ABCOF

INTERVENTIONALCARDIOLOGY

Edited by Ever D Grech

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ABC OF INTERVENTIONAL CARDIOLOGY

For Lisa, Alexander, and Frances

ABC OF INTERVENTIONAL CARDIOLOGY

Edited by

EVER D GRECHConsultant Cardiologist, South Yorkshire Cardiothoracic Centre,

Northern General Hospital, Sheffield, UK

© BMJ Publishing Group 2004

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording and/or otherwise, without the prior written permission of the publishers.

First published in 2004 by BMJ Publishing Group Ltd, BMA House, Tavistock Square,

London WC1H 9JR

www.bmjbooks.com

British Library Cataloguing in Publication DataA catalogue record for this book is available from the British Library

ISBN 0 7279 1546 0

Cover shows coloured arteriogram of arteries of the heart. With permission from Science Photo Library.

Typeset by BMJ Electronic Production and Newgen Imaging SystemsPrinted and bound in Spain by GraphyCems, Navarra

v

Contents

Contributors vi

Preface vii

Acknowledgements viii

1 Pathophysiology and investigation of coronary artery disease 1Ever D Grech

2 Percutaneous coronary intervention. I: History and Development 5Ever D Grech

3 Percutaneous coronary intervention. II: The procedure 8 Ever D Grech

4 Chronic stable angina: treatment options 12Laurence O’Toole, Ever D Grech

5 Acute coronary syndrome: unstable angina and non-ST segment elevation myocardial infarction 16Ever D Grech, David R Ramsdale

6 Acute coronary syndrome: ST segment elevation myocardial infarction 19Ever D Grech, David R Ramsdale

7 Percutaneous coronary intervention: cardiogenic shock 22John Ducas, Ever D Grech

8 Interventional pharmacotherapy 25Roger Philipp, Ever D Grech

9 Non-coronary percutaneous intervention 29Ever D Grech

10 New developments in percutaneous coronary intervention 33Julian Gunn, Ever D Grech, David Crossman, David Cumberland

11 Percutaneous interventional electrophysiology 37Gerry C Kaye

12 Implantable devices for treating tachyarrhythmias 41Timothy Houghton, Gerry C Kaye

13 Interventional paediatric cardiology 45Kevin P Walsh

Index 49

vi

David CrossmanProfessor of Clinical Cardiology, Cardiovascular ResearchGroup, Clinical Sciences Centre, Northern General Hospital,Sheffield

David CumberlandConsultant Cardiovascular Interventionist, Ampang PuteriSpecialist Hospital, Kuala Lumpur, Malaysia

John DucasConsultant Cardiologist, Health Sciences Centre and St Boniface Hospital, Winnipeg, Manitoba and AssociateProfessor, University of Manitoba, Winnipeg, Canada

Ever D GrechConsultant Cardiologist, South Yorkshire CardiothoracicCentre, Northern General Hospital, Sheffield, UK

Julian GunnSenior Lecturer and Honorary Consultant Cardiologist,Cardiovascular Research Group, Clinical Sciences Centre,Northern General Hospital, Sheffield

Timothy HoughtonRegistrar in Cardiology, Hull and East Yorkshire Trust, CastleHill Hospital, Hull

Gerry C KayeConsultant Cardiologist, Hull and East Yorkshire Trust, CastleHill Hospital, Hull

Laurence O’TooleConsultant Cardiologist and Physician, Royal HallamshireHospital, Sheffield

Roger PhilippFellow in Interventional Cardiology, Health Sciences Centreand St Boniface Hospital, Winnipeg, Manitoba, Canada

David R RamsdaleConsultant Cardiologist, Cardiothoracic Centre, Liverpool

Kevin P WalshConsultant Paediatric Cardiologist, Our Lady’s Hospital for Sick Children, Crumlin, Dublin, Republic of Ireland

Contributors

vii

Preface

It is only 26 years since the first percutaneous transluminal coronary angioplasty (PTCA) was carried out by the pioneering Swissradiologist, Andreas Greuntzig, heralding the dawn of interventional cardiology. In this short time, interventional cardiology hasovercome 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 numberscontinue 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 becomingwidely used in the management of unstable angina and acute myocardial infarction with definite benefits in terms of morbidity andmortality. The effectiveness and safety of these procedures has undoubtedly been enhanced by the adjunctive use of new anti-plateletand 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, andmulti-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 alternativesto surgery, as have paediatric interventional procedures. A greater understanding of cardiac electrophysiology has led to importantadvances 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 technologygenerated by industry and new techniques coupled with high levels of expertise are fuelling advances in almost all areas ofinterventional cardiology. As drug-eluting stents address the Achilles’ heel of angioplasty and stenting—restenosis—the hugeincrease in percutaneous coronary procedures seen over recent years is likely to increase even further, and will probably be doublethe rate of bypass surgery within a decade.

In writing and editing this book, I have endeavoured to present broad (and sometimes complex) aspects of interventionalcardiology 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 GRECHSheffield, July 2003

viii

Acknowledgements

I have many people to thank for helping me develop and produce this book. I am very grateful to my coauthors who have allwillingly contributed their time and expertise. I would also like to recognise the positive efforts and invaluable assistance of theBritish Medical Journal editors and illustrators. These include Trish Groves, Mary Banks, Eleanor Lines, Greg Cotton, and NaomiWilkinson.

Finally, my enduring gratitude goes to my family for their unfailing encouragement, patience, and love.

1 Pathophysiology and investigation of coronaryartery diseaseEver D Grech

In affluent societies, coronary artery disease causes severedisability and more death than any other disease, includingcancer. It manifests as angina, silent ischaemia, unstable angina,myocardial infarction, arrhythmias, heart failure, and suddendeath.

PathophysiologyCoronary artery disease is almost always due to atheromatousnarrowing and subsequent occlusion of the vessel. Earlyatheroma (from the Greek athera (porridge) and oma (lump)) ispresent from young adulthood onwards. A mature plaque iscomposed of two constituents, each associated with a particularcell population. The lipid core is mainly released from necrotic“foam cells”—monocyte derived macrophages, which migrateinto the intima and ingest lipids. The connective tissue matrix isderived from smooth muscle cells, which migrate from themedia into the intima, where they proliferate and change theirphenotype 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 flowthrough the coronary artery during exertion may lead toangina. Acute coronary events usually arise when thrombusformation follows disruption of a plaque. Intimal injury causesdenudation of the thrombogenic matrix or lipid pool andtriggers thrombus formation. In acute myocardial infarction,occlusion is more complete than in unstable angina, wherearterial occlusion is usually subtotal. Downstream embolism ofthrombus may also produce microinfarcts.

InvestigationsPatients presenting with chest pain may be identified as havingdefinite or possible angina from their history alone. In theformer group, risk factor assessment should be undertaken,both to guide diagnosis and because modification of someassociated risk factors can reduce cardiovascular events andmortality. A blood count, biochemical screen, and thyroidfunction tests may identify extra factors underlying the onset ofangina. Initial drug treatment should include aspirin, a� blocker, and a nitrate. Antihypertensive and lipid loweringdrugs may also be given, in conjunction with advice on lifestyleand risk factor modification.

All patients should be referred to a cardiologist to clarify thediagnosis, optimise drug treatment, and assess the need andsuitability for revascularisation (which can improve bothsymptoms and prognosis). Patients should be advised to seekurgent medical help if their symptoms occur at rest or onminimal exertion and if they persist for more than 10 minutesafter sublingual nitrate has been taken, as these may herald theonset of an acute coronary syndrome.

Foamcells

Fattystreak

Intermediatelesion

Atheroma Fibrousplaque

Complicatedlesion or rupture

From first decade From third decade From fourth decade

Growth mainly by lipid accumulationSmoothmuscle

and collagen

Thrombosis,haematoma

Progression of atheromatous plaque from initial lesion to complex andruptured plaque

Intima (endothelium and internal elastic lamina)

Media (smooth muscle cells and elastic tissue)

Adventitia (fibroblasts and connective tissue)

Media

Adventitia

Intima

Collagen

Key

Dividing smoothmuscle cell

Oxidised lowdensity lipoprotein

Monocyte

Monocyte-derivedmacrophages(foam cells)

Normal coronaryartery

Developmentof atheroma

Plasma low density lipoproteinMonocyte Lumen

Lumen

Lumen

Lumen

Schematic representation of normal coronary artery wall (top) anddevelopment of atheroma (bottom)

Priorities for cardiology referralx Recent onset of symptomsx Rapidly progressive symptomsx Possible aortic stenosisx Threatened employment

x Severe symptoms (minimalexertion or nocturnal angina)

x Angina refractory to medicaltreatment

Cardiovascular risk factorsNon-modifiable risk factorsx Positive family history

Modifiable risk factorsx Hypercholesterolaemiax Left ventricular

hypertrophyx Overweight and obesity

Uncertain risk factorsx Hypertriglyceridaemiax Microalbuminuriax Hyperhomocysteinaemia

x Age

x Hypertensionx Sedentary lifestylex Excessive alcohol

intake

x Lp(a) lipoproteinx Fibrinogenx C reactive protein

x Male sex

x Smokingx Diabetes

x Uric acidx Renin

1

Non-invasive investigationsElectrocardiographyAn abnormal electrocardiogram increases the suspicion ofsignificant coronary disease, but a normal result does notexclude it.

Chest x rayPatients with angina and no prior history of cardiac diseaseusually have a normal chest x ray film.

Exercise electrocardiographyThis is the most widely used test in evaluating patients withsuspected angina. It is generally safe (risk ratio of major adverseevents 1 in 2500, and of mortality 1 in 10 000) and providesdiagnostic as well as prognostic information. The averagesensitivity and specificity is 75%. The test is interpreted in termsof achieved workload, symptoms, and electrocardiographicresponse. A 1 mm depression in the horizontal ST segment isthe usual cut-off point for significant ischaemia. Poor exercisecapacity, an abnormal blood pressure response, and profoundischaemic electrocardiographic changes are associated with apoor prognosis.

Stress echocardiographyStress induced impairment of myocardial contraction is asensitive marker of ischaemia and precedeselectrocardiographic changes and angina. Cross sectionalechocardiography can be used to evaluate regional and globalleft ventricular impairment during ischaemia, which can beinduced by exercise or an intravenous infusion of drugs thatincrease myocardial contraction and heart rate (such asdobutamine) or dilate coronary arterioles (such as dipyridamoleor adenosine). The test has a higher sensitivity and specificitythan exercise electrocardiography and is useful in patientswhose physical condition limits exercise.

Radionuclide myocardial perfusion imagingThallium-201 or technetium-99m (99mTc-sestamibi,99mTc-tetrofosmin) is injected intravenously at peak stress, and itsmyocardial distribution relates to coronary flow. Images areacquired with a gamma camera. This test can distinguishbetween reversible and irreversible ischaemia (the lattersignifying infarcted tissue). Although it is expensive andrequires specialised equipment, it is useful in patients whoseexercise test is non-diagnostic or whose exercise ability islimited.

Exercise stress testingIndicationsx Confirmation of suspected anginax Evaluation of extent of myocardial

ischaemia and prognosisx Risk stratification after myocardial

infarctionx Detection of exercise induced

symptoms (such as arrhythmias orsyncope)

x Evaluation of outcome ofinterventions (such aspercutaneous coronaryinterventions or coronary arterybypass surgery)

x Assessment of cardiac transplantx Rehabilitation and patient

motivation

Contraindicationsx Cardiac failurex Any feverish illnessx Left ventricular outflow tract

obstruction or hypertrophiccardiomyopathy

x Severe aortic or mitralstenosis

x Uncontrolled hypertensionx Pulmonary hypertensionx Recent myocardial infarctionx Severe tachyarrhythmiasx Dissecting aortic aneurysmx Left main stem stenosis or

equivalentx Complete heart block (in

adults)

I aVR V1 V4

II aVL V2 V5

III aVF V3 V6

I

Rest

Peak exercise

aVR V1 V4

II aVL V2 V5

III aVF V3 V6

Example of a strongly positive exercise test. After only 2 minutes and 24seconds of exercise (according to Bruce protocol), the patient developedchest pain and electrocardiography showed marked ischaemic changes(maximum 3 mm ST segment depression in lead V6)

99mTc-tetrofosmin perfusion scan showing reversible anterolateral wallischaemia, induced by intravenous dobutamine infusion (white arrows).Normal rest images are shown by yellow arrows

Main end points for exercise electrocardiographyx Target heart rate achieved ( > 85% of maximum predicted heart rate)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)x Decrease in systolic blood pressure > 20 mm Hgx Increase in diastolic blood pressure > 15 mm Hgx Progressive ST segment elevation or depressionx ST segment depression > 3 mm without painx Arrhythmias (atrial fibrillation, ventricular tachycardia)

Features indicative of a strongly positive exercise testx Exercise limited by angina to < 6 minutes of Bruce protocolx Failure of systolic blood pressure to increase > 10 mm Hg, or fall

with evidence of ischaemiax Widespread marked ST segment depression > 3 mmx Prolonged recovery time of ST changes ( > 6 minutes)x Development of ventricular tachycardiax ST elevation in absence of prior myocardial infarction

ABC of Interventional Cardiology

2

A multigated acquisition (MUGA) scan assesses leftventricular function and can reveal salvageable myocardium inpatients with chronic coronary artery disease. It can beperformed with either thallium scintigraphy at rest or metabolicimaging with fluorodeoxyglucose by means of either positronemission tomography (PET) or single photon emissioncomputed tomography (SPECT).

Invasive investigationsCoronary angiographyThe only absolute way to evaluate coronary artery disease is byangiography. It is usually performed as part of cardiaccatheterisation, which includes left ventricular angiography andhaemodynamic measurements, providing a more completeevaluation of an individual’s cardiac status. Cardiaccatheterisation is safely performed as a day case procedure.

Patients must be fully informed of the purpose of theprocedure as well as its risks and limitations. Majorcomplications, though rare in experienced hands, include death(risk ratio 1 in 1400), stroke (1 in 1000), coronary arterydissection (1 in 1000), and arterial access complications (1 in500). Risks depend on the individual patient, and predictorsinclude age, coronary anatomy (such as severe left main stemdisease), impaired left ventricular function, valvar heart disease,the clinical setting, and non-cardiac disease. The commonestcomplications are transient or minor and include arterial accessbleeding and haematoma, pseudoaneurysm, arrhythmias,reactions to the contrast medium, and vagal reactions (duringsheath insertion or removal).

Before the procedure, patients usually fast and may be givena sedative. Although a local anaesthetic is used, arterial access(femoral, brachial, or radial) may be mildly uncomfortable.Patients do not usually feel the catheters once they are insidethe arteries. Transient angina may occur during injection ofcontrast medium, usually because of a severely diseased artery.Patients should be warned that, during left ventricularangiography, the large volume of contrast medium may cause atransient hot flush and a strange awareness of urinaryincontinence (and can be reassured that this does not actuallyhappen). Modern contrast agents rarely cause nausea andvomiting.

Insertion of an arterial sheath with a haemostatic valveminimises blood loss and allows catheter exchange. Three typesof catheter, which come in a variety of shapes and diameters,are commonly used. Two have a single hole at the end and aredesigned to facilitate controlled engagement of the distal tipwithin the coronary artery ostium. Contrast medium is injectedthrough the lumen of the catheter, and moving x ray images areobtained and recorded. Other catheters may be used for graftangiography. The “pigtail” catheter has an end hole and severalside holes and is passed across the aortic valve into the leftventricle. It allows injection of 30-40 ml of contrast medium

Main indications for coronary angiographyx Uncertain diagnosis of angina (coronary artery disease cannot be

excluded by non-invasive testing)x Assessment of feasibility and appropriateness of various forms of

treatment (percutaneous intervention, bypass surgery, medical)x Class I or II stable angina with positive stress test or class III or IV

angina without positive stress testx Unstable angina or non-Q wave myocardial infarction (medium

and high risk patients)x Angina not controlled by drug treatmentx Acute myocardial infarction—especially cardiogenic shock,

ineligibility for thrombolytic treatment, failed thrombolyticreperfusion, re-infarction, or positive stress test

x Life threatening ventricular arrhythmiax Angina after bypass surgery or percutaneous interventionx Before valve surgery or corrective heart surgery to assess occult

coronary artery disease

Angiograms of normal coronary arteries (LAD=left anterior descendingartery, DG=diagonal artery, LCx=left circumflex artery, OM=obtuse marginalartery, SAN=sino-atrial node artery, RV=right ventricular branch artery,LV=left ventricular branch artery, PDA=posterior descending artery)

Left ventricularangiogram during diastole(top) and systole (bottom)after injection of contrastmedium via a pigtailcatheter, showing goodcontractility (LCA=leftcoronary artery)

Commonly used diagnostic catheters (from leftto right): right Judkins, left Judkins,multipurpose, left Amplatz, and pigtail

Pathophysiology and investigation of coronary artery disease

3

over three to five seconds by a motorised pump, providingvisualisation of left ventricular contraction over two to fourcardiac cycles. Aortic and ventricular pressures are alsorecorded during the procedure.

Intravascular ultrasound (IVUS)In contrast to angiography, which gives a two dimensionalluminal silhouette with little information about the vessel wall,intravascular ultrasound provides a cross sectional, threedimensional image of the full circumference of the artery. Itallows precise measurement of plaque length and thickness andminimum lumen diameter, and it may also characterise theplaque’s composition.

It is often used to clarify ambiguous angiographic findingsand to identify wall dissections or thrombus. It is most usefulduring percutaneous coronary intervention, when target lesionscan be assessed before, during, and after the procedure and atfollow up. The procedure can also show that stents which seemto be well deployed on angiography are, in fact, suboptimallyexpanded. Its main limitations are the need for an operatorexperienced in its use and its expense; for these reasons it is notroutinely used in many centres.

Doppler flow wire and pressure wireUnlike angiography or intravascular ultrasound, the Dopplerflow wire and pressure wire provide information on thephysiological importance of a diseased coronary artery. Theyare usually used when angiography shows a stenosis that is ofintermediate severity, or to determine the functional severity ofa residual stenosis after percutaneous coronary intervention.

Intracoronary adenosine is used to dilate the distal coronaryvessels in order to maximise coronary flow. The Doppler flowwire has a transducer at its tip, which is positioned beyond thestenosis to measure peak flow velocity. The pressure wire has atip micrometer, which records arterial pressures proximal anddistal to the stenosis.

The figure showing progression of atheromatous plaque from initial lesionis adapted with permission from Pepine CJ, Am J Cardiol 1998;82(suppl10A):23-7S.Competing interests: None declared.

IVUS catheter

IVUS catheter

Stent struts

Fibro-fattyplaque

Lumen

Media andadventitia

border

Vessel

Ultrasoundscan plane

The intravascular ultrasound (IVUS) catheter (above) and images showing astent within a diseased coronary artery (below)

Angina?

Definite or possible

Risk factor assessment, blood tests, electrocardiography

Unlikely

Drug treatment for symptoms and risk factor reduction

Refer to cardiologist

Stress test

Strongly positive Mildly positive Negative

Poor control Good control

Review diagnosis

Not anginaAngina

Continue medical treatment

Angiography

Revascularisation (PCI or CABG)

Medical treatment

Algorithm for management of suspected angina (PCI=percutaneouscoronary intervention, CABG=coronary artery bypass grafting)

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

et al. Prognostic value of a treadmill exercise score in outpatientswith suspected coronary artery disease. N Engl J Med 1991;325:849-53

x Marwick TH, Case C, Sawada S, Rimmerman C, Brenneman P,Kovacs R, et al. Prediction of mortality using dobutamineechocardiography. J Am Coll Cardiol 2001;37:754-60

x Scanlon PJ, Faxon DP, Audet AM, Carabello B, Dehmer GJ, EagleKA, et al. ACC/AHA guidelines for coronary angiography. A reportof the American College of Cardiology/American HeartAssociation Task Force on Practice Guidelines (Committee onCoronary Angiography). J Am Coll Cardiol 1999;33:1756-824

x Mintz GS, Nissen SE, Anderson WD, Bailey SR, Erbel R, FitzgeraldPJ, et al. American College of Cardiology clinical expert consensusdocument on standards for acquisition, measurement and reportingof intravascular ultrasound studies (IVUS). J Am Coll Cardiol2001;37:1478-92

ABC of Interventional Cardiology

4

2 Percutaneous coronary intervention.I: History and developmentEver D Grech

The term “angina pectoris” was introduced by Heberden in1772 to describe a syndrome characterised by a sensation of“strangling and anxiety” in the chest. Today, it is used for chestdiscomfort attributed to myocardial ischaemia arising fromincreased myocardial oxygen consumption. This is ofteninduced by physical exertion, and the commonest aetiology isatheromatous coronary artery disease. The terms “chronic” and“stable” refer to anginal symptoms that have been present for atleast several weeks without major deterioration. However,symptom variation occurs for several reasons, such as mentalstress, ambient temperature, consumption of alcohol or largemeals, and factors that may increase coronary tone such asdrugs and hormonal change.

ClassificationThe Canadian Cardiovascular Society has provided a gradedclassification of angina which has become widely used. Inclinical practice, it is important to describe accurately specificactivities associated with angina in each patient. This shouldinclude walking distance, frequency, and duration of episodes.

History of myocardialrevascularisationIn the management of chronic stable angina, there are twoinvasive techniques available for myocardial revascularisation:coronary artery bypass surgery and catheter attached devices.Although coronary artery bypass surgery was introduced in1968, the first percutaneous transluminal coronary angioplastywas not performed until September 1977 by AndreasGruentzig, a Swiss radiologist, in Zurich. The patient, 38 yearold Adolph Bachman, underwent successful angioplasty to a leftcoronary artery lesion and remains well to this day. After thesuccess of the operation, six patients were successfully treatedwith percutaneous transluminal coronary angioplasty in thatyear.

By today’s standards, the early procedures usedcumbersome equipment: guide catheters were large and couldeasily traumatise the vessel, there were no guidewires, andballoon catheters were large with low burst pressures. As aresult, the procedure was limited to patients with refractoryangina, good left ventricular function, and a discrete, proximal,concentric, and non-calcific lesion in a single major coronaryartery with no involvement of major side branches orangulations. Consequently, it was considered feasible in only10% of all patients needing revascularisation.

Developments in percutaneousinterventionDuring 1977-86 guide catheters, guidewires, and ballooncatheter technology were improved, with slimmer profiles andincreased tolerance to high inflation pressures. As equipmentimproved and experience increased, so more complex lesionswere treated and in more acute situations. Consequently,

Canadian Cardiovascular Society classification of anginaClass Ix No angina during ordinary physical activity such as walking or

climbing stairsx Angina during strenuous, rapid, or prolonged exertion

Class IIx Slight limitation of ordinary activityx Angina on walking or climbing stairs rapidly; walking uphill;

walking or climbing stairs shortly after meals, in cold or wind, whenunder emotional stress, or only in the first few hours after waking

x Angina on walking more than two blocks (100-200 m) on the levelor climbing more than one flight of stairs at normal pace and innormal conditions

Class IIIx Marked limitation of ordinary physical activityx Angina on walking one or two blocks on the level or climbing one

flight of stairs at normal pace and in normal conditions

Class IVx Inability to carry out any physical activity without discomfortx Includes angina at rest

Percutaneous transluminal coronary angioplasty (PTCA) 1977

Stents Athero-ablative devices(directional coronary atherectomy, rotablator, lasers)

New stent designsand "smart" stents• Pre-mounted• Increased flexibility and radial strength• Covered stents• Coated stents

• Biodegradable stents• Drug or gene delivery stents• Radioactive stents

Brachytherapy• β radiation emission• γ radiation emission

New balloon designs• Low profile• High inflation• Short or long balloons• Cutting balloons

Adjunctivepharmacotherapy• ADP antagonists• Glycoprotein IIb/ IIIa inhibitors

• "Designer" drugs

Mid1990s

onwards

Development in PTCA equipment(soft tipped guide catheters, steerable guidewires, lower profile balloon catheters)

Mid1980s

Major milestones in percutaneous coronary intervention

Modern ballooncatheter: its lowprofile facilitateslesion crossing, theflexible shaft allowstracking downtortuous vessels, andthe balloon can beinflated to highpressures withoutdistortion or rupture

5

percutaneous transluminal coronary angioplasty can now beundertaken in about half of patients needing revascularisation(more in some countries), and it is also offered to high-riskpatients for whom coronary artery bypass surgery may beconsidered too dangerous.

Although percutaneous transluminal coronary angioplastycauses plaque compression, the major change in lumengeometry 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 ofpercutaneous transluminal coronary angioplasty{acute vesselclosure and restenosis.

Acute vessel closure—This usually occurs within the first 24hours of the procedure in about 3-5% of cases and followsvessel dissection, acute thrombus formation, or both. Importantclinical consequences include myocardial infarction, emergencycoronary artery bypass surgery, and death.

Restenosis occurring in the first six months after angioplastyis caused largely by smooth muscle cell proliferation andfibrointimal hyperplasia (often called neointimal proliferation),as well as elastic recoil. It is usually defined as a greater than50% reduction in luminal diameter and has an incidence of25-50% (higher after vein graft angioplasty). Furtherintervention may be indicated if angina and ischaemia recur.

