can be attempted

with inotropic support or augmentation of blood pressure with

the intra-aortic balloon pump, the greatest mortality benefit is

1975

1978

1981

1984

1986

1988

1990

1991

1993

1995

1997

seen after urgent coronary angiography and revascularisation.

Year

Cardiogenic shock is a catheter laboratory emergency.

Mortality after myocardial infarction with or without cardiogenic shock (1975 to

1997). Mortality of patients in shock fell from roughly 80% to 60% in the 1990s

The diagram of patient mortality after myocardial infarction is adapted with

permission from Goldberg RJ et al, N Engl J Med 1999;340:1162-8.

Names of trials

Competing interests: None declared.

x GISSI—Gruppo Italiano per lo studio della sopravvivenza

nell’infarto miocardico

x GUSTO—global utilization of streptokinase and tissue plasminogen

activator for occluded coronary arteries

x SHOCK—should we emergently revascularize occluded coronaries

for cardiogenic shock

Further reading

x Hochman JS, Sleeper LA, Webb JG, Sanborn TA, White HD, Talley

x Golberg RJ, Samad NA, Yarzebski J, Gurwitz J, Bigelow C, Gore JM.

JD, et al. Early revascularization in acute myocardial infarction

Temporal trends in cardiogenic shock complicating acute

complicated by cardiogenic shock. N Engl J Med 1999;341:625-34

myocardial infarction. N Engl J Med 1999;340:1162-8

x Berger PB, Holmes DR Jr, Stebbins AL, Bates ER, Califf RM, Topol

x Hasdai D, Topol EJ, Califf RM, Berger PB, Holmes DR.

EJ. Impact of an aggressive invasive catheterization and

Cardiogenic shock complicating acute coronary syndromes. Lancet

revascularization strategy on mortality in patients with cardiogenic

2000;356:749-56

shock in the global utilization of streptokinase and tissue

x White HD. Cardiogenic shock: a more aggressive approach is now

plasminogen activator for occluded coronary arteries (GUSTO-I)

warranted. Eur Heart J 2000;21:1897-901

trial. Circulation 1997;96:122-7

Interventional pharmacotherapy

Roger Philipp, Ever D Grech

The dramatic increase in the use of percutaneous coronary

intervention has been possible because of advances in

Thrombin

inhibitors

Clopidogrel

adjunctive pharmacotherapy, which have greatly improved

Adhesion

Ticlopidine

safety. Percutaneous intervention inevitably causes vessel

Shear

Thrombin

stress

Adenosine

trauma, with disruption of the endothelium and atheromatous

diphosphate

Aspirin

plaque. This activates prothrombotic factors, leading to localised

Adrenaline

thrombosis; this may impair blood flow, precipitate vessel

Thromboxane A₂

occlusion, or cause distal embolisation. Coronary stents

Activation

exacerbate this problem as they are thrombogenic. For these

Platelet

reasons, drug inhibition of thrombus formation during

percutaneous coronary intervention is mandatory, although this

Serotonin

must be balanced against the risk of bleeding, both systemic and

Collagen

Glycoprotein

at the access site.

IIb/IIIa

Glycoprotein

inhibitors

IIb/IIIa

Aggregation

Fibrinogen

Coronary artery thrombosis

Platelet

Platelets are central to thrombus formation. Vessel trauma

during percutaneous intervention exposes subendothelial

collagen and von Willebrand factor, which activate platelet

Action of antiplatelet and antithrombotic agents in inhibiting arterial

surface receptors and induce the initial steps of platelet

thrombosis

activation. Further platelet activation ultimately results in

activation of platelet glycoprotein IIb/IIIa receptor—the final

common pathway for platelet aggregation.

Adjunctive pharmacology during percutaneous coronary

Vascular injury and membrane damage also trigger

intervention

coagulation by exposure of tissue factors. The resulting

Aspirin—For all clinical settings

thrombin formation further activates platelets and converts

Clopidogrel—For stenting; unstable angina or non-ST segment

fibrinogen to fibrin. The final event is the binding of fibrinogen

elevation myocardial infarction

to activated glycoprotein IIb/IIIa receptors to form a platelet

Unfractionated heparin—For all clinical settings

aggregate.

Glycoprotein IIb/IIIa receptor inhibitors

Understanding of these mechanisms has led to the

Abciximab—For elective percutaneous intervention for chronic stable

development of potent anticoagulants and antiplatelet

angina; unstable angina or non-ST segment elevation myocardial

inhibitors that can be used for percutaneous coronary

infarction (before and during percutaneous intervention); ST

segment elevation myocardial infarction (before and during

intervention. Since the early days of percutaneous transluminal

primary percutaneous intervention)

coronary angioplasty, heparin and aspirin have remained a

Eptifibatide—For elective percutaneous intervention for chronic stable

fundamental part of percutaneous coronary intervention

angina; unstable angina or non-ST segment elevation myocardial

treatment. Following the introduction of stents, ticlopidine and

infarction (before and during percutaneous intervention)

more recently clopidogrel have allowed a very low rate of stent

Tirofiban—For unstable angina or non-ST segment elevation

thrombosis. More recently, glycoprotein IIb/IIIa receptor

myocardial infarction (before and during percutaneous

antagonists have reduced procedural complications still further

intervention)

and improved the protection of the distal microcirculation,

especially in thrombus-containing lesions prevalent in acute

coronary syndromes.

Comparison of unfractionated heparin and low molecular

weight heparin

Unfractionated heparin

Low molecular weight heparin

Antithrombotic therapy

Molecular weight—3000-30 000 Da

Molecular weight—4000-6000 Da

Mechanism of action—Binds

Unfractionated heparin and low molecular weight heparin

antithrombin and inactivates

Unfractionated heparin is a heterogeneous

factor Xa and thrombin equally

factor Xa more than thrombin

mucopolysaccharide that binds antithrombin, which greatly

(1:1)

(2-4:1)

potentiates the inhibition of thrombin and factor Xa.

Pharmacokinetics—Variable

Pharmacokinetics—Minimal

binding to plasma proteins,

plasma protein binding and no

An important limitation of unfractionated heparin is its

endothelial cells, and

binding to endothelial cells and

unpredictable anticoagulant effect due to variable, non-specific

macrophages, giving

macrophages, giving predictable

binding to plasma proteins. Side effects include haemorrhage at

unpredictable anticoagulant

anticoagulant effects

the access site and heparin induced thrombocytopenia. About

effects

Longer half life

10-20% of patients may develop type I thrombocytopenia,

Short half life

Partially reversible with

which is usually mild and self limiting. However, 0.3-3.0% of

Reversible with protamine

protamine

Laboratory monitoring—Activated

Laboratory monitoring—Not required

patients exposed to heparin for longer than five days develop

clotting time

Cost—10-20 times more expensive

the more serious immune mediated, type II thrombocytopenia,

Cost—Inexpensive

than unfractionated heparin

which paradoxically promotes thrombosis by platelet activation.

ABC of Interventional Cardiology

Despite these disadvantages, unfractionated heparin is

Unfractionated heparin

cheap, relatively reliable, and reversible, with a brief duration of

anticoagulant effect that can be rapidly reversed by protamine.

It remains the antithrombotic treatment of choice during

percutaneous coronary intervention.

For patients already taking a low molecular weight heparin

who require urgent revascularisation, a switch to unfractionated

heparin is generally recommended. Low molecular weight

heparin is longer acting and only partially reversible with

Factor Xa

Thrombin

protamine. The use of low molecular weight heparin during

1:1

percutaneous intervention is undergoing evaluation.

Direct thrombin inhibitors

These include hirudin, bivalirudin, lepirudin, and argatroban.

They directly bind thrombin and act independently of

antithrombin III. They bind less to plasma proteins and have a

more predictable dose response than unfractionated heparin.

At present, these drugs are used in patients with immune

mediated heparin induced thrombocytopenia, but their

Antithrombin III-factor Xa and antithrombin III-thrombin complexes neutralised

potential for routine use during percutaneous intervention is

being evaluated, in particular bivalirudin.

Low molecular weight heparin

Key

Antiplatelet drugs

Antithrombin III

Aspirin

Unfractionated

heparin

Aspirin irreversibly inhibits cyclo-oxygenase, preventing the

synthesis of prothrombotic thromboxane-A2 during platelet

Factor Xa

activation. Aspirin given before percutaneous intervention

reduces the risk of abrupt arterial closure by 50-75%. It is well

Thrombin

Factor Xa

tolerated, with a low incidence of serious adverse effects. The

standard dose results in full effect within hours, and in patients

Low molecular

weight heparin

with established coronary artery disease it is given indefinitely.

However, aspirin is only a mild antiplatelet agent and has no

apparent effect in 10% of patients. These drawbacks have led to

the development of another class of antiplatelet drugs, the

thienopyridines.

Thienopyridines

Ticlopidine and clopidogrel irreversibly inhibit binding of

Antithrombin III-factor Xa complex neutralised

adenosine diphosphate (ADP) during platelet activation. The

combination of aspirin plus clopidogrel or ticlopidine has

Mechanisms of catalytic inhibitory action of unfractionated heparin and low

become standard antiplatelet treatment during stenting in order

molecular weight heparin. Unfractionated heparin interacts with antithrombin

to prevent thrombosis within the stent. As clopidogrel has fewer

III, accelerating binding and neutralisation of thrombin and factor Xa (in 1:1

serious side effects, a more rapid onset, and longer duration of

ratio). Dissociated heparin is then free to re-bind with antithrombin III. Low

molecular weight heparin is less able to bind thrombin because of its shorter

action, it has largely replaced ticlopidine. The loading dose is

length. This results in selective inactivation of factor Xa relative to thrombin.

300 mg at the time of stenting or 75 mg daily for three days

Irreversibly bound antithrombin III and factor Xa complex is neutralised, and

beforehand. It is continued for about four weeks, until new

dissociated low molecular weight heparin is free to re-bind with antithrombin

endothelium covers the inside of the stent. However, the recent

III

CREDO study supports the much longer term (1 year) use of

clopidogrel and aspirin after percutaneous coronary

Glycoprotein IIb/IIIa inhibitors currently in use

intervention, having found a significant (27%) reduction in

Abciximab Eptifibatide Tirofiban

combined risk of death, myocardial infarction, or stroke.

Source

Chimeric

Peptide

Non-peptide

monoclonal

mouse antibody

Glycoprotein IIb/IIIa receptor inhibitors

Time for platelet

24-48

4-6

4-8

These are potent inhibitors of platelet aggregation. The three

inhibition to return

drugs in clinical use are abciximab, eptifibatide, and tirofiban. In

to normal (hours)

combination with aspirin, clopidogrel (if a stent is to be

Approximate cost per

$1031, €1023,

$263, €260,

$404, €401,

deployed), and unfractionated heparin, they further decrease

percutaneous

£657

(12 hour

£167

£257

ischaemic complications in percutaneous coronary procedures.

coronary intervention

infusion)

(18 hour

infusion)

Glycoprotein IIb/IIIa receptor inhibition may be beneficial

Severe

1.0% (higher if

Similar to

in elective percutaneous intervention for chronic stable angina;

thrombocytopenia

readministered)

placebo

for unstable angina or non-ST segment elevation myocardial

Reversible with

Yes

infarction, for acute myocardial infarction with ST segment

platelet transfusion?

elevation.

Interventional pharmacotherapy

Elective percutaneous intervention for chronic stable angina

ADP, thrombin, plasmin

Glycoprotein

Large trials have established the benefit of abciximab and

adrenaline, serotonin,

IIb/IIIa receptor

thromboxane A₂, collagen,

eptifibatide during stenting for elective and urgent

platelet activating factor

percutaneous procedures. As well as reducing risk of myocardial

infarction during the procedure and the need for urgent repeat

Resting

Activated

percutaneous intervention by 35-50%, these drugs seem to

platelet

reduce mortality at one year (from 2.4% to 1% in EPISTENT

and from 2% to 1.4% in ESPRIT). In diabetic patients

Fibrinogen

Glycoprotein

undergoing stenting, the risk of complications was reduced to

IIb/IIIa

that of non-diabetic patients.

receptor

antagonist

Although most trials showing the benefits of glycoprotein

IIb/IIIa inhibitors during percutaneous coronary intervention

Aggregated platelets

relate to abciximab, many operators use the less expensive

caused by formation

Inhibition of platelet

of fibrinogen bridges

eptifibatide and tirofiban. However, abciximab seems to be

aggregation

occupying glycoprotein

superior to tirofiban, with lower 30 day mortality and rates of

IIb/IIIa receptors

non-fatal myocardial infarction and urgent repeat percutaneous

Mechanisms of activated platelet aggregation by fibrin cross linking and its

coronary intervention or coronary artery bypass graft surgery

blockade with glycoprotein IIb/IIIa inhibitors

in a wide variety of circumstances (TARGET study). In the

ESPRIT trial eptifibatide was primarily beneficial in stenting for

elective percutaneous intervention, significantly reducing the

combined end point of death, myocardial infarction, and urgent

repeat percutaneous procedure or bypass surgery at 48 hours

from 9.4% to 6.0%. These benefits were maintained at follow up.

