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Practical Cardiology An Approach to the Management of Problems in Cardiology Tracey Baker MB BS, FRACGP, Dip. RACOG General Practitioner, Canberra George Nikolic´ , OAM FRACP, FACC, FCCP, FCSANZ, FJFICM Senior Specialist, Intensive Care Unit, Consultant Physician in Cardiology, The Canberra Hospital Simon O’Connor FRACP, DDU, FCSANZ Cardiologist, The Canberra Hospital Sydney Edinburgh London New York Philadelphia St Louis Toronto Churchill Livingstone is an imprint of Elsevier Elsevier Australia (a division of Reed International Books Australia Pty Ltd) Tower 1, 475 Victoria Avenue, Chatswood, NSW 2067 ACN 001 002 357 This edition © 2008 Elsevier Australia This publication is copyright. Except as expressly provided in the Copyright Act 1968 and the Copyright Amendment (Digital Agenda) Act 2000, no part of this publication may be reproduced, stored in any retrieval system or transmitted by any means (including electronic, mechanical, microcopying, photocopying, recording or otherwise) without prior written permission from the publisher. Every attempt has been made to trace and acknowledge copyright, but in some cases this may not have been possible. The publisher apologises for any accidental infringement and would welcome any information to redress the situation. This publication has been carefully reviewed and checked to ensure that the content is as accurate and current as possible at the time of publication. We would recommend, however, that the reader verify any procedures, treatments, drug dosages or legal content described in this book. Neither the author, the contributors, nor the publisher assume any liability for injury and/or damage to persons or property arising from any error in or omission from this publication. National Library of Australia Cataloguing-in-Publication Data ___________________________________________________________________ Baker, Tracey. Practical cardiology : an approach to the management of problems in cardiology Tracey Baker ; George Nikolić ; Simon O’Connor. 2nd ed. Chatswood, N.S.W. : Elsevier Australia, 2008. ISBN: 978 0 7295 3841 1 (pbk.) Includes index. Bibliography. Cardiology Heart--Diseases--Diagnosis. Heart--Diseases--Treatment. Heart--Diseases--Patients--Hospital care. Nikolić, George. O’Connor, Simon. 616.12 ___________________________________________________________________ Publisher: Sophie Kaliniecki Developmental Editor: Sunalie Silva Publishing Services Manager: Helena Klijn Edited by Caroline Hunter, Burrumundi Pty Ltd Proofread by Tim Learner Cover and internal design by DiZign Index by Michael Ferreira Typeset by TnQ Books and Journals Pvt Ltd Printed in Hong Kong by 1010 Printing International Ltd Preface There have been many changes in cardiology—that most rapidly developing speciality—since  1999 when the first edition of this book was published. This edition, with a new publisher and  a third author (George Nikolić), aims to bring the subject right up to date. Much has changed.  Some previous recommendations such as hormone replacement therapy to reduce cardio- vascular risk have been reversed, and important new concepts such as total cardiovascular   risk have been introduced. No medical specialty has been so affected by the results of randomised trials. Some of the  more important trials have been listed and their results summarised. References have been  provided throughout the book for important management recommendations. Students and  medical staff are now expected to be able to back up their practice with evidence. We hope this  book will make that task easier. There is a new chapter devoted to electrocardiography. There are many basic books avail- able for those beginning to learn about ECG interpretation. We have not tried to reproduce  these but rather to provide a text for those with some basic knowledge that puts ECGs into  their clinical context. Other cardiac investigations are dealt with throughout the book and a DVD has been   provided to enable readers to see them in the way they are interpreted—as video images. Case-based