EMERGENCY CARDIOLOGY Second Edition Karim Ratib MBC H B BS C (H ONS ) MRCP Specialist Registrar in Cardiology, University Hospital of North Staffordshire, Stoke-on-Trent, UK Gurbir Bhatia M B C H B MD MRCP Specialist Registrar in Cardiology, University Hospital of North Staffordshire, Stoke-on-Trent, UK Neal Uren MD (H ONS ) FRCP Consultant Cardiologist, Edinburgh Heart Centre, Royal Infirmary, Edinburgh, UK James Nolan MBC H B MD FRCP Consultant Cardiologist, University Hospital of North Staffordshire, Stoke-on-Trent, UK EMERGENCY CARDIOLOGY AN EVIDENCE - BASED GUIDE TO ACUTE CARDIAC PROBLEMS Boca Raton London New York CRC Press is an imprint of the Taylor & Francis Group, an informa business Second Edition Karim Ratib MBC H B BS C (H ONS ) MRCP Specialist Registrar in Cardiology, University Hospital of North Staffordshire, Stoke-on-Trent, UK Gurbir Bhatia M B C H B MD MRCP Specialist Registrar in Cardiology, University Hospital of North Staffordshire, Stoke-on-Trent, UK Neal Uren MD (H ONS ) FRCP Consultant Cardiologist, Edinburgh Heart Centre, Royal Infirmary, Edinburgh, UK James Nolan MBC H B MD FRCP Consultant Cardiologist, University Hospital of North Staffordshire, Stoke-on-Trent, UK EMERGENCY CARDIOLOGY AN EVIDENCE - BASED GUIDE TO ACUTE CARDIAC PROBLEMS Boca Raton London New York CRC Press is an imprint of the Taylor & Francis Group, an informa business Second Edition Karim Ratib MBC H B BS C (H ONS ) MRCP Specialist Registrar in Cardiology, University Hospital of North Staffordshire, Stoke-on-Trent, UK Gurbir Bhatia M B C H B MD MRCP Specialist Registrar in Cardiology, University Hospital of North Staffordshire, Stoke-on-Trent, UK Neal Uren MD (H ONS ) FRCP Consultant Cardiologist, Edinburgh Heart Centre, Royal Infirmary, Edinburgh, UK James Nolan MBC H B MD FRCP Consultant Cardiologist, University Hospital of North Staffordshire, Stoke-on-Trent, UK EMERGENCY CARDIOLOGY AN EVIDENCE - BASED GUIDE TO ACUTE CARDIAC PROBLEMS Boca Raton London New York CRC Press is an imprint of the Taylor & Francis Group, an informa business CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works © 2011 Karim Ratib, Ghurbir Bhatia, Neal Uren and James Nolan. This book contains information obtained from authentic and highly regarded sources. While all reasonable efforts have been made to publish reliable data and information, neither the author[s] nor the publisher can accept any legal respon-sibility or liability for any errors or omissions that may be made. The publishers wish to make clear that any views or opinions expressed in this book by individual editors, authors or contributors are personal to them and do not neces-sarily reflect the views/opinions of the publishers. The information or guidance contained in this book is intended for use by medical, scientific or health-care professionals and is provided strictly as a supplement to the medical or other professional’s own judgement, their knowledge of the patient’s medical history, relevant manufacturer’s instructions and the appropriate best practice guidelines. Because of the rapid advances in medical science, any information or advice on dosages, procedures or diagnoses should be independently verified. The reader is strongly urged to consult the relevant national drug formulary and the drug companies’ and device or material manufacturers’ printed instructions, and their websites, before administering or utilizing any of the drugs, devices or materials mentioned in this book. This book does not indicate whether a particular treatment is appropriate or suitable for a particular individual. Ultimately it is the sole responsibility of the medical professional to make his or her own professional judgements, so as to advise and treat patients appropriately. The authors and publishers have also attempted to trace the copyright holders of all mate-rial reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or uti-lized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopy-ing, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically f rom this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com British Library Cataloguing in Publication Data CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works © 2011 Karim Ratib, Ghurbir Bhatia, Neal Uren and James Nolan. This book contains information obtained from authentic and highly regarded sources. While all reasonable efforts have been made to publish reliable data and information, neither the author[s] nor the publisher can accept any legal respon-sibility or liability for any errors or omissions that may be made. The publishers wish to make clear that any views or opinions expressed in this book by individual editors, authors or contributors are personal to them and do not neces-sarily reflect the views/opinions of the publishers. The information or guidance contained in this book is intended for use by medical, scientific or health-care professionals and is provided strictly as a supplement to the medical or other professional’s own judgement, their knowledge of the patient’s medical history, relevant manufacturer’s instructions and the appropriate best practice guidelines. Because of the