Drills, cutters, and lasersIn the 1980s, two main developments aimed at limiting theseproblems emerged. The first were devices to remove plaquematerial, such as by rotational atherectomy, directional coronaryatherectomy, transluminal extraction catheter, and excimerlaser. By avoiding the vessel wall trauma seen duringpercutaneous transluminal coronary angioplasty, it wasenvisaged that both acute vessel closure and restenosis rateswould be reduced.

However, early studies showed that, although acute closurerates were reduced, there was no significant reduction inrestenosis. Moreover, these devices are expensive, notparticularly user friendly, and have limited accessibility to moredistal stenoses. As a result, they have now become niche toolsused by relatively few interventionists. However, they may havean emerging role in reducing restenosis rates when used asadjunctive treatment before stenting (especially for largeplaques) and in treating diffuse restenosis within a stent.

Intracoronary stentsThe second development was the introduction of intracoronarystents deployed at the site of an atheromatous lesion. Thesewere introduced in 1986 with the objective of tacking downdissection flaps and providing mechanical support. They alsoreduce elastic recoil and remodelling associated with restenosis.

The first large randomised studies conclusively showed thesuperiority of stenting over coronary angioplasty alone, both inclinical and angiographic outcomes, including a significant 30%reduction in restenosis rates. Surprisingly, this was not due toinhibition of neointimal proliferation—in fact stents mayincrease this response. The superiority of stenting is that theinitial gain in luminal diameter is much greater than afterangioplasty alone, mostly because of a reduction in elasticrecoil.

Although neointimal proliferation through the struts of thestent occurs, it is insufficient to cancel out the initial gain,leading to a larger lumen size and hence reduced restenosis.Maximising the vessel lumen is therefore a crucial mechanismfor reducing restenosis. “Bigger is better” is the adage followedin this case.

Micrographs showing arterialbarotrauma caused by coronaryangioplasty. Top left: coronaryarterial dissection with large flap.Top right: deep fissuring withincoronary artery wall atheroma.Bottom: fragmented plaque tissue(dark central calcific plaquesurrounded by fibrin andplatelet-rich thrombus), which mayembolise in distal arterioles to causeinfarction

Tools for coronary atherectomy. Top:the Simpson atherocath has a cutter ina hollow cylindrical housing. The cutterrotates at 2000 rpm, and excisedatheromatous tissue is pushed into thedistal nose cone. Left: the Rotablatorburr is coated with 10 �m diamondchips to create an abrasive surface. Theburr, connected to a drive shaft and aturbine powered by compressed air,rotates at speeds up to 200 000 rpm

Coronary stents. Top: Guidant Zeta stent. Middle: BiodivYsio AS stent coatedwith phosphorylcholine, a synthetic copy of the outer membrane of redblood cells, which improves haemocompatibility and reduces thrombosis.Bottom: the Jomed JOSTENT coronary stent graft consists of a layer ofPTFE (polytetrafluoroethylene) sandwiched between two stents and is usefulin sealing perforations, aneurysms, and fistulae

ABC of Interventional Cardiology

6

Early stent problemsAs a result of initial studies, stents were predominantly usedeither as “bail out” devices for acute vessel closure duringcoronary angioplasty (thus avoiding the need for immediatecoronary artery bypass surgery) or for restenosis afterangioplasty.

Thrombosis within a stent causing myocardial infarctionand death was a major concern, and early aggressiveanticoagulation to prevent this led to frequent complicationsfrom arterial puncture wounds as well as major systemichaemorrhage. These problems have now been overcome by theintroduction of powerful antiplatelet drugs as a substitute forwarfarin. The risk of thrombosis within a stent diminishes whenthe stent is lined with a new endothelial layer, and antiplatelettreatment can be stopped after a month. The recognition thatsuboptimal stent expansion is an important contributor tothrombosis in stents has led to the use of intravascularultrasound to guide stent deployment and high pressureinflations to ensure complete stent expansion.

Current practiceA greater understanding of the pathophysiology of stentdeployment, combined with the development of more flexiblestents (which are pre-mounted on low-profile catheterballoons), has resulted in a massive worldwide increase in stentuse, and they have become an essential component of coronaryintervention. Low profile stents have also allowed “direct”stenting—that is, implanting a stent without the customaryballoon dilatation—to become prevalent, with the advantages ofeconomy, shorter procedure time, and less radiation fromimaging. Most modern stents are expanded by balloon andmade from stainless steel alloys. Their construction and design,metal thickness, surface coverage, and radial strength varyconsiderably.

Stents are now used in most coronary interventions and in awide variety of clinical settings. They substantially increaseprocedural safety and success, and reduce the need foremergency coronary artery bypass surgery. Proceduresinvolving stent deployment are now often referred to aspercutaneous coronary interventions to distinguish them fromconventional balloon angioplasty (percutaneous transluminalcoronary angioplasty).

A major recent development has been the introduction ofdrug eluting stents (also referred to as “coated stents”), whichreduce restenosis to very low rates. Their high cost currentlylimits their use, but, with increasing competition amongmanufacturers, they will probably become more affordable.

Competing interests: None declared.

Year

Sten

ts d

eplo

yed

(100

0s/y

ear)

1986 1994 1998 20010

500

1000

1500

2000

2500

Exponential increase in use of intracoronary stents since1986. In 2001, 2.3 million stents were implanted (morethan double the 1998 rate)

Unequivocal indications for use of coronary stentsx Acute or threatened vessel closure during angioplastyx Primary reduction in restenosis in de novo lesions in arteries

> 3.0 mm in diameterx Focal lesions in saphenous vein graftsx Recanalised total chronic occlusionsx Primary treatment of acute coronary syndromes

Further readingx Gruentzig AR. Transluminal dilatation of coronary artery stenosis.

Lancet 1978;1:263x Smith SC Jr, Dove JT, Jacobs AK, Kennedy JW, Kereiakes D, Kern

MJ, et al. ACC/AHA guidelines of percutaneous coronaryinterventions (revision of the 1993 PTCA guidelines)—executivesummary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines(committee to revise the 1993 guidelines for percutaneoustransluminal coronary angioplasty). J Am Coll Cardiol 2001;37:2215-39

x Meyer BJ, Meier B. Percutaneous transluminal coronary angioplastyof single or multivessel disease and chronic total occlusions. In:Grech ED, Ramsdale DR, eds. Practical interventional cardiology.2nd ed. London: Martin Dunitz, 2002:35-54

x Costa MA, Foley DP, Serruys PW. Restenosis: the problem and howto deal with it. In: Grech ED, Ramsdale DR, eds. Practicalinterventional cardiology. 2nd ed. London: Martin Dunitz, 2002:279-94

x Topol EJ, Serruys PW. Frontiers in interventional cardiology.Circulation 1998;98:1802-20

Coronary angiogram showingthree lesions (arrows) affectingthe left anterior descendingartery (top left). The lesionsare stented withoutpre{dilatation (top right), withgood results (bottom)

The micrographs showing deep fissuring within a coronary artery wallatheroma and fragmented plaque tissue caused by coronary angioplastywere supplied by Kelly MacDonald, consultant histopathologist at StBoniface Hospital, Winnipeg, Canada.

Percutaneous coronary intervention. I: History and development

7

3 Percutaneous coronary intervention.II: The procedureEver D Grech

A wide range of patients may be considered for percutaneouscoronary intervention. It is essential that the benefits and risks ofthe procedure, as well as coronary artery bypass graft surgery andmedical treatment, are discussed with patients (and their families)in detail. They must understand that, although the percutaneousprocedure is more attractive than bypass surgery, it has importantlimitations, including the likelihood of restenosis and potentialfor incomplete revascularisation compared with surgery. Thepotential benefits of antianginal drug treatment and the need forrisk factor reduction should also be carefully explained.

Clinical risk assessmentRelief of anginal symptoms is the principal clinical indicationfor percutaneous intervention, but we do not know whether theprocedure has the same prognostic benefit as bypass surgery.Angiographic features determined during initial assessmentrequire careful evaluation to determine the likely success of theprocedure and the risk of serious complications.

Until recently, the American College of Cardiology andAmerican Heart Association classified anginal lesions into types(and subtypes) A, B, or C based on the severity of lesioncharacteristics. Because of the ability of stents to overcomemany of the complications of percutaneous intervention, thisclassification has now been superseded by one reflecting low,moderate, and high risk.

Successful percutaneous intervention depends on adequatevisualisation of the target stenosis and its adjacent arterialbranches. Vessels beyond the stenosis may also be importantbecause of the potential for collateral flow and myocardialsupport if the target vessel were to occlude abruptly. Factorsthat adversely affect outcome include increasing age, comorbiddisease, unstable angina, pre-existing heart or renal failure,previous myocardial infarction, diabetes, a large area ofmyocardium at risk, degree of collaterisation, and multivesseldisease.

Preparation for interventionPatients must be fully informed of the purpose of the procedureas well as its risks and limitations before they are asked for theirconsent. The procedure must always be carried out (or directlysupervised) by experienced, high volume operators ( > 75procedures a year) and institutions ( > 400 a year).

A sedative is often given before the procedure, as well asaspirin, clopidogrel, and the patient’s usual antianginal drugs.In very high risk cases an intra-aortic balloon pump may beused. A prophylactic temporary transvenous pacemaker wiremay be inserted in some patients with pre-existing, high gradeconduction abnormality or those at high risk of developing it.

The procedureFor an uncomplicated, single lesion, a percutaneous proceduremay take as little as 30 minutes. However, the duration of theprocedure and radiation exposure will vary according tothenumber and complexity of the treated stenoses and vessels.

Percutaneous coronary intervention in progress. Above the patient’s chest isthe x ray imaging camera. Fluoroscopic images, electrocardiogram, andhaemodynamic data are viewed at eye level screens. All catheterisationlaboratory operators wear lead protection covering body, thyroid, and eyes,and there is lead shielding between the primary operator and patient

New classification system of stenotic lesions (AmericanCollege of Cardiology and American Heart Association)

Low risk Moderate risk High riskDiscrete ( < 10 mm) Tubular (10-20 mm) Diffuse ( > 20 mm)Concentric EccentricReadily accessible Proximal segment

moderately tortuousProximal segmentexcessively tortuous

Segment not angular( < 45°)

Segment moderatelyangular (45°- < 90°)

Segment extremelyangular (>90°)

Smooth contour Irregular contourLittle or nocalcification

Moderate or heavycalcification

Occlusion not total Total occlusion< 3 months old

Total occlusion> 3 months or bridgingcollateral vessels

Non-ostial OstialNo major sidebranch affected

Bifurcated lesionsrequiring doubleguidewires

Inability to protectmajor side branches

No thrombus Some thrombus Degenerated vein graftswith friable lesions.

Clinical indications for percutaneouscoronary interventionx Stable angina (and positive stress test)x Unstable anginax Acute myocardial infarctionx After myocardial infarctionx After coronary artery bypass surgery

(percutaneous intervention to native vessels,arterial or venous conduits)

x High risk bypass surgeryx Elderly patient

8

As with coronary angiography, arterial access (usuallyfemoral but also brachial or radial) under local anaesthesia isrequired. A guide catheter is introduced and gently engaged atthe origin of the coronary artery. The proximal end of thecatheter is attached to a Y connector. One arm of thisconnector allows continuous monitoring of arterial bloodpressure. Dampening or “ventricularisation” of this arterialtracing may indicate reduced coronary flow because ofover-engagement of the guide catheter, catheter tip spasm, or apreviously unrecognised ostial lesion. The other arm has anadjustable seal, through which the operator can introduce theguidewire and balloon or stent catheter once the patient hasbeen given heparin as an anticoagulant. A glycoprotein IIb/IIIainhibitor, which substantially reduces ischaemic events duringpercutaneous coronary intervention, may also be given.

Visualised by means of fluoroscopy and intracoronaryinjections of contrast medium, a soft tipped, steerable guidewire(usually 0.014" (0.36 mm) diameter) is passed down thecoronary artery, across the stenosis, and into a distal branch. Aballoon or stent catheter is then passed over the guidewire andpositioned at the stenosis. The stenosis may then be stenteddirectly or dilated before stenting. Additional balloon dilatationmay be necessary after deployment of a stent to ensure its fullexpansion.

Balloon inflation inevitably stops coronary blood flow,which may induce angina. Patients usually tolerate this quitewell, especially if they have been warned beforehand. If itbecomes severe or prolonged, however, an intravenous opiatemay be given. Ischaemic electrocardiographic changes are oftenseen at this time, although they are usually transient and returnto baseline once the balloon is deflated (usually after 30-60seconds). During the procedure, it is important to talk to thepatient (who may be understandably apprehensive) to let himor her know what is happening, as this encourages a goodrapport and cooperation.

RecoveryAfter the procedure the patient is transferred to a ward whereclose monitoring for signs of ischaemia and haemodynamicinstability is available. If a femoral arterial sheath was used, itmay be removed when the heparin effect has declined to anacceptable level (according to unit protocols). Arterial sealingdevices have some advantages over manual compression: theypermit immediate sheath removal and haemostasis, are morecomfortable for patients, and allow early mobilisation anddischarge. However, they are not widely used as they addconsiderably to the cost of the procedure.

After a few hours, the patient should be encouraged togradually increase mobility, and in uncomplicated casesdischarge is scheduled for the same or the next day. Beforedischarge, the arterial access site should be examined and thepatient advised to seek immediate medical advice if bleeding orchest pain (particularly at rest) occurs. Outpatient follow up anddrug regimens are provided, as well as advice on modificationof risk factors and lifestyle.

Complications and sequelaeComplications are substantially lower in centres where largenumbers of procedures are carried out by adequately trainedand experienced operators. Major complications areuncommon and include death (0.2% but higher in high riskcases), acute myocardial infarction (1%) which may requireemergency coronary artery bypass surgery, embolic stroke(0.5%), cardiac tamponade (0.5%), and systemic bleeding (0.5%).

Equipment commonly used in percutaneous coronary interventions

A

B

C

D

Deployment of a balloon-mounted stent across stenoticlesion. Once the guide catheter is satisfactorily engaged,the lesion is crossed with a guidewire and theballoon-mounted stent positioned to cover the lesion (A).It may be necessary to pre-dilate a severe lesion with aballoon to provide adequate passageway for the balloonand stent. The balloon is inflated to expand the stent (B).The balloon is then deflated (C) and withdrawn leavingthe guidewire (D), which is also removed once theoperator is satisfied that a good result has been obtained

Femoralartery

F6

B

A

Example of afemoral arteryclosure device.The Angio-Sealdevice creates amechanical sealby sandwichingthe arteriotomybetween ananchor placedagainst the innerarterial wall (A)and collagensponge (B), whichboth dissolvewithin 60-90 days

Percutaneous coronary intervention. II: The procedure

9

Minor complications are more common and include allergyto the contrast medium and nephropathy and complications ofthe access site (bleeding, haematoma, and pseudoaneurysm).

Restenosis within a stentAlthough stents prevent restenosis from vascular recoil andremodelling, restenosis within the stent (known as “in-stentrestenosis”) due to neointimal proliferation does occur and isthe most important late sequel of the procedure. In-stentrestenosis is the Achilles’ heel of percutaneous revascularisationand 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 coexistingconditions such as diabetes. Approximate rates of angiographicrestenosis after percutaneous angioplasty arex Angioplasty to de novo lesion in native artery—35%x Angioplasty and stent to de novo lesion in native artery—25%x Angioplasty and stent to restenotic lesion in native artery—20%x Angioplasty and stent to successfully recanalised chronictotal occlusion—30%x Angioplasty to de novo lesion in vein graft—60%x Angioplasty and stent to de novo lesion in vein graft—30%.

It should be noted that angiographically apparentrestenoses do not always lead to recurrent angina (clinicalrestenosis). In some patients only mild anginal symptoms recur,and these may be well controlled with antianginal drugs,thereby avoiding the need for further intervention.

Using repeat percutaneous angioplasty alone to re-dilatein{stent restenosis results in a high recurrence of restenosis(60%). Various other methods, such as removing restenotictissue by means of atherectomy or a laser device or re-dilatingwith a cutting balloon, are being evaluated. Another method isbrachytherapy, which uses a special intracoronary catheter todeliver a source of � or � radiation. It significantly reducesfurther in-stent restenosis, but it has limitations, including latethrombosis and new restenosis at the edges of the radiationtreated segments, giving rise to a “candy wrapper” appearance.

A

Stented artery with areaof in-stent restenosis

B

Balloon angioplasty catheterinside stented artery

C

Radiation source train placed attreatment site for < 5 minutes

D

Artery after balloon angioplastyand vascular brachytherapy

Diagrammatic representation of the Novoste Beta Cath system used forvascular brachytherapy. Pre-dilatation of the in-stent restenosis with aballoon catheter is usual and is followed by positioning of the radiationsource train, containing strontium-90, at the site for less than 5 minutes

Angiogram showing late “candywrapper” edge effect (arrows)because of new restenosis at theedges of a segment treated bybrachytherapy

Focal in-stent restenosis. A 2.0 mm stent had been deployed sixmonths earlier. After recurrence of angina, angiography showedfocal in-stent restenosis (arrow, top left). This was confirmed withintravascular ultrasound (top right), which also revealed that thestent was underexpanded. The stent was further expanded with aballoon catheter, with a good angiographic result (arrow, bottom left)and an increased lumen diameter to 2.7 mm (bottom right)

The cutting balloon catheter. The longitudinal cutting blades are exposedonly during balloon inflation (top left). In this case (top right) a severeostial in-stent restenosis in the right coronary artery (arrow) was dilatedwith a short cutting balloon (bottom left), and a good angiographic resultwas obtained (arrow, bottom right)

ABC of Interventional Cardiology

10

Drug eluting, coated stentsCoated stents contain drugs that inhibit new tissue growthwithin the sub-intima and are a promising new option forpreventing or treating in-stent restenosis. Sirolimus (animmunosuppressant used to prevent renal rejection whichinhibits smooth muscle proliferation and reduces intimalthickening after vascular injury), paclitaxel (the activecomponent 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 yetavailable, it seems probable that coated stents will be commonlyused in the near future.

Occupation and drivingDoctors may be asked to advise on whether a patient is “fit forwork” or “recovered from an event” after percutaneouscoronary intervention. “Fitness” depends on clinical factors(level of symptoms, extent and severity of coronary disease, leftventricular function, stress test result) and the nature of theoccupation, as well as statutory and non-statutory fitnessrequirements. Advisory medical standards are in place forcertain occupations, such as in the armed forces and police,railwaymen, and professional divers. Statutory requirementscover the road, marine, and aviation industries and somerecreational pursuits such as driving and flying.

Patients often ask when they may resume driving afterpercutaneous coronary intervention. In Britain, the Driver andVehicle Licensing Agency recommends that group 1 (privatemotor car) licence holders should stop driving when anginalsymptoms occur at rest or at the wheel. After percutaneouscoronary intervention, they should not drive for a week. Driversholding a group 2 licence (lorries or buses) will be disqualifiedfrom driving once the diagnosis of angina has been made, andfor at least six weeks after percutaneous coronary intervention.Re-licensing may be permitted provided the exercise testrequirement (satisfactory completion of nine minutes of theBruce protocol while not taking � blockers) can be met andthere is no other disqualifying condition.

The diagram of the Angio-Seal device is used with permission of St JudeMedical, Minnetonka, Minnesota, USA. The angiogram showing the “candywrapper” effect is reproduced with permission of R Waksman, WashingtonHospital Center, and Martin Dunitz, London.

Competing interests: None declared.

Top left: four months after twostents (yellow lines) were deployedin the proximal and middle rightcoronary artery, severe diffusein-stent restenosis has occurredwith recurrent angina. Top right:two sirolimus coated Cypher stents(red lines) were deployed withinthe original stents. Bottom: aftersix months there was norecurrence of restenosis, and the51 year old patient remainedasymptomatic

The incidence of restenosis isparticularly high with percutaneousrevascularisation of small vessels. Asmall diseased diagonal artery(arrows, top left) in a 58 year oldpatient with limiting angina wasstented with a sirolimus coatedCypher stent (red line, top right).After six months, no restenosis waspresent (left), and the patientremained asymptomatic

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

MJ, et al. ACC/AHA guidelines of percutaneous coronaryinterventions (revision of the 1993 PTCA guidelines)—executivesummary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines(committee to revise the 1993 guidelines for percutaneoustransluminal coronary angioplasty). J Am Coll Cardiol 2001;37:2215{39

x Morice MC, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, PerinM, et al. A randomized comparison of a sirolimus-eluting stent witha standard stent for coronary revascularization. N Engl J Med2002;346:1773-80

x Almond DG. Coronary stenting I: intracoronary stents—form,function future. In: Grech ED, Ramsdale DR, eds. Practicalinterventional cardiology. 2nd ed. London: Martin Dunitz, 2002:63-76

x Waksman R. Management of restenosis through radiation therapy.In: Grech ED, Ramsdale DR, eds. Practical interventional cardiology.2nd ed. London: Martin Dunitz, 2002:295-305

x Kimmel SE, Berlin JA, Laskey WK. The relationship betweencoronary angioplasty procedure volume and major complications.JAMA 1995;274:1137-42

x Rensing BJ, Vos J, Smits PC, Foley DP, van den Brand MJ, van derGiessen WJ, et al. Coronary restenosis elimination with a sirolimuseluting stent. Eur Heart J 2001;22:2125-30

Percutaneous coronary intervention. II: The procedure

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4 Chronic stable angina: treatment optionsLaurence O’Toole, Ever D Grech

In patients with chronic stable angina, the factors influencingthe choice of coronary revascularisation therapy (percutaneouscoronary intervention or coronary artery bypass surgery) arevaried and complex. The severity of symptoms, lifestyle, extentof objective ischaemia, and underlying risks must be weighedagainst the benefits of revascularisation and the patient’spreference, as well as local availability and expertise. Evidencefrom randomised trials and large revascularisation registers canguide these decisions, but the past decade has seen rapidchange in medical treatment, bypass surgery, and percutaneousintervention. Therefore, thought must be given to whether olderdata still apply to contemporary practice.

Patients with chronic stable angina have an average annualmortality of 2-3%, only twice that of age matched controls, andthis relatively benign prognosis is an important considerationwhen determining the merits of revascularisation treatment.Certain patients, however, are at much higher risk. Predictorsinclude poor exercise capacity with easily inducible ischaemiaor a poor haemodynamic response to exercise, angina of recentonset, previous myocardial infarction, impaired left ventricularfunction, and the number of coronary vessels with significantstenoses, especially when disease affects the left main stem orproximal left anterior descending artery. Although the potentialbenefits of revascularisation must be weighed against adversefactors, those most at risk may have the most to gain.

Treatment strategiesMedical treatmentAnti-ischaemic drugs improve symptoms and quality of life, buthave not been shown to reduce mortality or myocardialinfarction. � blockers may improve survival in hypertension, inheart failure, and after myocardial infarction, and so areconsidered by many to be first line treatment. Nicorandil hasrecently been shown to reduce ischaemic events and need forhospital admission.

Trials comparing medical treatment with revascularisationpredate the widespread use of antiplatelet and cholesterollowering drugs. These drugs reduce risk, both in patientstreated with drugs only and in those undergoingrevascularisation, and so may have altered the risk-benefit ratiofor a particular revascularisation strategy in some patients.

Coronary artery bypass graft surgeryCoronary artery bypass surgery involves the placement of graftsto bypass stenosed native coronary arteries, while maintainingcerebral and peripheral circulation by cardiopulmonary bypass.The grafts are usually saphenous veins or arteries (principallythe left internal mammary artery).

Operative mortality is generally 1-3% but may be muchhigher in certain subsets of patients. Scoring systems canpredict operative mortality based on clinical, investigational, andoperative factors. Important developments that have occurredsince trials of bypass surgery versus medical treatment wereconducted include increased use of arterial grafts (which havemuch greater longevity than venous grafts), surgery withoutextracorporeal circulation (“off-pump” bypass), and minimalaccess surgery.

Major factors influencing risks and benefits of coronaryrevascularisationx Advanced agex Femalex Severe anginax Smokingx Diabetesx Obesityx Hypertension

x Multiple coronary vessels affectedx Coexisting valve diseasex Impaired left ventricular functionx Impaired renal functionx Cerebrovascular or peripheral vascular diseasex Recent acute coronary syndromex Chronic obstructive airways disease

Left internalmammaryartery withpedicle

Saphenousvein graft

Top: Diagrams of saphenous vein and left internal mammary artery graftsfor coronary artery bypass surgery. Bottom: Three completed grafts—(1) leftinternal mammary artery (LIMA) to left anterior descending artery (LAD),and saphenous vein grafts (SVG) to (2) diagonal artery (DG) and (3) obtusemarginal artery (OM)

Risk score for assessing probable mortality from bypasssurgery in patients with chronic stable anginaRisk factor Weighted scoreAge > 60 Score 1 for every

5 years overFemale sex 1Chronic obstructive pulmonary disease 1Extracardiac arteriopathy 2Neurological dysfunction 2Previous cardiac surgery 3Serum creatinine > 200�mol/l 2Reduced left ventricular ejection fraction 1 for 30-50%

3 for < 30%Myocardial infarction in past 90 days 2Pulmonary artery systolic pressure > 60 mm Hg 2Major cardiac procedure as well as bypass surgery 2Emergency operation 2x Total score <2 predicts < 1% operative mortalityx Total score of 3-5 predicts 3% operative mortalityx Total score >6 predicts > 10% operative mortalityA more detailed assessment with logistic analysis is available at www.euroscore.org andis recommended for assessing high risk patients

12

Percutaneous coronary interventionThe main advantages of percutaneous intervention over bypasssurgery are the avoidance of the risks of general anaesthesia,uncomfortable sternotomy and saphenous wounds, andcomplications of major surgery (infections and pulmonaryemboli). Only an overnight hospital stay is necessary (and manyprocedures can be performed as day cases), and the procedurecan be easily repeated. The mortality is low (0.2%), and the mostserious late complication is restenosis.