As complication rates are already low during elective

percutaneous intervention and glycoprotein IIb/IIIa inhibitors

Risk

are expensive, many interventionists reserve these drugs for

Glycoprotein

Trial

No of

Risk ratio (95% CI)

Placebo

IIb/IIIa

higher risk lesions or when complications occur. However, this

patients

(%)

inhibitor (%)

may be misguided; ESPRIT showed that eptifibatide started at

PRISM

3232

7.1

5.8

the time of percutaneous intervention was superior to a

PRISM Plus

1915

11.9

10.2

glycoprotein IIb/IIIa inhibitor started only when complications

PARAGON A

2282

11.7

11.3

occurred.

PURSUIT

9461

15.7

14.2

PARAGON B

5165

11.4

10.5

Unstable angina and non-ST segment elevation myocardial infarction

GUSTO-IV ACS

7800

8.0

8.7

The current role of glycoprotein IIb/IIIa inhibitors has been

Total

29 855

0.92 (0.86 to 0.995)

11.5

10.7

P=0.037

defined by results from several randomised trials. In one group

0.5

1.0

1.5

of studies 29 885 patients (largely treated without percutaneous

P=0.339 Breslow-Day

Inhibitor better

Placebo better

homogeneity

intervention) were randomised to receive a glycoprotein

IIb/IIIa inhibitor or placebo. The end point of “30 day death or

Composite 30 day end point of death and myocardial infarction for six

non-fatal myocardial infarction” showed an overall significant

medical treatment trials of glycoprotein IIb/IIIa inhibitors in unstable

angina and non{ST segment elevation myocardial infarction

benefit of the glycoprotein IIb/IIIa inhibitor over placebo.

Surprisingly, the largest trial (GUSTO IV ACS) showed no

benefit with abciximab, which may be partly due to inclusion of

lower risk patients. The use of glycoprotein IIb/IIIa inhibitors in

all patients with unstable angina and non-ST segment elevation

myocardial infarction remains debatable, although the

consistent benefit seen with these drugs has led to the

recommendation that they be given to high risk patients

Risk

scheduled for percutaneous coronary intervention.

Glycoprotein

Trial

No of

Risk ratio (95% CI)

Placebo

IIb/IIIa

Another study (CURE) showed that the use of clopidogrel

patients

(%)

inhibitor (%)

rather than a glycoprotein IIb/IIIa inhibitor significantly

EPIC

2099

9.6

6.6

reduced the combined end point of cardiovascular death,

IMPACT-II

4010

8.5

7.0

non{fatal myocardial infarction, or stroke (from 11.4% to 9.3%).

EPILOG

2792

9.1

4.0

Similar benefits were seen in the subset of patients who

CAPTURE

1265

9.0

4.8

underwent percutaneous coronary intervention. The impact

RESTORE

2141

6.3

5.1

this study will have on the use of glycoprotein IIb/IIIa inhibitors

EPISTENT

2399

10.2

5.2

in this clinical situation remains unclear.

ESPRIT

2064

10.2

6.3

In another group of studies (n=16 770), patients were given

Total

16 770

0.62 (0.55 to 0.70)

8.8

5.6

a glycoprotein IIb/IIIa inhibitor or placebo immediately before

P<0.001

1.0

2.0

or during planned percutaneous intervention. All showed

P=0.014 Breslow-Day

Inhibitor better

Placebo better

unequivocal benefit with the active drug. Despite their efficacy,

homogeneity

however, some interventionists are reluctant to use glycoprotein

Composite 30 day end point of death and myocardial infarction for seven

IIb/IIIa inhibitors in all patients because of their high costs and

trials of glycoprotein IIb/IIIa inhibitors given before or during planned

reserve their use for high risk lesions or when complications

percutaneous coronary intervention for unstable angina and non-ST

occur.

segment elevation myocardial infarction

ABC of Interventional Cardiology

Acute ST segment elevation myocardial infarction

Names of trials

In many centres primary percutaneous intervention is the

x CAPTURE—C7E3 antiplatelet therapy in unstable refractory

preferred method of revascularisation for acute myocardial

angina

infarction. To date, randomised studies have shown that

x CREDO—Clopidogrel for the reduction of events during

abciximab is the only drug to demonstrate benefit in this

observation

setting. The development of low cost alternatives and the

x CURE—Clopidogrel in unstable angina to prevent recurrent

potential for combination with other inhibitors of the

events

coagulation cascade may increase the use of glycoprotein

x EPIC—Evaluation of C7E3 for prevention of ischemic

IIb/IIIa inhibitors.

complications

x EPILOG—Evaluation in PTCA to improve long-term outcome

with abciximab glycoprotein IIb/IIIa blockade

x EPISTENT—Evaluation of IIb/IIIa platelet inhibitor for stenting

Restenosis

Enhanced suppression of the platelet glycoprotein

x ESPRIT—

IIb/IIIa receptor using integrilin therapy

Although coronary stents reduce restenosis rates compared

x GUSTO IV-ACS—Global use of strategies to open occluded

with balloon angioplasty alone, restenosis within stents remains

arteries IV in acute coronary syndrome

a problem. Nearly all systemic drugs aimed at reducing

x IMPACT II—Integrilin to minimize platelet aggregation and

restenosis have failed, and drug eluting (coated) stents may

coronary thrombosis

ultimately provide the solution to this problem.

x PARAGON—Platelet IIb/IIIa antagonism for the reduction of

acute coronary syndrome events in the global organization

network

The future

x PRISM—Platelet receptor inhibition in ischemic syndrome

management

Improvements in adjunctive pharmacotherapy, in combination

x PRISM-PLUS—Platelet receptor inhibition in ischemic syndrome

with changes in device technology, will allow percutaneous

management in patients limited by unstable signs and symptoms

x PURSUIT—Platelet glycoprotein IIb/IIIa in unstable angina:

coronary intervention to be performed with increased

receptor suppression using integrilin therapy

likelihood of acute and long term success and with lower

x RESTORE—Randomized efficacy study of tirofiban for outcomes

procedural risks in a wider variety of clinical situations. Further

and restenosis

refinements in antiplatelet treatment may soon occur with

rapidly available bedside assays of platelet aggregation.

Competing interests: None declared.

Further reading

x ESPRIT Investigators. Novel dosing regimen of eptifibatide in

x Lincoff AM, Califf RM, Moliterno DJ, Ellis SG, Ducas J, Kramer JH,

planned coronary stent implantation (ESPRIT): a randomized,

et al. Complementary clinical benefits of coronary-artery stenting

placebo-controlled trial. Lancet 2000;356:2037-44

and blockade and blockade of platelet glycoprotein IIb/IIIa

x Boersma E, Harrington RA, Moliterno DJ, White H, Theroux P,

receptors. N Engl J Med 1999;341:319-27

Van de Werf F, et al. Platelet glycoprotein IIb/IIIa inhibitors in

x PURSUIT Trial Investigators. Inhibition of platelet glycoprotein

acute coronary syndromes: a meta-analysis of all major

IIb/IIIa with eptifibatide in patients with acute coronary syndromes.

randomized clinical trials. Lancet 2002;359:189-98

Platelet glycoprotein IIb/IIIa in unstable angina: receptor

x Chew DP, Lincoff AM. Adjunctive pharmacotherapy and

suppression using integrilin therapy. N Engl J Med 1998;339:436-43

coronary intervention. In: Grech ED, Ramsdale DR, eds. Practical

x PRISM-PLUS Study Investigators. Inhibition of the platelet

interventional cardiology. 2nd ed. London: Martin Dunitz,

glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and

2002:207{24

non-Q wave myocardial infarction. Platelet receptor inhibition in

x Steinhubl SR, Berger PB, Mann JT 3rd, Fry ET, DeLago A, Wilmer

ischemic syndrome management in patients limited by unstable

C, et al. Early and sustained dual oral antiplatelet therapy

signs and symptoms. N Engl J Med 1998;338:1488-97

following percutaneous coronary intervention. A randomized

controlled trial. JAMA 2002;288:2411-20

Non-coronary percutaneous intervention

Ever D Grech

Although most percutaneous interventional procedures involve

the coronary arteries, major developments in non-coronary

transcatheter cardiac procedures have occurred in the past 20

years. In adults the commonest procedures are balloon mitral

valvuloplasty, ethanol septal ablation, and septal defect closure.

These problems were once treatable only by surgery, but

selected patients may now be offered less invasive alternatives.

Carrying out such transcatheter procedures requires

supplementary training to that for coronary intervention.

Balloon mitral valvuloplasty

Acquired mitral stenosis is a consequence of rheumatic fever

and is commonest in developing countries. Commissural fusion,

thickening, and calcification of the mitral valve leaflets typically

occur, as well as thickening and shortening of the chordae

tendinae. The mitral valve stenosis leads to left atrial

enlargement, which predisposes patients to atrial fibrillation

Stenotic mitral valve showing distorted, fused, and calcified valve leaflets.

and the formation of left atrial thrombus.

(AMVL=anterior mitral valve leaflet, PMVL=posterior mitral valve leaflet,

LC=lateral commissure, MC=medial commissure)

In the 1980s percutaneous balloon valvuloplasty techniques

were developed that could open the fused mitral commissures

in a similar fashion to surgical commissurotomy. The resulting

fall in pressure gradient and increase in mitral valve area led to

symptomatic improvement. Today, this procedure is most often

performed with the hourglass shaped Inoue balloon. This is

introduced into the right atrium from the femoral vein, passed

across the atrial septum by way of a septal puncture, and then

positioned across the stenosed mitral valve before inflation.

Left

atrium

Patient selection

In general, patients with moderate or severe mitral stenosis

Right

atrium

(valve area < 1.5 cm²) with symptomatic disease despite optimal

Left

medical treatment can be considered for this procedure.

ventricle

Further patient selection relies heavily on transthoracic and

transoesophageal echocardiographic findings, which provide

Right

ventricle

structural information about the mitral valve and subvalvar

apparatus.

A scoring system for predicting outcomes is commonly used

to screen potential candidates. Four characteristics (valve

Inferior

vena cava

mobility, leaflet thickening, subvalvar thickening, and

calcification) are each graded 1 to 4. Patients with a score of <8

are more likely to have to have a good result than those with

scores of > 8. Thus, patients with pliable, non-calcified valves

and minimal fusion of the subvalvar apparatus achieve the best

immediate and long term results.

Relative contraindications are the presence of pre-existing

significant mitral regurgitation and left atrial thrombus.

Successful balloon valvuloplasty increases valve area to

> 1.5 cm² without a substantial increase in mitral regurgitation,

resulting in significant symptomatic improvement.

Complications—The major procedural complications are

death (1%), haemopericardium (usually during transseptal

catheterisation) (1%), cerebrovascular embolisation (1%), severe

mitral regurgitation (due to a torn valve cusp) (2%), and atrial

septal defect (although this closes or decreases in size in most

patients) (10%). Immediate and long term results are similar to

those with surgical valvotomy, and balloon valvuloplasty can be

Top: Diagram of the Inoue balloon catheter positioned

repeated if commissural restenosis (a gradual process with an

across a stenosed mitral valve. Bottom: Fluoroscopic

incidence of 30-40% at 6-8 years) occurs.

image of the inflated Inoue balloon across the valve

ABC of Interventional Cardiology

In patients with suitable valvar anatomy, balloon

valvuloplasty has become the treatment of choice for mitral

stenosis, delaying the need for surgical intervention. It may also

be of particular use in those patients who are at high risk of

surgical intervention (because of pregnancy, age, or coexisting

Postmortem appearance of

a heart with hypertrophic

pulmonary or renal disease).

cardiomyopathy showing

In contrast, balloon valvuloplasty for adult aortic stenosis is

massive ventricular and

associated with high complication rates and poor outcomes and

septal hypertrophy causing

is only rarely performed.

obstruction of the left

ventricular outflow tract

(LVOT). This is

compounded by the

Ethanol septal ablation

anterior mitral valve leaflet

(AMVL), which presses

Hypertrophic cardiomyopathy

against the ventricular

Hypertrophic cardiomyopathy is a disease of the myocytes

septum (VS). Note the

caused by mutations in any one of 10 genes encoding various

coincidental right atrial

(RAE) and right ventricular

components of the sarcomeres. It is the commonest genetic

(RVE) pacing electrodes

cardiovascular disease, being inherited as an autosomal

dominant trait and affecting about 1 in 500 of the population. It

Characteristics of hypertrophic cardiomyopathy

has highly variable clinical and pathological presentations.

