Series Editor Peter Mills Education in Hear t Volume 3 British Cardiac Society EDUCATION IN HEART Volume 3 Series Editor PETER MILLS Consultant Cardiologist, London Chest Hospital © BMJ Publishing Group 2003 BMJ Books is an imprint of the BMJ Publishing Group 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 wr itten permission of the publishers. First published in 2003 by BMJ Books, BMA House, Tavistock Square, London WC1H 9JR www.bmjbooks.com British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN 0 7279 1764 1 Typeset by BMJ Electronic Production PrintedinMalaysiabyTimesOffset CONTENTS Contributors vi Introduction viii SECTION I: CORONARY DISEASE 1 Carotid artery surgery for people with existing coronary artery disease 3 Ian Lane, John Byrne 2 The “no-reflow” phenomenon: basic science and clinical correlates 8 Thorsten Reffelmann, Robert A Kloner 3 Screening relatives of patients with premature coronary heart disease 15 Gilbert R Thompson 4 Acute myocardial infarction: reperfusion and treatment 20 Flavio Ribichini, William Wijns 5 Off-pump coronary artery bypass surgery 28 Peter P Th de Jaegere, Willem J L Suyker 6 Management of cardiogenic shock complicating acute myocardial infarction 34 Venu Menon, Judith S Hochman SECTION II: HEART FAILURE 7 Cardiac transplantation 43 Marcio C Deng 8 The need for palliative care in the management of heart failure 51 Cristopher Ward 9 Exercise testing in the assessment of chronic congestive heart failure 56 John G Lainchbury, A Mark Richards SECTION III: CARDIOMYOPATHY 10 Hypertrophic cardiomyopathy: management, risk stratification, and prevention of sudden death 65 William J McKenna, Elijah R Behr SECTION IV: VALVE DISEASE 11 Timing of mitral valve surgery 75 Maurice Enriquez-Sarano 12 The medical management of valvar heart disease 82 N A Boon, P Bloomfield 13 Choice of heart valve prosthesis 88 Peter Bloomfield SECTION V: ELECTROPHYSIOLOGY 14 Which patient should be referred to an electrophysiologist: supraventricular tachycardia 97 Richard J Schilling iii 15 Arrhythmias in adults with congenital heart disease 103 JohnKTriedman 16 Quality of life and psychological functioning of ICD patients 110 Samuel F Sears, Jamie B Conti 17 Novel mapping techniques for cardiac electrophysiology 116 PaulAFriedman 18 Treatment of atr ial fibrillation 124 Y Blaauw, I C Van Gelder, HJGMCrijns 19 Patients with ventricular arrhythmias: who should be referred to an electrophysiologist? 130 John M Morgan SECTION VI: CONGENITAL HEART DISEASE 20 Heart failure in the young 139 Michael Burch 21 Sudden death in children and adolescents 144 Christopher Wren 22 Pulmonary hypertension in the young 150 Sheila G Haworth SECTION VII: IMAGING TECHNIQUES 23 Understanding coronary artery disease: tomographic imaging with intravascular ultrasound 159 Paul Schoenhagen, Steven Nissen 24 Role of echocardiography in acute coronary syndromes 165 Sally C Greaves 25 Doppler echocardiographic assessment of valvar regurgitation 171 James D Thomas SECTION VIII: HYPERTENSION 26 Cardiovascular and coronary risk estimation in hypertension management 181 Erica J Wallis, Lawrence E Ramsay, Peter R Jackson SECTION IX: GENERAL CARDIOLOGY 27 Anaesthesia and the cardiac patient: the patient versus the procedure 191 James B Froehlich, Kim A Eagle 28 Myocardial molecular biology: an introduction 197 Nigel J Brand, PaulJRBarton 29 Heart disease, guidelines, regulations, and the law 207 M C Petch 30 Apoptosis in the cardiovascular system 215 Martin R Bennett 31 To whom do the research findings apply? 223 Curt D Furberg 32 Management of Marfan syndrome 228 JohnCSDean 33 Development and structure of the atr ial septum 235 Robert H Ander son, Nigel A Brown, Sandra Webb 34 Arteriosclerotic renal artery stenosis: conser vative versus interventional management 242 Christlieb Haller iv 35 Effect of partial compliance on cardiovascular medication effectiveness 247 Joyce A Cramer 36 Myotonic dystrophy and the heart 251 G Pelargonio, A Dello Russo, T Sanna, G de Martino, F Bellocci Index 257 Citation Index 265 v Robert A Kloner The Heart Institute, Good Samaritan Hospital, University of Southern California, Los Angeles, USA John G Lainchbury Department of Medicine, Christchurch School of Medicine and Health Sciences, University of Otago, Christchurch, New