JACC: CARDIOONCOLOGY VOL. 2, NO.

2, 2020

ª 2020 THE AUTHORS. PUBLISHED BY ELSEVIER ON BEHALF OF THE AMERICAN

COLLEGE OF CARDIOLOGY FOUNDATION. THIS IS AN OPEN ACCESS ARTICLE UNDER

THE CC BY-NC-ND LICENSE (http://creativecommons.org/licenses/by-nc-nd/4.0/).

STATE-OF-THE-ART REVIEW

Magnetic Resonance Imaging to

Detect Cardiovascular Effects of
Cancer Therapy
JACC CardioOncology State-of-the-Art Review

Iwan Harries, MBBCH,a Kate Liang, MBBCH,a Matthew Williams, MBCHB,a Bostjan Berlot, MD,a,b
Giovanni Biglino, PHD,a,c Patrizio Lancellotti, MD, PHD,d,e Juan Carlos Plana, MD,f Chiara Bucciarelli-Ducci, MD, PHDa

ABSTRACT

This paper aims to empower and inform cardio-oncologists by providing a practical guide to the clinical application of
cardiac magnetic resonance (CMR) in the rapidly evolving field of cardio-oncology. Specifically, we describe how CMR can
be used to assess the cardiovascular effects of cancer therapy. The CMR literature, relevant societal guidelines,
indication-specific imaging protocols, and methods to overcome some of the challenges encountered in performing and
accessing CMR are reviewed. (J Am Coll Cardiol CardioOnc 2020;2:270–92) © 2020 The Authors. Published by Elsevier
on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).

A dvances in treatment and supportive care

have led to improved survival for patients
with cancer. However, cancer therapy con-
fers cardiovascular risk, and patients with established
potential in cardio-oncology. This article aims to
empower and inform cardio-oncologists by providing
a practical guide to the clinical applications of CMR in
patients during and after cancer therapy. The CMR
cardiovascular disease receiving cancer treatment are literature, relevant guidelines, indication-specific im-
particularly susceptible to cardiovascular complica- aging protocols, and methods to overcome some of
tions (1). Consequently, collaboration between cardi- the limitations and challenges encountered in CMR
ologists and oncologists and the emergence of are also discussed. We describe each CMR imaging
dedicated specialists in the emerging field of cardio- sequence, its potential application, and guideline-
oncology are becoming increasingly important. Car- directed indications for CMR. We also refer the reader
diac magnetic resonance (CMR) is a multiparametric to the recently published appropriate use criteria (2),
imaging modality that is changing clinical practice, the Society for Cardiovascular Magnetic Resonance
and has a wide variety of applications and enormous guidelines for standardized CMR protocols (3), CMR

From the aBristol Heart Institute, Bristol National Institute of Health Research (NIHR) Biomedical Research Centre, University
Hospitals Bristol NHS Trust and University of Bristol. Bristol, United Kingdom; bDepartment of Cardiology, University Medical
Centre Ljubljana, Slovenia; cNational Heart and Lung Institute, Imperial College London, London, United Kingdom; dUniversity of
Liège Hospital, GIGA Cardiovascular Sciences, Departments of Cardiology, Heart Valve Clinic, CHU Sart Tilman, Liège, Belgium;
e
Gruppo Villa Maria Care and Research, Anthea Hospital, Bari, Italy; and the fTexas Heart Institute at Baylor St. Luke’s Medical
Center, Baylor College of Medicine, Houston, Texas. Dr. Bucciarelli-Ducci is in part supported by the National Institutes of HealthR
Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The views expressed
in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research, or the
Department of Health and Social Care. Dr. Bucciarelli-Ducci is the CEO of the Society for Cardiovascular Magnetic Resonance (part-
time). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions
and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC:
CardioOncology author instructions page.

Manuscript received December 6, 2019; revised manuscript received April 12, 2020, accepted April 15, 2020.

ISSN 2666-0873 https://doi.org/10.1016/j.jaccao.2020.04.011

JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020 Harries et al. 271
JUNE 2020:270–92 MRI to Detect Cardiovascular Effects

CARDIAC FUNCTION, VENTRICULAR VOLUMES, ABBREVIATIONS

HIGHLIGHTS AND MASS: STEADY-STATE FREE PRECESSION AND ACRONYMS

Cancer therapy improves cancer survival CINE SEQUENCES. CMR is the reference stan-
CMR = cardiac magnetic
but can result in a variety of cardiovas- dard for the assessment of ventricular vol- resonance
cular toxicities. umes and ejection fraction with high levels of
ECV = extracellular volume
accuracy and reproducibility, both in health fraction

Cardiovascular magnetic resonance is an
and disease in the left (7,8) and right ventricle EGE = early gadolinium
extremely versatile and useful tool to (9). Steady-state free precession (SSFP) cine enhancement
assess cardiovascular toxicities of cancer sequences provide high resolution, time- ICI = immune checkpoint
therapy. resolved images that allow excellent inhibitors

Technological improvement, collabora- discrimination of the endocardial and LGE = late gadolinium
enhancement
tion, research, and education are essen- epicardial borders, which are subsequently
LVEF = left ventricular
tial to the evolving use of cardiovascular contoured to provide 3-dimensional (3D)
ejection fraction
magnetic resonance in cardio-oncology. estimations of ventricular volumes, function,
MACE = major adverse cardiac
and mass. The left ventricle is conventionally event
image interpretation and post-processing (4), and assessed in 3 long-axis planes and a stack of
SSFP = balanced steady state
principles of CMR reporting (5) for additional useful contiguous short-axis “slices” from the left free precession

references. ventricular base in the atrioventricular plane

to the apex (Figure 4). The long-axis planes are similar
CMR IMAGING SEQUENCES AND REFERRAL to those obtained by echocardiography: 4-chamber
(4C), 3-chamber (3C) and 2-chamber (2C) (Figure 4).
CMR uses different imaging sequences to provide
The right ventricle can also be evaluated in the same
comprehensive information about the cardiovascular
short-axis stack (Figure 4) or alternatively with an
system that is tailored to the clinical question posed.
axial stack with similarly high levels of interobserver
The CMR protocol is typically chosen based on the
and intraobserver reliability reported for each
information provided by the referring physician. It is
method (10).
therefore important that all relevant background in-
Endocardial borders are contoured at end-
formation is included, and the clinical question
diastole and end-systole in each of the short-axis
clearly formulated in the study request (Central
(or axial) slices to provide 3D volumes that do not
Illustration). Each sequence provides specific
rely on the geometric assumptions of 2D methods.
anatomical, tissue characteristics, functional, flow, or
However, volume estimation by CMR relies on
perfusion data (Table 1). A combination of sequences
different geometric assumptions, and although the
is selected to create the CMR protocol (Figure 1).
papillary muscles are part of the myocardium, in
ANATOMY: DARK BLOOD (T1- AND T2-WEIGHTED) clinical practice, they are often included as part of
AND WHITE BLOOD IMAGING. CMR protocols typi- the blood pool and thus contribute to ventricular
cally begin with cross-sectional axial and/or coronal volume (11). Regional wall motion can be assessed
images that describe the anatomy of the thorax and either subjectively or objectively (using wall-
upper abdomen (Figure 2). Major incidental extrac- thickening or myocardial strain) and is convention-
ardiac findings were reported to occur in 12% of ally reported by dividing the left ventricle into 17
CMR studies that were performed for any indication equally weighted segments, as recommended by the
in a recent meta-analysis (6). These findings may American Heart Association writing group on
prompt additional investigations, and can contribute myocardial segmentation and registration for car-
to contextualizing the underlying cardiovascu- diac imaging (12).
lar diagnosis. Measurement of left ventricular volumes, ejection
Anatomical sequences can provide both direct fraction, and mass by CMR are highly accurate and
anatomical information, for example, pericardial have been shown to be more reproducible (coefficient
thickening following radiation (Figure 3A), and indi- of variation for left ventricular ejection fraction
rect information relating to the hemodynamic con- [LVEF] in normal subjects is 2.4%) than left ventric-
sequences of underlying disease, for example, pleural ular volumes and mass by echocardiography (coeffi-
effusions (Figure 3B). Incidental findings, such as cient of variation for LVEF in normal subjects up to
primary or secondary malignancies, may also be 8.6%) or radionuclide ventriculography (7,8). Conse-
encountered (Figures 3C and 3D). Anatomical se- quently, CMR has been used in some cardio-oncology
quences also help to describe tissue properties; for research trials for precise serial evaluation of cardiac
example, fluid appears bright on T2-weighted images. structure and function (13,14).
272 Harries et al. JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020

MRI to Detect Cardiovascular Effects JUNE 2020:270–92

C E NT R AL IL L U STR AT IO N Typical Cardiovascular Effects of Classes of Cancer Therapy With Suggested

Cardiovascular Magnetic Resonance Imaging Protocols

Harries, I. et al. J Am Coll Cardiol CardioOnc. 2020;2(2):270–92.

The typical cardiovascular effects of various classes of cancer therapy, together with suggested cardiovascular magnetic resonance (CMR) imaging protocols and key
metrics provided by each sequence. “Recommended” and “aspirational” CMR imaging sequences to characterize the respective pathologies are suggested. For specific
data on the timing and incidence of toxicity, please see relevant literature (1,66,72,80,81,91,110-113). *Contrast administration may not necessarily be required for
serial evaluation of left ventricular function. ACS ¼ acute coronary syndrome; CAD ¼ coronary artery disease; ECV ¼ extracellular volume fraction; HER2þ ¼ human
epidermal growth factor receptor; LV ¼ left ventricular; TKI ¼ tyrosine kinase inhibitor; VEGF ¼ vascular endothelial growth factor.

