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Concise Cardiology
Concise Cardiology
Evidence-Based Handbook,
1st Edition 2008
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Table Of Contents
1. cover ......................................................................................................................................... 2
2. Copyright ................................................................................................................................... 4
3. contents .................................................................................................................................... 8
4. Editor......................................................................................................................................... 8
5. Dedication ............................................................................................................................... 13
6. FOREWORD ............................................................................................................................. 14
7. CHAPTER 1 - Physical Examination of the Cardiovascular System .......................................... 14
8. CHAPTER 2 - Stress Testing ..................................................................................................... 37
9. CHAPTER 3 - Chest Pain and the Acute Coronary Syndromes ................................................ 60
10. CHAPTER 4 - Cardiogenic Shock ............................................................................................ 96
11. CHAPTER 5 - Bradyarrhythmias and Pacing ........................................................................ 108
12. CHAPTER 6 - Wide and Narrow Complex Tachyarrhythmias .............................................. 128
13. CHAPTER 7 - Sudden Cardiac Death and ICD Therapy ........................................................ 141
14. CHAPTER 8 - Atrial Fibrillation ............................................................................................ 156
15. CHAPTER 9 - Heart Failure .................................................................................................. 185
16. CHAPTER 10 - Pulmonary Hypertension ............................................................................. 213
17. CHAPTER 11 - Transplant Medicine .................................................................................... 231
18. CHAPTER 12 - Valvular Diseases ......................................................................................... 250
19. CHAPTER 13 - Endocarditis ................................................................................................. 300
20. CHAPTER 14 - Pericardial Disease ....................................................................................... 309
21. Appendix ............................................................................................................................. 313
21.1 APPENDIX A - Central Vascular Access Techniques ...................................................... 313
21.2 APPENDIX B - Clinical Pharmacology ............................................................................ 334
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
1. cover
2
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
3
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
2. Copyright
Lippincott Williams & Wilkins
Philadelphia
978-0-7817-8509-9
0-7817-8509-X
P.iv
Philadelphia, PA 19106
LWW.com
All rights reserved. This book is protected by copyright. No part of this book may be reproduced in any
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system without written permission from the copyright owner, except for brief quotations embodied in
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Concise cardiology : an evidence-based handbook / editor, David V. Daniels; associate editors, Stanley
p. ; cm.
ISBN 978-0-7817-8509-9
RC669.15C66 2008
616.1′2—dc22
2008009965
Care has been taken to confirm the accuracy of the information presented and to describe generally
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The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage
set forth in this text are in accordance with current recommendations and practice at the time of
publication. However, in view of ongoing research, changes in government regulations, and the
constant flow of information relating to drug therapy and drug reactions, the reader is urged to check
the package insert for each drug for any change in indications and dosage and for added warnings and
precautions. This is particularly important when the recommended agent is a new or infrequently
employed drug.
Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA)
clearance for limited use in restricted research settings. It is the responsibility of health care providers
to ascertain the FDA status of each drug or device planned for use in their clinical practice.
The publishers have made every effort to trace copyright holders for borrowed material. If they have
inadvertently overlooked any, they will be pleased to make the necessary arrangements at the first
opportunity.
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
3. contents
4. Editor
Editor
David V. Daniels MD
Stanford, California
Associate Editors
Stanley G. Rockson MD
Stanford, California
Randall Vagelos MD
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Cardiovascular Medicine
Stanford, California
P.ix
CONTRIBUTORS
Amin Al-Ahmad MD
Stanford University
Stanford, California
Cardiovascular Medicine
Stanford University
Stanford, California
Todd J. Brinton MD
Lecturer in Bioengineering
Interventional Cardiology
Stanford, California
Stanford, California
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
University of California
Clarke G. Daniels MD
David V. Daniels MD
Stanford, California
P.x
Ramona L. Doyle MD
Associate Professor
Department of Medicine
Stanford University
Stanford, California
Stanford University
Stanford, California
Anurag Gupta MD
Electrophysiology Fellow
Stanford, California
François Haddad MD
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Attending Cardiologist
Stanford, California
Henry Hsia MD
Stanford, California
David Kao MD
Stanford University
Stanford, California
David P. Lee MD
Assistant Professor
Stanford, California
P.xi
Nurse Practitioner
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Stanford University
Stanford, California
Clinical Pharmacist
(Cardiovascular) Pharmacy
Stanford, California
Shriram Nallamshetty MD
Cardiology Fellow
Boston, Massachusetts
Stanley G. Rockson MD
Stanford, California
Stanford, California
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
P.xii
Randall Vagelos MD
Cardiovascular Medicine
Stanford University
Stanford, California
Paul J. Wang
Professor of Medicine
Stanford, California
Stanford, California
5. Dedication
First, to Mom and Dad: You are the best parents anyone could ever hope for and you will always be
with me. I am forever grateful for the infinite lessons, constant patience, and values you have
bestowed upon me. You always had faith in me, often when I was unsure of myself, and I can only
aspire to have the same courage and compassion with my own children someday.
My sister Ana, my brother-in law Bart, and my princess Stefanie: We are family forever, and it is one
of the only things in this world I am truly sure of. I am blessed with best friends that are closer than
many boys are to their own brothers and I hope to never take that for granted.
I want to thank the many great teachers in my life, especially the ones who nurtured a rigorous
academic approach tempered with habitual common sense. These are lessons that no textbook can
confer.
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
6. FOREWORD
To study the phenomenon of disease without books is to sail an uncharted sea, while to study books
While we recognize the comprehensive nature of classic textbooks like Braunwald's Heart Disease and
cutting-edge resources like Up-to-Date, a void still remains in the cardiology literature. Residents in
training, cardiology fellows, and those in practice alike operate in a fast-paced environment where
realistically the ability to look something up depends on having a resource that can be consulted in the
time it takes the elevator to go from floor 1 to floor 3. Such a resource must be concise and current,
and must present the most reasonable clinical approach and the landmark evidence to back it up.
Written as a collaborative effort by residents and fellows in training and experienced attending
physicians, Concise Cardiology: An Evidence-Based Handbook will serve a niche in our field. It is a truly
comprehensive handbook that covers topics from acute coronary syndromes to electrophysiology to
valvular heart disease. Each chapter begins with a robust dissection of the clinical problem, starting
with relevant historical and physical exam findings to aid in the diagnostic process. Therapies are
organized in chart format where appropriate, presenting indications, patient selection, and side
effects. Choice of treatment is of course influenced by the best available evidence, and this handbook
delivers—not only with a strong base of recommendations from the ACC/AHA but also with a review of
“landmark clinical trials,” from the historical data to the latest therapies. One of the most unique
aspects of our handbook is this easy-to-use, no-nonsense tabular presentation of the landmark evidence
that shapes cardiology today. The evidence is pared down to the most critical information clinicians
need to make rational treatment decisions, such as level of evidence, patient population studied,
intervention, background therapies, outcomes, and number needed to treat. The initial portion of each
chapter focuses on management and is targeted primarily toward residents, while the landmark
Alan Yeung
Professor of Medicine
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Clarke G. Daniels
David V. Daniels
Kamalendu Chatterjee
An 81-year-old patient presented to the emergency room complaining of weakness and fatigue. His
family had noted mild disorientation. Physical exam revealed blood pressure (BP) 113/73, temperature
100°F, and heart rate (HR) 130. The lungs were clear. He was given 2 liters of intravenous normal
saline. The chest x-ray subsequently showed pulmonary congestion, and the patient was found to have
Doctors at all levels of training and experience make errors in diagnosis. Every doctor has made many
mistakes for a variety of reasons; many of these are unavoidable. Failure to recognize heart failure
when physical findings are present is not a rare occurrence. I believe this also applies to other common
cardiovascular disorders. Did the doctor in this hypothetical narrative know how to evaluate the venous
pressure and how to listen for a third heart sound? These are skills that, with practice, can be learned
Accordingly, the emphasis in this section will be limited to physical findings that I think a trainee should
know in detail in order to evaluate the following diseases. Many findings discussed in a standard
textbook of medicine are not covered. The focus will be on physical findings in common diseases and
conditions that demand early recognition because of their serious nature, such as the following:
P.2
Innocent murmurs
HEART SOUNDS
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Intensity of the first heart sound is related to the rapidity of closure of the mitral valve, which
is dependent on the left ventricular-left atrial pressure gradient in late diastole, the position
of the mitral valve immediately before complete closure, and left ventricular dp/dt.
The first heart sound is best appreciated at the apical impulse in the left decubitus position.
Narrow splitting of the S1 representing tricuspid and mitral closure sounds may be heard in
normals.
The intensity of the A2 or P2 is related to the pressures against which aortic and pulmonary
valves close. Because aortic diastolic pressure is normally significantly higher than the
pulmonary artery diastolic pressure, A2 is much louder than the P2 (for abnormal intensity of
Splitting of S2 is usually heard best at the left sternal border in the second and third interspace
Normally, P2 occurs later than A2 because pulmonary artery “hang out time” is longer than the
aortic “hang out time.” The pulmonary hang out normally is about 60 msec and that of the
aorta is about 20 to 30 msec. The difference between these two hang out times explains why
P2 follows A2 and also the differences in normal splitting of the second heart sound. The hang
out times are primarily determined by pulmonary artery and aortic compliance, pulmonary and
artery hang out time due to transient increase in right ventricular stroke volume during
inspiration. (Note that decreased impedance decreases ventricular ejection time, and
increased impedance prolongs ventricular ejection time. Normal earlier electrical activation of
the left ventricle causes a minor contribution for earlier A2, and higher LV dp/dt similarly also
The normal second heart sound is thus usually split with inspiration and single with expiration
in children and younger adults. In older adults (over age 50) it is commonly single in all phases
of respiration.2 (for abnormal splitting of heart sounds, see Table 1-2).
P.3
A2 is louder than P2 when listening in the second left interspace in 70% of normal subjects
under age 20, and it is always louder than P2 in subjects over age 20. 2
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
“Normal children, young adults, and trained athletes, may have persistent splitting of S2 when
examined supine, which disappears when they sit or stand owing to decreased venous return.
By contrast, S2 remains audibly split during expiration in pathologic conditions, even when the
patient is examined sitting or standing.”3
Soft Loud
children, hyperthyroidism,
contractility
with
valve cusps
valve ring
• Variability of intensity of S1
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
hypertension, or acute as in
pulmonary embolism
• Since this latter condition occurs
P.4
P.5
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
is referred to as
paradoxical splitting
S1 • Right bundle
branch block
• Premature
ventricular
complexes (PVCs)
• Ventricular
tachycardia
• Atrial septal
defects
• Ebstein's anomaly3
increased delayed
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
result
delayed P2 and of S2
increase cardiomyopathy
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
ventricular stroke
volume is also
fixed
P.6
This sound may normally be heard in children and young adults, pregnant women, and trained
athletes.
In the context of other evidence of heart disease, an S3 correlates with elevated ventricular
end diastolic pressure and also to elevated B-type natriuretic peptide (BNP) in patients with
It is best timed by focusing on the second heart sound followed by a brief interval after S2,
followed by S3. The interval is longer than the A2-P2 interval and longer than the S2 opening
snap interval. It may be faint and best heard when focusing on the instant when it is expected;
It is a low-frequency sound, best heard with soft application of the bell over the apical
impulse, with the patient lying on the left side. An outward movement of the apex may be
noted that is synchronous with the S3 (visible and audible). This is further confirmation that
The most practical way to recognize the S3 or S4 is by listening with the bell of the
stethoscope, which is useful to appreciate these lower frequency sounds, and then to listen
with the diaphragm of the stethoscope, which cuts off the lower frequency sounds. Thus the S3
This description applies to a left ventricular gallop. A right ventricular S3 gallop is best heard
over the lower left sternal border or rarely below the xiphoid process. It is best heard with the
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
bell and may be heard as the patient inspires. It is heard in patients with right ventricular
systolic or diastolic failure and indicates elevated right ventricular diastolic pressure.
This sound results from forceful atrial contraction against a ventricle with decreased
It is a low-frequency sound occurring just before S1 and best heard with the bell. A left
ventricular S4 is best heard at the apex with the patient lying on the left side and may be
accompanied by a presystolic outward movement of the apex, which is palpable and visible. A
right ventricular S4 may be heard at the left sternal border.
P.7
It may also be heard in first degree A-V block. It is also commonly heard in acute mitral
Close attention is required to differentiate an S4 from a split S1. Proctor Harvey points out the
A split S1 is heard at the left sternal border and not at the apex or base. In contrast to an S4,
it is of higher frequency and is not affected by pressure with the bell of the stethoscope
A right-sided S4 may be heard at the left sternal border and becomes more apparent with
inspiration.
A striking finding which, if present, may help dispel doubt about equivocal ausculatory findings
is the presence of quadruple rhythm that is audible, palpable, and visible at the apex with the
patient lying on the left side. This is the result of an S1, S2, S3, and S4 sequence. Focus should
start with visually observing the overall rhythm rather than individual events and then focus on
each separate sound and apical movement. This finding may be seen in dilated
cardiomyopathy.
When both an S3 and S4 are present and are close together, as when the heart rate is rapid,
the combined sound closely simulates a diastolic rumble and has been mistaken for the
murmur of mitral stenosis.
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
It is important to recognize the jugular venous pulses adequately and properly (take care in being
certain that the pulse is venous in origin). To assess venous pressure it is necessary that the top of the
venous column is appropriately identified. Correct evaluation of venous pulse and pressure often
clarifies the diagnosis. The statement “There was no jugular venous distention (JVD)” is a summary but
The venous pressure should be determined by observing the internal jugular (IJ) pulse that
The external jugular pulse may be a reliable indicator of venous pressure with attention to
The pulsations may be more easily seen when their inward and outward movements are
P.8
Though the right IJ is traditionally examined for a variety of reasons, the left IJ can be
examined as well and may be useful in some patients.
Shining a penlight tangentially across the neck may also enhance observation.
The venous pulse has a characteristic sharp inward movement whereas the carotid pulse has a
sharp outward movement and is often the most useful differentiator of the two.
The height of the venous column will usually vary depending upon degree of head elevation.
It will often vary with different phases of respiration, normally falling slightly with inspiration.
It may normally be seen to rise transiently during hand pressure on the periumbilical region.
The venous pulse is often multi-phasic and rippling and usually not palpable whereas the
carotid pulse is usually mono-phasic with a sharp palpable upstroke, sometimes with a
shoulder.
The venous pulse is often obliterated or markedly dampened by pressure with the thumb at the
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
In severe tricuspid regurgitation, the pulsations may be vigorous and difficult to obliterate with
pressure, and the top of the venous column may be difficult to identify. Inward and outward
pulsations of the ear-lobes may be noted. These findings may closely simulate carotid
pulsations. Observing the venous column with the patient sitting on the edge of the bed or
even standing may be helpful in identifying the height of the column and distinguishing it from
the carotid pulse in this setting.
Identify the top of the venous column as indicated by the top of the venous pulsations. The
degree of elevation of the patient's head above horizontal is determined by the level at which
the top of the column is best seen and not necessarily by an arbitrary angle such as 45 degrees.
If the height of the venous column is equal to or lower than the sternal angle the venous
pressure is normal.
An elevation of the venous pressure is said to be present if the height of the venous column is
two to three cm above the sternal angle.3
Elevation of jugular venous pressure (JVP) reflects an increase in right atrial pressure and occurs in
heart failure, reduced complance of the right ventricle, pericardial disease, hypervolemia, obstruction
P.9
Starting at 30 degrees identify the EJ and occlude it at the base of the neck.
The height of the column that refills from below is the JVP in centimeters.
If the EJ cannot be visualized or the column extends above your finger, adjust the bed height
accordingly.
The “A” wave precedes the carotid pulse upstroke and first heart sound and is due to right
atrial systole. It is followed by the “X” descent as the atrium relaxes and the right atrial floor
descends.
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
The “V” wave begins after the arterial pulse and is due to filling of the right atrium during
systole. The subsequent “Y” descent follows the second heart sound and is related to the fall
in right atrial pressure as blood flows through the tricuspid valve into the right ventricle.
A giant “A” wave may be seen in right ventricular hypertrophy, as in pulmonary hypertension.
Intermittent cannon “A” waves may be seen in complete heart block when sinus rhythm is
present or in ventricular tachycardia and may aid in the diagnosis of a wide complex
tachyarrhythmia.
An increase or no fall in the venous pressure during inspiration is called the Kussmaul sign and
ventricular infarction, and also in patients with partial venacaval obstruction and pulmonary
embolism.
MURMURS
Systolic Murmurs
Innocent Murmurs
THE 4 S's
P.10
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Although these findings are characteristic, the diagnosis of innocent murmur is one of exclusion since a
similar murmur may be heard in pathologic conditions such as atrial septal defect and aortic and
pulmonary stenosis.
The characteristic fixed splitting of the second heart sound in atrial septal defect is not heard with
innocent murmurs. If there is doubt about the presence of fixed splitting when splitting is narrowly split
in expiration, listening with the patient standing may be helpful. When standing, narrow splitting of S2
in expiration may become single and this makes atrial septal defect unlikely.
Ventricular Septal
Location Usually best heard at the apex Left lower sternal Left lower
base
inspiration
(decompensated) (larger
gradient)
differentiate it from AS in
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
pause increases
P.11
Not infrequently, a new systolic murmur will be noted in a patient with a recent myocardial infarction.
The murmur may be detected incidentally or may accompany the onset of hypotension or congestive
heart failure.
Mitral regurgitation secondary to left ventricular dilation or ischemic papillary muscle. In these
conditions, mitral regurgitation is often mild and the murmur may be early or late systolic.
Mitral regurgitation due to rupture of a papillary muscle head: May not be loud or accompanied
by a thrill at the apex, and the murmur may be absent in patients who develop cardiogenic
shock.
Ventricular septal defect due to rupture of the interventricular septum. Often accompanied by
a murmur and thrill along the left sternal border.
Both acute VSD and ruptured papillary muscle are frequently accompanied by hypotension and heart
failure. The murmurs may become softer or disappear as arterial pressure falls.
These conditions are often difficult to differentiate at the bedside. The presence of a systolic murmur
in the setting of an acute myocardial infarction (AMI), particularly if new, is an indication to obtain a
conditions. It should be emphasized that pulmonary artery catheterization is not required to confirm
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Diastolic Murmurs
CARDIAC TAMPONADE
When a patient is found to have a pericardial effusion, the presence or absence of cardiac
The hemodynamic consequences of cardiac tamponade such as low cardiac out-put result from
P.12
stroke volume, hypotension and reflex tachycardia result. With increasing intrapericardial
pressure, right atrial pressure increases to maintain cardiac filling. This compensatory increase
in right atrial pressure may become inadequate when intrapericardial pressure increases more
than 20 mm Hg. Thus shock syndrome occurs when right atrial pressure approaches 20 mm Hg.
It has been thought that the gold standard for cardiac tamponade is the invasive demonstration
of elevated and equal intra-pericardial, right atrial, pulmonary artery diastolic, and pulmonary
capillary wedge pressures at the time of pericardiocentesis coupled with a significant increase
Several echocardiographic findings including systolic right atrial collapse, diastolic right
ventricular collapse, inferior vena caval plethora, and respirophasic exaggeration of flow
velocities across the mitral and tricuspid valves are highly suggestive of cardiac tamponade
In patients with cardiac tamponade, elevated jugular venous pressure, tachycardia, and pulsus
paradoxus are almost invariably present. Rarely pulsus paradoxus may not be present with
patients in shock; however, in these patient's there is almost always right ventricular collapse
It needs to be appreciated that the patient may have dyspnea; hemodynamic pulmonary
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Tamponade remains a clinical diagnosis and the mere presence of an effusion with some
P.13
to axilla
late systolic
murmur is
superimposed
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
the intensity
of P2 may
be obtunded
of Valsalva moves → S2
(shorter) during
squatting,
supine position3
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
should be
appreciated that
in elderly
patients, even
with severe
calcific aortic
stenosis, the
carotid pulse
features may be
absent
beat (triple
ripple) as a
result of a
presystolic
impulse, normal
apical thrust,
and mid-systolic
outward
movement of
the apex3
An S4 may be
heard at the
apex
accompanied by
a visible and
audible
presystolic
impulse
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
HOCM, hypertrophic obstructive cardiomyopathy; AS, aortic stenosis; PS, pulmonary stenosis;
MVP, mitral valve prolapse; RSB, right sternal border; LSB, left sternal border; LLSB, lower left
sternal border
P.14
P.15
Location Apex or just medial RSB or LSB apex. LSB with LSB,
rumbling
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
accentuation decrescendo
in presence of
mitral
regurgitation,
regurgitation.
Murmur increases
in intensity and
relative duration
with exercise,
during pregnancy,
overload
vasodilator such
as amyl nitrite
decreasing
intensity and
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
duration of the
Austin Flint
murmur
base valvular
lesions to
make the
diagnosis
S2→OS interval
shortens with
increasing severity
RV heave of
pulmonary
hypertension and
secondary tricuspid
regurgitation
signify significant
disease
Soft S1 secondary
to premature
closure of the
mitral valve
indicates severe
AR
Diastolic Flow Murmurs: A diastolic rumbling murmur similar to that heard in stenosis of the
tricuspid or mitral valve may be heard because of increased flow in the absence of obstruction.
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Examples include atrial septal defect and mitral regurgitation. Similarly, a third heart sound or
summation gallop (S3, S4) may simulate a diastolic rumble suggesting a stenotic valve.
MS, mitral stenosis; AR, aortic regurgitation; PR, pulmonary regurgitation; RSB, right sternal
P.16
P.17
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
TABLE 1-7 Operating characteristics of the arterial line pulsus in patients with known
effusion9
In a single study in which patients with a documented pericardial effusion were referred for
pericardiocentesis and had intra-pericardial pressures and cardiac output changes measured, arterial
line pulsus paradoxus were predictive of tamponade. Sensitivity and specificity of pulsus paradoxus are
A pulsus of >25 mm Hg was highly predictive of a >50% increase in cardiac output after
pericardiocentesis.
These patients were known to have a pericardial effusion; thus the stated sensitivity and
specificity may not be applicable to patients who have not yet had an echocardiogram.
Other conditions resulting in pulsus paradoxus include COPD, congestive heart failure, mitral
stenosis, massive pulmonary embolism, severe hypovolemic shock, obesity, and tense ascites. 8
REFERENCES
1. Topol EJ, et al. Textbook of Cardiovascular Medicine. Lippincott, Williams, & Wilkins. 2006.
2. Constant J. Bedside Cardiology. 5th ed. Philadelphia: Lippincott, Williams, & Wilkins: 1999: 147-148.
3. Chizner MA. Classic Teachings in Clinical Cardiology: A Tribute to W Proctor Harvey M.D. Cedar
Saunders, 1997:19.
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
P.18
5. Forrester JS, Diamond G,McHugh TJ, et al. Filling pressures in the right and left sides of the heart in
1971;285(4):190-193.
6. Vinayak AG, Levitt J, Gehlbach B, et al. Usefulness of the external jugular vein examination in
detecting abnormal central venous pressure in critically ill patients. Arch Intern Med.
2006;166(19):2132-2137.
1967;42(4):617-619.
8. Curtiss EI, Reddy PS, Uretsky BF, et al. Pulsus paradoxus: definition and relation to the severity of
9. Roy CL, Minor MA, Brookhart MA, et al. Does this patient with a pericardial effusion have cardiac
Donald Schreiber
Stress testing is one diagnostic instrument currently available to medical professionals for the
evaluation and risk stratification of patients with known or suspected coronary artery disease (CAD).
Stress testing may be done with concurrent electrocardiogram (ECG) monitoring, nuclear scintigraphy,
or echocardiography. Indeed, the different tests and the wide variety of patients tested have made
stress testing an increasingly complex and challenging area for practitioners. This chapter is aimed at
providing the reader with an enhanced understanding of the subject. The first portion of this chapter
examines exercise stress testing, describing which patients would benefit from exercise stress tests, the
appropriate timing for these tests, and test protocols. The next section details pharmacologic and
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
imaging alternatives, reviewing the indications for each and comparing the different modalities. The
INDICATIONS
Stress tests have two primary indications: to diagnose CAD and to riskstratify patients with known CAD.
For patients with symptoms of chest pain, or possible anginal equivalent, the medical provider reviews
the history, physical, and ECG to help establish the likelihood that symptoms are due to CAD (Table 2-
1). If the diagnosis is unclear, the physician can use a stress test to assist in the diagnosis of CAD.1
Stress tests are most useful in patients with intermediate pretest probability of CAD. If the patient has
a high pretest probability of CAD, then the results of a stress test are not likely to change the
management. If the patient has a low pretest probability, then the frequency of false positive tests may
lead to overtreatment and/or unnecessary procedures. Note that inTable 2-1, a 40-year-old male with a
clinical diagnosis of nonanginal chest pain is still considered intermediate pretest probability for CAD.
This underscores the limitations of clinical evaluation for ruling out CAD. Table 2-2 lists indications for
P.20
39
49
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
59
69
From Gibbons RJ, Balady GJ, Timothy Bricker J, et al. ACC/AHA 2002 guideline update for
Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines).
2002; and from Diamond G, Forrester J. Analysis of probability as an aid in the clinical diagnosis
Stress tests also play an important role in evaluating CAD in the context of preoperative risk evaluation.
Stress testing is most useful in patients with intermediate clinical cardiac risk who either have poor
functional capacity (<4 METS) or who have better functional capacity (≥4 METS) but are undergoing a
high-risk surgical procedure. Stress testing is also useful in patients who are in a low clinical cardiac risk
group but have poor functional capacity and are undergoing a high-risk surgical procedure. A stepwise
approach to preoperative cardiac risk evaluation for non-cardiac surgery is explored elsewhere.4
In patients with suspected or confirmed CAD, stress tests may be used for risk assessment: to develop a
prognosis, and to help guide treatment. Table 2-3 shows indications for stress tests in these patients.
P.21
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
• Patients with an intermediate pretest probability of CAD on basis of gender, age, and
Class III (Evidence/Opinion that Procedure is Not Useful and May be Harmful)
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
• Complete LBBB
left bundle branch block. From Gibbons RJ, Balady GJ, Timothy Bricker J, et al. ACC/AHA 2002
guideline update for exercise testing: A report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise
Testing Guidelines).
Stress tests are useful to help predict survival. Risk stratification is improved when the stress test
augments the history of the patient and the description of the pain. There are many risk stratification
are reviewed in more detail in the last section of this chapter. High-risk patients may benefit from
For patients presenting with symptoms of acute coronary syndrome (ACS)—that is, with unstable angina
(UA) or myocardial infarct (MI)—stress tests are useful to predict short-term risk.
P.22
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
• Patients with suspected or known CAD who present with significant change in status
• Low-risk UA patients, 8-12 hours after presentation, who have been free of active
• Intermediate-risk UA patients, 2-3 days after presentation, who have been free of active
• Intermediate-risk UA patients who have initial normal cardiac markers, repeat ECG
without significant change, normal cardiac markers 6-12 hours after the onset of
• Patients with stable clinical course who undergo periodic monitoring to guide treatment
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Class III (Evidence/Opinion that Procedure is Not Useful and May be Harmful)
• Patients with severe comorbidity likely to limit life expectancy and/or candidacy for
revascularization
• High-risk UA patients
CAD, Coronary artery disease; UA, unstable angina; ECG, electrocardiogram; WPW, Wolff-
Parkinson-White; LBBB, left bundle branch block; IVCD, interventricular conduction defect. From
Gibbons RJ, Balady GJ, Timothy Bricker J, et al. ACC/AHA 2002 guideline update for exercise
testing: A report of the American College of Cardiology/American Heart Association Task Force
on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). 2002.
The ability to rule out imminent ischemia is based on the test's negative predictive value. The negative
predictive value of a stress test is dependent upon the specific test used; however, for low to moderate
risk patients who rule out by enzymes and have an adequate negative exercise stress test, the short-
term event rate is generally very low. Gibler et al. showed that only 1 of 1010 patients in a chest pain
unit who ruled out for acute myocardial infarction and had a negative stress test died (cause unknown)
within 30 days.6 In
P.23
another study, 0 of 374 patients had a combined endpoint of death or acute MI at 150 days. 7
CONTRAINDICATIONS
Stress tests are generally safe procedures.8 In a large national survey of exercise stress test facilities,
encompassing both inpatient and outpatients, Stuard et al. enumerated complications including
arrhythmias (<0.05%), infarcts (<0.04%), and death (<0.01%).9 Looking at a higher risk group—632
hospitalized subjects evaluated for unstable angina symptoms—Stein et al. reported the combined
incidence of MI and death within 24 hours of exercise testing as 0.5%. 10 Complications can be reduced by
a careful history and physical, reviewing an ECG, and a pretest chest radiograph. Contraindications for
exercise stress tests are shown in Table 2-4. Most of these contraindications are also applicable to
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Absolute
Relative
• Electrolyte abnormalities
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
• Tachyarrhythmias or bradyarrhythmias
From Gibbons RJ, Balady GJ, Timothy Bricker J, et al. ACC/AHA 2002 guideline update for
Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines).
2002.