Zealand Ian Lane Cardiff Vascular Unit, University Hospital of Wales, Cardiff, UK G de Martino Department of Cardiovascular Medicine, Institute of Cardiology, Catholic University of Rome, Rome, Italy William J McKenna Department of Cardiological Sciences, St George’s Hospital Medical School, London, UK Venu Menon Division of Cardiology, University of North Carolina, Chapel Hill, North Carolina, USA John M Morgan Wessex Cardiothoracic Centre, Southampton, UK Steven Nissen Department of Cardiology, The Cleveland Clinic F ounda tion, Cleveland, Ohio , USA G Pelargonio Department of Cardiovascular Medicine, Institute of Cardiology, Catholic University of Rome, Rome, Italy M C Petch Papworth Hospital, Cambridge, UK Lawrence E Ramsay Section of Clinical Pharmacology and Therapeutics, Royal Hallamshire Hospital, Sheffield, UK Thorsten Reffelmann The Heart Institute, Good Samaritan Hospital, University of Southern California, Los Angeles, USA Flavio Ribichini Universita del Piemonte Orientale, Division of Cardiology, Nov ara, Italy A Mark Richards Department of Medicine, Christchurch School of Medicine and Health Sciences, University of Otago, Christchurch, New Zealand T Sanna Department of Cardiovascular Medicine, Institute of Cardiology, Catholic University of Rome, Rome, Italy Richard J Schilling Cardiology Department, St Barts Hospital, London, UK Paul Schoenhagen Department of Cardiology, The Cleveland Clinic F ounda tion, Cleveland, Ohio , USA Samuel F Sears University of Florida, Department of Clinical and Health Psychology, UF Health Science Center, Gainesville, Florida, USA Willem J L Suyker Department of Cardiothoracic Surgery, Isala Clinics, Weezenlanden Hospital, Zwolle, The Netherlands James D Thomas Department of Cardiology, The Cleveland Clinic F ounda tion, Cleveland, Ohio , USA Gilbert R Thompson Metabolic Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, UK John K Triedman Department of Cardiology, Children’s Hospital, Boston, Massachusetts, USA I C Van Gelder Thoraxcenter, Department of Cardiology, University Hospital Groningen, Groningen, The Netherlands Erica J Wallis Section of Clinical Pharmacology and Therapeutics, Royal Hallamshire Hospital, Sheffield, UK Christopher Ward Heart F ailure Clinic, South Manchester University Hospital NHS Trust, Manchester, UK Sandra Web b Department of Anatomy and Developmental Biology, St George’s Hospital Medical School, London, UK William Wijns Cardiov ascular Centre, OLV Hospital, Moorselbaan, Belgium Christopher Wren Department of Paediatric Cardiology, Freeman Hospital, Newcastle upon Tyne, UK Contributors vii of blood flow, but the technique can also measure arterial diameter from an image. Although it does not give the same detailed information on proximal or intracranial disease as angiography, in patients with appropriate symptoms further imaging is not required before surgery. Duplex scanning may not differentiate between a tight stenosis (95%) with “trickle flow” and an occluded carotid artery. In these cases magnetic resonance angiography provides an accurate alternative to arteriography (fig 1.2). There is no indication for surgery on an occluded carotid artery as the risk of embolisation has disap- peared and re-establishment of flow may propel distal throm- bus into the brain. There is little need in modern practice for formal intra-arterial angiography. As well as local complica- tions at the site of arterial puncture, there is a small but significant risk of stroke even without selective carotid catheterisation. Intravenous digital angiography has proved disappointing in providing sufficient resolution of the carotid bifurcation. Carotid imaging at the time of coronary angio- graphy should be reserved for cases where proximal arterial or intracranial disease is suspected as a cause for symptoms. MANAGEMENT OF THE DISEASE PROCESS Atherosclerosis should be treated by correction of risk factors such as hyperlipidaemia, smoking, hypertension, diabetes, and polycythaemia. In the presence of classic symptoms and appropriate carotid stenosis a decision to intervene can be based on duplex scan alone. Unless there is a contraindication, aspirin 300 mg/day will significantly reduce the incidence of further neurological events. The role of new antiplatelet agents such as clopidogrel and ticlopidine have not been sub- jected to trial. Anticoagulants are unproven and carry signifi- cant side effects, but may be useful when other treatment modalities have failed. CAROTID INTERVENTION Carotid endarterectomy under general anaesthetic carries a lowmortalityinfitpatients.Cardiacdiseasewasresponsible for 49% of deaths in one large series of patients undergoing carotid endarterectomy with mortality due to myocardial infarction. 