rapid advances in medical science, any information or advice on dosages, procedures or diagnoses should be independently verified. The reader is strongly urged to consult the relevant national drug formulary and the drug companies’ and device or material manufacturers’ printed instructions, and their websites, before administering or utilizing any of the drugs, devices or materials mentioned in this book. This book does not indicate whether a particular treatment is appropriate or suitable for a particular individual. Ultimately it is the sole responsibility of the medical professional to make his or her own professional judgements, so as to advise and treat patients appropriately. The authors and publishers have also attempted to trace the copyright holders of all mate-rial reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or uti-lized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopy-ing, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically f rom this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress ISBN-13 9781138422575 (hbk) The Open Access version of this book, available at www.taylorfrancis.com, has been made available under a Creative Commons Attribution-Non Commercial-No Derivatives 4.0 license. CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works © 2011 Karim Ratib, Ghurbir Bhatia, Neal Uren and James Nolan. This book contains information obtained from authentic and highly regarded sources. While all reasonable efforts have been made to publish reliable data and information, neither the author[s] nor the publisher can accept any legal respon-sibility or liability for any errors or omissions that may be made. The publishers wish to make clear that any views or opinions expressed in this book by individual editors, authors or contributors are personal to them and do not neces-sarily reflect the views/opinions of the publishers. The information or guidance contained in this book is intended for use by medical, scientific or health-care professionals and is provided strictly as a supplement to the medical or other professional’s own judgement, their knowledge of the patient’s medical history, relevant manufacturer’s instructions and the appropriate best practice guidelines. Because of the rapid advances in medical science, any information or advice on dosages, procedures or diagnoses should be independently verified. The reader is strongly urged to consult the relevant national drug formulary and the drug companies’ and device or material manufacturers’ printed instructions, and their websites, before administering or utilizing any of the drugs, devices or materials mentioned in this book. This book does not indicate whether a particular treatment is appropriate or suitable for a particular individual. Ultimately it is the sole responsibility of the medical professional to make his or her own professional judgements, so as to advise and treat patients appropriately. The authors and publishers have also attempted to trace the copyright holders of all mate-rial reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or uti-lized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopy-ing, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically f rom this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress ISBN-13 978 0 340 974 223 CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works © 2011 Karim Ratib, Ghurbir Bhatia, Neal Uren and James Nolan. This book contains information obtained from authentic and highly regarded sources. While all reasonable efforts have been made to publish reliable data and information, neither the author[s] nor the publisher can accept any legal respon-sibility or liability for any errors or omissions that may be made. The publishers wish to make clear that any views or opinions expressed in this book by individual editors, authors or contributors are personal to them and do not neces-sarily reflect the views/opinions of the publishers. The information or guidance contained in this book is intended for use by medical, scientific or health-care professionals and is provided strictly as a supplement to the medical or other professional’s own judgement, their knowledge of the patient’s medical history, relevant manufacturer’s instructions and the appropriate best practice guidelines. Because of the rapid advances in medical science, any information or advice on dosages, procedures or diagnoses should be independently verified. The reader is strongly urged to consult the relevant national drug formulary and the drug companies’ and device or material manufacturers’ printed instructions, and their websites, before administering or utilizing any of the drugs, devices or materials mentioned in this book. This book does not indicate whether a particular treatment is appropriate or suitable for a particular individual. Ultimately it is the sole responsibility of the medical professional to make his or her own professional judgements, so as to advise and treat patients appropriately. The authors and publishers have also attempted to trace the copyright holders of all mate-rial reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or