P.24
Stress tests should not be performed until the patient is clinically stable. Low-risk outpatients being
evaluated for ACS symptoms should have a stress test within 72 hours.1 The majority of low-risk patients
admitted to the hospital can safely obtain their stress tests as outpatients. Current guidelines
recommend that the stress test be obtained within 72 hours of discharge. 5 In general, outpatient stress
tests for patients presenting via the emergency department (ED) with symptoms should be reserved for
patients who are either at low risk for having ACS or low risk for short-term death or MI.11,12 Outpatient
Observation or chest pain units are increasingly common and provide a middle ground between
inpatient and outpatient testing. Patient selection and management are based on accelerated rule-out
protocols that ideally include stress testing.5, 6, and 7,10,13 These units have been shown to decrease
unnecessary admissions, reduce the rate of missed MIs, reduce costs, and increase patient satisfaction.
The patient should be informed of the purpose, risks, benefits, and details of the stress test
procedure.14 The patient should be instructed not to eat, drink, or smoke for 3 hours before the exam.
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Patients undergoing an exercise stress test should be instructed to wear comfortable clothing and
footwear.
The physician should review the patient's medication list and decide what medications should be
discontinued for the test. It is usually recommended that patients hold their dose(s) of beta-blocker 24-
48 hours prior to exercise stress testing. A beta-blocker may blunt the chronotropic response to
exercise and prevent the patient from reaching their target heart rates. This limits the diagnostic utility
of the stress test. However, if there is risk involved in discontinuing beta-blocker therapy, there is some
evidence to support that exercise tolerance or diagnostic accuracy is not affected. 15 In addition, the
stress test can be used to test the medical management regimen that may include beta-blockers.
Pharmacologic agents can be substituted for physical exercise to cause increased myocardial work and
myocardial oxygen demand. The two major categories of imaging—echocardiography and myocardial
perfusion imaging—can be used as an adjunct to either an exercise or pharmacologic stress test to
delineate the extent, severity, and location of myocardial injury. Figure 2-1 gives an overview of the
clinical context of stress testing, and provides a guide to the type of stress test that may be
appropriate.
P.25
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
FIGURE 2-1 Clinical context for exercise testing for patients with coronary heart disease. ACC/AHA
P.26
SPECIFIC THERAPIES
For an exercise stress test, the patient must be able to use the available exercise equipment (usually a
treadmill, or less often in the United States, a cycle ergometer) to elevate the heart rate to ≥85% of
predicted maximum heart rate (HRMax = 220 - age). If the patient is elderly, has significant comorbidity
(e.g., chronic obstructive pulmonary disease [COPD], arthritis), or has other physical or mental
limitation that would limit the ability to exercise, a pharmacologic stress test should be substituted.
The two choices for pharmacologic agents are vasodilators or dobutamine (the latter with or without
atropine). Adenosine and dipyridamole are the current vasodilators of choice. Both agents are equally
effective. They increase the heart rate, decrease the blood pressure, and increase myocardial oxygen
demand, but may cause bronchospasm. Caution is warranted if there is a history of asthma or COPD.
They may cause worsening angina. Both are contraindicated in high-degree A-V block and sick sinus
syndrome. The short half-life of adenosine has a theoretical advantage if potential side effects are a
concern. Theophylline and ideally caffeine must be withheld for 24 hours before the procedure.
Calcium channel blockers, and nitroglycerin should ideally be withheld for 24 hours and beta-blockers
for 48 hours, as they decrease the sensitivity of pharmacologic myocardial perfusion imaging. 18, 19, and 20
A dobutamine stress test is preferred in patients with history of bronchospasm or recent use of a
methylxanthine. Dobutamine, an inotropic and chronotropic agent, is usually used in conjunction with
echocardiography imaging but can also be used with myocardial perfusion imaging (MPI). Beta-blockers
should be withheld for 24-48 hours.21,22 unless the indication for the test is to evaluate the effectiveness
of a medical regimen. Specific contraindications to a dobutamine stress test include the following: 18
Ventricular arrhythmias
ACS
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Systemic hypertension.
The accuracy of a dobutamine stress echo is comparable to both adenosine and dipyridamole MPI
(sensitivity ~80%-90% and specificity ~75%-85%). The choice of pharmacologic agent often has more to
do with local expertise and individual patient characteristics rather than the advantages of each
agent.23 Since exercise tolerance and symptoms during exercise are important prognostic factors (see
below), a submaximal exercise test can be combined with a pharmacologic protocol. 18,24, 25, and 26
P.27
Imaging
Moderate-risk patients, and any patients for whom there is a need to localize ischemia or assess the
viability of myocardium, benefit from imaging in addition to ECG testing. For low-risk patients with
normal ECGs who are not on digoxin, a standard (exercise) ECG stress test without imaging is
sufficient.1,27 However, there are guidelines28 that recommend stress imaging in the risk stratification of
low-risk as well as moderate-risk patients with symptoms. A stress test patient who has any of the
following ECG abnormalities that can make ECG interpretation difficult (including low-risk patients)
ST depression >1mm
If imaging were not used, these pre-existing ECG abnormalities would limit the ECG diagnosis of
ischemia.1
MPI can be done with positron emitting tomography (PET) scanning, single photon emission computed
tomography (SPECT) imaging, or planar imaging. Stress PET imaging, while more sensitive, is
considerably more expensive23 and less readily available than SPECT imaging (Table 2-5). The only class I
recommendation for an adenosine or dipyridamole perfusion PET is for cases where a SPECT scan
produced equivocal results.28 SPECT MPI, while still occasionally referred to as “thallium” MPI, is now
(lower radiation exposure and ability to use higher doses) with technetium, and to the high false-
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
positive rates associated with thallium attenuation in soft tissue. SPECT imaging is considered to be
Echocardiograms are used to detect the presence of CAD and to risk-stratify patients. An
echocardiogram can localize the area of ischemia by identifying segments with wall motion
exercise stress test, the patient must move quickly from the point of peak exercise to an exam table
where the echocardiogram can be performed and prior to the resolution of any ischemia that may be
present. Echocardiograms are somewhat quicker to perform and less expensive than MPIs, but are more
P.28
Adenosine 90 75
Dipyridamole 89 65
Dobutamine 82 75
Adenosine 72 91
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Dipyridamole 70 93
Dobutamine 80 84
(PCI) $11,685
Modified from Garber AM, Solomon NA. Cost-effectiveness of alternative test strategies for the
diagnosis of coronary artery disease. Ann Intern Med. 1999;130:719-728; and Kim C, Kwok YS,
Heagerty P, et al. Pharmacologic stress testing for coronary disease diagnosis: A meta-analysis.
Am Heart J. 2001;142:934-944. These numbers reflect the average taken over all studies in the
meta-analysis.
Patient variables can influence the choice of imaging modalities. In patients with left ventricular
hypertrophy, stress echocardiograms have a superior specificity.31 Vasodilator stress MPI is superior to
exercise stress MPI or stress echo in patients with left bundle branch block or paced ventricular
rhythms.27 MPI is preferred if the patient's body habitus creates a poor echocardiographic acoustic
window.
The choice of imaging modality is usually based on local expertise and availability rather than individual
P.29
specificity of these tests are given in Table 2-5. Some studies have shown that SPECT MPI has a higher
sensitivity than echocardiography, while others have shown the two modalities to have comparable
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
sensitivities. As expected, higher sensitivities are found in populations with higher prevalence and/or
severity of disease. The specificity of stress echocardiography is slightly higher than for MPI. 23,31,32 These
two options have similar performance characteristics for risk stratification and predicting outcomes. 33
In addition to these two established imaging modalities, stress testing with magnetic resonance imaging
(MRI) has shown encouraging results. It can be combined with either dobutamine or a vasodilator. In
one study, sensitivity, when compared to dobutamine stress echo, was significantly higher, 86.2% versus
74.3%, and specificity was 85.7% versus 69.8%.34 In addition to being accurate in diagnosing ischemic
TEST INTERPRETATION
The provider must first determine whether the study was adequate. For the exercise portion of a stress
test, the heart rate ideally should reach 85% or more of the patient's predicted maximum heart rate;
lower heart rates increase the probability of a false negative result. For echocardiographic studies,
satisfactory acoustic windows must be obtained to evaluate cardiac wall motion.
What is considered a positive or negative result on a stress test is somewhat arbitrary and depends on
the desired sensitivity versus specificity of the test.1 Predictors of adverse outcomes can be physiologic,
electrocardiographic, or imaging abnormalities (Table 2-6).36,37 Any one of these findings constitutes a
poor prognosis. Not surprisingly, the inability to exercise is the strongest physiologic predictor of
adverse cardiac outcomes. Downsloping ST segment depression, particularly in lead V5, is the strongest
electrocardiographic predictor. Decreased left ventricular function is the strongest imaging predictor. 1
The provider is not limited to considering these factors individually; there are tools available that allow
prediction of mortality using multiple prognostic factors. Perhaps the best-established of these tools is
the Duke Treadmill Score (DTS), which incorporates the depth of ST depression, the length of time on
the treadmill, and the presence of angina (DTS = exercise time - [5 * ST deviation] - [4 * exercise
use, but has some limits: it considers only three variables, and is somewhat dependent on patient
morphology. It is most useful as a predictor when the score is either particularly high or low. These
scores can be augmented with imaging information. Table 2-7 is an example of a risk stratification
scheme that combines information from various aspects of the stress test, including echocardiographic
P.30
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Exercise
Echocardiography
• Rest images
• Stress images
• Reversible dyssynergy
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Myocardial Perfusion
• Delayed redistribution
EKG
• ST segment elevation (in leads without pathologic Q waves and not in a VR)
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Adapted from Weiner D. Exercise ECG testing to determine prognosis of coronary heart disease.
P.31
TABLE 2-7 Prognosis based on Duke treadmill score and echocardiographic findings
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
LVEF, left ventricular ejection fraction adapted from Gibbons RJ, Chatterjee K, Daley J, et al.
ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: A
report of the American College of Cardiology/American Heart Association Task Force on Practice
Cardiol. 1999;33:2092-2197.
REFERENCES
1. Gibbons RJ, Balady GJ, Timothy Bricker J, et al. ACC/AHA 2002 guideline update for exercise testing:
A report of the American College of Cardiology/American Heart Association Task Force on Practice
2. Gibbons LW, Mitchell TL, Wei M, et al. Maximal exercise test as a predictor of risk for mortality from
P.32
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
4. Eagle KA, Berger PB, Calkins H, et al. ACC/AHA guideline update for perioperative cardiovascular
Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the
2002;105:1257-1267.
5. Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA 2002 guideline update for the management of
patients with unstable angina and non-ST-segment elevation myocardial infarction: A report of the
6. Gibler W, Runyon J, Levy R, et al. A rapid diagnostic and treatment center for patients with chest
7. Mikhail MG, Smith FA, Gray M, et al. Cost-effectiveness of mandatory stress testing in chest pain
center patients. Ann Emerg Med. 1997;29:88-98.
8. Gordon NF, Kohl HW. Exercise testing and sudden cardiac death. J Cardiopulm Rehabil. 1993;13:381-
386.
9. Stuart R Jr, Ellestad M. National survey of exercise stress testing facilities. Chest. 1980;77:94-97.
10. Stein RA, Chaitman BR, Balady GJ, et al. Safety and utility of exercise testing in emergency room
chest pain centers: An advisory from the Committee on Exercise, Rehabilitation, and Prevention,
11. Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guideline update for the management of
patients with unstable angina and non-ST-segment elevation myocardial infarction—2002: Summary
Article: A report of the American College of Cardiology/American Heart Association Task Force on
Practice Guidelines (Committee on the Management of Patients With Unstable Angina). Circulation.
2002;106:1893-1900.
12. Meyer MC, Mooney RP, Sekera AK. A critical pathway for patients with acute chest pain and low risk
for short-term adverse cardiac events: Role of outpatient stress testing. Ann Emerg Med. 2006;47:435.
e1-435.e3.
13. Amsterdam EA, Kirk JD, Diercks DB, et al. Exercise testing in chest pain units: Rationale,
P.33
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
14. Pina IL, Balady GJ, Hanson P, et al. Guidelines for clinical exercise testing laboratories. A statement
for healthcare professionals from the Committee on Exercise and Cardiac Rehabilitation, American
15. Herbert WG, Dubach P, Lehmann KG, et al. Effect of beta-blockade on the interpretation of the
16. Fletcher GF, Balady G, Froelicher VF, et al. Exercise standards. A statement for healthcare
professionals from the American Heart Association. Writing Group. Circulation. 1995;91:580-615.
17. Gibbons RJ, Balady GJ, Timothy Bricker J, et al. ACC/AHA 2002 Guideline update for exercise
testing: Summary Article: A Report of the American College of Cardiology/American Heart Association
Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines).
Circulation. 2002;106:1883-1892.
18. Heller GV. Pharmacologic stress myocardial perfusion imaging in the diagnosis and prognosis of
19. Taillefer R, Ahlberg AW, Masood Y, et al. Acute beta-blockade reduces the extent and severity of
myocardial perfusion defects with dipyridamole Tc-99m sestamibi SPECT imaging. J Am Coll Cardiol.
2003;42:1475-1483.
20. Sharir T, Rabinowitz B, Livschitz S, et al. Underestimation of extent and severity of coronary artery
21. Heller GV, Kapetanopoulos A. Pharmacologic stress myocardial perfusion imaging: Testing
22. Shehata AR, Gillam LD, Mascitelli VA, et al. Impact of acute propranolol administration on
23. Garber AM, Solomon NA. Cost-effectiveness of alternative test strategies for the diagnosis of
24. Casale PN, Guiney TE, Strauss, HW, et al. Simultaneous low level treadmill exercise and intravenous
25. Pennell DJ, Mavrogeni SI, Forbat SM, et al. Adenosine combined with dynamic exercise for
P.34
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
26. Thomas GS, Prill NV, Majmundar H, et al. Treadmill exercise during adenosine infusion is safe,
results in fewer adverse reactions, and improves myocardial perfusion image quality. J Nucl Cardiol.
2000;7:439-446.
27. Gibbons RJ, Chatterjee K, Daley J, et al. ACC/AHA/ACP-ASIM guidelines 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 (Committee on Management of Patients With Chronic
28. Klocke FJ, Baird MG, Lorell BH, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac
Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995
Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). Circulation. 2003;108:1404-1418.
29. Fintel DJ, Links JM, Brinker JA, et al. Improved diagnostic performance of exercise thallium-201
single photon emission computed tomography over planar imaging in the diagnosis of coronary artery
30. Kim C, Kwok YS, Heagerty P, et al. Pharmacologic stress testing for coronary disease diagnosis: A
31. Marwick T, D'Hondt A, Baudhuin T, et al. Optimal use of dobutamine stress for the detection and
32. Fleischmann KE, Hunink MG, Kuntz KM, et al. Exercise echocardiography or exercise SPECT imaging?
33. Olmos LI, Dakik H, Gordon R, et al. Long-term prognostic value of exercise echocardiography
compared with exercise 201Tl, ECG, and clinical variables in patients evaluated for coronary artery
34. Nagel E, Lehmkuhl HB, Bocksch W, et al. Noninvasive diagnosis of ischemia-induced wall motion
abnormalities with the use of high-dose dobutamine stress MRI: Comparison with dobutamine stress
35. Jahnke C, Nagel E, Gebker R, et al. Prognostic value of cardiac magnetic resonance stress tests:
Adenosine stress perfusion and dobutamine stress wall motion imaging. Circulation. 2007;115:1769-
1776.
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
36. Weiner D. Exercise ECG testing to determine prognosis of coronary heart disease. In: UpToDate;
2006.
37. Yao S-S, Rozanski A. Principal uses of myocardial perfusion scintigraphy in the management of
patients with known or suspected coronary artery disease. Prog Cardiovasc Dis. 2001;43:281-302.
P.35
38. Mark D, Shaw L, Harrell F, et al. Prognostic value of a treadmill exercise score in outpatients with
39. Kwok JMF, Miller TD, Christian TF, et al. Prognostic value of a treadmill exercise score in
symptomatic patients with nonspecific ST-T abnormalities on resting ECG. JAMA. 1999;282:1047-1053.
40. Mark DB, Hlatky MA, Harrell FE, et al. Exercise treadmill score for predicting prognosis in coronary
Todd J. Brinton
David P. Lee
There are over 5 million emergency department visits each year in the United States for acute chest
pain.1 Annually, over 800,000 people experience an acute myocardial infarction (AMI), of which 213,000
die and half do so before reaching the hospital. In-hospital mortality in the pre-CCU era reached >30%.
With the advent of the coronary care unit (CCU), mortality dropped to 15%, and in the modern era of
percutaneous coronary intervention (PCI) with stenting, combination antithrombotic therapy, and
routine use of adjunctive medical treatment, in-hospital mortality of ST segment elevation MI (STEMI)
has reached a low of 6%-7%. In this chapter we review the initial recognition, triage, acute
management, and definitive therapy across the spectrum of the acute coronary syndromes (ACS).
CLINICAL PRESENTATIONS
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
The spectrum of acute ischemia-related syndromes ranges from unstable angina to acute myocardial
infarction (MI), with or without ST elevation (see Figure 3-1), that are secondary to acute plaque
rupture or plaque erosion. The clinical diagnosis relies on the combination of at least two of the
following:
P.38
Unstable Angina
Occurring at rest or with minimal exertion and usually lasting >20 minutes (if not interrupted
by nitroglycerin)
Occurring with a crescendo pattern (i.e., more severe, prolonged, or frequent than previously)
No evidence of myocardial infarction by biomarkers
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Myocardial Infarction 2
The typical rise and fall of troponin or creatinine kinase MB fraction (CK-MB) with at least one of the
following:
Ischemic symptoms
NQWMI/QWMI
The older literature makes reference to Q wave MI (QWMI) and Non-Q wave MI (NQWMI). The
implication was that Q wave MI was associated with transmural infarction and Non-Q wave MI was
limited to the subendocardium. Pathology studies have shown that Q waves are neither sensitive nor
specific for transmural infarction. While there may be prognostic value in the identification of Q waves
in patients with myocardial infarction, the modern terms STEMI and NSTEMI are preferred as they have
more immediate implications with regard to acute management strategies (i.e., STEMI is triaged toward
emergent reperfusion)
P.39
Normal Variants
Normal male pattern: Often with 1-3 mm of concave sinus tachycardia (ST) elevation greatest
lead V2
Early repolarization: Often with 1-3 mm of concave ST elevation, often with notching at the J
point in V4
Variant ST elevation with T wave inversion: Seen often in young black men, convex ST
elevation, T wave inversion, thought to represent persistent juvenile T wave inversion + early
repol, may look like STEMI
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Other Pathology
Left bundle branch block (LBBB): Typical pattern of LBBB present with anterior ST elevation
elevation: T wave height (> 0.25 measured using PR segment as the baseline in this case) in V6
TABLE 3-1 Immediately life-threatening causes (must consider these every time)
syndrome
- May see ST
elevation, classically
dissection
- Widened
mediastinum
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
- Good positive
predictors of the
diagnosis: Pulse
CP3
- New AI murmur
- Poor negative
clinical predictors—if
exclude it
Pulmonary Acute onset, sharp, pleuritic CP, dyspnea, - Always consider with
RBBB, RAD
- S1Q3T3 uncommon
ray
- Shock if under
tension
P.40
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elevation
- PR elevation in AVR
the PR segment)4
Pulmonary DOE, anginal-like pain - Elevated JVP, loud P2, parasternal lift,
HTN (? RV ischemia), S4
history-middle age
women>men
- Stigmata of R sided HF
- See chapter on PH
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esophagitis
history of gallstones,
n/v
- Jaundice if common duct
- Abnormal LFTs
of pancreatitis or
gallstones
sputum production
- Rhonchi, rales
P.41
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
- Promptly
relieved with GI
cocktail (be
careful here)
- Guaiac positive
stools
(remember it's
smooth muscle
too!)
look at the
chest!
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antidepressants/benzodiazepines exclusion
ACS, acute coronary syndrome; CAD, coronary artery disease; HTN, hypertension; DM, diabetes
mellitus; MR, mitral regurgitation; CP, chest pain; RCA, right coronary artery; DVT, deep venous
thrombosis; PE, pulmonary embolism; OCP, oral contraceptive pill; CXR, chest x-ray; TWI, t wave
inversion; RBBB, right bundle branch block; RAD, right axis deviation; COPD, chronic obstructive
pulmonary disease; AVR, aortic value replacement; JVP, jugular venous pressure; P2, pulmonic
second sound; DOE, dyspnea on exertion; RV, right ventricle; PA, pulmonary artery; RUQ, right
upper quadrant; LFT, liver function test; WBC, white blood count; GERD, gastroesophageal reflux
disease; EGD, esophagogastroduodenoscopy; PUD, peptic ulcer disease; NTG, hitroglycerin; GAD,
P.42
HISTORY
The history should be methodically taken and may be aided by remembering the “SOCRATES”
mnemonic.
Self assessment: Knowing the patient's fears is important for many reasons
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Also look for history of CAD, details of prior angiography, CABG or percutaneous coronary
intervention (PCI), recent stress tests or echoes, other risk factors (DM, smoking, HTN,
hyperlipidemia, cocaine use)
P.43
PHYSICAL EXAM
The physical exam in someone having an ACS may be entirely normal. Its purpose is to identify early
Look for:
Hypotension/hypertension
Arrhythmias
Tachypnea or hypoxia
Fever
Rectal exam—evaluate for melena or guaiac positive stool (? how aggressive to anticoagulate)
Rash on the chest (Zoster), make sure to examine the chest on hospital day 2, the pain often
precedes the skin findings!
Troponin I or T may be detectable as early as 2 hours after injury and CK-MB become
Must obtain serial tests q4-6 h for at least 10 hours after the start of CP to definitively r/o MI
Look for typical rise and fall of enzymes in the context of CP and the ECG to make a diagnosis
of NSTEMI
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Heart failure can be responsible for persistent low-grade elevation of troponin thought to be
from elevated LVEDP leading to subendocardial necrosis often with normal CKs
Additional Labs
WBC: Likely mildly elevated in AMI but may also establish infectious etiology for current state
Electrolytes: Monitor for potassium and calcium abnormalities which may alter the ECG,
Evaluate for infectious etiologies, electrolyte abnormalities
P.44
Creatinine: Usually elevated in patients with longstanding HTN and DM. Elevated creatinine is a
contrast nephropathy
LFTs: Elevated in cases of hypotension due to shock or passive congestion due to elevated
Urine toxicology: Should be obtained for all young or at-risk patients with concerning chest
pain (cocaine-induced MI can result from thrombosis in addition to vasospasm and therefore
B-type natriuretic peptide (BNP): May be helpful in establishing the diagnosis of congestive
heart failure (CHF) (see chapter on complications of AMI)
ECG
Repeat every 15 minutes ×2 if nondiagnostic, this has been shown to increase sensitivity
Dynamic T wave and ST changes should greatly increase your suspicion for ACS
Reoccurrence of CP should be re-evaluated with additional ECG recordings prior to giving NTG
Obtain right-sided leads in those with inferior distribution injury to evaluate for RV injury or
infarct
Obtain posterior leads in patients with only anterior ST depression to r/o posterior wall STEMI
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Chest X-ray
pneumothorax
Echo
Useful test for evaluating systolic function, regional WMAs, effusion, valvular lesions, and to
May be helpful in a high risk patient with ongoing CP and a nondiagnostic ECG or when the
diagnosis of STEMI is in doubt
P.45
Used to assess for proximal PE and aortic dissection and to assess for other noncardiac
Consider MRI if patient has CRI or is high risk for contrast nephropathy
Different phase of contrast often needed for optimal evaluation of PE and aortic dissection
to optimal management. These two entities have vastly different priorities as STEMI often involves a
completely occluded artery and clinical data indicate that revascularization is both an emergency and
that outcomes are tied to time to reperfusion. Management of NSTE ACS, both from a pathophysiologic
and a clinical outcomes perspective focus on initial treatment with drugs that inhibit thrombosis and
platelet aggregation usually in conjunction with a nonemergent early interventional approach and early
adjunctive medical therapies. The major difference is the prioritization of treatments and the
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P.46
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P.47
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History Prolonged anginal CP or CP relieved only New CCS II-IV angina in the past
TIMI risk ≥3 ≤2
score
Low High
risk risk
B-Blockers6 X X
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Nitroglycerin X X
SL, Paste, IV
Morphine X X
DVT prophylaxis X X
(SQ heparin or LMWH prophylaxis for those not already on full anticoagulation)
Enoxaparin or UFH7 X
(If Cr > 2.5, CrCl < 30 ml/min, or weight > 150 kg use UFH, relative
Clopidogrel8 X
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GPIIB/IIIA inhibitor9 X
guidance)
Captopril 6.25 mg po tid and titrate to goal 50 mg tid Ramipril 2.5 mg po and
Adapted from the ACC/AHA 2002/2004 practice guidelines. (TIMI), thrombolysis in myocardial
infarction
P.48
STEMI MANAGEMENT
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As mentioned above, STEMI is often associated with a completely occluded coronary artery (>90%) and
outcomes are directly tied to timeliness and adequacy of revascularization. The goal of reperfusion
using PCI is a door-to-balloon time of <90 minutes in an experienced center and is preferred over
thrombolysis when possible. If thrombolysis is employed the goal is a door-to-needle time of <30
minutes in the absence of contraindications (see below). Additional antithrombotic, antiplatelet, and
adjunctive medical therapies are indicated in STEMI as above in NSTEMI ACS but should not delay
P.49
Skilled PCI lab with surgical backup available (Door- Early presentation (<3 h from onset of
to-balloon time <90 min) or rapid transport (<2 h) symptoms) with a delay (>2 h) to an
SPECIFIC THERAPIES
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Thrombolytic Regimens
Rescue PCI
Thrombolysis success is associated with resolution of chest pain, >50% resolution of ST elevations,
hemodynamic stability, and reperfusion rhythms such as an accelerated idioventricular rhythm (do not
treat unless unstable). Indications of thrombolysis failure include ongoing chest pain, hemodynamic
instability <50% resolution of ST elevations, and malignant ventricular tachycardia. In such cases rescue
PCI is the optimal management strategy, and if not locally available, arrangements for critical care air
Antithrombotic therapy is associated with increases in the risk of major and minor bleeding and
therefore decisions about appropriateness of therapy should also take into account relative
contraindications so that a decision about the relative risks and benefits can be made. Remember that
most patients with these contraindications were excluded from major clinical trials of advanced
antithrombotic/antiplatelet therapy, and therefore bleeding rates in these trials likely underestimate
P.50
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Streptokinase 1.5 million units Inferior to TPA, patient ASA, +/- heparin
exposure
compared to
1000 U/h)
then 75 mg/d
75 mg/d
TNK in
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>90 kg = 50 mg administer
bolus at 30 min
Also consider that patients with acute anemia, significant hyper- or hypotension, superimposed severe
aortic stenosis, and other factors known to alter myocardial supply-demand relationships may not have
plaque rupture as an etiology of myocardial infarction.Therefore, they may derive less benefit, and
potentially more harm, from these therapies. The following are generally considered contraindications
to thrombolytic therapy and should be considered individually for patients getting multiple
P.51
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Absolute Relative
neoplasm
mo
menses)
trauma
w/in 3 mo • Thrombocytopenia
• Pregnancy
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HR >100 2 4 7.3
Age ≥ 75 3 7 23.4
>8 35.9
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Intervention Comments
rehabilitation
daily
Plavix 75 mg At least 9-12 months after NSTEMI or STEMI w/o PCI. predischarge stress
Minimum 2 weeks s/p bare metal stent and 3 months s/p d post MI drug
Statin Target LDL <70 mg/dl w/LFTs and repeat lipid profile in 1 month
ACE -I or ARB Probably most useful with large anterior infarcts or those with post MI LV
2 weeks2
Nitroglycerin NTG Sl for occasional angina. Isordil, Imdur, or nitro patch for patients
Aldosterone Indicated in post MI patients with an EF <40% and CHF. Must monitor K
antagonist and renal function carefully or don't prescribe! at 1 week and 4 weeks
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management
cessation
Rehabilitation
Stress testing For patients who are not revascularized: Submaximal predischarge stress
P.52
P.53
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Streptokinase (S) vs. GISSI-1 (Lancet, Streptokinase → 18% RRR (P 13% S 10.7%)
weeks NNT = 20
Primary PTCA (P) vs. Metanalysis PTCA → 34% RRR of (T 6.5% P 4.4%) death
= 2606
Primary PCI w/stenting Danami 2 PCI w/stenting → 45% RRR (T 13.7% P 8.0)
Primary PCI w/Sirolimus STRATEGY Sirolimus stent → 65% RRR (B 20% D 7%)
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analysis NNT = 63
(JACC,
200617)
Early invasive Meta- Early invasive → 15% RRR (S 12.2% S 14.4%) D/MI @ 17 mo
selectively (JAMA,
200518) n =
9212
invasive (S) ICTUS (Troponin positive subgroup) Early invasive → 30% RRR
200519) n =
1200
invasive groups.
stress testing.
