1830 PART 6 Disorders of the Cardiovascular System
slow sinusoidal type of mechanism (“sine-wave” pattern) followed by
asystole. Hypokalemia (Fig. 240-15) prolongs ventricular repolarization, often with prominent U waves. Prolongation of the QT interval
is also seen with drugs that increase the duration of the ventricular
action potential: class 1A antiarrhythmic agents and related drugs
(e.g., quinidine, disopyramide, procainamide, tricyclic antidepressants,
phenothiazines) and class III agents (e.g., amiodarone [Fig. 240-15],
dofetilide, sotalol, ibutilide). Systemic hypothermia (Fig. 240-15) also
prolongs repolarization, usually with a distinctive convex elevation of
the J point (Osborn wave). Marked QT prolongation, sometimes with
deep, wide T-wave inversions, may occur with intracranial bleeds,
particularly subarachnoid hemorrhage (“CVA T-wave” pattern) (Fig.
240-15). Hypocalcemia typically prolongs the QT interval (ST portion),
whereas hypercalcemia shortens it (Fig. 240-16). Digitalis glycosides
also shorten the QT interval, often with a characteristic “scooping” of
the ST–T-wave complex (digitalis effect).
■ NONSPECIFIC ST-T CHANGES AND LOW QRS
VOLTAGE
Many other factors are associated with ECG changes, particularly
alterations in ventricular repolarization. T-wave flattening, minimal
T-wave inversions, or slight ST-segment depression (“nonspecific
ST–T-wave changes”) may occur with a variety of electrolyte and acidbase disturbances, infectious or inflammatory processes, central nervous system disorders, endocrine abnormalities, many drugs, ischemia,
hypoxia, and virtually any type of cardiopulmonary abnormality, in
addition to physiologic changes (e.g., with posture or with meals). Low
QRS voltage is arbitrarily defined as peak-to-trough QRS amplitudes of
≤5 mm in the six limb leads and/or ≤10 mm in the chest leads. Multiple
factors may be responsible. Among the most serious include pericardial (Fig. 240-17) or pleural effusions, chronic obstructive pulmonary
disease, infiltrative cardiomyopathies, and anasarca.
■ ELECTRICAL ALTERNANS SYNDROMES
Electrical alternans—a beat-to-beat alternation in one or more components of the ECG signal—is a common type of nonlinear cardiovascular response to a variety of hemodynamic and electrophysiologic
perturbations. Total electrical alternans (P-QRS-T) with sinus tachycardia is a relatively specific sign of pericardial effusion, usually with
cardiac tamponade (Fig. 240-17). In contrast, pure repolarization
(ST-T or U wave) alternans is a sign of electrical instability and may
precede ventricular tachyarrhythmias.
■ CLINICAL INTERPRETATION OF THE ECG
Accurate analysis of ECGs requires thoroughness and care. The
patient’s age, gender, and clinical status should always be taken into
account. Many mistakes in ECG interpretation are errors of omission. Therefore, a systematic approach is essential. The following 14
points should be analyzed carefully in every ECG: (1) standardization
(calibration) and technical features (including lead placement and
artifacts), (2) rhythm, (3) heart rate, (4) PR interval/AV conduction,
(5) QRS interval, (6) QT/QTc
intervals, (7) mean QRS electrical axis,
(8) P waves, (9) QRS voltages, (10) precordial R-wave progression, (11)
abnormal Q waves, (12) ST segments, (13) T waves, and (14) U waves.
Comparison with any previous ECGs is invaluable.
■ COMPUTERIZED ELECTROCARDIOGRAPHY
Computerized systems are widely used for immediate retrieval of
thousands of ECG records. Fully automated computerized ECG analyses still have major limitations and, therefore, should not be accepted
without careful clinician review of both waveforms and intervals.
TABLE 240-1 Differential Diagnosis of ST-Segment Elevations
Myocardial ischemia/infarction
Noninfarction, transmural ischemia (Prinzmetal’s syndrome due to localized
coronary spasm)
Acute myocardial infarction (especially due to epicardial coronary occlusion)
Takotsubo syndrome (“stress cardiomyopathy”)
Postmyocardial infarction (ventricular aneurysm pattern)
Acute pericarditis
Normal variants (including benign “early repolarization” patterns)
Left ventricular hypertrophy/left bundle branch blocka
Other (rarer)
Acute pulmonary embolisma
Brugada patterns (right bundle branch block–like morphology with ST
elevations in right precordial leads)
Class 1C antiarrhythmic drugsa
DC cardioversion (transient)
Hypercalcemiaa
Hyperkalemiaa
Hypothermia (J [Osborn] waves)
Nonischemic myocardial injury
Myocarditis syndromes (infectious and non-infectious)
Tumor invading left ventricle
Trauma to ventricles
a
Usually localized to V1
–V2
or V3
.
Source: Modified from AL Goldberger et al: Goldberger’s Clinical
Electrocardiography: A Simplified Approach, 9th ed. Philadelphia, Elsevier/
Saunders, 2017.
Hyperkalemia
Mild-Moderate Moderate-Severe Very Severe
Lead I
Lead II
V1
V2
V1
P
T
P
T
V2
1s
1mV
FIGURE 240-14 The earliest ECG change with hyperkalemia is usually peaking (“tenting”) of the T waves. With further increases in the serum potassium concentration,
the QRS complexes widen, the P waves decrease in amplitude and may disappear, and finally a sine-wave pattern leads to asystole unless emergency therapy is given.
(Reproduced with permission from AL Goldberger et al: Goldberger’s cinical electrocardiography: A simplified approach, 9th ed. Philadelphia, Elsevier/Saunders, 2017.)
Electrocardiography
1831CHAPTER 240
Hypokalemia Hypothermia Amiodarone
II
Tricyclic overdose
I
Subarachnoid hemorrhage
III V3
V2
V3
U
V5 V4
T
FIGURE 240-15 A variety of metabolic derangements, drug effects, and other factors may prolong ventricular repolarization with QT prolongation or prominent U waves.
Prominent repolarization prolongation, particularly if due to hypokalemia, inherited “channelopathies,” or certain pharmacologic agents, indicates increased susceptibility
to torsades des pointes ventricular tachycardia (Chap. 254). Marked systemic hypothermia is associated with a distinctive convex “hump” at the J point (Osborn wave,
arrow) due to altered ventricular action potential characteristics. Note QRS and QT prolongation along with sinus tachycardia in the case of tricyclic antidepressant
overdose.
Hypocalcemia Normal Hypercalcemia
QT 0.48 s
QTc 0.51
QT 0.36 s
QTc 0.40
QT 0.26 s
QTc 0.35
II II II
I I I
FIGURE 240-16 Prolongation of the Q-T interval (ST-segment portion) is typical of hypocalcemia. Hypercalcemia may cause abbreviation of the ST segment and relative or
absolute shortening of the QT interval.
