100 Questions in Cardiology-, PDF
100 Questions in Cardiology-, PDF
100 Questions in Cardiology-, PDF
Cardiology
z.f
Diana Holdright
BMJ Books
100 QUESTIONS IN CARDIOLOGY
100 QUESTIONS IN CARDIOLOGY
Edited by
Diana Holdright
and
Hugh Montgomery
Honorary Consultant, UCL Hospitals Intensive Care Unit,
and
Lecturer in Cardiovascular Genetics, UCL Hospitals,
The Middlesex Hospital, London, UK
BMJ
Books
BMJ Books 2001
BMJ Books is an imprint of the BMJ Publishing Group
www.bmjbooks.com
A catalogue record for this book is available from the British Library
ISBN 0-7279-1489-8
Contributors xii
Introduction xvii
Index 216
Contributors
Prithwish Banerjee
Specialist Registrar in Cardiology, Hull and East Yorkshire
Hospitals, Hull Royal Infirmary, Hull, UK
Matthew Barnard
Consultant Anaesthetist, UCL Hospitals, The Middlesex Hospital,
London,UK
J Benhorin
Associate Chief, The Heiden Department of Cardiology, Bikur
Cholim Hospital and The Hebrew University, Jerusalem, Israel
John Betteridge
Professor of Endocrinology and Metabolism, UCL Hospitals, The
Middlesex Hospital, London, UK
Kieran Bhagat
Regional Facilitator (Cardiovascular Programme), World Health
Organisation and Honorary Professor of Clinical Pharmacology,
Medical School, University of Zimbabwe, Harare, Zimbabwe
Aidan Bolger
Clinical Research Fellow, Department of Cardiac Medicine,
National Heart and Lung Institute, London, UK
David J Brull
British Heart Foundation Junior Fellow, UCL Cardiovascular
Genetics, Rayne Institute, London, UK
R Cesnjevar
Cardiothoracic Surgeon, Great Ormond Street Hospital for
Children NHS Trust, London, UK
Peter Clifton
Director Clinical Research Unit, CSIRO Health Sciences and
Nutrition, Adelaide, Australia
John Cockcroft
General Practitioner, CAA Authorised Medical Examiner, Billericay
Health Centre, Billericay, Essex, UK
Martin Cowie
Senior Lecturer in Cardiology and Honorary Consultant
Cardiologist, University of Aberdeen and Grampian University
Hospitals Trust, Department of Cardiology, Aberdeen Royal
Infirmary, Aberdeen, UK
xii
Contributors xiii
Seamus Cullen
Senior Lecturer, Department of Grown Up Congenital Cardiology,
UCL Hospitals, The Middlesex Hospital, London, UK
Vincent S DeGeare
Lecturer, Great Ormond Street Hospital for Children NHS Trust,
London, UK
Vic Froelicher
Consultant Cardiologist, Cardiology Division, Veterans Affairs
Palo Alto Health Care System, Stanford University, California, USA
Anthony Gershlick
Professor of Medicine, Department of Academic Cardiology,
University of Leicester, UK
Cindy L Grines
Director of the Cardiac Catheterization Laboratories, Division of
Cardiology, William Beaumont Hospital, Royal Oak, Michigan,
USA
Suzanna Hardman
Senior Lecturer in Cardiology with an interest in Community
Cardiology, University College London Medical School, and
Honorary Consultant Cardiologist, the UCL and Whittington
Hospitals
Address for correspondence: UCLMS (Whittington campus),
Academic & Clinical Department of Cardiovascular Medicine,
Whittington Hospital, London, UK
Martin Paul Hayward
Cardiothoracic Surgeon, The Austin and Repatriation Medical
Centre, Melbourne, Australia
Daniel E Hillman
Professor and Chair, Department of Pharmacy Practice, Creighton
University, Omaha, Nebraska, USA
Aroon Hingorani
Senior Lecturer in Clinical Pharmacology and Therapeutics,
British Heart Foundation Intermediate Fellow, Centre for Clinical
Pharmacology, UCL, Rayne Institute, London, UK
Diana Holdright
Consultant Cardiologist, Department of Cardiology, UCL
Hospitals, The Middlesex Hospital, London, UK
xiv 100 Questions in Cardiology
Rachael James
Cardiology SpR, The Royal Sussex County Hospital Brighton,
Brighton, UK
Roy M John
Associate Director, Cardiac Electrophysiology Laboratory, Lahey
Clinic Medical Center, Burlington, MA, USA
Robin Kanagasabay
SpR Cardiothoracic Surgery, St Georges Hospital Medical School,
London, UK
RA Kenny
Head of Department of Medicine (Geriatric), University of
Newcastle Upon Tyne, Institute for Health of the Elderly, Royal
Victoria Infirmary, Newcastle Upon Tyne, UK
Brendan Madden
Consultant Cardiothoracic and Transplant Surgeon, Cardiothoracic
Transplant Unit, St Georges Hospital, London, UK
Kenneth W Mahaffey
Assistant Professor of Medicine, Duke Clinical Research Institute,
Durham, NC, USA
Niall G Mahon
Specialist Registrar in Cardiology, St Georges Hospital Medical
School, London, UK
Joseph F Malouf
Associate Professor, Mayo Medical School, and Consultant, Division
of Cardiovascular Diseases and Internal Medicine, Mayo Clinic,
Rochester, Minnesota, USA
Richard Mansfield
Lecturer in Cardiology, Cardiovascular Repair and Remodeling
Group, Middlesex Hospital, London, UK
W McKenna
Registrar in Cardiology, St Georges Hospital Medical School,
London, UK
Hugh Montgomery
Honorary Consultant, UCL Hospitals Intensive Care Unit, and
Lecturer in Cardiovascular Genetics, UCL Hospitals, London, UK
Contributors xv
Marc R Moon
Assistant Professor of Cardiothoracic Society Department of
Cardiothoracic Surgery, Washington University School of
Medicine, St Louis, Missouri, USA
Stan Newman
Professor of Psychology, Deptartment of Psychological Medicine,
UCL Hospitals, The Middlesex Hospital, London, UK
Petros Nihoyannopoulos
Senior Lecturer and Consultant Cardiologist, Cardiology
Department, Imperial College School of Medicine, National Heart
and Lung Institute, Hammersmith Hospital, London, UK
Michael S Norrell
Consultant Cardiologist, Hull and East Yorkshire Hospitals, Hull
Royal Infirmary, Hull, UK
Lionel H Opie
Co-Director, Cape Heart Centre and Medical Research Council,
Inter-University Cape Heart Group, University of Cape Town,
and Consultant Physician, Groote Schuur Hospital, Cape Town,
South Africa
Diarmuid OShea
Consultant Physician, Department of Geriatric Medicine, St
Vincents University Hospital, Dublin, Ireland
Krishna Prasad
Specialist Registrar in Cardiology, Department of Cardiology,
University of Wales College of Medicine, Cardiff, UK
Liz Prvulovich
Consultant Physician in Nuclear Medicine, Institute of Nuclear
Medicine, Middlesex Hospital, London, UK
Henry Purcell
Senior Fellow in Cardiology, Royal Brompton and Harefield NHS
Trust, London, UK
Michael Schachter
Senior Lecturer in Clinical Pharmacology, Department of Clinical
Pharmacology, Imperial College School of Medicine, and
Honorary Consultant Physician, St Marys Hospital, London, UK
Rakesh Sharma
Clinical Research Fellow, Department of Cardiac Medicine,
National Heart and Lung Institute, London, UK
xvi 100 Questions in Cardiology
Alistair Slade
Consultant Cardiologist, Royal Cornwall Hospitals Trust, Treliske
Hospital, Truro, Cornwall, UK
Simon Sporton
Specialist Registrar in Cardiology, Department of Cardiology, St
Bartholomews Hospital, London, UK
Mark Squirrell
Senior Technician, Department of Cardiology, UCL Hospitals, The
Middlesex Hospital, London, UK
Matthew Streetly
Specialist Registrar in Haematology, Department of Haematology,
University College Hospital, London, UK
Jan Stygall
Clinical Psychologist, The Middlesex Hospital, London, UK
DP Taggart
Consultant Cardiothoracic Surgeon, John Radcliffe Hospital,
Oxford, UK
Sara Thorne
Consultant Cardiologist, Department of Cardiology, Queen
Elizabeth Hospital, Birmingham
Adam D Timmis
Consultant Cardiologist, Department of Cardiology, London
Chest Hospital, London, UK
Tom Treasure
Consultant Cardiothoracic Surgeon, Department of Cardiothoracic
Surgery, St Georges Hospital, London, UK
Victor T Tsang
Consultant Cardiothoracic Surgeon, Great Ormond Street Hospital
for Children NHS Trust, London, UK
Jonathan Unsworth-White
Consultant Cardiothoracic Surgeon, Department of Cardiothoracic
Surgery, Derriford Hospital, Plymouth, Devon, UK
Peter Wilson
Consultant Microbiologist, Department of Clinical Microbiology,
University College Hospital, London, UK
Introduction
Acknowledgement
We would like to acknowledge Dr Chris Newman whose initial
suggestion led to this book.
xvii
100 Questions in Cardiology 1
Aroon Hingorani
Further reading
McMahon S. Blood pressure and risks of cardiovascular disease. In: Swales
JD, ed. Textbook of hypertension. Oxford: Blackwell Scientific,1994:46.
Collins R, Peto R. Antihypertensive drug therapy. Effects on stroke and
coronary heart disease. In: Swales JD, ed. Textbook of hypertension. Oxford:
Blackwell Scientific, 1994:1156.
100 Questions in Cardiology 3
Kieran Bhagat
Further reading
Clement D, De Buyzere M, Duprez D. Prognostic value of ambulatory
blood pressure monitoring. J Hypertens 1994;112: 85764.
Davies RJO, Jenkins NE, Stradling JR. Effects of measuring ambulatory
blood pressure on sleep and on blood pressure during sleep. BMJ
308: 8203.
1994;3
Devereux RB, Pickering TG. Relationship between the level, pattern and
variability of ambulatory blood pressure and target organ damage in
9(suppl 8): S348.
hypertension. J Hypertens 1991;9
100 Questions in Cardiology 5
Kieran Bhagat
Further testing
If routine testing reveals abnormalities or the patient has been
referred for resistant hypertension then further investigations
are justified. These should be determined by clinical suspicion
(for example, symptoms or signs of phaeochromocytoma,
Cushingoid appearance etc.) and the outcome of routine investi-
gations (for example proteinuria, haematuria, hypokalaemia etc.).
Aroon Hingorani
Who to treat
The primary aim of blood pressure (BP) treatment is to reduce the
risk of stroke and CHD. Assuming secondary causes of hyper-
tension have been excluded, the decision to treat a particular level
of BP is based on an assessment of the risk of stroke, coronary
heart disease (CHD) and hypertensive renal disease in the
individual patient.
All patients with evidence of target organ damage (left ventricular
hypertrophy, retinopathy, or hypertensive nephropathy) are
considered to be at high risk and should receive treatment whatever
the level of BP. Similarly, all patients who have previously suffered
a stroke or CHD should have their BP lowered if it is above
140/90mmHg.
Difficulties arise in those without end-organ damage or a
previous cardiovascular event. Guidelines in the UK have
advocated antihypertensive treatment for sustained BP levels
above 160/100mmHg since in these individuals the risks of stroke
and renal disease are unacceptably high. Absolute risk of stroke
or CHD depends, however, not only on BP but also on the combi-
nation of other risk factors (age, gender, total cholesterol, HDL-
cholesterol, smoking, diabetes, and left ventricular hypertrophy).
Their synergistic interaction in any individual makes universal
application of BP thresholds perhaps inappropriate and some
individuals with BP >140/90mmHg will benefit from treatment.
Recent guidelines on treatment have also advocated a global
assessment of risk rather than focusing on individual risk factors.
The risk of stroke or CHD in an individual can be calculated using
tables1 or computer programmes2 based on a validated risk
function (for example Framingham Risk Equation). Having
calculated absolute risk (based on the variables above), one has to
decide what level of risk is worth treating. A low threshold for
treatment will result in a larger number of individuals exposed to
antihypertensive drugs and a higher cost, but a greater number of
cardiovascular events saved. Meta-analysis has shown that (for a
8 100 Questions in Cardiology
Young patients
Since age is a major determinant of absolute risk, treatment
thresholds based on absolute risk levels will tend to postpone
treatment to older ages. However, younger patients with elevated
BP who have a low absolute risk of stroke and CHD exhibit
greatly elevated relative risks of these events compared to their
normotensive age-matched peers. Deciding on the optimal age of
treatment in such individuals presents some difficulty and the
correct strategy has yet to be determined.
Elderly patients
The absolute risk of CHD and stroke in elderly hypertensive
patients is high and, consequently, the absolute benefit from
treatment is much greater than in younger patients. Decisions to
treat based on absolute risk are therefore usually straightforward.
However, there is little in the way of firm trial evidence for the
benefits of treatment in individuals aged more than 80. In these
patients, decisions could be made on a case-by-case basis taking
into account biological age.
References
1 New Zealand guidelines and tables available at http: //www.nzgg.org.nz
2 Hingorani AD, Vallance P. A simple computer programme for guiding
management of cardiovascular risk factors and prescribing. BMJ
318: 1015
1999;3
3 Hansson L, Zanchetti A, Carruthers SG et al. Effects of intensive blood
pressure lowering and low-dose aspirin in patients with hypertension:
351: 175562.
principal results of the HOT trial. Lancet 1998;3
Further reading
Ramsay LE et al. British Hypertension Society guidelines for hyper-
tension management 1999: summary. BMJ 1999;3319: 6305.
10 100 Questions in Cardiology
Kieran Bhagat
References
1 MRC Working Party. Medical Research Council trial of treatment of
304: 40512.
hypertension in older adults: principal results. BMJ 1992;3
100 Questions in Cardiology 11
Kieran Bhagat
References
1 Psaty BM, Heckbert SR, Koepsell TD et al. The risk of myocardial
infarction associated with antihypertensive drug therapies. JAMA
1995; 274: 6205.