uti-lized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopy-ing, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically f rom this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress ISBN-13 978 0 340 974 223 CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works © 2011 Karim Ratib, Ghurbir Bhatia, Neal Uren and James Nolan. This book contains information obtained from authentic and highly regarded sources. While all reasonable efforts have been made to publish reliable data and information, neither the author[s] nor the publisher can accept any legal respon-sibility or liability for any errors or omissions that may be made. The publishers wish to make clear that any views or opinions expressed in this book by individual editors, authors or contributors are personal to them and do not neces-sarily reflect the views/opinions of the publishers. The information or guidance contained in this book is intended for use by medical, scientific or health-care professionals and is provided strictly as a supplement to the medical or other professional’s own judgement, their knowledge of the patient’s medical history, relevant manufacturer’s instructions and the appropriate best practice guidelines. Because of the rapid advances in medical science, any information or advice on dosages, procedures or diagnoses should be independently verified. The reader is strongly urged to consult the relevant national drug formulary and the drug companies’ and device or material manufacturers’ printed instructions, and their websites, before administering or utilizing any of the drugs, devices or materials mentioned in this book. This book does not indicate whether a particular treatment is appropriate or suitable for a particular individual. Ultimately it is the sole responsibility of the medical professional to make his or her own professional judgements, so as to advise and treat patients appropriately. The authors and publishers have also attempted to trace the copyright holders of all mate-rial reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or uti-lized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopy-ing, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically f rom this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress ISBN-13 978 0 340 974 223 CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works © 2011 Karim Ratib, Ghurbir Bhatia, Neal Uren and James Nolan. This book contains information obtained from authentic and highly regarded sources. While all reasonable efforts have been made to publish reliable data and information, neither the author[s] nor the publisher can accept any legal respon-sibility or liability for any errors or omissions that may be made. The publishers wish to make clear that any views or opinions expressed in this book by individual editors, authors or contributors are personal to them and do not neces-sarily reflect the views/opinions of the publishers. The information or guidance contained in this book is intended for use by medical, scientific or health-care professionals and is provided strictly as a supplement to the medical or other professional’s own judgement, their knowledge of the patient’s medical history, relevant manufacturer’s instructions and the appropriate best practice guidelines. Because of the rapid advances in medical science, any information or advice on dosages, procedures or diagnoses should be independently verified. The reader is strongly urged to consult the relevant national drug formulary and the drug companies’ and device or material manufacturers’ printed instructions, and their websites, before administering or utilizing any of the drugs, devices or materials mentioned in this book. This book does not indicate whether a particular treatment is appropriate or suitable for a particular individual. Ultimately it is the sole responsibility of the medical professional to make his or her own professional judgements, so as to advise and treat patients appropriately. The authors and publishers have also attempted to trace the copyright holders of all mate-rial reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or uti-lized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopy-ing, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically f rom this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress ISBN-13 978 0 340 974 223 CONTENTS Abbreviations vi CHAPTER 1 Acute Coronary Syndromes 1 CHAPTER 2 Resuscitation 84 CHAPTER 3 Arrhythmias 104 CHAPTER 4 Hypertensive Emergencies 135 CHAPTER 5 Acute Aortic Syndromes 149 CHAPTER 6 Acute Pulmonary Embolism 167 CHAPTER 7 Infective Endocarditis 188 CHAPTER 8 Drug-related Cardiac Problems 203 CHAPTER 9 Pericarditis 218 CHAPTER 10 Cardiac Trauma 225 CHAPTER 11 Cardiac Tamponade 234 Appendices 239 Index 269 vi ABBREVIATIONS ACC American College of Cardiology ACD active and compression–decompression ACE angiotensin converting enzyme ACS acute coronary syndrome ACT activated clotting time ADP adenosine diphosphate AF atrial fibrillation AHA American Heart Association aPTT activated partial thromboplastin time ATP adenosine triphosphate A-V arteriovenous AV