FIGURE 240-17 Classic triad of findings for pericardial effusion with cardiac tamponade: (1) sinus tachycardia; (2) low QRS voltages; and (3) electrical alternans (best seen
in leads V3
and V4
in this case; arrows). This triad is highly suggestive of pericardial effusion, usually with tamponade physiology, but is of limited sensitivity. (Adapted from
LA Nathanson et al: ECG Wave-Maven. http://ecg.bidmc.harvard.edu.)
1832 PART 6 Disorders of the Cardiovascular System
■ FURTHER READING
Clerkin KJ et al: Coronavirus disease (COVID-2019) and cardiovascular disease. Circulation 141:1648, 2020.
Goldberger AL et al: Goldberger’s Clinical Electrocardiography: A
Simplified Approach, 9th ed. Philadelphia, Elsevier, 2017.
Kligfield P et al: Recommendations for the standardization and
interpretation of the electrocardiogram: Part I: The electrocardiogram and its technology: A scientific statement from the American
Heart Association Electrocardiography and Arrhythmias Committee,
Council on Clinical Cardiology; the American College of Cardiology
Foundation; and the Heart Rhythm Society Endorsed by the International Society for Computerized Electrocardiology. J Am Coll Cardiol
49:1109, 2007.
Mirvis DM, Goldberger AL: Electrocardiography, in Braunwald’s
Heart Disease: A Textbook of Cardiovascular Medicine, 11th ed, Zipes
DP et al (eds). Philadelphia, Elsevier, 2019, pp. 117-153.
Nathanson LA et al: ECG Wave-Maven. Self-assessment program
for students and physicians. https://ecg.bidmc.harvard.edu. Accessed
June 2021.
Sandauke KE et al: Update to practice standards for electrocardiographic monitoring in hospital settings. A scientific statement from
the American Heart Association. Circulation 136:e273, 2017.
Sharma S et al: International recommendations for electrocardiographic interpretation in athletes. J Am Coll Cardiol 69:1057, 2017.
Surawicz B, Knilans T: Chou’s Electrocardiography in Clinical Practice:
Adult and Pediatric, 6th ed. Philadelphia, Elsevier/Saunders, 2008.
The ability to image the heart and blood vessels noninvasively has
been one of the greatest advances in cardiovascular medicine since
the development of the electrocardiogram (ECG). Cardiac imaging
complements history taking and physical examination, blood and laboratory testing, and exercise testing in the diagnosis and management
of most diseases of the cardiovascular system. Modern cardiovascular
imaging consists of echocardiography (cardiac ultrasound), nuclear
scintigraphy including positron emission tomography (PET) imaging,
magnetic resonance imaging (MRI), and computed tomography (CT).
These studies, often used in conjunction with exercise or pharmacologic stress testing, can be used independently or in concert depending
on the specific diagnostic needs. In this chapter, we review the principles of each of these modalities and the utility and relative benefits of
each for the most common cardiovascular diseases.
PRINCIPLES OF MULTIMODALITY
CARDIAC IMAGING
■ ECHOCARDIOGRAPHY
Echocardiography uses high-frequency sound waves (ultrasound) to
penetrate the body, reflect from relevant structures, and generate an
image. The basic physical principles of echocardiography are identical
241 Noninvasive Cardiac
Imaging: Echocardiography,
Nuclear Cardiology, and
Magnetic Resonance/
Computed Tomography
Imaging
Marcelo F. Di Carli, Raymond Y. Kwong,
Scott D. Solomon
to other types of ultrasound imaging, although the hardware and software are optimized for evaluation of cardiac structure and function.
Early echocardiography machines displayed “M-mode” echocardiograms in which a single ultrasound beam was displayed over time
on a moving sheet of paper (Fig. 241-1, left panel). Modern echocardiographic machinery uses phased array transducers that contain
up to 512 elements and emit ultrasound in sequence. The reflected
ultrasound is then sensed by the receiving elements. A “scan converter” uses information about the timing and magnitude of the reflected
ultrasound to generate an image (Fig. 241-1, right panel). This
sequence happens repeatedly in “real time” to generate moving images
with frame rates that are typically greater than 30 frames per second,
but can exceed 100 frames per second. The gray scale of the image features indicates the intensity of the reflected ultrasound; fluid or blood
appears black, and highly reflective structures, such as calcifications on
cardiac valves or the pericardium, appear white. Tissues such as myocardium appear more gray, and tissues such as muscle display a unique
speckle pattern. Although M-mode echocardiography has largely been
supplanted by two-dimensional (2D) echocardiography, it is still used
because of its high temporal resolution and accuracy for making linear
measurements.
The spatial resolution of ultrasound is dependent on the wavelength: the smaller the wavelength and the higher the frequency of the
ultrasound beam, the greater are the spatial resolution and ability to
discern small structures. Increasing the frequency of ultrasound will
increase resolution but at the expense of reduced penetration. Higher
frequencies can be used in pediatric imaging or transesophageal echocardiography where the transducer can be much closer to the structures
being interrogated, and this is a rationale for using transesophageal
echocardiography to obtain higher quality images.
Three-dimensional ultrasound transducers use a waffle-like matrix
array transducer and receive a pyramidal data sector. Three-dimensional
echocardiography is being increasingly used for assessment of congenital heart disease and valves, although current image quality lags behind
2D ultrasound (Fig. 241-2).
In addition to the generation of 2D images that provide information
about cardiac structure and function, echocardiography can be used to
interrogate blood flow within the heart and blood vessels by using the
Doppler principle to ascertain the velocity of blood flow. When ultrasound emitted from a transducer reflects off red blood cells that are
moving toward the transducer, the reflected ultrasound will return at a
slightly higher frequency than emitted; the opposite is true when flow
moves away from the transducer. That frequency difference, termed
the Doppler shift, is directly related to the velocity of the flow of the
red blood cells. The velocity of blood flow between two chambers will
be directly related to the pressure gradient between those chambers. A
modified form of the Bernoulli equation,
p = 4v2
where p = the pressure gradient and v = the velocity of blood flow in
meters per second, can be used to calculate this pressure gradient in
the majority of clinical circumstances. This principle can be used to
determine the pressure gradient between chambers and across valves
and has become central to the quantitative assessment of valvular heart
disease.
There are three types of Doppler ultrasound that are typically used
in standard echocardiographic examinations: spectral Doppler, which
consists of both pulsed wave Doppler and continuous wave Doppler,
and color flow Doppler. Both types of spectral Doppler will display
a waveform representing the velocity of blood flow, with time on the
horizontal axis and velocity on the vertical axis. Pulsed wave Doppler
is used to interrogate relatively low velocity flow and has the ability to
determine blood flow velocity at a particular location within the heart.
Continuous wave Doppler is used to assess high-velocity flow, but it
can only identify the highest velocity in a particular direction and cannot interrogate the velocity at a specific depth location. Both of these
techniques can only accurately assess velocities that are in the direction
of the ultrasound scan lines, and velocities that are at an angle to the
direction of the ultrasound beam will be underestimated. Color flow
Noninvasive Cardiac Imaging: Echocardiography, Nuclear Cardiology, and Magnetic Resonance/Computed Tomography Imaging
1833CHAPTER 241
Doppler is a form of pulsed wave Doppler in which the velocity of
blood flow is color encoded according to a scale and superimposed on
a 2D grayscale image in real time, giving the appearance of real-time
flow within the heart. The Doppler principle can also be used to assess
the velocity of myocardial motion, which is a sensitive way to assess
myocardial function (Fig. 241-3). A standard full transthoracic echocardiographic examination consists of a series of 2D views made up of
different imaging planes from various scanning locations and spectral
and color flow Doppler assessment.