The left ventricular myocardium is an architectur- myocardial deformation, or “strain,” rely on the
ally complex structure that deforms in longitudinal principle of tracking distinctive features over suc-
(along the long axis, apex to base), circumferential cessive images and several CMR sequences have been
(along the circular axis) and radial (towards the center developed for this purpose. These include tagging,
of the ventricle) planes. Methods to quantify displacement encoding with simulated echoes, phase
JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020 Harries et al. 273
JUNE 2020:270–92 MRI to Detect Cardiovascular Effects

T A B L E 1 Key Features of Common CMR Imaging Sequences and Relevant Uses

Sequence Features Relevant Clinical Uses

Anatomy and localizers Rapidly acquired Assessment of extracardiac structures (Figure 3)

Dark blood (Figures 2A to 2D) which can be: Localizers used to plan cardiac imaging planes
T1-weighted (better anatomic definition)* or
T2-weighted (better tissue characterization)†
White blood (Figures 2E to 2H)
Cines Use SSFP (a type of gradient echo pulse sequence) to produce Assessment of ventricular volumes, systolic function, and dynamic
a short movie or “cine” of the heart moving (Figures 4, 5, motion of thrombus (e.g., Figure 6A)
and 10A to 10B)
Edema T2-weighted imaging (e.g., T2 STIR) Qualitative assessment of myocardial edema, as in ICI-associated
Must be acquired before contrast administration myocarditis or Takotsubo cardiomyopathy
Native T1 mapping Popular methods include MOLLI and SASHA Quantitative assessment of myocardial fibrosis (Figure 8)
Quantifies native (noncontrast) T1 relaxation time Quantitative assessment of myocardial edema (both display
prolonged T1 relaxation time)
Native T2 mapping Typically uses SSFP sequence preceded by T2 preparation module. Quantitative assessment of myocardial edema (prolonged T2
Quantifies native (noncontrast) T2 relaxation time relaxation time)
Perfusion T1-weighted saturation recovery gradient echo pulse sequence Assessment of vascularity, e.g., an intracardiac mass
Gadolinium contrast administered and imaged over >40 heart beats
Stress perfusion As above but performed under conditions of pharmacologic stress, Assessment of coronary artery disease; perfusion defects evident in
e.g., adenosine or dobutamine ischemic myocardium (Figure 10A)
EGE Inversion recovery gradient echo sequence Assessment of intracardiac thrombus, which is avascular and
Performed 1-3 min after contrast administration therefore appears black (Figures 6B and 6D)
LGE Inversion recovery gradient echo sequence Assessment of focal fibrosis, e.g., in myocardial infarction, which
Performed >10 min after contrast administration (delay may appears white (Figures 7A to 7C and 10B)
need to be adjusted according to dose, cardiac output)
Normal myocardium is “nulled” to appear black
Post-contrast T1 mapping Popular methods include MOLLI and SASHA Allows calculation of ECV using hematocrit, native and post-
Quantifies post-contrast T1 relaxation time contrast T1 relaxation times of myocardium, and blood pool.
ECV is elevated in conditions associated with expansion of the
myocardial interstitium (e.g., amyloid)
Phase contrast Uses bipolar gradients Assessment of valvular heart disease, including velocity and
Typically acquired in a plane perpendicular to blood flow direction of blood flow (Figure 11C)
Allows estimation of severity of stenotic and regurgitant lesions.

*T2-weighted relies on transverse relaxation: fluid ¼ high signal intensity (white), muscle ¼ intermediate signal intensity (grey), fat ¼ high signal intensity (white). †T1-weighted relies on longitudinal
relaxation: fluid ¼ low signal intensity (black); muscle ¼ intermediate signal intensity (grey); fat ¼ high signal intensity (white).
CMR ¼ cardiovascular magnetic resonance; ECV ¼ extracellular volume; EGE ¼ early gadolinium enhancement; ICI ¼ immune checkpoint inhibitor; LGE ¼ late gadolinium enhancement; MOLLI ¼ modified
look-locker; SASHA ¼ saturation recovery single shot acquisition; SSFP ¼ steady-state free precession; STIR ¼ short Tau inversion recovery

velocity mapping, strain-encoded imaging and detectible temporal changes in circumferential

latterly, feature tracking. An advantage of the (18-20) and longitudinal (20) strain in patients
feature-tracking strain is that it can be calculated receiving cardiotoxic chemotherapy. The sensitivity
from standard cine sequences (Figure 5), whereas the of strain in comparison to LVEF-based techniques
other methods require dedicated sequences to be suggests that it has the potential to play an important
acquired. There is emerging evidence of a significant role in the early detection of cardiotoxicity, although
incremental prognostic role for CMR strain when large-scale confirmatory evidence is currently lacking.
added to LVEF and late gadolinium enhancement In comparison to speckle-tracking echocardiography,
(LGE) techniques in both ischemic and dilated car- CMR-based feature tracking shows good agreement
diomyopathies (15). A systematic review of and appears to have comparable levels of reproduc-
echocardiography-derived myocardial deformation ibility (21). However, strain has limitations. The range
studies confirmed the value of these parameters for of vendors (hardware and software), acquisition
the early detection of myocardial changes and pre- techniques, and post-processing algorithms means
diction of cardiotoxicity (16). The utility of strain- that normal reference ranges are difficult to establish.
guided echocardiography monitoring of patients Furthermore, interobserver and intraobserver vari-
receiving cardiotoxic cancer therapy in comparison to ability as well as interstudy reproducibility continue
standard care is currently being evaluated by the to present barriers to widespread clinical use.
SUCCOUR (Strain Surveillance of Chemotherapy for
Improving Cardiovascular Outcomes) randomized EDEMA/INFLAMMATION: T2-WEIGHTED IMAGING
controlled trial (17). Although the CMR-derived strain AND NATIVE T2 MAPPING. CMR is the reference
literature is in its infancy, initial reports confirm standard imaging technique to detect myocardial
274 Harries et al. JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020

MRI to Detect Cardiovascular Effects JUNE 2020:270–92

F I G U R E 1 Typical Composition of a CMR Imaging Protocol

CMR protocols are composed of different imaging sequences and tailored to the clinical question posed. Example additional imaging se-
quences are represented in grey. Native (non-contrast) and contrast-enhanced sequences occur before and after gadolinium administration,
respectively. CMR ¼ cardiovascular magnetic resonance; LV ¼ left ventricle; RV ¼ right ventricle.

hyperemia and edema using both T2- and T1- ratio of signal intensity between the myocardium and
weighted imaging sequences (22,23). Regions of skeletal muscle; whereas others are assessed quanti-
edema/inflammation exhibit higher signal intensity/ tatively by drawing “regions of interest” that provide
enhancement on these sequences. The T2-weighted a T2 mapping value in milliseconds (e.g., T2 map-
short-tau inversion recovery (T2 STIR) sequence is ping). Native myocardial T2 mapping is reported to be
commonly used, although T2 mapping and early the most reproducible method in the setting of edema
gadolinium enhancement (T1-weighted) are also associated with myocardial infarction (24) and the
used. Some of these sequences are assessed qualita- utility of parametric mapping methods was recog-
tively (e.g., T2 STIR) by adjudicating signal intensity nized by the updated Lake Louise criteria for the
in different myocardial segments, or by obtaining a evaluation of nonischemic myocardial inflammation

F I G U R E 2 Example Anatomical CMR Sequences

Sequential axial black blood (A to D) and coronal white blood (E to H) images through the thorax and upper abdomen. Abbreviation as in Figure 1.
JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020 Harries et al. 275
JUNE 2020:270–92 MRI to Detect Cardiovascular Effects

F I G U R E 3 Abnormalities Detected on Anatomical Sequences

(A) T1-weighted black blood turbo spin echo showing diffuse pericardial thickening (arrows). (B) White blood T2-weighted axial sequence
showing bilateral pleural effusions (arrows) due to constrictive pericarditis (same patient A). (C) Incidental right lung tumor (arrow).
(D) Incidental right renal tumor (arrow).