Patient suitability is primarily determined by technical factors.A focal stenosis on a straight artery without proximal vesseltortuousness or involvement of major side branches is ideal forpercutaneous intervention. Long, heavily calcified stenoses intortuous vessels or at bifurcations and chronic total occlusions areless suitable. This must be borne in mind when interpreting datafrom trials of percutaneous intervention and bypass surgery, asonly a minority of patients were suitable for both procedures.Nowadays, more and more patients undergo percutaneousintervention, and referral rates for bypass surgery are falling.

Comparative studies ofrevascularisation strategiesCoronary artery bypass surgery versus medical treatmentIn a meta-analysis of seven trials comparing bypass surgery withmedical treatment, surgery conferred a survival advantage inpatients with severe left main stem coronary disease, threevessel disease, or two vessel disease with severely affectedproximal left anterior descending artery. The survival gain wasmore pronounced in patients with left ventricular dysfunctionor a strongly positive exercise test. However, only 10% of trialpatients received an internal mammary artery graft, only 25%received antiplatelet drugs, and the benefit of lipid loweringdrugs on long term graft patency was not appreciated whenthese studies were carried out. Furthermore, 40% of themedically treated patients underwent bypass surgery during 10years of follow up. Thus, these data may underestimate thebenefits of surgery compared with medical treatment alone.

In lower risk patients bypass surgery is indicated only forsymptom relief and to improve quality of life when medicaltreatment has failed. Surgery does this effectively, with 95% ofpatients gaining immediate relief from angina and 75%remaining free from angina after five years. Unfortunately,venous grafts have a median life span of only seven years, andafter 15 years only 15% of patients are free from recurrentangina or death or myocardial infarction. However, theincreased use of internal mammary artery grafts, which haveexcellent long term patency (85% at 10 years), has increasedpostoperative survival and reduced long term symptoms.

Subgroup analysis of mortality benefit from coronary arterybypass surgery compared with medical treatment at 10 yearsafter randomisation for patients with chronic stable angina

Subgroup Mean (1.96 SE) increasedsurvival time (months)

P value ofdifference

Vessel disease:1 or 2 vessels 1.8 (3.0) 0.253 vessels 5.7 (3.6) 0.001Left main stem 19.3 (13.7) 0.005

Left ventricular function:Normal 2.3 (2.4) 0.06Abnormal 10.6 (6.1) < 0.001

Exercise test:Normal 3.3 (4.4) 0.14Abnormal 5.1 (3.3) 0.002

Severity of angina:CCS class 0, I, II 3.3 (2.7) 0.02CCS class III, IV 7.3 (4.8) 0.002

CCS=Canadian Cardiovascular Society

Left: Angiogram of a 10 year old diseased venous graft to the obtusemarginal artery showing proximal aneurysmal dilatation (A) and severestenosis in middle segment (B). Right: Removal of this graft after repeatbypass surgery shows its gross appearance (graft longitudinally opened inright image), with atherosclerosis in a thin walled aneurysm and a smallresidual lumen

Old saphenous vein grafts may contain large amounts of necrotic clotted debris, friable laminated thrombus, and ulcerated atheromatous plaque and areunattractive for percutaneous intervention because of the high risk of distal embolisation. However, distal embolisation protection devices such as theFilterWire 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 subtotallyoccluded 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)

Chronic stable angina: treatment options

13

Percutaneous coronary intervention versus medicaltreatmentMost percutaneous procedures are undertaken to treat singlevessel or two vessel disease, but few randomised controlled trialshave compared percutaneous intervention with medicaltreatment. These showed that patients undergoing thepercutaneous procedure derived greater angina relief and tookless drugs but required more subsequent procedures and hadmore complications (including non-fatal myocardial infarction),with no mortality difference. Patients with few symptoms didnot derive benefit. Therefore, percutaneous intervention issuitable for low risk patients with one or two vessel disease andpoor symptom control with drugs, at a cost of a slightly higherrisk of non-fatal myocardial infarction. However, the proceduremay not be indicated if symptoms are well controlled.

Percutaneous intervention versus bypass surgerySingle vessel diseaseIn a meta-analysis by Pocock et al percutaneous intervention inpatients with single vessel disease resulted in mortality similar tothat found with bypass surgery (3.7% v 3.1% respectively) but ahigher rate of non-fatal myocardial infarction (10.1% v 6.1%,P=0.04). Angina was well treated in both groups, but persistenceof symptoms was slightly higher with percutaneousintervention. Rates of repeat revascularisation were muchhigher with percutaneous intervention than bypass surgery.

Multivessel diseaseSince comparative trials could recruit only those patients whowere suitable for either revascularisation strategy, only 3-7% ofscreened patients were included. These were predominantly“low risk” patients with two vessel disease and preserved leftventricular function—patients in whom bypass surgery has notbeen shown to improve survival—and thus it is unlikely that apositive effect in favour of percutaneous intervention wouldhave been detected. The generally benign prognosis of chronicstable angina means that much larger trials would have beenrequired to show significant differences in mortality.

A meta-analysis of data available to the end of 2000revealed similar rates of death and myocardial infarction withboth procedures, but repeat revascularisation rates were higherwith percutaneous intervention. The prevalence of appreciableangina was greater with percutaneous intervention at one year,but this difference disappeared at three years.

The nature of percutaneous coronary intervention haschanged considerably over the past 10 years, with importantdevelopments including stenting and improved antiplateletdrugs. The integrated use of these treatments clearly improvesoutcomes, but almost all of the revascularisation trials predatethese developments.

A more recent trial comparing percutaneous interventionand stenting with bypass surgery in multivessel diseaseconfirmed similar rates of death, myocardial infarction, andstroke at one year, with much lower rates of repeatrevascularisation after percutaneous intervention comparedwith earlier trials. There was also a cost benefit of nearly $3000(£1875) per patient associated with percutaneous interventionat 12 months. The recent introduction of drug eluting (coated)stents, which seem to reduce substantially the problem ofrestenosis, is likely to extend the use of percutaneousintervention in multivessel disease over the next few years.

DiabetesBypass surgery confers a survival advantage in symptomaticdiabetic patients with multivessel disease The BARI trial

Coronary angiogramshowing a severefocal stenosis (arrow)in a large obliquemarginal branch ofthe left circumflexartery (LCx), suitablefor percutaneouscoronaryintervention. The leftanterior descendingartery (LAD) has noimportant disease

Coronary angiograms of 70 yearold woman with limiting angina.There were severe stenoses(arrows) in the proximal andmiddle left anterior descendingartery (LAD, top) and in the distalright coronary artery (RCA, left).Because of the focal nature ofthese lesions, percutaneouscoronary intervention was thepreferred option

Coronary angiograms of a69 year old man withlimiting angina andexertional breathlessness.There was severe proximaldisease (arrows) of the leftanterior descending (LAD)and left circumflex arteries(LCx) (top) and occlusion ofthe right coronary artery(RCA, left). The patient wasreferred for coronary arterybypass surgery on prognosticand symptomatic grounds

ABC of Interventional Cardiology

14

revealed a significant difference in five year mortality (21% withpercutaneous intervention v 6% with bypass surgery). Similartrends have been found in other large trials. However, therecent RAVEL and SIRIUS studies, in which the sirolimuseluting Cypher stent was compared with the same stentuncoated, showed a remarkable reduction in restenosis rateswithin the stented segments in diabetic patients (0% v 42% and18% v 51% respectively). Ongoing trials will investigate thisissue further.

Other study dataLarge registries of outcomes in patients undergoingrevascularisation have the advantage of including all patientsrather than the highly selected groups included in randomisedtrials. The registry data seem to agree with those fromrandomised trials: patients with more extensive disease farebetter with bypass surgery, whereas percutaneous interventionis preferable in focal coronary artery disease.An unusual observation is that patients screened andconsidered suitable for inclusion in a trial fared slightly better ifthey refused to participate than did those who enrolled. Theheterogeneous nature of coronary disease means that certainpatient subsets will probably benefit more from one treatmentthan another. The better outcome in the patients who weresuitable but not randomised may indicate that cardiologists andsurgeons recognise which patients will benefit more from aparticular strategy—subtleties that are lost in the randomisationprocess of controlled trials.

Refractory coronary artery diseaseIncreasing numbers of patients with coronary artery diseasehave angina that is unresponsive to both maximal drugtreatment and revascularisation techniques. Many will havealready undergone multiple percutaneous interventions orbypass surgery procedures, or have diffuse and distal coronaryartery disease. In addition to functional limitations, theirprognosis may be poor because of impaired ventricularfunction. Emerging treatments may provide alternativesymptomatic improvement for some patients. There is alsorenewed interest in the potential anti-ischaemic effects ofangiotensin converting enzyme inhibitors and the plaquestabilising properties of statins.

The picture showing three completed coronary artery bypass grafts andthe pictures of a 10 year old diseased venous graft to the obtuse marginalartery were provided by G Singh, consultant cardiothoracic surgeon,Heath Sciences Centre, Winnipeg, E Pascoe, consultant cardiothoracicsurgeon, St Boniface Hospital, Winnipeg, and J Scatliff, consultantanaesthetist, St Boniface Hospital. The picture of the FilterWire EX distalembolisation protection device was provided by Boston ScientificCorporation, Minneapolis, USA.

Competing interests: None declared.

Names of trialsx BARI—Bypass angioplasty revascularisation investigationx SIRIUS—Sirolimus-coated velocity stent in treatment of patients

with de novo coronary artery lesions trialx RAVEL—Randomised study with the sirolimus-eluting velocity

balloon-expandable stent in the treatment of patients with de novonative coronary artery lesions

Emerging treatment options for refractory anginax Drugs—Analgesics, statins, angiotensin converting enzyme

inhibitors, antiplatelet drugsx Neurostimulation—Interruption or modification of afferent

nociceptive signals: transcutaneous electric nerve stimulation(TENS), spinal cord stimulation (SCS)

x Enhanced external counterpulsation—Non-invasive pneumatic legcompression, improving coronary perfusion and decreasing leftventricular afterload

x Laser revascularisation—Small myocardial channels created by laserbeams: transmyocardial laser revascularisation (TMLR),percutaneous transmyocardial laser revascularisation (PTMLR)

x Therapeutic angiogenesis—Cytokines, vascular endothelial growthfactor, and fibroblast growth factor injected into ischaemicmyocardium, or adenoviral vector for gene transport to promoteneovascularisation

x Percutaneous in situ coronary venous arterialisation (PICVA)—Flowredirection from diseased coronary artery into adjacent coronaryvein, causing arterialisation of the vein and retroperfusion intoischaemic myocardium

x Percutaneous in situ coronary artery bypass (PICAB)—Flow redirectionfrom diseased artery into adjacent coronary vein and then reroutedback into the artery after the lesion

x Heart transplantation—May be considered when all alternativetreatments have failed

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

Effect of coronary artery bypass graft surgery on survival; overviewof 10-year results from randomised trials by the Coronary ArteryBypass Graft Surgery Trialists Collaboration. Lancet 1994; 344:563-70

x Pocock SJ, Henderson RA, Rickards AF, Hampton JR, King SB 3rd,Hamm CW, et al. Meta-analysis of randomised trials comparingcoronary angioplasty with bypass surgery. Lancet 1995;345:1184-9

x Raco DL, Yusuf S. Overview of randomised trials of percutaneouscoronary intervention: comparison with medical and surgicaltherapy for chronic coronary artery disease. In: Grech ED,Ramsdale DR, eds. Practical interventional cardiology. 2nd ed.London: Martin Dunitz, 2002:263-77

x Serruys PW, Unger F, Sousa JE, Jatene A, Bonnier HJ, SchonbergerJP, et al for the Arterial Revascularisation Therapies Study (ARTS)Group. Comparison of coronary-artery bypass surgery and stentingfor multivessel disease. N Engl J Med 2001;344:1117-24

x Kim MC, Kini A, Sharma SK. Refractory angina pectoris.Mechanisms and therapeutic options. J Am Coll Cardiol 2002;39:923-34

x Morice M-C, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, PerinM, et al. A randomized comparison of a sirolimus-eluting stent witha standard stent for coronary revascularization. N Engl J Med2002;346:1773-80

x Scottish Intercollegiate Guidelines Network. Coronaryrevascularisation in the management of stable angina pectoris.Edinburgh: SIGN, 1998 (SIGN Publication No 32)

Chronic stable angina: treatment options

15

5 Acute coronary syndrome: unstable angina andnon-ST segment elevation myocardial infarctionEver D Grech, David R Ramsdale

The term acute coronary syndrome refers to a range of acutemyocardial ischaemic states. It encompasses unstable angina,non-ST segment elevation myocardial infarction (ST segmentelevation generally absent), and ST segment elevation infarction(persistent ST segment elevation usually present). This articlewill focus on the role of percutaneous coronary intervention inthe management of unstable angina and non-ST segmentelevation myocardial infarction; the next article will address therole of percutaneous intervention in ST segment elevationinfarction.

Although there is no universally accepted definition ofunstable angina, it has been described as a clinical syndromebetween stable angina and acute myocardial infarction. Thisbroad definition encompasses many patients presenting withvarying histories and reflects the complex pathophysiologicalmechanisms operating at different times and with differentoutcomes. Three main presentations have been described—angina at rest, new onset angina, and increasing angina.

PathogenesisThe process central to the initiation of an acute coronarysyndrome is disruption of an atheromatous plaque. Fissuring orrupture of these plaques—and consequent exposure of coreconstituents such as lipid, smooth muscle, and foam cells—leadsto the local generation of thrombin and deposition of fibrin.This in turn promotes platelet aggregation and adhesion andthe formation of intracoronary thrombus.

Unstable angina and non-ST segment elevation myocardialinfarction are generally associated with white, platelet-rich, andonly partially occlusive thrombus. Microthrombi can detach andembolise downstream, causing myocardial ischaemia andinfarction. In contrast, ST segment elevation (or Q wave)myocardial infarction has red, fibrin-rich, and more stableocclusive thrombus.

EpidemiologyUnstable angina and non-ST segment elevation myocardialinfarction account for about 2.5 million hospital admissionsworldwide and are a major cause of mortality and morbidity inWestern countries. The prognosis is substantially worse than forchronic stable angina. In-hospital death and re-infarction affect5-10%. Despite optimal treatment with anti-ischaemic andantithrombotic drugs, death and recurrent myocardialinfarction occur in another 5-10% of patients in the month afteran acute episode. Several studies indicate that these patientsmay have a higher long term risk of death and myocardialinfarction than do patients with ST segment elevation.

DiagnosisUnstable angina and non-ST segment elevation myocardialinfarction are closely related conditions with clinicalpresentations that may be indistinguishable. Their distinctiondepends on whether the ischaemia is severe enough to causemyocardial damage and the release of detectable quantities of

Plaque disruption or erosion

Acute coronary syndromes

Thrombus formation with or without embolisation

Acute cardiac ischaemia

No ST segment elevation

Non-ST segment elevationmyocardial infarction

(Q waves usually absent)

ST segment elevationmyocardial infarction

(Q waves usually present)

Unstableangina

Elevated markers ofmyocardial necrosis

Markers of myocardialnecrosis not elevated

ST segment elevation

Elevated markers ofmyocardial necrosis

Spectrum of acute coronary syndromes according to electrocardiographicand biochemical markers of myocardial necrosis (troponin T, troponin I, andcreatine kinase MB), in patients presenting with acute cardiac chest pain

Three main presentations of unstable anginax Angina at rest—Also prolonged, usually > 20 minutesx Angina of new onset—At least CCS class III in severityx Angina increasing—Previously diagnosed angina that has become

more frequent, longer in duration, or lower in threshold (change inseverity by >1 CCS class to at least CCS class III)

CCS=Canadian Cardiovascular Society

Collagen

Key

Dividing smoothmuscle cell

Oxidised lowdensity lipoprotein

Lysosomes

Media

Adventitia

Intima

Platelet-rich thrombus

Activated platelets

Lumen

Diagram of an unstable plaque with superimposed luminal thrombus

Distal embolisation of aplatelet-rich thrombus causingocclusion of intramyocardialarteriole (arrow). Such anevent may result inmicro-infarction and elevationof markers of myocardialnecrosis

16

markers of myocyte necrosis. Cardiac troponin I and T are thepreferred markers as they are more specific and reliable thancreatine kinase or its isoenzyme creatine kinase MB.

An electrocardiogram may be normal or show minornon{specific changes, ST segment depression, T wave inversion,bundle branch block, or transient ST segment elevation thatresolves spontaneously or after nitrate is given. Physicalexamination may exclude important differential diagnoses suchas pleuritis, pericarditis, or pneumothorax, as well as revealingevidence of ventricular failure and haemodynamic instability.

ManagementManagement has evolved considerably over the past decade. Asplatelet aggregation and thrombus formation play a key role inacute coronary syndrome, recent advances in treatment (such asthe glycoprotein IIb/IIIa inhibitors, low molecular weightheparin, and clopidogrel) and the safer and more widespreaduse of percutaneous coronary intervention have raisedquestions about optimal management.

As patients with unstable angina or non-ST segmentelevation myocardial infarction represent a heterogeneousgroup with a wide spectrum of clinical outcomes, tailoringtreatment to match risk not only ensures that patients who willbenefit the most receive appropriate treatment, but also avoidspotentially hazardous treatment in those with a good prognosis.Therefore, an accurate diagnosis and estimation of the risk ofadverse outcome are prerequisites to selecting the mostappropriate treatment. This should begin in the emergencydepartment and continue throughout the hospital admission.Ideally, all patients should be assessed by a cardiologist on theday of presentation.

Medical treatmentMedical treatment includes bed rest, oxygen, opiate analgesicsto relieve pain, and anti-ischaemic and antithrombotic drugs.These should be started at once on admission and continued inthose with probable or confirmed unstable angina or non-STsegment elevation myocardial infarction. Anti-ischaemic drugsinclude intravenous, oral, or buccal nitroglycerin, � blockers,and calcium antagonists. Antithrombotic drugs include aspirin,clopidogrel, intravenous unfractionated heparin or lowmolecular weight heparin, and glycoprotein IIb/IIIa inhibitors.

Conservative versus early invasive strategy“Conservative” treatment involves intensive medicalmanagement, followed by risk stratification by non-invasivemeans (usually by stress testing) to identify patients who mayneed coronary angiography. This approach is based on theresults of two randomised trials (TIMI IIIB and VANQWISH),which showed no improvement in outcome when an “earlyinvasive” strategy was used routinely, compared with a selectiveapproach.

These findings generated much controversy and have beensuperseded by more recent randomised trials (FRISC II,TACTICS-TIMI 18, and RITA 3), which have taken advantage ofthe benefits of glycoprotein IIb/IIIa inhibitors and stents. Allthree studies showed that an early invasive strategy(percutaneous coronary intervention or coronary artery bypasssurgery) produced a better outcome than non-invasivemanagement. TACTICS-TIMI 18 also showed that the benefitof early invasive treatment was greatest in higher risk patientswith raised plasma concentrations of troponin T, whereas theoutcomes for lower risk patients were similar with early invasiveand non-invasive management.

I aVR V1 V4

II aVL V2 V5

III aVF V3 V6

II

Electrocardiogram of a 48 year old woman with unstable angina (top). Notethe acute ischaemic changes in leads V1 to V5 (arrows). Coronaryangiography revealed a severe mid-left anterior descending coronary arterystenosis (arrow, bottom left), which was successfully stented (bottom right)

Right coronary arteryangiogram in patient withnon-ST segment elevationmyocardial infarction (topleft), showing hazyappearance of intraluminalthrombus overlying a severestenosis (arrow). Abciximabwas given before directstenting (top right), withgood angiographic outcome(bottom)

Names of trialsx TIMI IIIB—Thrombolysis in myocardial infarction IIIBx VANQWISH—Veterans affairs non-Q-wave infarction strategies in

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

arteries-IV in acute coronary syndromesx RITA 3—Randomised intervention treatment of anginax FRISC II—Fast revascularisation during instability in coronary

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

of therapy with an invasive or conservative strategy-thrombolysis inmyocardial infarction

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

17

Identifying higher risk patientsIdentifying patients at higher risk of death, myocardial infarction,and recurrent ischaemia allows aggressive antithrombotictreatment and early coronary angiography to be targeted to thosewho will benefit. The initial diagnosis is made on the basis of apatient’s history, electrocardiography, and the presence ofelevated plasma concentrations of biochemical markers. Thesame information is used to assess the risk of an adverseoutcome. It should be emphasised that risk assessment is acontinuous process.

The TIMI risk scoreAttempts have been made to formulate clinical factors into auser friendly model. Notably, Antman and colleagues identifiedseven independent prognostic risk factors for early death andmyocardial infarction. Assigning a value of 1 for each risk factorpresent provides a simple scoring system for estimating risk, theTIMI risk score. It has the advantage of being easy to calculateand has broad applicability in the early assessment of patients.

Applying this score to the results in the TACTICS-TIMI 18study indicated that patients with a TIMI risk score of >3benefited significantly from an early invasive strategy, whereasthose with a score of <2 did not. Therefore, those with an initialTIMI score of >3 should be considered for early angiography(ideally within 24 hours), with a view to revascularisation bypercutaneous intervention or bypass surgery. In addition, anypatient with an elevated plasma concentration of troponinmarker, ST segment changes, or haemodynamic instabilityshould also undergo early angiography.

ConclusionThe diagnosis of unstable angina or non-ST segment elevationmyocardial infarction demands urgent hospital admission andcoronary monitoring. A clinical history and examination, 12lead electrocardiography, and measurement of troponinconcentration are the essential diagnostic tools. Bed rest,aspirin, clopidogrel, heparin, antianginal drugs, and opiateanalgesics are the mainstay of initial treatment.

Early risk stratification will help identify high risk patients,who may require early treatment with glycoprotein IIb/IIIainhibitors, angiography, and coronary revascularisation. Thosedeemed suitable for percutaneous intervention should receive aglycoprotein IIb/IIIa inhibitor and stenting as appropriate.There seems to be little merit in prolonged stabilisation ofpatients before percutaneous intervention, and an early invasivestrategy is generally preferable to a conservative one except forpatients at low risk of further cardiac events. This approach willshorten hospital stays, improve acute and long term outcomes,and reduce the need for subsequent intervention.

In the longer term, aggressive modification of risk factors iswarranted. Smoking should be strongly discouraged, and statinsshould be used to lower blood lipid levels. Long term treatmentwith aspirin, clopidogrel (especially after stenting), � blockers,angiotensin converting enzyme inhibitors, and antihypertensivedrugs should also be considered. Anti-ischaemic drugs may bestopped when ischaemia provocation tests are negative.

The picture of a microthrombus occluding an intramyocardial arteriolewas provided by K MacDonald, consultant histopathologist, St BonifaceHospital, Winnipeg.

Competing interests: None declared.

The seven variables for the TIMI risk scorex Age >65 yearsx >3 risk factors for coronary artery diseasex >50% coronary stenosis on angiographyx ST segment change > 0.5 mmx >2 anginal episodes in 24 hours before presentationx Elevated serum concentration of cardiac markersx Use of aspirin in 7 days before presentation

No of TIMI risk factors present

Deat

h or

myo

card

ial i

nfar

ctio

nat

14

days

(%)

0 or 1 2

Low risk Higher risk

3 4 5 6 or 70

10

15

20

5

Rates of death from all causes and non-fatal myocardial infarction at 14days, by TIMI risk score. Note sharp rate increase when score >3

Unstable angina or non-ST segment elevation myocardial infarction

TIMI risk assessment on presentation(aspirin, clopidogrel, heparin, nitrates, β blockers)

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

Conservative management

Higher risk(TIMI risk score >3, positive

troponin test, dynamic ST changes,or haemodynamically unstable)

Stress test

Negative

Discharge

Positive

Percutaneous coronaryintervention plus

glycoprotein IIb/IIIa inhibitor

Medicaltreatment

Coronaryartery bypass

surgery

Possible glycoprotein IIb/IIIa inhibitor

Invasive management

Coronary angiography

Simplified management pathway for patients with unstable angina ornon-ST segment elevation myocardial infarction

Further readingx Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD,

Hochman JS, et al. ACC/AHA 2002 guideline update for themanagement of patients with unstable angina and non-ST-segmentelevation myocardial infarction: a report of the American Collegeof Cardiology/American Heart Association task force on practiceguidelines. J Am Coll Cardiol 2002;40:1366-74

x Bertrand ME, Simoons ML, Fox KA, Wallentin LC, Hamm CW,McFadden E, et al. Management of acute coronary syndromes:acute coronary syndromes without persistent ST segment elevation.Recommendations of the Task Force of the European Society ofCardiology. Eur Heart J 2000;21:1406-32

x Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T,Papuchis G, et al. The TIMI risk score for unstable angina/non-STelevation MI: a method for prognostication and therapeuticdecision making. JAMA 2000;284:835-42

x Ramsdale DR, Grech ED. Percutaneous coronary interventionunstable angina and non-Q-wave myocardial infarction. In: GrechED, Ramsdale DR, eds. Practical interventional cardiology. 2nd ed.London: Martin Dunitz, 2002:165-87

ABC of Interventional Cardiology

18

6 Acute coronary syndrome: ST segment elevationmyocardial infarctionEver D Grech, David R Ramsdale

Acute ST segment elevation myocardial infarction usuallyoccurs when thrombus forms on a ruptured atheromatousplaque and occludes an epicardial coronary artery. Patientsurvival depends on several factors, the most important beingrestoration of brisk antegrade coronary flow, the time taken toachieve this, and the sustained patency of the affected artery.