P.54
P.55
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Aspirin vs. Canadian multicenter ASA → 43% RRR all cause death @ 18 mo
199020) n = 796
Heparins (UFH Metanalysis (Lancet, 47% RRR of D/MI at 1 week (background: ASA)
placebo)
ASA)
eptifibatide)
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
vs. placebo *
2001 ) n = 12, 562
8
management) NNT = 48
NNT = 67
2002 ) n = 2, 116
24
vs. placebo strong trend (p = 0.051) of 39%
gp2b/3a 45%)
vs. placebo 25
) n = 1, 863 angiography in 3 d postthrombolysis STEMI →
GPIIB/IIIA vs. ADMIRALstemi (NEJM, Abciximab (A) → 60% RRR (P 14.6% A 6%) of
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placebo *
2001 26) n = 300 D/MI/uTVR @ 30 d NNT = 12
(Circulation, 2001 ) n 28
= 6, 458
PCI @ 30 d NNT = 26
*
Studies showed benefit primarily in patients stratified as “High risk”
stemi
Primarily STEMI patient population
nstemi
Primarily NSTEMI patient population
RRR, relative risk reduction; NNT, number needed to treat; D/MI, death/MI
P.56
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Acute beta Goteborg study Metoprolol 15 mg IV, then total 100 mg po bid →
blockade vs. (Lancet, 198129) n 36% RRR (P 8.9% M 5.7%) of death @ 90 d NNT = 32
placebo = 1, 395
in re-infarction at 6 d
= 1, 959
Metanalysis
(NEJM, 1998)
Statins 4S (Lancet, 199434) In patients with CHD Simvastatin (S) → 30% RRR (P
prevention
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
mg vs. pravastatin
(P) 40 mg
(NEJM, 200436) n =
4, 162
(JAMA, 2001 ) n =
10
ischemia. NNT = 39
3, 086
ACE inhibitor SAVE - EF <40%stemi Captopril (S) 50 mg TID vs. placebo → 19% RRR (P
ACE inhibitor SAVE - EF <40%stemi Captopril (S) 50 mg TID vs. placebo → 19% RRR (P
1995 )
38
1993 ) n = 2, 006
39
death at 15 mo NNT = 17
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
antagonist - 2003 )
40
Eplerenone (E) 25 mg → 15% RRR (P 16.7% E 14.4%)
stemi
Primarily STEMI patient population
nstemi
Primarily NSTEMI patient population
P.57
REFERENCES
1. Fuster V, Alexander RW, O'Rourke RA. Hurst's the Heart. 11th ed.New York: McGraw-Hill Medical
2. Alpert JS, Thygesen K, Antman E, et al. Myocardial infarction redefined—a consensus document of
The Joint European Society of Cardiology/American College of Cardiology Committee for the
P.58
3. Klompas M. Does this patient have an acute thoracic aortic dissection? JAMA. 2002;287(17):2262-
2272.
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
4. Ginzton LE, Laks MM. The differential diagnosis of acute pericarditis from the normal variant: New
5. Cairns JA, Gent M, Singer J, et al. Aspirin, sulfinpyrazone, or both in unstable angina. Results of a
6. Freemantle N, Cleland J, Young P, et al. Beta blockade after myocardial infarction: Systematic
unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous
8. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute
9. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary
syndromes. The PURSUIT Trial Investigators. Platelet glycoprotein IIb/IIIa in unstable angina: Receptor
10. Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic
events in acute coronary syndromes: The MIRACL study: A randomized controlled trial. JAMA.
2001;285(13):1711-1718.
11. Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score for unstable angina/non-ST elevation MI:
12. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Gruppo Italiano
13. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of
suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival)
14. Weaver WD, Simes RJ, Betriu A, et al. Comparison of primary coronary angioplasty and intravenous
thrombolytic therapy for acute myocardial infarction: A quantitative review. JAMA. 1997;278(23):2093-
2098.
15. Andersen HR, Nielsen TT, Rasmussen K, et al. A comparison of coronary angioplasty with fibrinolytic
P.59
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
16. Valgimigli M, Percoco G, Malagutti P, et al. Tirofiban and sirolimuseluting stent vs abciximab and
bare-metal stent for acute myocardial infarction: A randomized trial. JAMA. 2005;293(17):2109-2117.
17. Bavry AA, Kumbhani DJ, Rassi AN, et al. Benefit of early invasive therapy in acute coronary
2006;48(7):1319-1325.
18. Mehta SR, Cannon CP, Fox KAA, et al. Routine vs selective invasive strategies in patients with acute
2917.
19. de Winter RJ, Windhausen F, Cornel JH, et al. Early invasive versus selectively invasive management
20. Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous
heparin in men with unstable coronary artery disease. The RISC Group. Lancet. 1990;336(8719):827-830.
21. Eikelboom JW, Anand SS, Malmberg K, et al. Unfractionated heparin and low-molecular-weight
1936-1942.
22. Goodman SG, Fitchett D, Armstrong PW, et al. Randomized evaluation of the safety and efficacy of
enoxaparin versus unfractionated heparin in high-risk patients with non-ST-segment elevation acute
2003;107(2):238-244.
23. Mehta SR,Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by
long-term therapy in patients undergoing percutaneous coronary intervention: The PCI-CURE study.
Lancet. 2001;358(9281):527-533.
24. Steinhubl SR, Berger PB, Mann JT, et al. Early and sustained dual oral antiplatelet therapy following
25. Sabatine MS, Cannon CP, Gibson CM, et al. Effect of clopidogrel pretreatment before percutaneous
coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: The
26. Montalescot G, Barragan P, Wittenberg O, et al. Platelet glycoprotein IIb/IIIa inhibition with
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
27. Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute
2002;359(9302):189-198.
28. Roffi M, Chew DP, Mukherjee D, et al. Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in
2001;104(23):2767-2771.
P.60
29. Hjalmarson A, Elmfeldt D, Herlitz J, et al. Effect on mortality of metoprolol in acute myocardial
30. Randomised trial of intravenous atenolol among 16,027 cases of suspected acute myocardial
infarction: ISIS-1. First International Study of Infarct Survival Collaborative Group. Lancet.
1986;2(8498):57-66.
31. Roberts R, Rogers WJ, Mueller HS, et al. Immediate versus deferred beta-blockade following
thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in
32. Chen ZM, Pan HC, Chen YP, et al. Early intravenous then oral metoprolol in 45,852 patients with
33. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-
34. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease:The
35. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with
36. Cannon CP, Braunwald E, McCabe CH,et al. Intensive versus moderate lipid lowering with statins
37. Pfeffer MA, Braunwald E, Moyé 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
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
zofenopril on mortality and morbidity after anterior myocardial infarction. The Survival of Myocardial
39. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with
clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators.
Lancet. 1993;342(8875):821-828.
40. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left
Todd J. Brinton
Randall Vagelos
BACKGROUND
Cardiogenic shock is a state of inadequate tissue perfusion and dysoxia due to primary cardiac
Shock criteria often absent on admission (<10% of patients) but usually develops early in the
hospitalization (mean time MI to onset 5.5 hours in the SHOCK trial registry)
Multifactorial etiologies (LV failure - 79%, Severe MR - 7%, acute ventricular septal defect (VSD)
Majority of cases secondary to AMI present with ST segment elevation myocardial infarct
(STEMI)
Persistent systemic hypotension: systolic blood pressure (SBP) <90mm Hg or mean arterial
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Cardiac index <1.8 liters/min/m2 or inotrope dependence to maintain cardiac output and blood
pressure (BP)
HISTORY
Rapid diagnosis essential: history and physical exam should be focused and brief with
Inquire about time course of symptoms, new or changing angina, shortness of breath (SOB),
paroxysmal nocturnal dyspnea (PND), orthopnea, edema, weight changes, or fatigue
P.62
PHYSICAL EXAM
Look for the following:
Narrow pulse pressure (pulse pressure <25% of the SBP has a sensitivity and specificity of 91%
Peripheral edema suggests some component of chronic HF and can be absent with acute HF
New systolic murmur suggests acute mitral regurgitation (MR) or VSD, assess for a thrill
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Complete blood count (CBC) w/ diff, comprehensive metabolic panel (CMP), cardiac enzymes,
APTT/PT, BNP
Serial lactate measurements and ABGs useful in following tissue perfusion and response to
therapy
ECG
Rapid assessment of potential acute coronary syndrome (ACS), arrhythmia, or heart block
Although most ACS associated with cardiogenic shock presents as a STEMI, significant ST
depression or other signs of ischemia should prompt consideration of early angiography in the
setting of shock
Inferior ST elevation should prompt R sided leads to assess for RV injury or infarct
Isolated anterior ST depression should prompt posterior leads to assess for true posterior STEMI
Chest X-ray
P.63
Pulmonary edema (1/3 of patients without pulmonary edema in the SHOCK trial)
Clear lungs with hypotension +/- hypoxia, consider massive PE
Echo
An extremely useful test for systolic function, regional WMAs, RV infarct, mechanical
Useful to assess for proximal pulmonary embollism (PE) and aortic dissection (sensitivity only
Even if patient is in acute renal failure (ARF) the benefits of IV contrast likely outweigh the
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Different phase of contrast needed for optimal PE and aortic dissection evaluations
P.64
Etiology Findings
shock)
- ST elevation often seen
decompensation
AMI
equalization of LV → LA pressure
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
in!)
effusion)
- Pulsus paradoxus
collapse, PW Doppler
rupture)
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
RCA ACS
syndrome”
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
- Cardiac tamponade
compromised by dissection
ventricular escape
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LV, left ventricular; LAD, left anterior descending; LVOT, left ventricular outfloor tract.
P.65
SPECIFIC THERAPIES
Patients with STEMI or ACS should be treated with ASA, heparin, GPIIB/IIIA inhibitors (see
Strongly consider withholding Clopidogrel if early angiography planned and patient is a surgical
candidate (lack of comorbidities and multiorgan system disease) as up to 40% of patients may
benefit from emergent CABG and bleeding may complicate an already critically ill patient
Improvement in TIMI 3 flow with the use of GPIIB/IIIA inhibitors in TIGER-PA trial prior to PCI
Revascularization
Timing of reperfusion is highly correlated with outcomes: 44% mortality if admitted within 3
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TIMI flow grade of infarct related artery (IRA) highly correlated with mortality: 27% in IRAs
with TIMI grade 3 flow versus 47% with TIMI grade 0/1 flow8
shocK” (SHOCK) randomized trial, successful angioplasty (TIMI grade 2 or 3 flow) associated
with 38% 30 day mortality versus 79% in unsuccessful angioplasty (TIMI grade 0 or 1 flow),
lending support to the open artery hypothesis9
P.66
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FIGURE 4-1 Initial evaluation and treatment of cardiogenic shock. Markers of poor tissue perfusion
include altered mentation, oliguria, cool extremities, azotemia, and lactic acidosis.
SHOCK trial mortality 50% with emergent revascularization (60% PCI, 40% CABG) versus 63% at
Benefit is probably beyond thrombolysis as 63% of initial medical therapy group and 49% of
Thrombolysis + IABP
Suggestion of mortality benefit with thrombolytic therapy (TT) in post-hoc analysis of the
SHOCK trial in the medical treatment group 60% mortality with versus 78% without TT though
assignment to TT was not randomized and results may represent selection bias10
with the use of an IABP + TT,11 and there is NO proven benefit with TT alone (see Figure 4-2)
Given high rate of thrombolysis in the early revascularization arm of SHOCK (and lack of harm),
P.67
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FIGURE 4-2 Effect of IABP added to thrombolysis on mortality in cardiogenic shock (GUSTO I, JACC
1997).
Placed in the cath lab with a left atrial inflow catheter (via transeptal puncture) and a femoral
Initial study in cardiogenic shock showed improvement of cardiac index from 1.7 → 2.4
Randomized trial of PVAD versus intra-aortic balloon pump (IABP) revealed improvement in
hemodynamic parameters in the PVAD group but with higher bleeding and leg ischemia
Can consider PVAD as an aggressive support intervention if IABP support is inadequate in the
setting of refractory cardiogenic shock
REFERENCES
1. Holmes DR, Berger PB, Hochman JS, et al. Cardiogenic shock in patients with acute ischemic
P.68
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
2. Hochman JS, Buller CE, Sleeper LA, et al. Cardiogenic shock complicating acute myocardial
infarction—etiologies, management and outcome: A report from the SHOCK Trial Registry. Should we
emergently revascularize Occluded Coronaries for cardiogenic shocK? J Am Coll Cardiol. 2000;36(3
Suppl A):1063-1070.
3. Stevenson LW, Perloff JK. The limited reliability of physical signs for estimating hemodynamics in
4. Hasdai D, Harrington RA, Hochman JS, et al. Platelet glycoprotein IIb/IIIa blockade and outcome of
cardiogenic shock complicating acute coronary syndromes without persistent ST-segment elevation. J
5. Fuster V, Alexander RW, O'Rourke RA. Hurst's the Heart. 11th ed. New York: McGraw-Hill Medical
6. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization and long-term survival in
7. Zeymer U, Vogt A, Zahn R, et al. Predictors of in-hospital mortality in 1333 patients with acute
myocardial infarction complicated by cardiogenic shock treated with primary percutaneous coronary
intervention (PCI): Results of the primary PCI registry of the Arbeitsgemeinschaft Leitende
8. Wong SC, Sanborn T, Sleeper LA, et al. Angiographic findings and clinical correlates in patients with
cardiogenic shock complicating acute myocardial infarction: A report from the SHOCK Trial Registry.
SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK? J Am Coll Cardiol.
9. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction
10. French JK, Feldman HA, Assmann SF, et al. Influence of thrombolytic therapy, with or without intra-
aortic balloon counterpulsation, on 12-month survival in the SHOCK trial. Am Heart J. 2003;146(5):804-
810.
11. Hayashi T, Hirano Y, Takai H, et al. Usefulness of ST-segment elevation in the inferior leads in
predicting ventricular septal rupture in patients with anterior wall acute myocardial infarction. Am J
Cardiol. 2005;96(8):1037-1041.
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12. Thiele H, Lauer B, Hambrecht R, et al. Reversal of cardiogenic shock by percutaneous left atrial-to-
13. Thiele H, Sick P, Boudriot E, et al. Randomized comparison of intra-aortic balloon support with a
percutaneous left ventricular assist device in patients with revascularized acute myocardial infarction
Paul J. Wang
BACKGROUND
Bradyarrhythmias result from abnormalities of sinus node function or A-V conduction. In this chapter we
review the initial recognition, triage, acute management, and definitive therapy for the
bradyarrhythmias.
DEFINITIONS
Bradycardia
Bradycardia is defined as a ventricular heart rate <60 beats per minute (bpm), and sinus bradycardia
exists when each QRS complex is preceded by a P wave of sinus node origin on the electrocardiogram
(ECG).
Sinoatrial blocks: Sinoatrial (S-A) blocks are uncommon and occur when there is disturbance of the
conduction of the electrical impulse from the heart's normal pacemaker, the S-A node, to the
surrounding atrium. (See Figure 5-1.) The severity of dysfunction can vary widely and there are many
ECG findings associated with S-A blocks (also called S-A exit blocks).1 The S-A blocks can be categorized
as first, second, and third degree based on the characteristics of the conduction disturbance.
First Degree
In first-degree S-A block, there is an increased time for the S-A node's impulse to reach and depolarize
the rest of the atrium and form a P wave on ECG (Figure 5-1). There are no abnormalities seen on the
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12-lead tracing with first-degree S-A block because impulse origination from the S-A node still produces
P.70
FIGURE 5-1 Sinoatrial (S-A) block. Normal sinus rhythms with various degrees of S-A block. Sinus
impulses not seen on the body surface ECG are represented by the vertical lines. With first-degree S-A
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block, although there is prolongation of the interval between the sinus impulses and the P wave, such a
delay cannot be detected on the ECG. A: Persistent 2:1 S-A block cannot be distinguished from marked
sinus bradycardia. B: The diagnosis of second-degree S-A block depends on the presence of pause or
pauses that are the multiple of the basic P-P interval. C: When there is a Wenckebach phenomenon,
there is gradual shortening of the P-P interval before the pause. With third-degree S-A block, the ECG
records only the escape rhythm. (Used with permission from Suawicz B, Knilans TK. Chou's
Second Degree
Type I (Wenkebach): In second-degree S-A block type I, there is a progressively increasing interval for
each S-A nodal impulse to depolarize the atrial myocardium and produce a P wave on ECG (Figure 5-1).
This
P.71
interval continues to lengthen until the S-A node's impulse does not depolarize the atrium at all, which
is manifested on ECG by a gradual shortening of the P-P interval with an eventual dropping of a P wave.
Type II: In second-degree S-A block type II, there is a fixed interval between the S-A node impulse and
the depolarization of the atrium with an intermittent S-A nodal impulse that fails to conduct to the
atrium (Figure 5-1). This manifests on ECG as a dropped P wave with a P-P interval surrounding the
pause that is two to four times the length of the baseline P-P interval.3
In second-degree S-A block with 2:1 conduction, every other impulse from the S-A node causes atrial
depolarization while the other is dropped. It is impossible to differentiate this from sinus bradycardia
on ECG unless the beginning or termination of the S-A block is recorded, in which case it manifests as a
Third Degree
In third-degree S-A block, none of the S-A nodal impulses depolarize the atrium, which appears on ECG
as either atrial stand-still or P waves retrogradely conducted from a junctional rhythm (Figure 5-1).
Sometimes there can be a long pause on the ECG until a normal sinus rhythm is resumed, which can be
difficult to distinguish from sinus pause or arrest due to abnormalities of sinus impulse formation.
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Sinus pause/sinus arrest: Sinus pause and sinus arrest are characterized by the failure of the S-A node
to form an impulse, manifesting on the ECG as a sinus pause of varying length. 1 Some sinus pauses
follow the spontaneous termination of atrial fibrillation because of the overdrive suppression of the
sinus node.
Sick sinus syndrome: Sick sinus syndrome includes a range of S-A node dysfunction that includes
inappropriate sinus bradycardia, sinus arrhythmia, sinus pause/arrest, S-A block, A-V junctional
chapter).4
Atrioventricular block: In atrioventricular block, electrical conduction is disturbed between the atrium
and the ventricle. As with S-A blocks, A-V blocks are categorized into first-, second-, and third-degree
P.72
First Degree
First-degree A-V block is defined as a prolonged P-R interval, greater than 200 milliseconds, which
remains constant. (See Figure 5-2.) On ECG, the P wave and QRS complex have normal morphology, and
a P wave precedes each QRS complex. The lengthening of the P-R interval results from a conduction
delay from within the atrium, the A-V node, or the His-Purkinje system.
Second Degree
Mobitz Type I (Wenckebach): Second-degree A-V block Mobitz type I is characterized by a P-R interval
that lengthens progressively until an impulse fails to conduct to the ventricles and a QRS complex is
dropped. (See Figure 5-3.) This block usually occurs at the level of the A-V node and above the His
bundle. The patient's QRS complex is usually narrow (less than or equal to 120 milliseconds) although
there may be a concomitant lower conduction disturbance leading to bundle branch block. On ECG, the
P-R interval lengthens as the R-R interval shortens, and the R-R interval that contains the dropped beat
is less than the sum of two of the shortest R-R intervals seen on the ECG. Also, on the ECG rhythm strip,
a grouping of beats can be seen.2,7 A consistent and diagnostic feature of Wenkebach is that the PR
interval after the dropped beat is shorter than those immediately preceding the AV block.
Mobitz Type II: Second-degree A-V block Mobitz type II is defined by a constant P-R interval that may be
normal or prolonged (>0.20 s) and periodic abrupt failure of the atrial impulse to conduct to the
ventricles. (See Figure 5-4.) The QRS complex is nearly always widened, since development of Mobitz
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Type II block almost always follows development of bundle branch block. This rule is so strong that
apparently abrupt A-V block without measurable preceding P-R prolongation in a patient with a narrow
QRS complex is more likely to be at the level of the A-V node and thus be an atypical Mobitz Type I A-V
FIGURE 5-2 First degree AV block: The PR interval here is > 200 ms with a 1:1 relationship of P waves to
2006, Mosby.)
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FIGURE 5-3 Mobitz Type I (Wenkebach) Second degree AV block: Fixed P-P interval with progressive PR
prolongation with development of AV block. Note the PR interval on the beat after the pause is the
Second-degree A-V block with 2:1 conduction: In second-degree A-V block with 2:1 conduction, every
other QRS complex is dropped, causing two P waves for each QRS complex. Since there is no way to
determine on ECG if the P-R interval lengthens before the dropped QRS complex, the primary method
of determining the level of the block is examining the QRS width. If the QRS complex is narrow, the 2:1
A-V block almost certainly exists at the level of the A-V node. If the QRS complex is widened, the level
of the block could be either at the level of the A-V node or infrahisian.
FIGURE 5-4 Second degree type II AV block: Fixed P-P interval with fixed PR interval and development
of AV block. Note the PR interval on the beat after the pause is identical to the one prior. This is in
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Third Degree
Third-degree A-V block, or complete heart block, occurs when no electrical impulses from the atria
conduct through to the ventricles. (See Figure 5-5.) The atria and ventricles thus depolarize and beat
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independently. An escape rhythm originating from the A-V junction or the ventricles below the level of
the block maintains the ventricular rate. In third-degree A-V block, the P waves march out regularly and
independently of the regular ventricular depolarization (QRS complexes). The atrial rate is generally
faster than the ventricular rate, because the latter is an escape rhythm, and the ventricular rate can
vary depending upon where the ventricular depolarization originates. 1 In some cases, the P-P interval
encompassing the escape QRS complex may be shorter than otherwise in the tracing, a phenomenon
Escape Rhythms
When electrical impulses fail to conduct to the ventricles from the atria, whether due to S-A block or A-
V block, ventricular depolarization can originate from more distal locations in the conduction system
that also possess automaticity. Generally the more distal the site of impulse origination, the slower the
rate generated. The ventricular rate is generally 40 to 60 bpm with a narrow QRS complex when it is
driven by a junctional pacemaker within the A-V node or above the His bundle. A ventricular pacemaker
is characterized by a widened QRS and a rate less than 40 bpm (except an accelerated idioventricular
rhythm with a rate >40 bpm). These rhythms originate in the His-Purkinje system and are usually
associated with a poorer prognosis.7 If no escape impulse is generated, then the result is an asystolic
arrest.
FIGURE 5-5 Third degree (Complete) AV block: Fixed P-P interval with AV dissociation: No relationship
between P waves and the QRS complexes. In this case the escape pacemaker is junctional and hence
the QRS is narrow and rate is relatively faster than a ventricular escape. (With permission: Goldberger:
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CAUSES
Intrinsic abnormalities of conduction may occur as the result of many complex changes in the cardiac
conduction system:
Congenital
Genetic abnormalities
Immunologic
o Lyme disease
Infectious
o Endocarditis
o Lyme disease
Ischemia or infarction
Infiltrative diseases
o Sarcoidosis
o Amyloidosis
Trauma
o Extra-cardiac causes:
Electrolyte abnormalities
Hypothyroidism
Hypothermia
Vasovagal reactions
CLINICAL PRESENTATIONS
Bradycardia can result in cerebral hypoperfusion leading to symptoms such as presyncope, syncope,
confusion, memory loss, and, rarely, seizure activity. Inability of the heart rate to increase in response
to increased physiologic demand, called chronotropic incompetence, can occur even when true
bradycardia is not present and can result in subjective effort intolerance, fatigue, weakness, and
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dyspnea.10 Sometimes, patients with advanced A-V block appear to be asymptomatic. Patients with
sinus node dysfunction and atrial arrhythmias, the tachycardia-bradycardia syndrome, can present with
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It is extremely important to take a careful medication history with particular focus on medications that
PHYSICAL EXAM
If some P waves are blocked, there will be a lack of coordination of the A wave in the jugular
venous waves with the carotid impulse. With complete A-V block or prolongation of the P-R
interval to more than 300 milliseconds, asynchronous atrial and ventricular contraction can
Cardiac enzymes to rule out myocardial infarction or ischemia as the predisposing condition
Electrolyte abnormalities
Chest X-ray
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Examine lung fields for evidence of pulmonary congestion and abnormal chamber size
Echocardiogram
Useful to evaluate for wall motion abnormalities, effusions, or valvular lesions secondary to
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MRI/CT
May play a role in identifying areas of ischemia/infarction and in ruling out rare infiltrative
INITIAL MANAGEMENT
Initial management of patients with bradycardia should be directed at identifying and treating
reversible causes and at providing rate support for those that are symptomatic. Temporary pacing is
generally indicated in patients with symptomatic bradycardia that is likely to recur, particularly in the
setting of syncope. Pacing may be performed initially transcutaneously, but this method is not well
tolerated due to pain and is unreliable for prolonged periods. Thus, transvenous pacing is generally
preferred. For mild degrees of bradycardia, particularly in reversible settings, acutely, sinus
bradycardia or A-V block with a narrow QRS complex may be treated with intravenous atropine, usually
0.5 to 1.0 mg. For a wide QRS complex, atropine may worsen the degree of A-V block since it may
increase the sinus rate but not improve A-V block below the level of the His bundle. Isoproterenol or
epinephrine is generally used in this setting. Figure 5-6 also indicates that IV dopamine may be used.
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FIGURE 5-6 ACLS bradycardia treatment algorithm. (From 2005 American Heart Association Guidelines
for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care; Part 7.3: Management of
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Oral theophylline has been used with some success in the treatment of sinus bradycardia that is likely
to be transient.11
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All patients with a severe or symptomatic bradycardia should be admitted to a monitored setting to
ensure prompt diagnosis and treatment. Patients who require temporary or permanent pacemaker
therapy according to the American College of Cardiology/American Heart Association Task Force
guidelines should be hospitalized for pacemaker implantation. (See Tables 5-1, 5-2, 5-3, and 5-4.)
Patients should be admitted to the cardiac intensive care unit (CCU) or an intermediate cardiac care
unit if the cause of the bradyarrhythmia necessitates admission (e.g., acute coronary syndrome), or if
accomplished
c. Type I second-degree A-V block with wide QRS complexes at slow rate
Adapted from Hongo RH, Goldschlager NF. Bradycardia and pacemakers. In Wachter RM,
Goldman L, Hollander H, eds. Hospital Medicine. 2nd ed. Philadelphia: Lippincott Williams &
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Wilkins. 2005.10
P.79
Class I (conditions for which there is evidence and/or general agreement that a given procedure
sinus pauses that produce symptoms; in some patients, bradycardia is iatrogenic and
occurs as a consequence of essential long-term drug therapy of a type and dose for
Class II (conditions for which there is conflicting evidence and/or divergence of opinion about
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therapy, with heart rate <40 bpm when a clear association between significant
symptoms consistent with bradycardia and the actual presence of bradycardia has not
2. Syncope of unexplained origin when major abnormalities of sinus node function are
1. In minimally symptomatic patients, chronic heart rate <40 bpm while awake (Level of
evidence C)
Class III (conditions for which there is evidence and/or general agreement that a
sinus bradycardia (heart rate <40 bpm) is a consequence of long-term drug treatment
2. Sinus node dysfunction in patients with symptoms suggestive of bradycardia and clearly
3. Sinus node dysfunction with symptomatic bradycardia due to nonessential drug therapy
*
The weight of the evidence was ranked highest (A) if the data were derived from multiple
randomized clinical trials that involved large numbers of patients and intermediate (B) if the
data were derived from a limited number of randomized trials that involved small numbers of
rank (C) was given when expert opinion was the primary basis for the recommendation.
Adapted with permission from Gregoratos G, Abrams J, Epstein AE, et al. ACC/AHA/NASPE 2002
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Class I
1. Third-degree and advanced second-degree A-V block at any anatomic level, associated
b. Arrhythmias and other medical conditions that require drugs that result in
c. Documented periods of asystole ≥3.0 s or any escape rate <40 bpm in awake,
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e. Postoperative A-V block that is not expected to resolve after cardiac surgery
(Level of evidence C)
Class IIa
1. Asymptomatic third-degree A-V block at any anatomic site with average awake
2. Asymptomatic type II second-degree A-V block with narrow QRS; when type II second-
degree A-V block occurs with a wide QRS, pacing becomes a Class I recommendation
(Level of evidence B)
Class IIb
1. Marked first-degree A-V block (>0.30 s) in patients with left ventricular dysfunction and
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limb-girdle dystrophy, and peroneal muscular atrophy) with any degree of A-V block
(including first-degree A-V block) with or without symptoms, because there may be
Class III
2. Asymptomatic type I second-degree A-V block at the supra-His (A-V node) level or not
3. A-V block expected to resolve and/or unlikely to recur (e.g., drug toxicity, Lyme
evidence B)
a
A symptom complex of fatigue, weakness, dizziness, hypotension, effort intolerance, and
pulmonary and central venous hypertension caused by inappropriate relationships between atrial
Adapted with permission from Gregoratos G, Abrams J, Epstein AE, et al. ACC/AHA/NASPE 2002
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TABLE 5-4 Indications for permanent pacing after the acute phase of a myocardial
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infarction
Class I
1. Persistent second-degree A-V block in the His-Purkinje system with bilateral bundle-
branch block or third-degree A-V block within or below the His-Purkinje system (Level
of evidence B)
Class IIa
None
Class IIb
1. Persistent second- or third-degree A-V block at the A-V node level (Level of evidence B)
Class III
evidence B)
2. Transient A-V block in the presence of isolated left anterior fascicular block (Level of
evidence B)
3. Acquired left anterior fascicular block in the absence of A-V block (Level of evidence B)
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4. Persistent first-degree A-V block in the presence of bundle-branch block that is old or
See Table 5-2 for definitions of classes and levels of evidence. (Adapted with permission from
Gregoratos G, Abrams J, Epstein AE, et al. ACC/AHA/NASPE 2002 guideline update for
Cardiol. 2002;40:1703-1719. Copyright 2002 by the American College of Cardiology and American
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Dual chamber pacing vs. VPS (J Am Coll Cardiol 199914) Dual chamber pacing with
syncope. NNT = 2
Pacing with rate drop VPS II (Card Electrophysiol Pacing with rate drop sensing
sensing vs. sensing alone Rev 200315) N = 100 → 23% RRR in risk of syncope
syncope
Atrial vs. ventricular Prospective randomized trial Atrial pacing → 69% RRR of
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REFERENCES
1. Ufberg JW, Clark, JS. Bradydysrhythmias and atrioventricular conduction blocks. Emerg Med Clin
2. Olgin JE, Zipes DP. Specific arrhythmias: Diagnosis and treatment. In: Braunwald E, Zipes DP, Libby
P, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 6th ed. Philadelphia: WB
Saunders; 2001:815-889.