(25). Recent animal (26) and human (27) studies have DETECTION OF INTRACARDIAC THROMBUS AND
reported the potential utility of native myocardial T2 MYOCARDIAL HYPEREMIA/EDEMA: T1-WEIGHTED
mapping as a biosignature of early cancer therapy– EARLY GADOLINIUM ENHANCEMENT IMAGING.
associated toxicity. Following the administration of a gadolinium-based
contrast agent, the contrast redistributes from the
TISSUE PERFUSION: STRESS PERFUSION SEQUENCES. blood pool into the myocardium. Between 2 and 5 min
Perfusion sequences performed in conjunction with after contrast administration, this results in the blood
pharmacologic stress are designed to determine if pool and myocardium appearing hyperintense in
there is inducible myocardial hypoperfusion due to early gadolinium enhancement (EGE) sequences.
epicardial coronary stenosis. Typically, a stack of 3 Therefore, these sequences can be useful in dis-
short-axis slices (base, mid, and apex) are acquired. tinguishing between intracardiac thrombus, the most
Myocardium supplied by a stenotic vessel appears common cardiac pseudotumor (28), and true cardiac
dark and “hypoperfused” in comparison to well- tumors by virtue of the fact that thrombi are inher-
perfused myocardium, which appears bright. ently avascular, do not uptake gadolinium, and
276 Harries et al. JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020

MRI to Detect Cardiovascular Effects JUNE 2020:270–92

F I G U R E 4 Steady-State Free Precession “Cine” Images of the Left Ventricle

Example long-axis views: (A) 4-chamber, (B) 2-chamber, and (C) 3-chamber. (D) A stack of short axis “slices” from base to apex.

therefore appear markedly hypointense (dark) criteria (25). In a study of 22 patients using EGE se-
(Figure 6) on EGE sequences when surrounding quences, an increase in myocardial signal intensity
structures appear hyperintense (bright). 3 days after the administration of anthracyclines
The distribution of the contrast in the myocardium predicted subsequent declines in LVEF at 28 days
is also a function of the permeability of the tissue. In (29).
the setting of myocardial edema, there is enhanced MYOCARDIAL SCARRING/FIBROSIS: LGE SEQUENCES.
vasodilatation and vascular permeability of inflamed LGE is the cornerstone of CMR tissue characterization
tissue; EGE sequences have been used as a marker of and its presence predicts adverse outcomes in a va-
myocardial injury in patients with myocarditis (23) riety of cardiomyopathies, including coronary artery
and form part of the Lake Louise diagnostic disease (30), nonischemic cardiomyopathy (31),
JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020 Harries et al. 277
JUNE 2020:270–92 MRI to Detect Cardiovascular Effects

F I G U R E 5 Feature Tracking Strain Overlay on Steady-State Free Precession Images of the Left Ventricle

Diastole (A to D) and systole (E to H). A and E show a 2-chamber view. B and F show a 4-chamber view. C and G show a mid-ventricular short axis view. D and H show
a composite 3-dimensional reconstruction. Red line represents endocardial border; green represents epicardial border; and yellow represents tracked myocardial
features.

hypertrophic cardiomyopathy (32), cardiac sarcoid- associated with adverse left ventricular remodeling in
osis (33), myocarditis (34), and cardiac amyloidosis 1 study (43). A histopathologic study of 10 explanted
(35). Gadolinium preferentially accumulates in areas hearts with advanced anthracycline cardiomyopathy
of interstitial expansion (typically scar and fibrosis) (1 mortality and 9 following cardiac transplant) re-
giving these areas a hyperintense (bright) appearance ported interstitial fibrosis in all cases but with a
on T1-weighted sequences in comparison to sur- spectrum of distributions: 6 with multifocal fibrosis, 3
rounding healthy myocardium, which appears of with diffuse fibrosis, and 1 with focal fibrosis. A
lower signal intensity (darker) because of the porcine model of anthracycline cardiotoxicity re-
comparative absence of contrast. The accumulation ported that LGE appeared relatively late and in a
pattern of contrast in the myocardium mirrors the patchy distribution that became more apparent as
pathophysiology of the underlying disease, defining time progressed (26).
ischemic patterns (subendocardial or transmural, INTRACELLULAR AND INTERSTITIAL MYOCARDIAL
following the ischemic necrotic wave-front phenom- FIBROSIS AND EDEMA/INFLAMMATION: NATIVE T1
enon) and nonischemic patterns (mid-wall, epicar- MAPPING AND EXTRACELLULAR VOLUME FRACTION
dial) (Figure 7). Data on the presence and distribution SEQUENCES. Novel tissue characterization sequences
of LGE in human populations treated with anthracy- such as native T1 mapping and extracellular volume
clines are conflicting. Prospective CMR studies have (ECV) fraction estimation have shown promise to
generally reported the absence of new segments of detect diffuse fibrosis and inflammation/edema by
LGE (18,36-38), whereas some studies report an inci- quantitatively assessing its presence and extent
dence of between 23% (39) and 30% (40), with a mid- (Figure 8). When conducted in accordance with
myocardial or subepicardial distribution described. recognized guidelines (44), these techniques have
Retrospective studies conducted over a longer period shown excellent reproducibility and robust validation
of follow-up in different populations have reported against biopsy-proven collagen volume fraction and
that LGE was an infrequent finding (41-43) that was extracellular space reported in explanted hearts (45)
278 Harries et al. JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020

MRI to Detect Cardiovascular Effects JUNE 2020:270–92

F I G U R E 6 Examples of Intracardiac Thrombus on CMR

(A) Axial SSFP showing PICC-associated thrombus prolapsing through the tricuspid valve (arrow). (B) T1-weighted EGE image showing
marked hypointensity of the same thrombus (arrow). (C) RV 2-chamber cine showing 2 separate thrombi (arrows) in the same patient.
(D) T1-weighted RV 2-chamber EGE image of the same patient, with thrombus indicated by an arrow. EGE ¼ early gadolinium enhancement;
PICC ¼ peripherally inserted central catheter; SSFP ¼ steady-state free precession; other abbreviations as in Figure 1.

and biopsied patients with dilated cardiomyopathy BLOOD FLOW, VELOCITY, AND VOLUME:
(46). Using this technique, an increased ECV, used as PHASE-CONTRAST SEQUENCES. Phase contrast or
a surrogate marker of myocardial fibrosis, was re- velocity-encoded sequences enable CMR to accu-
ported in a cohort of patients receiving anthracy- rately assess and characterize blood flow, which is
clines, as compared to age- and sex-matched controls particularly relevant in valvular and congenital heart
(47); this has also been shown to occur independently disease. Whereas echocardiography is the first-line
of underlying cancer or cardiovascular comorbidities imaging modality, CMR can provide complementary
3 years after anthracycline treatment (48). However, a information where initial results are discrepant, of
precise role for these sequences in the setting of limited quality or not obtainable, or when an alter-
cancer therapy is yet to be established, and the tem- nate imaging plane or additional information (e.g.,
poral variability of ECV and T1 mapping in healthy myocardial viability) is required (50). In addition,
controls was comparable to that seen in patients vessel “stiffness” and distensibility can be assessed
receiving cancer therapy, which poses a challenge to by phase-contrast imaging of the aorta. Aortic pulse
routine clinical application (49). wave velocity increases significantly in after
JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020 Harries et al. 279
JUNE 2020:270–92 MRI to Detect Cardiovascular Effects

F I G U R E 7 Patterns of Myocardial Scarring in Post-Contrast Images (Late Myocardial Enhancement)

T1-weighted post-contrast short-axis mid ventricular images. (A) Ischemic LGE (arrows) due to transmural infarction in the right coronary artery territory.
(B) Mid-myocardial LGE in dilated cardiomyopathy (arrow). (C) Subepicardial LGE (arrows). LGE ¼ late gadolinium enhancement.

anthracycline (18,51), although the impact on clinical variety of overlapping symptoms (Figure 9) and are
outcomes in cardio-oncology populations is interpreted in the context of an underlying cancer
not known. diagnosis, which may itself express a significant
symptom burden. In this regard, CMR can be a useful
CLINICAL INDICATIONS FOR CMR
diagnostic tool. Furthermore, knowledge of cardio-
vascular effects according to therapeutic class, inci-
Diagnosis of cardiovascular disease during and after
dence, and time of onset can be invaluable. In the
cancer therapy through symptoms alone can pose a
following paragraphs, we describe the relevant clin-
diagnostic challenge to cardio-oncologists. This is
ical indications for CMR in cardio-oncology patients.
because cardiovascular effects can manifest through a
Table 2 also summarizes these indications and

F I G U R E 8 Native Short-Axis Mid-Ventricular T1 Map

(A) Normal native myocardial measurements (1,010 ms) and (B) abnormal measurements (1,136 ms) in the mid-ventricular septum.
280 Harries et al. JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020

MRI to Detect Cardiovascular Effects JUNE 2020:270–92

changes in LVEF, which is a product of end-diastolic

F I G U R E 9 Overlapping Symptomatology of Cardiovascular Effects of
Cancer Therapy
and end-systolic left ventricular volumes. One study
of 120 adults reported that among patients with de-
clines in LVEF meeting criteria for cardiotoxicity, 19%
were due to an isolated decrease in end-diastolic
Dyspnea
LV Dysfunction
Chest Pain
volume, thought principally to represent volume
Cancer CAD/ACS depletion (53). Furthermore, declines in LVEF driven
Arterial Hypertension
by an increase in end-systolic volume can be caused
Valvular Heart Disease Takotsubo
Myocarditis
Pericarditis both by extrinsic factors such as increased afterload,
Restrictive as well as intrinsic myocardial dysfunction (54).
Cardiomyopathy