Transesophageal echocardiography is a form of echocardiography
in which the transducer is located on the tip of an endoscope that
can be inserted into the esophagus. This procedure allows closer, less
obstructed views of cardiac structures, without having to penetrate
through chest wall, muscle, and ribs. Because less penetration is needed,
a higher frequency probe can be used, and image quality and spatial
resolution are generally higher than with standard transthoracic imaging, particularly for structures that are more posterior. Transesophageal
echocardiography has become the test of choice for assessment of small
lesions in the heart such as valvular vegetations, especially in the setting of a prosthetic valve disease, and intracardiac thrombi, including
assessment of the left atrial appendage, which is difficult to visualize
with standard transthoracic imaging, and for assessment of congenital
M-mode image
Echoes
Processing and scan conversion
Ultrasound
pulses
Image Generation in M-Mode and 2D Echocardiography
Heart
Time
Piezoelectric
elements
Phased array
transducer
timeDistance (depth)
2-D image
FIGURE 241-1 Principle of image generation in two-dimensional (2D) echocardiography. An electronically steerable phased-array transducer emits ultrasound from
piezoelectric elements, and returning echoes are used to generate a 2D image (right) using a scan converter. Early echocardiography machines used a single ultrasound
beam to generate an “M-mode” echocardiogram (see text), although modern equipment generates M-mode echocardiograms digitally from the 2D data. LV, left ventricle.
3D scan
Matrix array
elements
3D
I L
3D matrix array
transducer
FIGURE 241-2 Three-dimensional (3D) probe and 3D image.
A B C
FIGURE 241-3 Three types of Doppler ultrasound. A and B. Pulsed and continuous wave Doppler waveforms with time on horizontal axis and velocity of blood flow on
vertical axis. C. Color flow Doppler, where velocities are encoded by colors according to scale on right side of screen and superimposed on a two-dimensional grayscale
image.
1834 PART 6 Disorders of the Cardiovascular System
FIGURE 241-4 Two examples of hand-held ultrasound equipment: V-Scan (General Electric, left)
and Sonosite (right).
TABLE 241-1 Radiopharmaceuticals for Clinical Nuclear Cardiology
RADIOPHARMACEUTICAL IMAGING TECHNIQUE PHYSICAL HALF-LIFE APPLICATION
99mTc-sestamibi SPECT 6 h Myocardial perfusion imaging
99mTc-tetrofosmin SPECT 6 h Myocardial perfusion imaging
201Tl SPECT 72 h Myocardial perfusion imaging
123I-metaiodobenzylguanidine (MIBG) SPECT 13 h Cardiac sympathetic innervation
82Ru PET 76 s Myocardial perfusion imaging
13N-ammonia PET 10 min Myocardial perfusion imaging
18F-fluorodeoxyglucose PET 110 min Myocardial viability and inflammation imaging
Abbreviations: PET, positron emission tomography; SPECT, single-photon emission computed tomography.
abnormalities. Transesophageal echocardiography requires both topical and systemic anesthesia, generally conscious sedation, and carries
additional risks such as potential damage to the esophagus, including
the rare possibility of perforation, aspiration, and anesthesia-related
complications. Patients generally need to give consent for transesophageal echocardiography and be monitored during and subsequent to the
procedure. Transesophageal echocardiography can be carried out in
intubated patients and is routinely used for intraoperative monitoring
during cardiac surgery.
Stress echocardiography is routinely used to assess cardiac function
during exercise and can be used to identify myocardial ischemia or to
assess valvular function under exercise conditions. Stress echocardiography is typically performed in conjunction with treadmill or bicycle
exercise testing, but it can also be performed using pharmacologic
stress, most typically with an intravenous infusion of dobutamine (see
section on stress imaging below).
Whereas typical echocardiographic equipment is large, bulky, and
expensive, small hand-held or point-of-care ultrasound (POCUS)
equipment developed over the past decade now offers diagnostic
quality imaging in a package small enough to be carried on rounds
(Fig. 241-4). These relatively inexpensive point-of-care devices are
slowly gaining full diagnostic capabilities but currently represent an
excellent screening tool if used by an experienced operator. As these
units become even smaller and less expensive, they are being increasingly used not just by cardiologists but also by emergency medicine
physicians, intensivists, anesthesiologists, and internists.
Nevertheless, echocardiography is a nontomographic modality. The
image obtained is dependent on the skill of the operator who, holding
a transducer, identifies standard views from which measurements can
be made. Images that are obtained off-axis can result in incorrect measurements, such as chamber volumes or ejection fraction. As point-ofcare echocardiography becomes more commonplace, practitioners will
need sufficient training to obtain and interpret images.
Myocardial strain or deformation imaging has emerged as an alternative way to assess cardiac contractile performance. Global and/or
regional myocardial strain can be assessed either by Doppler or, more
commonly, by 2D echocardiography. Global longitudinal
strain is assessed from the apical view and calculated as
the endocardial perimeter length in end diastole minus
the endocardial perimeter length in end systole divided
by the endocardial perimeter length in end diastole. It
is more robust as a measure of contractile function than
volumetric-based ejection fraction and has been shown
to be predictive of outcome in a variety of cardiac diseases, including heart failure and following myocardial
infarction.
■ RADIONUCLIDE IMAGING
Radionuclide imaging techniques are commonly used
for the evaluation of patients with known or suspected
coronary artery disease (CAD), including for initial
diagnosis and risk stratification as well as the assessment
of myocardial viability. In addition, radionuclide imaging is commonly used in the evaluation of patients with
suspected cardiac amyloidosis, myocardial and vascular
inflammation, and infective endocarditis. These techniques use small amounts of radiopharmaceuticals (Table 241-1),
which are injected intravenously and trapped in the heart and/or
vascular cells. Radioactivity within the heart and vasculature decays
by emitting gamma rays. The interaction between these gamma rays
and the detectors in specialized scanners (single-photon emission
computed tomography [SPECT] and PET) creates a scintillation event
or light output, which can be captured by digital recording equipment
to form an image of the heart and vasculature. Like CT and MRI, radionuclide images also generate tomographic (three-dimensional) views
of the heart and vasculature.
Radiopharmaceuticals Used in Clinical Imaging Table 241-1
summarizes the most commonly used radiopharmaceuticals in clinical
SPECT and PET imaging.