4. Shaw DB, Southall DP. Sinus node arrest and sino-atrial block. Eur Heart J. 1984;5(Suppl A):83-87.
5. Suawicz B, Knilans TK. Chou's Electrocardiography in Clinical Practice. 5th ed. Philadelphia: WB
Saunders; 2001:321.
http://www.frca.co.uk/article.aspx?articleid=
7. Rardon DP, Miles WM, Zipes DP. Atrioventricular block and dissociation. In: Zipes DP, Jalife J, eds.
Cardiac Electrophysiology: From Cell to Bedside. 3rd ed. Philadelphia: WB Saunders; 2000:451-459.
8. Denes P, Levy L, Pick A, et al. The incidence of typical and atypical A-V Wenckebach periodicity. Am
Heart J. 1975;89:26-31.
10. Hongo RH, Goldschlager NF. Bradycardia and pacemakers. In Wachter RM, Goldman L, Hollander H,
eds. Hospital Medicine. 2nd ed. Philadelphia: Lippincott Williams & Wilkins. 2005.
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P.83
11. Benditt DG, Benson DW Jr, Kreitt J, et al. Electrophysiologic effects of theophylline in young
12. 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care; Part 7.3: Management of Symptomatic Bradycardia and Tachycardia. Circulation.
2005;112:IV-67-IV-77.
13. Gregoratos G, Abrams J, Epstein AE, et al. ACC/AHA/NASPE 2002 guideline update for implantation
1719.
14. Connolly SJ, Sheldon R, Roberts RS, et al. The North American Vasovagal Pacemaker Study (VPS). A
randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope. J Am Coll
15. Sheldon R, Connolly S, Vasovagal Pacemaker Study II Investigators. Second Vasovagal Pacemaker
Study (VPS II): Rationale, design, results, and implications for practice and future clinical trials Card
16. Andersen HR,Thuesen L, Bagger JP, et al. Prospective randomized trial of atrial versus ventricular
Amin Al-Ahmad
The tachyarrhythmias presented in this chapter and the approach to their differential diagnosis,
workup, and treatment are among the most common problems encountered in inpatient cardiology.
These entities range in gravity from arrhythmias that are a nuisance, allowing for careful consideration
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DEFINITIONS
Wide complex tachycardia: QRS duration >120 milliseconds with or without pre-excitation
Pre-excitation: Initial “slurring” of the QRS complex implying manifest antegrade conduction
down an accessory bypass tract (e.g., WPW pattern); may see in sinus rhythm atrial fibrillation
Though technically SVT includes AF, some exclude AF as a separate entity for the purposes of
nomenclature for multiple reasons
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Ventricular tachycardia (VT): A tachycardia arising from and exclusively involving the tissue
beneath the compact portion of the AV node, including the His bundle, bundle branches, and
ventricular myocardium
10% of VT occurs in structurally normal hearts arising both from the endocardium1,2 and
epicardium3
HISTORY
History of myocardial infraction (MI), congestive heart failure (CHF) increase the risk of
Drop attack (sudden syncope without prodrome) is suggestive of cardiac mediated syncope but
its absence should not dissuade you from considering the diagnosis4
Palpitations are also commonly felt in the recovery phase of neurocardiogenic syncope
amiodarone
etc.
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o Digoxin toxicity
PHYSICAL EXAM
Hypotension or clinical instability does not distinguish between SVT and VT!
Cannon A waves may be observed in the jugular venous pulse and in the setting of a wide
complex tachycardia are indicative of A-V dissociation and highly suggestive of ventricular
tachycardia
Crackles or wheezes may suggest heart failure but also consider concomitant pulmonary
Examine chest wall for the presence of an ICD or pacemaker that you can interrogate to reveal
Murmurs may point to cardiac disease in general, which is useful, but an S3 is suggestive of
decompensated heart failure and can be the cause or result of an arrhythmia
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FIGURE 6-1 Algorithm for initial approach to tachyarrhythmias. DDX, differential diagnosis; VT,
AVNRT, A-V nodal reentrant tachycardia; AT, atrial tachycardia; JET, junctional ectopic tachycardia.
INITIAL MANAGEMENT
If the patient has an ICD or pacemaker (particularly dual chamber), consider interrogation to
help with workup of the arrhythmia
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Differential diagnosis includes VT versus SVT with aberrancy or pre-excited tachycardias. (See
Table 6-1.)
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disease
QRS widening
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concordance
pattern) 7
>50:1 LR for VT V6: rS (small r,
favors SVT
QRS
favors SVT
P.89
Therefore, approach WCT with a prejudice toward the diagnosis of VT and consider SVT w/ aberrancy
Polymorphic VT with normal QT interval: Strongly consider acute ischemia as the etiology
Torsade de pointes
Brugada syndrome: Characteristic atypical RBBB with ST elevation (leads to VF rather than VT)
Bidirectional VT: Associated with digoxin toxicity
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AVNRT is the most common cause of paroxysmal SVT in adults (50%), followed by AVRT (40%)
If regular, rhythm useful to divide into short R-P, long R-P, or no R-P where the “R-P” interval
o Short R-P tachycardia: R-P interval < P-R interval: AVNRT, AVRT, atypical atrial
tachycardia (AT)
o Long R-P tachycardia: R-P interval > P-R interval: Sinus tachycardia, SNRT, AT,
o No R-P tachycardia (no visible P waves): AVNRT most likely, atrial flutter, rarely AT or
JET
Rarely fascicular VT can present with minimally prolonged QRS, also can terminate with
verapamil or diltiazem and therefore mimic SVT9
In an unselected population Valsalva followed by carotid sinus massage terminated PSVT in 28%
of patients10
P.90
neurologic complications in 16,000 occurrences of carotid sinus massage (CSM) and only 2 had
permanent disability11
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FIGURE 6-2 Algorithm for the management of wide complex tachycardias. * VT can occasionally be
irregular especially during initiation = If WCT is actually VT, adenosine can precipitate VF, have
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FIGURE 6-3 Algorithm for the management of narrow complex tachycardias. A-V block, atrioventricular
block; AT, atrial tachycardia; AVNRT, atrioventricular nodal reentrant tachycardia; AVRT,
atrioventricular reentrant tachycardia; JET, junctional ectopic tachycardia; SNRT, sinus node reentrant
tachycardia
*
Caution with WPW pattern on baseline ECG, can→ AF → VF (have defibrillator immediately available)
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interaction
min up to max 3
mg/kg
Therapeutic level:
1.5-5.0 µg/mL
mg/min
12 mg/kg and
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de pointes
Lidocaine As above
bradycardia hyperglycemia
dyspnea
proximal peripheral
Central line
preferred if
already in place
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doses hypotension
over 2 min
infusion: 5-15
mg/h
infusion: 0.125
mg/min
pre-
excitation
Amiodarone As above, not FDA As above
approved but
reasonable
failure reasonable
AF See chapter on AF
Modified from Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the
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Cardiology/American Heart Association Task Force on Practice Guidelines and the European
Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001
Guidelines for the Management of Patients With Atrial Fibrillation): Developed in collaboration
with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation.
2006;114(7):e257-354.12
P.93
REFERENCES
P.94
2. Ohe T, Shimomura K, Aihara N, et al. Idiopathic sustained left ventricular tachycardia: Clinical and
3. Daniels DV, Lu YY, Morton JB, et al. Idiopathic epicardial left ventricular tachycardia originating
remote from the sinus of Valsalva: Electrophysiological characteristics, catheter ablation, and
4. Fuster V, Alexander RW, O'Rourke RA. Hurst's the Heart. 11th ed. New York: McGraw-Hill Medical
5. Tchou P, Young P, Mahmud R, et al. Useful clinical criteria for the diagnosis of ventricular
6. Zipes DP, Jalife J. Cardiac Electrophysiology: From Cell to Bedside. 4th ed. Philadelphia: WB
Saunders; 2004.
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7. Lau EW, Pathamanathan RK, Ng GA, et al. The Bayesian approach improves the electrocardiographic
8. Josephson ME. Clinical Cardiac Electrophysiology: Techniques and Interpretations. 3rd ed.
9. Elswick BD, Niemann JT. Fascicular ventricular tachycardia: An uncommon but distinctive form of
10. Lim SH, Anantharaman V, Teo WS, et al. Comparison of treatment of supraventricular tachycardia
by Valsalva maneuver and carotid sinus massage. Ann Emerg Med. 1998;31(1):30-35.
11. Davies AJ, Kenny RA. Frequency of neurologic complications following carotid sinus massage. Am J
Cardiol. 1998;81(10):1256-1257.
12. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of
Patients with Atrial Fibrillation: A report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for
Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients
With Atrial Fibrillation): Developed in collaboration with the European Heart Rhythm Association and
Henry Hsia
BACKGROUND
Sudden cardiac death (SCD) is defined as death from cardiovascular causes shortly after the onset of
symptoms in a person without a condition that would otherwise appear fatal.1 Estimates as to the
impact of SCD on our health care system put the total annual mortality up to 450,000, which is 63% of
Ventricular arrhythmia (60% to 80%): Most commonly VT → VF, also primary VF, or torsade de
pointes
Bradyarrhythmia/asystole
Pulseless electrical activity (PEA)
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In a series of young sudden death patients <40 years old without known heart disease, the most
common etiology was still cardiac (73%). Coronary heart disease (CHD) was the most common cause in
those >30 (58%), while myocarditis (22%), hypertrophic cardiomyopathy (HCM) (22%), and conduction
system disease (13%) were more common in those <20 years of age.5 (See Table 7-1.)
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syndrome common)
• Dilated cardiomyopathy
cardiomyopathy VF
(HOCM)
• Trauma
associated
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(ARVD)
• Short QT syndrome
• Inflammatory and
infiltrative myocardial
disease
• Ventricular
noncompaction
• Congenital heart
disease
OUTCOMES
SCD is associated with a high incidence of mortality, and the ability to rescue the patient probably
depends most on timely interventions that restore perfusion to and protect vital organs. Unfortunately,
many patients will die in the prehospital setting or early in the resuscitative effort. For out-of-hospital
sudden death, 20% make it to the hospital, half of them will die in the hospital, and only about half of
the survivors will have any “meaningful” survival. Hence in total only about 5% of patients who sustain
an out-of-hospital sudden death in the absence of ICD therapy will have a good outcome. In contrast,
the survival with early defibrillation when the initial rhythm is VT or VF is substantially higher with up
to 40% of those being discharged with a good neurologic outcome and is the single factor most strongly
associated with a good outcome.4,6 Those that regain a sustained perfusing rhythm are candidates for
Survival decreases by ~10% for each minute of lapsed time before restoration of a viable
rhythm
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Asystole (0% to 2% survival) or pulseless electrical activity (PEA) (11% survival) as the initial
rhythm
End tidal CO2 by capnography <10mm Hg after 20 minutes of resuscitation in patients with PEA
predicts death with 100% sensitivity and specificity7
FIGURE 7-1 Approach to sudden cardiac death. ACLS, advanced cardiac life support; ABC, airway,
breathing, circulation; VF, ventricular fibrillation; PCI, percutaneous coronary intervention; ICD,
internal cardioverter defibrillator; CCU, coronary care unit; DVT, deep venous thrombosis
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*
See above for details.
‡ Especially if planned angiography. Intracranial hemorrhage is the most common noncardiac cause of
sudden death. Also trauma secondary to cardiac arrest may → bleeding which can be complicated by
therapeutic anticoagulation.
**
See following for details.
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High degree of obstructive coronary artery disease (CAD) (71%) in an unselected population of
SCD
ST elevation+chest pain are highly predictive of recent coronary occlusion (87%), ST elevation
alone (63%)
Up to 25% of those with recent total coronary occlusions have NO pathologic ST elevation
Therefore, coronary angiography is reasonable in all survivors of SCD, especially in those with
Consider for patients who do not regain consciousness immediately after cardiac arrest
Induced hypothermia 32-34 degrees Celsius by cooling blankets, ice packs, or central venous
Sedation with midazolam or Diprivan, analgesia with fentanyl, paralysis with nondepolarizing
Further Testing
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In the absence of CHD, other less common structural, metabolic, and primary electrical etiologies
Review of History
History of known structural heart disease: prior myocardial infarct/coronary artery disease
(MI/CAD), hypertrophic cardiomyopathy (HCM), rheumatic heart disease, valvular CM, dilated
cardiomyopathy (DCM)
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o Amyloidosis (low volts), epsilon wave for arrhythmogenic right ventricular dysplasia
(ARVD)
Pre-excitation suggestive of a bypass tract which could → rapid A-V conduction and VF
Brugada syndrome:
Echocardiography
Looks for anatomical correlates of the underlying substrate: Wall motion abnormalities,
May reveal evidence of left ventricular hypertrophy (LVH), dilated cardiomyopathy (DCM),
While often performed early, should consider repeating if abnormal LV function >48 hours after
resuscitation because early myocardial stunning may improve11
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Cardiac MRI
Correlates with increased progression of disease and risk factors for sudden death in patients
Late gadolinium enhancement correlates with risk of SCD in patients with nonischemic
cardiomyopathy16
Contraindicated with pacemakers, ICD, or ferromagnetic medical devices
Electrophysiology Study
Primarily indicated in those with an accessory pathway (WPW pattern) to assess the
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In pts who had a SCD and sustained monomorphic VT is suspected, in a setting of MI, to induce
VT and determine the number, morphology, rate of VT and its response to antitachycardia
Except in the case of a clear link to an accessory pathway → sudden death, most patients
should still get an ICD despite RF ablation
SECONDARY PREVENTION
ICD Therapy
Likely greater benefit in those with left ventricular ejection fraction (LVEF) <35%17
Beta Blockers
Beta blockade is associated with significant reductions in mortality in systolic heart failure
from both reductions in progressive pump failure and sudden death. 18,19
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Amiodarone
In contrast to most other antiarrhythmic drugs (see Table 7-2), amiodarone is not pro-
Should not replace beta blockers if indicated for heart failure as they have proven mortality
Should not replace ICD therapy but may consider as an adjunct to reduce shocks
800 to 1200 mg/day in divided doses while in hospital, 400 mg/day for 3 to 4 weeks, 200
mg/day maintenance
Attention to toxicities: Baseline and interval TSH, PFTs (w/ DLCO), chest X-ray, LFTs, Optho
exam
P.101
acquired long QT
syndrome
If cardioverted and
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infusion
3 mg/kg
1-4 mg/min
infusion
Nausea, vomiting
Therapeutic level:
1.5-5.0 µg/mL
mg/min diarrhea
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significant hypokalemia,
bradycardia hypoglycemia
Transvenous HR 80-100,
with bradycardia
P.102
Acute therapies
Coronary angiography with Spaulding et al. (N Odds ratio 5.2 (95% CI 1.2-24.5) for
angioplasty
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Combined PCI and induced Knafelj et al. Hypothermia combined with PCI in
NNT = 3
Antiarrhythmics
NNT = 5
<40% at 21 mo
NNT = 91
NO difference in mortality
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
NNT = 42
NO difference in mortality
mortality
ICD Therapy
Secondary prevention
ICD vs. amiodarone in AVID27 (N Engl J Med ICD → 24% RRR of total mortality (A
SCD or with
hemodynamically
NNT = 13
significant VT
ICD vs. amiodarone or CASH28 (Circulation ICD → 23% RRR of total mortality
significantly underpowered
ICD vs. amiodarone Meta-analysis ICD → Hazard ratio 0.72 for total
NNT = 29
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Primary prevention
ICD vs. conventional MADIT II29 (N Engl J ICD → 31% RRR of total mortality (C
therapy for primary Med 2002) n= 19.8% I 14.2%) at 20 mo. Avg EF 23%
MI with EF <30%
NNT = 18
ICD vs. amiodarone vs. SCD-HeFT20 (N Engl J ICD 23% RRR of total mortality (P
placebo with EF <35% and Med 2005) n= 29% A 28% I 22%) at 4 y. Avg EF 25%
and placebo
NNT = 15
P.103
REFERENCES
1. Goldstein S. The necessity of a uniform definition of sudden coronary death: Witnessed death within
P.104
2. Zheng ZJ, Croft JB, Giles WH, et al. Sudden cardiac death in the United States, 1989 to 1998.
Circulation. 2001;104(18):2158-2163.
3. Bayes de Luna A, Coumel P, Leclercq JF. Ambulatory sudden cardiac death: Mechanisms of
production of fatal arrhythmia on the basis of data from 157 cases. Am Heart J. 1989;117(1):151-159.
153
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
4. Rea TD, Eisenberg MS, Becker LJ, et al. Temporal trends in sudden cardiac arrest: A 25-year
5. Drory Y, Turetz Y, Hiss Y, et al. Sudden unexpected death in persons less than 40 years of age. Am J
Cardiol. 1991;68(13):1388-1392.
6. Bunch TJ, White RD, Gersh BJ, et al. Outcomes and in-hospital treatment of out-of-hospital cardiac
arrest patients resuscitated from ventricular fibrillation by early defibrillation. Mayo Clin Proc.
2004;79(5):613-619.
7. Levine RL, Wayne MA, Miller CC. End-tidal carbon dioxide and outcome of out-of-hospital cardiac
8. Spaulding CM, Joly LM, Rosenberg A, et al. Immediate coronary angiography in survivors of out-of-
9. Knafelj A, Radsel A, Ploj A, et al. Primary percutaneous coronary intervention and mild induced
10. Al-Senani FM, Graffagnino C, Grotta JC, et al. A prospective, multicenter pilot study to evaluate the
feasibility and safety of using the CoolGard System and Icy catheter following cardiac arrest.
Resuscitation. 2004;62(2):143-150.
11. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac
12. Bednar MM, Harrigan EP, Anziano RJ, et al. The QT interval. Prog Cardiovasc Dis. 2001;43(5 Suppl
1):1-45.
13. Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: Report of the second consensus
conference: Endorsed by the Heart Rhythm Society and the European Heart Rhythm Association.
Circulation. 2005;111(5):659-670.
14. Gaita F, Giustetto C, Bianchi F, et al. Short QT Syndrome: A familial cause of sudden death.
15. Moon JCC, McKenna WJ, McCrohon JA, et al. Toward clinical risk assessment in hypertrophic
2003;41(9):1561-1567.
16. Assomull RG, Prasad SK, Lyne J, et al. Cardiovascular magnetic resonance, fibrosis, and prognosis in
154
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P.105
17. Connolly SJ, Hallstrom AP, Cappato R, et al. Meta-analysis of the implantable cardioverter
defibrillator secondary prevention trials. AVID, CASH and CIDS studies. Antiarrhythmics vs Implantable
Defibrillator study. Cardiac Arrest Study Hamburg. Canadian Implantable Defibrillator Study. Eur Heart
J. 2000;21(24):2071-2078.
18. Goldstein S, Fagerberg B, Hjalmarson AJ, et al. Metoprolol controlled release/extended release in
patients with severe heart failure: Analysis of the experience in the MERIT-HF study. J Am Coll Cardiol.
2001;38(4):932-938.
19. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in
patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med.
1996;334(21):1349-1355.
20. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for
21. Sim I, McDonald KM, Lavori PW, et al. Quantitative overview of randomized trials of amiodarone to
22. Bashir Y, Paul VE, Griffith MJ, et al. A prospective study of the efficacy and safety of adjuvant
metoprolol and xamoterol in combination with amiodarone for resistant ventricular tachycardia
23. Bokhari F, Newman D, Greene M, et al. Long-term comparison of the implantable cardioverter
24. Randomized antiarrhythmic drug therapy in survivors of cardiac arrest (the CASCADE Study). The
25. Julian DG, Camm AJ, Frangin G, et al. Randomized trial of effect of amiodarone on mortality in
patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. European
26. Cairns JA, Connolly SJ, Roberts R, et al. Randomized trial of outcome after myocardial infarction in
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from near-fatal ventricular arrhythmias. The Antiarrhythmics versus Implantable Defibrillators (AVID)
P.106
28. Kuck KH, Cappato R, Siebels J, et al. Randomized comparison of antiarrhythmic drug therapy with
implantable defibrillators in patients resuscitated from cardiac arrest: The Cardiac Arrest Study
29. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with
Paul J. Wang
BACKGROUND
Atrial fibrillation (AF) is the most common chronic cardiac dysrhythmia. The estimated prevalence of
atrial fibrillation and atrial flutter is greater than 2.2 million individuals in the United States, with
estimated incidence of greater than 75,000 cases per year.1 The median age of individuals with AF is
approximately 75 years. The estimated lifetime risk for the development of AF, when studied in all
individuals age 40 years or older free of AF in the Framingham Heart Study, was estimated to be
approximately 1 in 4.2 The morbidity and mortality attributable to AF is significant as its presence
confers an increased risk for congestive heart failure (CHF), embolic events including stroke, and death.
ELECTROPHYSIOLOGIC FEATURES
under investigation with proposed, possibly coexisting, models that include the following:
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heterogeneous, fibrillatory conduction. Of note, numerous foci have been identified though
the region of the pulmonary veins in the left atrium appears to be most common 3
P.108
Heterogeneity of autonomic innervation likely plays a further role in the initiation and
maintenance of AF
AF appears to be initiated by atrial premature beats (most commonly), as well as by atrial flutter and
The ECG appearance of AF is most immediately suggested by an irregular ventricular rhythm with no
Atrial activity: P waves are replaced by f waves, typically smaller waves characterized by
variable morphology, amplitude, and intervals, with rapid rate generally between 350 and 600
Ventricular response: The ventricular response (R-R interval) is generally irregular with rate of
90 to 170 bpm in an untreated individual. The ventricular rate is significantly less than the
atrial rate due to block at the A-V node and possibly due to collision of fibrillatory wave fronts.
However, the ventricular rate varies significantly depending upon multiple factors including
o action of drugs
o autonomic tone
Accessory pathways? Assess for the possible presence of an accessory pathway(s) capable of
antegrade conduction, as ventricular rates can be greater than 300 bpm and deteriorate into
typical appearance on an electrocardiogram during sinus rhythm (namely, short P-R interval
with delta wave), by extremely rapid ventricular rates greater than 200 bpm during AF, and/or
INITIAL MANAGEMENT
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Attempt to identify and address underlying etiologies, risk factors, and/or triggers for AF,
Assess the acute and/or chronic effects of AF including associated symptoms and its
hemodynamic consequences. This will help guide decisions of whether or not to pursue a
strategy of attempting to restore and maintain sinus rhythm.
P.109
CLINICAL CONSEQUENCES
Hemodynamic Compromise
The hemodynamic derangements in AF may or may not be accompanied with symptoms, most commonly
palpitations, dyspnea, decreased exercise tolerance, lightheadedness, syncope, and chest discomfort.
Loss of effective atrial contraction and thus atrioventricular (A-V) synchrony; this may be
Inappropriately elevated heart rate. Chronically elevated atrial rates may lead to adverse
atrial remodeling (including atrial dilatation), and persistently elevated ventricular rates may
Thromboembolic Risk
Multiple factors contribute to increased thromboembolic events in individuals with AF, although static
flow within the left atrial appendage (LAA) appears most significant. The rate of ischemic stroke varies
significantly depending upon the presence of associated stroke risk factors, but on average is estimated
to be approximately 5% per year in individuals with nonvalvular AF (that is, AF not associated with
rheumatic mitral valve disease, valve replacement, or valve repair). This represents an approximately
sixfold increase in the risk of thromboembolic events in individuals with nonvalvular AF as compared to
individuals without AF. The attributable risk of stroke in individuals with AF increases significantly with
advancing age.5
CLASSIFICATION 6
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The following definitions apply to episodes of AF lasting longer than 30 seconds without a reversible
cause. It is useful to identify a first-detected episode of AF, acknowledging that the duration of that
episode is generally unknown and prior undetected episodes may have been present. When AF has been
Paroxysmal: AF episode(s) usually lasts 7 days or less (and most less than 24 hours) and
terminates spontaneously
Persistent: AF episode(s) usually lasts greater than 7 days and does not terminate
spontaneously
Permanent: Cardioversion has failed and/or attempts have been foregone
P.110
ETIOLOGIES
The delineation of the following risk factors for AF is somewhat arbitrary, overlap exists, and multiple
etiologies are often present in one individual. Nonetheless, “secondary” AF is intended to draw
attention to cases in which AF may not be the primary problem, and may be ameliorated or terminated
“Primary” AF
Advancing age
hypertrophy
Coronary heart disease, especially when complicated by history of myocardial infarction (MI) or
CHF
Valvular heart disease, especially mitral regurgitation, mitral stenosis, and tricuspid
regurgitation. In developed nations, this etiology is decreasing in frequency due to the reduced
Heart failure
intracardiac (or adjacent) tumors or thrombi, obstructive sleep apnea, and obesity
Lone or “idiopathic” AF is said to be present in individuals younger than 60 years of age with
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assessment. The risk profile, including thromboembolic complications and death, is typically
lower, though these individuals generally progress beyond the lone AF category with time.
conduction disease, and other electrophysiologic abnormalities likely account for a significant
proportion of incident AF but their role remains incompletely defined at present.
“Secondary” AF
Potentially reversible, “acute” causes and/or triggers for AF include the following:
Pericarditis
Myocarditis
Infection
Postoperative state, especially with cardiac, pulmonary, or esophageal interventions
P.111
Toxins, such as alcohol, cocaine, amphetamines, and caffeine, including withdrawal states
EVALUATION
It is critical to carefully consider in every single patient potential etiologies and risk factors
predisposing one to AF. This provides an opportunity to identify and modify significant concomitant
medical disease. However, one must be cognizant that even despite correction of a suspected
reversible cause of AF, a patient may have underlying paroxysmal AF necessitating long-term therapy.
To evaluate possible etiologies of AF and to guide management decisions, it is reasonable to obtain the
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Characterize the patient's pattern of AF; define her symptoms; document her response to prior
therapies; identify possible etiologies, risk factors, and triggers; and assess for clinical evidence of
heart failure.
ECG
Verify the presence of AF, assess for accessory pathways, determine ventricular rate, document
concomitant cardiac disease (e.g., atrial size, left ventricular hypertrophy [LVH], prior MI), monitor
Determine LV size and function, screen for valvular and pericardial disease, measure atrial size, assess
for LVH, and estimate pulmonary pressure. The sensitivity for detection of LA thrombus is low for TTE
as opposed to TEE.
Laboratory Tests
Tests include thyroid panel, serum electrolytes, complete blood count (CBC), renal and hepatic
function, and coagulation tests in part to assess for possible risk factors for AF and to guide
pharmacologic therapy.
P.112
Additional tests may be indicated. This notably may include but is not limited to the following:
Chest imaging
Holter monitoring or event recording (in part to assess rate control, confirm diagnosis of AF,
Exercise testing (in part to evaluate for ischemia prior to using Class 1C antiarrhythmic drugs,
assess rate control, define exercise tolerance, and possibly reproduce exercise-induced AF)
MANAGEMENT—OVERALL STRATEGY
While the management of patients with AF is highly individualized, principal components include the
following:
Carefully consider and address the potential etiologies, risk factors, and/or triggers for AF
stroke risk
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Consider employing measures to restore and maintain sinus rhythm, if indicated, generally via
Specific guidelines regarding each of these components are discussed in depth for the remainder of the
chapter.
In all stable patients with atrial fibrillation of any clinical pattern, it is recommended that they be
started on appropriate antithrombotic therapy (if safe) and rate control (if needed). However, the
issue of whether or not attempts should also be made to maintain sinus rhythm is debatable. Despite
the hypothesized benefits of maintaining sinus rhythm over rate control alone, randomized clinical
trials comparing these two strategies have failed to show a statistically significant difference in
mortality, stroke, or quality of life (see “Landmark Clinical Trials” section for further details).7, 8, 9, 10,
and 11
Importantly, regardless of the strategy pursued, appropriate antithrombotic therapy is generally
warranted.
MANAGEMENT—RATE CONTROL
Acute Setting
The goal for the ventricular rate will vary significantly depending upon the clinical scenario.