2 Furberg CD, Psaty BM, Meyer JV. Nifedipine. Dose-related increase
in mortality in patients with coronary heart disease.Circulation 1995;
92: 132631.
100 Questions in Cardiology 13
3 Cavis BR, Cutler JA, Gordon DJ et al. Rationale and design for the anti-
hypertensive and lipid lowering treatment to prevent heart attack trial
(ALLHAT). Am J Hypertens 1996; 9: 34260.
14 100 Questions in Cardiology
Aroon Hingorani
INITIAL ASSESSMENT
Measure BP*
History (including drug and family history) and examination
Baseline screen for secondary causes of hypertension**:
urinalysis, creatinine and electrolytes
Assessment of end-organ damage***:
ECG, fundoscopy
Assessment of other cardiovascular risk factors:
age, gender, BP, total and HDL-cholesterol
ECG-LVH, diabetes, smoking status
REVIEW
Adequacy of treatment: BP and cholesterol target
Side effects from treatment
Lifestyle modifications
* Sitting position. Mean of 2-3 measurements over 46 weeks unless severity of BP dictates
earlier treatment.
** Abnormalities identified from history, examination or baseline screen dictate further investi-
gation to confirm/exclude renal parenchymal, renovascular, endocrine or other secondary
causes of hypertension.
*** The presence of hypertensive retinopathy or LVH is an indication for BP lowering irrespective
of the absolute BP level.
****For references to risk calculators see Qu4, page 7.
Reference: Vallance P. CME Cardiology II. Hypertension, J Roy Coll Phys Lon 1999; 33: 119-23
100 Questions in Cardiology 15
Aroon Hingorani
John Betteridge
References
1 Shepherd J, Cobbe SM, Ford I et al. for the West of Scotland Coronary
Prevention Study Group. Prevention of coronary heart disease with
pravastatin in men with hypercholesterolaemia. N Engl J Med 1995;
333: 13017.
2 Downs GR, Clearfield M, Weiss S et al. Primary prevention of acute
coronary events with lovastatin in men and women with average
cholesterol levels: results of AFCAPS/TEXCAPS. Air Force/Texas
coronary atherosclerosis study. JAMA 1998; 279: 161522.
3 Joint British recommendations on prevention of coronary heart disease
in clinical practice. British Cardiac Society, British Hyperlipidaemia
Association, British Hypertension Society endorsed by the British
Diabetic Association. Heart 1998; 80 (suppl 2): S1S29.
18 100 Questions in Cardiology
John Betteridge
References
1 Scandinavian Simvastatin Survival Study Group. Randomised trial of
cholesterol lowering in 4444 patients with coronary heart disease. The
Scandinavian simvastatin survival study. Lancet 1994; 344: 13839.
2 Sacks FM, Pfeffer MA, Moye LA et al. The effect of pravastatin on
coronary events after myocardial infarction in patients with average
cholesterol levels. N Engl J Med 1996; 335: 10019.
3 The Long-Term Intervention with Pravastatin in Ischaemic Disease
(LIPID) Study Group. Prevention of cardiovascular events and death
with pravastatin in patients with coronary heart disease and a broad
range of initial cholesterol levels. N Engl J Med 1998; 339: 134957.
100 Questions in Cardiology 19
John Betteridge
Further reading
Betteridge DJ, Morrell JM. Clinicians guide to lipids and coronary heart
disease. London: Chapman & Hall Medical, 1998.
Betteridge DJ, Illingworth DR, Shepherd J, eds. Lipoproteins in health and
disease. London: Edward Arnold, 1999.
22 100 Questions in Cardiology
John Betteridge
Statins
These are generally well tolerated. In the major end point trials,
adverse events were little different from placebo.
Fibrates
These are also generally well tolerated but can also cause myositis
and hepatic dysfunction. Clofibrate (in the WHO trial) was
associated with increased gallstone formation through increased
biliary cholesterol content. This drug is now redundant and the
newer fibrates have less impact on biliary composition. Doubt
remains concerning long term safety with the fibrate class in
terms of non-cardiac mortality. However the WHO clofibrate trial
was the major contributor to this concern. The recent VA HIT
study (reported at the AHA meeting in Dallas, November 1998)
showed that gemfibrozil reduced risk by approximately a quarter
100 Questions in Cardiology 23
Drug interactions
Care should be exercised when statins are combined with fibrates
or used in patients taking cyclosporin (e.g. transplant patients) as
the risk of side effects (particularly myositis) is increased. Dosage
should be limited in transplant patients taking cyclosporin as
drug levels are increased. Care should also be exercised when
used in combination with drugs metabolised through the
cytochrome P450 pathway (e.g. antifungals, erythromycin) as
there is a potential for interactions. There is a theoretical potential
for interaction with warfarin but the author has not found this a
problem in practice.
Resins
The resins are associated with a high frequency of gastrointestinal
side effects which limit their use. They may interfere with the
absorption of other drugs so should be taken either one hour
before or four hours after other therapeutic agents. The resins
theoretically may interfere with the absorption of fat soluble
vitamins and folic acid but this is not a major problem in practice.
However, perhaps with increasing indication of the role of homo-
cysteine as a risk factor, folic acid supplements might be
recommended in patients on resins.
24 100 Questions in Cardiology
Peter Clifton
References
1 Stephens NG, Parsons A, Schofield PM et al. Randomised controlled
trial of vitamin E in patients with coronary disease: Cambridge Heart
Antioxidant Study. Lancet 1996;3347: 7816.
2 Rapola JM, Virtamo J, Ripatti S et al. Randomised trial of alpha-
tocopherol and beta-carotene supplements on incidence of major
coronary events in men with previous myocardial infarction. Lancet
1997;3 349: 171520.
100 Questions in Cardiology 25
Vic Froelicher
References
1 Gianrossi R, Detrano R, Mulvihill D et al. Exercise-induced ST
depression in the diagnosis of coronary artery disease: a meta-analysis.
80: 8798.
Circulation 1989;8
2 Froelicher VF, Lehmann KG, Thomas R et al. The ECG exercise test in a
population with reduced workup bias: diagnostic performance,
computerized interpretation, and multivariable prediction. Veterans
26 100 Questions in Cardiology
Joseph F Malouf
References
1. Gibbons RJ, Chatterjee K, Daley J et al. ACC/AHA/ACP-ASIM guide-
lines for the management of patients with chronic stable angina: a
report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines. J Am Coll Cardiol
1999;333: 2092197.
100 Questions in Cardiology 29
Vic Froelicher
References
1 Morrow K, Morris CK, Froelicher VF et al. Prediction of cardiovascular
death in men undergoing noninvasive evaluation for CAD. Ann Int Med
118: 68995.
1993;1
30 100 Questions in Cardiology
Liz Prvulovich
References
1 Underwood SR, Godman B, Salyani S et al. Economics of myocardial
perfusion imaging in Europe The Empire Study. Eur Heart J 1999;2 20:
15766.
2 De Bono D, for the joint working party of the British Cardiac Society and
Royal College of Physicians of London. Investigation and management
81: 54655.
of stable angina: revised guidelines. Heart 1999;8
3 Brown KA. Prognostic value of myocardial perfusion imaging: state of
the art and new developments. J Nucl Cardiol 1996;3 3: 51638.
4 Ladenheim ML, Kotler TS, Pollock BH et al. Incremental prognostic
power of clinical history, exercise electrocardiography and myocardial
perfusion scintigraphy in patients with suspected coronary disease.
Am J Cardiol 1987;559: 2707.
32 100 Questions in Cardiology
Petros Nihoyannopoulos
References
1 Fallavollita JA, Canty JM. Differential 18F-2-Deoxyglucose uptake in
viable dysfunctional myocardium with normal resting perfusion.
99: 2798805.
Circulation 1999;9
2 Di Carli MF, Asgrzadie F, Schelbert H et al. Quantitative relation
between myocardial viability and improvement in heart failure
symptoms after revascularisation in patients with ischaemic cardio-
92: 343644.
myopathy. Circulation 1995;9
3 Senior R, Kaul S, Lahiri A. Myocardial viability on echocardiography
predicts long-term survival after revascularisation in patients with
33: 184854.
ischaemic congestive heart failure. J Am Coll Cardiol 1999;3
4 Baumgartner H, Porenta G, Lau Y-K et al. Assessment of myocardial
viability by dobutamine echocardiography, positron emission
tomography and thallium-201 SPECT. J Am Coll Cardiol 1998;3 32: 17018.
100 Questions in Cardiology 35
Henry Purcell
Nitrates
All patients with angina pectoris should have sublingual glyceryl
trinitrate (GTN) for the rapid relief of acute pain. Long-acting
isosorbide dinitrate (ISDN) and isosorbide mononitrate (ISMN)
preparations are also available but have not been shown to
influence mortality in post-myocardial infarction (MI) patients.
Beta blockers
In the absence of contraindications, beta blockers are preferred as
initial therapy for angina.1 Evidence for this is strongest for
patients with prior MI. Long term trials show that there is a 23%
reduction in the odds of death among MI survivors randomised to
beta blockers.2
Calcium antagonists
Calcium antagonists (especially those which reduce heart rate)
are suitable as initial therapy when beta blockers are contra-
indicated or poorly tolerated. Outcome trials are underway but
there is currently little evidence to suggest they improve prog-
nosis post-MI, although diltiazem and verapamil may reduce the
risk of reinfarction in patients without heart failure,3 and
amlodipine may benefit certain patients with heart failure.
Other agents
Nicorandil, a potassium channel opener with a nitrate moiety,
and the metabolic agent, trimetazidine, may also be useful, but
these have not been tested in outcome studies.
Many patients with exertional symptoms may need a
combination of anti-anginals, but there is little evidence to
support the use of triple therapy. Patients requiring this should
be assessed for revascularisation. There are no important differ-
ences in the effectiveness of the principal classes of anti-anginal
36 100 Questions in Cardiology
References
1 ACC/AHA/ACP-ASIM Guidelines for the management of patients
with chronic stable angina: executive summary and recommendations.
99: 282948.
Circulation 1999;9
2 Freemantle N, Cleland J, Young P et al. blockade after myocardial
infarction: systematic review and meta regression analysis. BMJ
1999;3318: 17307.
3 Task Force of the European Society of Cardiology. Management of
stable angina pectoris. Eur Heart J 1997;118: 394413.
4 Petticrew M, Sculpher M, Kelland J et al. Effective management of
stable angina. Qual Health Care 1998;77: 10916.
100 Questions in Cardiology 37
David J Brull
Risk stratification
The initial step in risk stratification is an ECG. Patients with
acute ST elevation are considered to have an acute MI and
require reperfusion therapy according to local protocols.
Individuals with ST depression are also at high risk and require
admission for further evaluation. The presence of a positive
troponin T in this group further confirms them as high risk. In
situations where patients present either with a normal ECG or
with T wave changes only, the value of a positive troponin T is
vital in risk stratification. All patients who are troponin T
positive should be considered as high risk, whilst in contrast, a
negative troponin T 12 hours or more after the onset of
symptoms puts the individual in a low risk group. If the result
of a negative troponin T test taken 12 hours or more after the
onset of chest pain is taken in conjunction with a pre-discharge
exercise test, this further reduces the chance of an inappropriate
discharge.4 Figure 20.1 illustrates one possible management
algorithm.
100 Questions in Cardiology 39
Positive Negative
High-risk
Admit
Positive Negative
High-risk Low-risk
Admit
Conclusion
Troponin T has a vital role in the triage of patients presenting
with chest pain. A positive test identifies high-risk individuals
who may benefit from aggressive anti-platelet therapy or early
intervention, whilst negative troponin T tests 12 or more hours
after the onset of symptoms identify those at low risk who can be
considered for early hospital discharge.
References
1 Hamm CW, Goldmann BU, Heeschen C et al. Emergency room triage of
patients with acute chest pain by means of rapid testing for cardiac
troponin T or troponin I. N Engl J Med 1997; 337: 164853.
2 Lindahl B, Venge P, Wallentin L, for the FRISC Study Group. Relation
between troponin T and the risk of subsequent cardiac events in
unstable coronary artery disease. Circulation 1996;9 93: 165157.
3 Ohman EM, Armstrong PW, Christensen RH et al. for the GUSTO IIa
Investigators. Cardiac troponin T levels for risk stratification in acute
myocardial ischemia. N Engl J Med 1996;3 335: 133341.
4 Lindahl B, Andren B, Ohlsson J et al. Risk stratification in unstable
coronary artery disease. Additive value of troponin T determinations
18: 76270.
and pre-discharge exercise tests. Eur Heart J 1997;1
100 Questions in Cardiology 41
Diana Holdright
References
1 Van Miltenburg AJ, Simoons ML, Veerhoek RJ et al. Incidence and
follow-up of Braunwald subgroups in unstable angina pectoris. J Am
25: 128692.
Coll Cardiol 1995;2
2 Yusuf S, Flather M, Pogue J et al. for the OASIS (Organisation to
Assess Strategies for Ischaemic Syndromes) Registry Investigators.
Variations between countries in invasive cardiac procedures and
outcomes in patients with suspected unstable angina or myocardial
352: 50714.
infarction without initial ST elevation. Lancet 1998;3
3 Boden WE, ORourke RA, Crawford MH et al. for the Veterans Affairs
Non-Q Wave Infarction Strategies in Hospital (VANQWISH) Trial
Investigators. Outcomes in patients with acute non-Q-wave
myocardial infarction randomly assigned to an invasive as compared
with a conservative management strategy. N Engl J Med 1998;3 338 :
178592.
100 Questions in Cardiology 43
Diana Holdright
Anti-ischaemic therapy
Nitrates relieve ischaemic pain but there is no evidence of
prognostic benefit from their use.