Cancer
These factors should be considered when interpreting
Therapy CMR imaging results in patients receiving cancer
therapy.
Syncope Palpitations The precision of CMR in measuring dynamic
changes in ventricular volumes and ventricular mass
make it an important tool to monitor and identify
early subtle cardiac changes associated with cancer
therapy used by a number of prospective studies
Cardiovascular effects of cancer therapy can manifest with a variety of
cardiovascular symptoms and occur in the context of cancer and cancer
(Table 3) (55). From a clinical standpoint, it is partic-
therapy, which can themselves cause similar symptoms, independent of ularly helpful in determining biventricular function
cardiovascular disease, highlighting the diagnostic challenges faced by in challenging cases (e.g., patients who have under-
cardio-oncologists. ACS ¼ acute coronary syndrome; CAD ¼ coronary gone left sided breast surgery or with LVEF results
artery disease.
that are borderline or conflicting) or in determining
the etiology of the cardiomyopathy (1,56).
Chimeric antigen receptor (CAR) T cell therapy is
revolutionizing the treatment of relapsed or re-
includes the suggested protocol and data provided by fractory hematologic malignancy and is likely to ac-
each sequence. quire other indications in time. Despite these
MYOCARDIAL DYSFUNCTION AND HEART FAILURE. advances, a significant complication is cytokine
Left ventricular dysfunction that manifests clinically release syndrome, and the limited data describing
as heart failure is 1 of the most concerning compli- cardiovascular involvement are of particular rele-
cations of cancer therapy, not only because it may vance. Cardiovascular manifestations include tachy-
lead to cancer treatment interruption, but also cardia, hypotension, troponin elevation, left
because it carries an adverse prognosis, particularly ventricular dysfunction, pulmonary edema, and, in
when detected late (52). severe cases, cardiogenic shock; although for most
In a porcine model of anthracycline toxicity, Galan- patients with adequate physiologic reserve, the
Arriola (26) has shown that T2 relaxation-time pro- myocardial insult appears to be reversible (57). Data
longation (a marker of edema) was the earliest CMR are currently limited to case reports and early clinical
parameter to change. This occurred at week 6 trials (58) but it is hoped that a prospective observa-
(2 weeks after the third dose of intracoronary doxo- tional study addressing the cardiovascular effects of
rubicin), corresponded with intracardiomyocyte CAR T cell therapy will be instructive (NCT04026737).
edema at the tissue level, and importantly, identified One pediatric study reported that impaired systolic
toxicity at a reversible stage. Other parameters such and diastolic function before CAR-T were associated
as T1 mapping, ECV (markers of fibrosis), and left with subsequent hypotension requiring inotropic
ventricular wall motion only occurred at a later stage, support (59). Although the use of CMR in the setting
when fibrotic histologic changes became irreversible. of CAR T cell therapy is, to the best of our knowledge,
These data are yet to be replicated in a human pop- yet to be fully described, its unique ability to non-
ulation but highlight the potential utility of T2 map- invasively assess acute cardiomyopathic processes
ping to inform treatment and monitoring strategies. mean that CMR is well placed to provide important
Although the noninvasive evaluation of LVEF has insights, and led to its inclusion in a recently pro-
several limitations, it is the most widely accepted posed screening and monitoring algorithm (60).
strategy for monitoring cardiac function in cardio- CMR is also a valuable tool to evaluate cardiomy-
oncology. With this in mind, it is important to un- opathy late after chemotherapy, which is particularly
derstand that different mechanisms can drive relevant when managing the increasing population of
JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020 Harries et al. 281
JUNE 2020:270–92 MRI to Detect Cardiovascular Effects

T A B L E 2 Protocols for Assessment of Specific Clinical Cardiotoxicity Indications

Recommended Protocol and Parameters Reported

Perfusion* Phase
Anatomy Cine Edema Native T1/T2 ( Stress) EGE* LGE* PC T1* Contrast

Presence Presence and

LVEDV (ml), LVESV (ml), Vascularity of Edema Extent of Flow (ml),
Guideline LVEF (%), LVM (g), Presence Global/ Regional Presence of Presence Scarring/ Velocity (m/s),
Indication Support Descriptive (FT-Strain [%]) and Extent Values (ms) Hypoperfusion of Thrombus Fibrosis ECV (%) RF (%)

LV dysfunction
Baseline evaluation Yes U U U (U)  Stress U U (U)
(second-line)
Serial evaluation Yes U U  (U)
(second-line)
Etiological evaluation Yes U U U (U)  Stress U U (U)
(second-line)
Myocarditis/TCM Yes U U U (U) U U (U)
restrictive Yes U U  (U) U U (U)
CAD Yes U U (U) U U U (U)
VHD Yes U U (U)   (U) U
(second-line)
Arterial hypertension No U U (U) U U (U) U
Pericardium Yes U U  ()  U U () U

*Requires gadolinium contrast administration. U ¼ recommended, (U) ¼ aspirational,  ¼ can be included in appropriate clinical context; () ¼ aspirational.
CAD ¼ coronary artery disease; FT ¼ feature tracking; LV ¼ left ventricular; LVEDV ¼ left ventricular end-diastolic volume; LVEF ¼ left ventricular ejection fraction; LVESV ¼ left ventricular end systolic
volume; LVM ¼ left ventricular mass; PC ¼ postcontrast; RF ¼ regurgitant fraction; TCM ¼ Takotsubo cardiomyopathy; VHD ¼ valvular heart disease; other abbreviations as in Table 1.

pediatric and adult cancer survivors. CMR identified a remains the cornerstone of assessing diastolic func-
higher prevalence (14%) of cardiomyopathy tion, the ability of CMR to: 1) determine left atrial and
(LVEF <50%) in 114 asymptomatic childhood cancer left ventricular volumes; 2) derive dynamic time-
survivors assessed 27.8 years after anthracycline volume filling curves; 3) assess flow in any plane
chemotherapy compared to 2D or 3D echocardiogra- (e.g., pulmonary vein and transmitral); 4) yield
phy (55). In fact, 11% of the study population was myocardial strain data; and 5) characterize the
misclassified as having a normal LVEF by 2D echo- myocardium means that CMR can potentially add
cardiography in comparison to CMR with the higher value to the diagnostic work-up and may also identify
cutoffof 60% improving the detection of cardiomy- alternative pathologies (63).
opathy. In another study, 62 asymptomatic childhood Left ventricular mass is another CMR-derived
cancer survivors were assessed a median of 7.8 years marker of interest for quantifying cardiotoxicity. An
after anthracycline treatment; the prevalence of car- inverse association between anthracycline dose and
diomyopathy (ejection fraction <55%) in the right and left ventricular mass was reported in a study of 91
left ventricles was 81% and 79%, respectively (61). A patients with cardiomyopathy a median of 88 months
subsequent study by the same group using 2D and 3D after chemotherapy (41), which is in keeping with the
echocardiography and CMR reported the prevalence report of Armstrong et al. (55) which found that 48%
of cardiomyopathy (LVEF <55%) as 78% in 71 survi- of patients had a left ventricular mass that was 2
vors of childhood cancer (62). standard deviations below normal. Furthermore, in
In addition to the assessment of heart failure with the former study, left ventricular mass showed a
reduced ejection fraction, accumulating evidence strong inverse association with major adverse car-
identifies a role for CMR in the challenging and het- diovascular events (MACE). A recent report (65) pro-
erogeneous cohort of patients with heart failure with vided additional pathophysiologic insight by
preserved ejection fraction (63). A study of contem- suggesting that this decrease may be due to car-
porary radiotherapy for breast cancer reported that diomyocyte apoptosis.
the risk of heart failure with preserved ejection frac-
tion increased with increasing cardiac radiation dose; MYOCARDITIS. CMR is a key noninvasive test for the
the odds ratio per log mean cardiac radiation dose diagnosis of myocarditis, with an approach that
was 16.9 (95% confidence interval: 3.9 to 73.7) combines imaging sequences (e.g., T1 mapping and
compared to controls (64). While echocardiography LGE) reported to improve sensitivity and specificity
282 Harries et al. JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020