It is usually diagnosed by echocardiography and is

Anatomical—Ventricular hypertrophy of unknown cause, usually with

disproportionate involvement of the interventricular septum

characterised by the presence of unexplained hypertrophy in a

Physiological—Well preserved systolic ventricular function, impaired

non-dilated left ventricle. In a quarter of cases septal

diastolic relaxation

enlargement may result in substantial obstruction of the left

Pathological—Extensive disarray and disorganisation of cardiac

ventricular outflow tract. This is compounded by Venturi

myocytes and increased interstitial collagen

suction movement of the anterior mitral valve leaflet during

ventricular systole, bringing it into contact with the

hypertrophied septum. The systolic anterior motion of the

anterior mitral valve leaflet also causes mitral regurgitation.

Treatment

Although hypertrophic cardiomyopathy is often asymptomatic,

common symptoms are dyspnoea, angina, and exertional

syncope, which may be related to the gradient in the left

ventricular outflow tract. The aim of treatment of symptomatic

patients is to improve functional disability, reduce the extent of

obstruction of the left ventricular outflow tract, and improve

diastolic filling. Treatments include negatively inotropic drugs

such as blockers, verapamil, and disopyramide. However, 10%

of symptomatic patients fail to respond to drugs, and surgery—

Echocardiogram showing anterior mitral valve

ventricular myectomy (which usually involves removal of a small

leaflet (AMVL) and septal contact (***) during

amount of septal muscle) or ethanol septal ablation—can be

ventricular systole. Note marked left ventricular (LV)

considered.

free wall and ventricular septal (VS) hypertrophy.

Injection of an echocontrast agent down the septal

The objective of ethanol septal ablation is to induce a

artery results in an area of septal echo-brightness

localised septal myocardial infarction at the site of obstruction

(dotted line). (LA=left atrium, AoV=aortic valve)

of the left ventricular outflow tract. The procedure involves

threading a small balloon catheter into the septal artery

supplying the culprit area of septum. Echocardiography with

injection of an echocontrast agent down the septal artery allows

the appropriate septal artery to be identified and reduces the

number of unnecessary ethanol injections.

Once the appropriate artery is identified, the catheter

balloon is inflated to completely occlude the vessel, and a small

amount of dehydrated ethanol is injected through the central

lumen of the catheter into the distal septal artery. This causes

immediate vessel occlusion and localised myocardial infarction.

The infarct reduces septal motion and thickness, enlarges the

left ventricular outflow tract, and may decrease mitral valve

systolic anterior motion, with consequent reduction in the

gradient of the left ventricular outflow tract. Over the next few

Angiograms showing ethanol septal

ablation. The first septal artery (S1,

months the infarcted septum undergoes fibrosis and shrinkage,

top left) is occluded with a balloon

which may result in further symptomatic improvement.

catheter (top right) before ethanol

The procedure is performed under local anaesthesia with

injection. This results in permanent

sedation as required. Patients inevitably experience chest

septal artery occlusion (bottom)

and a localised septal myocardial

discomfort during ethanol injection, and treatment with

infarction. (LAD=left anterior

intravenous opiate analgesics is essential. Patients are usually

descending artery, TPW=temporary

discharged after four or five days.

pacemaker wire)

Non-coronary percutaneous intervention

Complications

Heart block is a frequent acute complication, so a temporary

pacing electrode is inserted via the femoral vein beforehand

and is usually left in situ for 24 hours after the procedure,

during which time the patient is monitored.

The main procedural complications are persistent heart

block requiring a permanent pacemaker (10%), coronary artery

dissection and infarction requiring immediate coronary artery

bypass grafting (2%), and death (1-2%). The procedural

mortality and morbidity is similar to that for surgical myectomy,

as is the reduction in left ventricular outflow tract gradient.

Micrograph of hypertrophied myocytes in haphazard

Surgery and ethanol septal ablation have not as yet been

alignments characteristic of hypertrophic

directly compared in randomised studies.

cardiomyopathy. Interstitial collagen is also increased

Simultaneous aortic and left ventricular pressure waves before (left) and after (right) successful ethanol septal ablation. Note the difference

between left ventricular peak pressure and aortic peak pressure, which represents the left ventricular outflow tract gradient, has been

reduced from 80 mm Hg to 9 mm Hg

Septal defect closure

Indications and contraindications for percutaneous closure

of atrial septal defects

Atrial septal defects

Indications

Atrial septal defects are congenital abnormalities characterised

Clinical

by a structural deficiency of the atrial septum and account for

x If defect causes symptoms

x Pulmonary:systemic flow ratio

about 10% of all congenital cardiac disease. The commonest

x Associated cerebrovascular

> 1.5 and reversible pulmonary

atrial septal defects affect the ostium secundum (in the fossa

embolic event

hypertension

ovalis), and most are suitable for transcatheter closure. Although

x Divers with neurological

x Right-to-left atrial shunt and

atrial septal defects may be closed in childhood, they are the

decompression sickness

hypoxaemia

commonest form of congenital heart disease to become

Anatomical

apparent in adulthood.

x Defects within fossa ovalis

x Presence of > 4 mm rim of tissue

Diagnosis is usually confirmed by echocardiography,

(or patent foramen ovale)

surrounding defect

allowing visualisation of the anatomy of the defect and Doppler

x Defects with stretched

diameter < 38 mm

estimation of the shunt size. The physiological importance of

the defect depends on the duration and size of the shunt, as well

Contraindications

x Sinus venosus defects

x Ostium secundum defects with other

as the response of the pulmonary vascular bed. Patients with

x Ostium primum defects

important congenital heart defects

significant shunts (defined as a ratio of pulmonary blood flow to

requiring surgical correction

systemic blood flow > 1.5) should be considered for closure

when the diagnosis is made in later life because the defect

reduces survival in adults who develop progressive pulmonary

hypertension. They may also develop atrial tachyarrhythmias,

which commonly precipitate heart failure.

Patients within certain parameters can be selected for

transcatheter closure with a septal occluder. In those who are

unsuitable for the procedure, surgical closure may be considered.

Patent foramen ovale

A patent foramen ovale is a persistent flap-like opening

between the atrial septum primum and secundum which occurs

in roughly 25% of adults. With microbubbles injected into a

peripheral vein during echocardiography, a patent foramen

Deployment sequence of the Amplatzer septal occluder for closing an atrial

ovale can be demonstrated by the patient performing and

septal defect

ABC of Interventional Cardiology

releasing a prolonged Valsalva manoeuvre. Visualisation of

microbubbles crossing into the left atrium reveals a right-to-left

shunt mediated by transient reversal of the interatrial pressure

gradient.

Although a patent foramen ovale (or an atrial septal

aneurysm) has no clinical importance in otherwise healthy

adults, it may cause paradoxical embolism in patients with

cryptogenic transient ischaemic attack or stroke (up to half of

whom have a patent foramen ovale), decompression illness in

divers, and right-to-left shunting in patients with right

ventricular infarction or severe pulmonary hypertension.

Patients with patent foramen ovale and paradoxical embolism

Amplatzer occluder devices for patent foramen ovale (left) and muscular

ventricular septal defects (right)

have an approximate 3.5% yearly risk of recurrent

cerebrovascular events.

Secondary preventive strategies are drug treatment (aspirin,

Further reading

clopidogrel, or warfarin), surgery, or percutaneous closure using

a dedicated occluding device. A lack of randomised clinical

x Inoue K, Lau K-W, Hung J-S. Percutaneous transvenous mitral

commissurotomy. In: Grech ED, Ramsdale DR, eds. Practical

trials directly comparing these options means optimal

interventional cardiology. 2nd ed. London: Martin Dunitz, 2002:

treatment remains uncertain. However, percutaneous closure

373{87

offers a less invasive alternative to traditional surgery and allows

x Bonow RO, Carabello B, de Leon AC, Edmunds LH Jr, Fedderly

patients to avoid potential side effects associated with

BJ, Freed MD, et al. ACC/AHA guidelines for the management of

anticoagulants and interactions with other drugs. In addition,

patients with valvular heart disease: A report of the American

divers taking anticoagulants may experience haemorrhage in

College of Cardiology/American Heart Association Task Force on

the ear, sinus, or lung from barotrauma.

Practice Guidelines (Committee on Management of Patients with

Valvular Heart Disease). J Am Coll Cardiol 1998;32:1486-582

x Wilkins GT, Weyman AE, Abascal VM, Bloch PC, Palacios IF.

Congenital ventricular septal defects

Percutaneous balloon dilatation of the mitral valve: an analysis of

Untreated congenital ventricular septal defects that require

echocardiographic variables related to outcome and the

intervention are rare in adults. Recently, there has been interest

mechanism of dilatation. Br Heart J 1998;60:299-308

in percutaneous device closure of ventricular septal defects

x Wigle ED, Rakowski H, Kimball BP, Williams WG. Hypertrophic

acquired as a complication of acute myocardial infarction.

cardiomyopathy: clinical spectrum and treatment. Circulation 1995;

92:1680-92

However, more experience is necessary to assess the role of this

x Nagueh SF, Ommen SR, Lakkis NM, Killip D, Zoghbi WA, Schaff

procedure as a primary closure technique or as a bridge to

HV, et al. Comparison of ethanol septal reduction therapy with

subsequent surgery.

surgical myectomy for the treatment of hypertrophic obstructive

cardiomyopathy. J Am Coll Cardiol 2001;38:1701-6

x Braun MU, Fassbender D, Schoen SP, Haass M, Schraeder R,

Scholtz W, et al. Transcatheter closure of patent foramen ovale in

The picture of a stenotic mitral valve and micrograph of myocytes showing

patients with cerebral ischaemia. J Am Coll Cardiol 2002;39:

hypertrophic cardiomyopathy were provided by C Littman, consultant

2019-25

histopathologist at the Health Sciences Centre, Winnipeg, Manitoba,

x Waight DJ, Cao Q-L, Hijazi ZM. Interventional cardiac

Canada. The postmortem picture of a heart with hypertrophic

catheterisation in adults with congenital heart disease. In: Grech

cardiomyopathy was provided by T Balachandra, chief medical examiner for

ED, Ramsdale DR, eds. Practical interventional cardiology. 2nd ed.

the Province of Manitoba, Winnipeg. The pictures of Amplatzer occluder

London: Martin Dunitz, 2002:390-406

devices were provided by AGA Medical Corporation, Minnesota, USA.

New developments in percutaneous coronary

intervention

Julian Gunn, Ever D Grech, David Crossman, David Cumberland

Percutaneous coronary intervention has become a more

common procedure than coronary artery bypass surgery in

many countries, and the number of procedures continues to

rise. In one day an interventionist may treat four to six patients

with complex, multivessel disease or acute coronary syndromes.

Various balloons, stents, and other devices are delivered by

means of a 2 mm diameter catheter introduced via a peripheral

artery. The success rate is over 95%, and the risk of serious

complications is low. After a few hours patients can be

mobilised, and they are usually discharged the same or the next

day. Even the spectre of restenosis is now fading.

Refinements of existing techniques

The present success of percutaneous procedures is largely

because of refinement of our “basic tools” (intracoronary

guidewires and low profile balloons), which have greatly

contributed to the safety and effectiveness of procedures.

Triple vessel disease is no longer a surgical preserve, and particularly

However, the greatest technological advance has been in the

good results are expected with drug eluting stents. In this case, lesions in

development of stents. These are usually cut by laser from

the left anterior descending (LAD), circumflex (Cx), and right coronary

stainless steel tubes into a variety of designs, each with different

arteries (RCA) (top row) are treated easily and rapidly by stent (S)

implantation (bottom row)

radial strength and flexibility. They are chemically etched or

electropolished to a fine finish and sometimes coated.