learning sections have been provided for each area of cardiology to help students  to understand the principles of this teaching method. We hope this modern problem- and evidence-based cardiology text will be helpful to    doctors and students. Tracey Baker George Nikolić Simon O’Connor Canberra, April 2008 ix Some important cardiology trials The number of possible cardiology trials is limited only by the number of possible trial  acronyms. ACADEMIC: Azithromycin in Coronary Artery Disease Elimination of Myocardial Infection with Chlamydia. Anderson JL, et al. Circulation 1999; 99:1540–1547. In this trial 302 patients  with known coronary artery disease were treated with either azithromycin, an antibiotic active  against Chlamydia, or a placebo for three months. There was no difference in coronary events  between the two groups over the following two years. AFFIRM: Atrial Fibrillation Follow­up Investigation of Rhythm Management. Olshansky B,  Rosenfeld LE, Warner AL, et al. J Am Coll Cardiol 2004; 43:1201–1208. This trial assessed the  efficacy of rate control for patients with AF, comparing beta-blockers and calcium channel  blockers in 2027 patients. Beta-blockers were more effective. APSIS: Angina Prognosis Study in Stockholm. Forslund L, Hjemdahl P, Held C, et al.   Eur Heart J 2000; 21:901–910. In this study patients with angina (n = 731) and a positive  exercise test were randomised to treatment with verapamil or a beta-blocker and then  performed another exercise test. The maximal ST depression and the exercise duration were  independent predictors of outcome over the following 40 months.  ARTS: Arterial Revascularisation Therapy Study. Serruys P, et al. N Engl J Med 2001; 344:  1117–1124. This trial studied the effectiveness of CABG compared with angioplasty and bare  metal stenting for diabetics with multi-vessel coronary disease. Diabetics in the CABG arm  had a better outcome than those having angioplasty. ASSENT-2: Assessment of the Safety and Efficacy of a New Thrombolytic–2. ASSENT-2  investigators. Lancet 1999; 354:716–722. This trial compared tenectoplase and alteplase for  16,949 patients with acute myocardial infarction. There was no difference in mortality at   30 days and one year between the two groups. BAATAF: Boston Area Anticoagulation Trial for Atrial Fibrillation. The Boston Area  Anticoagulation Trial for AF Investigators. New Engl J Med 1990; 323:1505–1511. Warfarin  with a target INR of 1.5–2.7 was effective in preventing stroke in 212 AF patients compared  with 208 AF patients treated with aspirin or nothing. The risk reduction was 86%.  CAPRIE: Clopidogrel vs Aspirin in Patients at Risk of Ischaemic Events. CAPRIE Steering  committee. Lancet 1996; 348:1329–1339. The combined risk of stroke, infarction or vascular  death was compared for 19,185 patients with vascular disease on treatment with aspirin or  clopidogrel. There was a reduction in combined risk for the clopidogrel group, who also had  a lower risk of gastrointestinal side effects.  CARE­HF: Cardiac Resynchronisation­Heart Failure. Cleland JG, Daubert JC, Erdmann E, et al.  Cardiac Resynchronisation-Heart Failure Investigators. The effect of cardiac resynchronisation  on morbidity and mortality in heart failure. N Engl J Med 2005; 352:1539–1549. Patients  with severe heart failure were randomised to optimal conventional heart failure treatment  or optimal treatment and CRT. CRT improved symptoms, and reduced the frequency of  hospital admissions and mortality.  xi xii Some important cardiology trials CASS: Coronary Artery Surgery Study. CASS Investigators. New Engl J Med 1984; 310:750–758.  This open label study looked at 780 randomised patients with mild angina or who were  asymptomatic after infarction to CABG or medical treatment for six years. There was no  difference in the survival rate.  CHARM—Alternative: Candesartan in Heart Failure; Assessment of Reduction in Mortality and Morbidity—Alternative. Granger CB, McMurray JJV, Yusef S, et al. Lancet 2003; 362:  772–776. This angiotensin receptor antagonist was successful in reducing morbidity and  cardiovascular mortality in patients with chronic heart failure who were intolerant of ACE  inhibitors.  