MRI to Detect Cardiovascular Effects JUNE 2020:270–92

T A B L E 3 Selected Prospective Adult Human Studies of Cardiotoxicity Using CMR

First Author, Mean Age (yrs); Definition and Incidence of

Year (Ref. #) N % Female Treatment Follow-Up Imaging Cardiotoxicity Findings

Wassmuth et al., 22 43; 77% First course: doxorubicin 3 and 28 days after treatment LVEF <55% occurred in 27% Significant decrease in LVEF 67.8  1.4%
2001 (29) 67 mg/m2 or initiation (n ¼ 6) to 58.9  1.9%; LVEF decreased
epirubicin 76 mg/m2 significantly at 28 days in patients
with an increase in relative contrast
enhancement of >5 on day 3
Chaosuwannakit 40 52; 70% Doxorubicin 215 mg/m2 4 months after treatment Not reported Significant decrease in LVEF 58.6 
et al., 2010 (51) or daunorubicin initiation 6.3% to 53.9  6.4%; significant
265 mg/m2 or increase in aortic stiffness
trastuzumab 920 mg (p < 0.0001)
Fallah-Rad et al., 42 47; 100% Epirubicin or adriamycin, 12 months after treatment LVEF decline of 10% to Significant decrease in LVEF 66  5% to
2011 (39) followed by initiation <55% occurred in 24% 47  4% in 10 with cardiotoxicity, all
trastuzumab (n ¼ 10); determined by of whom exhibited subepicardial LGE
echo
Drafts et al., 53 50; 58% 50-375 mg/m2 1, 3, and 6 months after Of those with LVEF >50% Significant decrease in LVEF 58  1% to
2013 (18) doxorubicin treatment initiation at baseline (n ¼ 47), 53  1%; significant decrease in
equivalent 26% (n ¼ 12) had mean mid wall circumferential strain
LVEF <50% after (-17.7  0.4% to -15.1  0.4%;
6 months p ¼ 0.0003)
No new LGE
Jordan et al., 65 51; 86% 55% (n ¼ 36) received 3 months after treatment Not reported Significant decrease in LVEF 57  6% to
2014 (37) median 240 mg/m2 initiation 54  7%; significant increase in T1-
doxorubicin weighted signal intensity 14.1  5.1
equivalent, 38% to 15.9  6.8
(n ¼ 25) received a No LGE
monoclonal antibody
Lunning et al., 10 59; 40% 300 mg/m2 doxorubicin 3 months after treatment LVEF decrease by >10% Significant decrease in FT-GCS
2015 (40) completion occurred in 50% (p ¼ 0.018); trend to FT-GLS
decrease (p ¼ 0.073)
30% exhibited 1 new or progressive
segment of LGE
Nakano et al., 9 62.3; 100% 67% had epirubicin; 3, 6, and 12 months after No cardiotoxicity Significant decrease in LVEF (68.4 
2016 (38) 100% had treatment initiation 6.6% to 61.7  8.7) at 6 and
trastuzumab 12 months (62.9  7.8%) but not at
3 months (65.4  8.7%); significant
decrease in SENC-GLS and SEND-GCS
at 6 months but not at 3 or 12 months
Barthur et al., 41 52; 100% 56% received 6, 12, and 18 months No cardiotoxicity Significant decrease in LVEF at 6 (60.4 
2017 (114) anthracycline; 100% 4.2% to 58.3  5.1%) and 12 (57.9 
received 18 cycles of 4.8%) months but not at 18 months;
trastuzumab significant decrease in RVEF at 6
(58.3% to 53.9%) and 12 (55%),
which had recovered at 18 months
(56.6%)
Muehlberg et al., 23 59; 52% 360-40 mg/m2 48 h after treatment initiation and LVEF decrease by >10% Significant decrease in subgroup with
2018 (36) doxorubicin on treatment completion occurred in 39% (n ¼ 9) cardiotoxicity (63.5  5.8% to 49.9
equivalent  5.0%) but not in those without
cardiotoxicity (59.2  10.3% to 58.3
 7.8%); at 48 h, the subgroup who
developed cardiotoxicity had
significantly lower native T1 times
than those who did not
Ong et al., 41 52; 100% 56% (n ¼ 23) received 6, 12, and 18 months after 2.4% (n ¼ 1) experienced Significant decrease in LVEF at 6 months
2018 (20) anthracycline, 100% treatment initiation cardiotoxicity (60.4% to 58.4%) and 12 months
received trastuzumab (57.9%) but not at 18 months
(60.2%); significant decrease in FT-
GLS and FT-GCS at 6 and 12 months
but not at 18 months

GCS ¼ global circumferential strain; GLS ¼ global longitudinal strain; RVEF ¼ right ventricular ejection fraction; SENC ¼ strain-encoded imaging; other abbreviations as in Tables 1 and 2.

(25). Immune checkpoint inhibitors (ICIs) have revo- rate of 46% in affected individuals (66) that occurs at
lutionized cancer treatment, but their mechanism of a median of 34 days from treatment initiation (66).
action can lead to immune reactions against normal In addition to being rare, ICI-associated myocar-
tissue, including the myocardium. ICI-associated ditis has a notoriously variable clinical presentation
myocarditis is a rare but serious side effect with an and until recently had no widely accepted definition.
estimated incidence of 0.06% to 1.14%, and MACE Furthermore, clinical practice guidelines on the
JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020 Harries et al. 283
JUNE 2020:270–92 MRI to Detect Cardiovascular Effects

F I G U R E 1 0 CMR and Angiographic Case Example of Ischemic Heart Disease

(A) T1-weighted mid-ventricular short-axis stress perfusion image showing an extensive inducible perfusion defect in the inferior and
inferoseptal walls (arrows). (B) T1-weighted short-axis image showing minimal scar according to small volume of LGE (arrows). (C) Coronary
angiography of the distally occluded (*) dominant right coronary artery. (D) Coronary angiography of the unobstructed left coronary artery.
The left circumflex is recessive and the posterior descending and posterior left ventricular branches of the right coronary artery are missing.
Abbreviations as in Figures 1 and 7.

management of ICI-associated myocarditis have not ICI-associated myocarditis evaluated with CMR, the
traditionally described a diagnostic role for CMR mean LVEF was 50%, but the majority of patients
(67,68). However, more recently, Bonaca et al. (69) (61%) had an LVEF >50% overall (70). LGE was pre-
published a proposed definition of ICI-associated sent in 48% of the cohort overall; 55% in those with
myocarditis describing CMR as the preferred imag- reduced LVEF; and 43% in those with preserved
ing modality to establish the diagnosis. CMR findings LVEF. The presence of LGE increased from 21.6%
of ICI-associated myocarditis have been described in when CMR was performed within 4 days of admission
2 case series (66,70). In the first series of 35 cases, 27 to 72% when performed on day 4 or later. Fifty-one
(77%) patients exhibited LGE on CMR in a pattern patients (40%) suffered from MACE over a follow-up
typical of myocarditis (subepicardial [n ¼ 6], mid- of 5 months, although LGE was not predictive of
myocardial [n ¼ 12], and diffuse [n ¼ 9]), although the MACE (70). Therefore, increasing awareness of this
majority (51%) of these patients had a normal LVEF entity and recognition of the unique diagnostic ca-
(66). In a large recent series of 103 patients with pabilities of CMR may see its use in this setting
284 Harries et al. JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020

MRI to Detect Cardiovascular Effects JUNE 2020:270–92

increase in the coming years. However, a normal CMR disease, heart failure, diabetes mellitus requiring in-
does not exclude ICI-associated myocarditis and sulin, or renal dysfunction) before cancer surgery
critically ill patients may not be suitable for CMR (79). Radiation-related coronary heart disease may
scanning (71). not manifest for 15 to 20 years after treatment, and
Takotsubo cardiomyopathy (TCM) is a clinical younger patients may be more susceptible (80).
syndrome presenting with symptoms (chest pain) and Furthermore, the risk of a major coronary events in-
objective evidence (electrocardiogram abnormalities, creases linearly with the mean cardiac radiotherapy
including ST-segment elevation, troponin rise, and dose (7.4% per Gray), starting 5 years after exposure
segmental myocardial dysfunction) of a myocardial (81). A higher prevalence of stress test abnormalities
infarction (MI) but with unobstructed coronary ar- has been reported among women irradiated for left-
teries on angiography. It is characteristically precipi- sided breast cancer compared to right-sided breast
tated by an emotional or physical stressor that leads cancer (82), and in a study of 31 patients assessed 24
to acute segmental dysfunction of the left ventricular years after treatment for Hodgkin’s disease, 68%
apex, leading to “apical ballooning” morphology. exhibited a perfusion defect (83). Stem cell trans-
Cancer therapies reported to trigger TCM include 5- plantation is associated with accelerated cardiovas-
flourouracil, capecitabine, rituximab, and ICIs, cular disease in later life, with a 22% incidence of
although a broad range of onset between 26 h and cerebrovascular disease, coronary artery disease,
3 months from treatment initiation has been reported and/or peripheral arterial disease at 25 years in a
(72). Patients with a history of malignancy may have a single-center study of 265 long-term survivors (84).
greater risk of developing Takotsubo (73), although
the mechanisms underlying this are incompletely VALVULAR HEART DISEASE. Chemotherapeutic

understood (54). In addition to the typical morpho- agents do not typically affect heart valves (1,56),
logic appearance of the left ventricle, TCM is readily although valvular heart disease is clearly encoun-
identifiable on CMR by the presence of myocardial tered in patients with cancer. Thoracic radiation in-
edema on T2-weighted imaging, elevated T2 mapping creases the risk of cardiovascular disease (85), with
values, and the typical absence of fibrosis (LGE) (74). valvular heart disease reported to affect 6.2% of
Hodgkin lymphoma patients 22 years after treatment
CORONARY ARTERY DISEASE. CMR provides a and an observed-to-expected ratio for valve surgery
comprehensive assessment of acute and chronic cor- of 8.3 in 1 study (86). In a separate CMR study of 31
onary artery disease presentations, which is recog- patients assessed 24 years after radiotherapy (mean
nized by international societal guidelines (75,76). dose, 40 Gray), the prevalence of hemodynamically
In the short term, cancer therapies such as fluo- significant valvular dysfunction was 42% (83). How-
ropyrimidines and platinum compounds can cause ever, these risks are somewhat mitigated by modern
myocardial ischemia and infarction (1,56). CMR can radiotherapy dosing and administration tech-
readily detect MI and its complications (left ventric- niques (87).
ular thrombus, pseudoaneurysm, and microvascular In the assessment of valvular heart disease,
obstruction) (77) and can be particularly helpful to echocardiography is typically the first-line imaging
assess patients with MI and nonobstructed coronary investigation, but CMR can provide complementary
arteries (who often present a clinical dilemma). information and is particularly useful when echo-
In stable coronary artery disease, CMR can detect cardiographic findings are inconclusive, discrepant,
myocardial ischemia (Figure 10) and allows differen- or not available (1,50). Using a combination of se-
tiation of viable from nonviable myocardium to quences, detailed anatomical and functional infor-
inform coronary revascularization strategies when mation about valve morphology (e.g., cuspidity and
there is myocardial dysfunction (76). In a multicenter leaflet thickness) and the presence, location, and
study of 918 patients with stable angina and risk severity of valvular heart disease can be assessed
factors for coronary artery disease, stress perfusion either by estimating valve area and transvalvular
CMR was associated with a lower incidence of revas- gradient, or regurgitant volume and regurgitant
cularization than invasive fractional flow reserve fraction for stenotic and regurgitant lesions,
assessment (35.7% vs. 45.0%; p ¼ 0.005, respectively) respectively (85). Phase-contrast assessment of
and was noninferior with respect to MACE at 1 year aortic stenosis has shown good agreement with
(3.6% vs. 3.7%, 95% CI: -2.7% to 2.4%) (78). It can also both Doppler measurements (88) and invasive he-
be used to risk-stratify asymptomatic patients with modynamic data (89). In addition to quantifying
poor functional capacity and at least 2 clinical risk the severity of valve disease, CMR provides a
factors (ischemic heart disease, cerebrovascular precise estimation of its hemodynamic
JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020 Harries et al. 285
JUNE 2020:270–92 MRI to Detect Cardiovascular Effects