Antithrombotic therapy
Aspirin has an important and undisputed role in the treatment of
unstable angina, reducing the risk of fatal/non-fatal MI by 70%
acutely, by 60% at 3 months and by 52% at 2 years.1 A first dose of
160-325mg should be followed by a maintenance dose of 75mg
daily.
References
1. Theroux P, Fuster V. Acute coronary syndromes. Circulation 1998;9 97:
1195206.
2. National Institute for Clinical Excellence. Guidance on the use of glycoprotein
IIb/IIIa inhibitors in the treatment of acute coronary syndromes. Technology
Appraisal Guidance-No. 12, September 2000. (www.nice.org.uk)
3 Oler A, Whooley MA, Oler J. Grady D. Adding heparin to aspirin
reduces the incidence of myocardial infarction and death in patients
with unstable angina. JAMA 1996;2 276: 81115.
4 Cohen M, Demers C, Gurfinkel EP et al. A comparison of low-
molecular weight heparin with unfractionated heparin for unstable
coronary artery disease: Efficiency and Safety of Subcutaneous
Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) Study
Group. N Engl J Med; 1997;3 337: 44752.
100 Questions in Cardiology 45
Diana Holdright
References
1 Fragmin and Fast Revascularisation during InStability in Coronary
artery disease (FRISC II) Investigators. Invasive compared with non-
invasive treatment in unstable coronary-artery disease: FRISC II
354: 70815.
prospective randomised multicentre study. Lancet 1999;3
2 Anderson HV, Cannon CP, Stone PH et al. One-year results of the
Thrombolysis in Myocardial Infarction (TIMI) IIIB clinical trial: a
randomised comparison of tissue-type plasminogen activator versus
placebo and early invasive versus early conservative strategies in
unstable angina and non-Q wave myocardial infarction. J Am Coll
26: 164350.
Cardiol 1995;2
3 Boden WE, ORourke RA, Crawford MH et al. for the Veterans Affairs
Non-Q Wave Infarction Strategies in Hospital (VANQWISH) Trial
100 Questions in Cardiology 47
Richard Mansfield
Pharmacological approaches
To date no pharmacological agent has had a significant effect on
reducing the incidence of restenosis. There are a number of
reasons for this including the lack of correlation between animal
models and the situation in man, the drug doses used or the
power of some of the trials. Recent interest has focused on the use
of antiproliferative agents such as paclitaxel and tranilast.
The antioxidant Probucol has been shown to be effective in
limiting restenosis after balloon angioplasty. However, lack of
licensing in some countries, limited data on the clinical impact of
treatment, and the fact that pre-treatment for 4 weeks is required,
may all be factors in limiting its use.
Gene therapy involves the transfer of DNA into host cells with
the aim of inducing specific biological effects. Vectors for gene
delivery include plasmid DNA-liposome complexes and viral
vectors such as the replication deficient recombinant adenovirus.
Design of appropriate delivery devices has taken a number of
directions including double balloon catheters and perforated
balloons allowing high pressure injection through radial pores.
Various approaches have been used to limit experimental
restenosis by inducing cell death (e.g. fas ligand gene to induce
apoptosis), inhibiting smooth muscle cell migration (e.g. over-
expression of TIMP-1 and eNOS) or by inhibiting cell cycle
regulators of smooth muscle cell proliferation (e.g. antisense
100 Questions in Cardiology 49
Brachytherapy
Over the last few years there has been considerable interest in
intravascular brachytherapy (radiation therapy). The ability of
ionising radiation to halt cell growth by damaging the DNA of
dividing cells, and the view that neointimal hyperplasia
represented a benign proliferative condition led to its application
in vascular disease. A variety of catheter based delivery systems
and radioactive stents are available using either beta (e.g. 32P) or
gamma (e.g. 192Ir) sources. A number of studies have shown
impressive results on reducing restenosis rates and many more
are underway but enthusiasm for the technique should be
tempered because there are concerns about long term safety.
Indeed there are very recent reports of unexpected late thrombotic
occlusion.
Photodynamic therapy (PTD) involves the local activation of a
systemically administered photosensitising agent by non-
ionising radiation in the form of non-thermal laser light. Many of
the sensitising agents that have been studied have been products
of porphyrin metabolism such as 5-aminolaevulinic acid. Much
of the work in this field to date has been in the treatment of cancer
but there is an accumulation of small and large animal data
showing a reduction in neointimal hyperplasia after balloon
injury. Favourable vessel wall remodelling has also been
observed in a pig model of balloon coronary and iliac angioplasty.
Reports of the clinical application of photodynamic therapy are
limited but a clinical pilot study of adjuvant PDT in superficial
femoral angioplasty showed it to be a safe and effective
technique. Further work needs to be done to establish its role in
coronary disease.
Further reading
Jenkins MP, Buonaccorsi GA et al. Reduction in the response to coronary
and iliac artery injury with photodynamic therapy using 5-amino-
laevulinic acid. Cardiovasc Res 2000;445: 47885.
Kullo IJ, Simari RD, Schwartz RS. Vascular gene transfer; from bench to
19: 196207.
bedside. Arterioscler Thromb Vasc Biol 1999;1
50 100 Questions in Cardiology
Anthony Gershlick
Thrombolysis
Natural thrombolysis occurs via the action of plasmin on fibrin
thrombi. Plasmin is formed from plasminogen by cleavage of a
single peptide bond. Plasmin is a non-specific protease and
dissolves coagulation factors as well as fibrin clots. Three
thrombolytic agents are currently available. Streptokinase (SK)
forms a non-covalent link with plasminogen. The resultant con-
formational change exposes the active site on plasminogen to
induce the formation of plasmin. Tissue plasminogen activator
(tPA) is a serine protease and binds directly to fibrin via a lysine
site, activating fibrin-bound plasminogen. The theoretical advan-
tages of tPA are its increased specificity and potency because of its
direct effect on fibrin-bound plasminogen. Being the product of
recombinant DNA technology, there should be no allergic
reaction to tPA. Unlike SK which should be used only once, tPA
can be used repeatedly. Some, but not all, of these theoretical
advantages translate into definite clinical benefit. Recently
reteplase, a variation of tPA, has become available.
The Fibrinolytic Therapy Trialists Collaborative Group 1
summarised results from thrombolytic trials encompassing
more than 100,000 patients. The overall relative risk reduction
in 35 day mortality with treatment was 18% (p < 0.00001). The
mortality at this time was ~13%, reduced to 89% with
treatment. However, in real life where the population is older
than in the trials the true mortality is about 1820%.
Administration of a thrombolytic saves about 30 lives in a 1000
in those presenting within 6 hours of symptom onset but only
20 lives in a 1000 when patients receive treatment between 6
and 12 hours after symptom onset. Aspirin has an independent
beneficial effect on mortality and can be chewed.2 The LATE
Trial showed no benefit 12 hours after onset of symptoms.3
Judging the onset of symptoms can be difficult and may be
influenced by collateral flow from another artery. If a patient
presents with stuttering symptoms over 24 hours or so but has
52 100 Questions in Cardiology
What to give
Currently, the choice of thrombolytic varies by country and
depends especially on the type of health care system and funding
in place. In many countries, in the absence of previous
administration the first line thrombolytic is SK (1.5 million units
in 100 mls 5% dextrose/0.9% NaCl over 3060 minutes).
Alternatively, tPA is given as a 15mg bolus followed by 50mg
over 60 minutes, then 35mg over a further 30 minutes. Based on
the GUSTO study a case can be made for tPA in those presenting
very early (<4 hours with large anterior infarcts). New plas -
minogen activators such as recombinant plasminogen activator (r-
PA) and prourokinase are currently the subject of a number of
clinical studies. Reteplase (rPA), is a nonglycosylated deletion
mutant of wild type tPA. It is the first member of the third gener-
ation thrombolytics, has a longer half life and is given as a double
bolus (10IU + 10IU). Equivalence trials comparing tPA and
reteplase have demonstrated no difference in outcome and
currently these two drugs are interchangeable, with decisions
about use being based on availability and price.6 Lanoteplase has
been withdrawn prior to launch because of patent issues and
TNK-tPA is being trialled against tPA (ASSENT 2).7 Bleeding
with this new agent was between 2.8% and 7.4% dependent on
dose (ASSENT 1).8 Data suggest that there may be a role for
rescue angioplasty in patients who fail to show electrocardio-
graphic evidence of reperfusion.9 However, results of randomised
trials addressing this issue are awaited.
References
1 Fibrinolytic Therapy Trialists (FTT) Collaborative Group. Indications
for fibrinolytic therapy in suspected acute myocardial infarction:
collaborative overview of early mortality and major morbidity from all
343: 31122.
randomised trials of more than 1000 patients. Lancet 1994;3
2 Feldman M, Cryer B. Aspirin absorption rates and platelet inhibition
times with 325mg buffered aspirin tablets (chewed or swallowed
whole) and with buffered aspirin solution. Am J Cardiol 1999;8 84 :
4049.
3 LATE Study Group. Late assessment of thrombolytic efficiency (LATE)
study with alteplase 624 hours after onset of acute myocardial
342: 75966.
infarction. Lancet 1993;3
4 The European Myocardial Infarction Project Group. Pre-hospital
thrombolytic therapy in patients with suspected acute myocardial
329: 3839.
infarction. N Engl J Med 1993;3
54 100 Questions in Cardiology
References
1 Grines CL, Browne KF, Marco J et al. for the Primary Angioplasty in
Myocardial Infarction Study Group. A comparison of immediate
angioplasty with thrombolytic therapy for acute myocardial infarction.
328: 6739.
N Engl J Med 1993;3
56 100 Questions in Cardiology
Kenneth W Mahaffey
Further reading
Fibrinolytic Therapy Trialists (FTT) Collaborative Group. Indications
for fibrinolytic therapy in suspected acute myocardial infarction:
collaborative overview of early mortality and major morbidity results
343:
from all randomised trials of more than 1000 patients. Lancet 1994;3
31122.
Gunnar RM, Passamani ER, Bourdillon PDV et al. Guidelines for the
early management of patients with acute myocardial infarction. A report
of the American College of Cardiology/American Heart Association task
force on assessment of diagnostic and therapeutic cardiovascular
16: 249292.
procedures. J Am Coll Cardiol 1990;1
Mahaffey KW, Granger CB, Toth CA et al. for the GUSTO-I Investigators.
Diabetic retinopathy should not be a contraindication for thrombolytic
therapy for acute myocardial infarction: review of ocular hemorrhage
30:
incidence and location in the GUSTO-I trial. J Am Coll Cardiol 1997;3
160610.
Ryan TJ, Anderson JL, Antman EM et al. ACC/AHA guidelines for the
management of patients with acute myocardial infarction. J Am Coll
28: 13281428.
Cardiol 1996;2
Sane DC, Califf RM, Topol EJ, Stump DC, Mark DB, Greenberg CS.
Bleeding during thrombolytic therapy for acute myocardial infarction:
mechanisms and management. Ann Intern Med 1989;1 111: 101022.
100 Questions in Cardiology 59
Adam D Timmis
References
1 Stevenson R, Ranjadayalan K, Wilkinson P et al. Short and long term
prognosis of acute myocardial infarction since introduction of
thrombolysis. BMJ 1993;3 307: 34953.
2 Peterson ED, Shaw LJ, Califf RM. Clinical guideline: part II. Risk
stratification after myocardial infarction. Ann Intern Med 1997;1 126 :
56182.
3 Shaw LJ, Peterson ED, Kesler K et al. A metaanalysis of predischarge
risk stratification after acute myocardial infarction with stress electro-
cardiographic, myocardial perfusion, and ventricular function
imaging. Am J Cardiol 1996;7 78: 132737.
4 Stevenson R, Wilkinson P, Marchant B et al. Relative value of clinical
variables, treadmill stress testing and Holter ST monitoring for post-
74: 2215.
infarction risk stratification. Am J Cardiol 1994;7
5 Stevenson R, Umachandran V, Ranjadayalan K et al. Reassessment of
treadmill stress testing for risk stratification in patients with acute
myocardial infarction treated by thrombolysis. Br Heart J 1993;7 70 :
41520.
100 Questions in Cardiology 61
Adam D Timmis
References
1 Tunstall-Pedoe H, Kuulasmaa K, Amouyel P et al. Myocardial infarc-
tions and coronary deaths in the World Health Organisation MONICA
Project. Registration procedures, event rates, and case fatality rates in
62 100 Questions in Cardiology
Michael Schachter
At least half the patients who suffer an acute infarct will survive
at least one month, though 1020% will die within the next year.
It is to be hoped and expected that more active early intervention
will bring about further improvements in short term survival.
There is therefore a large and growing number of patients where
there is a need to prevent further cardiovascular events and to
maintain and improve the quality of life.
Aspirin
Aspirin at low to medium doses (75325mg daily) reduces
mortality, reinfarction and particularly stroke by 1045% after
myocardial infarction. It has been estimated that there is about
one serious haemorrhage, gastrointestinal or intracerebral, for
every event prevented. At the moment there is no comparable
evidence for dipyridamole, ticlopidine or clopidogrel.
Beta blockers
There is overwhelming evidence for the beneficial effect of beta
blockers, both within the first few hours of myocardial infarction
and for up to three years afterwards. Reduction in mortality
ranges from 15 to 45%, almost all of it accounted for by fewer
instances of sudden death. All beta blockers appear equally
suitable, except those with partial agonist activity. The contraindi-
cations are controversial, but most would include asthma, severe
heart block and otherwise untreated heart failure, but patients
with poor left ventricular function benefit most. In asthmatic
patients, particularly, heart rate limiting calcium channel blockers
(verapamil or diltiazem) may be useful alternatives to beta
blockers in the absence of uncontrolled heart failure.
Lipid-lowering drugs
The large secondary prevention trials with simvastatin and prava-
statin (4S, CARE, LIPID) have demonstrated unequivocally the
64 100 Questions in Cardiology
ACE inhibitors
These drugs would of course be used in patients with
symptomatic heart failure but should also be used in asymptomatic
patients with ejection fractions <40%. This is associated with
significant decreases in mortality (2030%) and in sudden death,
as well as in reinfarction. All ACE inhibitors so far tested share
these effects. Treatment should be started within 12 days of the
infarct and should be continued indefinitely. Whether all patients
should be given these drugs post-infarction, in the absence of
contraindications, is a more difficult issue. In unselected
populations the benefits of treatment are much less clear cut.