As outlined below, amiodarone may be an acceptable agent for rate control despite its
P.113
TABLE 8-1 Selected agents for rate control in the acute setting
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IVCI HF or hypotension
life
HF or hypotension
exercise extreme
caution if used despite
HF or hypotension
Diltiazem 0.25 mg/kg (~20 5-15 mg/h IVCI ↓BP, HB, HF; exercise
in 15 min at hypotension
IV over 2 min
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in 15-30 min
Patients with accessory pathway: Rate control may be appropriate though conversion to sinus
rhythm and/or catheter ablation of the accessory pathway is generally recommended. Agents
that slow conduction across the A-V node (including nondihydropyridine CCB, β-blockers, and
digoxin) are not recommended as they may lead to rapid antegrade conduction across the
ventricular arrhythmia
(attention to QTc),
pulmonary toxicity,
hepatotoxicity, hyper-
or hypothyroidism,
discoloration, warfarin
if used in renal
insufficiency)
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10 min IVCI
↓BP, hypotension; IVCI, intravenous continuous infusion; HB, heart block; HF, heart failure; ↓HR,
Modified from Fuster et al. ACC/AHA/ESC 2006 guidelines for the management of patients with
P.114
Chronic Setting
It is reasonable to pursue a goal ventricular rate of 60 to 80 bpm at rest and 90 to 115 bpm
It is reasonable to consider using a 24-hour Holter monitor (with a goal overall average rate of
approximately ≤100 bpm) and/or exercise testing as an adjunct in assessing the adequacy of
rate control therapy.
nonpharmacologic attainment of rate control via catheter ablation of the A-V node in
conjunction with permanent ventricular pacing has been demonstrated to be effective and is
associated with improvement in symptoms.12
P.115
TABLE 8-2 Selected agents for rate control in the nonacute and/or chronic setting
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min
upon formulation
Verapamil 120-360 mg PO total daily, in 1-2 ↓BP, HB, HF, digoxin interaction
upon formulation
Amiodarone Multiple dosing regimens are Days ↓BP (though less significant than
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↓BP, hypotension; IVCI, intravenous continuous infusion; HB, heart block; HF, heart failure; ↓HR,
Modified from Fuster et al. ACC/AHA/ESC 2006 guidelines for the management of patients with
MANAGEMENT—RHYTHM CONTROL
Direct-current (DC) cardioversion is generally more effective and reliable than pharmacologic
P.116
Direct-Current Cardioversion
anticoagulation therapy.
o The patient should be fasting with electrolytes and drug levels (including digoxin)
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monophasic (or 200J biphasic) as the initial shock for external cardioversion in most
conduction system disease including sick sinus syndrome who are at risk for prolonged
Pharmacologic Cardioversion
o Class IC drugs, such as propafenone and flecainide, are thought to be more effective
than agents such as amiodarone (Class III) in effecting cardioversion for recent-onset
AF. However, Class IC agents are thought to be less effective than Class III agents for
pharmacologic cardioversion if the AF episode has been present for more than 7
days.15
o IV preparations are associated with greater success rates than oral preparations.
o Of the wide array of pharmacologic agents available for cardioversion, five of the
more studied and well proven agents are included in Table 8-3.
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P.118
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Drug (Vaughan
β-blocker or nondihydropyridine
CCB)
IV: 1.5-3 mg/kg over 10-20
min
below)
β-blocker or nondihydropyridine
CCB)
IV: 1.5-2 mg/kg over 10-20
min
Amiodarone Oral: Load 1.2-1.8 g per day • ↓BP, HB, ↓HR, GI upset,
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renal insufficiency;
contraindicated if creatinine
• Use restricted and need for
clearance <20 mL/min)
continuous monitoring given
pointes
United States
pointes
↓BP, hypotension; HB, heart block; HF, heart failure; ↓HR, bradycardia; HTN, hypertension; QTc,
corrected QT interval; CAD, coronary artery disease; HTN, hypertension; LVH, left ventricular
a
Factors that predispose one to ventricular proarrhythmia with Class IC agents include, but are
not limited to, structural heart disease (including CAD, CHF, HTN with substantial LVH), QRS >
120 ms, concomitant VT, depressed LV function, rapid ventricular response rate, rapid dose
increase, high dose (drug accumulation), and addition of other drugs with negative inotropic
properties.
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b
Factors that predispose one to ventricular proarrhythmia with Class III agents include, but are
not limited to, QTc >460 ms, long QT interval syndrome, excessive QT lengthening after drug
proarrhythmia, rapid dose increase, high dose (drug accumulation), and addition of other QT-
Modified from Fuster et al. ACC/AHA/ESC 2006 guidelines for the management of patients with
P.119
FIGURE 8-1 Antiarrhythmic drug therapy to maintain sinus rhythm in patients with recurrent paroxysmal
or persistent atrial fibrillation. Within each box, drugs are listed alphabetically and not in order of
suggested use. The vertical flow indicates order of preference under each condition. The seriousness of
heart disease proceeds from left to right, and selection of therapy in patients with multiple conditions
depends on the most serious condition present. LVH indicates left ventricular hypertrophy. (From Fuster
et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. Circulation.
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2006;114:700-752.)6
P.120
Pharmacologic and nonpharmacologic options (including catheter ablation) are available if a strategy of
rhythm control is attempted (Figure 8-1). Catheter ablation is not discussed here, as published long-
term outcomes and larger trial data are lacking at present. However, it represents a promising
treatment modality with a growing clinical experience. Although treatment decisions must be
individualized, Figure 8-1 represents a framework for safely initiating therapy based on the
proarrhythmic risks of these agents. Table 8-4 presents the maintenance dosing for some of the more
commonly used agents. Drug guidelines must be consulted for safely initiating and monitoring
antiarrhythmic therapy.
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interaction
below)
States
requires in-hospital
• Additionally with β-blocking
initiation phase
properties including exacerbation of
bronchospastic disease
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↓BP, hypotension; HB, heart block; HF, heart failure; ↓HR, bradycardia; HTN, hypertension; QTc,
corrected QT interval; CAD, coronary artery disease; HTN, hypertension; LVH, left ventricular
a
Factors that predispose one to ventricular proarrhythmia with Class IC agents include, but are
not limited to, structural heart disease (including CAD, CHF, HTN with substantial LVH), QRS
>120 ms, concomitant VT, depressed LV function, rapid ventricular response rate, rapid dose
increase, high dose (drug accumulation), and addition of other drugs with negative inotropic
properties.
b
Factors that predispose one to ventricular proarrhythmia with Class III agents include, but are
not limited to, QTc >460 ms, long QT interval syndrome, excessive QT lengthening after drug
proarrhythmia, rapid dose increase, high dose (drug accumulation), and addition of other QT-
Modified from Fuster et al. ACC/AHA/ESC 2006 guidelines for the management of patients
P.121
MANAGEMENT—ANTITHROMBOTIC THERAPY
TABLE 8-5 Risk factors for ischemic stroke and systemic embolism in AF
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embolism
disease
Modified from Fuster et al. ACC/AHA/ESC 2006 guidelines for the management of patients with
P.122
based on overall risk versus benefit of therapy with specific attention to (a) assessment of one's overall
stroke risk, (b) assessment of one's bleeding risk, and (c) patient preference, including ability to comply
with proposed therapy. Notably, current practice places less emphasis on guiding decisions regarding
antithrombotic therapy based on the pattern of AF—that is, paroxysmal, persistent, or permanent.
Unless contraindications exist, antithrombotic therapy is generally recommended in all individuals with
AF unless they have lone AF. Despite considerable debate among providers, particularly regarding
individuals at intermediate risk for stroke, a framework for individualizing decisions based on
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function (“stunning”) of the left atrium (LA) and left atrium appendage (LAA). Given
often advisable.
o In hemodynamically stable patients, one may consider either (a) the conventional
2 and 3) or (b) a TEE-guided approach.19 For further details describing these two
approaches, refer to Figure 8-2 as well as the “Landmark Trials” section. In either
One moderate risk factor (or ≥1 less Aspirin (81-325 mg PO daily), or warfarin (INR 2-3
more debated)
Any high-risk factor or more than 1 Warfarin (INR 2-3 with target 2.5); if a mechanical
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Modified from Fuster et al. ACC/AHA/ESC 2006 guidelines for the management of patients with
P.123
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FIGURE 8-2 Figure 1 study protocol published by Klein AL, et al. (From Klein AL, Grimm RA, Murray RD,
P.124
In patients without high-risk for stroke (notably including mechanical prosthetic heart valve; see Table
8-5), it may be reasonable to interrupt anticoagulation for up to 1 week without using heparin.
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No clear data exist to guide optimal therapy. One potentially reasonable strategy is to use warfarin and
clopidogrel for maintenance therapy with duration depending upon the type of stent implanted (aspirin
may be added acutely until the INR is therapeutic); again, in the absence of data, this is an area of
f/u 3.5 y
age 69.7) with other 7.1% in rhythm control vs. 5.5% in rate
or death (70.8%
individuals
in rhythm control at
some point)
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• Diltiazem first-line
group; amiodarone
first-line agent in
P.125
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P.126
Strategy Comments/Findings
analysis16
(NNT = 12)
significantly different)
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
meta-analysis16
patients with nonvalvular AF
38%)
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Aspirin AND Clopidogrel • 3,335 patients with AF and ≥1 stroke risk factor
(VKA)
and vascular death (3.93% annual risk with VKA vs. 5.6%
ACTIVE A arm
Use of TEE to guide • (see preceding text for flow sheet of study design)
duration of
anticoagulation prior to
• In 1,222 patients with AF for >2 d scheduled for elective
elective cardioversion in
cardioversion, comparable safety of a conventional
patients with AF19
approach (3 wk empiric anticoagulation with warfarin) to a
P.127
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REFERENCES
1. Thom T, Haase N, Rosamond W, et al. American Heart Association. Heart disease and stroke
2. Lloyd-Jones DM, Wang TJ, Leip EP, et al. Lifetime risk for development of atrial fibrillation.
Circulation. 2004;110:1042-1046.
3. Haissaguerre M, Jais P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats
4. Olgin JE, Zipes DP. Specific arrhythmias: Diagnosis and treatment. In: Zipes DP, Libby P, Bonow RO,
Braunwald E, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed.
5. Wolf PA, Abbott RD, Kannell WB. Atrial fibrillation as an independent risk factor for stroke: The
6. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients
with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines
(Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial
7. Wyse DG, Waldo AL, DiMarco JP, et al. Atrial fibrillation follow-up investigation of rhythm
management (AFFIRM) investigators. A comparison of rate control and rhythm control in patients with
8. Van Gelder IC, Hagens VE, Bosker HA, et al., for the Rate Control versus Electrical Cardioversion for
Persistent Atrial Fibrillation Study Group (RACE). A comparison of rate control and rhythm control in
9. Hohnloser SH, Kuck KH, Lilienthal J, for the PIAF Investigators. Rhythm or rate control in atrial
2000;356:1789-1794.
10. Opolski G, Torbicki A, Kosior DA, et al. Rate control vs. rhythm control in patients with nonvalvular
persistent atrial fibrillation: The results of the Polish How to Treat Chronic Atrial Fibrillation (HOT
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11. Carlsson J, Miketic S, Windeler J, et al., for the STAF Investigators. Randomized trial of rate-control
versus rhythm-control in persistent atrial fibrillation: The Strategies of Treatment of Atrial Fibrillation
P.128
12. Wood MA, Brown-Mahoney C, Kay GN, et al. Clinical outcomes after ablation and pacing therapy for
13. Joglar JA, Hamdan MH, Ramaswamy K, et al. Initial energy for elective external cardioversion of
14. Hersi A, Wyse G. Medical management of atrial fibrillation. Curr Cardiol Rep. 2006;8:323-329.
15. Rudo T, Kowey P. Atrial fibrillation: Choosing an antiarrhythmic drug. Curr Cardiol Rep. 2006;8:370-
376.
16. Hart RG, Benavente O, McBride R, et al. Antithrombotic therapy to prevent stroke in patients with
17. Stroke Prevention in Atrial Fibrillation (SPAF) investigators. Stroke Prevention in Atrial Fibrillation
18. The ACTIVE Writing Group. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation
in the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events (ACTIVE W): A
randomized controlled trial. Lancet. 2006:367:1903-1912.
19. Klein AL, Grimm RA, Murray RD, et al. Use of transesophageal echocardiography to guide
David V. Daniels
Euan Ashley
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Approximately 5 million people throughout the United States have heart failure (HF); 550,000 are
diagnosed each year, and it represents the primary diagnosis in over 1 million hospitalizations
annually.1,2 We will focus our efforts on the recognition and management of HF as an inpatient problem
with the understanding that encounters may be prompted by everything from new onset HF,
decompensation of patients with known HF, to refractory HF. We will make recommendations on
reasonable strategies of acute HF management and initialization of chronic therapies known to have
DEFINITION
Failure of the heart to pump blood forward at a sufficient rate to meet the metabolic demands of
peripheral tissues, or the ability to do so only at the expense of abnormally high cardiac filling
pressures.3
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Type
Up to 44% isolated diastolic dysfunction, often mixed diastolic and systolic dysfunction
Systolic Dysfunction
Most commonly secondary to ischemic heart disease (50%-75%) or primary valvular disease
Differential diagnosis for nonischemic dilated cardiomyopathy (DCM) is very broad including
Diastolic Dysfunction
Associated most commonly with chronic hypertension (HTN), left ventricular hypertrophy
Can be seen acutely with ischemia as well as chronic coronary artery disease (CAD) after
multiple myocardial infarctions (MI)
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worsening of hypoperfusion
weight,
azotemia,
increased extremities
minimal
edema
sided
present
including ↑
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creatinine often
with hemodynamics
elevated
minimal diuresis
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Anemia/Arrhythmias
Ischemia/Infection
Renal failure
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Embolism (PE)
HISTORY
Recent palpitations
Functional status/exercise capacity (e.g., flights of stairs or number of blocks before having to
rest)
Changes in weight (e.g., clothes or rings not fitting recently), dependent edema, nocturia,
Recent changes in eating habits such as dining out, special events (e.g., holidays and
weddings)
PHYSICAL EXAM
SIGNS OF RIGHT VENTRICULAR (RV) FAILURE
Ascites
Parasternal heave
S3 or S4 at lower R sternal edge
Tachypnea, diaphoresis
Early inspiratory rales (often not present in chronic failure) and hypoxemia
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Cool extremities
Oliguria
Narrow pulse pressure (pulse pressure <25% of the systolic blood pressure (SBP) has a
sensitivity and specificity of 91% and 83% for a cardiac index of <2.2 L/min/m 2)4
Low-grade troponin may be detectable and even expected with significantly elevated left
ventricular end diastolic pressure (LVEDP), CKMB often negative, and enzymes do not follow
the typical rise and fall seen in an acute coronary syndrome
Chronic renal failure is often associated with CHF, termed the “cardio-renal syndrome”
Remember that decreased cardiac output (CO) is one cause of prerenal azotemia
Rising creatinine during treatment of acute HF is associated with worse in-hospital and long-
term outcomes
Often “volume overload” presentations associated with creatinine improvement in the face of
diuresis …? Improved CO versus lowering venous back pressure/congestion on kidneys
>150 pg/mL had a sensitivity and specificity of 85% and 83% and LR (+) of 5.3, LR (-) 0.18 for
Elevated BNP in the setting of intact systolic function (nl EF) is highly suggestive of diastolic
dysfunction5
BNP >400 pg/mL is virtually diagnostic of LV failure contributing to symptoms6
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Use caution in interpreting test in patients with chronic renal insufficiency (CRI), where brain
o 50 to 75 = 900 pg/mL
URINE TOXICOLOGY
Rule out cocaine or amphetamine use as an etiology of heart failure in suspected patients
ECG
Useful for rapidly detecting ST segment elevation MI (STEMI) as a cause of new onset HF but
Q waves and left bundle branch block (LBBB) are good predictors of systolic dysfunction. QRS
CHEST X-RAY
ECHO
Universally the single most important test in the evaluation of new onset HF
Useful for assessing viability of myocardium and potential for response to revascularization
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Dobutamine echo may help determine response to aortic valve replacement (AVR) in critical
aortic stenosis
P.134
CORONARY ANGIOGRAPHY
Consider in newly diagnosed systolic dysfunction as the gold standard for evaluation of
coronary disease and potentially treatable lesions
Infrequently used in acute setting, can be useful for determining a cardiac or pulmonary cause
Pearls on Diuresis
In a hemodynamically stable patient who is volume overloaded, your goal should be at least 1
to 2 liters/day
In patients with renal insufficiency, consider continuous furosemide infusion rather than bolus
dosing8
Cardiac monitoring and frequent electrolyte checks (particularly magnesium and potassium)
Encourage the patient to take an active role by asking the nursing staff their weight daily
Most patients respond to aggressive diuresis despite theoretical concerns of decreasing cardiac
output
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nesiritide
Double the dose when switching from IV to oral furosemide to achieve equivalent diuretic
effect
Consider oral bumetanide as an alternative to oral furosemide (better absorption in CHF but
shorter elimination half-life)10
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Consider continuous positive airway pressure (CPAP) as a bridge while diuresing and has
recently been shown to have significant mortality benefit and decreases need for intubation in
a large meta-analysis11
Strongly consider in patients with increased work of breathing or persistent hypoxia despite
initial therapy
CPAP probably preferred to bilevel positive airway pressure (BIPAP) as there is some evidence
hemodynamic instability, high oxygen requirement that cannot be achieved with BIPAP,
nausea/vomiting due to risk of aspiration, and significant arrhythmias
Prevent worsening of ejection fraction (EF) via ischemic events, tachyarrhythmia, excess
afterload
Reduce risk of life-threatening arrhythmia
Multiple trials that show mortality benefit (see below). ACE-I12,13,14 or ARBs15 > nitrates and
hydralazine16
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ACE-Is are the preferred vasodilator and should be given a trial before hydralazine and nitrates
Start ACE-Is low and titrate while watching K and renal function closely
The lower the EF, the more benefit from ACE-I/ARB if tolerated
Allow for a 30% increase in creatinine with therapy before considering the patient intolerant
Hydralazine/Nitrates
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intolerant to ACE-I/ARB
May have an additive benefit to ACE-I/ARB, though only studied in self-identified “African
descent” patients so far18
Beta Blockers
CHOICE OF AGENT
Carvedilol (use caution in severe asthma because nonselective) > metoprolol succinate for
Metoprolol succinate (long acting) is the type of metoprolol best studied in CHF 25
Patients with low BP may tolerate metoprolol better and those who are hypertensive may get
Consider compliance when selecting regimen (once versus twice daily dosing—Coreg XR now
available however)
See landmark trials section below for starting doses in clinical trials
Symptomatic benefit may take months and patients may complain of initial worsening of
symptoms
Titrate primarily as an outpatient, increase dose to highest tolerated by blood pressure (BP),
Side effects include increased fatigue, hypotension, water retention, azotemia, decreased
Consider maintaining beta blockade while intensifying diuresis in patients treated for >3
months with increased congestive symptoms
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Decrease or hold in patients presenting with severe acute-HF, especially with low output
symptoms or significant azotemia
Indicated for NYHA class III-IV HF (RALES)27 and post-MI heart failure (EPHESUS)
Stop exogenous K replacement and monitor serum K and Cr at 3 days, 1 week, and monthly
Digoxin
May be considered after first-line therapies including RAAS inhibition, beta blockers, and
aldosterone antagonists are maximized or in conjunction with A-V nodal agents for improving
Post hoc analysis of the DIG trial suggests serum dig concentration (SDC) of 0.5 to 0.8 ng/mL
Nesiritide
More rapid improvement in PCWP and dyspnea over placebo but similar when compared to
transplant
Anticoagulation
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Those with severely depressed EF (<30%), large territory of akinetic LV, or evidence of LV
thrombus probably benefit from anticoagulation as well36
P.138
Revascularization Therapy
Evaluate for contribution of ischemia; see chapter on CAD for indications and strategy.
P.139
P.140
signs of HF of HF therapy
Aggressive BP control
• Goal <130/80 X X X X
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with CAD or DM
• Statins generally
preferred
Lifestyle modifications
• Facilitate cessation of
drugs
• Emphasize importance X X X X
monitoring of status
symptoms)
• Encourage exercise to
sx
antiarrhythmics except B-
blockers
if ischemic CM
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• Most antiarrhythmics X X X
dofetilide
• Calcium channel
mortality in patients
with ↓ EF except
dihydropyridine which
can be used as a BP
treatment maximized
Na restriction
• Refer to nutrionist,
compliance very
difficult
ACE Inhibitors/ARB
range
>3.0, history of in in
X X
angioedema, prior selected selected
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drug, or pregnancy
>5.5 meq/L
Beta-blockers
• Metoprolol succinate or
patients
• Caution: HR <60,
symptomatic
especially with a
significant reversible
component
Hydralazine/Nitrates
• Alternative to ACE-I or
ARB
adjunct to ACE-I/ARB in
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selected
patients
tolerated by BP, sx
• Contraindications: Use
Viagra)
Aldosterone antagonists
• Consider as adjunct to
ACE-I/ARB
• Goal: Spironolactone 25 X X
mg or eplerenone 50 mg
qd
hyperkalemia
Loop diuretics
• Cornerstone of volume,
sx management X X
• Bumetanide or
torsemide an alternative
to furosemide if concern
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Digoxin
• Consider as adjunct if
first-line therapy
insufficient
patients
• Contraindicated with
Nesiritide
• Comparable to
combined diuretics +
NTG
mcg/kg/min +/- 2 in in
patients patients
• Caution: Hypotension,
active ischemia
P.141
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Not nearly as well studied and the jury is still out on optimal treatment.
Rate Control
ACE-I
Results from an analysis of the HOPE study suggests ACE-Is have beneficial effects on structure
ARB
P.142
Spironolactone
Recent study suggests spironolactone improves hemodynamics in isolated diastolic HF, 39 though
no hard end-point data yet
P.143
P.144
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Digoxin DIG Trial - NEJM, 199731 6,800 pts 22% RRR of hospitalization NNT =
Nitrates + V-HeFT I - NEJM, 198616 642 men - Mortality same in prazosin vs.
H/N NNT = 11 at 2 y, 9 at 3 y
13
Inhibitors
SOLVD - NEJM, 199114 2,569 pts - 16% RRR of all-cause death NNT =
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= 10
10
Angiotensin ELITE - Lancet, 199740 722 pts - EF 8% ARR of d/c meds due to side
25 (unexpected result!)
effects
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already on ACE-inhibitor 23
placebo
placebo
16% RRR of admit for CHF NNT =
41
Aldosterone RALES - NEJM, 199927 1,663 pts - Stopped early due to mortality
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pain
25%)
Beta-Blockers CIBIS - Circulation, 199419 641 pts All-cause mortality not stat
= 20
NNT = 9
199621 1,094 pts - EF <35%, NYHA benefit 65% RRR of death NNT =
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placebo
placebo
33% RRR of death NNT = 26 / pt y
13
MERIT-HF
Nesiritide VMAC - JAMA, 200233 489 pts - At 3 hrs: PCWP -5.8 vs -3.8 vs -2
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vs placebo gtt
different
RR, relative risk; RRR, relative risk reduction; ARR, absolute risk reduction; NNT, number needed
to treat = 1/ARR
P.145
REFERENCES
1. American Heart Association. Heart Disease and Stroke Statistics: 2005 Update. Dallas, TX: American
2. Koelling TM, Chen RS, Lubwama RN, et al. The expanding national burden of heart failure in the
United States: The influence of heart failure in women. Am Heart J. 2004;147: 74-78.
P.146
4. Stevenson LW, Perloff JK. The limited reliability of physical signs for estimating hemodynamics in
5. Maisel AS, et al. Bedside B-Type natriuretic peptide in the emergency diagnosis of heart failure with
reduced or preserved ejection fraction. Results from the Breathing Not Properly Multinational Study. J
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6. Maisel A. B-type natriuretic peptide levels: Diagnostic and prognostic in congestive heart failure:
7. Januzzi JL, van Kimmenade R, Lainchbury J, et al. NT-proBNP testing for diagnosis and short-term
prognosis in acute destabilized heart failure: An international pooled analysis of 1256 patients: The
8. Dormans T, et al. Diuretic efficacy of high-dose furosemide in severe heart failure: Bolus injection
9. Rosenberg J, et al. Combination therapy with metolazone and loop diuretics in outpts with refractory
heart failure: An observational study and review of the literature. Cardiovasc Drugs Ther. 2005;19:301-
306.
10. Brater DC, et al. Bumetanide and furosemide in heart failure. Kidney Int. 1984;26:183-189.
11. Peter JV, et al. Effect of non-invasive positive pressure ventilation (NIPPV) on mortality in patients
12. The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in
asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med. 1992;327:685.
13. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart
failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J
Med. 1987;316:1429.
14. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular
15. Granger CB, et al. Effects of candesartan in patients with chronic heart failure and reduced left-
16. Cohn JN, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure.
17. Cohn JN, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of
P.147
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18. Taylor AL, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N
19. CIBIS Investigators. A randomized trial of beta-blockade in heart failure: The Cardiac Insufficiency
20. CIBIS-II Investigators. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): A randomized trial.
Lancet. 1999;353:9-13.
21. Packer M, et al., for the US Carvedilol Heart Failure Study Group. The effect of carvedilol on
morbidity and mortality in patients with chronic heart failure. N Engl J Med. 1996;334:1349-1355.
22. Packer M,et al., for the Carvedilol Prospective Randomized Cumulative Survival Study Group
2001;344:1651-1658.
23. Goldstein S, et al. Metoprolol controlled release/extended release in patients with severe heart
failure. Analysis of the experience in the MERIT-HF study. J Am Coll Cardiol. 2001;38:932.
24. The BEST Trial Investigators. A trial of the beta-blocker bucindolol in patients with advanced
25. Poole-Wilson PA, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients
with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET):Randomised
26. Bakris GL, et al. Metabolic effects of carvedilol vs. metoprolol in patients with type 2 diabetes
27. Pitt B, Zannad F, Remme WJ, et al., for The Randomized Aldactone Evaluation Study (RALES)
Investigators. The effect of spironolactone on morbidity and mortality in patients with severe heart
28. Shah KB, et al. The adequacy of laboratory monitoring in patients treated with spironolactone for
29. Juurlink DN, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation
30. Neaton J. et al., for the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and
Survival Study (EPHESUS) Investigators. Eplerenone, a selective aldosterone blocker, in patients with
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31. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with
P.148
32. Rathore SS, Curtis JP, Wang Y, et al. Association of serum digoxin concentration and outcomes in
33. Publication Committee for the Vasodilation in the Management of Acute CHF (VMAC) Investigators.
Intravenous nesiritide vs. nitroglycerin for treatment of decompensated congestive heart failure: A
34. Colucci WS, Elkayam U, Horton DP, et al. Intravenous nesiritide, a natriuretic peptide, in the
treatment of decompensated congestive heart failure. Nesiritide Study Group. N Engl J Med.
2000;343:246.
35. Burger AJ, Elkayam U, Neibaur MT, et al. Comparison of the occurrence of ventricular arrhythmias
in patients with acutely decompensated congestive heart failure receiving dobutamine versus nesiritide
36. Hunt SA, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart
Failure in the Adult: A report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and
37. Palazzuoli A, Carrera A, Calabria P, et al. Effects of carvedilol therapy on restrictive diastolic filling
38. Lonn E, et al. Effects of ramipril on left ventricular mass and function in cardiovascular patients
with controlled blood pressure and with preserved left ventricular ejection fraction: A substudy of the
Heart Outcomes Prevention Evaluation (HOPE)Trial. J Am Coll Cardiol. 2004 Jun 16;43(12):2200-2206.
39. Mottram PM,et al. Effect of aldosterone antagonism on myocardial dysfunction in hypertensive
40. Pitt B, et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure
41. Pitt B, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic
heart failure: Randomized trial—the Losartan Heart Failure Survival Study ELITE II. Lancet.
2000;355:1582-1587.
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42. Pfeffer MA, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart
P.149
43. McMurray JJV, et al. Effects of candesartan in patients with chronic heart failure and reduced left-
ventricular systolic function taking angiotension-converting enzyme inhibitors: The CHARM-Added trial.
Lancet. 2003;362:767-771.
44. Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and preserved left-
45. Cohn JN, Tognoni G, for the Valsartan Heart Failure Trial (ValHeFT) Investigators. A Randomized
trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med.
2001;345:1667-1675.
Ramona L. Doyle
Juliana C. Liu
Roham T. Zamanian
BACKGROUND
Pulmonary hypertension (PH) refers to a state in which pulmonary artery pressure is elevated. By expert
consensus, PH is defined as a mean pulmonary arterial pressure (mPAP) greater than 25 mm Hg at rest
or greater than 30 mm Hg with exercise as measured by right heart catheterization. 1 Pulmonary arterial
hypertension (PAH) refers to disease states that localize to small pulmonary muscular arterioles. It is
characterized as PH in the presence of (a) a pulmonary capillary wedge pressure (PCWP) <15 mm Hg,
(b) pulmonary vascular resistance (PVR) >240 dynes/s/cm5 (3 Wood units), and (c) a transpulmonary
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The severity of PH may be described in terms of pulmonary arterial pressure (Table 10-1), pulmonary
classification [Table 10-2]). When assessing the severity of PH using levels of pulmonary arterial
pressure, it is important to always consider cardiac output (CO). In fact, lower pulmonary arterial
pressure may reflect a failing right ventricle and more advanced pulmonary vascular disease. Pulmonary
vascular resistance (PVR) takes into account pulmonary pressure and flow and is measured as the
difference between mean PAP and wedge pressure divided by cardiac output (PVR = (mPAP-PCWP)/CO).