atrioventricular AVNRT atrioventricular nodal re-entry tachycardia AVRT atrioventricular re-entry tachycardia BP blood pressure BSAC British Society of Antimicrobial Chemotherapy CABG coronary artery bypass graft CAD coronary artery disease cAMP cyclic adenosine monophosphate CCS Canadian Cardiovascular Society CCU coronary care unit CK creatine kinase CMV cytomegalovirus COPD chronic obstructive pulmonary disease CPR cardiopulmonary resuscitation CRP C-reactive protein CT computed tomography CTPA computed tomography pulmonary angiography CVA cerebrovascular accident DAPT dual antiplatelet therapy DCC direct current cardioversion DES drug-eluting stent DVT deep venous thrombosis ECG electrocardiogram EF ejection fraction vii ABBREVIATIONS ELISA enzyme-linked immunoadsorbent assay EMD electromechanical dissociation EPS electrophysiological study ERC European Resuscitation Council ESR erythrocyte sedimentation rate ESC European Society of Cardiology FDP fibrin degradation products GI gastrointestinal GP glycoprotein GRF gelatin–resorcinol–formaldehyde GTN glyceryl trinitrate HIT heparin-induced thrombocytopenia IABP intra-aortic balloon counterpulsation IAC interposed abdominal compression ICD implantable cardioverter defibrillator IE infective endocarditis IHD ischaemic heart disease IMH intramural haematoma INR international normalized ratio IPG impedance plethysmography IRA infarct-related artery IRAD International Registry of Acute Aortic Dissection IV intravenous IVDU intravenous druge user JVP jugular venous pressure LAD left anterior descending (artery) LIMA left internal mammary artery LMWH low molecular weight heparin LSD lysergic acid diethylamide LVF left ventricular failure MACE major adverse cardiac event MEN multiple endocrine neoplasia MI myocardial infarction MIC minimum inhibitory concentration MRI magnetic resonance imaging MRSA methecillin resitant staphyloccocus aureus NICE National Institute for Health and Clinical Excellence NPCT non-penetrating cardiac trauma NSTEACS non-ST elevation ACS NSTEMI non-ST elevation MI PAU penetrating atherosclerotic ulceration ABBREVIATIONS viii PCI percutaneous coronary intervention PE pulmonary embolism PEA pulseless electrical activity PLS posterior leucoencephalopathy syndrome po per os (orally) PTCA percutaneous transluminal coronary angioplasty PTD percutaneous thrombolytic device PTFE polytetrafluoroethylene SBP systolic blood pressure SC subcutaenous SLE systemic lupus erythematosus STEMI ST elevation MI SVT supraventricular tachycardia TCAD tricyclic antidepressant TIA transient ischaemic attack TOE transoesophageal echocardiogram (echocardiography) tPA tissue plasminogen activator TVR target vessel revascularization UA unstable angina UFH unfractionated heparin V/Q ventilation/perfusion VF ventricular fibrillation VT ventricular tachycardia WCC white cell count WPW Wolff–Parkinson–White (syndrome) EPIDEMIOLOGY 1 EPIDEMIOLOGY Coronary heart disease is the most common cause of death in the United Kingdom. In total, 220 000 deaths were attributable to ischaemic heart disease in 2007. It is estimated that the incidence of acute coronary syndrome (ACS) is over 250 000 per year. Sudden death remains a frequent complication of ACS: approximately 50 per cent of patients with ST elevation myocardial infarction (STEMI) do not survive, with around two-thirds of the deaths occurring shortly after the onset of symptoms and before admission to hospital. Prior to the development of modern drug regimes and reperfusion strategies, hospital mortality after admission with ACS was 30–40 per cent. After the introduction of coronary care units in the 1960s, outcome was improved, predominantly reflecting better treatment of arrhythmias. Current therapy has improved outcome further for younger patients who present early in the course of their ACS. The last decade has seen a significant fall in the overall 30-day mortality rate. Most patients who die before discharge do so in the first 48 hours after admission, usually due to cardiogenic shock consequent upon extensive left ventricular damage. Most patients who survive to hospital discharge do well, with 90 per cent surviving at least 1 year. Surviving patients who are at increased risk of early death can be identified by a series of adverse clinical and investigational features, and their prognosis improved by intervention. ACUTE CORONARY SYNDROMES CHAPTER 1 Epidemiology 1 Definitions 2 Pathophysiology 3 Diagnosis 6 Initial treatment 17 Treatment of ST elevation MI 19 Primary PCI 20 Thrombolysis 23 Treatment of non-ST 31 elevation ACS Risk scores in NSTEACS 33 Revascularization strategies 36 in NSTEACS Bleeding risk in ACS 38 Adjunctive medical therapy 40 Complications of ACS 54 Early peri-infarction arrhythmias 65 Late post-infarction arrhythmias 76 Recovery and rehabilitation 77 Key points 79 Key references 80 ACUTE CORONARY SYNDROMES 2 DEFINITIONS DEFINITIONS The term ‘acute coronary syndrome’ (ACS) has been developed to describe the collection of ischaemic conditions that include a spectrum of diagnoses from unstable angina (UA) to non-ST elevation MI (NSTEMI) and STEMI. Patients presenting with ACS can be