3 Those with severe cardiac or respiratory dysfunc- tion can be treated under cervical block or local anaesthetic, which has the advantage that neurological events are immediately identified and corrected by shunting. There is a requirement for the patient to remain immobile for the proce- dure which may not be tolerated, although in one series 97% of 449 patients were successfully treated under local anaesthesia. 4 In one randomised controlled trial the rate of myocardial ischaemia in those treated under local anaesthetic was half that of general anaesthetic, although the results did not reach significance. The dilemma should be resolved by the multicentre general or local anaesthesia for carotid endarter- ectomy (GALA) trial. Carotid angioplasty is technically possi- ble and subject to clinical multicentre trial. While the cranial nerve injuries associated with surgery are avoided, distal embolisation following carotid mobilisation can produce stroke, although this may be prevented by synchronous distal balloon occlusion of the artery. In a multicentre study of 504 patients randomised to surgery or angioplasty the combined stroke and mortality rate at 30 days was 10% for both surgery and ang ioplasty. 5 There has been criticism of the high stroke rate in the surg ical arm of this trial. Modern interventional techniques, including the use of stents together with cerebral protection devices, require further long term evaluation. SURGERY FOR SYMPTOMATIC CAROTID STENOSIS Symptomatic carotid stenosis carries a stroke risk of approxi- mately 15% in the year following a motor or sensory neurological event, with the sequelae of amaurosis fugax hav- ing a more benign prognosis. While antiplatelet treatment will reduce the risk of further events to 8% per year, before 1992 the evidence for efficacy of carotid endarterectomy was not scientifically sound. Publications were based on personal series with poor classification of degree of stenosis, presence Figure 1.1 Colour duplex image showing internal carotid artery in red with a moderate stenosis characterised as soft plaque. Characterisation of plaque may be of prognostic value. Figure 1.2 Magnetic resonance angiogram with a critical stenosis of the origin of the internal carotid artery on the right. Duplex scan c No complications c Outpatient investigation c No information on intracerebral circulation c Requires operator expertise c Provides information on plaque morphology c May be inaccurate with ‘trickle flow’ c Consider magnetic resonance angiography for tight stenoses EDUCATION IN HEART * 4 or absence of symptoms, use of antiplatelet medication, and durationoffollowup. Indications for surgery Two multicentre randomised controlled trials have demon- strated an advantage of carotid endarterectomy combined with aspirin, compared to aspirin alone, in the prevention of stroke following a neurological event in patients with over 70% carotid stenosis. In a North American trial, patients with stroke or transient ischaemic attack within three months of entry, combined with symptomatic carotid stenosis of over 70%, were randomised to carotid endarterectomy or aspirin 1300 mg/day. The cumulative stroke risk for the surgical arm of the trial was 9% compared to 22% for medical treatment. 6 A multicentre European trial, in 80 centres, randomised patients with symptomatic carotid stenosis of over 70% to surgery or best medical treatment. The qualifying neurological event for entry into the trial had to have occur red within six months previously. The cumulative risk of stroke was 12.3% for surgery compared to 21.9% for medical treatment, although the 30 day combined stroke and mortality rate for surgery was considered high at 7.5%. This may be due to some centres per- forming only low numbers of carotid endar terectomies. 