PVR is considered a better marker of pulmonary vascular disease. A normal value of PVR is 1 Wood unit
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10 Wood units in PAH or value of PVR higher than 6 Wood units in left heart failure are considered
severe. Pulmonary vascular histological changes of the media and intima have also been associated with
the severity and reversibility of pulmonary arterial hypertension (PAH) associated with congenital heart
Pulmonary vascular reactivity refers to the decrease in PAP in response to vasodilators. Several agents
are of value in assessing acute vasoreactivity including oxygen, inhaled nitric oxide (usually 20 ppm),
Pulmonary vascular reactivity studies provide useful prognostic information and guide the choice of
therapy in PAH, help predict the reparability of complex congenital heart disease, and help stratify the
risk of acute right failure after heart transplantation. A positive vasodilator response in PAH is defined
found in about 5% to 6% of PAH patients. These patients have a better response to calcium channel
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Severity Mean PA (mm Hg) Systolic PA (mm Hg) Relative PA (mm Hg)
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1.3.6. Other (thyroid disorders, glycogen storage disease, Gaucher disease, hereditary
splenectomy)
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5. Miscellaneous
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WHO CLASSIFICATION OF PH
The World Health Organization (WHO) classifies patients with PH into five groups based on etiology and
pathobiology. Pulmonary arterial hypertension (PAH) describes group 1 PAH; group 2 describes patients
with pulmonary venous hypertension; group 3 refers to PH associated with lung disease and/or
hypoxemia; group 4 describes PH associated with chronic thrombotic and/or embolic disease and group
5 refers to miscellaneous causes of PH.1 This revised classification provides a useful framework for the
diagnosis and management of PH patients. Modifications to this classification have been made at the
latest WHO meeting in 2008. Formal publication of the classifications is still pending.
PATHOPHYSIOLOGY OF PH
Multiple molecular pathways have been implicated in the pathogenesis of PAH. These include nitric
oxide, prostacyclin, endothelin-1, and serotonin pathways.A dysfunction in these pathways can lead to
which leads to progressive vascular disease. In patients with pulmonary venous hypertension, PH can be
explained by left ventricular diastolic failure, left-sided valvular heart disease, or pulmonary vein
stenosis. In patients with lung disease, PH can be explained by hypoxemic vasoconstriction and/or by
the loss of pulmonary vascular bed. In chronic thromboembolic PH (CTEPH), in situ thrombosis and/or
partially occluded proximal pulmonary arteries also contributes to the pathophysiology of CTEPH.
One of the most important consequences of PH is right ventricular (RV) failure. Survival in PH is closely
acquired), setting (acute versus chronic), and specific cause of PH. Hypoxemia can be seen in PH as a
result of right-to-left shunting through a patent foramen ovale or congenital defect, ventilation-
perfusion mismatches, or decreased diffusion capacity. Hemoptysis, although rare, can be associated
with significant morbidity and mortality. Hemoptysis may originate from a rupture of a bronchial artery
or pulmonary trunk.
CLINICAL PRESENTATIONS
Most patients initially experience exertional dyspnea and fatigue, which reflects low cardiac output
during exercise (low exercise reserve). As the PH progresses and RV failure develops, peripheral edema,
exertional syncope, exertional chest pain, and passive liver congestion may occur. Less common
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syndrome, which is due to compression of the left recurrent laryngeal nerve by a dilated main
pulmonary artery). Other symptoms may also reflect the specific underlying cause.
Signs of RV failure are commonly found in patients with advanced PH; these include elevated jugular
veins, distended liver, peripheral edema, and occasionally ascites. An increased intensity of the
pulmonic component of the second heart sound is an initial physical finding in PH. Other signs include a
right-sided S3 gallop, a holosystolic parasternal murmur of tricuspid regurgitation, and in more severe
disease, a diastolic pulmonic regurgitation murmur.The right-sided murmurs and gallops are augmented
with inspiration.4
A comprehensive workup is necessary in order to confirm the presence of PH, assess its severity and
identify its cause.1,2,5 Echocardiography is very helpful in estimating pulmonary artery pressure and
assessing RV function. Signs of RV pressure overload may include D-shape left ventricle, tricuspid
regurgitation, decreased systolic performance, and RV hypertrophy (>5 mm wall thickness). Right heart
catheterization (RHC) is the most reliable method for measuring pulmonary arterial pressure,
pulmonary vascular resistance, and pulmonary vascular reactivity. RHC is often obtained to confirm the
diagnosis, assess pulmonary vascular reactivity, and evaluate the response to therapy.
Electrocardiography may reveal signs of RV or right atrial dilatation, right bundle branch block, or
metabolic panel, B-type natriuretic peptide (BNP), troponins, collagen vascular disease workup,
assessment for hypercoagulable states, hepatic serologies, and HIV screening. Functional studies such
as 6-minute walk test or cardiopulmonary exercise test are important for the assessment of functional
capacity and response to therapy. The diagnostic evaluation may also include a pulmonary function
test, a sleep study, chest x-ray, ventilation-perfusion scanning, and/or CT-angiography. Magnetic
Untreated idiopathic PAH (IPAH) is associated with a very poor prognosis with a 5-year survival rate of
34% according to the NIH registry.6 PH is also recognized to be a bad prognostic factor in heart failure,
valvular heart disease, pulmonary disease, and in systemic diseases such as scleroderma. 7 In PAH,
factors associated with poor outcome include (a) low exercise capacity (NYHA: IV, 6 Minute Walk
Distance <300m [984 feet]); (b) markers of severe RV dysfunction including high right atrial
P.156
pressure (RAP >15 mm Hg), low cardiac index, significant RV dysfunction, elevated BNP, and troponins;
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(c) rapid progression; (d) pericardial effusion; (e) poor response to prostacyclin therapy (persistence of
NYHA III or IV); and (f) persistent supraventricular arrhythmias or sudden death. 2,8 In chronic
thromboembolic PH, patients who are not considered suitable for pulmonary endarterectomy are
MANAGEMENT OF PH
The management of pulmonary hypertension should be tailored to its cause, hemodynamic consequence
(degree of RV failure), and vascular reactivity. Patients with significant PH should follow a low sodium
diet (<2 grams of sodium), participate in graded physical activity, and avoid isometric activities such as
weight lifting as well as medications that can exacerbate heart failure such as nonsteroidal anti-
inflammatory medication. Pregnancy is also not advisable as maternal and fetal mortality can exceed
50%.
This revised WHO classification provides a useful framework for the management of PH patients.
Patients with PAH (WHO class I) may benefit from prostanoid therapy (epoprostenol, treprostinil,
ambrisentan). Anticoagulation with a goal INR between 1.5 to 2.5 is also recommended. 10 The minimal
dose of diuretics is used to prevent fluid retention. The role of cardiac glycoside in pulmonary
hypertension is controversial with only one study showing short-term hemodynamic benefits. The value
associated with PH has not been comprehensively studied. In patients presenting with acute
decompensation, inhaled nitric oxide and vasopressor/inotropic support (usually with dobutamine 2 to 5
µg/kg/min) may be required (Figure 10-1 and Table 10-4). Atrial septostomy should only be considered
In patients with pulmonary venous hypertension (WHO class II), optimization of left-sided heart failure
and valvular disease management is the most important component of therapy. Small studies also
suggest that sildenafil may be beneficial in selected patients with pulmonary hypertension.11 In patients
with PH secondary to lung disease and/or hypoxemia (WHO class III), primary therapy consists of oxygen
therapy and ventilatory support (CPAP, BIPAP) as required. These patients usually do not benefit from
treatment with pulmonary vasodilators. In patients with chronic thromboembolic disease (WHO class
IV), therapy consists of anticoagulation and careful evaluation for candidacy for pulmonary
endarterectomy.
P.157
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FIGURE 10-1 Algorithm for the management of PAH. Please refer to text for the definition of pulmonary
reactivity and the description of higher risk patients. ETRA indicates endothelin receptor inhibitors;
VV, McGoon MD. Pulmonary arterial hypertension. Circulation. 2006 September 26;114[13]:1417-1431.)
P.158
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Prostanoids
IV
HD ng/kg/min
ng/kg/min
thrombosis
Rebound PH if
D/C
Thrombocytopen
ia
except less
rebound PH
(Remodulin) NYHA III-IV 2. Better Initiate: 1
Possible ↑
HD ng/kg/min
incidence Gram -
catheter sepsis
Randomiz Usual: 40-
Site pain with SQ
ed 60
form
ng/kg/min
PC trials Half-life 3-
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
12 weeks 4h
ed PC of on 6 to 9
weeks nt ↑ 6MWT /d
Endothelin
receptor
blockers
Randomiz
2. Better
ed PC
HD
trials; 12
weeks
2. Better
HD
Phosphodiester
ase inhibitors
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
ed PC HD nitrates
trials
daily
2. Better
HD
3. ↑ QL life
e studies n
controlled; 6MWT, 6-minute walk test; HD, hemodynamic; NYHA, New York Heart
P.159
P.160
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
the prostacyclin
group
2. HD
improvement
3. Survival
benefit
comparative) in
the prostacyclin
group
2. HD
improvement
3. No survival
benefit
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
al. 15
compared to the
long term
al. 16
HD and exercise
12 weeks
2. Dose-related
improvement
Tapson et al. 18
meters
Open-label
prospective 12
2. Improvement
weeks
in HD
to epoprostenol
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
weeks
2. No
improvement in
HD
Randomized 1 improvement in
meters
comparative)
2. Improvement
in time to clinical
worsening
al. 23
NYHA III-IV bosentan ↑
Observational survival
historical control
weeks syndrome
2. HD
improvement
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
3. No
compromise
peripheral oxygen
saturation
mg group
2. ↑ 6MWT
weeks dose)
Randomized 12 meters
weeks
2. HD
improvement
weeks corrected
treatment effect
2. HD
improvement
P.161
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
REFERENCES
1. Simonneau G, Galie N, Rubin LJ, et al. Clinical classification of pulmonary hypertension. J Am Coll
2. McLaughlin VV, McGoon MD. Pulmonary arterial hypertension. Circulation. 2006 September
26;114(13):1417-1431.
3. Heath D, Edwards JE. The pathology of hypertensive pulmonary vascular disease; a description of six
grades of structural changes in the pulmonary arteries with special reference to congenital cardiac
4. Rubin JR, Hopkins W. Overview of pulmonary hypertension. In: Rose BD, ed. Up to Date. Waltham,
MA: 2007.
5. Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J
6. D'Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension.
Results from a national prospective registry. Ann Intern Med. 1991 September 1;115(5):343-349.
7. Haddad F, Doyle RL, Murphy DJ, et al. Right Ventricular Function in Cardiovascular Disease, Part II
P.162
10. McLaughlin VV, Rich S. Pulmonary hypertension. Curr Probl Cardiol. 2004 October;29(10):575-634.
11. Lewis GD, Lachmann J, Camuso J, et al. Sildenafil improves exercise hemodynamics and oxygen
uptake in patients with systolic heart failure. Circulation. 2007 January 2;115(1):59-66.
12. Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol
(prostacyclin) with conventional therapy for primary pulmonary hypertension. The Primary Pulmonary
229
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
13. Badesch DB, Tapson VF, McGoon MD, et al. Continuous intravenous epoprostenol for pulmonary
hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann Intern
14. Sitbon O, Humbert M, Nunes H, et al. Long-term intravenous epoprostenol infusion in primary
pulmonary hypertension: Prognostic factors and survival. J Am Coll Cardiol. 2002 August 21;40(4):780-
788.
15. McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension:The impact of
16. Rosenzweig EB, Kerstein D, Barst RJ. Long-term prostacyclin for pulmonary hypertension with
17. Simonneau G, Barst RJ, Galie N, et al. Continuous subcutaneous infusion of treprostinil, a
18. Tapson VF, Gomberg-Maitland M, McLaughlin VV, et al. Safety and efficacy of IV treprostinil for
pulmonary arterial hypertension: A prospective, multicenter, open-label, 12-week trial. Chest. 2006
March;129(3):683-688.
19. Gomberg-Maitland M, Tapson VF, Benza RL, et al. Transition from intravenous epoprostenol to
intravenous treprostinil in pulmonary hypertension. Am J Respir Crit Care Med. 2005 December
15;172(12):1586-1589.
20. Olschewski H, Simonneau G, Galie N, et al. Inhaled iloprost for severe pulmonary hypertension. N
21. Galie N, Humbert M, Vachiery JL, et al. Effects of beraprost sodium, an oral prostacyclin analogue,
P.163
22. Barst RJ, McGoon M, McLaughlin V, et al. Beraprost therapy for pulmonary arterial hypertension. J
23. McLaughlin VV, Sitbon O, Badesch DB, et al. Survival with first-line bosentan in patients with
230
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
24. Galie N, Beghetti M, Gatzoulis MA, et al. Bosentan therapy in patients with Eisenmenger syndrome:
54.
25. Barst RJ, Langleben D, Frost A, et al. Sitaxsentan therapy for pulmonary arterial hypertension. Am J
26. Barst RJ, Langleben D, Badesch D, et al. Treatment of pulmonary arterial hypertension with the
selective endothelin-A receptor antagonist sitaxsentan. J Am Coll Cardiol. 2006 May 16;47(10):2049-
2056.
28. Galie N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial
BACKGROUND
The first human heart transplant was performed in South Africa in 1967, followed by the first U.S.
procedure in 1968 by Dr. Norman Shumway at Stanford University. Over 4,000 heart transplants are
performed worldwide each year; the number of procedures is currently limited by the availability of
organ donors. Survival rates are 81%, 74%, 68%, and 50% at 1, 3, 5, and 10 years. 1
Systolic heart failure with severe functional limitation and/or refractory symptoms despite
o Left ventricular ejection fraction (LVEF) usually <35%, but a low LVEF is not an
o Myocarditis
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P.166
CONTRAINDICATIONS
by most programs
Advanced age: Many programs are moving away from “absolute” age limits and considering
evaluating older patients. Some programs still have an age cutoff between 65 and 70 years of
age.
Active systemic infection: Patients can typically be listed after the infection has been
identified and adequately treated (i.e., absence of fever, leukocytosis, and bacteremia).
Active malignancy or recent malignancy with high risk of recurrence. Exceptions include
nonmelanoma skin cancers, primary cardiac tumors restricted to the heart, and low-grade
Diabetes mellitus with either poor glycemic control (variable definitions, but usually HbA1c
Marked obesity (body mass index [BMI] >30 kg/m2 or >140% of ideal body weight). Most
o Amyloidosis
o Sarcoidosis
o Hemochromatosis
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Recent or unresolved pulmonary infarction due to the high probability of progression into
Psychosocial factors that may impact on patient's ability to receive posttransplant care
P.167
PRETRANSPLANT EVALUATION
History
Psychosocial Evaluation
Assess for uncontrolled psychiatric illness or active/recent substance abuse that may impact
posttransplant care.
Blood tests: Complete blood count, electrolytes, renal and hepatic function, ABO typing;
human leukocyte antigens (HLA) antibody screen against panel of common antigens (PRA);
Chest x-ray
Electrocardiogram
Echocardiogram
Coronary angiography (or review most recent study) if known coronary artery disease (CAD) or
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
intervention with vasodilators (intravenous nitride or inhaled nitric oxide) may be used to
Age and sex-appropriate cancer screening (PAP smear, mammogram, colonoscopy, prostate-
specific antigen (PSA) with DRE)
Most candidacy determinations are made after review of patient's history and workup by a
Recipients and donors are matched by blood type, weight, priority status (Table 11-1), and
Prospective HLA matching between donor and recipient is typically not performed unless a
Waiting times range from days to years and are dependent upon priority status (shortest for
1A, longest for 2), blood type (longest for blood group O), weight (longer for large recipients),
and geographic location.
P.168
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
1A Mechanical ventilation
mcg/kg/min)
1B • 1 inotrope, or
outpatient
SURGICAL TECHNIQUE
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Most donor hearts are implanted in the orthotopic position (i.e., in the same position as the
explanted heart).
The original technique involved anastomosis of the donor heart at the level of the atria
(biatrial technique), leaving a cuff of donor atria. In recent years, the biatrial technique has
been modified to make the anastomoses at the level of the superior and inferior vena cavae
and pulmonary veins (bicaval technique). This results in less A-V valve regurgitation, decreased
incidence of atrial arrhythmias, and decreased incidence of donor sinus node dysfunction and
P.169
The transplanted heart is initially completely denervated. Cardiac denervation has several
o Patients exhibit a faster resting heart rate (usually between 95 to 110 bpm)
o Many patients will not experience angina. Typical presentations of ischemia include
o Drugs that act through the autonomic nervous system (e.g., atropine) will have little
to no effect on a transplanted heart.
IMMUNOSUPPRESSION
General Principles
The risk of rejection is highest immediately after transplantation and decreases over time.
Most rejection episodes occur during the first year; therefore, immunosuppression is highest
The goal of immunosuppression is to use the lowest doses of drugs to prevent rejection while
Induction Therapy
immunosuppression in the early (first 6 months) posttransplant period, when the risk of
rejection is highest.
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Advantages: Decreases the incidence of rejection during the first 6 months, allows delayed
after surgery
Disadvantages: May simply be shifting rejection to the late period (6-12 months) after
Maintenance Immunosuppression
Most maintenance protocols employ a two- to three-drug regimen with no more than one agent from
each class to avoid overlapping toxicities (see Table 11-2). The dosing, target drug levels, and side
P.170
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Calcineurin inhibitors
doses, titrated
Hypertension
12-h trough
levels
200-250 ng/mL Hypokalemia and
Neurotoxicity
(encephalopathy, seizures,
tremors, neuropathy,
posterior reversible
encephalopathy syndrome
[PRES])
Gingival hyperplasia
Hirsutism
divided doses,
Hypertension
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
trough levels
10 ng/mL
Hyperkalemia
Hypomagnesemia
Neurotoxicity (tremors,
headaches, PRES)
Antiproliferative agents
mg/kg/d,
titrated to keep
Hepatitis (rare)
WBC ~3,000
Pancreatitis
Malignancy
Leukopenia
mTOR inhibitors
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
titrated to keep
therapeutic 24-h
Hypercholesterolemia and
trough levels
hypertriglyceridemia
Pneumonitis
thrombocytopenia
Potentiation of CNI
nephrotoxicity
Corticosteroids
two divided
doses, tapered
Hypertension
to 0.05 mg/kg/d
by 6-12 mo
Hyperlipidemia
Osteopenia
Hyperglycemia
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Proximal myopathy
Cataracts
Growth retardation
P.171
production and preventing both T- and B-cell differentiation and proliferation. They are the
o Cyclosporine (Sandimmune, Neoral, Gengraf) was introduced in the 1980s and led to a
dramatic decrease in acute rejection and subsequent increase in life expectancy after
heart transplantation.
P.172
Antiproliferative agents: Block purine synthesis and inhibit proliferation of both T- and B-
lymphocytes
o Mycophenolate mofetil (CellCept) has replaced the older agent, azathioprine (Imuran)
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Mammalian Target of Rapamycin (mTOR) inhibitors5,6 are a newer class of agents that block
proliferation of T-cells, B-cells, and vascular smooth muscle cells by causing cell cycle arrest
at the G1 to S phase. They are used in patients with cardiac allograft vasculopathy (CAV) due
to their antiproliferative effects on vascular smooth muscle cells and in patients with renal
o Sirolimus (Rapamune)
o Everolimus (Certican) is used in Europe and undergoing Phase III clinical trials in the
United States.
Glucocorticoids are nonspecific agents that are typically used in high doses in the early
posttransplant period and then tapered to low doses or discontinued altogether after the first
6 to 12 months.
DRUG INTERACTIONS
Many drugs can alter the metabolism of the immunosuppressive agents, and vice versa (Table 11-4).7
REJECTION
Even with modern immunosuppressive regimens, acute rejection is still experienced by 30% to 50% of
Types of Rejection
Hyperacute rejection: Very rare and may occur immediately after transplantation in the
setting of high levels of preformed antibodies to the ABO blood group (in cases of
Acute cellular rejection (ACR): The most common form of rejection and mediated by T-
P.173
activation, myocardial injury, and eventual graft dysfunction. Compared to ACR, AMR is more
likely to cause hemodynamic instability and is associated with a worse prognosis. It is detected
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
and by measuring HLA antibodies in the circulation that are directed against known donor
antigens.
Nifedipine
Nicardipine
Verapamil
Fluconazole
Ketoconazole
Voriconazole
Posaconazole
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Phenobarbital
Miscellaneous Saint-John's-wort
Aminoglycoside antibiotics
Amphotericin B
Colchicine
Drugs whose concentrations are increased when used with with cyclosporine or tacrolimus
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Lovastatin
Simvastatin
Atorvastatin
Ezetimibe
P.174
Old
(1990) Revised
rejection
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
500-1,000 mg IV daily × 3
days) Hemodynamic
compromise Pulse
ATGAM, or
Thymoglobulin)
hemorrhage, or vasculitis
immunofluorescence or
immunoperoxidase
P.175
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Treatment
depends upon the type of rejection, histologic severity of rejection episode, and presence of
Any rejection episode should prompt an investigation for precipitating causes (CMV infection,
a rejection episode.
Recurrent or recalcitrant rejection can be treated with total lymphoid irradiation.
angiographically in 10% of patients by the first postoperative year and in 30% to 50% of patients by the
P.176
CAV Pathogenesis
The pathogenesis of CAV is not completely understood, but it is thought to involve both immune and
nonimmune mechanisms. It manifests as diffuse coronary intimal thickening with tapering or pruning of
CAV Diagnosis
CAV is detected on the basis of surveillance coronary angiography, although the disease can be difficult
to detect due to its diffuse nature. Some centers use intravascular ultrasound (IVUS) as a more sensitive
tool for early CAV detection. Dobutamine stress echocardiography (DSE) provides a reasonable
alternative to yearly coronary angiography when used to screen for CAV. In this setting, a normal DSE
predicts a low risk of major adverse cardiac events over the next year. 9
CAV Treatment
The mTOR inhibitors (sirolimus and everolimus) have been shown to slow progression of the disease. 5,6
PCI with stenting can be effective for focal lesions. 10 Outcomes following coronary artery bypass graft
(CABG) for CAV have been poor.11 The most definitive form of treatment is retransplantation and is
typically reserved for patients with severe, symptomatic CAV and graft failure. 12
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
New onset of heart failure signs or symptoms in a transplant patient constitutes a medical
emergency.
Heart failure can be caused by both systolic and diastolic dysfunction. The echocardiogram can
be useful to document a reduction in LV systolic function, but a normal LVEF does not exclude
o Early period (years 1-2): Acute rejection >> CAV resulting in silent ischemia or
infarction
o Late period (years 2 and beyond): CAV >> acute rejection
Workup includes an echocardiogram, electrocardiogram, right heart catheterization, heart biopsy (if
The patient's transplant team should be contacted immediately, and prompt transfer to a
In the early period (years 1-2 after transplantation), consider administration of high-dose
P.177
OPPORTUNISTIC INFECTIONS
Infections are a major cause of death during the first year and remain a threat throughout the life of a
specific microbiological diagnosis (i.e., bronchoscopy with bronchoalveolar lavage for pneumonias, fine
needle aspiration for pulmonary nodules, detection of CMV viremia via quantitative PCR of the serum).
Bacterial pathogens are more likely to cause disease in the first month and are typically
Viral pathogens include cytomegalovirus (CMV) and herpes simplex virus (HSV).
REFERENCES
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
1. Taylor DO, Edwards LB, Boucek MM, et al. Registry of the International Society for Heart and Lung
2. Taylor DO, Barr ML, Radovancevic B, et al. A randomized, multicenter comparison of tacrolimus and
3. Reichart B, Meiser B, Vigano M, et al. European Multicenter Tacrolimus (FK506) Heart Pilot Study:
One-year results—European Tacrolimus Multicenter Heart Study Group. J Heart Lung Transplant. Aug
1998;17(8):775-781.
1998;66(4):507-515.
5. Keogh A, Richardson M, Ruygrok P, et al. Sirolimus in de novo heart transplant recipients reduces
acute rejection and prevents coronary artery disease at 2 years: A randomized clinical trial.
6. Eisen HJ, Tuzcu EM, Dorent R, et al. Everolimus for the prevention of allograft rejection and
7. Page RL II, Miller GG, Lindenfeld J. Drug therapy in the heart transplant recipient: Part IV: Drug-drug
P.178
8. Stewart S, Winters GL, Fishbein MC, et al. Revision of the 1990 working formulation for the
standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant. Nov
2005;24(11):1710-1720.
9. Spes CH, Klauss V, Mudra H, et al. Diagnostic and prognostic value of serial dobutamine stress
10. Bader FM, Kfoury AG, Gilbert EM, et al. Percutaneous coronary interventions with stents in cardiac
11. Halle AA III, DiSciascio G, Massin EK, et al. Coronary angioplasty, atherectomy and bypass surgery in
249
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
12. Topkara VK, Dang NC, John R, et al. A decade experience of cardiac retransplantation in adult
Stanley G. Rockson
AORTIC STENOSIS
Background
The normal aortic valve orifice area (AVA) is 3 to 4 cm2; clinically significant gradients occur
when AVA is reduced by one half, and symptoms usually arise when AVA is one fourth of normal
size.
Grading severity is based on valve area, gradients, and aortic jet velocity. 1,2 (See Table 12-1.)
Gradients are less predictive (a mean gradient > 50 mm Hg has >90% positive predictive value
for severe AS, but there is no clear cutoff for a good negative predictive value 3).
Etiology
Most common etiologies: Congenital, rheumatic, and calcific (degenerative) (See Table 12-2.)
Pathophysiology
Pressure gradient between the left ventricle (LV) and aorta (increased afterload)
If preload reserve is exceeded or if LV function declines, cardiac output fails to increase (fixed
cardiac output).
History
Cardinal manifestations: Classic triad of angina, exertional syncope, and congestive heart
failure (CHF).
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Syncope can be due to exercise-related vasodilation in the setting of fixed cardiac output, 7 as
Sudden cardiac death occurs in a minority of patients (less than 1% of asymptomatic patients;
higher rates among symptomatic patients).2,9,10
P.180
Etiology Notes
Congenital
stenosis
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Acquired
disease
Natural History
Rate of progression
o - Decrease in valve area of 0.1 to 0.3 cm2/year and increase in peak pressure gradient
The onset of symptoms marks an important transition with a marked decline in survival (50%
survival over 2, 3, and 5 years for patients with CHF, syncope, and exertional angina,
respectively).16
Presence of symptoms may be difficult to gauge, especially in sedentary/elderly individuals.
P.181
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P.182
Physical Exam
Systolic ejection murmur is heard best in the aortic area/apex radiating to neck and right
clavicle.
Gallavardin phenomenon (disappearance of the murmur over the sternum and reappearance
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
asymptomatic patients (BNP >66 pg/mL has predictive accuracy of 84% for symptomatic AS). 17,18
Chest x-ray can show dilated proximal ascending aorta (poststenotic dilatation) and
Electrocardiogram
Echo
o - Useful for diagnosis, determining severity (AVA, velocity, gradient; see Table 12-1)
o - Accuracy compared to cardiac catheterization:19 Valve area is within ±0.3 cm;2 Peak
gradient is within ±10mm Hg; Gradients usually higher than cath due to pressure
recovery20
Provocative Testing
EXERCISE TESTING
P.183
Employed in patients with AS, depressed LVEF with two primary goals
DSE can help distinguish severe stenosis from pseudo (flow dependent) AS.22
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DSE can help to identify patients with pre-operative cardiac reserve (increase in stroke volume
by >20%, or in mean transvalvular gradient of 10 mm Hg) as this subset of patients with low EF
tends to have better outcomes (surgical mortality of 6% vs. 33%). 23
gradient (simultaneous aortic, LV pressures are most accurate) and calculation of AVA by
The gradient is dependent on transvalvular flow, so errors occur in patients with low cardiac
output.
Dobutamine can be used to distinguish pseudostenosis from true anatomically severe AS.
Identify patients that warrant surgery with close monitoring for onset of symptoms.
Medical therapy has a limited role in providing a survival benefit or slowing progression.
Symptomatic severe AS should be referred for surgery: Mortality high without surgery16; age-
Patients with asymptomatic severe AS generally have a good prognosis, 25 but there is a risk of
Identify subset of asymptomatic severe AS patients at risk for SCD and/or onset symptoms that
Patients at highest risk for symptom onset/needing surgery in the short term include: Peak
aortic velocity >4m/s;24 Severe calcification of the aortic valve;10 Rapid progression of aortic
Exercise testing: A negative test has a strong negative predictive value (85%-87%) for event-
free survival20 but is positively predictive (79%) only in physically active patients <70 years
old.21
No randomized controlled data support the strategy of referring “high-risk” patients with
asymptomatic severe AS for AVR, but this is a Class II recommendation (see Table 12-3).
Medical Therapy
Antibiotic prophylaxis is indicated if high risk for endocarditis (see Chapter 13).26
data is lacking)
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Afterload reducing agents have been shown to be beneficial in patients with severe AS and bw
Recent retrospective data suggest statins may slow progression of AS. 33, 34, and 35
P.184
Class I
Class II
Patients with moderate AS undergoing CABG, surgery of the aorta, or other heart valves
1. (IIa)
- Critical AS (valve area <0.6 cm2, mean gradient >60mm Hg, aortic jet velocity
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>5m/s)
Adapted from AHA/ACC 2006 Guidelines on Management of Patients with Valvular Heart
Disease.1
Operative mortality for AVR ~5% to 30% depending on the patient population
Predictors of higher operative mortality and lower late survival: CHF, low LVEF, chronic kidney
Outcomes similar in patients with preserved LV function and with moderate LV dysfunction
Patients with low EF/low gradient AS have higher operative mortality (20%).40,41
Provocative testing (DSE) can identify patients with contractile reserve; this subgroup may
have better surgical outcomes.23
P.185
Surgical mortality is very high (30%-50%) in patients with severe AS and decompensated heart
failure who are taken directly to surgery42 (balloon valvuloplasty and medical optimization are
In patients with severe AS who need surgical intervention, but are poor candidates,
percutaneous AVR may represent a safe, viable alternative.43
AORTIC REGURGITATION
Background
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The prevalence of chronic AR increases with age; the majority of patients with AR have trace
or mild AR.44
Grading of severity is based on several qualitative and/or quantitative measures. (See Table
12-4.)