RecanalisationThere are two main methods of re-opening an occluded artery:administering a thrombolytic agent or primary percutaneoustransluminal coronary angioplasty.

Although thrombolysis is the commonest form of treatmentfor acute myocardial infarction, it has important limitations: arate of recanalisation (restoring normal flow) in 90 minutes ofonly 55% with streptokinase or 60% with accelerated alteplase;a 5-15% risk of early or late reocclusion leading to acutemyocardial 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.

Primary angioplasty (also called direct angioplasty)mechanically disrupts the occlusive thrombus and compressesthe underlying stenosis, rapidly restoring blood flow. It offers asuperior alternative to thrombolysis in the immediate treatmentof ST segment elevation myocardial infarction. This differs fromsequential angioplasty, when angioplasty is performed afterthrombolysis. After early trials of thrombolytic drugs, there wasmuch interest in “adjunctive” angioplasty (angioplasty used as asupplement to successful thrombolysis) as this was expected toreduce recurrent ischaemia and re-infarction. Later studies,however, not only failed to show any advantage, but foundhigher rates of major haemorrhage and emergency bypasssurgery. In contrast, “rescue” (also known as “salvage”)angioplasty, which is performed if thrombolysis fails to restorepatency after one to two hours, may confer benefit.

Pros and cons of primary angioplastyAdvantagesLarge randomised studies have shown that thrombolysissignificantly reduces mortality compared with placebo, and thiseffect is maintained long term. Primary angioplasty confers

Histological appearance of aruptured atheromatous plaque(bottom arrow) and occlusivethrombus (top arrow) resultingin acute myocardial infarction

Acute ST segment elevationmyocardial infarction

Thrombolytic treatment Primary angioplasty

Infarct artery recanalised,but significant residual stenosis

Rescue angioplasty(1-2 hours after failed thrombolysis)

Elective angioplasty (if continued ischaemia)

Adjunctive angioplastyDeferred angioplasty

(1-7 days after thrombolysis)

Infarct artery not recanalised

Methods of recanalisation for acute myocardial infarction

Inci

denc

e (%

)

P<0.0001

09 studies

(n=58 600)*

* FTT Collaborative Group, Lancet 1994;343:311-22✝ Keeley et al, Lancet 2003;361:13-20

23 studies(n=7437)✝

9 studies(n=58 600)*

23 studies(n=6271)✝

23 studies(n=6497)✝

0

10

15

5

P=0.0002 2

3Mortality

P<0.0001

0

4

6

8

2

Re-infarctionCerebrovascular events

1

P<0.0001

P=0.0004

Controls Thrombolytic PCI

Effects of treatment with placebo, thrombolyticdrugs, or primary percutaneous coronaryintervention (PCI) on mortality, incidence ofcerebrovascular events, and incidence ofnon-fatal re-infarction after acute myocardialinfarction in randomised studies. Of the 1%incidence of cerebrovascular events in patientsundergoing primary percutaneous intervention,only 0.05% were haemorrhagic. In contrastpatients receiving thrombolytic drugs had a 1%incidence of haemorrhagic cerebrovascularevents (P<0.0001) and an overall 2% incidenceof cerebrovascular events (P=0.0004)

Comparison of methods of recanalisation

ThrombolysisRescue

angioplastyPrimary

angioplastyTime from admissionto recanalisation

1-3 hoursafter start ofthrombolysis

Time to start ofthrombolysisplus 2 hours

20-60minutes

Recanalisation withbrisk antegrade flow

55-60% 85% 95%

Systemic fibrinolysis +++ +++ −Staff and catheterlaboratory “burden”

− + +++

Cost of procedure + +++ +++

19

extra benefits in terms of substantial reductions in rates ofdeath, cerebrovascular events, and re-infarction.

The information provided by immediate coronaryangiography is valuable in determining subsequentmanagement. Patients with severe three vessel disease, severeleft main coronary artery stenosis, or occluded vesselsunsuitable for angioplasty can be referred for bypass surgery.Conversely, patients whose arteries are found to havespontaneously recanalised or who have an insignificant infarctrelated artery may be selected for medical treatment, and thusavoid unnecessary thrombolytic treatment.

DisadvantagesThe morbidity and mortality associated with primaryangioplasty is operator dependent, varying with the skill andexperience of the interventionist, and it should be consideredonly for patients presenting early ( < 12 hours after acutemyocardial infarction).

Procedural complications are more common than withelective angioplasty for chronic angina, and, even though it isusual to deal only with the occluded vessel, procedures may beprolonged. Ventricular arrhythmias are not unusual onrecanalisation, but these generally occur while the patient is stillin the catheterisation laboratory and can be promptly treated byintravenous drugs or electrical cardioversion. Right coronaryartery procedures are often associated with sinus arrest,atrioventricular block, idioventricular rhythm, and severehypotension. Up to 5% of patients initially referred for primaryangioplasty require urgent coronary artery bypass surgery, sosurgical backup is essential if risks are to be minimised.

There are logistical hurdles in delivering a full 24 hourservice. Primary angioplasty can be performed only whenadequate facilities and experienced staff are available. The timefrom admission to recanalisation should be less than 60 minutes,which may not be possible if staff are on call from home.However, recent evidence suggests that, even with longer delays,primary angioplasty may still be superior to thrombolysis.

A catheterisation laboratory requires large initial capitalexpenditure and has substantial running costs. However, in anexisting, fully supported laboratory operating at high volume,primary angioplasty is at least as cost effective as thrombolysis.

Primary angioplasty and coronarystentsAlthough early randomised studies of primary angioplastyshowed its clinical effectiveness, outcomes were marred by highrates of recurrent ischaemia (10-15% of patients) and earlyreinfarction of the affected artery (up to 5%). Consequently,haemodynamic and arrhythmic complications arose, with theneed for repeat catheterisation and revascularisation, prolongedhospital stay, and increased costs. Furthermore, restenosis ratesin the first six months remained disappointingly high (25-45%),and a fifth of patients required revascularisation.

Although stenting the lesion seemed an attractive answer, itwas initially thought that deploying a stent in the presence ofthrombus over a ruptured plaque would provoke furtherthrombosis. However, improvements in stent deployment andadvances in adjunctive pharmacotherapy have led to greatertechnical success. Recent studies comparing primary stentingwith balloon angioplasty alone have shown that stented patientshave significantly less recurrent ischaemia, reinfarction, andsubsequent need for further angioplasty. Economic analysis hasshown that, as expected, the initial costs were higher but wereoffset by lower follow up costs after a year.

Severe distal left mainstem stenosis (arrow 1)and partially occludedmid-left anteriordescending artery due tothrombus (arrow 2). Inview of the severity of thelesion salvage angioplastywas contraindicated. Anintra-aortic balloonpump was used toaugment blood pressureand coronary flow beforesuccessful bypass surgery

Pros and cons of primary angioplasty* compared withthrombolysisAdvantagesx High patency rates ( > 90%) with brisk, antegrade flowx Lower mortalityx Better residual left ventricular functionx More rapid electrocardiographic normalisationx Less recurrent ischaemia (angina, reinfarction, exercise induced

ischaemia)x No systemic fibrinolysis, therefore bleeding problems avoidedx Improved risk stratification by angiography with identification of

patients suitable for coronary artery bypass surgery

Disadvantagesx Higher procedural cost than streptokinase or alteplase (although

long term costs lower)x Can be performed only when cardiac catheterisation facilities and

experienced staff availablex Recanalisation more rapid than thrombolysis only if 24 hour

on-call team availablex Risks and complications of cardiac catheterisation and

percutaneous interventionx Reperfusion arrhythmias probably more common because of more

rapid recanalisation*With or without stenting

Anterior myocardial infarction of 4 hours’ duration and severehypotension, caused by a totally occluded proximal left anteriordescending artery (arrow, top left). After treatment with abciximab, a stentwas positioned. Initial inflation showed “waisting” of the balloon (topright), due to fibrous lesion resistance, which resolved on higher inflation(bottom left). Successful recanalisation resulted in brisk flow (bottom right),and the 15 minute procedure completely resolved the patient’s chest pain

ABC of Interventional Cardiology

20

However, one study (Stent-PAMI) showed that stenting wasassociated with a small (but significant) decrease in normalcoronary flow and a trend towards increased six and 12 monthmortality. This led some to examine the use of adjunctiveglycoprotein IIb/IIIa inhibitors as a solution.

Stenting and glycoprotein IIb/IIIa inhibitorsThe first study (CADILLAC) to examine the potential benefitsof glycoprotein IIb/IIIa inhibitors combined with stentingshowed that abciximab significantly reduced early recurrentischaemia and reocclusion due to thrombus formation. Therewas no additional effect on restenosis or late outcomescompared with stenting alone. The slightly reduced rate ofnormal coronary flow that had been seen in other studies wasagain confirmed, but did not translate into a significant effecton mortality.

Another study (ADMIRAL) examined the potential benefitof abciximab when given before (rather than during) primarystenting. Both at 30 days’ and six months’ follow up, abciximabsignificantly reduced the composite rate of reinfarction, theneed for further revascularisation, and mortality. In addition,abciximab significantly improved coronary flow ratesimmediately after stenting, which persisted up to six monthswith a significant improvement in residual left ventricularfunction.

Future of primary angioplastyPrimary stenting is not only safe but, by reducing recurrentischaemic events, also confers advantages over balloonangioplasty alone. Abciximab treatment seems to furtherimprove flow characteristics, prevents distalthrombo{embolisation, and reduces the need for repeatangioplasty. A strategy of primary stenting in association withabciximab seems to be the current gold standard of care forpatients with acute myocardial infarction. Future studies willexamine the potential benefit of other glycoprotein IIb/IIIainhibitors. The question of whether on-site surgical cover is stillessential for infarct intervention continues to be debated.

Inferior myocardial infarction of 2.5 hours’ duration caused by a totallyoccluded middle right coronary artery (arrow, top left). A guide wire passedthrough the fresh thrombus produced slow distal filling (top right).Deployment of a stent (bottom left) resulted in brisk antegrade flow, a goodangiographic result, and relief of chest pain (bottom right). A temporarypacemaker electrode was used to counter a reperfusion junctionalbradycardia. Note resolution in ST segments compared with top angiograms

Names of trialsx CADILLAC—Controlled abciximab and device

investigation to lower late angioplastycomplications

x ADMIRAL—Abciximab before direct angioplastyand stenting in myocardial infarction regardingacute and long-term follow-up

x Stent-PAMI—Stent primary angioplasty inmyocardial infarction

Further readingx Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group.

Indications for fibrinolytic therapy in suspected acute myocardialinfarction: collaborative overview of early mortality and majormorbidity results from all randomised trials of more than 1000patients. Lancet 1994;343:311-22

x Keeley EC, Boura JA, Grines CL. Primary angioplasty versusintravenous thrombolytic therapy for acute myocardial infarction: aquantitative review of 23 randomised trials. Lancet 2003;361:13-20

x De Boer MJ, Zijlstra F. Coronary angioplasty in acute myocardialinfarction. In: Grech ED, Ramsdale DR, eds. Practical interventionalcardiology. 2nd ed. London: Martin Dunitz, 2002:189-206

x Lieu TA, Gurley RJ, Lundstrom RJ, Ray GT, Fireman BH, WeinsteinMC, et al. Projected cost-effectiveness of primary angioplasty foracute myocardial infarction. J Am Coll Cardiol 1997;30:1741-50

x Grines CL, Cox DA, Stone GW, Garcia E, Mattos LA,Giambartolomei A, et al, for the Stent Primary Angioplasty inMyocardial Infarction Study Group. Coronary angioplasty with orwithout stent implantation for acute myocardial infarction. N Engl JMed 1999;341: 1949-56

x Montalescot G, Barragan P, Wittenberg O, Ecollan P, Elhadad S,Villain P, et al. Platelet glycoprotein IIb/IIIa inhibition withcoronary stenting for acute myocardial infarction. N Engl J Med2001;344:1895-903

x Stone GW, Grines CL, Cox DA, Garcia E, Tcheng JE, Griffin JJ, et al.Comparison of angioplasty with stenting, with or withoutabciximab, in acute myocardial infarction. N Engl J Med2002;346:957-66

Acute coronary syndrome: ST segment elevation myocardial infarction

21

7 Percutaneous coronary intervention:cardiogenic shockJohn Ducas, Ever D Grech

Cardiogenic shock is the commonest cause of death after acutemyocardial infarction. It occurs in 7% of patients with STsegment elevation myocardial infarction and 3% with non-STsegment elevation myocardial infarction.

Cardiogenic shock is a progressive state of hypotension(systolic blood pressure < 90 mm Hg) lasting at least30 minutes, despite adequate preload and heart rate, whichleads to systemic hypoperfusion. It is usually caused by leftventricular systolic dysfunction. A patient requiring drug ormechanical support to maintain a systolic blood pressure over90 mm Hg can also be considered as manifesting cardiogenicshock. As cardiac output and blood pressure fall, there is anincrease in sympathetic tone, with subsequent cardiac andsystemic effects—such as altered mental state, cold extremities,peripheral cyanosis, and urine output < 30 ml/hour.

Effects of cardiogenic shockCardiac effectsIn an attempt to maintain cardiac output, the remainingnon{ischaemic myocardium becomes hypercontractile, and itsoxygen consumption increases. The effectiveness of thisresponse depends on the extent of current and previous leftventricular damage, the severity of coexisting coronary arterydisease, and the presence of other cardiac pathology such asvalve disease.

Three possible outcomes may occur:x Compensation—which restores normal blood pressure andmyocardial perfusion pressurex Partial compensation—which results in a pre-shock state withmildly depressed cardiac output and blood pressure, as well asan elevated heart rate and left ventricular filling pressurex Shock—which develops rapidly and leads to profoundhypotension and worsening global myocardial ischaemia.Without immediate reperfusion, patients in this group havelittle potential for myocardial salvage or survival.

Systemic effectsThe falling blood pressure increases catecholamine levels,leading to systemic arterial and venous constriction. In time,activation of the renin-aldosterone-angiotensin axis causesfurther vasoconstriction, with subsequent sodium and waterretention. These responses have the effect of increasing leftventricular filling pressure and volume. Although this partlycompensates for the decline in left ventricular function, a highleft ventricular filling pressure leads to pulmonary oedema,which impairs gas exchange. The ensuing respiratory acidosisexacerbates cardiac ischaemia, left ventricular dysfunction, andintravascular thrombosis.

Time course of cardiogenic shockThe onset of cardiogenic shock is variable. In the GUSTO-Istudy, of patients with acute myocardial infarction, 7%developed cardiogenic shock—11% on admission and 89% inthe subsequent two weeks. Almost all of those who developedcardiogenic shock did so by 48 hours after the onset ofsymptoms, and their overall 30 day mortality was 57%,compared with an overall study group mortality of just 7%.

A 65 year old man with a3-4 hour history of acuteanterior myocardialinfarction had cardiogenicshock and acutepulmonary oedema,requiring mechanicalventilation and inotropicsupport. He underwentemergency angiography(top), which showed atotally occluded proximalleft anterior descendingartery (arrow). A softtipped guidewire waspassed across theocclusive thromboticlesion, which wassuccessfully stented(middle). Restoration ofbrisk antegrade flow downthis artery (bottom)followed by insertion ofan intra-aortic balloonpump markedly improvedblood pressure and organperfusion. The next dayhe was extubated andweaned off all inotropicdrugs, and the intra-aorticballoon pump wasremoved

Fall in cardiac output

Increased sympathetic tone

Non-ischaemic zone hypercontractilityIncreased myocardial oxygen demand

Extent of:• Left ventricular damage?

• Associated coronary artery disease?• Other cardiac disease?

Compensation(Restoration of normal

perfusion pressure)

Pre-shock(Increased heart rate,

increased left ventricularend diastolic pressure)

Shock(Impaired left ventricular

perfusion, worseningleft ventricular function)

Cardiac compensatory response to falling cardiac output after acutemyocardial infarction.

22

Differential diagnosisHypotension can complicate acute myocardial infarction inother settings.

Right coronary artery occlusionAn occluded right coronary artery (which usually supplies asmaller proportion of the left ventricular muscle than the leftcoronary artery) may lead to hypotension in various ways:cardiac output can fall due to vagally mediated reflexvenodilatation and bradycardia, and right ventricular dilationmay displace the intraventricular septum towards the leftventricular cavity, preventing proper filling.

In addition, the right coronary artery occasionally supplies asizeable portion of left ventricular myocardium. In this caseright ventricular myocardial infarction produces a unique set ofphysical findings, haemodynamic characteristics, and STsegment elevation in lead V4R. When this occurs aggressivetreatment is indicated as the mortality exceeds 30%.

Ventricular septal defect, mitral regurgitation, or myocardialruptureIn 10% of patients with cardiogenic shock, hypotension arisesfrom a ventricular septal defect induced by myocardialinfarction or severe mitral regurgitation after papillary musclerupture. Such a condition should be suspected if a patientdevelops a new systolic murmur, and is readily confirmed byechocardiography—which should be urgently requested. Suchpatients have high mortality, and urgent referral for surgerymay be needed. Even with surgery, the survival rate can be low.

Myocardial rupture of the free wall may cause low cardiacoutput as a result of cardiac compression due to tamponade. Itis more difficult to diagnose clinically (raised venous pressure,pulsus paradoxus), but the presence of haemopericardium canbe readily confirmed by echocardiography. Pericardialaspiration often leads to rapid increase in cardiac output, andsurgery may be necessary.

ManagementThe left ventricular filling volume should be optimised, and inthe absence of pulmonary congestion a saline fluid challenge ofat least 250 ml should be administered over 10 minutes.Adequate oxygenation is crucial, and intubation or ventilationshould be used early if gas exchange abnormalities are present.Ongoing hypotension induces respiratory muscle failure, andthis is prevented with mechanical ventilation. Antithrombotictreatment (aspirin and intravenous heparin) is appropriate.

Supporting systemic blood pressureBlood pressure support maintains perfusion of vital organs andslows or reverses the metabolic effects of organ hypoperfusion.Inotropes stimulate myocardial function and increase vasculartone, allowing perfusion pressures to increase. Intra-aorticballoon pump counterpulsation often has a dramatic effect onsystemic blood pressure. Inflation occurs in early diastole,greatly increasing aortic diastolic pressure to levels above aorticsystolic pressure. In addition, balloon deflation during the startof systole reduces the aortic pressure, thereby decreasingmyocardial oxygen demand and forward resistance (afterload).

ReperfusionAlthough inotropic drugs and mechanical support increasesystemic blood pressure, these measures are temporary andhave no effect on long term survival unless they are combinedwith coronary artery recanalisation and myocardial reperfusion.

Hallmarks of right ventricular infarctionx Rising jugular venous pressure, Kassmaul sign, pulsus paradoxusx Low output with little pulmonary congestionx Right atrial pressure > 10 mm Hg and > 80% of pulmonary

capillary wedge pressurex Right atrial prominent Y descentx Right ventricle shows dip and plateau pattern of pressurex Profound hypoxia with right to left shunt through a patent foramen

ovalex ST segment elevation in lead V4R

Main indications and contraindications for intra-aorticballoon pump counterpulsationIndicationsx Cardiogenic shockx Unstable and refractory anginax Cardiac support for high risk

percutaneous interventionx Hypoperfusion after coronary

artery bypass graft surgeryx Septic shock

Contraindicationsx Severe aortic regurgitationx Abdominal or aortic aneurysm

x Enhancement of coronary flowafter succesful recanalisation bypercutaneous intervention

x Ventricular septal defect andpapillary muscle rupture aftermyocardial infarction

x Intractable ischaemicventricular tachycardia

x Severe aorto-iliac disease orperipheral vascular disease

Catheter tip

Catheter

Sheath seal

Y fitting

Stylet wire

One way valve

Suture pads

Central lumen

Balloon membrane

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

Systole: deflationDecreased afterload

• Decreases cardiac work• Decreases myocardial oxygen consumption

• Increases cardiac output

Diastole: inflationAugmentation of diastolic pressure

• Increases coronary perfusion

Effects of intra-aortic balloon pump during systole and diastole

Percutaneous coronary intervention: cardiogenic shock

23

Thrombolysis is currently the commonest form of treatmentfor myocardial infarction. However, successful fibrinolysisprobably depends on drug delivery to the clot, and as bloodpressure 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 patientswho either presented with cardiogenic shock or who developedit after enrolment and survived for at least an hour after itsonset. Thirty day mortality was considerably less in thoseundergoing early angiography (38%) than in patients with lateor no angiography (62%). Further analysis suggested that earlyangiography was independently associated with a 43%reduction in 30 day mortality.

In the SHOCK trial, patients with cardiogenic shock weretreated aggressively with inotropic drugs, intra-aortic balloonpump counterpulsation, and thrombolytic drugs. Patients werealso randomised to either coronary angiography pluspercutaneous intervention or bypass surgery within six hours,or medical stabilisation (with revascularisation only permittedafter 54 hours). Although the 30 day primary end point did notachieve statistical significance, the death rates progressivelydiverged, and by 12 months the early revascularisation groupshowed a significant mortality benefit (55%) compared with themedical stabilisation group (70%). The greatest benefit was seenin those aged < 75 years and those treated early ( < 6 hours).Given an absolute risk reduction of 15% at 12 months, one lifewould be saved for only seven patients treated by aggressive,early revascularisation.

Support and reperfusion: impact on survivalOver the past 10 years, specific measures to improve bloodpressure and restore arterial perfusion have been instituted.Mortality data collected since the 1970s show a significant fallin mortality in the 1990s corresponding with increased use ofcombinations of thrombolytic drugs, the intra-aortic balloonpump, and coronary angiography with revascularisation byeither percutaneous intervention or bypass surgery. Beforethese measures, death rates of 80% were consistently observed.

Cardiogenic shock is the commonest cause of death in acutemyocardial infarction. Although thrombolysis can be attemptedwith inotropic support or augmentation of blood pressure withthe intra-aortic balloon pump, the greatest mortality benefit isseen after urgent coronary angiography and revascularisation.Cardiogenic shock is a catheter laboratory emergency.

The diagram of patient mortality after myocardial infarction is adapted withpermission from Goldberg RJ et al, N Engl J Med 1999;340:1162-8.

Competing interests: None declared.

P

R

QS

T

A B

C

D

A =B =

Unassisted systolic pressureDiastolic augmentation

C =D =

Unassisted aortic end diastolic pressureReduced aortic end diastolic pressure

Electrocardiogram

Arterialpressure

Diagram of electrocardiogram and aortic pressure wave showingtiming of intra-aortic balloon pump and its effects of diastolicaugmentation (D) and reduced aortic end diastolic pressure

Aortic pressure wave recording before (left) and during (right) intra-aorticballoon pump counterpulsation in a patient with cardiogenic shock aftermyocardial infarction. Note marked augmentation in diastolic pressure (arrowA) and reduction in end diastolic pressures (arrow B). (AO=aortic pressure)

Year

Mor

talit

y (%

)

0

20

40

60

80

1975 1978 1981 1984 1986 1988 1990 1991 1993 1995 1997

Shock present Shock absent

Mortality after myocardial infarction with or without cardiogenic shock (1975 to1997). Mortality of patients in shock fell from roughly 80% to 60% in the 1990s

Names of trialsx GISSI—Gruppo Italiano per lo studio della sopravvivenza

nell’infarto miocardicox GUSTO—global utilization of streptokinase and tissue plasminogen

activator for occluded coronary arteriesx SHOCK—should we emergently revascularize occluded coronaries

for cardiogenic shock

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

JD, et al. Early revascularization in acute myocardial infarctioncomplicated by cardiogenic shock. N Engl J Med 1999;341:625-34

x Berger PB, Holmes DR Jr, Stebbins AL, Bates ER, Califf RM, TopolEJ. Impact of an aggressive invasive catheterization andrevascularization strategy on mortality in patients with cardiogenicshock in the global utilization of streptokinase and tissueplasminogen activator for occluded coronary arteries (GUSTO-I)trial. Circulation 1997;96:122-7

x Golberg RJ, Samad NA, Yarzebski J, Gurwitz J, Bigelow C, Gore JM.Temporal trends in cardiogenic shock complicating acutemyocardial infarction. N Engl J Med 1999;340:1162-8

x Hasdai D, Topol EJ, Califf RM, Berger PB, Holmes DR.Cardiogenic shock complicating acute coronary syndromes. Lancet2000;356:749-56

x White HD. Cardiogenic shock: a more aggressive approach is nowwarranted. Eur Heart J 2000;21:1897-901

ABC of Interventional Cardiology

24

8 Interventional pharmacotherapyRoger Philipp, Ever D Grech

The dramatic increase in the use of percutaneous coronaryintervention has been possible because of advances inadjunctive pharmacotherapy, which have greatly improvedsafety. Percutaneous intervention inevitably causes vesseltrauma, with disruption of the endothelium and atheromatousplaque. This activates prothrombotic factors, leading to localisedthrombosis; this may impair blood flow, precipitate vesselocclusion, or cause distal embolisation. Coronary stentsexacerbate this problem as they are thrombogenic. For thesereasons, drug inhibition of thrombus formation duringpercutaneous coronary intervention is mandatory, although thismust be balanced against the risk of bleeding, both systemic andat the access site.