CHARM—Added: Candesartan in Heart Failure; Assessment of Reduction in Mortality and Morbidity—Added. McMurray JJV, Ostergren J, Swedberg J, et al. Lancet 2003; 362:  767–771. The addition of candesartan to an ACE inhibitor in patients with heart failure causes  a further reduction in cardiovascular events. CHARM—Preserved: Candesartan in Heart Failure; Assessment of Reduction in Mortality and Morbidity—Preserved. Yusuf S, Pfeffer MA, Swedberg K, et al. Lancet 2003; 362:  777–781. Candesartan has a moderate effect on the prevention of hospitalisation for patients  with chronic heart failure but with an ejection fraction of greater than 40%. CIBIS II: Cardiac Insufficiency Bisoprolol Study II. The CIBIS scientific committee. Lancet  1999; 353:9–13. In this study of the treatment of heart failure with bisoprolol, 2647 patients  were treated with the drug or a placebo for a period of one to three years. All-cause mortality  was 11.8% in the treated group and 17% in the placebo group (P < 0.0006).  CIBIS III: Cardiac Insufficiency Bisoprolol Study III. Willenheimer R, et al. Circulation  2005;112:2426–2435. In this heart failure trial, initiation of treatment with bisoprolol  followed by enalapril was compared with the opposite (conventional) sequence. There were   505 patients in each group and outcomes were the same at 1.22 years.  CLARITY–TIMI 28: Clopidogrel as Adjunctive Reperfusion Therapy. Sabatine MS, et al.   Am Heart J 2005; 149:222–233. In this trial, 3491 patients with an acute ST elevation myocardial  infarction and having standard reperfusion treatment were given a 300 mg loading dose of  clopidogrel and then 75 mg a day in addition to aspirin or a placebo and aspirin. At 30 days  the clopidogrel group had a significantly lower risk of death or re-infarction (CI 0.21–0.65).  CLARITY: Clopidogrel as Adjunctive Reperfusion Therapy­Thrombolysis in Myocardial Infarction. Sabatine MS, Cannon CP, Gobson M, et al. N Engl J Med 2005; 352. In this study  the addition of clopidogrel to aspirin and fibrinolytic therapy for patients with an acute ST  elevation infarct improved the patency rate and reduced ischaemic complications. COBRA: Association Between Erectile Dysfunction and Coronary Artery Disease. Role of Clinical Presentation and Extent of Coronary Vessels Involvement: The Cobra Trial. Montorosi P, Ravagnani PM, Galli S, et al. Eur Heart J 2006; 27:2632–2639. Erectile  dysfunction as assessed by a questionnaire was present some years before clinical coronary  disease in these patients. COMPANION: Comparison of Medical Therapy, Pacing and Defibrillation in Chronic Heart Failure. Bristow MR, Feldman AM, Saxon LA, et al. N Engl J Med 2004; 350:2140. This study  looked at cardiac resynchronisation therapy with or without an implantable defibrillator in  advanced chronic heart failure. Resynchronisation treatment in these heart failure patients reduced  mortality and the frequency of hospital admissions compared with normal pacing. Patients whose  resynchronisation pacemaker was also a defibrillator had a lower mortality again. CONSENSUS: Cooperative North Scandinavian Enalapril Survival Study. N Engl J Med  1987; 316:1429–1435; Circulation 1990; 82:1730–1736; Am J Cardiol 1990; 66:40D–45D;  Am J Cardiol 1992; 69:103–107. This trial of enalapril in severe heart failure showed a 27%  reduction in mortality at 12 months compared with the placebo. Some important cardiology trials xiii DASH: Dietary Approaches to Stop Hypertension. Moore TJ, Volmer WM, Appel LJ, et al.  