Table Of ContentPractical
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
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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