Digital angiography is a great advance over cine-based

systems, and relatively benign contrast media have replaced the

toxic media used in early angioplasty. Although magnetic

resonance and computed tomographic imaging may become

Performance of percutaneous coronary intervention

useful in the non-invasive diagnosis of coronary artery disease,

General statistics

angiography will remain indispensable to guide percutaneous

x Success rate of procedure

> 95%

interventions for the foreseeable future.

x Symptoms improved after procedure

90%

x Complications*

x Restenosis

15% (range 5-50%)

Interventional devices and their uses

x Duration of procedure

15 minutes-3 hours

x Access point:

Device

Use (% of cases)

Types of lesion

Femoral artery

95%

Balloon catheter

100%

Multiple types

Radial or brachial artery

Stent

70-90%

Most types

x Time in hospital after procedure:

Drug eluting stent

0-50%

High risk of restenosis

(possibly all)

Overnight

60%

Day case

20%

Cutting balloon

1-5%

In-stent restenosis, ostial

lesions

Longer

20%

Rotablator

1-3%

Calcified, ostial, undilatable

x Intravenous contrast load

100-800 ml

lesions

x X ray dose to patient

75 Gy/cm²†

Brachytherapy

1-3%

In-stent restenosis

Special conditions

Atherectomy

< 1%

Bulky, eccentric, ostial lesions

x Success of direct procedure for acute myocardial infarction

> 95%

Stent graft

< 1%

Aneurysm, arteriovenous

x Success for chronic ( > 3 month) occluded vessel

50-75%

malformation, perforation

x Mortality for procedure in severe cardiogenic shock

50%

Thrombectomy

< 1%

Visible thrombus

x Restenosis:

Laser

< 1%

Occlusions, in-stent restenosis

Vessels < 2.5 mm in diameter, > 40 mm length

60%

Distal protection

< 1%

Degenerate vein graft

Vessels > 3.5 mm diameter, < 10 mm length

x Lesion recurrence later than 6 months after procedure

< 5%

x Re-restenosis:

After repeat balloon dilatation

30-50%

New device technology

After brachytherapy

< 15%

Pre-eminent among new devices is the drug eluting (coated)

*Death, myocardial infarction, coronary artery bypass surgery, cerebrovascular

accident

stent, which acts as a drug delivery device to reduce restenosis.

†Equivalent to 1-2 computed tomography scans

The first of these was the sirolimus coated Cypher stent.

ABC of Interventional Cardiology

Sirolimus is one of several agents that have powerful antimitotic

Names of trials

effects and inhibit new tissue growth inside the artery and stent.

In a randomised controlled trial (RAVEL) this stent gave a six

x ASPECT—Asian paclitaxel-eluting stent clinical trial

month restenosis rate of 0% compared with 27% for an

x RAVEL—Randomized study with the sirolimus eluting velocity

balloon expandable stent in the treatment of patients with de novo

uncoated stent of the same design. A later randomised study

native coronary artery lesions

(SIRIUS) of more complex stenoses (which are more prone to

x SIRIUS—Sirolimus-coated velocity stent in treatment of patients

recur) still produced a low rate of restenosis within stented

with de novo coronary artery lesions trial

segments (9% v 36% with uncoated stents), even in patients with

x TAXUS II—Study of the safety and superior performance of the

diabetes (18% v 51% respectively). Other randomised studies

TAXUS drug-eluting stent versus the uncoated stent on de novo

such as ASPECT and TAXUS II have also shown that coated

lesions

stents (with the cytotoxic agent paclitaxel) have significantly

lower six month restenosis rates than identical uncoated stents

(14% v 39% and 6% v 20% respectively). By reducing the

incidence of restenosis (and therefore recurrent symptoms),

drug eluting stents will probably alter the balance of treating

coronary artery disease in favour of percutaneous intervention

rather than coronary artery bypass surgery. However, coated

stents will not make any difference to the potential for

percutaneous coronary intervention to achieve acute success in

any given lesion; nor do they seem to have any impact on acute

and subacute safety.

Although coated stents may, paradoxically, be too effective at

altering the cellular response and thus delay the desirable

process of re-endothelialisation, there is no evidence that this is

a clinical problem. However, this problem has been observed

Angiograms showing severe, diffuse, in-stent restenosis in the left anterior

with brachytherapy (catheter delivered radiotherapy over a

descending artery and its diagonal branch (L and D, left). This was treated

short distance to kill dividing cells), a procedure that is generally

with balloon dilatation and brachytherapy with irradiation (Novoste) from

reserved for cases of in-stent restenosis. This may lead to late

a catheter (Br, centre), with an excellent final result (right)

thrombosis as platelets readily adhere to the “raw” surface that

results from an impaired healing response. This risk is

minimised by prolonged treatment with antiplatelet drugs and

avoiding implanting any fresh stents at the time of

brachytherapy.

Other energy sources may also prove useful. Sonotherapy

(ultrasound) may have potential, less as a treatment in its own

right than as a facilitator for gene delivery, and is “benign” in its

effect on healthy tissue. Photodynamic therapy (the interaction

of photosensitising drug, light, and tissue oxygen) is also being

investigated but is still in early development. Laser energy, when

delivered via a fine intracoronary wire, is used in a few centres

to recanalise blocked arteries.

New work practices

Angiogram of an aortocoronary vein graft with an

Twenty years ago, a typical angioplasty treated one proximally

aneurysm and stenoses (A and S, top). Treatment by

located lesion in a single vessel in a patient with good left

implantation of a membrane-covered stent excluded the

aneurysm and restored a tubular lumen (bottom)

ventricular function. Now, it commonly treats two or three vessel

disease, perhaps with multiple lesions (some of which may be

complex), in patients with impaired left ventricular function,

advanced age, and comorbidity. Patients may have undergone

Unprotected left main

stem stenoses (LMS, top)

may, with careful selection,

be treated by stent

implantation (S, bottom).

Best results (similar to

coronary artery bypass

surgery) are achieved in

stable patients with good

left ventricular function

and no other disease.

Close follow up to detect

restenosis is important.

(LAD=left anterior

Bifurcation lesions, such as of the left anterior descending

descending artery, Cx=

artery and its diagonal branch (L and D, left), are technically

circumflex coronary

challenging to treat but can be well dilated by balloon

artery)

dilatation and selective stenting (S, right)

New developments in percutaneous coronary intervention

coronary artery bypass surgery and be unsuitable for further

heart surgery. Isolated left main stem and ostial right coronary

artery lesions, though requiring more experience and

variations on traditional techniques, are also no longer a

surgical preserve.

Role of percutaneous coronary intervention

The role of percutaneous intervention has extended to the

point where up to 70% of patients treated have acute coronary

syndromes. Trial data now support the use of a combination of

a glycoprotein IIb/IIIa inhibitor and early percutaneous

intervention to give high risk patients the best long term results.

The same applies to acute myocardial infarction, where

An acute coronary syndrome was found to be due to stenoses and an

percutaneous procedures achieve a much higher rate of arterial

ulcerated plaque in the right coronary artery (S and U, left). This was

patency than thrombolytic treatment. Even cardiogenic shock,

treated with a glycoprotein IIb/IIIa inhibitor followed by stent implantation

(right). This is an increasingly common presentation of coronary artery

the most lethal of conditions, may be treated by an aggressive

disease to catheterisation laboratories

combination of intra-aortic balloon pumping and percutaneous

intervention.

The potential for percutaneous procedures to treat a wide

range of lesions successfully with low rates of restenosis raises

the question of the relative roles of percutaneous intervention

and bypass surgery in everyday practice. It takes time to

accumulate sufficient trial data to make long term

generalisations possible.

Early trials comparing balloon angioplasty with bypass

surgery rarely included stents and few patients with three vessel

disease (as such disease carried higher risk and percutaneous

intervention was not as widely practised as now). The long term

results favoured bypass surgery, but theses trials are now

outdated. In the second generation of studies, stents were used

in percutaneous intervention, improving the results. As in the

Right coronary artery containing large,

early studies, surgery and intervention had similarly low

lobulated thrombus (T, left) on a substantial

complications and mortality. The intervention patients still had

stenosis. After treatment with glycoprotein

more need for repeat procedures because of restenosis than the

IIb/IIIa inhibitor, the lesion was stented

bypass surgery patients, but the differences were less.

successfully (St, right)

The major drawback of all these studies was an exclusion

rate approaching 95%, making the general clinical application

General roles of percutaneous coronary intervention (PCI)

of the findings questionable. This was because it was unusual at

and coronary artery bypass surgery (CABG)

that time to find patients with multivessel disease who were

PCI

technically suitable for both methods and thus eligible for

Condition

1993

2003

CABG

inclusion in the trials. Now that drug eluting stents are available,

Acute presentation

more trials are under way: the balance will now probably tip in

Acute coronary syndrome

+++

favour of percutaneous coronary intervention. Meanwhile, the

Cardiogenic shock

+/ −

decision of which treatment is better for a patient at a given

Acute full thickness myocardial infarction

+++

−

time is based on several factors, including the feasibility of

Bailout after failed thrombolysis

−

percutaneous intervention (which is generally considered as the

Chronic presentation

first option), completeness of revascularisation, comorbidity,

Impaired left ventricle with left main stem

− −

−

+++

age, and the patient’s own preferences.

stenosis and blocked right coronary artery

Impaired left ventricle and 3 vessel disease

+++

Impaired left ventricle and 3 vessel disease

−

+++

Implications for health services

with >1 occlusion

These issues are likely to pose major problems for health

Diabetes and 3 vessel disease

+++

services. Modern percutaneous techniques can be used both to

Good left ventricle and 3 vessel disease

+++

shorten patients’ stay in hospital and to make their treatment

2 occluded vessels

−

minimally hazardous and more comfortable. They can also be

Good left ventricle and 2 vessel disease

+++

used in the first and the last (after coronary artery bypass

Repeat revascularisation after PCI

+++

surgery) stages of a patient’s “ischaemic career.”

Good left ventricle and 1 vessel disease

+++

On the other hand, for the role of percutaneous coronary

2-3 vessel diffuse or distal disease

intervention in acute infarction to be realised, universal

Repeat revascularisation after CABG

emergency access to this service will be needed. However, most

Palliative partial revascularisation

−

health systems cannot afford this—the main limiting factor

Revascularisation of frail patient or with

−

being the number of interventionists and supporting staff

severe comorbidity

required to allow a 24 hour rota compatible with legal working

+++ highly effective role, ++ useful role, + limited role, − treatment not preferred, − −

hours and the survival of routine elective work.

treatment usually strongly advised against

ABC of Interventional Cardiology

The future for percutaneous coronary

Further reading

intervention

x Morice M-C, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, Perin

M, et al. A randomized comparison of a sirolimus-eluting stent with

Will percutaneous coronary intervention exist in 20 years time,

a standard stent for coronary revascularization. N Engl J Med

or, at least, be recognisable as a logical development of today’s

2002;346:1773-80

x Park SJ, Shim WH, Ho DS, Raizner AE, Park SW, Hong MK, et al.

procedures? Will balloons and stents still be in use? It is likely

A paclitaxel-eluting stent for the prevention of coronary restenosis.

that percutaneous procedures will expand further, although

N Engl J Med 2003;348:1537-45

some form of biodegradable stent is a possibility. A more

x Raco DL, Yusuf S. Overview of randomised trials of percutaneous

“biological” stent might also be able to act as an effective drug

coronary intervention: comparison with medical and surgical

or gene reservoir, which may extend local drug delivery into

therapy for chronic coronary artery disease. In: Grech ED,

new areas of coronary artery disease. We may find ourselves

Ramsdale DR, eds. Practical interventional cardiology. 2nd ed.

detecting inflamed (“hot”) plaques with thermography catheters

London: Martin Dunitz, 2002:263-77

x Teirstein PS, Kuntz RE. New frontiers in interventional cardiology:

and treating these before they rupture. We may even be able to

intravascular radiation to prevent restenosis. Circulation 2001;104:

modify the natural course of coronary artery disease by

2620-6

releasing agents “remotely” (possibly using an external

x Tsuji T, Tamai H, Igaki K, Kyo E, Kosuga K, Hata T, et al.

ultrasound trigger) or by injecting an agent that activates the

Biodegradable stents as a platform to drug loading. Int J Cardiovasc

molecular cargo in a stent.

Intervent 2003;5:13-6

A persistent challenge still limiting the use of percutaneous

x Hariawala MD, Sellke FW. Angiogenesis and the heart: therapeutic

implications. J R Soc Med 1997;90:307-11

coronary intervention is that of chronic total occlusions, which

x Serruys PW, Unger F, Sousa JE, Jatene A, Bonnier HJ, Schonberger

can be too tough to allow passage of an angioplasty guidewire.

JP, et al, for the Arterial Revascularization Therapies Study Group.