Etiology
AR can be due to primary valvular disease and/or aortic pathology (see Table 12-5).
AR can be acute or chronic, and the clinical presentation of each entity is distinct.
Pathophysiology
ACUTE AR
Large regurgitant volume into a nondilated LV leads to an abrupt increase in LV end diastolic
pressure (LVEDP).
Poor hemodynamic tolerance: LVEDP equalizes with diastolic aortic pressure with subsequent
pulmonary edema and cardiogenic shock.
Qualitative
Angiographic grade 1+ 2+ 3+
Quantitative
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Adapted from AHA/ACC 2006 Guidelines on Management of Patients with Valvular Heart Disease. 1
P.186
Etiology Notes
VSD
Subvalvular AS
unicommissural/quadricusp valve
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disease
- Connective
tissue disease
- Chest radiation
1. Annulus/Aortic root
dilatation
dilatation
ectasia
- Ehlers-Danlos
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syndrome
- Osteogenesis
imperfecta
2. Aortitis
syndrome
3. Aortic dissection
CHRONIC AR
Pressure overload due to increased afterload (hypertension [HTN] from increased aortic stroke
volume)
Three compensatory mechanisms initially preserve cardiac output: Increased LV end diastolic
volume; increased chamber compliance; LVH (eccentric/concentric).
P.187
History
Patients with acute AR present with marked dyspnea and pulmonary edema.
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Angina without structural coronary artery disease is due to decreased coronary perfusion (due
to high LVEDP).
Exertional dyspnea is the most common presenting symptom in chronic AR (late stage).
Syncope and sudden cardiac death are rare in absence of other symptoms.
Natural History
Mild AR: Minimal data on natural history; Most patients with mild AR probably do not progress
to severe AR.
Moderate to severe AR
year46,47
- Up to one fourth develop systolic dysfunction or die suddenly. 46, 47, 48, and 49
dimension at end diastole (LVIDd), and LVEF during exercise46,47,48,49, 50, and 51
o Symptomatic patients
Physical Exam
The high-frequency decrescendo blowing diastolic murmur is heard best over the left lower
sternal border (LLSB) through stethoscope's diaphragm with patient sitting upright during
forced expiration.
Murmurs that are louder over right lower scapular border (RLSB) are more likely due to aortic
Duration of murmur correlates with severity (mild AR - short murmur; severe AR - typically
holodiastolic).
In acute AR, the diastolic murmur and peripheral signs (see Table 12-6) may be absent (the
Austin Flint murmur (mid-late diastolic rumble that resembles MS - due to vibration from AR
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P.188
Chest x-ray can be normal or demonstrate pulmonary edema, cardiomegaly, or dilated aorta.
ECG shows LAD, LVH and signs of LV diastolic volume overload (high QRS amplitude and tall T
waves with ST depression), and conduction abnormalities.
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Echocardiography
Estimation of severity is based on color flow and Doppler parameters (Table 12-4)
Supportive findings:
o - AR pressure half time: Mild >500 milliseconds and severe <200 milliseconds
severe AR
o - Patients with advanced LV dilation (LVIDs >50 mm, LVIDd >70 mm): Risk of
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TABLE 12-6 Auscultatory and peripheral findings in severe AR: A glossary of eponyms
Sign Description
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Traube sign Loud systolic “pistol shots” over the femoral artery
a
Signs identified in a recent review of physical findings in AR as the most significant findings
based on a review of available literature (peer-reviewed journals and classic text books). Babu
Close monitoring for onset of symptoms and evidence of changes in LV size and function
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Surgery is indicated in symptomatic patients, and in patients with severe LV chamber dilation
Medical Therapy
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Antibiotic prophylaxis is indicated in high risk patients with AR (prosthetic valves, prior
Acute AR
o - Negative chromotropes should be avoided; they lengthen diastole and may increase
o - The goal of medical therapy is to reduce systolic blood pressure and mitigate the
afterload mismatch.
o - Vasodilator therapy with hydralazine59 and nifedipine60 have been shown in small
o - Nifedipine delayed surgery when compared with digoxin,61 but recent trials showed
no effect of nifedipine or enalapril on timing of surgery. 62
In chronic AR, AVR is the only effective treatment for symptomatic patients.
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Class I
Class II
1. Asymptomatic patients with severe AR with normal LVEF but severe LV dilation (LVIDd
2. Patients with moderate AR undergoing CABG or surgery of the aorta or other heart
valves
Adapted from AHA/ACC 2006 Guidelines on Management of Patients with Valvular Heart
Disease.1
MITRAL REGURGITATION
Background
Dysfunction of any part of the valve apparatus (leaflets, annulus, chordae tendineae, papillary
Etiology
The most common etiologies in patients with chronic severe MR include mitral valve prolapse
(MVP), ischemic MR, rheumatic heart disease, and endocarditis.67, 68, 69, 70, 71, and 72 (see Table
12-9)
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Acute MR can result from structural (papillary muscle dysfunction/rupture, chordal rupture due
to myxomatous changes) and infectious (endocarditis, acute rheumatic fever) etiologies.
Pathophysiology
ACUTE MR
The regurgitant volume in LV produces an abrupt increase in LVEDP and left atrial pressure.
Higher preload (abrupt volume overload), lower afterload (systolic runoff into LA) 73 and
There is a modest increase in cardiac output, but overall LV function declines: Majority of the
CHRONIC MR
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cardiac output.
The compensated phase can persist for years, with high-normal LVEF.
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Qualitative
Doppler central jet width <20% LA area 20%-40% LA area >40% LA area
Quantitative
(mL/beat)
Adapted from AHA/ACC 2006 Guidelines on Management of Patients with Valvular Heart Disease. 1
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Etiology Notes
valvular disease
chordal rupture
Leaflet fenestration
8. Drugs Methysergide
9. Radiation therapy
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Secondary MR
1. Cardiac disease
LV chamber dilation
- Endomyocardial fibrosis
2. Systemic disease
- Systemic lupus
erythematosus (SLE)
- Hypereosinophilic
syndrome
- Rheumatoid arthritis
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- Marfan syndrome
III)
- Scleroderma
- Pseudoxanthoma
elasticum
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History
Symptoms include the insidious onset of dyspnea on exertion and exercise intolerance and
Natural History
The clinical course depends on the etiology of MR, the status of both ventricles and of the left
atrium.
The compensated phase of MR may last for several years (up to 10-15 years).76
There are limited data on the progression of mild/moderate MR, with wide individual
variability.77
In MVP/MR, the 5-year event-free rates are 85% to 95% for mild-moderate MR.78
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P.194
Physical Exam
Auscultation
Soft S1 with normal S2 early on; later a loud P2 appears when pulmonary HTN develops.
Posterolateral jets (radiating to axilla/back) are heard with ischemic disease, anterior leaflet
Anterior jets (radiating to sternum/base/carotids mimicking AS) are heard with posterior
leaflet prolapse.
Maneuvers to distinguish from AS: Handgrip (increased afterload) augments MR and softens AS
(lower transvalvular gradients); AS murmer increases post PVC while MR murmer changes; AS
Chest x-ray can be normal early, shows left atrial enlargement and cardiomegaly later in the
course of disease.
o - Anatomic mechanism of MR
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TEE is useful if TTE images are suboptimal, and pre-operatively for mapping to determine type
Estimation of severity is based on a combination of color flow and Doppler (see table).
Recommendations for serial studies (in the absence of symptoms): mild MR and normal LV size
and function, Every 2 to 3 years; severe MR, Every 6 to 12 months
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Exercise Testing
The precise role of exercise testing in determining need for surgery is not clearly defined
because many of the patients studied were already symptomatic.
Performed pre-operatively to screen for CAD if cardiac risk factors are present
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Close monitoring for onset of symptoms and evidence of changes in LV size and function
LV size and systolic function have a significant impact on prognosis (see Table 12-11).
Surgery is indicated in symptomatic patients, and patients with LV chamber dilation and/or LV
Medical Therapy
Acute MR
o - Main goals: (a) ↓ MR; (b) ↑ forward cardiac output; (c) ↓ pulmonary congestion
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o - There has been sustained interest in vasodilator therapy, but there are no data to
and hydralazine have been shown to decrease MR, LV, and increase forward cardiac
output.
o - ACE inhibitors do not consistently reduce severity of primary MR. 88, 89, and 90
Surgical Intervention
In chronic MR, surgery is the only effective treatment for symptomatic patients.
o - MV repair
o - MV replacement (MVR)
o Symptomatic patients (NHYA Class II-IV): LVEF 30-60%; no severe LV dysfunction (LVEF
o Asymptomatic patients: LVIDs > 40 mm and/or LVIDd > 75 mm; new onset AF;
MV repair preserves the native valve apparatus, although technically more difficult, leads to
better post-operative LV function and survival.91, 92, 93, 94, 95, 96, and 97
MVR is associated with higher operative mortality and less favorable outcomes compared to
Overall surgical mortality with MVR is 5-10%(higher for ischemic than for rheumatic/
MVR with preservation of chordal apparatus is better post-operative LV function and survival.99,
100
, and ,
101 102
MVR with resection of chordal apparatus is rarely performed given the better outcomes with
preserved chordal apparatus (necessary in rheumatic cases where the valve apparatus is
deformed).
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Class I
2. Chronic severe MR
>40 mm)
Class II
- New onset AF
- MV repair in patients with preserved LV function (LVEF >60% and LVIDs <40 mm) if
- MV repair in patients with severe LV dysfunction (LVEF <30% and/or LVIDs >40
Adapted from AHA/ACC 2006 Guidelines on Management of Patients with Valvular Heart
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Disease.1
Parameter
Adapted from AHA/ACC 2006 Guidelines on Management of Patients with Valvular Heart Disease. 1
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MITRAL STENOSIS
Background
A diastolic transmitral gradient and symptoms appear at valve areas <2 cm2.103
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Etiology
Rheumatic heart disease is the major cause of acquired MS; congenital MS is rare (see Table
12-12).
Other rare causes of acquired mitral inflow obstruction include atrial myxoma, valve thrombus,
mucopolysaccharidosis, and severe mitral annular calcification.
Pathophysiology
Obstruction leads to increased diastolic pressure between the left atrium and LV.
Transmitral gradients increase with more severe obstruction and higher flow rates across the
Progressive limitation of cardiac output with rise in left atrial pressure (LAP) and pulmonary
HTN.
AF develops due to high LAP and rheumatic insults to the left atrium.
AF further reduces flow velocity (especially in LA appendage), leading to a very high risk of
thrombus.
Pulmonary HTN develops due to high LAP and pulmonary vascular remodeling.
LV systolic function is typically preserved, but forward stroke volume may be impaired due to
impaired diastolic filling from the MS or RV overload.
History
Insidious onset of fatigue and exercise intolerance due to decreased forward cardiac output
Dyspnea on exertion, paroxysmal nocturnal dyspnea (PND), and pulmonary edema from
Right heart failure (edema, ascites) can arise from pulmonary HTN.
Less common presentations include hemoptysis (severe MS) and hoarseness (compression of the
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Etiology Notes
Acquired causes
disease
7. Atrial tumor
8. Large vegetation
9. Whipple disease
10. Gout
Congenital
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Natural History
Stable course initially, followed by accelerated progression in later life 104, 105, and 106
Rate of progression 0.09 to 0.32 cm2/year (slower in United States and Europe107,108)
The interval between acute rheumatic fever and symptomatic MS is ~15 years. 109
Once symptoms develop, another ~10 years before symptoms become disabling 104
Overall, the 10-year survival of untreated patients is 50% to 60%,105,106 but 0% to 15% once
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FIGURE 12-4 Management algorithm: aortic stenosis. PBMV, perculaneous balloon mitral valvuloplasty;
Physical Exam
Loud snapping S1
Opening snap (medium-high pitch) not heard with heavy calcification, mixed mitral disease,
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Chest x-ray is normal early in disease but LAE and pulmonary HTN develop later.
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Echocardiography
o Quantification of stenosis severity (see Table 12-11) based on valve area, transmitral
leaflet/immobility of posterior leaflet) and evaluation for MR, as well as other valve
o Rule out other causes of obstruction (LA myxoma, parachute MV, Cor triatrium).
Formal exercise testing with measurement of transmitral gradient and PA pressures may help
Serial follow-up of asymptomatic patients: Severe MS - yearly TTE; moderate MS - TTE every 1
Identification of patients who will benefit from intervention (see Table 12-13)
Annual follow-up with the indication for chest x-ray, ECG, or TTE based on severity of MS
Holter monitoring in patients with palpitations in the absence of documented AF
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Medical Therapy
Patients with AF or atrial flutter (30%-40%) have high risk for thromboembolism and need
Patients with MS/AF should have efforts to restore sinus rhythm (balloon valvulotomy or
Avoidance of strenuous activity (increases in HR lead to high LAP) but low-level aerobic activity
Beta blockers are useful for patients with exertional symptoms (blocks tachycardia).
Salt restriction and diuretics for patients with pulmonary congestion
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Class I
thrombus or moderate/severe MR
thrombus/significant MR
Class II
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2. Symptomatic patients (NYHA II-IV) with valve area >1.5 cm2 if there is evidence of
Class III
1. Mild MS
Class I
present
Class II
1. MV replacement for symptomatic patients with severe MS and severe pulmonary HTN
2. MV repair for asymptomatic patients with moderate or severe MS who have had
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Class III
Adapted from AHA/ACC 2006 Guidelines on Management of Patients with Valvular Heart
Disease.1
P.203
The preferred procedure in select patients with pliable, noncalcified valves and minimal fusion
In these patients, immediate and long-term results (3-7 years) are comparable to surgical
The mean valve area usually doubles, with a 50% decrease in transmitral gradient in the
immediate postprocedure period.
Long term follow-up (3-7 years): 90% of patients free of events remain in NYHA I-II.
Complications include severe MR (2%-10%), large residual ASD (5%), LV perforation (0.5%-4 %),
Postprocedure: Baseline TTE at 72 hours and consideration for immediate surgery if either
Relative contraindications to PMV include: Significant (3-4+) MR; Left atrial thrombus;
Unfavorable valve anatomy (calcied valve, high Wilkins score)
Surgical Intervention
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Closed procedures are procedures of choice in developing countries whereas open procedures
Long-term outcomes are clearly better for commissurotomy than for medical therapy. 118, 119, 120,
and 121
MVR is an acceptable option in patients who are not candidates for surgical commissurotomy or
percutaneous valvulotomy.
The risk of surgery is lower in young patients with normal LV function, good functional status,
Preservation of the mitral valve apparatus is preferable (to preserve LVEF) but often not
P.204
Secondary TR is due to conditions that affect the RV (pulmonary HTN, chronic obstructive
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Primary causes include congenital etiologies (Ebstein anomaly) and acquired conditions
Patients s/p TV resection tolerate severe TR well for several years. 122
Other concomitant valve disease is usually present and usually dictates clinical course.
Physical exam: Prominent jugular V wave, jugular venous distension, hepatomegaly +/-
pulsatility, a classic holosystolic murmur at the LLSB that increases with inspiration (murmur
The most common procedure is annuloplasty (surgical plication vs. complete ring vs.
semicircular ring).
Variable outcomes
Tricuspid Stenosis
Primarily due to rheumatic heart disease127; only 3% to 5% of patients with rheumatic heart
P.205
There are limited data on natural history, but TS usually takes a slowly progressive course.
Physical exam notable: OS, diastolic murmur at RLSB (murmur often inaudible)
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Echocardiography
Doppler evaluation
Pulmonic Stenosis
The majority of cases (95%) are due to congenital abnormalities; 85% occur as an isolated
defect, but can occur in association with other congenital defects (tetralogy of Fallot,
Other rare etiologies include carcinoid disease and rheumatic heart disease.
Patients with mild PS (gradient <50 mm Hg) are rarely symptomatic, and outcomes are good
Severe PS (>80 mm Hg) typically leads to fatigue and dyspnea on exertion, and right heart
Overall survival at 25 years was 96% in a natural history study,129 and predictors of poor
Physical examination
Echocardiography
Severity based on transpulmonic velocity and gradient (severe: Velocity >1.2m/s and gradient
>80mm Hg)
Pulmonary HTN
Cardiac catheterization is not typically required unless clinical data and noninvasive data are
discordant.
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The intervention of choice for severe PS is balloon valvuloplasty, which has low morbidity and
Pulmonary Regurgitation
Pathologic PR occurs after intervention for congenital heart disease (tetralogy of Fallot), and
PA/annular dilatation due to pulmonary HTN, Marfan syndrome, or volume overload (as seen in
Patients with moderate/severe PR can develop chronic RV volume overload, dilation, and
failure.
Physical exam
The soft, diastolic, decrescendo diastolic murmur over LUSB may be difficult to hear.
Echocardiogram
dilation/dysfunction.
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97. Tischler, MD, et al., Mitral valve replacement versus mitral valve repair. A Doppler and quantitative
98. Mohty, D, et al., Very long-term survival and durability of mitral valve repair for mitral valve
P.213
99. Okita, Y, et al., Comparative evaluation of left ventricular performance after mitral valve repair or
valve replacement with or without chordal preservation. J Heart Valve Dis, 1993. 2(2): p. 159-166.
100. Hennein, HA, et al., Comparative assessment of chordal preservation versus chordal resection
during mitral valve replacement. J Thorac Cardiovasc Surg, 1990. 99(5): p. 828-836; discussion 836-837.
101. Rozich, JD, et al., Mitral valve replacement with and without chordal preservation in patients with
102. Horskotte, D, et al., The effect of chordal preservation on late outcome after mitral valve
103. Gorlin, R and SG Gorlin,Hydraulic formula for calculation of the area of the stenotic mitral valve,
other cardiac valves, and central circulatory shunts. I. Am Heart J, 1951. 41(1): p. 1-29.
104. Wood, P, An appreciation of mitral stenosis. I. Clinical features. Br Med J, 1954. 1(4870): p. 1051-
1063; contd.
105. Rowe, JC, et al., The course of mitral stenosis without surgery: tenand twenty-year perspectives.
106. Olesen, KH, The natural history of 271 patients with mitral stenosis under medical treatment. Br
107. Dubin, AA, et al., Longitudinal hemodynamic and clinical study of mitral stenosis. Circulation,
108. Gordon, SP, et al., Two-dimensional and Doppler echocardiographic determinants of the natural
history of mitral valve narrowing in patients with rheumatic mitral stenosis: implications for follow-up.
109. Horstkotte, D, R Niehues, and BE Strauer, Pathomorphological aspects, aetiology and natural
history of acquired mitral valve stenosis. Eur Heart J, 1991. 12 Suppl B: p. 55-60.
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110. Selzer, A and KE Cohn, Natural history of mitral stenosis: a review. Circulation, 1972. 45(4): p.
878-890.
111. van den Brink, RB, et al., The value of Doppler echocardiography in the management of patients
with valvular heart disease: analysis of one year of clinical practice. J Am Soc Echocardiogr, 1991. 4(2):
p. 109-120.
112. Sagie, A, et al., Echocardiographic assessment of mitral stenosis and its associated valvular lesions
in 205 patients and lack of association with mitral valve prolapse. J Am Soc Echocardiogr, 1997. 10(2):
p. 141-148.
113. Abernathy, WS and PW Willis, 3rd, Thromboembolic complications of rheumatic heart disease.
114. Adams, GF, et al., Cerebral embolism and mitral stenosis: survival with and without
P.214
115. Hwang, JJ, et al., Significance of left atrial spontaneous echo contrast in rheumatic mitral valve
disease as a predictor of systemic arterial embolization. Am Heart J, 1994. 127(4 Pt 1): p. 880-885.
116. Pan, M, et al., Factors determining late success after mitral balloon valvulotomy. Am J Cardiol,
117. Cohen, DJ, et al., Predictors of long-term outcome after percutaneous balloon mitral
118. Dean, LS, et al., Four-year follow-up of patients undergoing percutaneous balloon mitral
119. Dahl, JC, P Winchell, and CW Borden, Mitral stenosis. A long term postoperative follow-up. Arch
120. Ellis, LB, et al., Fifteen-to twenty-year study of one thousand patients undergoing closed mitral
121. John, S, et al., Closed mitral valvotomy: early results and long-term follow-up of 3724 consecutive
122. Frater, RW, Surgical management of endocarditis in drug addicts and long-term results. J Card
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123. Muller, O and J Shillingford, Tricuspid incompetence. Br Heart J, 1954. 16(2): p. 195-207.
124. Sepulveda, G and DS Lukas, The diagnosis of tricuspid insufficiency; clinical features in 60 cases
125. Duran, CM, Tricuspid valve surgery revisited. J Card Surg, 1994. 9(2 Suppl): p. 242-247.
126. Jugdutt, BI, et al., Long-term survival after tricuspid valve replacement. Results with seven
127. Kitchin, A and R Turner, Diagnosis and Treatment of Tricuspid Stenosis. Br Heart J, 1964. 26: p.
354-379.
128. Johnson, LW, et al., Pulmonic stenosis in the adult. Long-term follow-up results. N Engl J Med,
129. Nugent, EW, et al., Clinical course in pulmonary stenosis. Circulation, 1977. 56(1 Suppl): p. I38-
I47.
130. Therrien, J, et al., Pulmonary valve replacement in adults late after repair of tetralogy of fallot:
Fred A. Lopez
Randall Vagelos
Etiologies , 1 2
Other less common organisms, which are often “culture negative”: HACEK organisms
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Clinical Presentation 3
Fever, weight loss, fatigue, anorexia, arthritis/arthralgias, myalgias, skin manifestations, cough, mental
Risk Factors
Mitral valve prolapse (most common), other valvular abnormalities, hemodialysis, indwelling vascular
Atrial myxoma, carcinoid valve disease, myxomatous valve degeneration, papillary fibroelastoma,
Lambl excrescence, ruptured chordae, thrombus or stitch after valvular surgery, eosinophilic heart
disease, acute rheumatic fever, pulmonary embolus, CVA.
PHYSICAL EXAM
Cardiac auscultation for evidence of new heart murmur (in particular, murmur of valvular
regurgitation), Janeway's lesions, Osler's nodes (painful), splinter hemorrhages, Roth spots, skin
petechiae, oral petechiae, conjunctival hemorrhage, splenomegaly, clubbing, S3 gallop, lung crackles.
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Electrocardiogram (ECG)
Evaluate for prolonged P-R interval or high-grade A-V block suggestive of aortic perivalvular abscess, or
DIAGNOSIS5
Modified Duke Criteria for definite infective endocarditis: 2 major criteria or; 1 major and 3 minor
Major criteria: blood culture positive for typical organism from two separate blood cultures or
persistent culture positive from specimens greater than 12 hours apart or all of 3 or a majority of
greater than 4 separate cultures with an organism consistent with endocarditis, new valvular
regurgitation, echocardiogram positive for endocarditis (oscillating mass, abscess, or partial dehiscence
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of prosthetic valve), evidence of endocardial involvement, blood culture positive for Coxiella burnetti
Minor criteria: temperature > 38°C, vascular ( Janeway's lesions, emboli, mycotic aneurysm),
immunologic (Osler's nodes, Roth's spots, glomerulonephritis, positive rheumatoid factor), positive
blood culture not meeting major criteria or serological data supporting infection with organism known
Laboratory evaluation:6 Blood cultures prior to antibiotics; if initial cultures are negative
(approximately 10%) and diagnosis is still suspected, alert lab to hold for fastidious organisms (HACEK
organisms); May also be associated with leukocytosis, anemia, and/or microscopic hematuria
Chest radiograph: May reveal septic pulmonary emboli from right-sided endocarditis
Echocardiography7, 8, and 9: Transsthoracic echo: Starting point for suspected native valve
endocarditis: Sensitivity: 32% to 63%; Specificity: 98% to 100%; Transesophageal echo: Next step if
transthoracic echocardiogram (TTE) nondiagnostic and endocarditis is still suspected; First step in
evaluation of patient with prosthetic valve (see section below), high clinical suspicion, or anticipated
difficulty imaging with TTE; Also perform pre-operatively if patient will undergo valve surgery:
Sensitivity: 94% to 100%; Specificity: 98% to 100%; Additional considerations for transesophageal
TREATMENT 10
Early cardiothoracic surgery consultation and evaluation with coordination of care involving infectious
P.217
with the addition of gentamicin for 2 weeks OR Vancomycin for 4 weeks with penicillin allergy
Penicillin-sensitive Enterococcus: Ampicillin for 4-6 weeks with the addition of gentamicin for
4-6 weeks; penicillin G for 4-6 weeks with the addition of gentamicin for 4-6 weeks;
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Inpatient parenteral antibiotics first 2 weeks of treatment when risk of embolism and other
High risk for outpatient therapy: congestive heart failure (CHF), arrhythmia, altered mental
status, perivalvular abscess, aortic valve disease, prosthetic valve disease, infection with S.
Indications for surgery:10 Class I: heart failure secondary to valve stenosis or insufficiency, aortic or
mitral insufficiency with elevated left ventricular end-diastolic or left atrial pressures, aortic
insufficiency with mitral valve preclosure, fungal endocarditis, infection with highly resistant organism,
heart block, abscess, fistula formation, or mitral leaflet perforation. Class IIa: recurrent embolic
events, persistent vegetation with appropriate antimicrobial therapy. Class IIb: mobile vegetation > 10
mm.
OUTCOMES
Overall mortality of 10% to 20% for hospitalized patients, 30% to 40% 1-year mortality12
Significant increase in 6-month survival with valve replacement surgery for left-sided
endocarditis using current criteria for valve replacement (16% vs. 33%); most significant
decrease in mortality seen in patients with evidence of moderate to severe CHF (14% vs. 51%)14
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Comorbid medical conditions, Altered mental status, Moderate to severe CHF, Organism other
than S. viridans, Medical therapy without valve replacement
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Complications , , 4 16 17
Embolism: 20% to 40% of cases of endocarditis, of these cerebral - 62%, splenic - 49%, renal -
22%, coronary - 2%
Risk of embolization increases with the size and mobility of the vegetation and mitral valve
Vertebral osteomyelitis
Septic arthritis
Immune-complex glomerulonephritis
Renal infarction
Mycotic aneurysm
Fistula: Most commonly between paravalvular infection and sinuses of Valsalva, aorta, or
Valvular perforation
Cardiogenic shock
Arrhythmias (A-V block): Increased mortality associated with infranodal conduction block
Sepsis
Relapse Rate 1
Most common in 4 weeks following termination of antibiotics: Higher relapse rates with Enterococcus, S.
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pulmonary emboli
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infection (i.e., absence of aortic/mitral valve involvement, not MRSA, no high-level gentamicin
Enterobacteriaceae, Pseudomonas
Cleveland Clinic series of device endocarditis in 123 patients with pacemaker or ICD: 68%
polymicrobial18
Clinical Presentation: May have erythema or pain over device pocket, fever, chills, malaise,
anorexia
In one series, 41% mortality with antibiotic therapy alone compared with 19% mortality with
organism isolated
delay with patient remaining afebrile and with negative repeat blood cultures. Plan for
If pacemaker dependent, place temporary pacing wire with change every 5-10 days until
If at high risk for lethal arrhythmia, patient may wear external defibrillator vest until ICD can
be replaced.
Higher incidence of early prosthetic valve endocarditis with surgery performed during active
infective endocarditis
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P.220
Indications for surgery10: Class I: heart failure, dehiscence of prosthetic valve, increasing obstruction
or insufficiency of the infected prosthetic valve, paravalvular abscess. Class IIa: persistent bacteremia
therapy.
Fungal prosthetic valve endocarditis will require surgery plus long-term antifungal therapy.
discontinue aspirin. Discontinue heparin if focal neurologic symptoms develop and image brain
Early mortality: Older age, female, longer bypass times, emergency surgery, Staph etiology,
Late mortality: Older age, male, decreased ejection fraction, fungal etiology, extent of
One series reported a 36% incidence of myocardial abscess and a 63% incidence of paravalvular
abscess with prosthetic valve endocarditis. Relapse rate:1 10% to 15%
Libman-Sacks: Patients with systemic lupus erythematosus: Most commonly involves mitral
valve
Increased prevalence in lupus patients with positive anticardiolipin and/or lupus anticoagulant
antibodies
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Suggestion of predisposition to bacterial endocarditis from valvular damage and need for
antibiotic prophylaxis
P.221
Surgically or percutaneously repaired congenital heart disease with residual defect that
Prophylaxis is recommended for dental procedures that will disrupt gingival or periapical tissue
or oral mucosa.26
Prophylaxis is no longer indicated for gastrointestinal or genitourinary procedures.24
REFERENCES
1. Mylonakis E, Calderwood SB. Infective endocarditis in adults. N Engl J Med. 2001;345:1318-1330.
2. Hoen B, Epidemiology and antibiotic treatment of infective endocarditis: an update. Heart. 92:1694-
1700, 2006.
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3. Crawford MH, Durack DT. Clinical presentation of infective endocarditis. Cardiology Clinics. 21:159-
166, 2003.
5. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of
7. Erbel R, Rohmann S, Drexler M, et al. Improved diagnostic value of echocardiography in patients with
8. Shively BK, Gurule FT, Roldan CA, et al. Diagnostic value of transesophageal compared with
P.222
9. Fowler VG, Li J, Corey GR, et al. Role of echocardiography in evaluation of patients with
10. Bonow RO, et al. ACC/AHA 2006 Guidelines for the management of patients with valvular heart
11. Andrews MM, von Reyn CF. Patient selection criteria and management guidelines for outpatient
parenteral antibiotic therapy for native valve infective endocarditis. Clin Infect Dis. 2001;33:203-209.