However, data from the recent HOPE trial1 suggest substantial risk
reduction for higher risk vascular patients which may include a
large proportion of patients who have suffered a myocardial
infarction. Other ongoing trials (such as EUROPA, using
Perindopril) may help clarify this issue.
Other action
In addition to these relatively specific measures, diabetes and
hypertension must of course be treated as required, and smoking
discouraged. Some have advocated the use of fish oils especially
in dyslipidaemic patients, either as supplements or as fish. The
use of warfarin has been controversial for many years. It is highly
effective in preventing cardiovascular events, particularly stroke,
but at the cost of more adverse effects than aspirin and the
inconvenience of monitoring. It is therefore not recommended for
first-line use by most cardiologists.
100 Questions in Cardiology 65
References
1 Heart Outcomes Prevention Evaluation Study Investigators. Effects of
ramipril on cardiovascular and microvascular outcomes in people with
diabetes mellitus: results of the HOPE study and MICRO-HOPE
355: 2539.
substudy. Lancet 2000;3
Further reading
Frishman WH, Cheng A. Secondary prevention of myocardial infarction:
role of beta-adrenergic blockers and angiotensin converting enzyme
inhibitors. Am Heart J 1999;1 137: S2534
Kendall MJ, Horton RC, eds. Preventing coronary artery disease.
Cardioprotective therapeutics in practice. London: Martin Dunitz, 1998.
Michaels AD. The secondary prevention of myocardial infarction. Current
Probl Cardiol 1999;1 10: 61777
Velasco JA. After 4S, CARE and LIPID is evidence-based medicine being
practised? Atherosclerosis 1999;1 147 (suppl 1): S3944
66 100 Questions in Cardiology
John Cockcroft
Private pilots are subject to the same regulations but may fly
with a suitably qualified safety pilot in a dual control aircraft
without undergoing angiography. Symptomatic or treated angina,
arrhythmia or cardiac failure disqualifies any pilot from flying.
Professional drivers may be relicenced 3 months after
myocardial infarction provided that there is no angina,
peripheral vascular disease or heart failure. Arrhythmia, if
present, must not have caused symptoms within the last 2 years.
Treatment is allowed provided that it causes no symptoms likely
to impair performance.
Further reading
Joint Aviation Authorities. Joint Aviation Requirements FCL3(Medical)
1997.
The Medical Commission on Accident Prevention. Medical aspects of
fitness to drive 1995.
68 100 Questions in Cardiology
The advent of the thrombolytic era has not altered the incidence
or mortality rate for cardiogenic shock complicating myocardial
infarction (MI). It still represents almost 10% of patients with MI,
with almost 90% dying within 30 days. 1
Pooled results from retrospective, unrandomised data or
historical reviews, which examined the effects of early re-
vascularisation, have suggested reduced mortality following bypass
surgery (CABG) or coronary angioplasty (PTCA) to 33%2 and 42% 3
respectively. Recently, a few randomised trials have attempted to
compare such early (within 48 hours) revascularisation with a
strategy of initial medical stabilisation. The latter might include
thrombolysis, inotropic support and intra-aortic balloon pump
counterpulsation (IABP), still with the option of delayed inter-
vention. It is unfortunate that most of these studies have faltered on
slow patient recruitment 4 leaving only one completed study
(SHOCK, SHould we emergently revascularise Occluded
Coronaries for Shock) to guide our management of these patients.5
Over a 5 year period, the SHOCK trial randomised 302 patients
to receive either early revascularisation within hours from
randomisation, or initial medical stabilisation with the option of
delayed intervention. Thirty day mortality was reduced in the
early intervention group (46% vs 56%) with this benefit
extending out to 6 months and particularly apparent in the
younger (<75 years) age group. The low mortality in the control
group is striking, and explains the lack of a large difference
between the two groups. Nevertheless, it suggests benefit even
with a relatively aggressive conservative policy in these patients.
Because of trial recruitment difficulties it is unlikely that
further randomised data will emerge in the foreseeable future.
Evidence from the SHOCK trial would seem to suggest that at
present it would be reasonable to consider an aggressive
approach with early revascularisation in patients with shock
complicating myocardial infarction. However, access to surgery
should be available 36% of patients required this intervention
100 Questions in Cardiology 69
References
1 Walters MI, Burn S, Houghton T et al. Cardiogenic shock: are HEROICS
96(suppl I): 168A.
justified? Circulation 1997;9
2 ONeil WW. Angioplasty therapy for cardiogenic shock: are
19: 91517.
randomised trials necessary? J Am Coll Cardiol 1992;1
3 Bolooki H. Emergency cardiac procedures in patients in cardiogenic
shock due to complications of coronary artery disease. Circulation
1989;7 79(suppl I): I13748.
4 Norell MS. Randomised trials in cardiogenic shock: whats the
problem? Eur Heart J 1999;2 20: 9878.
5 Hochman J, Boland J, Sleeper L et al. Early revascularisation in acute
myocardial infarction complicated by cardiogenic shock. N Engl J Med
1999;3 341: 62534.
70 100 Questions in Cardiology
Tom Treasure
Reference
1 Treasure T. Cerebral protection in adults. In: Yacoub M, Pepper J, eds.
Annual of cardiac surgery, 7th edition. London and Philadelphia: Current
Science, 1994: 1619
72 100 Questions in Cardiology
Tom Treasure
Reference
1 Dellborg M, Held P, Swedberg K et al. Rupture of the myocardium.
Occurrence and risk factors. Br Heart J 1985;5 54: 1116.
2 Dalrymple-Hay MJ, Langley SM, Sami SA et al. Should coronary artery
bypass grafting be performed at the same time as repair of a post-infarct
13: 28692.
ventricular septal defect? Eur J Cardio-Thorac Surg 1998;1
100 Questions in Cardiology 73
Many factors have influenced the short and long term results of
bypass surgery, not least the improvements in surgical
techniques and experience, changes in the population of patients
undergoing surgery, many of whom would never have been
deemed suitable for surgery even 10 years ago, improvements in
postoperative medical management and the use of the left
internal mammary artery (LIMA) as the graft of choice for the left
anterior descending coronary artery (LAD) in virtually all
patients today.
The patients who gain most from surgery are those most at risk
from dying with medical therapy alone. Pertinent high-risk
characteristics included left main stem (LMS) disease, triple
vessel disease or double vessel disease that included a proximal
LAD lesion, and triple vessel disease associated with impaired LV
function. The VA study at 18 years2 demonstrated superior
surgical survival throughout the 18 years, but was only
significant overall at 7 years (med. vs surg. survival 53% vs 79%
p = 0.007); benefit was much greater in the high risk group with
LMS stenosis >50%, single or double vessel disease with
impaired LV function, and triple vessel disease with LV EF <40%.
In 1988 ECSS3 reported 12 year results demonstrating signifi-
cantly higher cumulative survival in the surgical group, notably
again in patients with 3 vessel disease (med. vs surg. survival
82% vs 94% (p = 0.0002) at 5 years and 68% vs 78% (p = 0.01) at
10 years). Proximal LAD disease >95% in two or three vessel
disease was an outstanding anatomical predictor of survival
(med. vs surg. survival at 10 years 65% vs 77% (p = 0.007)), again
with significant crossover into the surgery group. The CASS
study4 demonstrated no difference in survival for any subset at 5
years, but did not include any patients with poor LV function,
LMS disease, angina greater than class 2, co-morbid disease or
unstable angina. It is therefore difficult to extrapolate data from
this trial to modern patient populations.
Combining results from seven of these early randomised trials
led to the publication of survival figures for 5, 7 and 10 years.5
Medical vs surgical mortality for all patients was 15.8% vs 10.2%
(p = 0.0001) at 5 years, with attenuation of this benefit to a
mortality of 30.5% (med.) and 26.4% (surg.) (p = 0.03) at 10
years. Extension of life for all patients having surgery was 4.3
months at 10 years. High-risk patients once again benefited the
most from surgery, but in lower risk groups, a survival extension
for those with proximal LAD disease (14 months), triple vessel
disease (7 months) or LMS disease (19 months) was identified.
This survival benefit was independent of degree of LV
impairment or abnormal stress testing. Median survival for
patients with LMS disease was 13.1 years in the surgical group
and 6.2 years for those treated medically. The superior patency of
the LIMA graft compared with saphenous vein grafts has been
established beyond any doubt and additional survival benefit, up
to 18 years, has been demonstrated.6
100 Questions in Cardiology 75
References
1 Edwards FH, Clark RE, Schwarz M. Coronary artery bypass grafting:
Society of Thoracic Surgeons National Database experience. Ann Thorac
Surg 1994;557;1219.
2 The Veterans Administration Coronary Artery Bypass Surgery
Cooperative Study Group. Eighteen year follow up in the Veterans
Affairs Cooperative study of coronary artery bypass surgery for
unstable angina. Circulation 1992;8 86: 1216.
3 The European Coronary Surgery Study Group. Twelve year follow up
of survival in the Randomised European Coronary Surgery Study.
N Engl J Med 1988;3 319: 3327.
4 CASS principle investigators. Myocardial infarction and mortality in
the Coronary Artery Study (CASS) randomised trial. N Engl J Med
1984;3310: 7508.
5 Yusuf S, Peduzzi P, Fisher LD et al. Effect of CABG surgery on survival:
overview of 10 year results from randomised trials by the CABG
344: 56370.
surgery triallists collaborations. Lancet 1994;3
6 Boylan MJ, Lytle BW, Loop FD et al. Surgical treatment of isolated left
anterior descending coronary stenosis comparison of LIMA and
venous autografts at 1820 years follow up. J Thorac Cardiovasc Surg
1994;1107: 65762.
76 100 Questions in Cardiology
DP Taggart
References
1 Yusuf S, Zucker D, Peduzzi P et al. Effect of coronary artery bypass graft
surgery on survival: overview of 10-year results from randomised
trials by the Coronary Artery Bypass Graft Surgery Trialists
344: 56370.
Collaboration. Lancet 1994;3
2 Nwasokwa ON. Coronary artery bypass graft disease. Ann Intern Med
1995;1123: 52845.
78 100 Questions in Cardiology
3 Lytle BW, Blackstone EH, Loop FD et al. Two internal thoracic artery
117: 85572.
grafts are better than one. J Thorac Cardiovasc Surg 1999;1
4 Taggart DP. The radial artery as a conduit for coronary artery bypass
grafting. Heart 1999;882: 40910.
100 Questions in Cardiology 79
Further reading
Arrowsmith JE, Harrison MJG, Newman SP et al. Neuroprotection of the
brain during cardiopulmonary bypass. A randomized trial of
Remacemide during coronary artery bypass in 171 patients. Stroke
1998;229: 235762.
Murkin JM, Newman SP, Stump DA et al. Statement of consensus on
assessment of neurobehavioral outcomes after cardiac surgery. Ann Thorac
Surg 1995;559: 128995.
Murkin JM, Stump DA, Blumenthal JA et al. Defining dysfunction:
group means versus incidence analysis: a statement of consensus. Ann
64: 9045.
Thorac Surg 1997;6
Newman SP, Harrison MJG, eds. The brain and cardiac surgery. London;
Harwood Academic, 2000.
82 100 Questions in Cardiology
Jonathan Unsworth-White
Further reading
Brady PA, Terzic A. The sulphonylurea controversy: more questions from
31: 9506.
the heart. J Am Coll Cardiol 1998;3
Smits P, Thien T. Cardiovascular effects of sulphonylurea derivatives.
38: 11621.
Implications for the treatment of NIDDM? Diabetologia 1995;3
84 100 Questions in Cardiology
Jonathan Unsworth-White
Common sense suggests that the more recent the infarction, the
higher the operative risk. This is because the infarcted area is
surrounded by a critically ischaemic zone. The ultimate survival
of this zone depends on many factors, not least of which is the
global function of the remaining myocardium. This function is
temporarily further compromised by the process of cardio-
pulmonary bypass for coronary artery surgery. The likely outcome
during this critical phase, therefore, is extension of the infarcted
area, with obvious implications for survival of the patient.
It is the duration of this critical phase which is most in doubt.
In a recent small retrospective analysis, Herlitz et al1 found that
amongst patients with a history of myocardial infarction,
infarction within 30 days of surgery was not an independent
predictor of total mortality within 2 years of surgery. However,
Braxton et al2 made a distinction between Q wave and non-Q
wave infarctions in the perioperative period. Although both types
rendered the use of balloon pumps and inotropes to wean from
bypass more likely, only Q wave infarctions were associated with
significantly increased surgical mortality and even then only if
surgery was performed within 48 hours of the infarction.
An older but much larger series from Floten et al3 seems to
support a high risk for the initial 2448 hours or so, but more
importantly emphasises the relationship between the number of
diseased vessels and the risk of surgery after recent infarction.
Applebaum et al4 found ejection fraction less than 30%, cardio-
genic shock and age greater than 70 years to be significant deter-
minants of death in patients operated upon within 30 days of
infarction. These are not surprising factors, fitting as they do with
the concept that it is the extent of the jeopardised myocardium
which is the determinant of risk, especially within the first day or
two after the myocardial infarction.
References
1 Herlitz J, Brandrup G, Haglid M et al. Death, mode of death, morbidity,
and rehospitalization after coronary artery bypass grafting in relation
100 Questions in Cardiology 85
Jonathan Unsworth-White
References
1 Antiplatelet Trialists Collaboration. Collaborative overview of
randomised trials of antiplatelet therapy-1: Prevention of death,
myocardial infarction, and stroke by prolonged antiplatelet therapy in
various categories of patients. BMJ 1994;3 308: 81106.