Coronary artery thrombosisPlatelets are central to thrombus formation. Vessel traumaduring percutaneous intervention exposes subendothelialcollagen and von Willebrand factor, which activate plateletsurface receptors and induce the initial steps of plateletactivation. Further platelet activation ultimately results inactivation of platelet glycoprotein IIb/IIIa receptor—the finalcommon pathway for platelet aggregation.

Vascular injury and membrane damage also triggercoagulation by exposure of tissue factors. The resultingthrombin formation further activates platelets and convertsfibrinogen to fibrin. The final event is the binding of fibrinogento activated glycoprotein IIb/IIIa receptors to form a plateletaggregate.

Understanding of these mechanisms has led to thedevelopment of potent anticoagulants and antiplateletinhibitors that can be used for percutaneous coronaryintervention. Since the early days of percutaneous transluminalcoronary angioplasty, heparin and aspirin have remained afundamental part of percutaneous coronary interventiontreatment. Following the introduction of stents, ticlopidine andmore recently clopidogrel have allowed a very low rate of stentthrombosis. More recently, glycoprotein IIb/IIIa receptorantagonists have reduced procedural complications still furtherand improved the protection of the distal microcirculation,especially in thrombus-containing lesions prevalent in acutecoronary syndromes.

Antithrombotic therapyUnfractionated heparin and low molecular weight heparinUnfractionated heparin is a heterogeneousmucopolysaccharide that binds antithrombin, which greatlypotentiates the inhibition of thrombin and factor Xa.

An important limitation of unfractionated heparin is itsunpredictable anticoagulant effect due to variable, non-specificbinding to plasma proteins. Side effects include haemorrhage atthe access site and heparin induced thrombocytopenia. About10-20% of patients may develop type I thrombocytopenia,which is usually mild and self limiting. However, 0.3-3.0% ofpatients exposed to heparin for longer than five days developthe more serious immune mediated, type II thrombocytopenia,which paradoxically promotes thrombosis by platelet activation.

Adhesion

Activation

Aggregation Fibrinogen

Serotonin

Collagen

Platelet

Platelet

Shearstress

AdrenalineThromboxane A2

Thrombin

GlycoproteinIIb/IIIa

Adenosinediphosphate

GlycoproteinIIb/IIIa

inhibitors

ClopidogrelTiclopidine

Thrombininhibitors

Aspirin

Action of antiplatelet and antithrombotic agents in inhibiting arterialthrombosis

Adjunctive pharmacology during percutaneous coronaryinterventionAspirin—For all clinical settingsClopidogrel—For stenting; unstable angina or non-ST segment

elevation myocardial infarctionUnfractionated heparin—For all clinical settings

Glycoprotein IIb/IIIa receptor inhibitorsAbciximab—For elective percutaneous intervention for chronic stable

angina; unstable angina or non-ST segment elevation myocardialinfarction (before and during percutaneous intervention); STsegment elevation myocardial infarction (before and duringprimary percutaneous intervention)

Eptifibatide—For elective percutaneous intervention for chronic stableangina; unstable angina or non-ST segment elevation myocardialinfarction (before and during percutaneous intervention)

Tirofiban—For unstable angina or non-ST segment elevationmyocardial infarction (before and during percutaneousintervention)

Comparison of unfractionated heparin and low molecularweight heparinUnfractionated heparinMolecular weight—3000-30 000 DaMechanism of action—Binds

antithrombin and inactivatesfactor Xa and thrombin equally(1:1)

Pharmacokinetics—Variablebinding to plasma proteins,endothelial cells, andmacrophages, givingunpredictable anticoagulanteffectsShort half lifeReversible with protamine

Laboratory monitoring—Activatedclotting time

Cost—Inexpensive

Low molecular weight heparinMolecular weight—4000-6000 DaMechanism of action—Binds

antithrombin and inactivatesfactor Xa more than thrombin(2-4:1)

Pharmacokinetics—Minimalplasma protein binding and nobinding to endothelial cells andmacrophages, giving predictableanticoagulant effectsLonger half lifePartially reversible withprotamine

Laboratory monitoring—Not requiredCost—10-20 times more expensive

than unfractionated heparin

25

Despite these disadvantages, unfractionated heparin ischeap, relatively reliable, and reversible, with a brief duration ofanticoagulant effect that can be rapidly reversed by protamine.It remains the antithrombotic treatment of choice duringpercutaneous coronary intervention.

For patients already taking a low molecular weight heparinwho require urgent revascularisation, a switch to unfractionatedheparin is generally recommended. Low molecular weightheparin is longer acting and only partially reversible withprotamine. The use of low molecular weight heparin duringpercutaneous intervention is undergoing evaluation.

Direct thrombin inhibitorsThese include hirudin, bivalirudin, lepirudin, and argatroban.They directly bind thrombin and act independently ofantithrombin III. They bind less to plasma proteins and have amore predictable dose response than unfractionated heparin.At present, these drugs are used in patients with immunemediated heparin induced thrombocytopenia, but theirpotential for routine use during percutaneous intervention isbeing evaluated, in particular bivalirudin.

Antiplatelet drugsAspirinAspirin irreversibly inhibits cyclo-oxygenase, preventing thesynthesis of prothrombotic thromboxane-A2 during plateletactivation. Aspirin given before percutaneous interventionreduces the risk of abrupt arterial closure by 50-75%. It is welltolerated, with a low incidence of serious adverse effects. Thestandard dose results in full effect within hours, and in patientswith established coronary artery disease it is given indefinitely.However, aspirin is only a mild antiplatelet agent and has noapparent effect in 10% of patients. These drawbacks have led tothe development of another class of antiplatelet drugs, thethienopyridines.

ThienopyridinesTiclopidine and clopidogrel irreversibly inhibit binding ofadenosine diphosphate (ADP) during platelet activation. Thecombination of aspirin plus clopidogrel or ticlopidine hasbecome standard antiplatelet treatment during stenting in orderto prevent thrombosis within the stent. As clopidogrel has fewerserious side effects, a more rapid onset, and longer duration ofaction, it has largely replaced ticlopidine. The loading dose is300 mg at the time of stenting or 75 mg daily for three daysbeforehand. It is continued for about four weeks, until newendothelium covers the inside of the stent. However, the recentCREDO study supports the much longer term (1 year) use ofclopidogrel and aspirin after percutaneous coronaryintervention, having found a significant (27%) reduction incombined risk of death, myocardial infarction, or stroke.

Glycoprotein IIb/IIIa receptor inhibitorsThese are potent inhibitors of platelet aggregation. The threedrugs in clinical use are abciximab, eptifibatide, and tirofiban. Incombination with aspirin, clopidogrel (if a stent is to bedeployed), and unfractionated heparin, they further decreaseischaemic complications in percutaneous coronary procedures.

Glycoprotein IIb/IIIa receptor inhibition may be beneficialin elective percutaneous intervention for chronic stable angina;for unstable angina or non-ST segment elevation myocardialinfarction, for acute myocardial infarction with ST segmentelevation.

Antithrombin III

Low molecularweight heparin

Factor Xa

1:1

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

Antithrombin III-factor Xa complex neutralised

Unfractionatedheparin

Thrombin

Thrombin

Unfractionated heparin

+

Low molecular weight heparin

Key

Factor Xa

Factor Xa

+

Mechanisms of catalytic inhibitory action of unfractionated heparin and lowmolecular weight heparin. Unfractionated heparin interacts with antithrombinIII, accelerating binding and neutralisation of thrombin and factor Xa (in 1:1ratio). Dissociated heparin is then free to re-bind with antithrombin III. Lowmolecular weight heparin is less able to bind thrombin because of its shorterlength. This results in selective inactivation of factor Xa relative to thrombin.Irreversibly bound antithrombin III and factor Xa complex is neutralised, anddissociated low molecular weight heparin is free to re-bind with antithrombinIII

Glycoprotein IIb/IIIa inhibitors currently in use

Abciximab Eptifibatide TirofibanSource Chimeric

monoclonalmouse antibody

Peptide Non-peptide

Time for plateletinhibition to returnto normal (hours)

24-48 4-6 4-8

Approximate cost perpercutaneouscoronary intervention

$1031, €1023,£657 (12 hour

infusion)

$263, €260,£167

(18 hourinfusion)

$404, €401,£257

(18 hourinfusion)

Severethrombocytopenia

1.0% (higher ifreadministered)

Similar toplacebo

Similar toplacebo

Reversible withplatelet transfusion?

Yes No No

ABC of Interventional Cardiology

26

Elective percutaneous intervention for chronic stable anginaLarge trials have established the benefit of abciximab andeptifibatide during stenting for elective and urgentpercutaneous procedures. As well as reducing risk of myocardialinfarction during the procedure and the need for urgent repeatpercutaneous intervention by 35-50%, these drugs seem toreduce mortality at one year (from 2.4% to 1% in EPISTENTand from 2% to 1.4% in ESPRIT). In diabetic patientsundergoing stenting, the risk of complications was reduced tothat of non-diabetic patients.

Although most trials showing the benefits of glycoproteinIIb/IIIa inhibitors during percutaneous coronary interventionrelate to abciximab, many operators use the less expensiveeptifibatide and tirofiban. However, abciximab seems to besuperior to tirofiban, with lower 30 day mortality and rates ofnon-fatal myocardial infarction and urgent repeat percutaneouscoronary intervention or coronary artery bypass graft surgeryin a wide variety of circumstances (TARGET study). In theESPRIT trial eptifibatide was primarily beneficial in stenting forelective percutaneous intervention, significantly reducing thecombined end point of death, myocardial infarction, and urgentrepeat percutaneous procedure or bypass surgery at 48 hoursfrom 9.4% to 6.0%. These benefits were maintained at follow up.

As complication rates are already low during electivepercutaneous intervention and glycoprotein IIb/IIIa inhibitorsare expensive, many interventionists reserve these drugs forhigher risk lesions or when complications occur. However, thismay be misguided; ESPRIT showed that eptifibatide started atthe time of percutaneous intervention was superior to aglycoprotein IIb/IIIa inhibitor started only when complicationsoccurred.

Unstable angina and non-ST segment elevation myocardial infarctionThe current role of glycoprotein IIb/IIIa inhibitors has beendefined by results from several randomised trials. In one groupof studies 29 885 patients (largely treated without percutaneousintervention) were randomised to receive a glycoproteinIIb/IIIa inhibitor or placebo. The end point of “30 day death ornon-fatal myocardial infarction” showed an overall significantbenefit of the glycoprotein IIb/IIIa inhibitor over placebo.Surprisingly, the largest trial (GUSTO IV ACS) showed nobenefit with abciximab, which may be partly due to inclusion oflower risk patients. The use of glycoprotein IIb/IIIa inhibitors inall patients with unstable angina and non-ST segment elevationmyocardial infarction remains debatable, although theconsistent benefit seen with these drugs has led to therecommendation that they be given to high risk patientsscheduled for percutaneous coronary intervention.

Another study (CURE) showed that the use of clopidogrelrather than a glycoprotein IIb/IIIa inhibitor significantlyreduced the combined end point of cardiovascular death,non{fatal myocardial infarction, or stroke (from 11.4% to 9.3%).Similar benefits were seen in the subset of patients whounderwent percutaneous coronary intervention. The impactthis study will have on the use of glycoprotein IIb/IIIa inhibitorsin this clinical situation remains unclear.

In another group of studies (n=16 770), patients were givena glycoprotein IIb/IIIa inhibitor or placebo immediately beforeor during planned percutaneous intervention. All showedunequivocal benefit with the active drug. Despite their efficacy,however, some interventionists are reluctant to use glycoproteinIIb/IIIa inhibitors in all patients because of their high costs andreserve their use for high risk lesions or when complicationsoccur.

GlycoproteinIIb/IIIa receptor

GlycoproteinIIb/IIIa

receptorantagonist

Activatedplatelet

Fibrinogen

ADP, thrombin, plasminadrenaline, serotonin,

thromboxane A2, collagen,platelet activating factor

Aggregated plateletscaused by formationof fibrinogen bridges

occupying glycoproteinIIb/IIIa receptors

Inhibition of plateletaggregation

Restingplatelet

Mechanisms of activated platelet aggregation by fibrin cross linking and itsblockade with glycoprotein IIb/IIIa inhibitors

Trial

PRISM

PRISM Plus

PARAGON A

PURSUIT

PARAGON B

GUSTO-IV ACS

Total

P=0.339 Breslow-Day homogeneity

No ofpatients

Risk

3232

1915

2282

9461

5165

7800

29 855

0.5 1.0 1.5Inhibitor better Placebo better

Placebo(%)

Risk ratio (95% CI)

7.1

11.9

11.7

15.7

11.4

8.0

11.5

GlycoproteinIIb/IIIa

inhibitor (%)

5.8

10.2

11.3

14.2

10.5

8.7

10.70.92 (0.86 to 0.995)P=0.037

Composite 30 day end point of death and myocardial infarction for sixmedical treatment trials of glycoprotein IIb/IIIa inhibitors in unstableangina and non{ST segment elevation myocardial infarction

Trial

EPIC

IMPACT-II

EPILOG

CAPTURE

RESTORE

EPISTENT

ESPRIT

Total

P=0.014 Breslow-Day homogeneity

No ofpatients

Risk

2099

4010

2792

1265

2141

2399

2064

16 770

0 1.0 2.0Inhibitor better

0.62 (0.55 to 0.70)P<0.001

Placebo better

Placebo(%)

Risk ratio (95% CI)

9.6

8.5

9.1

9.0

6.3

10.2

10.2

8.8

GlycoproteinIIb/IIIa

inhibitor (%)

6.6

7.0

4.0

4.8

5.1

5.2

6.3

5.6

Composite 30 day end point of death and myocardial infarction for seventrials of glycoprotein IIb/IIIa inhibitors given before or during plannedpercutaneous coronary intervention for unstable angina and non-STsegment elevation myocardial infarction

Interventional pharmacotherapy

27

Acute ST segment elevation myocardial infarctionIn many centres primary percutaneous intervention is thepreferred method of revascularisation for acute myocardialinfarction. To date, randomised studies have shown thatabciximab is the only drug to demonstrate benefit in thissetting. The development of low cost alternatives and thepotential for combination with other inhibitors of thecoagulation cascade may increase the use of glycoproteinIIb/IIIa inhibitors.

RestenosisAlthough coronary stents reduce restenosis rates comparedwith balloon angioplasty alone, restenosis within stents remainsa problem. Nearly all systemic drugs aimed at reducingrestenosis have failed, and drug eluting (coated) stents mayultimately provide the solution to this problem.

The futureImprovements in adjunctive pharmacotherapy, in combinationwith changes in device technology, will allow percutaneouscoronary intervention to be performed with increasedlikelihood of acute and long term success and with lowerprocedural risks in a wider variety of clinical situations. Furtherrefinements in antiplatelet treatment may soon occur withrapidly available bedside assays of platelet aggregation.

Competing interests: None declared.

Names of trialsx CAPTURE—C7E3 antiplatelet therapy in unstable refractory

anginax CREDO—Clopidogrel for the reduction of events during

observationx CURE—Clopidogrel in unstable angina to prevent recurrent

eventsx EPIC—Evaluation of C7E3 for prevention of ischemic

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

with abciximab glycoprotein IIb/IIIa blockadex EPISTENT—Evaluation of IIb/IIIa platelet inhibitor for stentingx ESPRIT—Enhanced suppression of the platelet glycoprotein

IIb/IIIa receptor using integrilin therapyx GUSTO IV-ACS—Global use of strategies to open occluded

arteries IV in acute coronary syndromex IMPACT II—Integrilin to minimize platelet aggregation and

coronary thrombosisx PARAGON—Platelet IIb/IIIa antagonism for the reduction of

acute coronary syndrome events in the global organizationnetwork

x PRISM—Platelet receptor inhibition in ischemic syndromemanagement

x PRISM-PLUS—Platelet receptor inhibition in ischemic syndromemanagement in patients limited by unstable signs and symptoms

x PURSUIT—Platelet glycoprotein IIb/IIIa in unstable angina:receptor suppression using integrilin therapy

x RESTORE—Randomized efficacy study of tirofiban for outcomesand restenosis

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

et al. Complementary clinical benefits of coronary-artery stentingand blockade and blockade of platelet glycoprotein IIb/IIIareceptors. N Engl J Med 1999;341:319-27

x PURSUIT Trial Investigators. Inhibition of platelet glycoproteinIIb/IIIa with eptifibatide in patients with acute coronary syndromes.Platelet glycoprotein IIb/IIIa in unstable angina: receptorsuppression using integrilin therapy. N Engl J Med 1998;339:436-43

x PRISM-PLUS Study Investigators. Inhibition of the plateletglycoprotein IIb/IIIa receptor with tirofiban in unstable angina andnon-Q wave myocardial infarction. Platelet receptor inhibition inischemic syndrome management in patients limited by unstablesigns and symptoms. N Engl J Med 1998;338:1488-97

x ESPRIT Investigators. Novel dosing regimen of eptifibatide inplanned coronary stent implantation (ESPRIT): a randomized,placebo-controlled trial. Lancet 2000;356:2037-44

x Boersma E, Harrington RA, Moliterno DJ, White H, Theroux P,Van de Werf F, et al. Platelet glycoprotein IIb/IIIa inhibitors inacute coronary syndromes: a meta-analysis of all majorrandomized clinical trials. Lancet 2002;359:189-98

x Chew DP, Lincoff AM. Adjunctive pharmacotherapy andcoronary intervention. In: Grech ED, Ramsdale DR, eds. Practicalinterventional cardiology. 2nd ed. London: Martin Dunitz,2002:207{24

x Steinhubl SR, Berger PB, Mann JT 3rd, Fry ET, DeLago A, WilmerC, et al. Early and sustained dual oral antiplatelet therapyfollowing percutaneous coronary intervention. A randomizedcontrolled trial. JAMA 2002;288:2411-20

ABC of Interventional Cardiology

28

9 Non-coronary percutaneous interventionEver D Grech

Although most percutaneous interventional procedures involvethe coronary arteries, major developments in non-coronarytranscatheter cardiac procedures have occurred in the past 20years. In adults the commonest procedures are balloon mitralvalvuloplasty, ethanol septal ablation, and septal defect closure.These problems were once treatable only by surgery, butselected patients may now be offered less invasive alternatives.Carrying out such transcatheter procedures requiressupplementary training to that for coronary intervention.

Balloon mitral valvuloplastyAcquired mitral stenosis is a consequence of rheumatic feverand is commonest in developing countries. Commissural fusion,thickening, and calcification of the mitral valve leaflets typicallyoccur, as well as thickening and shortening of the chordaetendinae. The mitral valve stenosis leads to left atrialenlargement, which predisposes patients to atrial fibrillationand the formation of left atrial thrombus.

In the 1980s percutaneous balloon valvuloplasty techniqueswere developed that could open the fused mitral commissuresin a similar fashion to surgical commissurotomy. The resultingfall in pressure gradient and increase in mitral valve area led tosymptomatic improvement. Today, this procedure is most oftenperformed with the hourglass shaped Inoue balloon. This isintroduced into the right atrium from the femoral vein, passedacross the atrial septum by way of a septal puncture, and thenpositioned across the stenosed mitral valve before inflation.

Patient selectionIn general, patients with moderate or severe mitral stenosis(valve area < 1.5 cm2) with symptomatic disease despite optimalmedical treatment can be considered for this procedure.Further patient selection relies heavily on transthoracic andtransoesophageal echocardiographic findings, which providestructural information about the mitral valve and subvalvarapparatus.

A scoring system for predicting outcomes is commonly usedto screen potential candidates. Four characteristics (valvemobility, leaflet thickening, subvalvar thickening, andcalcification) are each graded 1 to 4. Patients with a score of <8are more likely to have to have a good result than those withscores of > 8. Thus, patients with pliable, non-calcified valvesand minimal fusion of the subvalvar apparatus achieve the bestimmediate and long term results.

Relative contraindications are the presence of pre-existingsignificant 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 aredeath (1%), haemopericardium (usually during transseptalcatheterisation) (1%), cerebrovascular embolisation (1%), severemitral regurgitation (due to a torn valve cusp) (2%), and atrialseptal defect (although this closes or decreases in size in mostpatients) (10%). Immediate and long term results are similar tothose with surgical valvotomy, and balloon valvuloplasty can berepeated if commissural restenosis (a gradual process with anincidence of 30-40% at 6-8 years) occurs.

Stenotic mitral valve showing distorted, fused, and calcified valve leaflets.(AMVL=anterior mitral valve leaflet, PMVL=posterior mitral valve leaflet,LC=lateral commissure, MC=medial commissure)

Leftatrium

Leftventricle

Rightventricle

Inferiorvena cava

Rightatrium

Top: Diagram of the Inoue balloon catheter positionedacross a stenosed mitral valve. Bottom: Fluoroscopicimage of the inflated Inoue balloon across the valve

29

In patients with suitable valvar anatomy, balloonvalvuloplasty has become the treatment of choice for mitralstenosis, delaying the need for surgical intervention. It may alsobe of particular use in those patients who are at high risk ofsurgical intervention (because of pregnancy, age, or coexistingpulmonary or renal disease).

In contrast, balloon valvuloplasty for adult aortic stenosis isassociated with high complication rates and poor outcomes andis only rarely performed.

Ethanol septal ablationHypertrophic cardiomyopathyHypertrophic cardiomyopathy is a disease of the myocytescaused by mutations in any one of 10 genes encoding variouscomponents of the sarcomeres. It is the commonest geneticcardiovascular disease, being inherited as an autosomaldominant trait and affecting about 1 in 500 of the population. Ithas highly variable clinical and pathological presentations.

It is usually diagnosed by echocardiography and ischaracterised by the presence of unexplained hypertrophy in anon-dilated left ventricle. In a quarter of cases septalenlargement may result in substantial obstruction of the leftventricular outflow tract. This is compounded by Venturisuction movement of the anterior mitral valve leaflet duringventricular systole, bringing it into contact with thehypertrophied septum. The systolic anterior motion of theanterior mitral valve leaflet also causes mitral regurgitation.

TreatmentAlthough hypertrophic cardiomyopathy is often asymptomatic,common symptoms are dyspnoea, angina, and exertionalsyncope, which may be related to the gradient in the leftventricular outflow tract. The aim of treatment of symptomaticpatients is to improve functional disability, reduce the extent ofobstruction of the left ventricular outflow tract, and improvediastolic filling. Treatments include negatively inotropic drugssuch as � blockers, verapamil, and disopyramide. However, 10%of symptomatic patients fail to respond to drugs, and surgery—ventricular myectomy (which usually involves removal of a smallamount of septal muscle) or ethanol septal ablation—can beconsidered.

The objective of ethanol septal ablation is to induce alocalised septal myocardial infarction at the site of obstructionof the left ventricular outflow tract. The procedure involvesthreading a small balloon catheter into the septal arterysupplying the culprit area of septum. Echocardiography withinjection of an echocontrast agent down the septal artery allowsthe appropriate septal artery to be identified and reduces thenumber of unnecessary ethanol injections.

Once the appropriate artery is identified, the catheterballoon is inflated to completely occlude the vessel, and a smallamount of dehydrated ethanol is injected through the centrallumen of the catheter into the distal septal artery. This causesimmediate vessel occlusion and localised myocardial infarction.The infarct reduces septal motion and thickness, enlarges theleft ventricular outflow tract, and may decrease mitral valvesystolic anterior motion, with consequent reduction in thegradient of the left ventricular outflow tract. Over the next fewmonths the infarcted septum undergoes fibrosis and shrinkage,which may result in further symptomatic improvement.

The procedure is performed under local anaesthesia withsedation as required. Patients inevitably experience chestdiscomfort during ethanol injection, and treatment withintravenous opiate analgesics is essential. Patients are usuallydischarged after four or five days.

Characteristics of hypertrophic cardiomyopathyAnatomical—Ventricular hypertrophy of unknown cause, usually with

disproportionate involvement of the interventricular septumPhysiological—Well preserved systolic ventricular function, impaired

diastolic relaxationPathological—Extensive disarray and disorganisation of cardiac

myocytes and increased interstitial collagen

Echocardiogram showing anterior mitral valveleaflet (AMVL) and septal contact (***) duringventricular systole. Note marked left ventricular (LV)free wall and ventricular septal (VS) hypertrophy.Injection of an echocontrast agent down the septalartery results in an area of septal echo-brightness(dotted line). (LA=left atrium, AoV=aortic valve)

Angiograms showing ethanol septalablation. The first septal artery (S1,top left) is occluded with a ballooncatheter (top right) before ethanolinjection. This results in permanentseptal artery occlusion (bottom)and a localised septal myocardialinfarction. (LAD=left anteriordescending artery, TPW=temporarypacemaker wire)

Postmortem appearance ofa heart with hypertrophiccardiomyopathy showingmassive ventricular andseptal hypertrophy causingobstruction of the leftventricular outflow tract(LVOT). This iscompounded by theanterior mitral valve leaflet(AMVL), which pressesagainst the ventricularseptum (VS). Note thecoincidental right atrial(RAE) and right ventricular(RVE) pacing electrodes

ABC of Interventional Cardiology

30

ComplicationsHeart block is a frequent acute complication, so a temporarypacing electrode is inserted via the femoral vein beforehandand is usually left in situ for 24 hours after the procedure,during which time the patient is monitored.