12. Hasbun R, Vikram HR, Barakat LA, et al. Complicated left-sided native valve endocarditis in adults.
13. Moss R, Munt B. Injection drug use and right sided endocarditis. Heart. 2003;89:577-581.
14. Vikram HR, Buenconsejo J, Hasbun R, et al. Impact of valve surgery on 6-month mortality in adults
with complicated, left-sided native valve endocarditis: A propensity analysis. JAMA. 2003;290:3207-
3214.
15. Chu VH, Cabell CH,Benjamin DK,et al.Early predictors of in-hospital death in infective endocarditis.
Circulation. 2004;109:1745-1749.
17. Sexton DJ, Spelman D. Current best practices and guidelines. Cardiol Clin. 2003;21:273-282.
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18. Chua JD, Wilkoff BL, Lee I, et al. Diagnosis and management of infections involving implantable
19. Karchmer AW, Longworth DL. Infections of intracardiac devices. Cardiol Clin. 2003;21:253-271.
20. Darouiche RO. Treatment of infections associated with surgical implants. N Engl J Med.
2004;350:1422-1429.
21. Cacoub P, Leprince P, Nataf P, et al. Pacemaker infective endocarditis. Am J Cardiol 82:480-484,
1998.
22. Mahesh B, Angelini G, Caputo M, et al. Prosthetic valve endocarditis. Ann Thorac Surg.
2005;80:1151-1158.
24. Lockshin M, Tenedios F, Petri M, et al. Cardiac disease in the antiphospholipid syndrome:
25. Salem DN, Daudelin DH, Levine HJ, et al. Antithrombotic therapy in valvular heart disease. Chest.
2001;119:207-219.
26. Wilson W, et al. Prevention of infective endocarditis: Guidelines from the American Heart
Randall Vagelos
ACUTE PERICARDITIS , 1 2
transmural infarct and weeks to months postinfarction (Dressler syndrome), prior external
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Clinical presentation: Substernal chest pain, pleuritic in nature, +/- radiation to left arm,
often radiates to trapezius, pain diminished with sitting up and leaning forward, pain
Physical exam: Triphasic (ventricular systole, early diastole, and atrial contraction) friction
rub in 85% of patients, radiates from left lower sternal border to apex, exam often fluctuates
Electrocardiogram (ECG): Diffuse ST segment elevation with the exception of leads avR and V1
Laboratory evaluation: +/- Elevated white blood cell count with lymphocyte predominance,
elevated ESR suggests TB or autoimmune etiology, may see minimal troponin elevation (greater
elevation suggests
P.224
myocardial infarction or myocarditis), blood cultures if fever and elevated WBC, pericardial
fluid culture if purulent pericarditis is suspected and pericardiocentesis is performed
weeks
Colchicine (COPE Trial):3 One hundred twenty patients with first episode pericarditis from
aspirin+colchicine versus aspirin alone, and the aspirin+colchicine treatment arm resulted in
anticoagulation, large effusion greater than 20 mm, evidence of purulent pericarditis without
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effusive/constrictive pericarditis
PERICARDIAL EFFUSION , 1 2
trauma, infection (bacterial, fungal, HIV, mycobacterium), uremia, collagen vascular disease,
hypothyroidism
Cardiac tamponade: Pericardium exquisitely sensitive to fluctuations in volume over time and
Physical exam: Tachycardic, jugular venous distention, decreased heart sounds, paradoxical
pulse: >10mm Hg decrease in systolic arterial pressure with inspiration (can have absent
Invasive hemodynamic data:4 Characteristic fall in aortic pressure with inspiration and right
atrial pressure tracing pattern with steep x-descent and lack of y-descent
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Mitral inflow velocity: With inspiration mitral valve inflow velocity decreases and tricuspid
pericardiocentesis is performed.
Use caution with intubation and initiation of mechanical ventilation as positive end-expiratory
pressure may induce cardiovascular collapse from further decrease in preload.
Clinical presentation: Consistent with low cardiac output state manifested by decreased
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Kussmaul's sign: Lack of fall or increase in jugular venous distention (RA pressure) with
Pericardial knock: High-pitched, early diastolic sound due to sudden cessation of right
ventricular filling from rigid pericardium
Chest radiograph: Globular heart, calcified pericardium, pleural effusions, rarely pulmonary
edema
marked respiratory variation of greater than 25% in the mitral inflow E wave velocity
Echocardiographic evidence of marked respiratory variation of greater than 25% in the mitral
inflow E wave velocity (decreases with inspiration and increases with expiration)
imaging.
P.226
“Dip and plateau” or “square root sign” waveform of ventricular diastolic pressure due to
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(discordance) with increased right ventricular and decreased left ventricular systolic pressure
during inspiration.
Treatment: Pericardiectomy (mortality 6%-12% in various series)
REFERENCES
1. Little WC, Freeman GL. Pericardial disease. Circulation. 2006;113:1622-1632.
2. LeWinter MM, Kabbani S. Pericardial diseases. In: Zipes DP, Libby P, Bonow RO, Braunwald E, eds.
Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed. Philadelphia: Elsevier
Saunders; 2005:1757-1779.
3. Imazio M, et al. Colchicine in addition to conventional therapy for acute pericarditis: results of the
4. Sharkey SW. Beyond the wedge: Clinical physiology and the Swan-Ganz catheter. Am J Med.
1987;83:111-122.
5. Hancock EW. Differential diagnosis of restrictive cardiomyopathy and constrictive pericarditis. Heart.
2001;86:343-349.
6. Nishimura RA. Constrictive pericarditis in the modern era: A diagnostic dilemma. Heart. 2001;86:619-
623.
7. Talreja DR, et al. Constrictive pericarditis in the modern era: Novel criteria for diagnosis in the
8. Higano ST, et al. Hemodynamic Rounds Series II: Hemodynamics of constrictive physiology: Influence
21. Appendix
21.1 APPENDIX A - Central Vascular Access Techniques
APPENDIX A
Central Vascular Access Techniques
Ian Brown
ASEPTIC PROCEDURES
When performing elective central venipuncture, the provider must follow sterile procedures. Once the
skin is grossly clean, scrub a wide area with 2% chlorhexidine for 30 to 60 seconds. Chlorhexidine is
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The provider should wash hands with antibacterial soap and water or an alcohol-based waterless
product.3,4 For elective central venous catheter (CVC) placement, the provider should use surgical cap,
gown, sterile gloves, mask with face shield, and full-body drape.5 Scheduled line changes and reducing
the number of lumens of a catheter are not useful for preventing infection.1,6
Tips
Have all instruments, kits, and tubes ready at bedside, such that they can be opened in sterile
fashion if needed.
PREPARE
Most hospitals stock prepared kits containing the basic required equipment for placement of a central
venous catheter (CVC) except for sterile gloves, saline flushes, and needleless saline-lock hubs.
Equipment Needed
Preparation and drape: chlorhexidine (2% solution with applicator), full-body fenestrated
Placement: needle capable of passing guidewire, 10-mL syringe, guidewire, 11-blade scalpel,
Securing the catheter: needle driver, 4-0 or larger nonabsorbable suture material or stapler,
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Arterial
Hematoma
Extended need for IV access Risks for sclerosis or thrombosis (e.g., Infection
Nerve injury
placement
procedure
thrombosis
Arteriovenous
fistula
PROCEDURE
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Anesthetic: in conscious patients apply lidocaine. Superficially, use a skin wheal. Anesthetize
Catheter placement (see Figure A-1): While applying negative pressure (i.e., pulling back on
syringe plunger) advance needle into vessel (A) until flash of blood in the syringe. Pass the
guidewire through the needle (B) into the vessel. Remove the needle (C) while the guidewire
remains. Placing the flat edge of an 11-blade scalpel parallel to the wire (D), push down to
incise the skin. Depending on the kit used, dilation is either performed by a catheter-over-
dilator method (as with a Cordis introducer sheath kit), or a separate dilator and catheter. The
combined equipment is depicted in Figure A-1. The catheter-over-dilator is threaded onto the
guidewire (E). With a firm twisting motion, the dilator and catheter are advanced into the vein
(F). Then the dilator is removed with the catheter remaining in the vessel (G). (If a separate
dilator is used, after dilation, the dilator is removed while the wire remains. Then place the
catheter over the wire into the vessel.) Advance the catheter such that the tip is in the desired
position, usually in the vena cava near the right atrium. Remove the wire. Never let go of the
wire as long as it is in the patient.
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Flush - Perform phlebotomy as needed. Attach saline-lock hub. Attach flush-syringe and pull
back and confirm good blood flow into syringe. Flush with 10 mL of saline.
Secure the catheter to the skin with sutures or staples. Depending on the kit used, there is
often a butterfly clip and a locking cap that can be used for securing the catheter. Clean, dry,
and cover with antibiotic ointment and transparent dressing.
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TIPS
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Always order postprocedure chest radiograph after upper body CVC insertion. Specifically
If unsure whether catheter is in vein or artery, consider color and pressure of blood. If readily
available, check arterial blood gas (ABG) or use pressure transducer. Never dilate the vessel if
If using an upper extremity site, prepare both the neck and ipsilateral chest for all jugular and
subclavian approaches.
If multiple sticks are used, be sure to flush, or replace, needle after each stick (lidocaine can
be used).
When treating severe sepsis, consider placement of CVC capable of measuring central venous
oxygen saturation for use in early goal-directed therapy.8
Pros: Low rate of infection. Easily identifiable landmarks. Maximizes patient mobility.
Position: The patient should be supine to 15-degree Trendelenburg's position, as tolerated, to decrease
chance of air embolism. The head should face forward. A small rolled towel can be placed between the
scapulae. The right side is preferred9 because of a lower pleural dome and avoidance of the thoracic
duct, except when placing an introducer sheath for procedures (e.g., transvenous pacing or PA catheter
placement).
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pacemaker
access
Hemodialysis access
Procedure: Identify and palpate the landmarks—clavicle and sternal notch (Figure A-2). Prepare and
drape the patient. In the conscious patient, apply lidocaine, including to the periosteum of the clavicle
at point of intersection.
A preferred method9 is to enter the skin just caudal to the middle of the clavicle. Advance the needle
toward the sternal notch until it hits the clavicle at the junction of the medial two thirds. While
maintaining negative pressure, gently “walk” the needle down the clavicle until it passes directly
beneath it. Advance slowly with the needle horizontal to the plane of the patient. Blood “flash” is
often obtained at a depth of 1 to 2 inches. If the first approach does not yield blood, pull back to skin,
fan the needle cephalad, and reinsert. Keeping the needle bevel pointing caudal, pass the guidewire
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NOTES
Needle insertion at the medial aspect of the delta-pectoral groove (at the anterior clavicular
tubercle at the junction of the lateral two thirds of the clavicle), may make a technically
easier procedure than does midclavicle insertion, but increases the risk of complications
Don't be afraid to hit the clavicle; the attached vein is directly beneath it. Going too deep
Place the provider's nondominant index finger on the sternal notch (and thumb on clavicle) and
aim underneath the index finger, staying horizontal to the plane of the patient. Alternatively,
place a fingerprint of blood or povidone-iodine on the drape as a landmark.
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Cons: Difficult in obese patients. Interferes with patient neck movement. Interferes with intubation.
Position: The patient should be supine to 30-degree Trendelenburg's position, as tolerated. The head
should face approximately 45 degrees away from the procedure site. If the patient is awake, humming
or Valsalva is helpful to engorge the jugular system.11 The right side has a more direct path to the
superior vena cava and avoids the thoracic duct; thus, it is preferred, particularly if placing a Cordis
Procedure: Ultrasound guidance techniques are superior to landmark techniques alone, particularly in
IJ placement. Ultrasound decreases time of placement, increases chances of successful placement, and
CVC when training and equipment permits. , Ultrasound should be used in conjunction with the
1 12
Identify and palpate the landmarks:The clavicle, the sternocleidomastoid muscle, and the carotid
artery. Prepare and drape the patient. The IJ courses down the middle of the triangle formed by the
two straps of the sternocleidomastoid muscle heading toward the clavicle (Figure A-3A and B). Because
the IJ lies just lateral to the carotid artery, placing fingers from the provider's nondominant hand along
the carotid maintains identification of landmarks and decreases chances of arterial puncture.
Apply a wheal of lidocaine at the apex of the cephalad end of the triangle formed by the
sternocleidomastoid muscle. Aim at the ipsilateral nipple, while keeping the needle at a 20-degree
angle above the plane of the body. While maintaining negative pressure, puncture at this place.
Depending on body habitus, expect blood at about 0.5-inch depth. If the vessel is not successfully
cannulated, pull back to the skin and fan the needle to a point more medial. Some physicians prefer to
start with a 22-gauge “finder needle” attached to a 5-mL syringe to identify the IJ and then use this as
a guide for the larger needle through which the wire can be passed as described above.
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attempt
Coagulopathy/anticoagulation Tracheal
perforation
Concurrent intubation
Neck trauma
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P.235
NOTES
The right side of the neck is generally easier for right-hand-dominant physicians.
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If the carotid artery is punctured, simply hold pressure with the nondominant hand and
If using a finder needle, the provider can place the procedure needle parallel to the finder
needle, or when removing the finder needle, drip a thin line of blood to mark the course of the
IJ.
Pros: Good landmarks. Quick to place. Easy to apply pressure if artery is punctured.
Cons: Risk of infection and thrombosis. CPR can cause femoral vein pulsation.
Position: The patient should be in supine position. If the physician is right-hand dominant, the patient's
Procedure: Identify and palpate landmarks. Prepare and drape patient. Place the provider's
nondominant hand over the femoral artery pulsation just distal to the inguinal crease. The femoral vein
is directly medial to the artery. Apply lidocaine to the conscious patient. Enter the skin at
approximately a 45-degree angle. Advance the needle, with negative pressure, until a dark blood flash
access
perforation
perforation
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thrombosis (DVT)
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Emergency venous
access
needed
provider
Pros: The complication rate of an EJ is almost zero; compare to ~13% complication rate for IJ, including
very serious complications.19 For an experienced physician who can visualize the EJ, the excellent risk
profile may make the EJ an ideal line for the critically ill patient for whom a complication may be life
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threatening.20 An EJ peripheral line can later be converted to a CVC line, if needed. No pain from deep
puncture.
Cons: Extra time required for inexperienced physicians to manipulate the wire intrathoracically.
Uncommon. The rate of successful EJ placement is only ~76%, compared to ~91% for IJs. 19
Position: The patient should be supine to 30-degree Trendelenburg's position, as tolerated. The head
should face approximately 45 degrees away from the procedure site. If the patient is awake, humming
Procedure: In one version of this procedure, an 18-gauge angiocatheter can be placed in the EJ as a
peripheral line using sterile precautions. Later, if central venous access is indicated, the line can be
converted into a CVC. The site is sterilized, and the IV tubing and saline-lock are removed. A “J” tipped
wire21 is passed via the angiocatheter until an intrathoracic position is presumed (the length of the
guidewire must extend past the clavicle). The angiocatheter is then removed. A standard CVC can be
passed over the wire via the Seldinger technique.
Pros: No need to stop CPR or intubation.9 Only possible CVC for sitting patient.
Position: The patient can be in any position from sitting up to 30-degree Trendelenburg's position, as
tolerated.
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
CPR Hemothorax
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
P.238
TABLE A-7 Comparison of complication incidence by CVC method; Ease of use in code
329
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
situation
IC IJ Femoral EJ Super C
Mechanical
complications6,25,26
puncture
Pneumothorax 2%-3% 0% 0% 0% 1%
d d d da
situation
a
Most articles that give complication rate for subclavian vein cannulation do not delineate
approach.
Procedure: Identify and palpate landmarks. Prepare and drape the patient. The needle is inserted
above and behind the medial clavicle (Figure A-4). The syringe bisects the angle formed by the clavicle
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
and the sternal head of the sternocleidomastoid muscle. Aim just caudal to the contralateral nipple.
While pulling back on the syringe plunger, insert the needle initially horizontal to the body. If no blood
is returned, withdraw the needle to the surface and tilt it such that it is aiming slightly posterior.
Cannulation of the bulb where the subclavian vein meets the internal jugular is usually achieved when
COMPLICATIONS OF CVC
Methods for decreasing complications include maximizing physician experience, minimizing catheter
indwelling time, using maximum sterile precautions, and choosing a clinically appropriate line with
minimal complications (Table A-7). Antibiotic-impregnated catheters have been shown to decrease CVC
P.239
REFERENCES
1. O'Grady NP, Alexander M, Dellinger EP, et al. Guidelines for the prevention of intravascular catheter-
2. Maki DG, Alvarado CJ, Ringer M. Prospective randomised trial of povidone-iodine, alcohol, and
chlorhexidine for prevention of infection associated with central venous and arterial catheters. Lancet.
1991;338: 339-343.
3. Larson EL. APIC guideline for handwashing and hand antisepsis in health care settings. Am J Infect
Control. 1995;23:251-269.
4. Mimoz O, Pieroni L, Lawrence C, et al. Prospective, randomized trial of two antiseptic solutions for
prevention of central venous or arterial catheter colonization and infection in intensive care unit
5. Raad I, Hohn DC, Gilbreath BJ, et al. Prevention of central venous catheter-related infections by
using maximal sterile barrier precautions during insertion. Infect Control Hosp Epidemiol. 1994;15:231-
238.
6. McGee DC, Gould MK. Preventing complications of central venous catheterization. N Engl J Med.
2003;348:1123-1133.
7. Graham AS, Ozment C, Tegtmeyer K, et al. Central venous catheterization. N Engl J Med. 2007.
331
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
8. Rivers E, Nguyen B, Havstad S, et al., for the Early Goal-Directed Therapy Collaborative Group. Early
goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-
1377.
9. Mickiewicz M, Dronen S, Younger J. Central venous catheterization and central venous pressure
monitoring. In: Roberts J, Hedges J, eds. Roberts: Clinical Procedures in Emergency Medicine. 4th ed.
10. Simon RR. A new technique for subclavian puncture. JACEP. 1978;7:417.
11. Lewin MR, Stein J, Wang R, et al. Humming is as effective as Valsalva's maneuver and
Trendelenburg's position for ultrasonographic visualization of the jugular venous system and common
12. Guidance on the use of ultrasound locating devices for placing central venous catheters. In:
Technology Appraisals. 49th ed. London: National Institute for Clinical Excellence (NICE); 2002.
13. Teichgraber U, Benter T, Gebel M, et al. A sonographically guided technique for central venous
14. Bailey PL, Whitaker EE, Palmer LS, et al. The accuracy of the central landmark used for central
P.240
15. Randolph AG, Cook DJ, Gonzales CA, et al. Ultrasound guidance for placement of central venous
catheterization in the emergency department increases success rates and reduces complications: A
17. Hind D, Calvert N, McWilliams R, et al. Ultrasonic locating devices for central venous cannulation:
18. Rothschild J. Ultrasound guidance of central venous catheterization. In: Wachter R, ed. Evidence
Report/Technology Assessment No. 43, Making Health Care Safer: A Critical Analysis of Patient Safety
Practices. Rockville, MD: Agency for Healthcare Research and Quality; 2001.
19. Belani K, Buckley J, Gordon J, et al. Percutaneous cervical central venous line placement: A
comparison of the internal and external jugular vein routes. Anesth Analg. 1980;59:40-44.
332
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
20. Byth PL. Evaluation of the technique of central venous catheterisation via the external jugular vein
21. Blitt CD, Wright WA, Petty WC, et al. Central venous catheterization via the external jugular vein. A
22. Heard S, Wagle M, Vijayakumar E, et al. Influence of triple-lumen central venous catheters coated
with chlorhexidine and silver sulfadiazine on the incidence of catheter-related bacteremia. Arch Intern
Med. 1998;158:81-87.
23. Raad I, Darouiche R, Dupuis J, et al. Central venous catheters coated with minocycline and rifampin
for the prevention of catheter-related colonization and bloodstream infections: A randomized, double-
24. Maki DG, Stolz SM, Wheeler S, et al. Prevention of central venous catheter-related bloodstream
infection by use of an antiseptic-impregnated catheter: A randomized, controlled trial. Ann Intern Med.
1997;127:257-266.
25. Brahos G. Central venous catheterization via the supraclavicular approach. J Trauma. 1977;17:872-
877.
26. Eisen LA, Narasimhan M, Berger JS, et al. Mechanical complications of central venous catheters. J
27. Cho SK, Shin SW, Do YS, et al. Use of the right external jugular vein as the preferred access site
when the right internal jugular vein is not usable. J Vasc Interv Radiol. 2006;17:823-829.
28. Sterner S, Plummer DW, Clinton J, et al. A comparison of the supraclavicular approach and the
infraclavicular approach for subclavian vein catheterization. Ann Emerg Med. 1986;15:421-424.
P.241
29. Merrer J, De Jonghe B, Golliot F, et al., for the French Catheter Study Group in Intensive Care.
Complications of femoral and subclavian venous catheterization in critically ill patients: A randomized
30. McKinley S, Mackenzie A, Finfer S, et al. Incidence and predictors of central venous catheter related
31. Torok-Both CJ, Jacka MJ, Brindley PG. Best evidence in critical care medicine: Central venous
333
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
32. Timsit J, Farkas J, Boyer J, et al. Central vein catheter-related thrombosis in intensive care
patients: Incidence, risk factors, and relationship with catheter-related sepsis. Chest. 1998;114:207-
213.
33. Trottier SJ, Veremakis C, O'Brien J, et al. Femoral deep vein thrombosis associated with central
venous catheterization: Results from a prospective, randomized trial. Crit Care Med. 1995;23:52-59.
34. Knopp R, Dailey RH. Central venous cannulation and pressure monitoring. JACEP. 1977;6:358-366.
PCW Cautions/cli
/min + dopami
not nergic
reco DA1
mme recepto
nded rs in
the
renal
mesent
eric
and
coronar
y beds
resultin
g in
vasodil
ation
2-10 + + + ↑ ? 0 ? ↑ ↑ Causes
µg/kg + + + NE
334
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
/min release
from
nerve
termin
als
10-20 + + + ↑ ? ↑ ↑ ↑ ↑ ↑ MVO2
µg/kg + + 0
/min +
e n + tachyar
rhythm
+ ias
rine n + ↑ - tachyar
rhythm
ias and
myocar
dial
ischemi
ne µg/mi + reflex
n bradyc
ardia
335
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
units tion
/min smooth
muscle
V1
recepto
rs
Myocar
dial
ischemi
a,
cardiac
dysfunc
tion,
arrhyth
mias
reporte
/min + 0 0 0 mias
one - ↑ ↓ echola
0.75µ mine,
min VD,
ARR,
adjust
dose in
renal
failure
336
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
/min VD
n n 0 nsion,
toleran
ce
de /min ↓ ↓ ↓ nsion,
reflex
tachyca
rdia,
caution
in renal
insuffic
iency
second
ary
accumu
lation
of
thiocya
nate
and
cyanide
toxiciti
es
α, alpha agonist; β, beta agonist; Dop, dopaminergic-1 agonist; CO, cardiac output; PCWP,
pulmonary capillary wedge pressure; SVR, systemic vascular resistance; BP, blood pressure; HR,
337
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
heart rate; ARR, arrhythmias; min, minutes; NE, norepinephrine; PDI, phosphodiesterase
P.246
P.247
P.248
P.249
P.250
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
Adverse
Effects, Drug
s, Na +
proarrhyth mg q6h
exacerbati 12h
ons
liver 30 min,
dysfunctio then 2-4
n, active mg/min
metabolit Afib
e NAPA mainten
accumulat ance: 1-
es, 2 g/d in
lupuslike divided
syndrome doses
in 30% of VT
patients if (preserv
of >40%):
treatment 20
339
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
, mg/min
hypotensi loading
on (IV) dose
30% infusion
until 17
mg/kg,
arrhyth
mia
ceases,
or QRS
widens
>50% VT
mainten
ance: 2-
mg/min
mide Na and
+
h Anticholin conversi
blockade, effects: mg po
tachycardi ance
a, dry 400-600
Glaucoma divided
doses
340
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
seizures, or renal, or
degree A- mg/kg 5
block 0.5-0.75
mg/kg
q3-5
min
thereaft
er max
3 mg/kg
VT
mainten
ance: 1-
mg/min
11 h underlying mg q8h
conductio
disturbanc
es,
ventricula
arrhythmi
as
341
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
CI: Third-
degree A-
V heart
block
Propafe Na+ and (PM) t1/2 AE: Digoxi Afib Can use
none Ca2+
= 10-25 Metallic n ↑ by conversi in NYHA
(causes by mainten
disease, mg po
valvular q8-12h
disease
(torsade
de
pointes)
de Na +
= 14-20 exacerbati n ↑ by conversi 2.5
effects valvular
disease,
LV
hypertrop
hy,
342
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
(torsade
de
pointes)
Amiodar Na+, K+, t1/2 = 15- AE: Warfa Afib Does not
glycopro pointes (8 to 10
to (14%); ance:
Iodine conversi
tivity, mg IVP
hyperthyr × 1,
oidism, repeat
heart 150 mg
block IVP q 3-
5 min
(ARREST
trial), or
343
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
(ALIVE
trial): 5
mg/kg
IVP,
repeat
2.5
mg/kg
Stable
VT: 150
mg IVP
× 1 over
10
minutes
VT/VF
mainten
ance: 1
mg/min
× 6h
then 0.5
mg/min
(max =
2.2 g/d)
,K +
(3%-8%) within 3 days Afib QTc >440
mg bid hospitali
>60 zation
mL/min for
344
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
80 mg initiation
q36-48h
10-30
mL/min
80 mg >
q48h
<10
mL/min
trimethoprim, 60 ECG
po bid if dose
40 hospitali
mL/min zed
(efficac
y 12% at
1 mo)
Afib
mainten
ance:
Titrate
upward
345
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
based
on QTc
NTE 500
ms or
>15% ↑
in QTc
after
each
dose
Ibutilide Strong K+ t1/2 = 3-6 AE: Torsade risk (8%) Conversi Requires
also Na +
concomitant mg × 1 monitori
ineffecti rsion
ve
(efficac
y 47% at
90 min)
t1/2, half-life; AE, adverse effects; TR, therapeutic range; HF, heart failure; CI, contraindications;
CrCL, creatinine clearance; Afib, atrial fibrillation; NTE, not to exceed; LV, left ventricular; DI,
drug interactions; IV, intravenous; CAD, coronary artery disease; PM, poor metabolizers; EM,
extensive metabolizers.
P.251
P.252
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
TABLE B-3 Pharmacological rate control with atrial fibrillation: Acute setting (without
accessory pathway)
Adverse
Reactions, Drug
Interactions,
µg/kg/mi (dopamine,
n infusion dobutamine,
To epinephrine,
maximum isoproterenol)
200 , or glucagon
µg/kg/mi bradycardia,
n and asystole
intravenous
atropine,
pressors
(dopamine,
dobutamine,
epinephrine,
isoproterenol)
, or glucagon
and/or
temporary
ventricular
pacing may
347
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
be initiated
Beta atropine,
agonist pressors
(dopamine,
dobutamine,
epinephrine,
isoproterenol)
, or glucagon
bradycardia,
and asystole
intravenous
atropine,
pressors
(dopamine,
dobutamine,
epinephrine,
isoproterenol)
, or glucagon
and/or
temporary
ventricular
pacing may
be initiated
Diltiazem ↓S-A and Onset 2-7 HB, ↓BP, 0.25 Ca2+ overdose,
5-15 hypotension
mg/h IV Use
continuou intravenous
348
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
s atropine,
pressors
(dopamine,
dobutamine,
epinephrine,
isoproterenol)
, or glucagon
bradycardia,
and asystole
intravenous
atropine,
pressors
(dopamine,
dobutamine,
epinephrine,
isoproterenol)
, or glucagon
and/or
temporary
ventricular
pacing may
be initiated
Verapamil ↓S-A and Onset 3-5 HB, ↓BP, 0.075- Ca2+ overdose,
n over 2 to reverse
min hypotension
Use
intravenous
atropine,
pressors
(dopamine,
dobutamine,
epinephrine,
349
Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
isoproterenol)
, or glucagon
for
bradycardia,
asystole,
and/or
temporary
ventricular
pacing may
be initiated
t1/2, half-life; ADR, adverse drug reactions; BP, blood pressure; HR, heart rate; HF, heart failure;
HB, heart block; CI, contraindications; DI, drug interactions. From Fuster V, Ryden LE, Cannom
DS, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation:
Task Force on Practice Guidelines and the European Society of Cardiology Committee for
P.253
TABLE B-4 Heart rate control without accessory pathway with heart failure
Adverse Drug
Reactions,
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
d g accumulate
based in renal
on dysfunction
lean Some
body subgroup
wt. evidence to
0.25
mg
daily
IV
Symptomati
c digoxin
toxicity, use
Digoxin
Immune Fab
(Digibind)
Ca2+
m, then on vs.
blockade, neuropathy, on
vasodilator bradycardia
digoxin
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
t1/2, half-life; ADR, adverse drug reactions; HB, heart block; HR, heart rate; BP, blood pressure;
P.254
Adverse Drug
blockade, neuropathy, on
ry effects Warfarin,
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Concise Cardiology: An Evidence-Based Handbook, 1st Edition 2008
digoxin
t1/2, half-life; ADR, adverse drug reactions; BP, blood pressure; HB, heart block; DI, drug
interactions.
353