2 Antiplatelet Trialists Collaboration. Collaborative overview of
randomised trials of antiplatelet therapy-II: Maintenance of vascular
308: 15968.
graft or arterial patency by antiplatelet therapy. BMJ 1994;3
3 Kallis P, Tooze JA, Talbot S, et al. Pre-operative aspirin decreases
platelet aggregation and increases post-operative blood loss a
prospective, randomised, placebo controlled, double-blind clinical
trial in 100 patients with chronic stable angina. Eur J Cardio-thorac Surg
1994;8 8: 4049.
100 Questions in Cardiology 87
Tom Treasure
Further reading
Schlant RC. Timing of surgery for nonischemic severe mitral re-
99: 3389.
gurgitation. Circulation 1999;9
Treasure T. Timing of surgery in chronic mitral regurgitation: In: Wells
FC, Shapiro LM. Mitral valve disease. Oxford: Butterworth Heinemann,
1996: 187200.
Tribouilloy CM, Enriquez-Sarano M, Schaff HV et al. Impact of pre-
operative symptoms on survival after surgical correction of mitral re-
99: 4005.
gurgitation. Circulation 1999;9
100 Questions in Cardiology 89
Robin Kanagasabay
References
1 David TE, Omran A, Armstrong S et al. Long-term results of mitral
valve repair for myxomatous disease with and without chordal
replacement with expanded polytetrafluoroethylene sutures. J Thorac
115: 127985; discussion 12856.
Cardiovasc Surg 1998;1
2 Chitwood WR Jr. Mitral valve repair: an odyssey to save the valves! J
7: 25561.
Heart Valve Dis 1998;7
100 Questions in Cardiology 91
3 Lee EM, Shapiro LM, Wells FC. Superiority of mitral valve repair in
surgery for degenerative mitral regurgitation. Eur Heart J 1997;118 :
65563.
4 Gillinov AM, Cosgrove DM, Lytle BW et al. Reoperation for failure of
mitral valve repair. J Thorac Cardiovasc Surg 1997;1 113 : 46773;
discussion 4735.
5 Barlow CW, Imber CJ, Sharples LD et al. Cost implications of mitral
valve replacement versus repair in mitral regurgitation. Circulation
1997;996(9 suppl): II903; discussion II945.
92 100 Questions in Cardiology
after the Ross procedure. More than 90% of all patients are free of
any complications (death, degeneration, valve failure, endo-
carditis) after ten years. However, the subpulmonary homograft
may need replacement in the future. The Ross procedure is
technically demanding. It is the method of choice for aortic valve
replacement in the young, with excellent early postoperative
haemodynamic results and good mid-term results. Long term
results of the Ross procedure using current techniques are awaited.
Further reading
Elkins RC. The Ross operation: a twelve year experience. Ann Thorac Surg
1999;6 68(suppl 3): S1418.
Ross DN. Replacement of aortic and mitral valve with a pulmonary auto-
graft. Lancet 1967;iii: 9568.
94 100 Questions in Cardiology
Tom Treasure
Table 44.1 The annual incident rate of complications (per 100 patient
years)
Stroke TIA N Events
Mechanical mitral 2.4 4.2 380 6.5
Mechanical aortic 1.0 1.3 870 2.0
Tissue mitral 0 2.5 600 2.5
Tissue aortic 1.8 0.7 80 1.5
Seamus Cullen
Further reading
Athanassiadi K, Apostolakis E, Kalavrouziotis G et al. Surgical repair of
postinfarction ventricular septal defect: 10-year experience. World J Surg
23: 647.
1999;2
Backer CL, Winters RC, Zales VR et al. Restrictive ventricular septal
defect: how small is too small to close? [See comments]. Ann Thorac Surg
56: 101418.
1993;5
Benton JP, Barker KS. Transcatheter closure of ventricular septal defect: a
nonsurgical approach to the care of the patient with acute ventricular
septal rupture. Heart Lung 1992;2 21: 35664.
Kidd L, Driscoll DJ, Gersony WM et al. Second natural history study of
congenital heart defects. Results of treatment of patients with ventricular
septal defects. Circulation 1993;887: 13851.
Neumayer U, Stone S, Somerville J. Small ventricular septal defects in
adults. Eur Heart J 1998;1 19: 157382.
100 Questions in Cardiology 97
Seamus Cullen
Further reading
Berger F, Vogel M, Alexi-Meskishvili V et al. Comparison of results and
complications of surgical and Amplatzer device closure of atrial septal
118: 6748.
defects. J Thorac Cardiovasc Surg 1999;1
Gatzoulis MA, Redington AN, Somerville J et al. Should atrial septal
defects in adults be closed? Ann Thorac Surg 1996;661: 6579.
Rigby ML. The era of transcatheter closure of atrial septal defects. Heart
81: 2278.
1999;8
100 Questions in Cardiology 99
Seamus Cullen
Further reading
Cohen M, Fuster V, Steele PM et al. Coarctation of the aorta. Long-term
follow-up and prediction of outcome after surgical correction. Circulation
1989;880: 8405.
Gardiner HM, Celermajer DS, Sorensen KE et al. Arterial reactivity is
significantly impaired in normotensive young adults after successful
89: 174550.
repair of aortic coarctation in childhood. Circulation 1994;8
Kaplan S, Perloff JK. Survival patterns after cardiac surgery or
interventional catheterization: a broadening base. In: Perloff JK, Child JS.
Congenital heart disease in adults. London and New York: W B Saunders
Company, 1998.
100 Questions in Cardiology 101
Krishna Prasad
History
The investigation should begin with the taking of a detailed history.
This should include the construction of a family tree with at least
three generations.
Descriptive investigations
Electrocardiography. In the majority of patients, the 12-lead electro-
cardiogram (ECG) shows abnormalities such as voltage criteria
for left ventricular hypertrophy (LVH), minor intraventricular
conduction defects or bundle branch blocks. Only rarely (<5% of
cases) is the ECG completely normal.
Reading list
Spirito P, Seidman CE, McKenna WJ et al. The management of hyper-
trophic cardiomyopathy. N Engl J Med 1997;3336: 77585.
McKenna WJ, Camm AJ. Sudden death in hypertrophic cardiomy-
80: 148992.
opathy. Assessment of patients at high risk. Circulation 1989;8
Maron BJ, Bonow RO, Cannon RO III et al. Hypertrophic cardiomy-
opathy. Interrelations of clinical manifestations, pathophysiology, and
316: 7809.
therapy(1). N Engl J Med 1987;3
Maron BJ, Bonow RO, Cannon RO III et al. Hypertrophic cardiomy-
opathy. Interrelations of clinical manifestations, pathophysiology, and
316: 84452.
therapy(2). N Engl J Med 1987;3
100 Questions in Cardiology 103
Krishna Prasad
Treatment of symptoms
Typical symptoms include dyspnoea, palpitations and chest pain.
Dyspnoea is usually due to left ventricular diastolic dysfunction
while chest pain is frequently due to myocardial ischaemia. The
pain may however be atypical and occur in the absence of
demonstrable epicardial coronary disease. The treatment chosen
will depend on whether there is significant outflow tract
obstruction (outflow gradient 30mmHg). In those without
obstruction, the choice is between either a beta blocker or a calcium
antagonist, such as high dose verapamil (up to 480mg/day). In
those with obstruction a beta blocker with or without disopyramide
is usually the first choice for those patients with outflow obstruction
(~25% of patients). Both drugs reduce the outflow gradient and
improve diastolic function by their negative inotropism. Verapamil
should only be used with caution as it may worsen the outflow
obstruction (through the increased vasodilatation and consequent
ventricular emptying with contraction). Palpitations may be due to
supraventricular or ventricular arrhythmias. Supraventricular
arrhythmias including atrial fibrillation may be controlled with
beta blockers, verapamil or amiodarone.
Patients with refractory symptoms may be candidates for
invasive treatment modalities such as dual chamber pacing with a
short AV delay, alcohol septal ablation or surgical myectomy.
Surgical septal myectomy is long established and can be
combined with mitral valve replacement in patients with
associated significant mitral regurgitation. When patients present
with progressive ventricular dilatation and reduced systolic
function, cardiac transplantation may need to be considered.
104 100 Questions in Cardiology
Further reading
Seggewiss H, Gleichmann U, Faber L. Percutaneous transluminal septal
myocardial ablation in hypertrophic obstructive cardiomyopathy: acute
31:
results and 3-month follow-up in 25 patients. J Am Coll Cardiol 1998;3
2528.
Spirito P, Seidman CE, McKenna WJ et al. The management of hyper-
336: 77585.
trophic cardiomyopathy. N Engl J Med 1997 Mar 13;3
100 Questions in Cardiology 105
References
1 Nishimura RA, Trusty JM, Hayes DL et al. Dual chamber pacing for
hypertrophic cardiomyopathy: a randomised double blind crossover
29: 43541.
trial. J Am Coll Cardiol 1997;2
2 Kappenberger L, Linde C, Daubert C et al. Pacing in hypertrophic
obstructive cardiomyopathy. A randomised crossover study. PIC study
group. Eur Heart J 1997;1 18: 124956.
Further reading
Elliott PM, Sharma S, McKenna WJ. Hypertrophic cardiomyopathy. In:
Yusuf S, Cairns JA, Camm AJ et al. Evidence based cardiology. London: BMJ
Books, 1998:72243.
106 100 Questions in Cardiology
Electrocardiography
LVH + repolarisation changes Complete BBB or minor
interventricular conduction defect
in LV leads
Further reading
McKenna WJ, Spirito P, Desnos M et al. Experience from clinical genetics
in hypertrophic cardiomyopathy. Proposal for new diagnostic criteria in
77: 1302.
adult members of affected families. Heart 1997;7
108 100 Questions in Cardiology
References
1 Sugrue DD, Rodeheffer RJ, Codd MB et al. The clinical course of idio-
pathic dilated cardiomyopathy. A population-based study. Ann Intern
Med 1992;1 117: 11723.
2 Mancini DM, Fleming K, Britton N, Simson MB. Predictive value of
abnormal signal-averaged electrocardiograms in patients with non-
19: 72A.
ischemic cardiomyopathy. J Am Coll Cardiol 1992;1
3 Yi G, Keeling PJ, Goldman JH. et al. Comparison of time domain and
spectral turbulence analysis of the signal-averaged electrocardiogram
for the prediction of prognosis in idiopathic dilated cardiomyopathy.
19: 8008.
Clin Cardiol 1996;1
4 Felker GM, Thompson RE, Hare JM et al. Underlying causes and long-
term survival in patients with initially unexplained cardiomyopathy.
N Engl J Med 2000;3 342: 107784.
110 100 Questions in Cardiology
Further reading
Dec GW, Fuster V. Idiopathic dilated cardiomyopathy (review). N Engl J
Med 1994;3331: 156475.
100 Questions in Cardiology 111
Lionel H Opie
References
1 Hall AS, Murray GD, and Ball SG. Follow-up study of patients
randomly allocated ramipril or placebo for heart failure after acute
myocardial infarction: AIRE Extension (AIREX) Study. Acute
Infarction Ramipril Efficacy. Lancet 1997;3 349: 14937.
2 The SOLVD Investigators. Effects of enalapril on mortality and the
development of heart failure in asymptomatic patients with reduced
327: 68591.
left ventricular ejection fractions. N Engl J Med. 1992;3
3 Pfeffer MA, Braunwald E, Moye LA et al. Effect of captopril on
mortality and morbidity in patients with left ventricular dysfunction
after myocardial infarction. Results of the survival and ventricular
enlargement trial. N Engl J Med 1992;3 327: 66977.
4 Mancini GB, Schulzer M. Reporting risks and benefits of therapy by
use of the concepts of unqualified success and unmitigated failure:
applications to highly cited trials in cardiovascular medicine.
99: 37783.
Circulation 1999;9
100 Questions in Cardiology 113
5 Topol E. ACE inhibitors still the drug of choice for heart failure and
354: 1797.
more. Lancet 1999;3
6 Pitt B, Zannad F, Remme WJ et al. The effect of spironolactone on
morbidity and mortality in patients with severe heart failure.
Randomized Aldactone Evaluation Study Investigators. N Engl J Med
1999;3341: 70917.
114 100 Questions in Cardiology
Lionel H Opie
Nitrates alone
Nitrates on their own can be used intermittently for relief of
dyspnoea not well documented, but logical to try. For example,
intermittent sublingual or oral nitrates may benefit a patient
already on high doses of loop diuretics and an ACE inhibitor, but
who still has severe exertional or nocturnal dyspnoea, and needs
relief. The continuous use of nitrates does, however, run the risk
of nitrate tolerance, which in turn may be lessened by
combination with hydralazine.1
References
1 Gogia H, Mehra A, Parikh S et al. Prevention of tolerance to hemo-
dynamic effects of nitrates with concomitant use of hydralazine in
26: 157580.
patients with chronic heart failure. J Am Coll Cardiol 1995;2
2 Packer M, OConnor CM, Ghali JK et al. Effect of amlodipine on
morbidity and mortality in severe chronic heart failure. Prospective
Randomized Amlodipine Survival Evaluation Study Group. N Engl J
Med 1996;3335: 110714.
3 Mohler ER, Sorensen LC, Ghali JK et al. Role of cytokines in the mech-
anism of action of amlodipine: the PRAISE Heart Failure Trial.
Prospective Randomized Amlodipine Survival Evaluation. J Am Coll
30: 3541.
Cardiol 1997;3
4 Thadani U, Roden DM. FDA Panel Report. Circulation 1998;9 97: 22956.
116 100 Questions in Cardiology
Lionel H Opie
References
1 The effect of digoxin on mortality and morbidity in patients with
heart failure. The Digitalis Investigation Group. N Engl J Med
336: 52533.