The main procedural complications are persistent heartblock requiring a permanent pacemaker (10%), coronary arterydissection and infarction requiring immediate coronary arterybypass grafting (2%), and death (1-2%). The proceduralmortality and morbidity is similar to that for surgical myectomy,as is the reduction in left ventricular outflow tract gradient.Surgery and ethanol septal ablation have not as yet beendirectly compared in randomised studies.

Septal defect closureAtrial septal defectsAtrial septal defects are congenital abnormalities characterisedby a structural deficiency of the atrial septum and account forabout 10% of all congenital cardiac disease. The commonestatrial septal defects affect the ostium secundum (in the fossaovalis), and most are suitable for transcatheter closure. Althoughatrial septal defects may be closed in childhood, they are thecommonest form of congenital heart disease to becomeapparent in adulthood.

Diagnosis is usually confirmed by echocardiography,allowing visualisation of the anatomy of the defect and Dopplerestimation of the shunt size. The physiological importance ofthe defect depends on the duration and size of the shunt, as wellas the response of the pulmonary vascular bed. Patients withsignificant shunts (defined as a ratio of pulmonary blood flow tosystemic blood flow > 1.5) should be considered for closurewhen the diagnosis is made in later life because the defectreduces survival in adults who develop progressive pulmonaryhypertension. They may also develop atrial tachyarrhythmias,which commonly precipitate heart failure.

Patients within certain parameters can be selected fortranscatheter closure with a septal occluder. In those who areunsuitable for the procedure, surgical closure may be considered.

Patent foramen ovaleA patent foramen ovale is a persistent flap-like openingbetween the atrial septum primum and secundum which occursin roughly 25% of adults. With microbubbles injected into aperipheral vein during echocardiography, a patent foramenovale can be demonstrated by the patient performing and

Simultaneous aortic and left ventricular pressure waves before (left) and after (right) successful ethanol septal ablation. Note the differencebetween left ventricular peak pressure and aortic peak pressure, which represents the left ventricular outflow tract gradient, has beenreduced from 80 mm Hg to 9 mm Hg

Indications and contraindications for percutaneous closureof atrial septal defectsIndicationsClinicalx If defect causes symptomsx Associated cerebrovascular

embolic eventx Divers with neurological

decompression sickness

Anatomicalx Defects within fossa ovalis

(or patent foramen ovale)x Defects with stretched

diameter < 38 mm

Contraindicationsx Sinus venosus defectsx Ostium primum defects

x Pulmonary:systemic flow ratio> 1.5 and reversible pulmonaryhypertension

x Right-to-left atrial shunt andhypoxaemia

x Presence of > 4 mm rim of tissuesurrounding defect

x Ostium secundum defects with otherimportant congenital heart defectsrequiring surgical correction

Deployment sequence of the Amplatzer septal occluder for closing an atrialseptal defect

Micrograph of hypertrophied myocytes in haphazardalignments characteristic of hypertrophiccardiomyopathy. Interstitial collagen is also increased

Non-coronary percutaneous intervention

31

releasing a prolonged Valsalva manoeuvre. Visualisation ofmicrobubbles crossing into the left atrium reveals a right-to-leftshunt mediated by transient reversal of the interatrial pressuregradient.

Although a patent foramen ovale (or an atrial septalaneurysm) has no clinical importance in otherwise healthyadults, it may cause paradoxical embolism in patients withcryptogenic transient ischaemic attack or stroke (up to half ofwhom have a patent foramen ovale), decompression illness indivers, and right-to-left shunting in patients with rightventricular infarction or severe pulmonary hypertension.Patients with patent foramen ovale and paradoxical embolismhave an approximate 3.5% yearly risk of recurrentcerebrovascular events.

Secondary preventive strategies are drug treatment (aspirin,clopidogrel, or warfarin), surgery, or percutaneous closure usinga dedicated occluding device. A lack of randomised clinicaltrials directly comparing these options means optimaltreatment remains uncertain. However, percutaneous closureoffers a less invasive alternative to traditional surgery and allowspatients to avoid potential side effects associated withanticoagulants and interactions with other drugs. In addition,divers taking anticoagulants may experience haemorrhage inthe ear, sinus, or lung from barotrauma.

Congenital ventricular septal defectsUntreated congenital ventricular septal defects that requireintervention are rare in adults. Recently, there has been interestin percutaneous device closure of ventricular septal defectsacquired as a complication of acute myocardial infarction.However, more experience is necessary to assess the role of thisprocedure as a primary closure technique or as a bridge tosubsequent surgery.

The picture of a stenotic mitral valve and micrograph of myocytes showinghypertrophic cardiomyopathy were provided by C Littman, consultanthistopathologist at the Health Sciences Centre, Winnipeg, Manitoba,Canada. The postmortem picture of a heart with hypertrophiccardiomyopathy was provided by T Balachandra, chief medical examiner forthe Province of Manitoba, Winnipeg. The pictures of Amplatzer occluderdevices were provided by AGA Medical Corporation, Minnesota, USA.

Amplatzer occluder devices for patent foramen ovale (left) and muscularventricular septal defects (right)

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

commissurotomy. In: Grech ED, Ramsdale DR, eds. Practicalinterventional cardiology. 2nd ed. London: Martin Dunitz, 2002:373{87

x Bonow RO, Carabello B, de Leon AC, Edmunds LH Jr, FedderlyBJ, Freed MD, et al. ACC/AHA guidelines for the management ofpatients with valvular heart disease: A report of the AmericanCollege of Cardiology/American Heart Association Task Force onPractice Guidelines (Committee on Management of Patients withValvular Heart Disease). J Am Coll Cardiol 1998;32:1486-582

x Wilkins GT, Weyman AE, Abascal VM, Bloch PC, Palacios IF.Percutaneous balloon dilatation of the mitral valve: an analysis ofechocardiographic variables related to outcome and themechanism of dilatation. Br Heart J 1998;60:299-308

x Wigle ED, Rakowski H, Kimball BP, Williams WG. Hypertrophiccardiomyopathy: clinical spectrum and treatment. Circulation 1995;92:1680-92

x Nagueh SF, Ommen SR, Lakkis NM, Killip D, Zoghbi WA, SchaffHV, et al. Comparison of ethanol septal reduction therapy withsurgical myectomy for the treatment of hypertrophic obstructivecardiomyopathy. 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 inpatients with cerebral ischaemia. J Am Coll Cardiol 2002;39:2019-25

x Waight DJ, Cao Q-L, Hijazi ZM. Interventional cardiaccatheterisation in adults with congenital heart disease. In: GrechED, Ramsdale DR, eds. Practical interventional cardiology. 2nd ed.London: Martin Dunitz, 2002:390-406

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10 New developments in percutaneous coronaryinterventionJulian Gunn, Ever D Grech, David Crossman, David Cumberland

Percutaneous coronary intervention has become a morecommon procedure than coronary artery bypass surgery inmany countries, and the number of procedures continues torise. In one day an interventionist may treat four to six patientswith complex, multivessel disease or acute coronary syndromes.Various balloons, stents, and other devices are delivered bymeans of a 2 mm diameter catheter introduced via a peripheralartery. The success rate is over 95%, and the risk of seriouscomplications is low. After a few hours patients can bemobilised, and they are usually discharged the same or the nextday. Even the spectre of restenosis is now fading.

Refinements of existing techniquesThe present success of percutaneous procedures is largelybecause of refinement of our “basic tools” (intracoronaryguidewires and low profile balloons), which have greatlycontributed to the safety and effectiveness of procedures.However, the greatest technological advance has been in thedevelopment of stents. These are usually cut by laser fromstainless steel tubes into a variety of designs, each with differentradial strength and flexibility. They are chemically etched orelectropolished to a fine finish and sometimes coated.

Digital angiography is a great advance over cine-basedsystems, and relatively benign contrast media have replaced thetoxic media used in early angioplasty. Although magneticresonance and computed tomographic imaging may becomeuseful in the non-invasive diagnosis of coronary artery disease,angiography will remain indispensable to guide percutaneousinterventions for the foreseeable future.

New device technologyPre-eminent among new devices is the drug eluting (coated)stent, which acts as a drug delivery device to reduce restenosis.The first of these was the sirolimus coated Cypher stent.

Triple vessel disease is no longer a surgical preserve, and particularlygood results are expected with drug eluting stents. In this case, lesions inthe left anterior descending (LAD), circumflex (Cx), and right coronaryarteries (RCA) (top row) are treated easily and rapidly by stent (S)implantation (bottom row)

Performance of percutaneous coronary intervention

General statisticsx Success rate of procedure > 95%x Symptoms improved after procedure 90%x Complications* 2%x Restenosis 15% (range 5-50%)x Duration of procedure 15 minutes-3 hoursx Access point:

Femoral artery 95%Radial or brachial artery 5%

x Time in hospital after procedure:Overnight 60%Day case 20%Longer 20%

x Intravenous contrast load 100-800 mlx X ray dose to patient 75 Gy/cm2†

Special conditionsx Success of direct procedure for acute myocardial infarction > 95%x Success for chronic ( > 3 month) occluded vessel 50-75%x Mortality for procedure in severe cardiogenic shock 50%x Restenosis:

Vessels < 2.5 mm in diameter, > 40 mm length 60%Vessels > 3.5 mm diameter, < 10 mm length 5%

x Lesion recurrence later than 6 months after procedure < 5%x Re-restenosis:

After repeat balloon dilatation 30-50%After brachytherapy < 15%

*Death, myocardial infarction, coronary artery bypass surgery, cerebrovascularaccident†Equivalent to 1-2 computed tomography scans

Interventional devices and their uses

Device Use (% of cases) Types of lesionBalloon catheter 100% Multiple typesStent 70-90% Most typesDrug eluting stent 0-50% High risk of restenosis

(possibly all)Cutting balloon 1-5% In-stent restenosis, ostial

lesionsRotablator 1-3% Calcified, ostial, undilatable

lesionsBrachytherapy 1-3% In-stent restenosisAtherectomy < 1% Bulky, eccentric, ostial lesionsStent graft < 1% Aneurysm, arteriovenous

malformation, perforationThrombectomy < 1% Visible thrombusLaser < 1% Occlusions, in-stent restenosisDistal protection < 1% Degenerate vein graft

33

Sirolimus is one of several agents that have powerful antimitoticeffects and inhibit new tissue growth inside the artery and stent.In a randomised controlled trial (RAVEL) this stent gave a sixmonth restenosis rate of 0% compared with 27% for anuncoated stent of the same design. A later randomised study(SIRIUS) of more complex stenoses (which are more prone torecur) still produced a low rate of restenosis within stentedsegments (9% v 36% with uncoated stents), even in patients withdiabetes (18% v 51% respectively). Other randomised studiessuch as ASPECT and TAXUS II have also shown that coatedstents (with the cytotoxic agent paclitaxel) have significantlylower six month restenosis rates than identical uncoated stents(14% v 39% and 6% v 20% respectively). By reducing theincidence of restenosis (and therefore recurrent symptoms),drug eluting stents will probably alter the balance of treatingcoronary artery disease in favour of percutaneous interventionrather than coronary artery bypass surgery. However, coatedstents will not make any difference to the potential forpercutaneous coronary intervention to achieve acute success inany given lesion; nor do they seem to have any impact on acuteand subacute safety.

Although coated stents may, paradoxically, be too effective ataltering the cellular response and thus delay the desirableprocess of re-endothelialisation, there is no evidence that this isa clinical problem. However, this problem has been observedwith brachytherapy (catheter delivered radiotherapy over ashort distance to kill dividing cells), a procedure that is generallyreserved for cases of in-stent restenosis. This may lead to latethrombosis as platelets readily adhere to the “raw” surface thatresults from an impaired healing response. This risk isminimised by prolonged treatment with antiplatelet drugs andavoiding implanting any fresh stents at the time ofbrachytherapy.

Other energy sources may also prove useful. Sonotherapy(ultrasound) may have potential, less as a treatment in its ownright than as a facilitator for gene delivery, and is “benign” in itseffect on healthy tissue. Photodynamic therapy (the interactionof photosensitising drug, light, and tissue oxygen) is also beinginvestigated but is still in early development. Laser energy, whendelivered via a fine intracoronary wire, is used in a few centresto recanalise blocked arteries.

New work practicesTwenty years ago, a typical angioplasty treated one proximallylocated lesion in a single vessel in a patient with good leftventricular function. Now, it commonly treats two or three vesseldisease, perhaps with multiple lesions (some of which may becomplex), in patients with impaired left ventricular function,advanced age, and comorbidity. Patients may have undergone

Names of trialsx ASPECT—Asian paclitaxel-eluting stent clinical trialx RAVEL—Randomized study with the sirolimus eluting velocity

balloon expandable stent in the treatment of patients with de novonative coronary artery lesions

x SIRIUS—Sirolimus-coated velocity stent in treatment of patientswith de novo coronary artery lesions trial

x TAXUS II—Study of the safety and superior performance of theTAXUS drug-eluting stent versus the uncoated stent on de novolesions

Angiograms showing severe, diffuse, in-stent restenosis in the left anteriordescending artery and its diagonal branch (L and D, left). This was treatedwith balloon dilatation and brachytherapy with � irradiation (Novoste) froma catheter (Br, centre), with an excellent final result (right)

Angiogram of an aortocoronary vein graft with ananeurysm and stenoses (A and S, top). Treatment byimplantation of a membrane-covered stent excluded theaneurysm and restored a tubular lumen (bottom)

Bifurcation lesions, such as of the left anterior descendingartery and its diagonal branch (L and D, left), are technicallychallenging to treat but can be well dilated by balloondilatation and selective stenting (S, right)

Unprotected left mainstem stenoses (LMS, top)may, with careful selection,be treated by stentimplantation (S, bottom).Best results (similar tocoronary artery bypasssurgery) are achieved instable patients with goodleft ventricular functionand no other disease.Close follow up to detectrestenosis is important.(LAD=left anteriordescending artery, Cx=circumflex coronaryartery)

ABC of Interventional Cardiology

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coronary artery bypass surgery and be unsuitable for furtherheart surgery. Isolated left main stem and ostial right coronaryartery lesions, though requiring more experience andvariations on traditional techniques, are also no longer asurgical preserve.

Role of percutaneous coronary interventionThe role of percutaneous intervention has extended to thepoint where up to 70% of patients treated have acute coronarysyndromes. Trial data now support the use of a combination ofa glycoprotein IIb/IIIa inhibitor and early percutaneousintervention to give high risk patients the best long term results.The same applies to acute myocardial infarction, wherepercutaneous procedures achieve a much higher rate of arterialpatency than thrombolytic treatment. Even cardiogenic shock,the most lethal of conditions, may be treated by an aggressivecombination of intra-aortic balloon pumping and percutaneousintervention.

The potential for percutaneous procedures to treat a widerange of lesions successfully with low rates of restenosis raisesthe question of the relative roles of percutaneous interventionand bypass surgery in everyday practice. It takes time toaccumulate sufficient trial data to make long termgeneralisations possible.

Early trials comparing balloon angioplasty with bypasssurgery rarely included stents and few patients with three vesseldisease (as such disease carried higher risk and percutaneousintervention was not as widely practised as now). The long termresults favoured bypass surgery, but theses trials are nowoutdated. In the second generation of studies, stents were usedin percutaneous intervention, improving the results. As in theearly studies, surgery and intervention had similarly lowcomplications and mortality. The intervention patients still hadmore need for repeat procedures because of restenosis than thebypass surgery patients, but the differences were less.

The major drawback of all these studies was an exclusionrate approaching 95%, making the general clinical applicationof the findings questionable. This was because it was unusual atthat time to find patients with multivessel disease who weretechnically suitable for both methods and thus eligible forinclusion in the trials. Now that drug eluting stents are available,more trials are under way: the balance will now probably tip infavour of percutaneous coronary intervention. Meanwhile, thedecision of which treatment is better for a patient at a giventime is based on several factors, including the feasibility ofpercutaneous intervention (which is generally considered as thefirst option), completeness of revascularisation, comorbidity,age, and the patient’s own preferences.

Implications for health servicesThese issues are likely to pose major problems for healthservices. Modern percutaneous techniques can be used both toshorten patients’ stay in hospital and to make their treatmentminimally hazardous and more comfortable. They can also beused in the first and the last (after coronary artery bypasssurgery) stages of a patient’s “ischaemic career.”

On the other hand, for the role of percutaneous coronaryintervention in acute infarction to be realised, universalemergency access to this service will be needed. However, mosthealth systems cannot afford this—the main limiting factorbeing the number of interventionists and supporting staffrequired to allow a 24 hour rota compatible with legal workinghours and the survival of routine elective work.

An acute coronary syndrome was found to be due to stenoses and anulcerated plaque in the right coronary artery (S and U, left). This wastreated with a glycoprotein IIb/IIIa inhibitor followed by stent implantation(right). This is an increasingly common presentation of coronary arterydisease to catheterisation laboratories

Right coronary artery containing large,lobulated thrombus (T, left) on a substantialstenosis. After treatment with glycoproteinIIb/IIIa inhibitor, the lesion was stentedsuccessfully (St, right)

General roles of percutaneous coronary intervention (PCI)and coronary artery bypass surgery (CABG)

ConditionPCI

CABG1993 2003Acute presentationAcute coronary syndrome ++ +++ ++Cardiogenic shock +/ − + +/ −Acute full thickness myocardial infarction + +++ −Bailout after failed thrombolysis + ++ −

Chronic presentationImpaired left ventricle with left main stem

stenosis and blocked right coronary artery− − − +++

Impaired left ventricle and 3 vessel disease + ++ +++Impaired left ventricle and 3 vessel disease

with >1 occlusion− + +++

Diabetes and 3 vessel disease + ++ +++Good left ventricle and 3 vessel disease + ++ +++2 occluded vessels − − ++Good left ventricle and 2 vessel disease + +++ ++Repeat revascularisation after PCI ++ +++ ++Good left ventricle and 1 vessel disease +++ +++ +2-3 vessel diffuse or distal disease + ++ +Repeat revascularisation after CABG + ++ +Palliative partial revascularisation + ++ −Revascularisation of frail patient or with

severe comorbidity+ ++ −

+++ highly effective role, ++ useful role, + limited role, − treatment not preferred, − −treatment usually strongly advised against

New developments in percutaneous coronary intervention

35

The future for percutaneous coronaryinterventionWill percutaneous coronary intervention exist in 20 years time,or, at least, be recognisable as a logical development of today’sprocedures? Will balloons and stents still be in use? It is likelythat percutaneous procedures will expand further, althoughsome form of biodegradable stent is a possibility. A more“biological” stent might also be able to act as an effective drugor gene reservoir, which may extend local drug delivery intonew areas of coronary artery disease. We may find ourselvesdetecting inflamed (“hot”) plaques with thermography cathetersand treating these before they rupture. We may even be able tomodify the natural course of coronary artery disease byreleasing agents “remotely” (possibly using an externalultrasound trigger) or by injecting an agent that activates themolecular cargo in a stent.

A persistent challenge still limiting the use of percutaneouscoronary intervention is that of chronic total occlusions, whichcan be too tough to allow passage of an angioplasty guidewire.An intriguing technique is percutaneous in situ coronary arterybypass. With skill and ingenuity, a few enthusiasts haveanastomosed the stump of a blocked coronary artery to theadjacent cardiac vein under intracoronary ultrasound guidance,thereby using the vein as an endogenous conduit (with reversedflow). This technique may assist only a minority of patients.More practical, we believe, is the concept of drilling throughocclusions with some form of external guidance, perhapsmagnetic fields.

“Direct” myocardial revascularisation (punching an array ofholes into ischaemic myocardium) has had a mixed press overthe past decade. Some attribute its effect to new vesselformation, others cite a placebo effect. Although the channelsdo not stay open, they seem to stimulate new microvessels togrow. Injection of growth factors (vascular endothelial growthfactor and fibroblast growth factor) to induce new blood vesselgrowth also has this effect, and percutaneous injection of theseagents into scarred or ischaemic myocardium is achievable.However, we need a more thorough understanding ofbiological control mechanisms before we can be confident ofthe benefits of this technology.

Challenges to mechanical revascularisationDeaths from coronary artery disease are being steadily reducedin the Western world. However, with increasing longevity, it isunlikely that we will see a reduction in the prevalence of itschronic symptoms. More effective primary and secondaryprevention; antismoking and healthy lifestyle campaigns; andthe widespread use of antiplatelet drugs, � blockers, statins, andrenin-angiotensin system inhibitors may help prevent, or atleast delay, the presentation of symptomatic coronary arterydisease. In patients undergoing revascularisation, they areessential components of the treatment “package.” More effectiveanti-atherogenic treatments will no doubt emerge in the nearfuture to complement and challenge the dramatic progressbeing made in percutaneous coronary intervention.

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

M, et al. A randomized comparison of a sirolimus-eluting stent witha standard stent for coronary revascularization. N Engl J Med2002;346:1773-80

x Park SJ, Shim WH, Ho DS, Raizner AE, Park SW, Hong MK, et al.A paclitaxel-eluting stent for the prevention of coronary restenosis.N Engl J Med 2003;348:1537-45

x Raco DL, Yusuf S. Overview of randomised trials of percutaneouscoronary intervention: comparison with medical and surgicaltherapy for chronic coronary artery disease. In: Grech ED,Ramsdale DR, eds. Practical interventional cardiology. 2nd ed.London: Martin Dunitz, 2002:263-77

x Teirstein PS, Kuntz RE. New frontiers in interventional cardiology:intravascular radiation to prevent restenosis. Circulation 2001;104:2620-6

x Tsuji T, Tamai H, Igaki K, Kyo E, Kosuga K, Hata T, et al.Biodegradable stents as a platform to drug loading. Int J CardiovascIntervent 2003;5:13-6

x Hariawala MD, Sellke FW. Angiogenesis and the heart: therapeuticimplications. J R Soc Med 1997;90:307-11

x Serruys PW, Unger F, Sousa JE, Jatene A, Bonnier HJ, SchonbergerJP, et al, for the Arterial Revascularization Therapies Study Group.Comparison of coronary-artery bypass surgery and stenting for thetreatment of multivessel disease. N Engl J Med 2001;344:1117-24

x SoS Investigators. Coronary artery bypass surgery versuspercutaneous coronary intervention with stent implantation inpatients with multivessel coronary artery disease (the stent orsurgery trial): a randomised controlled trial. Lancet 2002;360:965-70

The coronary artery imaging was provided by John Bowles, clinicalspecialist radiographer, and Nancy Alford, clinical photographer, SheffieldTeaching Hospitals NHS Trust, Sheffield.

Competing interests: None declared.

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11 Percutaneous interventional electrophysiologyGerry C Kaye

Before the 1980s, cardiac electrophysiology was primarily usedto confirm mechanisms of arrhythmia, with managementmainly by pharmacological means. However, recognisedshortcomings in antiarrhythmic drugs spurred the developmentof non-pharmacological treatments, particularly radiofrequencyablation and implantable defibrillators.

The two major mechanisms by which arrhythmias occur areautomaticity and re-entrant excitation. Most arrhythmias are ofthe re-entrant type and require two or more pathways that areanatomically or functionally distinct but in electrical contact.The conduction in one pathway must also be slowed to asufficient degree to allow recovery of the other so that anelectrical impulse may then re-enter the area of slowedconduction.

Intracardiac electrophysiologicalstudiesIntracardiac electrophysiological studies give valuableinformation about normal and abnormal electrophysiology ofintracardiac structures. They are used to confirm themechanism of an arrhythmia, to delineate its anatomicalsubstrate, and to ablate it. The electrical stability of the ventriclescan also be assessed, as can the effects of an antiarrhythmicregimen.

Atrioventricular conductionElectrodes positioned at various sites in the heart can give onlylimited data about intracardiac conduction during sinus rhythmat rest. “Stressing” the system allows more information to begenerated, particularly concerning atrioventricular nodalconduction and the presence of accessory pathways.