consequences and relationship with the structure reported to occur 2 to 145 months after radiotherapy
and function of the heart and great vessels. Stroke with an absolute cumulative incidence of 2% to 5%
volume data from cine imaging can also be used to (1,56) and occasionally follows an immediate and
estimate regurgitant fraction and shunt volumes severe course, including large effusions and tampo-
(50). nade. Pericarditis is also a recognized side effect of
ARTERIAL HYPERTENSION. Hypertension is a highly chemotherapeutic agents such as doxorubicin, cytar-
prevalent, modifiable cardiovascular risk factor abine, bleomycin, and cyclophosphamide (95) and
whose presence in combination with other comor- may or may not be accompanied by myocarditis and
bidities was identified as an important independent pericardial effusion. Furthermore, cardiac graft-
prognostic factor of survival in a study of 19,268 versus-host disease following allogenic stem cell
cancer patients (90). Certain cancer therapies, such as transplantation may lead to pericardial effusions,
vascular endothelial growth factor inhibitors and tamponade, and constriction, with significant peri-
tyrosine kinase inhibitors, increase the risk of inci- cardial effusions identified in 4.4% of 205 patients at
dent hypertension and destabilization of previously a median of 30 days in 1 study (96).
controlled hypertension (1,56). In a meta-analysis of By combining anatomical information, tissue
sorafenib, the overall incidence of hypertension was characterization, and detailed functional assessment,
23.4%, with 5.7% experiencing high-grade hyperten- a comprehensive assessment of the pericardium and
sion (91). its hemodynamic consequences on ventricular filling
CMR can play an important role in the assessment is provided by CMR (97). This can be particularly
of the cardiovascular consequences (e.g., left ven- helpful when results from echocardiography are
tricular hypertrophy and fibrosis) of hypertension inconclusive (95). Abnormal pericardial thickening
(92) and also in the exclusion of underlying secondary (>3 mm) can accurately be defined by CMR and the
causes (renal artery stenosis and adrenal masses), signal intensity and late enhancement characteristics,
although dedicated sequences, such as magnetic with or without fat saturation, provides additional
resonance angiography in the case of renal artery diagnostic information, for example, in distinguish-
stenosis, would be required because they are not part ing pericardial inflammation from pericardial fat (98).
of a standard CMR protocol but rather part of general The presence, extent, and hemodynamic influence of
scanning. accompanying pericardial effusion is readily detected
by CMR with effusions as small as 30 ml reported to
PERIPHERAL VASCULAR DISEASE. Cancer therapies be detectible (97), although echocardiography is the
such as tyrosine kinase inhibitors have been associ- first-line imaging modality to detect pericardial ef-
ated with the occurrence of peripheral vascular dis- fusions. Pericardial calcification is best detected by
ease and adverse vascular events. Although the computerized tomography, although its presence can
reported incidence varies considerably, it may be also be suggested by very low signal intensity on
particularly high with some of the second- and third- CMR.
generation tyrosine kinase inhibitors, such as niloti- In the evaluation of pericardial constriction, CMR
nib and ponatinib (93). Radiation-induced vascular is reported to be 88% sensitive and 100% specific (99).
disease appears histopathologically similar to A real-time short-axis mid-ventricular slice that
atherosclerotic vascular disease including lipid typically spans 2 respiratory cycles is recommended
deposition, inflammation, and thrombosis (94). with abnormal diastolic septal flattening during
Contrast-enhanced angiography is a widely used inspiration, giving a D-shaped appearance to the left
and effective technique to evaluate both the central ventricle, being indicative of constrictive physiology
and peripheral vasculature that permits the anatom- (98) (Figure 11).
ical characterization of vascular lesions and assess-
ment of hemodynamic influence by phase-contrast or RESTRICTIVE CARDIOMYOPATHY. Restrictive car-
velocity-encoded CMR (85). These sequences would diomyopathy is a condition characterized by stiffness
require a specific request because they are not of the ventricular walls, which can be caused either
included in a typical CMR protocol. by myocardial infiltration (e.g., amyloid), or in the
PERICARDIAL DISEASE. CMR is 1 of the most versa- case of radiation-induced cardiomyopathy, myocar-
tile modalities to evaluate pericardial disease, which dial replacement fibrosis (100).
in the field of cardio-oncology principally relates to The inherent risks of invasive cardiac biopsy tend
pericardial thickening, pericardial inflammation and to preclude its routine clinical use in the assessment
effusion, pericardial masses and in the late stages, of restrictive cardiomyopathy, but with tissue char-
pericardial constriction. Pericarditis has been acterization sequences (LGE, T1 mapping, and ECV),
286 Harries et al. JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020

MRI to Detect Cardiovascular Effects JUNE 2020:270–92

F I G U R E 1 1 CMR Case Example of Pericardial Constriction

Real-time short-axis mid-ventricular SSFP cine imaging during deep breathing (A) during expiration, and (B) at onset of inspiration. Note the
D-shaped LV due to septal flattening (arrow). (C) Axial phase-contrast imaging of the inferior vena cava, with a flow pattern (D) showing
rapid and steep y descent with flow reversal in diastole (arrow) reminiscent of the jugular venous waveform encountered in pericardial
constriction. Abbreviations as in Figures 1 and 6.

CMR can assess the myocardium noninvasively (101). they are not specific to amyloidosis and do not obviate
Amyloid light chain amyloid, in particular, can result the need for a definitive histologic diagnosis (105).
in cardiac involvement leading to a form of restrictive
cardiomyopathy. Cardiac amyloid is readily detectible CURRENT INTERNATIONAL GUIDELINE
by CMR due to the interstitial deposition of amyloid RECOMMENDATIONS ON THE ROLE OF
proteins (elevated native T1 and elevated ECV are CMR IN CARDIO-ONCOLOGY
typical) (102,103). Patients with cardiac amyloidosis
also have markedly abnormal gadolinium kinetics CMR is becoming increasingly incorporated into so-
and a characteristic pattern of fibrosis (global sub- cietal cardio-oncology guidelines. The role identified
endocardial LGE) (104), which may permit the for CMR in the most recent publications is described
discrimination of amyloid from other wall-thickening in detail below. In brief, CMR is particularly useful
disorders. In addition, difficulty in obtaining when LVEF is difficult to obtain by other means (106)
myocardial nulling (myocardium appears black), (e.g., poor echocardiographic window due to left-
despite a T1 scout, may suggest underlying amyloid. sided breast surgery); when results obtained by
However, although these techniques are sensitive, other means are suboptimal, borderline, or conflicting
JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020 Harries et al. 287
JUNE 2020:270–92 MRI to Detect Cardiovascular Effects

(95); and where discontinuation of chemotherapy is equilibrium radionuclide angiographic calcula-

being contemplated (95). Furthermore, CMR is tion of LVEF (95).
particularly useful in the assessment of pericardial
If the quality of the echocardiogram is suboptimal,
disease (1,95), infiltrative diseases, and cardiac CMR is recommended.
masses (1,95), as well as in determining the etiology
CMR should be considered in evaluation of primary
of left ventricular dysfunction and presence of scar- tumors of the heart with or without compromise of
ring or fibrosis (1). the pericardium or when the diagnosis of
EUROPEAN SOCIETY OF CARDIOLOGY POSITION PAPER constrictive pericarditis remains uncertain after a
ON CANCER TREATMENTS AND CARDIOVASCULAR careful echocardiographic evaluation.
TOXICITY. When considering strategies for screening
Standard precautions for CMR safety need to be
and detecting cardiotoxicity, the choice of modality followed, including consideration of electromag-
depends on local expertise and availability but the netic interference. This may be particularly rele-
ESC describes several core principles, all of which are vant in patients with breast cancer, who had tissue
fulfilled by CMR (1): expanders placed for breast reconstruction may
represent a hazard.