An intriguing technique is percutaneous in situ coronary artery

Comparison of coronary-artery bypass surgery and stenting for the

bypass. With skill and ingenuity, a few enthusiasts have

treatment of multivessel disease. N Engl J Med 2001;344:1117-24

anastomosed the stump of a blocked coronary artery to the

x SoS Investigators. Coronary artery bypass surgery versus

adjacent cardiac vein under intracoronary ultrasound guidance,

percutaneous coronary intervention with stent implantation in

patients with multivessel coronary artery disease (the stent or

thereby using the vein as an endogenous conduit (with reversed

surgery trial): a randomised controlled trial. Lancet 2002;360:

flow). This technique may assist only a minority of patients.

965-70

More practical, we believe, is the concept of drilling through

occlusions with some form of external guidance, perhaps

magnetic fields.

“Direct” myocardial revascularisation (punching an array of

holes into ischaemic myocardium) has had a mixed press over

the past decade. Some attribute its effect to new vessel

formation, others cite a placebo effect. Although the channels

do not stay open, they seem to stimulate new microvessels to

grow. Injection of growth factors (vascular endothelial growth

factor and fibroblast growth factor) to induce new blood vessel

growth also has this effect, and percutaneous injection of these

agents into scarred or ischaemic myocardium is achievable.

The coronary artery imaging was provided by John Bowles, clinical

specialist radiographer, and Nancy Alford, clinical photographer, Sheffield

However, we need a more thorough understanding of

Teaching Hospitals NHS Trust, Sheffield.

biological control mechanisms before we can be confident of

the benefits of this technology.

Competing interests: None declared.

Challenges to mechanical revascularisation

Deaths from coronary artery disease are being steadily reduced

in the Western world. However, with increasing longevity, it is

unlikely that we will see a reduction in the prevalence of its

chronic symptoms. More effective primary and secondary

prevention; antismoking and healthy lifestyle campaigns; and

the widespread use of antiplatelet drugs, blockers, statins, and

renin-angiotensin system inhibitors may help prevent, or at

least delay, the presentation of symptomatic coronary artery

disease. In patients undergoing revascularisation, they are

essential components of the treatment “package.” More effective

anti-atherogenic treatments will no doubt emerge in the near

future to complement and challenge the dramatic progress

being made in percutaneous coronary intervention.

Percutaneous interventional electrophysiology

Gerry C Kaye

Before the 1980s, cardiac electrophysiology was primarily used

Tachyarrhythmias

to confirm mechanisms of arrhythmia, with management

mainly by pharmacological means. However, recognised

shortcomings in antiarrhythmic drugs spurred the development

Supraventricular tachycardias

Ventricular tachycardias

of non-pharmacological treatments, particularly radiofrequency

ablation and implantable defibrillators.

The two major mechanisms by which arrhythmias occur are

Ischaemic

Non-ischaemic

automaticity and re-entrant excitation. Most arrhythmias are of

the re-entrant type and require two or more pathways that are

anatomically or functionally distinct but in electrical contact.

Atrial

Atrioventricular

Junctional

flutter

fibrillation

ectopy

re-entry tachycardia

The conduction in one pathway must also be slowed to a

sufficient degree to allow recovery of the other so that an

electrical impulse may then re-enter the area of slowed

Focal

Multifocal

Type A

Type B

conduction.

Concealed

Overt accessory pathways (such as

accessory pathways

Wolff-Parkinson-White syndrome)

Classification of arrhythmias

Area of slow

conduction

Indications for electrophysiological studies

Investigation of symptoms

x History of persistent palpitations

Normal

Initiation by premature

Tachycardia

x Recurrent syncope

sinus

extrasystole (or

due

x Presyncope with impaired left ventricular function

rhythm

extrastimulus) causing

to re-entry

Interventions

unidirectional block due

continues

to longer refractory

x Radiofrequency ablation—Accessory pathways, junctional

period down one arm

tachycardias, atrial flutter, atrial fibrillation

x Investigation of arrhythmias (narrow and broad complex) with or

Mechanism of a re-entry circuit. An excitation wave is propagated at a

without radiofrequency ablation

normal rate down path A, but slowly down path B. An excitation wave from

x Assessment or ablation of ventricular arrhythmias

an extrasystole now encounters the slow pathway (B), which is still

Contraindications

refractory, creating unidirectional block. There is now retrograde

x Severe aortic stenosis, unstable coronary disease, left main stem

conduction from path A, which coincides with the end of the refractory

stenosis, substantial electrolyte disturbance

period in path B. This gives rise to a persistent circus movement

Intracardiac electrophysiological

studies

Intracardiac electrophysiological studies give valuable

information about normal and abnormal electrophysiology of

Tricuspid

intracardiac structures. They are used to confirm the

valve

mechanism of an arrhythmia, to delineate its anatomical

Mitral

valve

substrate, and to ablate it. The electrical stability of the ventricles

Coronary

HRA

can also be assessed, as can the effects of an antiarrhythmic

sinus

HBE

ostium

regimen.

CSE

Atrioventricular conduction

Electrodes positioned at various sites in the heart can give only

Tricuspid

valve

limited data about intracardiac conduction during sinus rhythm

RVA

at rest. “Stressing” the system allows more information to be

generated, particularly concerning atrioventricular nodal

Diagrams showing position of pacing or recording electrodes in the heart in

conduction and the presence of accessory pathways.

the right anterior oblique and left anterior oblique views (views from the

By convention, the atria are paced at 100 beats/min for

right and left sides of the chest respectively). HRA=high right atrial

electrode, usually on the lateral wall or appendage; HBE=His bundle

eight beats. The ninth beat is premature (extrastimulus), and the

electrode, on the medial aspect of the tricuspid valve; RVA=right ventricular

AH interval (the time between the atrial signal (A) and the His

apex; CSE=coronary sinus electrode, which records electrical deflections

signal (H), which represents atrioventricular node conduction

from the left side of the heart between the atrium and ventricle

ABC of Interventional Cardiology

time) is measured. This sequence is repeated with the ninth beat

made increasingly premature. In normal atrioventricular nodal

conduction, the AH interval gradually increases as the

extrastimulus becomes more premature and is graphically

represented as the atrioventricular nodal curve. The gradual

HBE1-2

prolongation of the AH interval (decremental conduction) is a

feature that rarely occurs in accessory pathway conduction.

CS1-2

CS3-4

700

600

CS5-6

500

A normal

CS7-8

400

atrioventricular nodal

“hockey stick” curve

CS9-10

300

during antegrade

conduction of atrial

200

extrastimuli. As the

HRA3-4

atrial extrastimulus

100

(A₁-A₂) becomes more

premature, the AH

100

200

300

400

500

600

700

interval (H₁-H₂) shortens

until the atrioventricular

A₁A₂ (msec)

node becomes

functionally refractory

HBE1-2

Retrograde ventriculoatrial conduction

Retrograde conduction through the atrioventricular node is

CS1-2

assessed by pacing the ventricle and observing conduction back

into the atria. The coronary sinus electrode is critically

CS3-4

important for this. It lies between the left ventricle and atrium

and provides information about signals passing over the left

CS5-6

side of the heart. The sequence of signals that pass from the

ventricle to the atria is called the retrograde activation

CS7-8

sequence.

If an accessory pathway is present, this sequence changes:

CS9-10

with left sided pathways, there is an apparent “short circuit” in

the coronary sinus with a shorter ventriculoatrial conduction

time. This is termed a concealed pathway, as its effect cannot be

HRA3-4

seen on a surface electrocardiogram. It conducts retrogradely

only, unlike in Wolff-Parkinson-White syndrome, where the

pathway is bidirectional. Often intracardiac electrophysiological

Coronary sinus electrode signals, with poles CS9-10

placed proximally near

studies are the only way to diagnose concealed accessory

the origin of the coronary sinus and poles 1-2 placed distally reflecting

pathways, which form the basis for many tachycardias with

changes in the left ventricular-left atrial free wall. Top: normal retrograde

narrow QRS complexes.

activation sequence with depolarisation passing from the ventricle back

through the atrioventricular node to the right atrium and simultaneously

across the coronary sinus to the left atrium. Bottom: retrograde activation

sequence in the presence of an accessory pathway in the free wall of the left

Supraventricular tachycardia

ventricle showing a shorter ventriculoatrial (VA) time than would be

expected in the distal coronary sinus electrodes (CS1-2). Such a pathway

Supraventricular tachycardias have narrow QRS complexes

would not be discernible from a surface electrocardiogram

with rates between 150-250 beats/min. The two common

mechanisms involve re-entry due to either an accessory

pathway (overt as in Wolff-Parkinson-White syndrome or

concealed) or junctional re-entry tachycardia.

Accessory pathways

These lie between the atria and ventricles in the atrioventricular

ring, and most are left sided. Arrhythmias are usually initiated

by an extrasystole or, during intracardiac electrophysiological

studies, by an extrastimulus, either atrial or ventricular. The

extrasystole produces delay within the atrioventricular node,

allowing the signal, which has passed to the ventricle, to re-enter

the atria via the accessory pathway. This may reach the

atrioventricular node before the next sinus beat arrives but

when the atrioventricular node is no longer refractory, thus

allowing the impulse to pass down the His bundle and back up

to the atrium through the pathway. As ventricular

depolarisation is normal, QRS complexes are narrow. This

Mechanisms for orthodromic (left) and antedromic (right)

circuit accounts for over 90% of supraventricular tachycardias in

atrioventricular re-entrant tachycardia

Percutaneous interventional electrophysiology

Wolff-Parkinson-White syndrome. Rarely, the circuit is reversed,

and the QRS complexes are broad as the ventricles are fully

V1 1

pre-excited. This rhythm is often misdiagnosed as ventricular in

origin.

CS DIST 1

Treatment—Pathway ablation effects a complete cure by

A V

destroying the arrhythmia substrate. Steerable ablation

CS PROX 1

catheters allow most areas within the heart to be reached. The

left atrium can be accessed either retrogradely via the aortic

ABL CATH 2.5

valve, by flexing the catheter tip through the mitral valve, or

transeptally across the atrial septum. Radiofrequency energy is

delivered to the atrial insertion of a pathway and usually results

V5 1

in either a rapid disappearance of pre-excitation on the surface

electrocardiogram or, in the case of concealed pathways,

Surface electrocardiogram leads V1 and V5 and signals from the distal

normalisation of the retrograde activation sequence. Accessory

coronary sinus electrodes (CS dist), proximal electrodes (CS prox), and the

pathway ablation is 95% successful. Failure occurs from an

tip of the ablation catheter (ABL CATH) during pathway ablation to treat

inability to accurately map pathways or difficulty in delivering

Wolff-Parkinson-White syndrome. The onset of radiofrequency energy (thin

enough energy, usually because of positional instability of the

arrow) produces loss of pre-excitation after two beats with a narrow

complex QRS seen at the fourth beat (broad arrow). Prolongation of the AV

catheter. Complications are rare ( < 0.5%) and are related to

signal in the coronary sinus occurs when pre-excitation is lost

vascular access—femoral artery aneurysms or, with left sided

pathways, embolic cerebrovascular accidents.

Junctional re-entry tachycardia

This is the commonest cause of paroxysmal supraventricular

tachycardia. The atrioventricular nodal curve shows a sudden

700

unexpected prolongation of the AH interval known as a “jump”

in the interval. The tachycardia is initiated at or shortly after the

600

jump. The jump occurs because of the presence of two

500

pathways—one slowly conducting but with relatively rapid

400

recovery (the slow pathway), the other rapidly conducting but

300

with relatively slow recovery (the fast pathway)—called duality of

200

atrioventricular nodal conduction. This disparity between

conduction speed and recovery allows re-entrance to occur. On

100

a surface electrocardiogram the QRS complexes are narrow,

100 200 300 400 500 600 700

and the P waves are often absent or distort the terminal portion

A1A2 (msec)

of the QRS complex. These arrhythmias can often be

terminated by critically timed atrial or ventricular extrastimuli.

Atrioventricular nodal curves. In a patient with slow-fast junctional

In the common type of junctional re-entry tachycardia (type

re-entrant tachycardia (left) there is a “jump” in atrioventricular nodal

A) the circuit comprises antegrade depolarisation of the slow

conduction when conduction changes from the fast to the slow pathway. In a

pathway and retrograde depolarisation of the fast pathway.

patient with accessory pathways conducting antegradely (such as

Rarely ( < 5% of junctional re-entry tachycardias) the circuit is

Wolff-Parkinson-White syndrome) there is no slowing of conduction as seen

in the normal atrioventricular node, and the curve reflects conduction

reversed (type B). The slow and fast pathways are anatomically

exclusively over the pathway (right)

separate, with both inputting to an area called the compact

atrioventricular node. The arrhythmia can be cured by mapping

and ablating either the slow or fast pathway, and overall success

occurs in 98% of cases. Irreversible complete heart block

requiring a permanent pacemaker occurs in 1-2% of cases, with

the risk being higher for fast pathway ablation. Therefore, slow

pathway ablation is the more usual approach.