By convention, the atria are paced at 100 beats/min foreight beats. The ninth beat is premature (extrastimulus), and theAH interval (the time between the atrial signal (A) and the Hissignal (H), which represents atrioventricular node conduction

Tachyarrhythmias

Ischaemic Non-ischaemic

Junctionalre-entry tachycardia

Atrioventricularre-entry tachycardia

Atrialectopy

Atrialfibrillation

Atrialflutter

Supraventricular tachycardias Ventricular tachycardias

Concealedaccessory pathways

Overt accessory pathways (such asWolff-Parkinson-White syndrome)

Focal Multifocal Type A Type B

Classification of arrhythmias

Indications for electrophysiological studiesInvestigation of symptomsx History of persistent palpitationsx Recurrent syncopex Presyncope with impaired left ventricular function

Interventionsx Radiofrequency ablation—Accessory pathways, junctional

tachycardias, atrial flutter, atrial fibrillationx Investigation of arrhythmias (narrow and broad complex) with or

without radiofrequency ablationx Assessment or ablation of ventricular arrhythmias

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

stenosis, substantial electrolyte disturbance

HRA HRAHBE HBE

CSE

CSE

Tricuspidvalve

Tricuspidvalve

Coronarysinus

ostium

RVARVA

Mitralvalve

Diagrams showing position of pacing or recording electrodes in the heart inthe right anterior oblique and left anterior oblique views (views from theright and left sides of the chest respectively). HRA=high right atrialelectrode, usually on the lateral wall or appendage; HBE=His bundleelectrode, on the medial aspect of the tricuspid valve; RVA=right ventricularapex; CSE=coronary sinus electrode, which records electrical deflectionsfrom the left side of the heart between the atrium and ventricle

ABAB

Normalsinus

rhythm

Initiation by prematureextrasystole (or

extrastimulus) causingunidirectional block due

to longer refractoryperiod down one arm

Tachycardiadue

to re-entrycontinues

Area of slowconduction

AB

Mechanism of a re-entry circuit. An excitation wave is propagated at anormal rate down path A, but slowly down path B. An excitation wave froman extrasystole now encounters the slow pathway (B), which is stillrefractory, creating unidirectional block. There is now retrogradeconduction from path A, which coincides with the end of the refractoryperiod in path B. This gives rise to a persistent circus movement

37

time) is measured. This sequence is repeated with the ninth beatmade increasingly premature. In normal atrioventricular nodalconduction, the AH interval gradually increases as theextrastimulus becomes more premature and is graphicallyrepresented as the atrioventricular nodal curve. The gradualprolongation of the AH interval (decremental conduction) is afeature that rarely occurs in accessory pathway conduction.

Retrograde ventriculoatrial conductionRetrograde conduction through the atrioventricular node isassessed by pacing the ventricle and observing conduction backinto the atria. The coronary sinus electrode is criticallyimportant for this. It lies between the left ventricle and atriumand provides information about signals passing over the leftside of the heart. The sequence of signals that pass from theventricle to the atria is called the retrograde activationsequence.

If an accessory pathway is present, this sequence changes:with left sided pathways, there is an apparent “short circuit” inthe coronary sinus with a shorter ventriculoatrial conductiontime. This is termed a concealed pathway, as its effect cannot beseen on a surface electrocardiogram. It conducts retrogradelyonly, unlike in Wolff-Parkinson-White syndrome, where thepathway is bidirectional. Often intracardiac electrophysiologicalstudies are the only way to diagnose concealed accessorypathways, which form the basis for many tachycardias withnarrow QRS complexes.

Supraventricular tachycardiaSupraventricular tachycardias have narrow QRS complexeswith rates between 150-250 beats/min. The two commonmechanisms involve re-entry due to either an accessorypathway (overt as in Wolff-Parkinson-White syndrome orconcealed) or junctional re-entry tachycardia.

Accessory pathwaysThese lie between the atria and ventricles in the atrioventricularring, and most are left sided. Arrhythmias are usually initiatedby an extrasystole or, during intracardiac electrophysiologicalstudies, by an extrastimulus, either atrial or ventricular. Theextrasystole produces delay within the atrioventricular node,allowing the signal, which has passed to the ventricle, to re-enterthe atria via the accessory pathway. This may reach theatrioventricular node before the next sinus beat arrives butwhen the atrioventricular node is no longer refractory, thusallowing the impulse to pass down the His bundle and back upto the atrium through the pathway. As ventriculardepolarisation is normal, QRS complexes are narrow. Thiscircuit accounts for over 90% of supraventricular tachycardias in

HBE1-2

V5

CS1-2

CS3-4

CS5-6

CS7-8

CS9-10

HRA3-4

HBE1-2

V5

CS1-2

CS3-4

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Coronary sinus electrode signals, with poles CS9-10 placed proximally nearthe origin of the coronary sinus and poles 1-2 placed distally reflectingchanges in the left ventricular-left atrial free wall. Top: normal retrogradeactivation sequence with depolarisation passing from the ventricle backthrough the atrioventricular node to the right atrium and simultaneouslyacross the coronary sinus to the left atrium. Bottom: retrograde activationsequence in the presence of an accessory pathway in the free wall of the leftventricle showing a shorter ventriculoatrial (VA) time than would beexpected in the distal coronary sinus electrodes (CS1-2). Such a pathwaywould not be discernible from a surface electrocardiogram

Mechanisms for orthodromic (left) and antedromic (right)atrioventricular re-entrant tachycardia

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A normalatrioventricular nodal“hockey stick” curveduring antegradeconduction of atrialextrastimuli. As theatrial extrastimulus(A1-A2) becomes morepremature, the AHinterval (H1-H2) shortensuntil the atrioventricularnode becomesfunctionally refractory

ABC of Interventional Cardiology

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Wolff-Parkinson-White syndrome. Rarely, the circuit is reversed,and the QRS complexes are broad as the ventricles are fullypre-excited. This rhythm is often misdiagnosed as ventricular inorigin.

Treatment—Pathway ablation effects a complete cure bydestroying the arrhythmia substrate. Steerable ablationcatheters allow most areas within the heart to be reached. Theleft atrium can be accessed either retrogradely via the aorticvalve, by flexing the catheter tip through the mitral valve, ortranseptally across the atrial septum. Radiofrequency energy isdelivered to the atrial insertion of a pathway and usually resultsin either a rapid disappearance of pre-excitation on the surfaceelectrocardiogram or, in the case of concealed pathways,normalisation of the retrograde activation sequence. Accessorypathway ablation is 95% successful. Failure occurs from aninability to accurately map pathways or difficulty in deliveringenough energy, usually because of positional instability of thecatheter. Complications are rare ( < 0.5%) and are related tovascular access—femoral artery aneurysms or, with left sidedpathways, embolic cerebrovascular accidents.

Junctional re-entry tachycardiaThis is the commonest cause of paroxysmal supraventriculartachycardia. The atrioventricular nodal curve shows a suddenunexpected prolongation of the AH interval known as a “jump”in the interval. The tachycardia is initiated at or shortly after thejump. The jump occurs because of the presence of twopathways—one slowly conducting but with relatively rapidrecovery (the slow pathway), the other rapidly conducting butwith relatively slow recovery (the fast pathway)—called duality ofatrioventricular nodal conduction. This disparity betweenconduction speed and recovery allows re-entrance to occur. Ona surface electrocardiogram the QRS complexes are narrow,and the P waves are often absent or distort the terminal portionof the QRS complex. These arrhythmias can often beterminated by critically timed atrial or ventricular extrastimuli.

In the common type of junctional re-entry tachycardia (typeA) the circuit comprises antegrade depolarisation of the slowpathway and retrograde depolarisation of the fast pathway.Rarely ( < 5% of junctional re-entry tachycardias) the circuit isreversed (type B). The slow and fast pathways are anatomicallyseparate, with both inputting to an area called the compactatrioventricular node. The arrhythmia can be cured by mappingand ablating either the slow or fast pathway, and overall successoccurs in 98% of cases. Irreversible complete heart blockrequiring a permanent pacemaker occurs in 1-2% of cases, withthe risk being higher for fast pathway ablation. Therefore, slowpathway ablation is the more usual approach.

Atrial flutter and atrial fibrillationAtrial flutter is a macro re-entrant circuit within the rightatrium. The critical area of slow conduction lies at the base ofthe right atrium in the region of the slow atrioventricular nodalpathway. Producing a discrete line of ablation between thetricuspid annulus and the inferior vena cava gives a line ofelectrical block and is associated with a high success rate interminating flutter. Flutter responds poorly to standardantiarrhythmic drugs, and ablation carries a sufficientlyimpressive success rate to make it a standard treatment.

Atrial fibrillation is caused by micro re-entrant waveletscirculating around the great venous structures, or it may berelated to a focus of atrial ectopy arising within the pulmonaryveins at their junction with the left atrium. The first indicationthat atrial fibrillation was electrically treatable came from theMaze operation (1990). Electrical dissociation of the atria fromthe great veins was carried out by surgical excision of the veins

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Surface electrocardiogram leads V1 and V5 and signals from the distalcoronary sinus electrodes (CS dist), proximal electrodes (CS prox), and thetip of the ablation catheter (ABL CATH) during pathway ablation to treatWolff-Parkinson-White syndrome. The onset of radiofrequency energy (thinarrow) produces loss of pre-excitation after two beats with a narrowcomplex QRS seen at the fourth beat (broad arrow). Prolongation of the AVsignal in the coronary sinus occurs when pre-excitation is lost

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Atrioventricular nodal curves. In a patient with slow-fast junctionalre-entrant tachycardia (left) there is a “jump” in atrioventricular nodalconduction when conduction changes from the fast to the slow pathway. In apatient with accessory pathways conducting antegradely (such asWolff-Parkinson-White syndrome) there is no slowing of conduction as seenin the normal atrioventricular node, and the curve reflects conductionexclusively over the pathway (right)

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Mechanism of slow-fast junctional re-entrant tachycardia. A premature atrialimpulse finds the fast pathway refractory, allowing retrograde conductionback up to the atria

Percutaneous interventional electrophysiology

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from their insertion sites and then suturing them back. Thescarred areas acted as insulation, preventing atrial wave-frontsfrom circulating within the atria. Similar lines of block can beachieved by catheter ablation within the right and left atria. Theresults look promising, although this is a difficult, prolongedprocedure with a high relapse rate. Of more interest is asub-group of patients with runs of atrial ectopy, whichdegenerate to paroxysms of atrial fibrillation. Theseextrasystoles usually originate from the pulmonary veins, andtheir ablation substantially reduces the frequency ofsymptomatic atrial fibrillation. With better understanding of theunderlying mechanisms and improved techniques, atrialfibrillation may soon become a completely ablatablearrhythmia.

Ventricular tachycardiaVentricular tachycardia carries a serious adverse prognosis,particularly in the presence of coronary artery disease andimpaired ventricular function. Treatment options include drugs,occasional surgical intervention (bypass or arrhythmia surgery),and implantable defibrillators, either alone or in combination.Ventricular tachycardia can be broadly divided into two groups,ischaemic and non-ischaemic. The latter includes arrhythmiasarising from the right ventricular outflow tract and thoseassociated with cardiomyopathies.

Since the radiofrequency energy of an ablation catheter isdestructive only at the site of the catheter tip, this approachlends itself more to arrhythmias where a discrete abnormalitycan be described, such as non-ischaemic ventricular tachycardia.In ischaemic ventricular tachycardia, where the abnormalsubstrate often occurs over a wide area, the success rate is lower.

Ideally, the arrhythmia should be haemodynamically stable,reliably initiated with ventricular pacing, and mapped to alocalised area within the ventricle. In many cases, however, thisis not possible. The arrhythmia may be unstable after initiationand therefore cannot be mapped accurately. The circuit mayalso lie deep within the ventricular wall and cannot be fullyablated. However, detailed intracardiac maps can be made withmultipolar catheters. A newer approach is the use of anon{contact mapping catheter, which floats freely within theventricles but senses myocardial electrical circuits.

Although the overall, long term, success rate forradiofrequency ablation of ischaemic ventricular tachycardia isonly about 65%, this may increase.

ConclusionThe electrophysiological approach to treating arrhythmias hasbeen revolutionised by radiofrequency ablation. Bettercomputerised mapping, improved catheters, and more efficientenergy delivery has enabled many arrhythmias to be treatedand cured. The ability to ablate some forms of atrial fibrillationand improvement in ablation of ventricular tachycardia isheralding a new age of electrophysiology. Ten years ago it couldhave been said that electrophysiologists were a relatively benignbreed of cardiologists who did little harm but little good either.That has emphatically changed, and it can now be attested thatelectrophysiologists exact the only true cure in cardiology.

Diagram of basket-shaped mapping catheter with severalrecording electrodes (red dots). The basket retracts into acatheter for placement in either the atria or ventricles.Once it is in position, retraction of the catheter allows thebasket to expand

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

In: Braunwald E, Zipes DP, Libby P, eds. Heart disease. 6th ed.Philadelphia: Saunders, 2001:1877-85

x McGuire MA, Janse MJ. New insights on the anatomical location ofcomponents of the reentrant circuit and ablation therapy foratrioventricular reentrant tachycardia. Curr Opin Cardiol 1995;10:3-8

x Jackman WM, Beckman KJ, McClelland JH, Wang X, Friday KJ,Roman CA, et al. Treatment of supraventricular tachycardia due toatrioventricular nodal re-entry by radiofrequency catheter ablationof the slow-pathway conduction. N Engl J Med 1992;327:313-8

x Calkins H, Leon AR, Deam AG, Kalbfleisch SJ, Langberg JJ,Morady F. Catheter ablation of atrial flutter using radiofrequencyenergy. Am J Cardiol 1994;73:353-6

x Schilling RJ, Peter NS, Davies DW. Feasibility of a non-contactcatheter for endocardial mapping of human ventriculartachycardia. Circulation 1999;99:2543-52

Competing interests: None declared.

The diagrams showing the mechanisms of orthodromic and antedromicatrioventricular re-entrant tachycardia and of slow-fast atrioventricularnodal re{entrant tachycardia are reproduced from ABC of ClinicalElectrocardiography, edited by Francis Morris, 2002.

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12 Implantable devices for treating tachyarrhythmiasTimothy Houghton, Gerry C Kaye

Pacing treatment for tachycardia control has achieved success,notably in supraventricular tachycardia. Pacing termination forventricular tachycardia has been more challenging, but anunderstanding of arrhythmia mechanisms, combined withincreasingly sophisticated pacemakers and the ability to deliverintracardiac pacing and shocks, have led to success withimplantable cardioverter defibrillators.

Mechanisms of pacing terminationThere are two methods of pace termination.

Underdrive pacing was used by early pacemakers to treatsupraventricular and ventricular tachycardias. Extrastimuli areintroduced at a constant interval, but at a slower rate than thetachycardia, until one arrives during a critical period,terminating the tachycardia. Because of the lack of sensing ofthe underlying tachycardia, there is a risk of a paced beat fallingon the T wave, producing ventricular fibrillation or ventriculartachycardia, or degenerating supraventricular tachycardias toatrial fibrillation. It is also not particularly successful atterminating supraventricular tachycardia or ventriculartachycardia and is no longer used routinely.

Overdrive pacing is more effective for terminating bothsupraventricular and ventricular tachycardias. It is painless,quick, effective, and associated with low battery drain of thepacemaker. Implantation of devices for terminatingsupraventricular tachycardias is now rarely required because ofthe high success rate of radiofrequency ablative procedures (seeprevious article). Overdrive pacing for ventricular tachycardia isoften successful but may cause acceleration or induceventricular fibrillation. Therefore, any device capable of pacetermination of ventricular tachycardia must also havedefibrillatory capability.

Implantable cardioverter defibrillatorsInitially, cardioverter defibrillator implantation was a majoroperation requiring thoracotomy and was associated with 3-5%mortality. The defibrillation electrodes were patches sewn on tothe myocardium, and leads were tunnelled subcutaneously tothe device, which was implanted in a subcutaneous abdominalpocket. Early devices were large and often shocked patientsinappropriately, mainly because these relatively unsophisticatedunits could not distinguish ventricular tachycardia fromsupraventricular tachycardia.

Current implantation proceduresModern implantable cardioverter defibrillators are transvenoussystems, so no thoracotomy is required and implantationmortality is about 0.5%. The device is implanted eithersubcutaneously, as for a pacemaker, in the left or rightdeltopectoral area, or subpectorally in thin patients to preventthe device eroding the skin.

The ventricular lead tip is positioned in the right ventricularapex, and a second lead can be positioned in the right atrialappendage to allow dual chamber pacing if required anddiscrimination between atrial and ventricular tachycardias. Theventricular defibrillator lead has either one or two shockingcoils. For two-coil leads, one is proximal (usually within thesuperior vena cava), and one is distal (right ventricular apex).

Changes in implantable cardioverter defibrillators over 10 years(1992-2002). Apart from the marked reduction in size, the implant techniqueand required hardware have also dramatically improved—from thesternotomy approach with four leads and abdominal implantation to thepresent two-lead transvenous endocardial approach that is no more invasivethan a pacemaker implant

Mechanisms of arrhythmiasUnicellularx Enhanced automaticityx Triggered activity—early or

delayed after depolarisations

Multicellularx Re-entryx Electrotonic interactionx Mechanico-electrical coupling

Arrhythmias associated with re-entryx Atrial flutterx Sinus node re-entry tachycardiax Junctional re-entry tachycardiax Atrioventricular reciprocating tachycardias (such

as Wolff-Parkinson-White syndrome)x Ventricular tachycardia

Chest radiograph of a dual chamber implantablecardioverter defibrillator with a dual coil ventricularlead (black arrow) and right atrial lead (white arrow)

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During implantation the unit is tested under conscioussedation. Satisfactory sensing during sinus rhythm, ventriculartachycardia, and ventricular fibrillation is established, as well aspacing and defibrillatory thresholds. Defibrillatory thresholdsshould be at least 10 joules less then the maximum output ofthe defibrillator (about 30 joules).

New developmentsAn important development is the implantable cardioverterdefibrillator’s ability to record intracardiac electrograms. Thisallows monitoring of each episode of anti-tachycardia pacing ordefibrillation. If treatment has been inappropriate, thenprogramming changes can be made with a programming unitplaced over the defibrillator site.

Current devices use anti-tachycardia pacing, with low andhigh energy shocks also available—known as tiered therapy.Anti-tachycardia pacing can take the form of adaptive burstpacing, with cycle length usually about 80-90% of that of theventricular tachycardia. Pacing bursts can be fixed (constantcycle length) or autodecremental, when the pacing burstaccelerates (each cycle length becomes shorter as the pacingtrain progresses). Should anti-tachycardia pacing fail, lowenergy shocks are given first to try to terminate ventriculartachycardia with the minimum of pain (as some patients remainconscious despite rapid ventricular tachycardia) and reducebattery drain, thereby increasing device longevity.

With the advent of dual chamber systems and improveddiagnostic algorithms, shocking is mostly avoided duringsupraventricular tachycardia. Even in single lead systems thealgorithms are now sufficiently sophisticated to differentiatebetween supraventricular tachycardia and ventriculartachycardia. There is a rate stability function, which assessescycle length variability and helps to exclude atrial fibrillation.

Device recognition of tachyarrhythmias is based mainly onthe tachycardia cycle length, which can initiate anti-tachycardiapacing or low energy or high energy shocks. With rapidtachycardias, the device can be programmed to give a highenergy shock as first line treatment.

ComplicationsThese include infection; perforation, displacement, fracture, orinsulation breakdown of the leads; oversensing or undersensingof the arrhythmia; and inappropriate shocks for sinus tachycardiaor supraventricular tachycardia. Psychological problems arecommon, and counselling plays an important role. Regular followup is required. If antiarrhythmic drugs are taken the potential useof an implantable cardioverter defibrillator is reduced.

Precautions—after patient death the device must be switchedoff before removal otherwise a severe electric shock can bedelivered to the person removing the device. The implantingcentre or local hospital should be informed that the patient hasdied and arrangements can usually be made to turn the ICDoff. The device must be removed before cremation.

Driving and implantable cardioverter defibrillatorsThe UK Driver and Vehicle Licensing Agency recommends thatgroup 1 (private motor car) licence holders are prohibited fromdriving for six months after implantation of a defibrillator whenthere have been preceding symptoms of an arrhythmia. If ashock is delivered within this period, driving is withheld for afurther six months.

Any change in device programming or antiarrhythmicdrugs means a month of abstinence from driving, and allpatients must remain under regular review. There is a five yearprohibition on driving if treatment or the arrhythmia isassociated with incapacity.

Posteroanterior and lateral chest radiographs of transvenous implantablecardioverter defibrillator showing the proximal and distal lead coils (arrows)

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Intracardiac electrograms from an implantable cardioverter defibrillator.Upper recording is intra-atrial electrogram, which shows atrial fibrillation.Middle and lower tracings are intracardiac electrograms from ventricle

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Intracardiac electrograms from implantable cardioverter defibrillators. Top:Ventricular tachycardia terminated with a single high energy shock. Seconddown: Ventricular tachycardia acceleration after unsuccessful ramp pacing,which was then terminated with a shock. Third down: Unsuccessful fixedburst pacing. Bottom: Successful ramp pacing termination of ventriculartachycardia

ABC of Interventional Cardiology

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Drivers holding a group 2 licence (lorries or buses) arepermanently disqualified from driving.

Indications for defibrillator usePrimary preventionPrimary prevention is considered in those who have had amyocardial infarction, depressed left ventricular systolicfunction, non-sustained ventricular tachycardia, and induciblesustained ventricular tachycardia at electrophysiological studies.

The major primary prevention trials, MADIT and MUSTT,showed that patients with implanted defibrillators had > 50%improvement in survival compared with control patients,despite 75% of MADIT control patients being treated with theantiarrhythmic drug amiodarone. A recent trial (MADIT-II)randomised 1232 patients with any history of myocardialinfarction and left ventricular dysfunction (ejection fraction< 30%) to receive a defibrillator or to continue medicaltreatment and showed that patients with the device had a 31%reduction in risk of death. Although these results are good newsclinically, they raise difficult questions about the potentiallycrippling economic impact of this added healthcare cost.

Implantation is also appropriate for cardiac conditions witha high risk of sudden death—long QT syndrome, hypertrophiccardiomyopathy, Brugada syndrome, arrhythmogenic rightventricular dysplasia, and after repair of tetralogy of Fallot.

Secondary preventionSecondary prevention is suitable for patients who have survivedcardiac arrest outside hospital or who have symptomatic,sustained ventricular tachycardia. A meta-analysis of studies ofimplanted defibrillators for secondary prevention showed thatthey reduced the relative risk of death by 28%, almost entirelydue to a 50% reduction in risk of sudden death.

When left ventricular function is impaired and heart failureis highly symptomatic, addition of a third pacing lead in thecoronary sinus allows left ventricular pacing andresynchronisation of ventricular contraction. Indications forthese new “biventricular” pacemakers include a broad QRScomplex ( > 115-130 ms), left ventricular dilatation, and severedyspnoea (New York Heart Association class 3). Biventricularpacing improves symptoms and, when combined with animplantable cardioverter defibrillator, confers a significant(40%) mortality benefit (COMPANION study).

Atrial flutter and fibrillationPacing to prevent atrial tachycardias, including atrial fibrillation,is presently under intense scrutiny as early results have beenfavourable. Atrial fibrillation is often initiated by atrialextrasystoles, and attention has focused on pacing to suppressatrial extrasystole, thereby preventing paroxysmal and sustainedatrial fibrillation.

Atrial flutterTermination of atrial flutter is most reliable with burst pacingfrom the coronary sinus or right atrium and usually requireslonger periods of pacing (5-30 s). The shorter the paced cyclelength, the sooner the rhythm converts to sinus. Directconversion to sinus rhythm is achievable with sustainedoverdrive pacing. However, the success of radiofrequencyablation means these techniques are rarely used.

Atrial fibrillationPrevention with pacing—Retrospective studies have shown that

atrial based pacing results in a reduced burden of atrialfibrillation compared with ventricular based pacing. Pacing the

Guidelines for implanting cardioverter defibrillatorsFor “primary prevention”x Non-sustained ventricular tachycardia on Holter monitoring (24

hour electrocardiography)x Inducible ventricular tachycardia on electrophysiological testingx Left ventricular dysfunction with an ejection fraction < 35% and no

worse than class 3 of the NYHA functional classification of heartfailure

For “secondary prevention”x Cardiac arrest due to ventricular tachycardia or ventricular

fibrillationx Spontaneous sustained ventricular tachycardia causing syncope or

substantial haemodynamic compromisex Sustained ventricular tachycardia without syncope or cardiac arrest

in patients who have an associated reduction in ejection fraction( < 35%) but are no worse than class 3 of NYHA functionalclassification of heart failure

NYHA = New York Heart Association

Names of trialsx MADIT—Multicenter automatic defibrillator implantation trialx MUSTT—Multicenter unsustained tachycardia trialx COMPANION—Comparison of medical therapy, pacing, and

defibrillation in chronic heart failure

Chest radiograph showing biventricular pacemaker withleads in the right ventricle, right atrium, and coronarysinus (arrows)

Continuous electrocardiogram showing sinus rhythm with frequent atrialextrasystoles (top) arising from the pulmonary veins degenerating into atrialfibrillation (bottom)

Implantable devices for treating tachyarrhythmias

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atria at high rates may prevent the conditions required forre{entry and thus prevent atrial fibrillation. Current research isbased on triggered atrial pacing, and specific preventive andanti-tachycardia pacing systems are now available for patientswith symptomatic paroxysmal atrial tachycardias that are notcontrolled by drugs. Such devices continually scan the sinus rateand monitor atrial extrasystoles. Right atrial overdrive pacing at10-29 beats per minute faster than the sinus rate suppresses thefrequency of extrasystoles. The pacing rate then slows to allowsinus activity to take over, provided no further extrasystoles aresensed. In some patients atrial fibrillation is initiated duringsleep, when the sinus rate is vagally slowed. Resynchronisation(simultaneous pacing at two different atrial sites) in patientswith intra-atrial conduction delay may be beneficial. Clinicaltrials will help answer the question of which form of pacing bestprevents atrial fibrillation.

Cardioversion with implantable atrial defibrillators—These areuseful in some patients with paroxysmal atrial fibrillation. It isknown that rapid restoration of sinus rhythm reduces the risk ofprotracted or permanent atrial fibrillation. Cardioversion issynchronised to the R wave, and shocks are given between thecoronary sinus and right ventricular leads. The problem is thatshocks of > 1 joule are uncomfortable, and the meandefibrillation threshold is 3 joules. Thus, sedation is requiredbefore each shock.