1997;3
100 Questions in Cardiology 117
Rakesh Sharma
More than 25 years ago it was proposed that beta blockers may be
of benefit in heart failure1 and yet, until recently, there has been a
general reluctance amongst the medical profession to prescribe
them for this indication. This is not entirely surprising, as not too
long ago heart failure was widely considered to be a major
contraindication for the use of beta blockers. There is now consid-
erable evidence from major clinical trials that beta blockers are
capable of improving both the symptoms and prognosis of
patients with congestive heart failure (CHF).
The results from the second Cardiac Insufficiency Bisoprolol
Study (CIBIS-II) and the Metoprolol CR/XL Randomised
Intervention Trial in Heart Failure (MERIT-HF) have shown that
selective 1 antagonists (i.e. bisoprolol and metoprolol
respectively) can improve survival in patients with CHF.2,3
Carvedilol, a relatively new agent, is a non-selective beta blocker,
which also has antioxidant effects and causes vasodilatation. A
multi-centre US study showed there to be a 65% mortality
reduction with carvedilol as compared with placebo.4 At present
it is not clear whether 1 selectivity is important with respect to
therapy in CHF, and this question is currently being addressed in
the Carvedilol and Metoprolol European Trial (COMET).
In the UK, carvedilol has been licensed for the treatment of
mild to moderate CHF (NYHA class II or III) and bisoprolol is
also likely to be approved in the near future. Prior to
commencement with beta blockers, patients should be clinically
stable and maintained on standard therapy with diuretics, ACE
inhibitors +/ digoxin. There is insufficient evidence at present to
recommend the treatment of unstable or NYHA class IV patients.
The Carvedilol Prospective Randomised Cumulative Survival
Trial (COPERNICUS), which is recruiting patients with severe
CHF, (NYHA class IIIB-IV) will hopefully be able to answer this
question in the future.
Treatment should be initiated at a low dose and be increased
gradually under supervised care. The patient should be
monitored for 23 hours after the initial dose and after each
100 Questions in Cardiology 119
References
1 Swedberg K. History of beta-blockers in congestive heart failure. Heart
1998;7 79: S2930.
2 The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised
353: 913.
trial. Lancet 1999;3
3 Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL
Randomised Intervention Trial in Congestive Heart Failure (MERIT-
HF). Lancet 1999;3 353: 20017.
4 Packer M, Colucci WS, Sackner-Bernstein JD et al. Double-blind,
placebo-controlled study of the effects of carvedilol in patients with
moderate to severe heart failure. The PRECISE Trial. Prospective
Randomized Evaluation of Carvedilol on Symptoms and Exercise.
94: 27939.
Circulation 1996;9
120 100 Questions in Cardiology
Aidan Bolger
References
1 The Criteria Committee of the New York Heart Association. Criteria for
diagnosis and treatment of heart disease, 9th edition, Little, Brown and
Company, 1994.
2 Keogh AM, Baron DW, Hickie JB. Prognostic guides in patients with
idiopathic or ischemic dilated cardiomyopathy assessed for cardiac
65: 9038.
transplantation. Am J Cardiol 1990;6
122 100 Questions in Cardiology
Brendan Madden
Further reading
Elbeery JR, Owen CH, Savitt MA et al. Effects of the left ventricular
assist device on right ventricular function. J Thorac Cardiovasc Surg
1990;999: 80916.
Kormos RL, Borovetz HS, Gasior T et al. Experience with univentricular
support in mortally ill cardiac transplant candidates. Ann Thorac Surg
1990;449: 26172.
100 Questions in Cardiology 125
Brendan Madden
Further reading
Madden B. Lung transplantation. In: Hodson MR, Geddes DM, eds. Cystic
fibrosis. London: Chapman & Hall, 1994: 32946.
Madden B, Geddes D. Which patients should receive lung transplants?
48: 34652.
Monaldi Arch Chest Dis 1993;4
Murday AJ, Madden BP. Surgery for heart and lung failure. Surgery
1996;1 14: 1824
128 100 Questions in Cardiology
Brendan Madden
Further reading
Madden B, Hodson M, Tsang V et al. Intermediate term results of heart-
339: 15837.
lung transplantation for cystic fibrosis. Lancet 1992;3
Madden B, Radley-Smith R, Hodson M et al. Medium term results of
heart and lung transplantation. J Heart Lung Transplant 1992;111: S2413.
Murday AJ, Madden BP. Surgery for heart and lung failure. Surgery
1996;114: 1824.
100 Questions in Cardiology 129
Brendan Madden
Further reading
Madden B. Late complications following cardiac transplantation. Br Heart J
1994;772: 8991.
Madden B, Kamalvand K, Chan CM et al. The medical management of
patients with cystic fibrosis following heart-lung transplantation. Eur
6: 96570.
Resp J 1993;6
Madden BP. Immunocompromise and opportunistic infection in organ
16: 3740.
transplantation. Surgery 1998;1
100 Questions in Cardiology 131
Brendan Madden
Further reading
Grant SCD, Brooks NH. Accelerated graft atherosclerosis after heart
69: 46970.
transplantation. Br Heart J 1993;6
Madden B, Shenoy V, Dalrymple-Hay M et al. Absence of bradycardic
response to apnoea and hypoxia in cardiac transplant recipients with
16: 3947.
obstructive sleep apnoea. J Heart Lung Transplant 1997;1
Mann J. Graft vascular disease in heart transplant patients. Br Heart J
68: 2534.
1992;6
100 Questions in Cardiology 133
Further reading
Falk RH, Knowlton AA, Bernard SA et al. Digoxin for converting recent-
onset atrial fibrillation to sinus rhythm. Ann Intern Med 1987;1106: 5036.
Jordaens L, Trouerbach PC, Tavernier R et al. Conversion of atrial
fibrillation to sinus rhythm and rate control by digoxin in comparison to
placebo. Eur Heart J 1997;1 18: 6438.
Rawles JM, Metcalfe MJ, Jennings K. Time of occurrence, duration, and
ventricular rate of paroxysmal atrial fibrillation: the effect of digoxin. Br
Heart J 1990;663: 2247.
100 Questions in Cardiology 135
References
1 Hart RG. Warfarin in atrial fibrillation: underused in the elderly, often
inappropriately used in the young. Heart 1999;8 82: 53940.
Further reading
Stroke Prevention in Atrial Fibrillation Investigators. Adjusted dose
warfarin versus low-intensity, fixed dose warfarin plus aspirin for
high-risk patients with atrial fibrillation: stroke prevention in atrial
348: 6338.
fibrillation III. Lancet 1996;3
Stroke Prevention In Atrial Fibrillation Investigators. Stroke Prevention
84: 52739.
in Atrial Fibrillation Study. Final results. Circulation 1991;8
Hardman SM, Cowie M. Fortnightly review(:) anticoagulation in heart
disease. BMJ: 1999;3 318: 23844 (website version at www.bmj.com).
Petersen P, Botsen G, Godfredsen J et al. Placebo-controlled, randomised
trial for prevention of thromboembolic complications in chronic atrial
fibrillation. The Copenhagen AFASAK Study. Lancet 1989;ii: 1759.
100 Questions in Cardiology 137
Roy M John
References
1 Ganz LI, Friedman PL. Medical progress: supraventricular tachycardia.
332: 16273.
N Engl J Med 1995;3
2 Kay GN, Epstein AE, Dailey SM et al. Role of radiofrequency ablation
in the management of supraventricular arrhythmias: experience in 760
4: 37189.
consecutive patients. J Cardiovasc Electrophysiol 1993;4
100 Questions in Cardiology 139
Further reading
Falk RH. Proarrhythmic responses to atrial antiarrhythmic therapy. In:
Falk RH, Podrid PJ, eds. Atrial fibrillation mechanisms and management, 2nd
edition. Philadelphia: Lippincott and Raven, 1997: 371379.
Janse MJ, Allessie MA. Experimental observations on atrial fibrillation.
In: Falk RH, Podrid PJ, eds. Atrial fibrillation mechanisms and management.
2nd edition. Philadelphia: Lippincott and Raven, 1997: 5373.
Nattel S, Courtemarche, Wang Z. Functional and ionic mechanisms of
antiarrhythmic drugs in atrial fibrillation. In: Falk RH, Podrid PJ, eds.
Atrial fibrillation mechanisms and management, 2nd edition. Philadelphia:
Lippincott and Raven, 1997: 7590.
100 Questions in Cardiology 141
Further reading
Black IW, Fatkin D, Sagar KB et al. Exclusion of atrial thrombus by trans-
oesoophageal echocardiography does not preclude embolism after
cardioversion of atrial fibrillation. A multicenter study. Circulation
1994;889: 250913.
Hardman SM, Cowie M. Fortnightly review: anticoagulation in heart
disease. BMJ 1999;3 318: 23844 (website version at www.bmj.com).
Stoddard MF, Dawkins PR, Prince CR et al. Left atrial appendage
thrombus is not uncommon in patients with acute atrial fibrillation and a
recent embolic event; a transoesophageal echocardiographic study. J Am
25: 4529.
Coll Cardiol 1995;2
100 Questions in Cardiology 143
Further reading
Hardman SMC. Ventricular function in atrial fibrillation. In: Falk RH,
Podrid PJ, eds. Atrial fibrillation mechanisms and management, 2nd edition.
Philadelphia: Lippincott and Raven, 1997: 91108.
Nakazawa H, Lythall DA, Noh J et al. Is there a place for the late
cardioversion of atrial fibrillation? A long-term follow-up study of patients
with post-thyrotoxic atrial fibrillation. Eur Heart J; 21: 327333.
Van Gelder IC, Crijns HJ, Van Gilst WH et al. Prediction of uneventful
cardioversion and maintenance of sinus rhythm from direct current
electrical cardioversion of chronic atrial fibrillation and flutter. Am J
Cardiol 1991;668: 416.
Wijffels MCEF, Kirchhof CJHJ, Dorland R et al. Atrial fibrillation begets
atrial fibrillation. A study in awake chronically instrumented goats.
Circulation 1995;992: 195468.
100 Questions in Cardiology 145
Further reading
Bjerkelund CJ, Orning OM. The efficacy of anticoagulant therapy in
preventing embolism related to DC electrical cardioversion of atrial
23: 20816.
fibrillation. Am J Cardiol 1969;2
146 100 Questions in Cardiology
Further reading
Bikkina M, Alpert MA, Madhuri M et al. Prevalence of intra-atrial
76;1869.
thrombus in patients with atrial flutter. Am J Cardiol 1995;7
Irani WN, Grayburn PA, Afrii I. Prevalence of thrombus, spontaneous
echo contrast, and atrial stunning in patients undergoing cardioversion
148 100 Questions in Cardiology
Further reading
Hardman SMC, Cowie M. Fortnightly review: anticoagulation in heart
disease. BMJ 1999;3 318: 238244 (website version at www.bmj.com.)
The Stroke Prevention in Atrial Fibrillation Investigators. Predictors of
thromboembolism in atrial fibrillation I. Clinical features of thrombo-
116: 15.
embolism in atrial fibrillation. Ann Intern Med 1992;1
The Stroke Prevention in Atrial Fibrillation Investigators. Predictors of
thromboembolism in atrial fibrillation II. Echocardiographic features of
116: 612.
patients at risk. Ann Intern Med 1992;1
100 Questions in Cardiology 151
Further reading
Aschenberg W, Schiuter M, Kremer P et al. Transoesophageal two-
dimensional echocardiography for the detection of left atrial appendage
7: 1636.
thrombus. J Am Coll Cardiol 1986;7
Manning WJ, Weintraub RM, Waksmonski CA et al. Accuracy of trans-
oesophageal echocardiography for identifying left atrial thrombi. A
prospective intraoperative study. Ann Intern Med 1995;1123: 81722.
Omran H, Jung W, Rabahieh R et al. Imaging of thrombi and assessment of
left atrial appendage function: a prospective study comparing trans-
thoracic and transoesophageal echocardiography. Heart 1999;8 81: 1928.
Schweizer P, Bardos P, Erbel R et al. Detection of left atrial thrombi by
echocardiography. Br Heart J 1981;445: 14856.
100 Questions in Cardiology 153
Diana Holdright
Further reading
Nighoghossian N, Perinetti M, Barthelet M et al. Potential cardioembolic
17:
sources of stroke in patients less than 60 years of age. Eur Heart J 1996;1
5904.
Pearson AC, Labovitz AJ, Tatineni S et al. Superiority of trans-
oesophageal echocardiography in detecting cardiac source of embolism
in patients with cerebral ischaemia of uncertain aetiology. J Am Coll
17: 6672.
Cardiol 1991;1
100 Questions in Cardiology 155
Diana Holdright
References
1 Cabanes L, Mas JL, Cohen A et al. Atrial septal aneurysm and patent
foramen ovale as risk factors for cryptogenic stroke in patients less than
24: 186573.
55 years of age. Stroke 1993;2
2 Lethen H, Flachskampf FA, Schneider R et al. Frequency of deep vein
thrombosis in patients with patent foramen ovale and ischemic stroke
or transient ischemic attack. Am J Cardiol 1997;880: 10669.
100 Questions in Cardiology 157
ECG
24 hour ECG
24 hour BP
Carotid sinus massage supine and erect (only if negative
supine)
External loop recorder
Electrophysiological studies
Head up tilt test
CT head and EEG if appropriate
Implantable loop recorder
158 100 Questions in Cardiology
Cardiogenic
Structural heart disease aortic Syncope on exertion
and mitral stenosis
Ischaemic heart disease
Non-cardiovascular
Seizures Witness fitting
Cerebrovascular disease Associated with vertigo, dysarthria,
diplopia or other motor and sensory
symptoms of brain stem ischaemia
Subclavian steal Syncope with arm exercise
Modified from Kenny RA ed., Syncope in the older patient. Chapman and Hall
Medical 1996.
100 Questions in Cardiology 159
References
1 Kenny RA, Ingram A, Bayliss J et al. Head-up tilt: a useful test for
investigating unexplained syncope. Lancet 1986;ii: 13524.
2 Parry SW, Kenny RA. The management of vasovagal syncope. Q J Med
92: 697705.