Atrial

beat

premature

Atrial flutter and atrial fibrillation

Atrial flutter is a macro re-entrant circuit within the right

atrium. The critical area of slow conduction lies at the base of

Slow

Fast

Slow

Fast

pathway

Circus

pathway

the right atrium in the region of the slow atrioventricular nodal

motion

pathway. Producing a discrete line of ablation between the

tricuspid annulus and the inferior vena cava gives a line of

electrical block and is associated with a high success rate in

terminating flutter. Flutter responds poorly to standard

antiarrhythmic drugs, and ablation carries a sufficiently

impressive success rate to make it a standard treatment.

Atrial fibrillation is caused by micro re-entrant wavelets

circulating around the great venous structures, or it may be

related to a focus of atrial ectopy arising within the pulmonary

veins at their junction with the left atrium. The first indication

that atrial fibrillation was electrically treatable came from the

Mechanism of slow-fast junctional re-entrant tachycardia. A premature atrial

Maze operation (1990). Electrical dissociation of the atria from

impulse finds the fast pathway refractory, allowing retrograde conduction

the great veins was carried out by surgical excision of the veins

back up to the atria

ABC of Interventional Cardiology

from their insertion sites and then suturing them back. The

scarred areas acted as insulation, preventing atrial wave-fronts

from circulating within the atria. Similar lines of block can be

achieved by catheter ablation within the right and left atria. The

results look promising, although this is a difficult, prolonged

procedure with a high relapse rate. Of more interest is a

sub-group of patients with runs of atrial ectopy, which

degenerate to paroxysms of atrial fibrillation. These

extrasystoles usually originate from the pulmonary veins, and

their ablation substantially reduces the frequency of

symptomatic atrial fibrillation. With better understanding of the

underlying mechanisms and improved techniques, atrial

fibrillation may soon become a completely ablatable

arrhythmia.

Ventricular tachycardia

Ventricular tachycardia carries a serious adverse prognosis,

particularly in the presence of coronary artery disease and

impaired ventricular function. Treatment options include drugs,

Diagram of basket-shaped mapping catheter with several

occasional surgical intervention (bypass or arrhythmia surgery),

recording electrodes (red dots). The basket retracts into a

catheter for placement in either the atria or ventricles.

and implantable defibrillators, either alone or in combination.

Once it is in position, retraction of the catheter allows the

Ventricular tachycardia can be broadly divided into two groups,

basket to expand

ischaemic and non-ischaemic. The latter includes arrhythmias

arising from the right ventricular outflow tract and those

associated with cardiomyopathies.

Since the radiofrequency energy of an ablation catheter is

destructive only at the site of the catheter tip, this approach

Further reading

lends itself more to arrhythmias where a discrete abnormality

can be described, such as non-ischaemic ventricular tachycardia.

x Olgin JE, Zipes DP. Specific arrhythmias: diagnosis and treatment.

In: Braunwald E, Zipes DP, Libby P, eds. Heart disease. 6th ed.

In ischaemic ventricular tachycardia, where the abnormal

Philadelphia: Saunders, 2001:1877-85

substrate often occurs over a wide area, the success rate is lower.

x McGuire MA, Janse MJ. New insights on the anatomical location of

Ideally, the arrhythmia should be haemodynamically stable,

components of the reentrant circuit and ablation therapy for

reliably initiated with ventricular pacing, and mapped to a

atrioventricular reentrant tachycardia. Curr Opin Cardiol 1995;

localised area within the ventricle. In many cases, however, this

10:3-8

is not possible. The arrhythmia may be unstable after initiation

x Jackman WM, Beckman KJ, McClelland JH, Wang X, Friday KJ,

Roman CA, et al. Treatment of supraventricular tachycardia due to

and therefore cannot be mapped accurately. The circuit may

atrioventricular nodal re-entry by radiofrequency catheter ablation

also lie deep within the ventricular wall and cannot be fully

of the slow-pathway conduction. N Engl J Med 1992;327:313-8

ablated. However, detailed intracardiac maps can be made with

x Calkins H, Leon AR, Deam AG, Kalbfleisch SJ, Langberg JJ,

multipolar catheters. A newer approach is the use of a

Morady F. Catheter ablation of atrial flutter using radiofrequency

non{contact mapping catheter, which floats freely within the

energy. Am J Cardiol 1994;73:353-6

ventricles but senses myocardial electrical circuits.

x Schilling RJ, Peter NS, Davies DW. Feasibility of a non-contact

Although the overall, long term, success rate for

catheter for endocardial mapping of human ventricular

tachycardia. Circulation 1999;99:2543-52

radiofrequency ablation of ischaemic ventricular tachycardia is

only about 65%, this may increase.

Conclusion

The electrophysiological approach to treating arrhythmias has

Competing interests: None declared.

been revolutionised by radiofrequency ablation. Better

The diagrams showing the mechanisms of orthodromic and antedromic

computerised mapping, improved catheters, and more efficient

atrioventricular re-entrant tachycardia and of slow-fast atrioventricular

energy delivery has enabled many arrhythmias to be treated

nodal re{entrant tachycardia are reproduced from ABC of Clinical

Electrocardiography, edited by Francis Morris, 2002.

and cured. The ability to ablate some forms of atrial fibrillation

and improvement in ablation of ventricular tachycardia is

heralding a new age of electrophysiology. Ten years ago it could

have been said that electrophysiologists were a relatively benign

breed of cardiologists who did little harm but little good either.

That has emphatically changed, and it can now be attested that

electrophysiologists exact the only true cure in cardiology.

Implantable devices for treating tachyarrhythmias

Timothy Houghton, Gerry C Kaye

Pacing treatment for tachycardia control has achieved success,

notably in supraventricular tachycardia. Pacing termination for

ventricular tachycardia has been more challenging, but an

understanding of arrhythmia mechanisms, combined with

increasingly sophisticated pacemakers and the ability to deliver

intracardiac pacing and shocks, have led to success with

implantable cardioverter defibrillators.

Mechanisms of pacing termination

There are two methods of pace termination.

Underdrive pacing was used by early pacemakers to treat

supraventricular and ventricular tachycardias. Extrastimuli are

introduced at a constant interval, but at a slower rate than the

tachycardia, until one arrives during a critical period,

terminating the tachycardia. Because of the lack of sensing of

the underlying tachycardia, there is a risk of a paced beat falling

on the T wave, producing ventricular fibrillation or ventricular

Changes in implantable cardioverter defibrillators over 10 years

tachycardia, or degenerating supraventricular tachycardias to

(1992-2002). Apart from the marked reduction in size, the implant technique

atrial fibrillation. It is also not particularly successful at

and required hardware have also dramatically improved—from the

sternotomy approach with four leads and abdominal implantation to the

terminating supraventricular tachycardia or ventricular

present two-lead transvenous endocardial approach that is no more invasive

tachycardia and is no longer used routinely.

than a pacemaker implant

Overdrive pacing is more effective for terminating both

supraventricular and ventricular tachycardias. It is painless,

quick, effective, and associated with low battery drain of the

Mechanisms of arrhythmias

pacemaker. Implantation of devices for terminating

Unicellular

Multicellular

supraventricular tachycardias is now rarely required because of

x Enhanced automaticity

x Re-entry

the high success rate of radiofrequency ablative procedures (see

x Triggered activity—early or

x Electrotonic interaction

previous article). Overdrive pacing for ventricular tachycardia is

delayed after depolarisations x Mechanico-electrical coupling

often successful but may cause acceleration or induce

ventricular fibrillation. Therefore, any device capable of pace

termination of ventricular tachycardia must also have

defibrillatory capability.

Arrhythmias associated with re-entry

x Atrial flutter

x Sinus node re-entry tachycardia

Implantable cardioverter defibrillators

x Junctional re-entry tachycardia

x Atrioventricular reciprocating tachycardias (such

Initially, cardioverter defibrillator implantation was a major

as Wolff-Parkinson-White syndrome)

operation requiring thoracotomy and was associated with 3-5%

x Ventricular tachycardia

mortality. The defibrillation electrodes were patches sewn on to

the myocardium, and leads were tunnelled subcutaneously to

the device, which was implanted in a subcutaneous abdominal

pocket. Early devices were large and often shocked patients

inappropriately, mainly because these relatively unsophisticated

units could not distinguish ventricular tachycardia from

supraventricular tachycardia.

Current implantation procedures

Modern implantable cardioverter defibrillators are transvenous

systems, so no thoracotomy is required and implantation

mortality is about 0.5%. The device is implanted either

subcutaneously, as for a pacemaker, in the left or right

deltopectoral area, or subpectorally in thin patients to prevent

the device eroding the skin.

The ventricular lead tip is positioned in the right ventricular

apex, and a second lead can be positioned in the right atrial

appendage to allow dual chamber pacing if required and

discrimination between atrial and ventricular tachycardias. The

ventricular defibrillator lead has either one or two shocking

Chest radiograph of a dual chamber implantable

coils. For two-coil leads, one is proximal (usually within the

cardioverter defibrillator with a dual coil ventricular

superior vena cava), and one is distal (right ventricular apex).

lead (black arrow) and right atrial lead (white arrow)

ABC of Interventional Cardiology

During implantation the unit is tested under conscious

sedation. Satisfactory sensing during sinus rhythm, ventricular

tachycardia, and ventricular fibrillation is established, as well as

pacing and defibrillatory thresholds. Defibrillatory thresholds

should be at least 10 joules less then the maximum output of

the defibrillator (about 30 joules).

New developments

An important development is the implantable cardioverter

defibrillator’s ability to record intracardiac electrograms. This

allows monitoring of each episode of anti-tachycardia pacing or

defibrillation. If treatment has been inappropriate, then

programming changes can be made with a programming unit

placed over the defibrillator site.

Current devices use anti-tachycardia pacing, with low and

high energy shocks also available—known as tiered therapy.

Anti-tachycardia pacing can take the form of adaptive burst

pacing, with cycle length usually about 80-90% of that of the

Posteroanterior and lateral chest radiographs of transvenous implantable

cardioverter defibrillator showing the proximal and distal lead coils (arrows)

ventricular tachycardia. Pacing bursts can be fixed (constant

cycle length) or autodecremental, when the pacing burst

accelerates (each cycle length becomes shorter as the pacing

train progresses). Should anti-tachycardia pacing fail, low

energy shocks are given first to try to terminate ventricular

tachycardia with the minimum of pain (as some patients remain

conscious despite rapid ventricular tachycardia) and reduce

battery drain, thereby increasing device longevity.

With the advent of dual chamber systems and improved

diagnostic algorithms, shocking is mostly avoided during

supraventricular tachycardia. Even in single lead systems the

(AS)

(AS) AF

AF AF

algorithms are now sufficiently sophisticated to differentiate

165

225

380

420

390

380

388

353

350AF

200

AF165

178

[AS]

353

505

238

208

188

350

170

between supraventricular tachycardia and ventricular

VP-M

435

418VS

420

383

373

523

VP-MT

500

tachycardia. There is a rate stability function, which assesses

410

418

410

385

375

703

500

cycle length variability and helps to exclude atrial fibrillation.

Intracardiac electrograms from an implantable cardioverter defibrillator.

Device recognition of tachyarrhythmias is based mainly on

Upper recording is intra-atrial electrogram, which shows atrial fibrillation.

the tachycardia cycle length, which can initiate anti-tachycardia

Middle and lower tracings are intracardiac electrograms from ventricle

pacing or low energy or high energy shocks. With rapid

tachycardias, the device can be programmed to give a high

energy shock as first line treatment.

Complications

These include infection; perforation, displacement, fracture, or

V V V V V V V V V V VC V V C

insulation breakdown of the leads; oversensing or undersensing

S S S S S S S S S S SE R S D

of the arrhythmia; and inappropriate shocks for sinus tachycardia

or supraventricular tachycardia. Psychological problems are

common, and counselling plays an important role. Regular follow

up is required. If antiarrhythmic drugs are taken the potential use

T T T T T T T T T T T V V V V V V V V V V V V C V V C V

V V V

of an implantable cardioverter defibrillator is reduced.

S S D P P P P P P P P S S S S S S S S S S S S E R S D S

S S S

Precautions—after patient death the device must be switched

off before removal otherwise a severe electric shock can be

delivered to the person removing the device. The implanting

centre or local hospital should be informed that the patient has

died and arrangements can usually be made to turn the ICD

off. The device must be removed before cremation.