Hypertension 1999; 34:472–477. In this study a combination diet rich in vegetables and low- fat dairy products significantly reduced blood pressure in hypertensive patients compared  with a control diet low in fruit and vegetables and high in dairy fats. DAVITT II: Danish Verapamil Infarction Trial II. The Danish Study Group on Myocardial  Infarction. Am J Cardiol 1990; 66:779–785. This study showed long-term treatment with  verapamil reduced major ischaemic events after myocardial infarction. DIG: Digitalis Investigation Group Trial. Rich MW, McSherry F, Williford WO, et al. J Am  Coll Cardiol 2001; 38:806–813. This trial of heart failure randomised 7788 patients with heart  failure to digoxin or a placebo and usual treatment. The treated group had a 27% reduction  in admission for heart failure and a 7% overall reduction in hospital admission. There was  no difference in mortality. EAFT: European Atrial Fibrillation Trial. EAFT Study Group. Lancet 1993; 342:1255–1262. This  study compared aspirin and warfarin for the prevention of recurrent stroke in patients with  non-rheumatic AF. The risk of stroke was reduced from 12% to 4% per year with warfarin. EPHESUS: Eplerenone Post­AMI Heart Failure Efficacy and Survival Study. Pitt B, Remme W,   Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients’ left ventricular  dysfunction after myocardial infarction. N Engl J Med 2003; 348:1309–1321. This study  showed improved outcomes for patients treated with eplerenone shortly after extensive  myocardial infarction. Four S: Scandinavian Simvastatin Survival Study. Scandinavian Simvastatin Survival Study  Group. Lancet 1994; 344:1383–1389. This important trial with 4444 patients showed a survival  advantage for patients with coronary artery disease who were treated with a statin. FRISC: I FRagmin and Fast Revascularisation During Instability in Coronary Artery Disease Study. FRISC-I Investigators. Lancet 1999; 354:708–715. FRISC II 1 year: FRagmin and Fast Revascularisation During Instability in Coronary artery Disease Study. FRISC Investigators.  Lancet 2000; 356:9–16. These studies showed a significant reduction in death, recurrent  infarction and hospital readmission for patients with unstable angina when they were treated  with early intervention. GUSTO V Global Utilisation of Streptokinase and t­Pa for Occluded coronary arteries V. Topol EJ. The GUSTO Investigators. Lancet 2001; 357:1905–1914. In this trial of ST elevation  infarction patients, reduced dose fibrinolytic treatment combined with glycoprotein IIb/IIIa  inhibition was compared with standard fibrinolytic treatment. There was no difference in  30-day mortality. Heart Protection Study. Heart Protection Study Collaborative Group. Lancet 2002; 360:7–22. In  this study high-risk patients (previous IHD or multiple risk factors) up to the age of 80 were  treated with simvastatin. Patients with average cholesterol levels were included. There was a  25% reduction in events over five years regardless of initial cholesterol level, age or sex.  HERS II Heart and Estrogen/progestogen Replacement Study. Shlipak MG, Chaput LA,  Vittinghoff E, et al. Am Heart J 2003; 146:870–875. In this part of the HERS studies, changes  in lipid levels associated with HRT were not predictive of cardiovascular outcome. HOT: Hypertension Optimal Treatment Study. Zanchetti A, Hansson L, Menard J, et al. Risk  assessment and treatment benefit in intensively treated hypertensive patients of the Hypertension  Optimal Treatment (HOT) study for the HOT study group. J Hypertens 2001; 19:819–825. In  this study, maximum reduction in cardiovascular mortality occurred at blood pressures of about  139/87. However, there was no increase in mortality at blood pressure levels below this.  IONA: Impact of Nicorandil in Angina. The IONA Study Group. Lancet 2002; 359:1269–1275.  In this study of 5126 patients with stable angina, in the group treated with nicorandil there  was a significant improvement in the composite endpoint of death, non-fatal infarction and  hospital admission with angina. xi Some important cardiology trials LIFE: Losartan Intervention for Endpoint Reduction Study. Daholf B, Devereux RB,  Kjeildsen SE, et al. Lancet 2002; 359:995–1003. In this trial more than 9000 hypertensive  patients with LVH were treated with losartan (an ARA) or atenolol (a beta-blocker). There  was similar reduction in blood pressure but the losartan group had fewer non-fatal strokes  and a 25% reduction in the new onset of diabetes.  