Protocols for Stress Myocardial Perfusion Imaging Both
exercise and pharmacologic stress can be used for myocardial perfusion imaging. Exercise stress is generally preferred because it is physiologic and provides additional clinically important information (i.e.,
clinical and hemodynamic responses, ST-segment changes, exercise
duration, and functional status). However, submaximal effort will
lower the sensitivity of the test and should be avoided, especially if
the test is requested for initial diagnosis of CAD. In patients who are
unable to exercise or who exercise submaximally, pharmacologic stress
offers an adequate alternative to exercise stress testing. Pharmacologic
stress can be accomplished either with coronary vasodilators, such
as adenosine, dipyridamole, or regadenoson, or β1
-receptor agonists,
such as dobutamine. For patients unable to exercise, vasodilators are
the most commonly used stressors in combination with myocardial
perfusion imaging. Dobutamine is a potent β1
-receptor agonist that
increases myocardial oxygen demand by augmenting contractility,
heart rate, and blood pressure similar to exercise. It is generally used as
an alternative to vasodilator stress in patients with chronic pulmonary
disease, in whom vasodilators may be contraindicated. Dobutamine is
also commonly used as a pharmacologic alternative to stress testing in
stress echocardiography.
Noninvasive Cardiac Imaging: Echocardiography, Nuclear Cardiology, and Magnetic Resonance/Computed Tomography Imaging
1835CHAPTER 241
Myocardial Perfusion and Viability Imaging Protocols
Imaging protocols are tailored to the individual patient based on the
clinical question, patient’s risk, ability to exercise, body mass index,
and other factors.
For SPECT imaging, technetium-99m (99mTc)-labeled tracers are
the most commonly used imaging agents because they are associated with the best image quality and the lowest radiation dose to the
patient (Fig. 241-5). Selection of the protocol (stress-only, single-day,
or 2-day) depends on the patient and clinical question. After intravenous injection, myocardial uptake of 99mTc-labeled tracers is rapid
(1–2 min). After uptake, these tracers become trapped intracellularly in
mitochondria and show minimal change over time. This is why 99mTc
tracers can be helpful in patients with chest pain of unclear etiology
occurring at rest, because patients can be injected while having chest
pain and imaged some time later after symptoms subside. Indeed,
a normal myocardial perfusion study following a rest injection in a
patient with active chest pain effectively excludes myocardial ischemia
as the cause of chest pain (high negative predictive value). While used
commonly in the past for perfusion imaging, thallium-201 protocols
are now rarely used because they are associated with a higher radiation
dose to the patient.
PET myocardial perfusion imaging is an alternative to SPECT and
is associated with improved diagnostic accuracy and lower radiation
dose to patients (Table 241-1). The ultra-short half-life of some PET
radiopharmaceuticals in clinical use (e.g., rubidium-82) is the primary
reason why imaging is generally combined with pharmacologic stress,
as opposed to exercise. However, exercise is possible for relatively
longer-lived radiotracers (e.g., 13N-ammonia). PET imaging protocols
are typically faster than SPECT but more expensive. In comparison to
SPECT, PET has improved spatial and contrast resolution and provides
absolute measures of myocardial perfusion (in mL/min per gram of tissue), thereby providing the patients’ regional and global coronary flow
reserve. The latter helps improve diagnostic accuracy and risk stratification, especially in obese patients, women, and higher risk individuals
(e.g., diabetes mellitus) (Fig. 241-6). Contemporary PET and SPECT
scanners are combined with a CT scanner (so-called hybrid PET/CT
and SPECT/CT). CT is used primarily to guide patient positioning
in the field of view and for correcting inhomogeneities in radiotracer
distribution due to attenuation by soft tissues (so-called attenuation
correction). However, it can also be used to obtain diagnostic data
including coronary artery calcium (CAC) score and/or CT coronary
angiography (discussed below).
For the evaluation of myocardial viability in patients with ischemic
cardiomyopathy, myocardial perfusion imaging (with SPECT or PET)
is usually combined with metabolic imaging (i.e., fluorodeoxyglucose
[FDG] PET). In hospital settings lacking access to PET scanning,
thallium-201 SPECT imaging is an excellent alternative. FDG PET is
also used in the evaluation of myocardial and vascular inflammation
and in patients with suspected infective endocarditis.
Bone scintigraphy with SPECT is currently used for the evaluation
of patients with suspected cardiac amyloidosis. As discussed below
under applications in new-onset heart failure, bone-seeking 99mTc
radiotracers (Table 241-1) are currently used to diagnose transthyretin
cardiac amyloidosis with high accuracy.
■ CARDIAC COMPUTED TOMOGRAPHY
CT acquires images by passing a thin x-ray beam through the body at
many angles to generate cross-sectional images. The x-ray transmission
measurements are collected by a detector array and digitized into pixels
that form an image. The grayscale information in individual pixels
is determined by the attenuation of the x-ray beam along its path by
tissues of different densities, referenced to the value for water in units
known as Hounsfield units. In the resulting CT images, bone appears
bright white, air is black, and blood and muscle show varying shades of
gray. However, due to the limited contrast between cardiac chambers
and vascular structures, iodinated contrast agents are necessary for
most cardiovascular indications. Cardiac CT produces tomographic
images of the heart and surrounding structures. With modern CT
scanners, a three-dimensional dataset of the heart can be acquired in
5–15 s with submillimeter spatial resolution.
Gated perfusion images
Short axis
Horizontal long axis
12 13 14 15 16 17
Perfusion Defect blackout map
LAD
RCA
LCX
506.0
0.0
100.0%
0.0%
Perfusion Defect blackout map
LAD
RCA
LCX
145.0
0.0
100.0%
Perfusion Defect blackout map
LAD
RCA
LCX
50.0% 100.0%
0.0%
0.0% 0.0%
18 19 20 21 22 23
24 25 26 27 28 29
Vertical long axis
Total perfusion deficit
FIGURE 241-5 Tomographic stress (top of each pair) and rest myocardial perfusion images with technetium-99m sestamibi single-photon emission computed tomography
imaging demonstrating a large perfusion defect throughout the anterior and anteroseptal walls. The right panel demonstrates the quantitative extent of the perfusion
abnormality at stress (top bull’s-eye), at rest (middle bull’s-eye), and the extent of defect reversibility (lower bull’s-eye). The lower left panel demonstrates electrocardiogramgated myocardial perfusion images from which one can determine the presence of regional wall motion abnormalities and calculate left ventricular volumes and ejection
fraction.
1836 PART 6 Disorders of the Cardiovascular System
CT Calcium Scoring CT calcium scoring is the
simplest application of cardiac CT and does not require
administration of iodinated contrast. The presence of
coronary artery calcification has been associated with
increased burden of atherosclerosis and cardiovascular
mortality. Coronary calcium is then quantified (e.g.,
Agatston score) and categorized as minimal (0–10),
mild (10–100), moderate (100–400), or severe (>400)
(Fig. 241-7). CAC scores are then normalized by age
and gender and reported as percentile scores. Population-based studies in asymptomatic cohorts have reported
high cardiac prognostic value of CT calcium score. With
appropriate techniques, the radiation dose associated
with CAC scanning is very low (~1–2 mSv).