7 Despite minor differences between these two trials in terms of assessment of the carotid stenosis and time interval from qualifying event, the conclusions were that surgery has an advantage over medical treatment in symptomatic carotid stenoses of 70% or over. Pre-occlusive lesions are considered high risk for stroke although this has recently been challenged. The role of surgery in patients with moderate stenosis of between 50–69% is unclear, but should be considered if symptoms are uncontrolled by conventional treatment and maximum perioperative death and disabling stroke rate of 2% can be achieved. 8 Occasionally embolisation can originate from a deep ulcerated plaque in the absence of stenosis (fig 1.3). While endothelial remodelling may occur, surgery should be considered if antiplatelet medication fails to control symptoms. Complications of surgery The success of carotid endarterectomy to prevent stroke depends on the perioperative stroke and death rate, which should be less than 3%. Factors that increase the risk of peri- operative stroke include transient ischaemic attacks rather than amaurosis fugax, contralateral carotid occlusion, and irregular or ulcerated plaque at the side of surgery. There is no significant effect of age above or below 65 years on stroke rate. 9 Patients must be provided with balanced information on the perioperative stroke rate and risk of damage to cranial nerves compared to non-operative management, in order to enable informed participation in their own management. An analysis of the North American symptomatic carotid endarter- ectomy trial revealed an overall perioperative stroke and death rate of 6.5%, with permanently disabling stroke combined withdeathof2.0%.Theriskofcranialnerveinjurieswas8.6%, affecting the facial, hypoglossal, and vagus nerves, although the majority were described as mild in severity. 9 MANAGEMENT OF ASYMPTOMATIC CAROTID STENOSIS Asymptomatic carotid stenosis carries a stroke risk of approximately 2% per year. This stroke risk appears related to the severity of stenosis and remains constant with time, unlike the risk following a neurological event in a sympto- matic carotid stenosis. 2 A trial comparing surgery to aspirin for asymptomatic carotid stenosis showed no benefit from surgery although randomisation was incomplete. 10 Inamulti- centre trial of 1662 patients (asymptomatic carotid atheroscle- rosis study, ACAS) with over 60% asymptomatic carotid sten- oses randomised to surgery or medical treatment, at five years the combined stroke and mortality rate for surgery was 5.1% compared to 11% for medical treatment. 3 Although all centres were validated for low surg ical morbidity, the stroke rate associated with arteriography was considered to be high at 1.2%. There should be caution when applying the results of this trial to a wide body of surgeons, especially as the absolute risk reduction for stroke was 1% per year. While surger y car- ries an advantage over antiplatelet medication, 20 patients have to undergo carotid endar terectomy to prevent one stroke in every five years. 3 This compares with four endarterecto- mies to prevent one stroke a year in symptomatic patients. 6 Surgery for asymptomatic disease may not be appropriate Figure 1.3 Digital subtraction carotid angiogram revealing a deep ulcerated plaque in the left carotid bulb and a severe irregular stenosis of the internal carotid artery on the right. Biplanar views are required to confirm the degree of stenosis on the right. The vertebral artery is filled on the left. Transient ischaemic attack c Correct risk factors for atherosclerosis c Duplex scan c Add antiplatelet treatment c Consider surgery for carotid stenosis over 70% c Angioplasty acceptable in high risk patients c Intervention should be performed urgently c Carotid restenosis is rarely symptomatic CAROTID ARTERY SURGERY FOR PEOPLE WITH EXISTING CORONARY ARTERY DISEASE * 5 [...]