LIPID: Long­Term Intervention with Pravastatin in Ischaemic Disease Study. LIPID  Investigators. Am J Cardiol 1995; 76:474–479; N Engl J Med 1998; 339:1349–1357. In  this study 9000 patients with recent infarction of an acute coronary syndrome and a total  cholesterol level of 4–7 mmol/L were randomised to treatment with this statin or dietary  advice. There was a relative risk reduction in death of 24%, as well as a significant reduction  in further ischaemic episodes, for those patients treated with the statin.  MADIT II: Multi­centre Automatic Defibrillator Implantation Trial II. Moss AJ, Zareba W,  Hall WJ, et al. New Engl J Med 2002; 346:877–883. In this trial 1232 patients with previous  infarction and an ejection fraction of less than 30% were randomised to medical treatment or  a defibrillator. There was a 4.5% relative risk reduction in death for the defibrillator group at  20 months. These were patients who had not had documented ventricular arrhythmias.  MERIT-HF: Metoprolol CR/xL Randomised Intervention Trial in Heart Failure. The MERIT- HF study group. JAMA 2000; 283:1295–1302. In this trial, 3991 patients with heart failure  (NYHA class II–IV) were treated with slow-release metoprolol or a placebo in addition to  conventional treatment. The trial was ended after one year because of a significant reduction  in all-cause mortality (7.2% vs 11% per patient year). This was a relative risk reduction of  0.60. MUSTT: Multi­centre Unsustained Tachycardia Trial. Buxton AE, Lee AL, Fisher JD, et al.  A randomised study of the prevention of sudden death in patients with coronary artery  disease. N Engl J Med 1999; 341:1883–1890. In this trial patients with inducible VT, coronary  artery disease and an ejection fraction less than 40% were randomised to EPS-guided  drug treatment or no treatment. Patients who had inducible arrhythmias had a small but  significantly different decrease in overall mortality and arrhythmic death when treated with  anti-arrhythmic drugs guided by EPS. PEP­CHF: The Perindopril in Elderly People with Chronic Heart Failure. PEP investigators.  Eur Heart J 2006; 27:2338–2345. This trial of an ACE inhibitor in patients with heart failure  and a preserved ejection fraction showed improved exercise tolerance and fewer admissions to  hospital for treated patients, but was not sufficiently powered to show a mortality benefit. PROGRESS: Perindopril Protection Against Recurrent Stroke Study. PROGRESS Collaborative  Study Group. Lancet 2001; 358:1033–1041. This randomised trial of a perindopril-based  blood pressure-lowering regimen among 6108 individuals with previous stroke or transient  ischaemic attack showed a significant reduction in stroke recurrence in treated patients.  SAVE: Survival and Ventricular Enlargement Study. Rutherford JD, Pfeffer MA, Moye LA, et al.  Circulation 1994; 90:1731–1738. In this study, patients with asymptomatic left ventricular  dysfunction had a better prognosis when treated with captopril than the placebo.  SCD­HeFT: Sudden Death in Heart Failure Trial. Bardy GH, Lee KL, Mark DB, et al. New  Engl J Med 2005; 352:225–237. This trial compared the anti-arrhythmic drug amiodarone,  a placebo and an ICD for patients with an ejection fraction of less than 35%. Follow-up was  for 45 months. ICD treatment reduced mortality by 23%; amiodarone was no different from  the placebo.  SOLVD: Studies of Left Ventricular Dysfunction. SOLVD Investigators. N Engl J Med 1991;  325:293–302. This study looked at the effect on survival of enalapril in patients with a reduced  left ventricular ejection fraction (< 35%) and congestive heart failure. In the treatment arm  of the trial there was a 16% relative risk reduction of death. Some important cardiology trials x SPAF I: Stroke Prevention in Atrial Fibrillation. SPAF Investigators. Circulation 1991; 83:  527–539. This study compared a placebo, aspirin and dose-adjusted warfarin for primary  prevention of stroke or thromboembolism in patients with non-rheumatic atrial fibrillation.  Follow-up was for three years. Warfarin reduced the risk by 67% compared with the placebo,  and aspirin reduced it by 42%. Annual event rates were 2.3%, 3.6% and 7%, respectively, for  warfarin, aspirin and the placebo.  