CT Coronary Angiography Coronary CT angiography (CTA) is a clinically important alternative to stress
testing in selected patients with suspected CAD. Imaging
of the coronary arteries by CT is challenging because
of their small luminal size and because of cardiac and
respiratory motion. Respiratory motion can be reduced
by breath-holding, and cardiac motion is best reduced
by slowing the patient’s heart rate, ideally to under 60
beats/min, using intravenous or oral beta blockade or
other rate-lowering drugs. When performing a coronary
CTA, image quality is further enhanced using sublingual
nitroglycerin to enlarge the coronary lumen just prior to
contrast injection. Imaging the whole-heart volume is
Myocardial perfusion images
23 31 36
19 21 23
GStrCTAC
Frame: 1 of 8
Stress time activity curves Mid-VLA
Mid-HLA
25 27
29 31 33 35 37
39
0
100
200
300
400
(kBq/ml) (kBq/ml) 500
600
700
800
900
5 10 15 20
Frame index
Rest time activity curves
25 30 35
0
100
200
300
400
500
600
5 10 15 20
Frame index
25 30 35
41 43 45 47
23 31 36
Total perfusion images
Quantitative myocardial blood flow and flow reserve
Flow (ml/min/g)
Region Stress Rest Reserve
LAD 2.32
LCX 2.29
RCA 2.30
TOT 2.30
1.09 2.12
1.08 2.12
0.99 2.33
1.06 2.18
Stress Rest
Gated perfusion images
FIGURE 241-6 Multidimensional cardiac imaging protocol with positron emission tomography. The left upper panel demonstrates stress and rest short-axis images of
the left and right ventricles demonstrating normal regional myocardial perfusion. The middle panel demonstrates the quantitative bull’s-eye display to evaluate the extent
and severity of perfusion defects. The lower right panel illustrates the time-activity curves for quantification of myocardial blood flow. The right upper panel demonstrates
electrocardiogram-gated myocardial perfusion images from which one can determine the presence of regional wall motion abnormalities and calculate left ventricular
volumes and ejection fraction. LAD, left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery; TOT, total left ventricle.
Mixed
Noncalcified
RCA
Ao
Ao
Ao
LAD
A B
C D
LAD
Calcified
PA
FIGURE 241-7 Examples of non-contrast- and contrast-enhanced coronary imaging with computed
tomography (CT). A. Calcified coronary plaques in the distal left main and proximal left anterior
descending coronary artery (LAD) in a noncontrast cardiac CT scan. Calcium deposits are dense
and present as bright white structures on CT, even without contrast enhancement. B, C, and D.
Different types of atherosclerotic plaques on contrast-enhanced CT scans. Importantly, noncalcified
plaques are evident only on contrast-enhanced CT scans. AO, aorta; PA, pulmonary artery; RCA,
right coronary artery.
Noninvasive Cardiac Imaging: Echocardiography, Nuclear Cardiology, and Magnetic Resonance/Computed Tomography Imaging
1837CHAPTER 241
synchronized to the administration of weight-based and appropriately
timed intravenous iodinated contrast. Image acquisition is linked to
the timing of the cardiac cycle through ECG triggering. The resulting
images are then postprocessed using a three-dimensional workstation,
which facilitates interpretation of the coronary anatomy and estimation
of the severity of atherosclerosis (Fig. 241-7). A modified version of the
enhanced protocol outlined for coronary CTA is used for the evaluation of patients with structural heart disease, especially for preprocedural planning of those undergoing transcatheter valve replacement.
■ CARDIAC MAGNETIC RESONANCE
Cardiac magnetic resonance (CMR) imaging is based on imaging of
protons in hydrogen, which is an advantage, given the abundance of
water in the human body. When the body is placed inside an MRI
scanner, protons in different tissues, such as in simple fluid or complex
macromolecules such as fat or protein, interact with the magnetic
field at their unique frequencies. A set of orthogonal gradient coils
in the scanner is designed to locate protons spatially so that radiofrequency (RF) pulses of energy can be delivered to select imaging
planes of interest. Once the RF pulses stop, the energy absorbed will
be released, collected by the phased-array receiver coils placed on the
patient’s body surface, digitally recorded in a data matrix known as
the K-space, and then reconstructed into a magnetic resonance image.
The large arrays of software methods of delivering RF pulses are known
as pulse sequences, which aim at extraction of different types of cardiac
structural or physiologic information. In CMR, T1-weighted pulse
sequences are most common, and they assess cardiac structure and
function, blood flow, and myocardial perfusion with pharmacologic
stress. T2-weighted and T2*
-weighted pulse sequences, on the other
hand, evaluate myocardial edema and myocardial iron infiltration,
respectively. In recent years, T1 and T2 mapping have become routinely
used in experienced centers in quantifying myocardial tissue characteristics, with T1 mapping most commonly used to scale the spectrum of
myocardial inflammation or fibrosis and T2 mapping for myocardial
edema. Using a combination of these methods (above), a CMR can
accurately assess cardiac structure and function, myocardial infarction,
ischemia, and infiltration. Currently, the most common indications
for CMR include assessing etiology of cardiomyopathy, detection of
myocardial ischemia from other chest pain syndromes, and defining
myocardial substrates of arrhythmias. Vector ECG-gating and repetitive patient breath-holding are used by convention to suppress cardiac
and respiratory motions, respectively. However, with technical advent,
rapid data collection algorithm and diaphragmatic position gating have
eliminated the need for ECG-gating and breath-holding in challenging
situations. A list of common pulse sequences used in CMR is shown
in Table 241-2.
ASSESSMENT OF CARDIAC STRUCTURE
AND FUNCTION
Echocardiography, CMR, and cardiac CT are all capable of assessing
cardiac structure and function, although echocardiography is generally
considered the primary imaging method for these assessments. Radionuclide imaging can also be used to assess left ventricular regional and
global systolic function. Echocardiography is most often used to assess
the size of all four chambers and thickness of ventricular walls, which
are affected by both cardiac and systemic diseases.
The structure of the left ventricle is generally assessed by determining its volume and mass. Left ventricular volumes can be easily
estimated from 2D echocardiography by using methods incorporating
geometric assumptions. The accuracy of these echocardiographic
methods is reduced when foreshortening of the imaging plane leads to
underestimation of volumes. Moreover, these methods require accurate
delineation of the endocardial border. In this regard, high-resolution
tomographic techniques such as CMR or cardiac CT are more accurate
for volumetric assessment. Three-dimensional (3D) echocardiography
does not require any geometric assumptions about the left ventricle for
quantification of volumes and ejection fraction. However, 3D echocardiographic imaging requires substantial expertise and currently is not
widely used in practice.