Future developmentsWith the development of anti-atrial fibrillation pacing, focalablation to the pulmonary veins, and flutter ablation,implantable cardioverter defibrillators will be used less often inyears to come. The future of device therapy for atrial fibrillationand atrial flutter probably lies in the perfection ofradiofrequency ablation and atrial pacing, although there willstill be a place for atrioventricular nodal ablation andpermanent ventricular pacing in selected patients.

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

tachyarrhythmias. In: Camm AJ, Ward DE, eds. Clinical aspects ofcardiac arrhythmias. London: Kluwer Academic Publishers,1988:337-57

x Cooper RAS, Ideker RE. The electrophysiological basis for theprevention of tachyarrhythmias. In: Daubert JC, Prystowsky EN,Ripart A, eds. Prevention of tachyarrhythmias with cardiac pacing.Armonk, NY: Futura Publishing, 1997:3-24

x Josephson ME. Supraventricular tachycardias. In: Bussy K, ed.Clinical cardiac electrophysiology. Philadelphia: Lea and Febiger,1993:181-274

x Connolly SJ, Hallstrom AP, Cappato R, Schron EB, Kuck KH,Zipes DP, et al. Meta-analysis of the implantable cardioverterdefibrillator secondary prevention trials. Eur Heart J 2000;21:2071-8

x Mirowski M, Mower MM, Staewen WS, Denniston RH, MendeloffAI. The development of the transvenous automatic defibrillator.Ann Intern Med 1973;129:773-9

Competing interests: TH has been reimbursed by Guidant for attending aconference in 2001.

The figure of implantable cardioverter defibrillators from 1992 and 2002 issupplied by C M Finlay, CRT coordinator, Guidant Canada Corporation,Toronto.

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13 Interventional paediatric cardiologyKevin P Walsh

Interventional paediatric cardiology mainly involves dilatationof stenotic vessels or valves and occlusion of abnormalcommunications. Many transcatheter techniques—such asballoon dilatation, stent implantation, and coil occlusion—havebeen adapted from adult practice. Devices to occlude septaldefects, developed primarily for children, have also foundapplication in adults.

Basic techniquesInterventional procedures follow a common method. Generalanaesthesia or sedation is required, and most procedures startwith percutaneous femoral access. Haemodynamicmeasurements and angiograms may further delineate theanatomy or lesion severity. A catheter is passed across thestenosis or abnormal communication. A guidewire is thenpassed through the catheter to provide a track over whichtherapeutic devices are delivered. Balloon catheters arethreaded directly, whereas stents and occlusion devices areprotected or constrained within long plastic sheaths.

DilatationsSeptostomyBalloon atrial septostomy, introduced by Rashkind 35 years ago,improves mixing of oxygenated and deoxygenated blood inpatients with transposition physiology or in those requiringventing of an atrium with restricted outflow. Atrial septostomyoutside the neonatal period, when the atrial septum is muchtougher, is done by first cutting the atrial septum with a blade.

Balloon valvuloplastyPulmonary valve stenosisBalloon valvuloplasty has become the treatment of choice forpulmonary valve stenosis in all age groups. It relieves thestenosis by tearing the valve, and the resultant pulmonaryregurgitation is mild and well tolerated. Surgery is used only fordysplastic valves in patients with Noonan’s syndrome, who havesmall valve rings and require a patch to enlarge the annulus.

Valvuloplasty is especially useful in neonates with criticalpulmonary stenosis, where traditional surgery carried a highmortality. In neonates with the more extreme form ofpulmonary atresia with an intact ventricular septum,valvuloplasty can still be done by first perforating thepulmonary valve with a hot wire. Pulmonary valvuloplasty canalso alleviate cyanotic spells in patients with tetralogy of Fallotwhose pulmonary arteries are not yet large enough to undergoprimary repair safely.

Aortic valve stenosisUnlike in adults, aortic valve stenosis in children (which isnon{calcific) is usually treated by balloon dilatation. A balloonsize close to the annulus diameter is chosen, as overdilatation(routinely done in pulmonary stenosis) can result in substantialaortic regurgitation. The balloon is usually introducedretrogradely via the femoral artery and passed across the aorticvalve. Injection of adenosine, producing brief cardiac standstillduring balloon inflation, avoids balloon ejection by powerful leftventricular contraction.

Balloon atrial septostomy.Under echocardiographiccontrol in a neonate withtransposition of the greatarteries, a balloon septostomycatheter has been passed viathe umbilical vein, ductusvenosus, inferior vena cava,and right atrium and throughthe patent foramen ovale intothe left atrium. The balloon isinflated in the left atrium (top)and jerked back across theatrial septum into the rightatrium (middle). Thismanoeuvre tears the atrialseptum to produce an atrialseptal defect (arrow, bottom)with improved mixing andarterial saturations

Balloon pulmonaryvalvuloplasty. A largevalvuloplasty balloon isinflated across a stenoticpulmonary valve, whichproduces a waist-like balloonindentation (A, top). Furtherinflation of the balloonabolishes the waist (bottom).This patient had previouslyundergone closure of amid{muscular ventricularseptal defect with a drumshaped Amplatzer ventricularseptal defect occluder (B, top).A transoesophagealechocardiogram probe is alsovisible

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In neonates with critical aortic stenosis and poor leftventricular function the balloon can be introduced in anantegrade fashion, via the femoral vein and across theinteratrial septum through the patent foramen ovale. Thisreduces the risk of femoral artery thrombosis and perforationof the soft neonatal aortic valve leaflets by guidewires. The longterm result of aortic valve dilatation in neonates depends onboth effective balloon dilatation of the valve and the degree ofassociated left heart hypoplasia.

AngioplastyBalloon dilatation for coarctation of the aorta is used for bothnative and postsurgical coarctation and is the treatment ofchoice for re-coarctation. Its efficacy in native coarctationdepends on the patient’s age and whether there is appreciableunderdevelopment of the aortic arch. Neonates in whom theductal tissue forms a sling around the arch have a good initialresponse to dilatation but a high restenosis rate, probablybecause of later contraction of ductal tissue. Older patients havea good response to balloon dilatation. However, overdilatationmay result in formation of an aneurysm.

StentsThe problems of vessel recoil or dissection have been addressedby the introduction of endovascular stents. This developmenthas been particularly important for patients with pulmonaryartery stenoses, especially those who have undergone correctivesurgery, for whom repeat surgery can be disappointing. Moststents are balloon expandable and can be further expandedafter initial deployment with a larger balloon to keep up with achild’s growth.

Results from stent implantation for pulmonary arterystenosis have been good, with sustained increases in vesseldiameter, 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 inpatients over 8 years old. Graded dilatation of a severely stenoticsegment over two operations may be required to avoidoverdistension and possible formation of an aneurysm. Inpatients with pulmonary atresia without true central pulmonaryarteries, stenotic collateral arteries can be enlarged by stentimplantation (often preceded by cutting balloon dilation) toproduce a useful increase in oxygen saturation.

An exciting new advance has been percutaneous valvereplacement. A bovine jugular vein valve is sutured to the inneraspect of a large stent, which is crimped on to a balloon deliverysystem and then expanded into a valveless outflow conduit thathas been surgically placed in the right ventricle. Several patientshave been treated successfully with this system, although followup is short.

OcclusionsTranscatheter occlusion of intracardiac and extracardiaccommunications has been revolutionised by the development ofthe Amplatzer devices. These are made from a cylindricalNitinol wire mesh and formed by heat treatment into differentshapes. A sleeve with a female thread on the proximal end ofthe device allows attachment of a delivery cable with a malescrew. The attached device can then be pulled and pushed intothe loader and delivery sheath respectively. A family of deviceshas been produced to occlude ostium secundum atrial septaldefects, patent foramen ovale, patent ductus arteriosus, andventricular septal defects.

Pulmonary artery stenting. Achild with previously repairedtetralogy of Fallot had severestenoses at the junction of rightand left branch pulmonaryarteries with main pulmonaryartery (top left). Two stents wereinflated simultaneously acrossthe stenoses in criss-crossarrangement (top right).Angiography shows completerelief of the stenoses (left)

Stenting of coarctation of the aorta. An aortogram in an adolescent boyshows a long segment coarctation (arrows, left). A cineframe shows thestent being inflated into place (middle). Repeat aortagraphy showscomplete relief of the coarctation (right)

Transcatheter closure of a perimembranous ventricular septal defect. Leftventriculogram shows substantial shunting of dye (in direction of arrow)through a defect in the high perimembranous ventricular septum (left).After placement of an eccentric Amplatzer membranous ventricular septaldefect device, a repeat left ventriculogram shows complete absence ofshunting (right)

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Atrial septal defectsThe Amplatzer atrial septal defect occluder has the shape oftwo saucers connected by a central stent-like cylinder that variesin diameter from 4 mm to 40 mm to allow closure of both smalland large atrial septal defects. Very large secundum atrial septaldefects with incomplete margins (other than at the aortic end ofthe defect) may require a surgically placed patch.

An atrial septal defect is sized with catheter balloons ofprogressively increasing diameter. An occluder of the correctsize is then introduced into the left atrium via a longtransvenous sheath. The left atrial disk of the occluder isextruded and pulled against the defect. The sheath is thenpulled back to deploy the rest of the device (central waist andright atrial disk) and released after its placement is assessed bytransoesophageal echocardiography. The defect is closed by theinduction of thrombosis on three polyester patches sewn intothe device and is covered by neocardia within two months.Aspirin is usually for given for six months and clopidrogrel for6-12 weeks.

Worldwide, several thousand patients have had their atrialseptal defects closed with Amplatzer devices, with highocclusion rates. Complications are unusual and consist of devicemigration ( < 1%), transient arrhythmias (1-2%), and, rarely,thrombus formation with cerebral thromboembolism or aorticerosion with tamponade. Transcatheter occlusion is now thetreatment of choice for patients with suitable atrial septaldefects. Other devices are available, but none has the sameapplicability or ease of use.

Patent foramen ovaleThe Amplatzer atrial septal defect occluder can also be used totreat adults with paradoxical thromboembolism via a patentforamen ovale. The Amplatzer patent foramen ovale occluderhas no central stent and is designed to close the flap-valve ofthe patent foramen ovale. Randomised trials are under way tocompare device closure with medical treatment for preventingrecurrent thromboembolism.

Patent ductus arteriosusAlthough premature babies and small infants with a largepatent ductus arteriosus are still treated surgically, most patientswith a patent ductus arteriosus are treated by transcatheter coilocclusion. This technique has been highly successful at closingsmall defects, but when the minimum diameter is > 3 mmmultiple and larger diameter coils are required, which prolongsthe procedure and increases the risk of left pulmonary arteryencroachment. The Amplatzer patent ductus arteriosus plug,which has a mushroom shaped Nitinol frame stuffed withpolyester, is used for occluding larger defects. The occlusionrates are close to 100%, higher than published results forsurgical ligation.

Cineframe showing the threecomponents of the Amplatzeratrial septal defect occluder—aleft atrial disk, central stent(arrows), and a right atrialdisk. The device has just beenunscrewed from the deliverywire, and the male screw onthe delivery wire can be seen(arrowhead)

Atrial septal defect occlusion. Transoesophageal echocardiograms of anatrial septal defect before (left) and after (right) occlusion with an Amplatzeratrial septal defect device. The three components of the device are easilyseen. (LA=left atrium, RA=right atrium)

Patent foramen ovale closure.A cine frame of an implantedAmplatzer patent foramenovale device shows that itdiffers from the atrial septaldefect device in not having acentral stent. Its right atrialdisk is larger than the leftatrial disk and faces in aconcave direction towards theatrial septum

Coil occlusion of a patent ductus arteriosus. An aortogram performed viathe transvenous approach shows dye shunting through the small conicalpatent ductus arteriosus into the pulmonary artery (left). After placement ofmultiple coils, a repeat aortogram shows no residual shunting (right)

Transcatheter plugging of a largepatent ductus arteriosus. Anaortogram shows a large tubularpatent ductus arteriosus with alarge shunt of dye from the aortato the pulmonary artery (top left).An Amplatzer plug is deployed inthe defect, still attached to itsdelivery wire (top right). A repeataortogram after release of thedevice shows no significant residualshunting (left)

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Ventricular septal defectsOcclusion devices are especially useful for multiple congenitalmuscular ventricular septal defects, which can be difficult tocorrect surgically. The Amplatzer occluder device has adrum{like shape and is deployed through long sheaths withrelatively small diameter.

Such devices have also been used to occludeperimembranous defects, although in this location they caninterfere with aortic valve function. A device with eccentricdisks, which should avoid interference with adjacent valves, hasrecently been introduced. The Amplatzer membranous devicehas two discs connected by a short cylindrical waist. The deviceis eccentric, with the left ventricular disc having no marginsuperiorly, where it could come near the aortic valve, and alonger margin inferiorly to hold it on the left ventricular side ofthe defect. The end screw of the device has a flat portion, whichallows it to be aligned with a precurved pusher catheter. Thispusher catheter then extrudes the eccentric left ventricular diskfrom the specially curved sheath with its longer marginorientated inferiorly in the left ventricle. Initial results arepromising, particularly for larger infants withhaemodynamically important ventricular septal defects.

Transcatheter occlusion has also been used to treatventricular septal defects in adults who have had a myocardialinfarction, and a specific occluder has been introduced. It differsfrom the infant device in having a 10 mm long central stent toaccommodate the thicker adult interventricular septum. Its rolein treatment is uncertain, but it offers an alternative for patientswho have significant contraindications to surgical closure.

Coil occlusion of unwanted blood vesselsCoil occlusion of unwanted blood vessels (aortopulmonarycollateral arteries, coronary artery fistulae, arteriovenousmalformations, venous collaterals) is increasingly effectivebecause of improvements in catheter and coil design.

Percutaneous intervention versussurgeryThe growth of interventional cardiology has meant that thesimpler defects are now dealt with in catheterisationlaboratories, and cardiac surgeons are increasingly operating onmore complex lesions such as hypoplastic left heart syndrome.More importantly, interventional cardiology can complementthe management of these complex patients, resulting in a betteroutcome for children with congenital heart disease.

Complications such as device embolisation, vessel orchamber perforation, thrombosis, and radiation exposure canbe reduced by careful selection of patients and devices,meticulous technique, low dose pulsed fluoroscopy, and, mostimportantly, operator experience. Further developments incatheter and device design will improve and widen treatmentapplications.

Competing interests: None declared.

Transcatheter closure of a mid-muscular ventricular septal defect. A leftventriculogram shows substantial shunting of dye through a defect in themid-muscular ventricular septum (left). After placement of an Amplatzermuscular ventricular septal defect device, a repeat left ventriculogram showsonly a small amount of shunting through the device (right), which ceasedafter three months

The Amplatzer perimembranousventricular septal defect device. Thetwo disks are offset from eachother to minimise the chance of theleft ventricular disk impinging onthe aortic valve. The central stent ismuch narrower than in themuscular ventricular septal defectdevice as the membranous septumis much thinner than the muscularseptum

Coil occlusion of a coronary fistula. A selective left coronary arteriogramshows a fistula arising from the left anterior descending coronary artery(arrow, left) draining to the right ventricle (RV). Multiple interlockingdetachable coils are placed to completely occlude the fistula (arrow, right)

Further readingx Kan JS, White RI Jr, Mitchell SE, Gardner TJ. Percutaneous balloon

valvuloplasty: a new method for treating congenital pulmonaryvalve stenosis. N Engl J Med 1982;307:540-2

x Waight DJ, Cao Q-L, Hijazi ZM. Interventional cardiaccatheterisation in adults with congenital heart disease. In: GrechED, Ramsdale DR, eds. Practical interventional cardiology. 2nd ed.London: Martin Dunitz, 2002:390-406

x Morrison WL, Walsh KP. Transcatheter closure of ventricular septaldefect 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 ductusarteriosus using the new Amplatzer duct occluder: immediate andshort-term results. J Am Coll Cardiol 1998;31:878-82

x Walsh KP, Maadi IM. The Amplatzer septal occluder. Cardiol Young2000;10:493-50

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balloon pump, intra–aortic 8, 20balloon septostomy 45, 45balloon valvuloplasty 29–30, 45–6, 45, 46barotrauma, arterial 6blood vessels, coil occlusion 48, 48brachytherapy 5, 10, 10, 34bypass surgery 12, 35

chronic stable angina 12, 12, 13, 13, 14–15, 14emergency 9, 24, 27percutaneous in situ 36

“candy wrapper” lesions 10, 10cardiac biochemical markers 16, 17, 18cardiac tamponade 9, 23, 47cardiac troponin I/T 17, 18cardiogenic shock 22–4, 22cardiology referral, priorities for 1, 1cardiomyopathy, hypertrophic 30–1, 30, 30, 31cardiovascular disease 1, 1

genetic 30see also coronary artery disease

cardioverter defibrillators 41–4, 43catheters

balloon 5, 5, 9, 9, 10, 10, 29diagnostic 3–4, 3guide 5, 9, 9intravascular ultrasound (IVUS) 4non-contact mapping 40, 40

cerebrovascular events 19, 20, 29chest pain 1chronic stable angina 12–15circumflex coronary arteries 14, 33, 34clinical trials, refusal to participate in 15clopidogrel 8, 17, 25, 25, 26, 27coarctation of the aorta 46, 46coil occlusion, transcatheter 47, 47, 48, 48congenital abnormalities 31–2, 45–8contrast medium 3, 9, 10, 33coronary arteries, normal 3coronary artery, right, occlusion 11, 14, 17, 21, 23, 33, 35coronary artery bypass graft surgery see bypass surgerycoronary artery disease 1–4, 15, 35coronary sinus electrode signals 38, 38coronary stents see stentscutting devices 6, 6, 10, 10

defibrillators 40, 41–4, 43diabetes

chronic stable angina and 14–15stents and 10, 27, 34

direct angioplasty see primary angioplastyDoppler flow wire and pressure wire 4

abciximab 21, 25, 26, 26, 27, 28ablation 30-1, 39–40accessory pathways 37–8, 37, 38, 39–40acute coronary events 1acute coronary syndromes 16–18, 16, 19–21

diagnosis 16–17management 35, 35

adjunctive pharmacotherapy see pharmacotherapy,interventional

AH interval 37–8Amplatz catheter 3, 3Amplatzer septal defect occluders 31–2, 31, 32, 47,

47, 48angina 1–4, 5, 15

see also chronic stable angina; unstable anginaangiography 3, 3, 3, 17, 17, 24, 33angioplasty 5, 5, 6, 6, 19–20

paediatric 46anterior descending arteries 14, 20, 22, 33, 34anticoagulent therapy see aspirin; heparinantiplatelet drugs 5, 7, 25, 26–8

see also abciximab; clopidogrel; glycoprotein IIb/IIIainhibitors

antithrombotic therapy 25–8, 25aortic valve stenosis 30, 45–6arrhythmias 37–40, 37, 41

driving and 42implantable devices 41–4reperfusion 20, 20, 21

arterial grafts 12, 13arteries

access 9, 9occlusion 6, 16, 19–21restenosis 6stenosis 1, 1, 4, 4, 8, 8, 45–6

aspirin 8, 17, 25, 25, 26athero-ablation/atherectomy 5, 6, 6, 10, 10atheroma 1, 1atheromatous plaques 1, 1, 4

rupture 16, 16, 19–21ulcerated 35, 36

atrial extrasystoles 43, 44atrial fibrillation 37, 39–40, 44atrial flutter 37, 39–40atrial septal defects 29, 31, 31, 31, 47, 47atrial septostomy 45, 45atrial tachycardias 43–4, 43atrioventricular conduction 37–8, 38

balloon angioplasty 20, 20balloon catheters 5, 5, 9, 9, 10, 10, 29balloon dilatation, paediatric 46

Index

Page numbers in bold type refer to figures; those in italics refer to tables.

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drills, plaque removal 6, 6driving fitness 11, 42

electrocardiography 2, 2, 17, 17intracardiac 42, 42

electrophysiology, percutaneous interventional 37–40endothelial layer, in stents 7, 34eptifibatide 25, 26, 26, 27ethanol septal ablation 30–1exercise tests 2, 2, 13, 13

fitness for work 11fluoroscopy 9

glycoprotein IIb/IIIa receptor inhibitors 9, 17, 21, 25, 25, 26–8, 26

see also abciximab; eptifibatide; tirofibanguide catheters 5, 9, 9guidewires 5, 9, 9

heart block, ablation-induced 31heparin 9, 17

low molecular weight 25, 26unfractionated 25–6, 25

“hockey stick” curve 38hypertrophic cardiomyopathy 30–1, 30, 30, 31hypotension, in myocardial infarction 22, 23, 24

implantable devices 40, 41–4, 43internal mammary artery graft 12, 12, 13intra-aortic balloon pump 22, 23, 23, 23, 24intravascular ultrasound (IVUS) 4, 4ischaemia 1–4, 2, 2, 16–17

in percutaneous procedures 9

junctional re-entry tachycardia 37, 39, 39

laser recanalisation 6, 10, 34left main stem coronary disease 13left ventricular angiography 3, 3left ventricular dysfunction 13, 13, 22, 43left ventricular function, assessment 3, 3left ventricular hypertrophy 30–1, 30

mitral regurgitation 23, 29, 30mitral valve stenosis 29–30, 29mortality rates

cardiogenic shock 22chronic stable angina 13glycoprotein IIb/IIIa inhibitors and 27, 27myocardial infarction 24

multigated acquisition scan (MUGA) 3multivessel disease 13, 13, 14, 33, 34, 34myocardial infarction 1–4, 35, 43

non-ST segment elevation 16–18percutaneous procedures and 9, 27, 27septal defects caused by 32ST segment elevation 19–21

myocardial revascularisation 5, 36myocardial rupture 23, 23

non-contact mapping catheters 40, 40non-ST segment elevation myocardial infarction 16–18, 27

occlusions, paediatric 46–8overdrive pacing 41oxygen need 17, 23, 23

pacemakers 31, 39, 41biventricular 43, 43temporary 8, 21

pacing termination 41paclitaxel coated stents 11, 34paediatric interventional cardiology 45–8paradoxical embolism 32, 47patent ductus arteriosus 47, 47patent foramen ovale 31–2, 32, 47, 47patients

high risk 17, 18, 18refusal to participate in trials 15

percutaneous coronary interventionsadjunctive pharmacotherapy 5, 25, 25, 27developments 5–7, 33–6devices 33indications for 8, 13, 14procedure 8–11risk assessment 8roles of 35statistics 33

percutaneous interventional electrophysiology 37–40

percutaneous interventions, non-coronary 29–32pharmacotherapy, interventional 25–8photodynamic therapy 34“pigtail” catheter 3–4, 3platelets 16, 16, 25

see also antiplatelet drugsprimary angioplasty 19–20pulmonary artery stenosis 46pulmonary hypertension 31, 32pulmonary oedema 22, 22pulmonary valve stenosis 45, 45pulsus paradoxus 23, 23

radiofrequency ablation 39, 40radionuclide myocardial perfusion imaging 2–3, 2recanalisation methods 19, 19re-endothelialisation, in stents 7, 34re-entrant arrhythmia 37, 37, 38, 39, 41refractory coronary artery disease 15reperfusion 23–4reperfusion arrhythmias 20, 20, 21restenosis see arteries; stentsretrograde ventriculoatrial conduction 38revascularisation 35–6right coronary artery occlusion 11, 14, 17, 21, 23, 33, 35right ventricular infarction 23, 23

saphenous vein graft 12, 12, 13, 13septal ablation, ethanol 30–1septal artery 30septal defect closure 31–2, 31, 32, 47, 47, 48septal enlargement 30, 30septostomy, balloon atrial 45, 45sirolimus coated stents 11, 11, 33smoking 1, 18, 36sonotherapy 34stents 5, 6–7, 6, 7, 7, 9, 9, 22

adjunctive pharmacotherapy 25, 27developments 33–4, 35–6, 35drug eluting 6, 7, 11, 11, 28, 33–4, 35paediatric 46, 46primary angioplasty and 20–1, 21PTFE coated 6

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re-endothelialisation 7, 34restenosis 10–11, 10, 11, 28, 34

stress echocardiography 2, 2, 2ST segment elevation myocardial infarction 19–21, 23, 23, 28supraventricular tachycardia 37, 38–9, 41–2systolic murmur, cardiogenic shock 23, 23

tachyarrhythmias, implantable devices 41–4tachycardias 37, 38–9, 40, 43–4, 43tetralogy of Fallot 45, 46thienopyridines (antiplatelet drugs) 26

see also clopidogrel; ticlopidenethrombin inhibitors 26thrombocytopenia, heparin–induced 25, 26thrombolytic drugs 19, 19, 23–4thrombosis 7, 22, 25–8, 25

thrombus formation 1, 16, 16, 35

see also antithrombotic therapyticlopidene 25, 26TIMI risk score 18, 18tirofiban 25, 26, 26, 27

ultrasonography 4, 4underdrive pacing 41unstable angina 16–18, 16, 27

valves see aortic valve; mitral valve; pulmonary valvevalvuloplasty 29–30, 45–6, 45, 46ventricular septal defects 23, 30–1, 32, 32, 46, 48, 48ventricular tachycardia 37, 40, 41–2, 43

Wolff-Parkinson-White syndrome 37, 38, 39, 39

x ray, chest pain 2, 3