1999;9
Further reading
Kenny RA, OShea D, Parry SW. The Newcastle protocols for head-up tilt
table testing in the diagnosis of vasovagal syncope and related disorders.
Heart 2000;883: 5649.
160 100 Questions in Cardiology
Still symptomatic
Salt loading
Still symptomatic
Still symptomatic Blocker/SSRI
Still symptomatic/
cannot tolerate/
contraindicated
Fludrocortisone
and/or Midodrine
References
1 Brady PA, Shen WK. Syncope evaluation in the elderly. Am J Geriatr
8: 11524.
Cardiol 1999;8
2 Kapoor W. Syncope in older persons. J Am Geriatr Soc 1994;442: 42636.
99: 92105.
3 Lipsitz L. Syncope in the elderly. Ann Intern Med 1983;9
4 Kapoor W. Diagnostic evaluation of syncope. Am J Med 1991;9 90: 91106.
5 Gibson TC, Heitzman MK. Diagnostic efficacy of 24 hour electro-
cardiographic monitoring for syncope. Am J Cardiol 1984;5 53: 101317.
6 Clark PI, Glasser SO, Spoto E. Arrhythmias detected by ambulatory
monitoring; lack of correlation with symptoms of dizziness and
77: 7225.
syncope. Chest 1990;7
100 Questions in Cardiology 163
Simon Sporton
Further reading
Gregoratos G, Cheitlin MD, Conill A et al. ACC/AHA guidelines for
implantation of cardiac pacemakers and antiarrhythmia devices. J Am Coll
31: 1175209.
Cardiol 1998;3
McAnulty JH, Rahimtoola SH, Murphy E et al. Natural history of high-
307: 13743.
risk bundle-branch block. N Engl J Med 1982;3
166 100 Questions in Cardiology
Alistair Slade
Many pacing enthusiasts argue that there are very few indications
for VVI pacing, perhaps confining its role to the very elderly with
established atrial fibrillation and documented pauses. Dual
chamber pacing (or more accurately physiological pacing which
may include single chamber atrial devices) is the preferred mode
in most common indications for pacemaker implantation.
The British Pacing group published its recommendations in
1991.1 These have led to widespread if gradual change in British
pacing practice. Physiological pacemakers can be recommended
in sinus node disease on the basis of many retrospective studies
and one prospective study.2 Ongoing prospective studies will
clarify the true role of physiological pacing in the elderly with AV
conduction disease. The British guidelines are similar to those in
the United States. A more comprehensive guide to pacemaker
implantation is given by the ACC/AHA joint guidelines which
supply the level of evidence for each recommendation and a
comprehensive reference list.3
Pacemaker implantation is a remarkably safe procedure.
Mortality is minimal and occurs due to unrecognised
pneumothorax, pericardial tamponade or great vessel trauma.
Complications at implant are those of subclavian puncture,
particularly pneumothorax, although these can be avoided if the
cephalic approach is used. There is some long term evidence that
the cephalic approach may avoid chronic lead failure in
polyurethane leads due to subclavian crush injury. Haematoma
requiring re-operation should occur in less than 1%. Infection
leading to explant similarly occurs in approximately 1%. Acute
lead displacement should be less than 1% for ventricular leads
and 12% for atrial leads.
References
1 Clark M, Sutton R, Ward DE et al. Recommendations for pacemaker
prescription for symptomatic bradycardia. Report of a working party
of the British Pacing and Electrophysiology Group. Br Heart J
66: 18591.
1991;6
100 Questions in Cardiology 167
Alistair Slade
Electric fences
Nobody should touch an electric fence but should electric shock
occur it would be wise to have the system checked by formal
interrogation in case electrical mode reversion has occurred.
Mobile phones
Mobile phones have been extensively investigated in terms of
interaction with implanted devices. Analogue phones do not interact
with implanted devices but more modern digital devices have the
potential to interfere with pacing systems when utilised within a
field of 1015 cm. Pacemaker patients with mobile phones are
therefore advised to carry mobile telephones on the opposite side
100 Questions in Cardiology 169
of the body from the site of the device implant and should hold the
device to the opposite ear.
Further reading
Gimbel JR, Johnson D, Levine PA et al. Safe performance of magnetic
resonance imaging on five patients with permanent cardiac pacemakers.
19: 91319.
Pacing Clin Electrophysiol 1996;1
Hayes DL, Wang PJ, Reynolds DW et al. Interference with cardiac pace-
336: 14739.
makers by cellular telephones. N Engl J Med 1997;3
170 100 Questions in Cardiology
Alistair Slade
Simon Sporton
Further reading
Buxton AE, Marchlinski FE, Waxman HL et al. Prognostic factors in
nonsustained ventricular tachycardia. Am J Cardiol 1984;553: 12759.
Campbell RWF. Ventricular ectopic beats and nonsustained ventricular
tachycardia. Lancet 1993;3341: 14548.
Moss AJ, Hall WJ, Cannom DS et al. Improved survival with an
implanted defibrillator in patients with coronary artery disease at high
335: 193340.
risk for ventricular arrhythmia. N Engl J Med 1996;3
100 Questions in Cardiology 173
Simon Sporton
Further reading
Haverkamp W, Shenasa M, Borggrefe M et al. Torsade de pointes. In: Zipes
DP, Jalife J, eds. Cardiac electrophysiology: from cell to bedside. WB Saunders,
1995: Chapter 79.
Tzivoni D, Banai S, Schuger C et al. Treatment of torsade de pointes with
magnesium sulfate. Circulation 1988;7 77: 3927.
100 Questions in Cardiology 175
J Benhorin
Further Reading
Benhorin J, Taub R, Goldmit M et al. Effects of flecainide in patients with
a new SCN5A mutation: mutation specific therapy for long QT
syndrome? Circulation 2000;1 101: 1698706.
Jiang C, Atkinson D, Towbin JA et al. Two long QT syndrome loci map to
chromosomes 3 and 7 with evidence for further heterogeneity. Nat Genet
1994;88: 1417.
Keating MT, Atkinson D, Dunn C et al. Linkage of a cardiac arrhythmia,
the long QT syndrome, and the Harvey ras-1 gene. Science 1991;2 252:
7046.
Moss AJ, Schwartz PJ, Crampton RS et al. The long QT syndrome:
prospective longitudinal study of 328 families. Circulation 1991;8 84 :
113644.
Schott JJ, Charpentier F, Pettier S et al. Mapping of a gene for the long QT
syndrome to chromosome 4q2527. Am J Hum Genet 1995;5 57: 111422.
Schwartz PJ, Priori SG, Locati EH et al. Long QT syndrome patients with
mutations on the SCN5A and HERG genes have differential responses to
Na+ channel blockade and to increases in heart rate: implications for
gene-specific therapy. Circulation 1995;9 92: 33816.
Vincent GM, Timothy KW. The spectrum of symptoms and QT intervals
in carriers of the gene for the long QT syndrome. N Engl J Med 1992;3 327:
84652.
100 Questions in Cardiology 177
Further reading
27:
Basilico FC. Cardiovascular disease in athletes. Am J Sports Med 1999;2
1081.
Corrado D, Basso C, Schiavon M et al. Screening for hypertrophic
cardiomyopathy in young athletes. N Engl J Med 1998;3339: 3649.
100 Questions in Cardiology 179
Daniel E Hillman
References
1 Amiodarone Trials Meta-Analysis Investigators. Effect of prophylactic
amiodarone on mortality after acute myocardial infarction and in
congestive heart failure: meta-analysis of individual data from 6500
350: 141724.
patients in randomized trials. Lancet 1997;3
2 Vorperian VR, Harighurst TC, Miller S et al. Adverse effects of low dose
amiodarone: a meta-analysis. J Am Coll Cardiol 1997;330: 7918.
3 Gleadhill IC, Wise RA, Schonfeld S et al. Serial lung function testing in
patients treated with amiodarone: a prospective study. Am J Med 1989
86: 410.
;8
100 Questions in Cardiology 181
Roy M John
References
1 Buxton AE, Lee KL, Fisher JD et al. A randomized study of the
prevention of sudden death in patients with coronary artery disease. N
Engl J Med 1999;3341: 188290.
2 Moss AJ, Hall WJ, Cannom DS et al. Improved survival with an
implanted defibrillator in patients with coronary disease at high risk
335: 193340.
for ventricular arrhythmia. N Engl J Med 1996;3
3 Mushlin AI, Hall WJ, Zwanziger J et al. The cost effectiveness of
automatic implantable cardiac defibrillators: results from MADIT.
Multicenter Automatic Defibrillator Implantation Trial. Circulation
1998;997: 212935.
4 Horowitz L. Safety of electrophysiologic studies. Circulation
1986;773(suppl): II2831.
184 100 Questions in Cardiology
Studies in the early 1980s showed that recurrence rates were high
for patients presenting with a malignant arrhythmia unrelated to
myocardial ischaemia or infarction. Survivors of cardiac arrest,
those presenting with sustained monomorphic VT and un-
explained syncope in the presence of heart disease clearly are
patients at high risk for sudden cardiac death. A series of clinical
trials completed in the recent past have confirmed the uniform
survival benefit from ICD therapy in such patients (AVID, CASH,
CIDS) when compared to therapy with amiodarone or sotalol. In
the largest prospective randomised trial (Antiarrhythmics versus
Implantable Defibrillators Trial AVID trial), the ICD reduced
mortality by 39% at 1 year and 31% at 3 years. Most patients
randomised to the antiarrhythmic arm of the trial were treated
with amiodarone.
With remarkable improvements in ICD technology allowing
easier implantation, the ICD is being embraced increasingly and
earlier in the course of cardiac disease. Attention has now
turned to primary prevention of sudden death. For patients with
asymptomatic non-sustained VT, there appears to be a clear
survival benefit from ICD in the presence of a remote myocardial
infarction, LVEF <40%, and inducible VT at electro-
physiological study (MADIT, MUSTT). Interestingly, this
benefit cannot be extrapolated to patients without non-
sustained VT or inducible VT. The CABG patch trial that
randomised patients with LVEF <36% and positive signal
averaged ECG to ICD or not during elective bypass surgery
failed to show a survival benefit. The role of the ICD in primary
prevention of sudden death in non-ischaemic dilated cardiomy-
opathy is also unclear at this time. Clinical trials are in progress.
The benefit from an ICD appears to be greatest for patients with
severe LV function and additive to conventional therapy with
ACE inhibitors and beta adrenergic blockers. In the AVID trial for
example, survival benefit with ICD was observed only when
LVEF was less than 35%. Similarly, in the primary prevention
trials, the mean LVEF was 30%. One could advance the argument
100 Questions in Cardiology 185
that the ICD should be reserved for those with the worst LV
function. Unfortunately, such patients have competing causes for
mortality such as pump failure and electromechanical
dissociation that are responsible for 50% of deaths. On the other
hand, patients with little or no impairment of LV function and a
single tachyarrhythmic event usually have late and rare recur-
rence leading to sudden death. An ICD can potentially restore
them to near normal life expectancy in the absence of ongoing
myopathic process. The long term studies requiring more than
one life span of an ICD are not available to define the true value of
ICD therapy in such patients.
Although the ability of the implantable cardioverter de-
fibrillator (ICD) to terminate potentially lethal ventricular
arrhythmias is well acknowledged there is less consensus as to
whom should receive an ICD. A good place to start is the
American College of Cardiology/American Heart Association
Practice Guidelines for Arrhythmia Devices.1 There are three
classes of indications: class one, where there is evidence and/or
general agreement that the treatment is beneficial, useful and
effective; class two, where there is conflicting evidence or a diver-
gence of opinion; and class three, where there is evidence and
general agreement that a treatment is not useful or effective.
The size of the risk reduction to patients and the degree of life
prolongation are only moderate in the trials showing benefit of
ICD over antiarrhythmic therapy. The cost per life year saved is
also wildly different in these trials giving us conflicting
information, e.g. $22,800 (MADIT) and $114,917 (AVID).
There is a wide variation in implant rates across the world
(Table 87.1).
Reference
1 Garrett C. A new evidence base for implantable cardioverter defibrillator
therapy. Eur Heart J 1998;1 19: 18991.
2 National Institute for Clinical Excellence. Guidance on the use of implantable
cardioverter defibrillators for arrhythmias. Technology Appraisal Guidance
No. 11, September 2000. (www.nice.org.uk)
Further reading
Bigger JT. Coronary artery bypass grafting (CABG)-patch trial. N Engl J
Med 1997;3 337: 156975.
Gregoratos G, Cheitlin MD, Conill A et al. The American College of
Cardiology/American Heart Association practice guidelines for
31: 1175209.
arrhythmia devices. J Am Coll Cardiol 1998;3
Moss AJ, Hall WJ, Cannom DS et al. Improved survival with an
implanted defibrillator in patients with coronary disease at high risk for
ventricular arrhythmia. The Multi-Center Automated Defibrillator
Implantation (MADIT) Trial. N Engl J Med 1996;3 335: 193340.
Zipes DP et al. A comparison of antiarrhythmic-drug therapy with
implantable defibrillators in patients resuscitated from near-fatal
ventricular arrhythmias. The anti-arrhythmics versus implantable defib-
337: 157683.
rillators (AVID). N Engl J Med 1997;3
188 100 Questions in Cardiology
Roy M John
Mark Squirrell
References
1 Troup P, Chapman P, Wetherbee J et al. Clinical features of AICD
system infections. Circulation 1988;778:155.
2 Badger JM, Morris PLP. Observations of a support group for automatic
implantable cardioverter defibrillator recipients and their spouses.
Heart Lung 1989;118: 23843.
3 Teplitz L, Egenes KJ, Brask L. Life after sudden death: the
development of a support group for automatic implantable
4: 2032.
cardioverter defibrillator patients. J Cardiovasc Nurs 1990;4
192 100 Questions in Cardiology
Sinus tachycardia
Lead fracture
Diaphragmatic muscle sensing
Electromagnetic interference.