T T T T

T T T T T T T T T T T

V F T

Driving and implantable cardioverter defibrillators

S S S S

S D P P P P P P P P P

S S S

The UK Driver and Vehicle Licensing Agency recommends that

group 1 (private motor car) licence holders are prohibited from

driving for six months after implantation of a defibrillator when

there have been preceding symptoms of an arrhythmia. If a

shock is delivered within this period, driving is withheld for a

T T T T T T T T T T T T T T T T T

further six months.

S S S S S S S S D P P P P P P P P

Any change in device programming or antiarrhythmic

Intracardiac electrograms from implantable cardioverter defibrillators. Top:

drugs means a month of abstinence from driving, and all

Ventricular tachycardia terminated with a single high energy shock. Second

down: Ventricular tachycardia acceleration after unsuccessful ramp pacing,

patients must remain under regular review. There is a five year

which was then terminated with a shock. Third down: Unsuccessful fixed

prohibition on driving if treatment or the arrhythmia is

burst pacing. Bottom: Successful ramp pacing termination of ventricular

associated with incapacity.

tachycardia

Implantable devices for treating tachyarrhythmias

Drivers holding a group 2 licence (lorries or buses) are

Guidelines for implanting cardioverter defibrillators

permanently disqualified from driving.

For “primary prevention”

x Non-sustained ventricular tachycardia on Holter monitoring (24

hour electrocardiography)

Indications for defibrillator use

x Inducible ventricular tachycardia on electrophysiological testing

Primary prevention

x Left ventricular dysfunction with an ejection fraction < 35% and no

worse than class 3 of the NYHA functional classification of heart

Primary prevention is considered in those who have had a

failure

myocardial infarction, depressed left ventricular systolic

For “secondary prevention”

function, non-sustained ventricular tachycardia, and inducible

x Cardiac arrest due to ventricular tachycardia or ventricular

sustained ventricular tachycardia at electrophysiological studies.

fibrillation

The major primary prevention trials, MADIT and MUSTT,

x Spontaneous sustained ventricular tachycardia causing syncope or

showed that patients with implanted defibrillators had > 50%

substantial haemodynamic compromise

improvement in survival compared with control patients,

x Sustained ventricular tachycardia without syncope or cardiac arrest

despite 75% of MADIT control patients being treated with the

in patients who have an associated reduction in ejection fraction

(<35%) but are no worse than class 3 of NYHA functional

antiarrhythmic drug amiodarone. A recent trial (MADIT-II)

classification of heart failure

randomised 1232 patients with any history of myocardial

NYHA = New York Heart Association

infarction and left ventricular dysfunction (ejection fraction

< 30%) to receive a defibrillator or to continue medical

treatment and showed that patients with the device had a 31%

reduction in risk of death. Although these results are good news

Names of trials

clinically, they raise difficult questions about the potentially

x MADIT—Multicenter automatic defibrillator implantation trial

crippling economic impact of this added healthcare cost.

x MUSTT—Multicenter unsustained tachycardia trial

Implantation is also appropriate for cardiac conditions with

x COMPANION—Comparison of medical therapy, pacing, and

a high risk of sudden death—long QT syndrome, hypertrophic

defibrillation in chronic heart failure

cardiomyopathy, Brugada syndrome, arrhythmogenic right

ventricular dysplasia, and after repair of tetralogy of Fallot.

Secondary prevention

Secondary prevention is suitable for patients who have survived

cardiac arrest outside hospital or who have symptomatic,

sustained ventricular tachycardia. A meta-analysis of studies of

implanted defibrillators for secondary prevention showed that

they reduced the relative risk of death by 28%, almost entirely

due to a 50% reduction in risk of sudden death.

When left ventricular function is impaired and heart failure

is highly symptomatic, addition of a third pacing lead in the

coronary sinus allows left ventricular pacing and

resynchronisation of ventricular contraction. Indications for

these new “biventricular” pacemakers include a broad QRS

complex ( > 115-130 ms), left ventricular dilatation, and severe

dyspnoea (New York Heart Association class 3). Biventricular

pacing improves symptoms and, when combined with an

implantable cardioverter defibrillator, confers a significant

Chest radiograph showing biventricular pacemaker with

(40%) mortality benefit (COMPANION study).

leads in the right ventricle, right atrium, and coronary

sinus (arrows)

Atrial flutter and fibrillation

Pacing to prevent atrial tachycardias, including atrial fibrillation,

is presently under intense scrutiny as early results have been

favourable. Atrial fibrillation is often initiated by atrial

extrasystoles, and attention has focused on pacing to suppress

atrial extrasystole, thereby preventing paroxysmal and sustained

atrial fibrillation.

Atrial flutter

Termination of atrial flutter is most reliable with burst pacing

from the coronary sinus or right atrium and usually requires

longer periods of pacing (5-30 s). The shorter the paced cycle

length, the sooner the rhythm converts to sinus. Direct

conversion to sinus rhythm is achievable with sustained

overdrive pacing. However, the success of radiofrequency

ablation means these techniques are rarely used.

Atrial fibrillation

Prevention with pacing—Retrospective studies have shown that

Continuous electrocardiogram showing sinus rhythm with frequent atrial

atrial based pacing results in a reduced burden of atrial

extrasystoles (top) arising from the pulmonary veins degenerating into atrial

fibrillation compared with ventricular based pacing. Pacing the

fibrillation (bottom)

ABC of Interventional Cardiology

atria at high rates may prevent the conditions required for

Further reading

re{entry and thus prevent atrial fibrillation. Current research is

x O’Keefe DB. Implantable electrical devices for the treatment of

based on triggered atrial pacing, and specific preventive and

tachyarrhythmias. In: Camm AJ, Ward DE, eds. Clinical aspects of

anti-tachycardia pacing systems are now available for patients

cardiac arrhythmias. London: Kluwer Academic Publishers,

with symptomatic paroxysmal atrial tachycardias that are not

1988:337-57

controlled by drugs. Such devices continually scan the sinus rate

x Cooper RAS, Ideker RE. The electrophysiological basis for the

and monitor atrial extrasystoles. Right atrial overdrive pacing at

prevention of tachyarrhythmias. In: Daubert JC, Prystowsky EN,

10-29 beats per minute faster than the sinus rate suppresses the

Ripart A, eds. Prevention of tachyarrhythmias with cardiac pacing.

frequency of extrasystoles. The pacing rate then slows to allow

Armonk, NY: Futura Publishing, 1997:3-24

x Josephson ME. Supraventricular tachycardias. In: Bussy K, ed.

sinus activity to take over, provided no further extrasystoles are

Clinical cardiac electrophysiology. Philadelphia: Lea and Febiger,

sensed. In some patients atrial fibrillation is initiated during

1993:181-274

sleep, when the sinus rate is vagally slowed. Resynchronisation

x Connolly SJ, Hallstrom AP, Cappato R, Schron EB, Kuck KH,

(simultaneous pacing at two different atrial sites) in patients

Zipes DP, et al. Meta-analysis of the implantable cardioverter

with intra-atrial conduction delay may be beneficial. Clinical

defibrillator secondary prevention trials. Eur Heart J 2000;21:

trials will help answer the question of which form of pacing best

2071-8

x Mirowski M, Mower MM, Staewen WS, Denniston RH, Mendeloff

prevents atrial fibrillation.

AI. The development of the transvenous automatic defibrillator.

Cardioversion with implantable atrial defibrillators—These are

Ann Intern Med 1973;129:773-9

useful in some patients with paroxysmal atrial fibrillation. It is

known that rapid restoration of sinus rhythm reduces the risk of

protracted or permanent atrial fibrillation. Cardioversion is

synchronised to the R wave, and shocks are given between the

Competing interests: TH has been reimbursed by Guidant for attending a

coronary sinus and right ventricular leads. The problem is that

conference in 2001.

shocks of > 1 joule are uncomfortable, and the mean

The figure of implantable cardioverter defibrillators from 1992 and 2002 is

defibrillation threshold is 3 joules. Thus, sedation is required

supplied by C M Finlay, CRT coordinator, Guidant Canada Corporation,

before each shock.

Toronto.

Future developments

With the development of anti-atrial fibrillation pacing, focal

ablation to the pulmonary veins, and flutter ablation,

implantable cardioverter defibrillators will be used less often in

years to come. The future of device therapy for atrial fibrillation

and atrial flutter probably lies in the perfection of

radiofrequency ablation and atrial pacing, although there will

still be a place for atrioventricular nodal ablation and

permanent ventricular pacing in selected patients.

Interventional paediatric cardiology

Kevin P Walsh

Interventional paediatric cardiology mainly involves dilatation

of stenotic vessels or valves and occlusion of abnormal

communications. Many transcatheter techniques—such as

balloon dilatation, stent implantation, and coil occlusion—have

been adapted from adult practice. Devices to occlude septal

defects, developed primarily for children, have also found

application in adults.

Basic techniques

Interventional procedures follow a common method. General

anaesthesia or sedation is required, and most procedures start

with percutaneous femoral access. Haemodynamic

measurements and angiograms may further delineate the

anatomy or lesion severity. A catheter is passed across the

stenosis or abnormal communication. A guidewire is then

passed through the catheter to provide a track over which

Balloon atrial septostomy.

therapeutic devices are delivered. Balloon catheters are

Under echocardiographic

threaded directly, whereas stents and occlusion devices are

control in a neonate with

transposition of the great

protected or constrained within long plastic sheaths.

arteries, a balloon septostomy

catheter has been passed via

the umbilical vein, ductus

Dilatations

venosus, inferior vena cava,

and right atrium and through

Septostomy

the patent foramen ovale into

Balloon atrial septostomy, introduced by Rashkind 35 years ago,

the left atrium. The balloon is

inflated in the left atrium (top)

improves mixing of oxygenated and deoxygenated blood in

and jerked back across the

patients with transposition physiology or in those requiring

atrial septum into the right

venting of an atrium with restricted outflow. Atrial septostomy

atrium (middle). This

outside the neonatal period, when the atrial septum is much

manoeuvre tears the atrial

septum to produce an atrial

tougher, is done by first cutting the atrial septum with a blade.

septal defect (arrow, bottom)

with improved mixing and

arterial saturations

Balloon valvuloplasty

Pulmonary valve stenosis

Balloon valvuloplasty has become the treatment of choice for

pulmonary valve stenosis in all age groups. It relieves the

stenosis by tearing the valve, and the resultant pulmonary

regurgitation is mild and well tolerated. Surgery is used only for

dysplastic valves in patients with Noonan’s syndrome, who have

small valve rings and require a patch to enlarge the annulus.

Valvuloplasty is especially useful in neonates with critical

pulmonary stenosis, where traditional surgery carried a high

mortality. In neonates with the more extreme form of

pulmonary atresia with an intact ventricular septum,

valvuloplasty can still be done by first perforating the

pulmonary valve with a hot wire. Pulmonary valvuloplasty can

also alleviate cyanotic spells in patients with tetralogy of Fallot

Balloon pulmonary

valvuloplasty. A large

whose pulmonary arteries are not yet large enough to undergo

valvuloplasty balloon is

primary repair safely.

inflated across a stenotic

pulmonary valve, which

produces a waist-like balloon

Aortic valve stenosis

indentation (A, top). Further

Unlike in adults, aortic valve stenosis in children (which is

inflation of the balloon

abolishes the waist (bottom).

non{calcific) is usually treated by balloon dilatation. A balloon

This patient had previously

size close to the annulus diameter is chosen, as overdilatation

undergone closure of a

(routinely done in pulmonary stenosis) can result in substantial

mid{muscular ventricular

aortic regurgitation. The balloon is usually introduced

septal defect with a drum

shaped Amplatzer ventricular

retrogradely via the femoral artery and passed across the aortic

septal defect occluder (B, top).

valve. Injection of adenosine, producing brief cardiac standstill

A transoesophageal

during balloon inflation, avoids balloon ejection by powerful left

echocardiogram probe is also

ventricular contraction.

visible

ABC of Interventional Cardiology

In neonates with critical aortic stenosis and poor left

ventricular function the balloon can be introduced in an

antegrade fashion, via the femoral vein and across the

interatrial septum through the patent foramen ovale. This

reduces the risk of femoral artery thrombosis and perforation

of the soft neonatal aortic valve leaflets by guidewires. The long

term result of aortic valve dilatation in neonates depends on

both effective balloon dilatation of the valve and the degree of

associated left heart hypoplasia.