The same imaging modality and/or biomarker
assay should be used for continued screening PREVENTION AND MONITORING OF CARDIAC
throughout the treatment pathway. Switching be- DYSFUNCTION IN SURVIVORS OF ADULT CANCERS:
tween modalities is strongly discouraged. AMERICAN SOCIETY OF CLINICAL ONCOLOGY

Modalities and tests with the best reproducibility CLINICAL PRACTICE GUIDELINE 2017. Imaging mo-
are preferred. dalities such as CMR or multigated acquisition may be

Imaging modalities that provide additional rele- considered if an echocardiogram is not available or
vant clinical information are preferred (e.g., right technically feasible (e.g., poor image quality as a
ventricular function, pulmonary pressures, result of body habitus, chronic lung conditions, or
valvular function, and pericardial evaluation). history of mediastinal surgery), with preference given

High-quality radiation-free imaging is preferred, if to CMR (106).
available.
CHALLENGES AND SAFETY IN CMR
In addition:

CMR is useful to determine the cause of left ven- CMR emerged as an important tool to evaluate the
tricular dysfunction and to clarify left and right cardiovascular system nearly 2 decades ago, but
ventricular function in challenging cases (i.e., significant barriers to its widespread use in routine
borderline or contradictory results from other im- clinical practice persist. CMR remains a compara-
aging modalities). tively time-consuming and complex investigation

CMR also serves to evaluate the pericardium, that is typically performed in academic centers. It
especially in patients with chest irradiation. requires a cooperative patient, ideally in sinus

LGE may be useful to detect scarring or fibrosis, rhythm, who can hold his or her breath to provide
which may have prognostic implications in the high-quality images. However, the advent of novel
context of impaired left ventricular function. technologies such as compressed sensing real-time
cine CMR, self-gating, and artificial intelligence
CMR is an excellent test for the comprehensive have the potential to simplify and reduce
evaluation of cardiac masses and infiltrative image acquisition time up to 20-fold without
conditions. compromising image quality (107). The cost and
general availability of MRI scanners is an additional
EXPERT CONSENSUS FOR MULTIMODALITY IMAGING
problem that may partially be addressed by collab-
EVALUATION OF ADULT PATIENTS DURING AND AFTER
orative use of resources and establishment of
CANCER THERAPY: AMERICAN SOCIETY OF ECHOCAR-
referral pathways between smaller and larger in-
DIOGRAPHY AND THE EUROPEAN ASSOCIATION OF
stitutions. Furthermore, most MRI scanners installed
CARDIOVASCULAR IMAGING.
in the last 10 years have the capacity to undertake

CMR may be particularly useful in situations cardiac imaging. Data indicate that use of CMR has
in which discontinuation of chemotherapy continued to increase in the United States during
is being entertained and/or when there is this period (108), with more than 600 centers sub-
concern regarding echocardiographic or mitting claims for CMR services according to 2018
288 Harries et al. JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020

MRI to Detect Cardiovascular Effects JUNE 2020:270–92

T A B L E 4 Safety Concerns in CMR and Possible Solutions

Category Safety Concern Possible Solution

MRI
Metallic foreign bodies (nonclinical) Removal; Intra-orbital metallic foreign bodies are an absolute contraindication to
MRI scanning.
Metallic foreign bodies (clinical) Patients with MRI-conditional devices that pose no hazard in specific conditions can
safely undergo MRI scanning. Consult MRI safety of specific product or device
(e.g. mrisafety.com).
There is increasing evidence that the risks attached to previously MRI-unsafe clinical
devices (e.g., legacy pacemakers, defibrillators, implantable loop recorders, and
tissue expanders) can be mitigated and that patients can safely undergo MRI
scanning (115,116). Consult MRI safety of specific product or device (e.g.,
mrisafety.com) and consult individuals/centers with expertise.
Pregnancy Often avoided during first trimester, although risk is not known.
No known risk during second or third trimester.
Gadolinium contrast
Allergy Gadolinium panel allergy testing.
Anaphylaxis Noncontrast study.
Pregnancy American College of Obstetricians and Gynecologists recommend that use should be
limited to cases where diagnostic performance is significantly improved and is
expected to improve fetal or maternal outcome.
Breast feeding American College of Obstetricians and Gynecologists recommend that breastfeeding
should not be interrupted after gadolinium administration.
Renal impairment Weigh benefit and risk, minimize dose of a low-risk agent, avoid repeat dose for
7 days.
Hemodialysis Noncontrast study; dialyze within 24 h of administration if benefit believed to
outweigh risk.

MRI ¼ cardiac magnetic resonance; other abbreviation as in Table 1.

billing data furnished by the Centers for Medicare protocols (e.g., 15-min noncontrast cine study for
and Medicaid Services. ventricular dimensions and systolic function)
There is an increasing number of physicians (car- coupled with increasing automation of acquisition,
diologists and radiologists) who are training and processing, and analysis, as well as the potential for
certifying worldwide, and CMR expertise at both the remote collaboration, image analysis, and interpre-
clinician and technologist level is increasing. To in- tation will also increase the accessibility of this
crease availability of technology and expertise, the important tool to clinicians working in a variety of
development of technologies that allow remote su- health care settings.
pervision (109) of CMR scanners may also have an Technical challenges in CMR can often be over-
important role to play in training staff in geographi- come. For example, CMR may be facilitated in claus-
cally remote locations. Shortened, simplified trophobic patients with a prone position, use of an

T A B L E 5 Relative Strengths and Limitations of Cardiovascular Imaging Modalities

CMR Echocardiography Nuclear CT

Advantages
Accuracy Availability Reproducibility Availability
Reproducibility Safety Availability Scan time
Tissue characterization Morphological and functional Spatial resolution
Lack of radiation information Morphological and extra-cardiac information
Morphological, functional and Lack of radiation Low cost
extra-cardiac information Low cost Multiplanar
Multiplanar
Limitations
Availability Acoustic window Radiation exposure Radiation exposure
Relative high cost Interobserver, intraobserver and Limited morphological and Limited functional information
Contrast reactions (rare) interscan variability functional information Contrast reactions
Renal impairment due to very rare risk Renal impairment due to risk of contrast-
(likely <0.07%) of nephrogenic induced nephropathy
systemic fibrosis with gadolinium (117)

CT ¼ computed tomography; other abbreviation as in Table 1.

JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020 Harries et al. 289
JUNE 2020:270–92 MRI to Detect Cardiovascular Effects

eye mask, preprocedural sedative or general anes- CONCLUSIONS

thetic (generally pediatric populations), or the
accompaniment of a friend or relative or by using a Cardio-oncology is a diverse and rapidly evolving
large bore scanner. Difficulty breath-holding can be field. CMR provides comprehensive, accurate, and
overcome by reducing the number of slices or phases reproducible cardiovascular data that can be
and thus the time required for acquisition, by using a applied to a wide variety of clinical scenarios
respiratory navigator, or by acquiring images during encountered by the cardio-oncologist. The use of
free breathing or inspiration, rather than held expi- CMR in this setting is supported by international
ration. Traditionally, CMR exams have lasted societal guidance and an expanding evidence base.
approximately 60 min; however, the adoption of Barriers to the widespread use of CMR persist,
shortened protocols (3) can reduce this to 20 to 25 min although technological advances and stakeholder
without compromising image acquisition quality collaboration will improve access to and awareness
while maximizing patient comfort and efficiency. of this increasingly indispensable investigation in
Image quality can be improved in patients with modern medicine.
arrhythmia by using arrhythmia rejection and/or
correction protocols, or by using prospective elec- ADDRESS FOR CORRESPONDENCE: Dr. Chiara
trocardiogram gating or real-time acquisition. Table 4 Bucciarelli-Ducci, Bristol Heart Institute, University
describes safety concerns and proposed solutions Hospitals Bristol NHS Foundation Trust, Upper
encountered in clinical CMR and Table 5 describes Maudlin Street, Bristol BS2 8HW, United Kingdom.
relative strengths and limitations of each imaging E-mail: [email protected]. Twitter:
modality. @chiarabd, @juancplana.