classified into two groups according to their electrocardiogram (ECG) (Figure 1.1): those with persistent STEMI and those without (non-ST elevation ACS or NSTEACS). The treatment of STEMI requires emergency restoration of blood flow within an occluded culprit coronary artery. Patients presenting with NSTEACS often have ECG changes including T-wave inversion, ST depression or transient ST elevation, although occasionally the ECG may be entirely normal. This group can be classified further according to the presence of detectable levels of cardiac proteins, troponins, in patients’ serum (see below). Thus, NSTEACS patients with undetectable cardiac troponins (UA) are distinguished from those in whom myocardial ischaemia is severe enough to cause myocardial necrosis, leading to troponin release into the circulation (NSTEMI). Detection of cardiac troponin following ACS is a strong predictor of recurrent ischaemia. However, it should be remembered that patients with UA are still at increased risk of further events, especially those with pain at rest or dynamic ST changes on their ECG. ACS ECS Diagnosis Management Persistent ST elevation STEMI Reperfusion Invasive / Non-invasive NSTEACS NSTEMI UA ST change T-wave inversion Normal ECG Figure 1.1 Definition, diagnosis and management of ACS. ACUTE CORONARY SYNDROMES PATHOPHYSIOLOGY 3 Myocardial infarction can also be classified with regards to underlying aetiology as defined by the European Society of Cardiology: Type 1 Spontaneous myocardial infarction related to ischaemia due to a primary coronary event such as plaque erosion and/or rupture, fissuring or dissection. Type 2 Myocardial infarction secondary to ischaemia due to either increased oxygen demand or decreased supply, e.g. coronary artery spasm, coronary embolism, anaemia, arrhythmias, hypertension or hypotension. Type 3 Sudden unexpected cardiac death, including cardiac arrest, often with symptoms suggestive of myocardial ischaemia, accompanied by presumably new ST elevation, or new LBBB, or evidence of fresh thrombus in a coronary artery by angiography and/or at autopsy, but death occurring before blood samples could be obtained, or at a time before the appearance of cardiac biomarkers in the blood. Type 4a Myocardial infarction associated with PCI (percutaneous coronary intrervention). Type 4b Myocardial infarction associated with stent thrombosis as documented by angiography or at autopsy. Type 5 Myocardial infarction associated with CABG (coronary artery bypass graft). PATHOPHYSIOLOGY ACSs are caused by an imbalance between myocardial oxygen demand and supply that results in cell death and myocardial necrosis. Primarily, this occurs due to factors affecting the coronary arteries, but may also occur as a result of secondary processes such as hypoxaemia or hypotension and factors that increase myocardial oxygen demand. The commonest cause is rupture or erosion of an atherosclerotic plaque that leads to complete occlusion of the artery or partial occlusion with distal embolization of thrombotic material. Atherosclerosis is a disease of large and medium-sized arteries, affecting predominantly the arterial intima. The precise mechanism responsible for the generation of atherosclerotic arterial disease remains open to debate, but it is likely that arterial endothelial injury is an initiating factor. It is clear that ACUTE CORONARY SYNDROMES 4 PATHOPHYSIOLOGY the extent and stability of atherosclerotic lesions is influenced by the common risk factors of smoking, hypertension, hyperlipidaemia and diabetes. There are a large number of other modifiable risk factors, such as homocysteine, oxidative stress, fibrinogen and psychosocial factors, which may play an important role in atherogenesis in some individuals. Individual susceptibility to the adverse effects of risk factors may relate to genetic predisposition. Atherosclerotic plaques are complex structures consisting of a fibrous cap and a core of lipid, connective tissue and inflammatory cells. The morphology of plaques is variable, and those with a thin fibrous cap, a large lipid core and an increase in inflammatory activity are highly unstable. An increase in inflammatory activity within plaques may be triggered by systemic infections ( Chlamydia, cytomegalovirus (CMV), Helicobacter or chronic dental sepsis) or stimuli such as stress, severe exercise and temperature change. ACS is initiated when the fibrous cap of an unstable atherosclerotic lesion ruptures (in 75 per cent of cases) or the overlying endothelium erodes (in 25 per cent of cases). Plaque erosion is more common in females. Both mechanisms expose highly thrombogenic subendothelial and core components of the unstable plaque to the blood, leading to localized platelet adhesion, activation of the clotting mechanism, and formation of an intraluminal thrombus that occludes the coronary artery. Prior to plaque rupture or erosion, other conformational changes may occur as a result of endothelial injury. This causes a proliferation of smooth muscle cells leading to a reduction of the luminal diameter, which increases shear stress, and causes further endothelial injury. Intravascular ultrasound