Pulmonary artery stenting. A

child with previously repaired

Angioplasty

tetralogy of Fallot had severe

Balloon dilatation for coarctation of the aorta is used for both

stenoses at the junction of right

native and postsurgical coarctation and is the treatment of

and left branch pulmonary

choice for re-coarctation. Its efficacy in native coarctation

arteries with main pulmonary

artery (top left). Two stents were

depends on the patient’s age and whether there is appreciable

inflated simultaneously across

underdevelopment of the aortic arch. Neonates in whom the

the stenoses in criss-cross

ductal tissue forms a sling around the arch have a good initial

arrangement (top right).

response to dilatation but a high restenosis rate, probably

Angiography shows complete

relief of the stenoses (left)

because of later contraction of ductal tissue. Older patients have

a good response to balloon dilatation. However, overdilatation

may result in formation of an aneurysm.

Stents

The problems of vessel recoil or dissection have been addressed

by the introduction of endovascular stents. This development

has been particularly important for patients with pulmonary

artery stenoses, especially those who have undergone corrective

surgery, for whom repeat surgery can be disappointing. Most

stents are balloon expandable and can be further expanded

after initial deployment with a larger balloon to keep up with a

child’s growth.

Results from stent implantation for pulmonary artery

stenosis have been good, with sustained increases in vessel

diameter, distal perfusion, and gradient reduction.

Complications consist of stent misplacement and embolisation,

in situ thrombosis, and vessel rupture.

Stents are increasingly used to treat native coarctation in

patients over 8 years old. Graded dilatation of a severely stenotic

segment over two operations may be required to avoid

Stenting of coarctation of the aorta. An aortogram in an adolescent boy

shows a long segment coarctation (arrows, left). A cineframe shows the

overdistension and possible formation of an aneurysm. In

stent being inflated into place (middle). Repeat aortagraphy shows

patients with pulmonary atresia without true central pulmonary

complete relief of the coarctation (right)

arteries, stenotic collateral arteries can be enlarged by stent

implantation (often preceded by cutting balloon dilation) to

produce a useful increase in oxygen saturation.

An exciting new advance has been percutaneous valve

replacement. A bovine jugular vein valve is sutured to the inner

aspect of a large stent, which is crimped on to a balloon delivery

system and then expanded into a valveless outflow conduit that

has been surgically placed in the right ventricle. Several patients

have been treated successfully with this system, although follow

up is short.

Occlusions

Transcatheter occlusion of intracardiac and extracardiac

communications has been revolutionised by the development of

the Amplatzer devices. These are made from a cylindrical

Nitinol wire mesh and formed by heat treatment into different

shapes. A sleeve with a female thread on the proximal end of

the device allows attachment of a delivery cable with a male

screw. The attached device can then be pulled and pushed into

Transcatheter closure of a perimembranous ventricular septal defect. Left

ventriculogram shows substantial shunting of dye (in direction of arrow)

the loader and delivery sheath respectively. A family of devices

through a defect in the high perimembranous ventricular septum (left).

has been produced to occlude ostium secundum atrial septal

After placement of an eccentric Amplatzer membranous ventricular septal

defects, patent foramen ovale, patent ductus arteriosus, and

defect device, a repeat left ventriculogram shows complete absence of

ventricular septal defects.

shunting (right)

Interventional paediatric cardiology

Atrial septal defects

The Amplatzer atrial septal defect occluder has the shape of

two saucers connected by a central stent-like cylinder that varies

in diameter from 4 mm to 40 mm to allow closure of both small

and large atrial septal defects. Very large secundum atrial septal

defects with incomplete margins (other than at the aortic end of

the defect) may require a surgically placed patch.

Cineframe showing the three

An atrial septal defect is sized with catheter balloons of

components of the Amplatzer

progressively increasing diameter. An occluder of the correct

atrial septal defect occluder—a

size is then introduced into the left atrium via a long

left atrial disk, central stent

(arrows), and a right atrial

transvenous sheath. The left atrial disk of the occluder is

disk. The device has just been

extruded and pulled against the defect. The sheath is then

unscrewed from the delivery

pulled back to deploy the rest of the device (central waist and

wire, and the male screw on

right atrial disk) and released after its placement is assessed by

the delivery wire can be seen

(arrowhead)

transoesophageal echocardiography. The defect is closed by the

induction of thrombosis on three polyester patches sewn into

the device and is covered by neocardia within two months.

Aspirin is usually for given for six months and clopidrogrel for

6-12 weeks.

Worldwide, several thousand patients have had their atrial

septal defects closed with Amplatzer devices, with high

occlusion rates. Complications are unusual and consist of device

migration ( < 1%), transient arrhythmias (1-2%), and, rarely,

thrombus formation with cerebral thromboembolism or aortic

erosion with tamponade. Transcatheter occlusion is now the

treatment of choice for patients with suitable atrial septal

defects. Other devices are available, but none has the same

Atrial septal defect occlusion. Transoesophageal echocardiograms of an

applicability or ease of use.

atrial septal defect before (left) and after (right) occlusion with an Amplatzer

atrial septal defect device. The three components of the device are easily

Patent foramen ovale

seen. (LA=left atrium, RA=right atrium)

The Amplatzer atrial septal defect occluder can also be used to

treat adults with paradoxical thromboembolism via a patent

foramen ovale. The Amplatzer patent foramen ovale occluder

has no central stent and is designed to close the flap-valve of

the patent foramen ovale. Randomised trials are under way to

Patent foramen ovale closure.

A cine frame of an implanted

compare device closure with medical treatment for preventing

Amplatzer patent foramen

recurrent thromboembolism.

ovale device shows that it

differs from the atrial septal

Patent ductus arteriosus

defect device in not having a

Although premature babies and small infants with a large

central stent. Its right atrial

disk is larger than the left

patent ductus arteriosus are still treated surgically, most patients

atrial disk and faces in a

with a patent ductus arteriosus are treated by transcatheter coil

concave direction towards the

occlusion. This technique has been highly successful at closing

atrial septum

small defects, but when the minimum diameter is > 3 mm

multiple and larger diameter coils are required, which prolongs

the procedure and increases the risk of left pulmonary artery

encroachment. The Amplatzer patent ductus arteriosus plug,

which has a mushroom shaped Nitinol frame stuffed with

polyester, is used for occluding larger defects. The occlusion

rates are close to 100%, higher than published results for

surgical ligation.

Transcatheter plugging of a large

patent ductus arteriosus. An

aortogram shows a large tubular

patent ductus arteriosus with a

large shunt of dye from the aorta

to the pulmonary artery (top left).

An Amplatzer plug is deployed in

the defect, still attached to its

Coil occlusion of a patent ductus arteriosus. An aortogram performed via

delivery wire (top right). A repeat

the transvenous approach shows dye shunting through the small conical

aortogram after release of the

patent ductus arteriosus into the pulmonary artery (left). After placement of

device shows no significant residual

multiple coils, a repeat aortogram shows no residual shunting (right)

shunting (left)

ABC of Interventional Cardiology

Ventricular septal defects

Occlusion devices are especially useful for multiple congenital

muscular ventricular septal defects, which can be difficult to

correct surgically. The Amplatzer occluder device has a

drum{like shape and is deployed through long sheaths with

relatively small diameter.

Such devices have also been used to occlude

perimembranous defects, although in this location they can

interfere with aortic valve function. A device with eccentric

disks, which should avoid interference with adjacent valves, has

recently been introduced. The Amplatzer membranous device

has two discs connected by a short cylindrical waist. The device

Transcatheter closure of a mid-muscular ventricular septal defect. A left

is eccentric, with the left ventricular disc having no margin

ventriculogram shows substantial shunting of dye through a defect in the

superiorly, where it could come near the aortic valve, and a

mid-muscular ventricular septum (left). After placement of an Amplatzer

muscular ventricular septal defect device, a repeat left ventriculogram shows

longer margin inferiorly to hold it on the left ventricular side of

only a small amount of shunting through the device (right), which ceased

the defect. The end screw of the device has a flat portion, which

after three months

allows it to be aligned with a precurved pusher catheter. This

pusher catheter then extrudes the eccentric left ventricular disk

from the specially curved sheath with its longer margin

orientated inferiorly in the left ventricle. Initial results are

The Amplatzer perimembranous

promising, particularly for larger infants with

ventricular septal defect device. The

haemodynamically important ventricular septal defects.

two disks are offset from each

other to minimise the chance of the

Transcatheter occlusion has also been used to treat

left ventricular disk impinging on

ventricular septal defects in adults who have had a myocardial

the aortic valve. The central stent is

infarction, and a specific occluder has been introduced. It differs

much narrower than in the

from the infant device in having a 10 mm long central stent to

muscular ventricular septal defect

device as the membranous septum

accommodate the thicker adult interventricular septum. Its role

is much thinner than the muscular

in treatment is uncertain, but it offers an alternative for patients

septum

who have significant contraindications to surgical closure.

Coil occlusion of unwanted blood vessels

Coil occlusion of unwanted blood vessels (aortopulmonary

collateral arteries, coronary artery fistulae, arteriovenous

malformations, venous collaterals) is increasingly effective

because of improvements in catheter and coil design.

Percutaneous intervention versus

surgery

The growth of interventional cardiology has meant that the

simpler defects are now dealt with in catheterisation

laboratories, and cardiac surgeons are increasingly operating on

more complex lesions such as hypoplastic left heart syndrome.

More importantly, interventional cardiology can complement

the management of these complex patients, resulting in a better

Coil occlusion of a coronary fistula. A selective left coronary arteriogram

outcome for children with congenital heart disease.

shows a fistula arising from the left anterior descending coronary artery

(arrow, left) draining to the right ventricle (RV). Multiple interlocking

Complications such as device embolisation, vessel or

detachable coils are placed to completely occlude the fistula (arrow, right)

chamber perforation, thrombosis, and radiation exposure can

be reduced by careful selection of patients and devices,

meticulous technique, low dose pulsed fluoroscopy, and, most

Further reading

importantly, operator experience. Further developments in

x Kan JS, White RI Jr, Mitchell SE, Gardner TJ. Percutaneous balloon

valvuloplasty: a new method for treating congenital pulmonary

catheter and device design will improve and widen treatment

valve stenosis. N Engl J Med 1982;307:540-2

applications.

x Waight DJ, Cao Q-L, Hijazi ZM. Interventional cardiac

catheterisation in adults with congenital heart disease. In: Grech

ED, Ramsdale DR, eds. Practical interventional cardiology. 2nd ed.

Competing interests: None declared.

London: Martin Dunitz, 2002:390-406

x Morrison WL, Walsh KP. Transcatheter closure of ventricular septal

defect post myocardial infarction. In: Grech ED, Ramsdale DR, eds.

Practical interventional cardiology. 2nd ed. London: Martin Dunitz,

2002:362-4

x Masura J, Walsh KP, Thanopoulous B, Chan C, Bass J, Goussous Y,

et al. Catheter closure of moderate- to large-sized patent ductus

arteriosus using the new Amplatzer duct occluder: immediate and

short-term results. J Am Coll Cardiol 1998;31:878-82

x Walsh KP, Maadi IM. The Amplatzer septal occluder. Cardiol Young

2000;10:493-50

Index

Page numbers in bold type refer to figures; those in italics refer to tables.

abciximab 21, 25, 26, 26, 27, 28

balloon pump, intra-aortic 8, 20

ablation

30-1, 39-40

balloon septostomy 45, 45

accessory pathways 37-8, 37, 38, 39-40

balloon valvuloplasty

29-30, 45-6, 45, 46

acute coronary events 1

barotrauma, arterial

acute coronary syndromes 16-18, 16, 19-21

blood vessels, coil occlusion

48, 48

diagnosis

16-17

brachytherapy 5, 10, 10, 34

management 35, 35

bypass surgery 12, 35

adjunctive pharmacotherapy see pharmacotherapy,

chronic stable angina 12, 12, 13, 13, 14-15, 14

interventional

emergency 9, 24, 27

AH interval 37-8

percutaneous in situ 36

Amplatz catheter 3, 3

Amplatzer septal defect occluders 31-2, 31, 32, 47,

“candy wrapper” lesions 10, 10

47, 48

cardiac biochemical markers 16, 17, 18

angina 1-4, 5, 15

cardiac tamponade 9, 23, 47

see also chronic stable angina; unstable angina

cardiac troponin I/T 17, 18

angiography 3, 3, 3, 17, 17, 24, 33

cardiogenic shock 22-4, 22

angioplasty

5, 5, 6, 6, 19-20

cardiology referral, priorities for

1, 1

paediatric

cardiomyopathy, hypertrophic 30-1, 30, 30, 31

anterior descending arteries

14, 20, 22, 33, 34

cardiovascular disease

1, 1

anticoagulent therapy see aspirin; heparin

genetic

antiplatelet drugs

5, 7, 25, 26-8