TABLE 241-2 Clinical Cardiac Magnetic Resonance Pulse Sequences
and Their Application
PULSE SEQUENCE KEY IMAGING INTERESTS
Cardiac Morphology
Still frame imaging (black or bright
blood)
Cardiac structures
Cardiac Function
Cine imaging Left ventricular volume and function
Cine myocardial tagging Left ventricular deformation (strain)
Blood Flow Imaging
Velocity-encoded phase contrast Cardiac and great vessel flow
Stress Testing
Myocardial perfusion imaging Regional myocardial blood flow
Cine imaging Regional wall motion
Myocardial Tissue Characterization
Late gadolinium enhancement Myocardial infarction and infiltrative
disease
T2-weighted imaging Myocardial edema
Iron content imaging Myocardial iron infiltration
Magnetic Resonance Angiography
Aorta, peripheral and coronary arteries Luminal stenosis and vessel wall
remodeling
Left ventricular dilatation is common to a number of cardiac diseases. For example, regional dysfunction secondary to myocardial
infarction can ultimately lead to progressive ventricular dilatation or
remodeling. Although dilatation often begins in the region affected
by the infarction, subsequent compensatory dilatation can occur in
remote myocardial regions as well. The presence of regional wall
motion abnormalities associated with ventricular thinning (reflecting
scar) in a coronary distribution is strongly suggestive of an ischemic
etiology. Regional wall motion can be accurately assessed by echocardiography, CMR, and cardiac CT. Direct assessment of infarcted
myocardium is possible with both CMR (evident as areas of late gadolinium enhancement [LGE]) and radionuclide imaging (as assessed
by regional perfusion or metabolic defects at rest). CMR can be particularly useful in determining etiology of cardiomegaly and ventricular
dysfunction, with LGE in coronary distributions being nearly pathognomonic for infarction (Video 241-1).
More global ventricular dilatation is seen in cardiomyopathy and
dilatation due to valvular heart disease. Idiopathic, nonischemic
cardiomyopathies will typically result in global ventricular dilatation
and dysfunction, with thinning of the walls. Patients with substantial
ventricular dyssynchrony due to conduction abnormalities will have a
typical pattern of contraction (e.g., delay of contraction of the lateral
wall with left bundle branch block). As discussed later in this chapter,
regurgitant lesions of either the mitral or aortic valves can lead to
substantial ventricular dilatation, and assessment of ventricular size is
integral in the evaluation and timing of surgical correction. Because
changes in ventricular size are used clinically to determine which
patients should undergo valve surgery, accurate assessment of changes
in ventricular size is essential. Although serial echocardiography can
provide these data, serial assessment by CMR may be more accurate
when appreciation of subtle changes over time is important.
Left ventricular wall thickness and mass are also important measures of cardiac and systemic disease. The left ventricle will hypertrophy under any condition in which its afterload is increased, including
conditions that obstruct outflow, such as aortic stenosis, hypertrophic
cardiomyopathy, and subaortic membranes; in postcardiac aortic
obstruction seen in coarctation; or in systemic conditions characterized by increased afterload, such as hypertension. The pattern of
ventricular hypertrophy can change depending on the etiology. Aortic
stenosis and hypertension are typically characterized by concentric
hypertrophy, in which the ventricular walls thicken “concentrically”
1838 PART 6 Disorders of the Cardiovascular System
and cavity size is usually small. In volume overload conditions such
as mitral or aortic regurgitation, there may be minimal increase in
ventricular wall thickness, but substantial ventricular dilatation leads
to marked increases in left ventricular mass.
Ventricular wall thickness can be measured and ventricular mass
can be calculated by either echocardiography or CMR. Although
radionuclide imaging and cardiac CT can also provide measures of
left ventricular mass, they are not generally used for this purpose.
Although measurement of wall thickness with echocardiography is
relatively straightforward and accurate, determining left ventricular
mass by echocardiography requires using one of several formulas that
takes into account both wall thickness and ventricular cavity dimensions. Assessment of left ventricular mass by CMR has the advantage
of not requiring geometric assumptions and is thus more accurate than
echocardiography.
■ ASSESSMENT OF LEFT VENTRICULAR SYSTOLIC
FUNCTION
Assessment of ejection fraction, or the percentage of blood ejected with
each beat, has been the primary method to assess systolic function
and is generally calculated by subtracting end-systolic volume from
end-diastolic volume and dividing by end-diastolic volume. All cardiac
imaging modalities can provide direct measurements of left ventricular
ejection fraction (LVEF). As discussed above, tomographic techniques
(e.g., CMR, CT, and radionuclide imaging) are generally more accurate
and reproducible than echocardiography because there are no geometric assumptions and these techniques are not dependent on operator
skill. An LVEF of 55% or greater is generally considered normal, and
an LVEF of 50–55% is considered in the low-normal range, although
these can vary widely; normal ejection fraction tends to be higher in
women than in men.
Newer methods to assess systolic function, such as myocardial strain
or deformation imaging using speckle-tracking methods on echocardiography, or myocardial tagging or feature tracking on CMR, can
provide a more sensitive approach to detection of systolic dysfunction,
in part, because these measures are geometry independent. Additional
assessments based on these novel methods include assessment of myocardial twist and torsion. Regional strain patterns can differ in various
diseases. For example, in cardiac amyloidosis, it is common to see a
reduction in myocardial strain at the base of the heart with relative
sparing of the apex. Strain imaging is being used more commonly in
conditions such as valvular heart disease and early detection of cardiotoxicity following chemotherapy and/or radiation therapy. In addition
to estimation or calculation of ejection fraction, stroke volume can be
assessed by any of the imaging methods, by subtracting the end-systolic
volume from the end-diastolic volume, or by quantifying forward flows
using echocardiographic Doppler methods or phase-contrast CMR
imaging. They offer measures of systolic function other than LVEF.
■ ASSESSMENT OF LEFT VENTRICULAR DIASTOLIC
FUNCTION
Echocardiography remains the primary method for clinical assessment of diastolic function, in part, because echocardiography has
the highest temporal resolution of all the imaging techniques. Recent
advances in Doppler tissue imaging allow for accurate assessment of
the velocity of myocardial wall motion by assessing the excursion of
the mitral annulus in diastole. Mitral annular relaxation velocity, or
E′, is inversely related to the time constant of relaxation, tau, and has
been shown to have prognostic significance in patients with heart
failure. Dividing the standard mitral inflow maximal velocity, E, by the
mitral annular relaxation velocity yields E/E′, which has been shown to
correlate with left ventricular filling pressures. The utility of standard
E and A wave ratios for assessment of diastolic function has been questioned. Mitral deceleration time can be a useful measure if very short
(<150 ms), suggesting restrictive physiology and severe diastolic dysfunction. Left atrial volume is considered an integrator of diastolic
function, and minimal volume may be more reflective of left ventricular filling pressures than maximal volume. Several grading methods for
diastolic function have been proposed that take into account a number
of diastolic parameters, including Doppler tissue-based relaxation
velocities, pulmonary venous Doppler, and left atrial size (Fig. 241-8).
Diastolic function worsens with aging, and most diastolic parameters
need to be adjusted for age.
■ ASSESSMENT OF RIGHT VENTRICULAR
FUNCTION
Right ventricular size and function have been shown to be prognostically important in a variety of conditions and can be assessed by
echocardiography, CMR, CT, or radionuclide imaging methods. CMR
is considered the most accurate noninvasive technique to evaluate the
structure and ejection fraction of the right ventricle (Video 241-2).