studies have confirmed that unstable coronary plaques are associated with more expansive arterial remodelling compared to stable coronary lesions, which may imply a more marked recent progression in extent and severity of plaque at the site of rupture/erosion. Angiographic and intravascular ultrasound studies of culprit lesions have demonstrated complex eccentric morphology consistent with ruptured plaque and superimposed thrombus. Vulnerable plaques that fissure or rupture are characterized by large eccentric lipid pools with foam cell infiltration and tend to rupture at the border of the fibrous cap and adjacent normal intima. This weakness in the integrity of the plaque is initiated by matrix metalloproteinases secreted by macrophages, and ultimately rupture occurs through an acute change in wall shear stress. The lipid core is a potent substrate for platelet-rich thrombus formation with the initiation of the coagulation cascade through the interaction of tissue factor with factor VIIa. Platelet adhesion to subendothelial collagen through PATHOPHYSIOLOGY 5 ACUTE CORONARY SYNDROMES the release of tissue factor and the expression of the vitronectin (α v ß 3 ) receptors leading to platelet activation and aggregation through the expression of the glycoprotein IIb/IIIa receptor is an important event in the development of thrombus. Platelet-rich thrombus is associated with cyclical reductions in coronary blood flow with additional coronary vasoconstriction resulting from endothelial disruption, and thromboxane A 2 (TXA 2 ) and serotonin production leading to reduced nitric oxide (NO) production. Inflammatory acute phase proteins, cytokines and systemic catecholamines stimulate the production of tissue factor, procoagulant activity and platelet hypercoagulability. A number of factors that can trigger the onset of ACS have been identified, acting by initiating plaque rupture or promoting thrombus formation. Some patients report heavy physical exertion or mental stress shortly before the onset of ACS. Circadian variation in coagulation and autonomic nervous system activity contribute to an increased incidence of ACS in the morning. Irrespective of this, the risk of an individual episode of exercise or stress precipitating the onset of ACS is low, and most episodes have no identifiable direct triggers. Other non-athersclerotic causes for ACS include arteritis, trauma, spontaneous coronary dissection, thromboembolism, cocaine use and congenital abnormalities such as anomalous coronary arteries. Patients who present as a result of these rare causes will usually not have the classical risk factors associated with atherosclerosis; typically the diagnosis is not established until after coronary angiography. Acute STEMI usually results from total occlusion of a coronary artery, with subsequent myocardial cell necrosis occurring in as little as 15 minutes. Continued occlusion results in a wavefront of necrosis spreading from the subendocardium to the subepicardium. The amount of myocardial injury depends on the duration of occlusion, the presence of collateral blood flow and the degree of preconditioning of the myocytes to ischaemia. In animal models, persistent occlusion of a coronary artery will usually result in complete infarction of the area subtended after 6 hours. Subendocardial and full thickness or transmural mycocardial infarction can be well demonstrated with cardiac magnetic resonance imaging (MRI) using late gadolinium enhanced images. These images correlate well with macroscopic histological findings. NSTEACS are usually associated with partial or transient occlusion of the coronary artery that may result in ST depression or T-wave changes on the ECG. Myocardial injury occurs as a result of a sudden decrease in luminal diameter leading to reduced perfusion or due to plaque ACUTE CORONARY SYNDROMES 6 DIAGNOSIS rupture/erosion and embolization of thrombotic material into the distal coronary bed. Most individuals with atherosclerotic coronary artery disease have a large number of minor lesions that do not significantly narrow the coronary lumen, as well as a smaller number of severe lesions. The severe lesions are more likely to intermittently limit antegrade blood flow during exercise (leading to stable angina). An ACS is more likely to occur due to instability in one of the more numerous minor lesions (two-thirds of ACS are related to angiographically minor lesions). Intravascular ultrasound studies have shown that patients with NSTEACS frequently have multiple ruptured plaques often occurring in arteries other than the initial culprit. UA can be caused by the same mechanisms as NSTEMI, although the detectable myocardial necrosis does not usually occur. UA may also be caused by a reduction in coronary flow due to a decrease in luminal diameter caused by increase in size of a non-ruptured plaque where endothelial damage leads to smooth muscle proliferation. For these reasons, patients even with negative biomarkers may still be at high risk of further events and this reinforces the need for effective risk stratification. DIAGNOSIS Presentation Chest pain is a common reason for patients to atten