References
1 Nunain SO, Roelke M, Trouton T et al. Limitations and late complications
of third-generation automatic cardioverter-defibrillators. Circulation
1995;991: 220413.
2 Pacifico A, Hohnloser SH, Williams JH et al. Prevention of implantable-
defibrillator shocks by treatment with sotalol. N Engl J Med 1999;3 340:
185562.
194 100 Questions in Cardiology
Sara Thorne
Maternal risk
This relates to the degree of ventricular dysfunction and the
ability to adapt to altered haemodynamics. Risk and management
can therefore be discussed in relation to New York Heart
Association (NYHA) functional class:
NYHA I-II
Should manage pregnancy without difficulty (maternal
mortality 0.4%)
May require admission for rest and diuretic therapy
Venous thrombosis prophylaxis with heparin for patients on
bedrest
NYHA III
At significant risk (maternal mortality for NYHA III-IV 6.8%)
Planned hospital admission for rest, treatment of heart failure
and monitoring
Risk of deterioration in ventricular function which may not
improve post-partum.
Early delivery if heart failure progressive despite optimal in-
patient management
NYHA IV
Should be advised not to become pregnant. Therapeutic
abortion should be considered.
100 Questions in Cardiology 195
Fetal risk
Fetal risk should be considered in terms of two factors:
Further reading
Oakley CM. Management of pre-existing disorders in pregnancy: heart
37: 10211.
disease. Presc J 1997;3
Salazar E, Izaguirre R, Verdejo J et al. Failure of adjusted doses of sub-
cutaneous doses of heparin to prevent thromboembolic phenomena in
pregnant patients with mechanical cardiac valve prostheses. J Am Coll
27: 1698703.
Cardiol 1996;2
196 100 Questions in Cardiology
Sara Thorne
Mechanical valves
Anticoagulation is the issue here: in particular, the risk of
warfarin embryopathy vs risk of valve thrombosis.
Note:
1 Mitral tilting disc prostheses at particular risk: fatal thrombotic
occlusion of these valves in pregnant women described despite
well-controlled heparin anticoagulation
2 Risk of significant warfarin embryopathy not as high as
previously thought, especially if the mother achieves adequate
anticoagulation on <5mg warfarin.
3 No data on low molecular weight heparin in this situation, so
its use cannot be recommended.
Further reading
Salazar E, Izaguirre R, Verdejo J et al. Failure of adjusted doses of sub-
cutaneous doses of heparin to prevent thromboembolic phenomena in
pregnant patients with mechanical cardiac valve prostheses. J Am Coll
27: 1698703.
Cardiol 1996;2
198 100 Questions in Cardiology
Sara Thorne
Further reading
Connelly MS, Webb GD, Someville J et al. Canadian consensus
14 :
conference on adult congenital heart disease. Can J Cardiol 1998;1
395452.
Oakley CM. Management of pre-existing disorders in pregnancy: heart
37: 10211.
disease. Presc J 1997;3
200 100 Questions in Cardiology
Rachael James
Management
Women who do not wish to continue warfarin throughout preg-
nancy can be reassured that conceiving on warfarin appears safe
but conversion to heparin, to avoid the risk of embryopathy,
needs to be carried out by 6 weeks. Breast-feeding on either
warfarin or heparin is safe. Possible regimes include:
References
1 Oakley CM. Anticoagulants in pregnancy. Br Heart J 1995;774: 10711.
2 Cotrufo M, de Luca TSL, Calabro R et al. Coumarin anticoagulation
during pregnancy in patients with mechanical valve prostheses. Eur J
Cardiothorac Surg 1991;55: 3005.
3 Maternal and Neonatal Haemostasis Working Party of the Haemostasis
and Thrombosis Task Force. Guidelines on the prevention, investi-
gation and management of thrombosis associated with pregnancy. J
Clin Pathol 1993;446: 48996.
4 Ginsberg JS, Hirsh J. Use of antithrombotic agents during pregnancy.
Chest 1995;1108(suppl 4): 305S11S.
5 Salazar E, Izaguirre R, Verdejo J et al. Failure of adjusted doses of
subcutaneous heparin to prevent thromboembolic phenomena in
pregnant patients with mechanical cardiac valve prostheses. J Am Coll
Cardiol 1996;227: 1698703.
6 Hirsh J. Low-molecular weight heparin for the treatment of venous
thromboembolism. Am Heart J 1998;1 135(suppl 6): S33642.
202 100 Questions in Cardiology
Matthew Streetly
Further reading
Ansell J. Oral anticoagulants for the treatment of venous thrombolism.
11: 64750.
Ball Clin Haematol 1998;1
Haemostasis and Thrombosis Task Force. Guidelines on oral anti-
coagulation: third edition. Br J Haematol 1998;1101: 37487.
Kearon C. Perioperative management of long-term anticoagulation.
Semin Thromb Haem 1998;2 24 (suppl 1): 7783.
Kearon C, Hirsch J. Management of anticoagulation before and after
elective surgery. N Engl J Med 1997;3336: 150611.
204 100 Questions in Cardiology
Marc R Moon
2. Persistent sepsis
This is defined as failure to achieve bloodstream sterility after 35
days of appropriate antibiotic therapy or a lack of clinical
improvement after one week.
4. Extravalvular extension
Annular abscesses are more common with aortic (25-50%) than
mitral (1-5%) infections; in either case, surgical intervention is
preferred (survival: 25% medical, 60-80% surgical). Conduction
disturbances are a typical manifestation.
5. Peripheral embolisation
This is common (30-40%), but the incidence falls dramatically
following initiation of antibiotic therapy. Medical therapy is
appropriate for asymptomatic aortic or small vegetations. Surgical
therapy is indicated for recurrent or multiple embolisation, large
mobile mitral vegetations or vegetations that increase in size
despite appropriate medical therapy.
6. Cerebral embolisation
Operation within 24 hours of an infarct carries a 50% exacerbation
and 67% mortality rate, but the risk falls after two weeks (exacer-
bation <10%, mortality <20%). Following a bland infarct, it is
ideal to wait 23 weeks unless haemodynamic compromise
obligates early surgical intervention. Following a haemorrhagic
infarct, operation should be postponed as long as possible (46
weeks).
Further reading
Moon MR, Stinson EB, Miller DC. Surgical treatment of endocarditis.
40: 23964.
Prog Cardiovasc Dis 1997;4
206 100 Questions in Cardiology
Peter Wilson
References
1 Tornos P, Sanz E, Permanyer-Miralda G et al. Late prosthetic valve endo-
carditis. Immediate and long term prognosis. Chest 1992;1101: 3741.
2 Tornos MP, Permanyer-Miralda G, Olona M et al. Long-term
complications of native valve infective endocarditis in non-addicts.
Ann Intern Med 1992;1117: 56772.
3 Verheul HA, Van Den Brink RBA, Van Vreeland T et al. Effects of
changes in management of active infective endocarditis on outcome in
72: 6827.
a 25 year period. Am J Cardiol 1993;7
100 Questions in Cardiology 207
Peter Wilson
References
1 Barnes PD, Crook DWM. Culture negative endocarditis. J Infect
1997;335: 20913.
2 Stein DS, Nelson KE. Endocarditis due to nutritionally deficient strepto-
9: 90816.
cocci: therapeutic dilemma. Rev Infect Dis 1987;9
3 Raoult D, Fournier PE, Drancourt M et al. Diagnosis of 22 new cases of
Bartonella endocarditis. Ann Intern Med 1996;1 125: 64652
4 Aronson MD, Bor DH. Blood cultures. Ann Intern Med 1987;1 106: 24653.
208 100 Questions in Cardiology
Peter Wilson
References
1 Van Der Meer JTM, Van Wijk W, Thompson J et al. Efficacy of antibiotic
prophylaxis for prevention of native valve endocarditis. Lancet
1992;3339: 1359.
2 Leport C, Horstkotte D, Burckhardt D, and the group of experts of the
International Society for Chemotherapy. Antibiotic prophylaxis for
infective endocarditis from an international group of experts towards a
European consensus. Eur Heart J 1995;1 16(suppl B): 12631.
Further reading
Dajani AS, Bisno AL, Chung KJ et al. Prevention of bacterial endo-
carditis. Recommendations by the American Heart Association. JAMA
1990;2264: 291922.
210 100 Questions in Cardiology
Matthew Barnard
Step 9
All patients have now been assigned to surgery, angiography or
non-invasive testing. The results of non-invasive tests must
incorporate both the absolute result (positive or negative) and
quantification of the result (e.g. magnitude and regional location
of ischaemic area). These results will determine which patients
should proceed to angiography. Significant abnormalities require
further assessment by angiography. Minor and intermediate
abnormalities only require further assessment in the presence of
low functional capacity or major surgical risk.
It should be noted that, at least in high-risk patients under-
going vascular surgery, beta blockade is the only medical inter-
vention proven to have major impact on outcome.2
Reference
1 ACC/AHA guidelines for perioperative cardiovascular evaluation for
93: 12801317.
noncardiac surgery. Circulation 1996;9
2 Poldermans D, Boersma E, Bax JJ et al. The effect of bisoprolol on peri-
operative mortality and myocardial infarction in high-risk patients
undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk.
341: 178994.
N Engl J Med 1999;3
212 100 Questions in Cardiology
Matthew Barnard
1 Clinical predictors
2 Functional status
3 Surgical magnitude
4 Results of non-invasive investigations.
Detsky
Class 1 015 5
Class 2 2030 27
Class 3 >30 60
Eagle
Class 1 0 03
Class 2 12 616
Class 3 >3 2950
*Modified from Palda VA, Detsky AS. Perioperative assessment and management
127: 31328.
of risk from coronary artery disease. Ann Intern Med 1997;1
214 100 Questions in Cardiology
Intermediate
Carotid endarterectomy
Head and neck
Intraperitoneal and intrathoracic
Orthopaedic
Prostate
Low
Endoscopic procedures
Superficial procedures
Breast
*Modified from ACC/AHA guidelines for perioperative cardiovascular
93: 1280317.
evaluation for noncardiac surgery. Circulation 1996;9
References
1 Mangano DT, Browner WS, Hollenberg M et al. Association of peri-
operative myocardial ischemia with cardiac morbidity and mortality in
men undergoing noncardiac surgery. The Study of Perioperative
Ischemia Research Group. N Engl J Med 1990;3 323: 17818.
2 Mangano DT, Golman L. Preoperative assessment of patients with known
333: 17506.
or suspected coronary artery disease. N Engl J Med 1995;3
3 Palda VA, Detsky AS. Perioperative assessment and management of
risk from coronary artery disease. Ann Intern Med 1997;1 127: 31328.
4 ACC/AHA guidelines for perioperative cardiovascular evaluation for
noncardiac surgery. Circulation 1996;993: 1280317.
5 LItalien GJ, Paul DS, Hendel RC et al. Development and validation of
a Bayesian model for perioperative cardiac risk assessment in a cohort
of 1081 vascular surgical candidates. J Am Coll Cardiol 1996;227: 77986.
Index
216
Index 217
fish oil capsules, high dose 21 pulmonary, pregnancy and 198, 199
flecainide secondary causes, screening for 56
atrial fibrillation cardioversion 139 treatment
ICD patients 189 decisions 79
paroxysmal atrial fibrillation 133 see also antihypertensive therapy
flying after myocardial infarction 667 24-hour monitoring 34
foramen ovale, patent, reference for white coat 4
closure 1556 Hypertension Optimal Treatment
Fragmin During Instability in (HOT) study 8
Coronary Artery Disease hypertensive encephalopathy 15
(FRISC) trial 38, 45 hyperthyroidism, amiodarone-
Framingham Heart Study, mortality induced 17980
data 1201 hypertrophic cardiomyopathy (HCM)
investigation/diagnosis 1012
gemfibrozil 21, 223 children 107
gene therapy, prevention of restenosis relatives of patients 1067
following PTCA 489 sudden death and 177, 178
GISSI-2 study 52 risk factors 1012, 104
glibenclamide 82 treatment 1034
glycaemia, control following CABG pacing 105
823 hypothyroidism, amiodarone-induced
glyceryl trinitrate (GTN), sublingual 35 180
glycoprotein IIb/IIIa inhibitors,
unstable angina 44 immunosuppressive therapy,
GUSTO trials 52, 53 transplant patients 12930
GUSTO IIa 38 implantable cardioverter defibrillator
GUSTO IIb angioplasty substudy 55 (ICD)
follow-up of patients 1901
heart failure hypertrophic cardiomyopathy 104
ACE inhibitors and AT1-receptor indications for 1857
blockers 11113 VT stimulation studies 182, 183
beta blockers 116, 11819 interaction with drugs 189
chronic, role of vasodilators 11415 long QT syndrome 175
congestive, endocarditis in 204 multiple shocks from 1923
digoxin in 11617 non-sustained ventricular
morbidity and mortality 2067 tachycardia 1712
prognosis, NYHA functional patient management 1889
capacity score and 1202 survival benefits 1845
Heart Outcomes Prevention implantable loop recorder (ILR) 162
Evaluation (HOPE) study 64 insulin, following CABG 823
heparin internal mammary artery grafts 767
elective surgery in mechanical heart ISIS-3 study 52
valve patients 2023 isosorbide dinitrate (ISDN) 35
unstable angina 44 isosorbide mononitrate (ISMN) 35
use in pregnancy 196, 197, 198,
2001 labetalol, hypertensive
hydralazine, malignant hypertension 15 encephalopathy 1516
hypercholesterolaemia lanoteplase 53
familial, drug treatment 20, 21 Late Assessment of Thrombolytic
lipid-lowering therapy 20, 21 Efficiency (LATE) study 51
asymptomatic patients 17 Left Ventricular Assist Device (LVAD)
hypertension 1234
after aortic coarctation repair 99100 left ventricular function, impaired,
cardiovascular risks 12, 8 ACE-inhibitor treatment 111
blood pressure lowering and 7 lipid-lowering therapy
essential, management plan 14 asymptomatic
malignant, management 1516 hypercholesterolaemia 17
220 Index