Assessment of the right ventricle by echocardiography has generally
been qualitative, owing in part to the unusual geometry of the right
ventricle. However, several quantitative methods are available for
assessment of right ventricular function, including fractional area
change (FAC = [diastolic area – systolic area]/diastolic area), which has
been shown to correlate with outcomes in heart failure and after myocardial infarction. Excursion of the tricuspid annulus (tricuspid annular plane systolic excursion [TAPSE]) is another method to assess right
ventricular function, although it is mostly used in research settings.
Abnormalities of right ventricular size and function are generally
secondary to either diseases that affect the right ventricle intrinsically
or disease in which the right ventricle responds to abnormalities elsewhere in the heart or pulmonary vasculature. Intrinsic diseases that
affect the right ventricle include congenital abnormalities, including
hypoplastic right ventricle and arrhythmogenic right ventricular dysplasia, and acquired conditions, such as right ventricular infarction and
infiltrative diseases. Right ventricular dilatation can occur due to both
chronic and acute processes. Long-standing pulmonary hypertension
or pulmonary outflow tract obstruction leads to right ventricular
hypertrophy and ultimately dilatation. An acute process that can cause
profound right ventricular dilatation and dysfunction is acute pulmonary embolism. In the setting of acute occlusion of a pulmonary artery
or branch, an acute rise in pulmonary vascular resistance causes a
previously normal right ventricle to dilate and fail due to the increased
afterload. In acute pulmonary embolism, right ventricular dilatation
and dysfunction are signs of substantial hemodynamic compromise
and are associated with a marked increased risk of death. In addition to
right ventricular dilatation, acute pulmonary embolism is often associated with a specific pattern of regional right ventricular dysfunction,
commonly referred to as the McConnell sign, characterized by preservation of right ventricular wall motion in the basal and apical regions
and dyskinesis in the region of the mid right ventricular free wall. This
abnormality is highly specific for acute pulmonary embolism and is
likely secondary to acute increases in right ventricular load.
Any disease that causes increased pulmonary vascular resistance can
lead to right ventricular dilatation and dysfunction. For example, longstanding chronic obstructive pulmonary disease increases pulmonary
vascular resistance and results in cor pulmonale. Acute pneumonia
can cause findings that are similar to acute pulmonary embolism, and
right ventricular dysfunction has been a hallmark of severe COVID-19
disease due to either macro- or microthrombosis in the pulmonary
vasculature. In patients with right ventricular dilatation without obvious pulmonary disease, intracardiac shunts should be considered.
The increased flow through the pulmonary vasculature as a result of
an atrial septal or ventricular septal defect can, over time, result in
elevation in pulmonary vascular resistance with subsequent dilatation
and hypertrophy of the right ventricle. Right ventricular dilatation and
dysfunction can be seen in left-sided heart disease, and patients who
develop RV dilatation and dysfunction due to predominantly left-sided
disease have worse outcomes.
In addition to assessment of left and right ventricular structure
and function, assessment of the other cardiac chambers also provides
important clues to intracardiac and systemic diseases. Enlargement of
the left atrium is common in patients with hypertension and is also
suggestive of increased left ventricular filling pressures; indeed, left
atrial size is often termed the “hemoglobin A1c” of diastolic function
because left atrial enlargement reflects long-standing increase in
Noninvasive Cardiac Imaging: Echocardiography, Nuclear Cardiology, and Magnetic Resonance/Computed Tomography Imaging
1839CHAPTER 241
left-sided filling pressures. Right atrial dilatation and dilatation of the
inferior vena cava are common in conditions in which central venous
pressure is elevated.
PATIENT SAFETY CONSIDERATIONS
■ RADIATION EXPOSURE
Both cardiac CT and radionuclide imaging expose patients to ionizing
radiation. Several recent publications have raised concern regarding the
potential harmful effects of ionizing radiation associated with cardiac
imaging. The effective dose is a measure used to estimate the biologic
effects of radiation and is expressed in millisieverts (mSv). However,
measuring the radiation effective dose associated with diagnostic imaging is complex and imprecise and often results in varying estimates, even
among experts. The effective dose from a typical myocardial perfusion
SPECT scan ranges between ~4 and 11 mSv, depending on the protocol
and type of scanner used. The effective dose from a typical myocardial
perfusion PET scan is lower, ~2.0–4 mSv. Radiation exposure associated
with cardiac CT is variable and, as with radionuclide imaging, also
depends on the imaging protocol and scanner used. Although historic
radiation doses with cardiac CT have been quite high, the introduction
of newer technologies (e.g., x-ray tube modulation, prospective ECG
gating) has resulted in a significant dose reduction. The current average radiation dose for a coronary CTA ranges from 3 to 15 mSv and,
in selected cases, can be as low as 1 mSv. Imaging laboratories follow
the ALARA (as low as reasonably achievable) principle when balancing
the clinical need and imaging approach. By comparison, the average
dose for invasive coronary angiography is ~7 mSv, whereas exposure
Mitral inflow without
Valsalva maneuver
Mitral inflow with
Valsalva maneuver
• Normal atrial
pressure
• Normal LV
relaxation
• Normal LV
compliance
• Normal atrial
pressure
• Impaired LV
relaxation
• Normal to ↓ LV
compliance
• ↑↑ atrial
pressure
• Impaired LV
relaxation
• ↓↓ LV
compliance
• ↑↑↑ atrial
pressure
• Impaired LV
relaxation
• ↓↓↓ LV
compliance
• ↑↑↑↑ atrial
pressure
• Impaired LV
relaxation
• ↓↓↓↓ LV
compliance
Normal
Mild diastolic dysfunction (impaired relaxation)
Moderate diastolic dysfunction (pseudonormal)
Severe diastolic dysfunction (reversible restrictive)
Severe diastolic dysfunction (fixed restrictive)
Adur
Adur
Adur
Adur
Adur
A
E S D
S
D
S
D
S
D
S
D
A
E
A
E
A
E
A
E
∆E/A<0.5
A
E
A
E
A
E
A
A
E
E
e’
a’
e’
a’
e’
a’
e’ a’
e’ a’
∆E/A≥0.5
∆E/A≥0.5
∆E/A≥0.5
∆E/A<0.5
0.75<E/A<1.5
Deceleration time>140 ms
0.75<E/A<1.5
Deceleration time>140 ms
E/A≥1.5
Deceleration time<140 ms
E/A>1.5
Deceleration time<140 ms
E/A≤0.75
E/e’<10
E/e’≥10
E/e’≥10
E/e’≥10
E/e’<10
S≥D
ARdur<Adur
S<D or
ARdur>Adur+30 ms
S<D or
ARdur>Adur+30 ms
S<D or
ARdur>Adur+30 ms
S>D
ARdur<Adur
>50 cm/s
E/Vp<1.5
>45 cm/s
E/Vp>2.5
>45 cm/s
E/Vp>2.5
>45 cm/s
E/Vp<2.5
>45 cm/s
E/Vp<1.5
ARdur
ARdur
ARdur
ARdur
ARdur
Vp
Vp
Vp
Vp
Vp
Doppler tissue
imaging
Pulmonary
venous flow
Flow
propagation
FIGURE 241-8 Stages of diastolic function based on various parameters, including mitral inflow (with and without Valsalva maneuver), Doppler tissue imaging, pulmonary
venous flow, and flow propagation. (Adapted from MM Redfield et al: Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of
the heart failure epidemic. JAMA 289:194, 2003.)