SPAF II: Stroke Prevention in Atrial Fibrillation. SPAF Investigators. Lancet 1994; 343:687–691.  This trial compared aspirin and warfarin for the prevention of embolic events in patients with  AF. Warfarin reduced the absolute event rate by 0.7% a year. SPORTIF V: Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation V. SPORTIF Investigators. JAMA 2005; 293:690–698. The oral thrombin inhibitor ximelagatran  was compared with warfarin in this high-risk AF group. Ximelagatran was as effective as  warfarin in preventing stroke. However, the drug has been withdrawn by the manufacturer  because of concerns about hepato-toxicity. STAF: Strategies of Treatment of Atrial Fibrillation. Carlson J, Miketic S, Windeler J, et al.  J Am Coll Cardiol 2003; 41:1690–1696. This trial compared rate control with rhythm control  for patients with AF. There was no difference between the groups in risk of death, stroke or  embolic event. TIBET: Total Ischaemic Burden European Trial. Fox KM, Mulcahy D, Findlay I, et al. Eur Heart J   1996; 17:96–103. In this trial patients with mild chronic angina were treated with atenolol,  nifedipine or both (c. 200 patients in each arm). Combination treatment was more effective  than either drug alone in improving exercise capacity.  TNT: Treating to New Targets Trial. Waters DD, Guyton JR, Herrington DM, et al. Does  lowering low density lipoprotein in cholesterol levels below currently recommended guidelines  yield incremental clinical benefits? Am J Cardiol 2004; 183:154. This trial was positive for  patients with a high risk of further cardiac events. UKPDS: UK Prospective Diabetes Study. UKPDS Group. Lancet 1998; 352:837–853. This  important trial compared macrovascular and microvascular complications of diabetes in  patients randomised to intensive blood glucose control and those with usual treatment.  Those in the intensive group had a reduction in microvascular complications of 25% over  10 years but there was not a significant reduction in macrovascular complications though the  reduction in risk of myocardial infarction came close to being significant.  ValHeFT: Valsartan Heart Failure Trial. Cohn JN, Tognoni G. N Engl J Med 2001; 345:  1667–1675. In this trial valsartan, an ARA, was compared with usual treatment for heart failure  in patients with NYHA class II–IV heart failure. There was no difference in mortality overall  between the groups but when compared against those patients not on an ACE inhibitor or  beta-blocker there was an improvement in the valsartan group. Abbreiations ABGs arterial blood gases ABI ankle brachial index ABLS adult basic life support  ABPM ambulatory blood pressure measurement ACC American College of Cardiology ACE angiotensin-converting enzyme ACLS advanced cardiac life support  ACS acute coronary syndrome ACT activated clotting time  AEB atrial ectopic beat AED automatic external defibrillator AF atrial fibrillation AHA American Heart Association AICD automatic implanted cardioverter defibrillator AIVR accelerated idioventricular rhythm  AMI acute myocardial infarction ANP A-type natriuretic peptide AP anteroposterior  APPT activated partial thromboplastin time ARA angiotensin receptor antagonist ASD atrial septal defect  ASH asymmetrical septal hypertrophy  ATP adenosine-triphosphate AV atrioventricular AV block atrioventricular block (ECG) BMI body mass index BMS bare metal stent BNP  B-type natriuretic peptide  BPEG British Pacing and Electrophysiology Group CABG coronary artery bypass grafting CCF congestive cardiac failure CCU coronary care unit CHD coronary heart disease COPD chronic obstructive pulmonary disease COX cyclo-oxygenase CPAP continuous positive airways pressure CPR cardiopulmonary resuscitation CRP C-reactive protein CRT cardiac resynchronisation therapy CSANZ Cardiac Society of Australia and New Zealand CTPA CT pulmonary angiogram CVD cardiovascular disease CW continuous wave CXR chest X-ray DC direct current xii

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