... even in zones of irreversibly damaged myocardium—which theoretically might have beneficial effects on ventricular remodelling, infarct healing, and collateral formation—is feasible with pharmacological interventions, remains to be investigated 10 11 12 c 13 14 15 16 17 c REFERENCES 1 Kloner RA, Ganote CE, Jennings RB The “no-reflow” phenomenon after temporary coronary occlusion in dogs J Clin Invest 19 74;54 :14 96–508... when exposed to flowing blood, contributes to the degree of no-reflow When active site-blocked factor VII was administered during reperfusion, a pronounced reduction of no-reflow was observed ,16 which 11 * EDUCATION IN HEART Table 2 .1 Interventions used in experimental animal models to reduce no-reflow Intervention * 12 Adenosine Adenosine, intracoronary and intravenous application during reperfusion Species... salvage in patients with acute myocardial infarction J Am Coll Cardiol 19 97 ;30 :11 93 9 Additional references appear on the Heart website– www.heartjnl.com EDUCATION IN HEART 40 Aorta n = 54 Coronary arteries n = 48 35 * LDL – C (mmol/l) 1. 2 – 1. 6 30 Figure 3. 1 Fatty streak involvement of aorta and coronary arteries, expressed as per cent of intimal surface, in children and young adults according to quartiles... risk (PAR) for CHD3 Factor * 18 Prevalence Relative odds PAR for (%) for CHD CHD (%) Familial hypercholesterolaemia e4 allele HDL cholesterol 3. 4 mmol/l LDL cholesterol >4 .1 mmol /1 0.2 24 23 67 30 35 1. 53 2 .39 1 .34 1. 41 6.4 11 24 18 11 PREVALENCE OF RISK FACTORS IN PATIENTS WITH PREMATURE CHD A large study of the prevalence of modifiable risk factors in US men with angiographically... imaging (MRI), hypoenhancement 1 2 minutes after contrast injection is assumed to represent zones of no-reflow A recent study validated the amount of hypoenhancement against anatomical no-reflow assessed by injection of thioflavin S and regional myocardial blood flow in a canine model of reperfused myocardial infarction .11 Assessing hypoenhancement after contrast injection, visualised in 44 patients 10 ... of no-reflow showed a rapid reduction of the ST segment elevation index within the first 30 minutes after successful primary PTCA, ST segment elevation in patients with no-reflow resolved to a significantly lesser degree Indeed, a (transient) re-elevation was observed in some of these patients. 13 Biochemical markers Serial measures of serum myoglobin, creatine kinase-MB or troponin I (or T) at baseline... al .1 1.6 – 1. 9 16 Percent 25 p < 0.00 01 1.9 – 2.4 2.4 – 3. 4 20 15 10 5 p < 0. 01 0 LDL quartiles the relative risks of manifesting non-fatal or fatal CHD were 2.8 and 5.0, respectively, if one or other parent had developed CHD before the age of 60.7 The effect of family history is largely independent of other major risk factors, implying the existence of a separate mechanism particularly increased in. .. perfusion defects and increase peak contrast intensity in MCE after primary PTCA for acute myocardial infarction.20 In summary, the best treatment strategy for no-reflow has not yet been characterised, and future investigations are 13 * EDUCATION IN HEART No-reflow phenomenon: key points c * 14 c c c Experimental no-reflow is characterised by microvascular dysfunction, evident as distinct areas of hypoperfusion,... guidelines Department of Health National service framework for coronary heart disease Modern standards and service models London: Department of Health, 2000 Department of Health recommendations for reducing morbidity and mortality from coronary heart disease in England and Wales by 2 010 Wray R, Neil H, Rees J Screening for hyperlipidaemia in childhood J R Coll Phys London 19 96 ;30 :11 5 18 Guidelines of... Investigators Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels N Engl J Med 19 99 ;34 0 :16 23 9 One of the most convincing studies on glycoprotein IIb/IIIa receptor blockade, which demonstrates the beneficial effects of glycoprotein IIb/IIIa receptor antagonism in unstable angina on clinical outcome Ito H, Taniyama Y, Iwakura K, et al Intravenous nicorandil can . from Berenson et al . 1 40 LDL quartiles Percent Aorta n = 54 Coronary arteries n = 48 LDL – C (mmol/l) p < 0.00 01 p < 0. 01 1.2 – 1. 6 1. 6 – 1. 9 1. 9 – 2.4 2.4 – 3. 4 35 30 25 20 15 10 5 0 Table 3. 1 Major. pharmacological interven- tions, remains to be investigated. REFERENCES 1 Kloner RA, Ganote CE, Jennings RB. The “no-reflow” phenomenon after temporary coronary occlusion in dogs. J Clin Invest 19 74;54 :14 96–508. c. lesser degree. Indeed, a (transient) re-elevation was observed in some of these patients. 13 Biochemical markers Serial measures of serum myoglobin, creatine kinase-MB or troponin I (or T) at baseline and