1840 PART 6 Disorders of the Cardiovascular System
to radiation from natural sources in the United States amounts to ~3
mSv annually.
The risk of a fatal malignancy from medical imaging–related radiation is difficult to estimate precisely but is likely small and difficult to
discern from the background risk of natural malignancies. The small
but potential radiation risks from imaging mandate an assessment of
the risk-versus-benefit ratio in the individual patient. In this context,
one must not fail to take into account the risks of missing important
diagnostic information by not performing a test (which could potentially influence near-term management and outcomes) for a theoretical
concern of a small long-term risk of malignancy. Before ordering any
test, especially one associated with ionizing radiation, we must ensure
the appropriateness of the study and that the potential benefits outweigh the risks. The likelihood that the study being considered will
affect clinical management of the patient should be addressed before
testing is performed. It is also important that “routine” follow-up scans
in asymptomatic individuals be avoided.
■ CONTRAST AGENTS
Contrast agents are commonly used in cardiac CT, CMR, and echocardiography. Although their use significantly enhances the diagnostic
information of each of these tests, there are also potential risks from the
administration of contrast agents that should be considered.
The risk of adverse reactions from iodinated contrast agents used
in cardiac CT is well established. The precise pathogenesis of contrast
reactions following intravascular administration of iodinated contrast
media is not known. The overall incidence of contrast reactions is
0.4–3% with nonionic formulations and higher for ionic formulations.
Most contrast adverse reactions are mild and self-limiting. The risk of
contrast-induced nephropathy (CIN) in patients with relatively normal
renal function (estimated glomerular filtration rate [eGFR] >60 mL/
min) is low. In most patients, CIN is self-limited, and renal function
usually returns to baseline within 7–10 days, without progressing to
chronic renal failure. However, this risk increases in patients with
GFR <60 mL/min, especially older diabetic subjects. In such patients,
appropriate screening and pre- and postscan hydration are necessary.
The use of gadolinium-based contrast agents (GBCAs) enhances the
versatility of CMR imaging. There are many commercially available
GBCAs in the United States, but their use in cardiac imaging is offlabel. Mild reactions from GBCAs, such as skin pruritus or erythema,
occur in ~1% of patients, but severe or anaphylactic reactions are very
rare at ~1 in 100,000 patients. All GBCAs are chelated to make the
compounds nontoxic and facilitate renal excretion. Older generation
(group I) linear-structured GBCAs have been associated with a rare
but serious condition known as nephrogenic systemic fibrosis (NSF),
which is an interstitial inflammatory reaction manifested as fibrosis of
tissues or internal organs and even death. Risk factors to developing
NSF include high-dose use in presence of severe renal dysfunction
(eGFR <30 mL/min per 1.73 m2
), need for hemodialysis, an eGFR
<15 mL/min per 1.73 m2
, acute renal deterioration, and concurrent proinflammatory/systemic illnesses. Newer-generation (group II)
macrocyclic-structured GBCAs have a substantially improved safety
profile, including in patients with chronic kidney dysfunction and,
indeed, have become the agents of choice in most MRI centers. The
American College of Radiology considers the use of group II agents
as safe, including in patients with renal dysfunction or dialysis. With
widespread use of group II GBCAs, routine pretest screening, and
weight-based dosing, a near-zero incidence of NSF has been reported
in the past decade.
Contrast agents can also be used in echocardiography. Injected
agitated saline is used routinely to assess cardiac shunts, because these
“bubbles” are too large to traverse the pulmonary circulation. After
saline injection, the presence of bubbles in the left side of the heart is
indicative of shunt, although the location can sometimes be difficult to
determine. The current U.S. Food and Drug Administration (FDA)–
approved use of echocardiographic contrast agents is for opacification
of left-sided chambers and to improve delineation of left ventricular
endocardial border in patients with suboptimal echocardiograms.
These agents are either albumin- or lipid-based microspheres filled
with inert gases, typically perfluorocarbons. They are considered
extremely safe, although they have, in extremely rare instances, been
associated with allergic reactions and neurologic events.
■ SAFETY CONSIDERATIONS OF CMR IN PATIENTS
WITH PACEMAKERS AND DEFIBRILLATORS
There are now multiple FDA-approved MRI-conditional internal cardiac defibrillators and pacemakers that are safe for patients who need
an MRI study. For non-FDA-approved cardiac devices (legacy devices),
collective evidence has indicated that MRI studies can be safely performed at 1.5 T under normal operational settings, in the absence of
fractured, epicardial, or abandoned leads, and when an experienced
staff is available to interrogate the cardiac device before and after the
MRI study. The Centers for Medicare and Medicaid Services have
approved and expanded coverage of MRI studies in patients with an
implanted legacy device.
PATIENT-CENTERED APPLICATIONS OF
CARDIAC IMAGING
■ CORONARY ARTERY DISEASE
The basis for the diagnostic application of imaging tests in patients
with known or suspected CAD should be viewed considering the
pretest probability of disease as well as the specific characteristics of
imaging tests (i.e., sensitivity and specificity). In symptomatic patients,
the prevalence or pretest probability of CAD differs based on the type
of symptom (typical angina, atypical angina, noncardiac chest pain),
as well as on age, gender, and coronary risk factors. In an individual
patient, the results of the initial test inform the posttest likelihood of
CAD. In patients undergoing sequential testing (e.g., ECG treadmill
testing followed by stress imaging), the posttest probability of disease
after the first test becomes the pretest likelihood of disease for the second test. Regardless of the sequence, the expectation is that a test will
provide sufficient information to confirm or exclude the diagnosis of
CAD and that such information will allow accurate risk stratification
to be able to guide management decisions.
Table 241-3 summarizes the relative diagnostic accuracies of cardiac
imaging modalities for the diagnosis of CAD.
TABLE 241-3 Comparative Diagnostic Accuracy of Cardiac Imaging Approaches to Coronary Artery Disease
IMAGING MODALITY PUBLISHED DATA SENSITIVITY SPECIFICITY
Exercise echocardiography 15 studies (n = 1849 patients) 84% 82%
Dobutamine echocardiography 28 studies (n = 2246 patients) 80% 84%
SPECT MPI 113 studies (n = 11,212 patients) 88% 76%
Myocardial perfusion PET 9 studies (n = 650 patients) 93% 81%
CMR perfusion 37 studies (n = 2841 patients) 91% 81%
CMR wall motion 14 studies (n = 754 patients) 83% 86%
Coronary CTA 18 studies (n = 1286 patients) 99% 89%
Note: In these studies, the diagnosis of coronary artery disease was based on the presence of a >50% or >70% stenosis on invasive coronary angiography.
Abbreviations: CMR, cardiac magnetic resonance; CTA, computed tomography angiography; MPI, myocardial perfusion imaging; PET, positron emission tomography; SPECT,
single-photon emission computed tomography.
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