REFERENCES

1. Zamorano JL, Lancellotti P, Rodriguez Muñoz D, resonance examinations. J Cardiovasc Magn Reson nomenclature for tomographic imaging of the
et al. 2016 ESC Position Paper on cancer treat- 2009;11:5. heart. A statement for health care professionals
ments and cardiovascular toxicity developed un- from the Cardiac Imaging Committee of the
6. Dunet V, Schwitter J, Meuli R, Beigelman-
der the auspices of the ESC Committee for Practice Council on Clinical Cardiology of the American
Aubry C. Incidental extracardiac findings on car-
Guidelines: The Task Force for cancer treatments Heart Association. Circulation 2002;105:539–42.
diac MR: systematic review and meta-analysis.
and cardiovascular toxicity of the European Soci-
J Magn Reson Imaging 2016;43:929–39. 13. Gulati G, Heck SL, Ree AH, et al. Prevention of
ety of Cardiology (ESC). Eur Heart J 2016;37:
7. Grothues F, Smith GC, Moon JC, et al. Com- cardiac dysfunction during adjuvant breast cancer
2768–801.
parison of interstudy reproducibility of cardiovas- therapy (PRADA): a 2  2 factorial, randomized,
2. Doherty JU, Kort S, Mehran R, et al. ACC/AATS/ placebo-controlled, double-blind clinical trial of
cular magnetic resonance with two-dimensional
AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2019 candesartan and metoprolol. Eur Heart J 2016;37:
echocardiography in normal subjects and in pa-
appropriate use criteria for multimodality imaging 1671–80.
tients with heart failure or left ventricular hyper-
in the assessment of cardiac structure and func-
trophy. Am J Cardiol 2002;90:29–34. 14. Pituskin E, Mackey JR, Koshman S, et al.
tion in nonvalvular heart disease: a report of the
8. Bellenger NG, Burgess MI, Ray SG, et al. Com- Multidisciplinary Approach to Novel Therapies in
American College of Cardiology Appropriate Use
parison of left ventricular ejection fraction and Cardio-Oncology Research (MANTICORE 101-
Criteria Task Force, American Association for
volumes in heart failure by echocardiography, Breast): a randomized trial for the prevention of
Thoracic Surgery, American Heart Association,
radionuclide ventriculography and cardiovascular trastuzumab-associated cardiotoxicity. J Clin
American Society of Echocardiography, American
magnetic resonance; are they interchangeable? Oncol 2017;35:870–7.
Society of Nuclear Cardiology, Heart Rhythm So-
ciety, Society for Cardiovascular Angiography and Eur Heart J 2000;21:1387–96. 15. Romano S, Judd RM, Kim RJ, et al. Association
Interventions, Society of Cardiovascular Computed 9. Mooij CF, de Wit CJ, Graham DA, Powell AJ, of feature-tracking cardiac magnetic resonance
Tomography, Society for Cardiovascular Magnetic Geva T. Reproducibility of MRI measurements of left ventricular global longitudinal strain with all-
Resonance, and the Society of Thoracic Surgeons. right ventricular size and function in patients with cause mortality in patients with reduced left
J Am Coll Cardiol 2019;73:488–516. normal and dilated ventricles. J Magn Reson Im- ventricular ejection fraction. Circulation 2017;135:
aging 2008;28:67–73. 2313–5.
3. Kramer CM, Barkhausen J, Bucciarelli-Ducci C,
Flamm SD, Kim RJ, Nagel E. Standardized cardio- 10. Clarke CJ, Gurka MJ, Norton PT, Kramer CM, 16. Thavendiranathan P, Poulin F, Lim KD,
vascular cardiac magnetic resonance (CMR) pro- Hoyer AW. Assessment of the accuracy and Plana JC, Woo A, Marwick TH. Use of myocar-
tocols: 2020 update. J Cardiovasc Magn Reson reproducibility of RV volume measurements by dial strain imaging by echocardiography for the
2020;22:17. CMR in congenital heart disease. J Am Coll Cardiol early detection of cardiotoxicity in patients
Img 2012;5:28–37. during and after cancer chemotherapy: a sys-
4. Schulz-Menger J, Bluemke DA, Bremerich J,
tematic review. J Am Coll Cardiol 2014;63:
et al. Standardized image interpretation and post- 11. Schulz-Menger J, Bluemke DA, Bremerich J,
2751–68.
processing in cardiovascular magnetic resonance — et al. Standardized image interpretation and post
2020 update: Society for Cardiovascular Magnetic processing in cardiovascular magnetic resonance: 17. Negishi T, Thavendiranathan P, Negishi K,
Resonance (SCMR): Board of Trustees Task Force Society for Cardiovascular Magnetic Resonance Marwick TH. Rationale and Design of the Strain
on Standardized Post-Processing. J Cardiovasc (SCMR) board of trustees task force on standard- Surveillance of Chemotherapy for Improving Car-
Magn Reson 2020;22:19. ized post processing. J Cardiovasc Magn Reson diovascular Outcomes: the SUCCOUR trial. J Am
2013;15:35. Coll Cardiol Img 2018;1:1098–105.
5. Hundley WG, Bluemke D, Bogaert JG, et al.
Society for Cardiovascular Magnetic Resonance 12. Cerqueira MD, Weissman NJ, Dilsizian V, et al. 18. Drafts BC, Twomley KM, D’Agostino R, et al.
guidelines for reporting cardiovascular magnetic Standardized myocardial segmentation and Low to moderate dose anthracycline-based
290 Harries et al. JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020

MRI to Detect Cardiovascular Effects JUNE 2020:270–92

chemotherapy is associated with early noninvasive 32. O’Hanlon R, Grasso A, Roughton M, et al. the Society for Cardiovascular Magnetic Reso-
imaging evidence of subclinical cardiovascular Prognostic significance of myocardial fibrosis in nance (SCMR) endorsed by the European Associ-
disease. J Am Coll Cardiol Img 2013;6:877–85. hypertrophic cardiomyopathy. J Am Coll Cardiol ation for Cardiovascular Imaging (EACVI).
2010;56:867–74. J Cardiovasc Magn Reson 2017;19:75.
19. Jolly MP, Jordan JH, Meléndez GC, McNeal GR,
D’Agostino RB, Hundley WG. Automated assess- 33. Hulten E, Agarwal V, Cahill M, et al. Presence 45. Miller CA, Naish JH, Bishop P, et al. Compre-
ments of circumferential strain from cine CMR of late gadolinium enhancement by cardiac mag- hensive validation of cardiovascular magnetic
correlate with LVEF declines in cancer patients netic resonance among patients with suspected resonance techniques for the assessment of
early after receipt of cardio-toxic chemotherapy. cardiac sarcoidosis is associated with adverse car- myocardial extracellular volume. Circ Cardiovasc
J Cardiovasc Magn Reson 2017;19:59. diovascular prognosis: a systematic review and Imaging 2013;6:373–83.
meta-analysis. Circ Cardiovasc Imaging 2016;9:
20. Ong G, Brezden-Masley C, Dhir V, et al. 46. Nakamori S, Dohi K, Ishida M, et al. Native T1
e005001.
Myocardial strain imaging by cardiac magnetic mapping and extracellular volume mapping for the
resonance for detection of subclinical myocardial 34. Gräni C, Eichhorn C, Bière L, et al. Prognostic assessment of diffuse myocardial fibrosis in
dysfunction in breast cancer patients receiving value of cardiac magnetic resonance tissue char- dilated cardiomyopathy. J Am Coll Cardiol Img
trastuzumab and chemotherapy. Int J Cardiol acterization in risk stratifying patients with sus- 2018;11:48–59.
2018;261:228–33. pected myocarditis. J Am Coll Cardiol 2017;70:
47. Neilan TG, Coelho-Filho OR, Shah RV, et al.
1964–76.
21. Erley J, Genovese D, Tapaskar N, et al. Echo- Myocardial extracellular volume by cardiac mag-
cardiography and cardiovascular magnetic reso- 35. Fontana M, Pica S, Reant P, et al. Prognostic netic resonance in patients treated with
nance based evaluation of myocardial strain and value of late gadolinium enhancement cardiovas- anthracycline-based chemotherapy. Am J Cardiol
relationship with late gadolinium enhancement. cular magnetic resonance in cardiac amyloidosis. 2013;111:717–22.
J Cardiovasc Magn Reson 2019;2:46. Circulation 2015;132:1570–9.
48. Jordan JH, Vasu S, Morgan TM, et al.
22. Ugander M, Bagi PS, Oki AJ, et al. Myocardial 36. Muehlberg F, Funk S, Zange L, et al. Native
Anthracycline-associated T1 mapping characteris-
edema as detected by pre-contrast T1 and T2 CMR myocardial T1 time can predict development of
tics are elevated independent of the presence of
delineates area at risk associated with acute subsequent anthracycline-induced cardiomyopa-
cardiovascular comorbidities in cancer survivors.
myocardial infarction. J Am Coll Cardiol Img 2012; thy. ESC Heart Fail 2018;5:620–9.
Circ Cardiovasc Imaging 2016;9:e004325.
5:596–603. 37. Jordan JH, D’Agostino RB, Hamilton CA, et al.
49. Altaha MA, Nolan M, Marwick TH, et al. Can
23. Friedrich MG, Sechtem U, Schulz-Menger J, Longitudinal assessment of concurrent changes in
quantitative CMR tissue characterization
et al. Cardiovascular magnetic resonance in left ventricular ejection fraction and left ventric-
adequately identify cardiotoxicity during chemo-
myocarditis: A JACC White Paper. J Am Coll Car- ular myocardial tissue characteristics after
therapy?: impact of temporal and observer vari-
diol 2009;53:1475–87. administration of cardiotoxic chemotherapies us-
ability. J Am Coll Cardiol Img 2020;13:951–62.
ing T1-weighted and T2-weighted cardiovascular
24. McAlindon E, Pufulete M, Lawton C, 50. Nayak KS, Nielsen JF, Bernstein MA, et al.
magnetic resonance. Circ Cardiovasc Imaging
Angelini GD, Bucciarelli-Ducci C. Quantification of Cardiovascular magnetic resonance phase contrast
2014;7:872–9.
infarct size and myocardium at risk: evaluation of imaging. J Cardiovasc Magn Reson 2015;17:71.
different techniques and its implications. Eur 38. Nakano S, Takahashi M, Kimura F, et al. Car-
Heart J Cardiovasc Imaging 2015;16:738–46. diac magnetic resonance-based myocardial strain 51. Chaosuwannakit N, D’Agostino R, Hamilton CA,
study for evaluation of cardiotoxicity in breast et al. Aortic stiffness increases upon receipt of
25. Ferreira VM, Schulz-Menger J, Holmvang G, cancer patients treated with trastuzumab: a pilot anthracycline chemotherapy. J Clin Oncol 2010;
et al. Cardiovascular magnetic resonance in non- study to evaluate the feasibility of the method. 28:166–72.
ischemic myocardial inflammation: expert recom- Cardiol J 2016;23:270–80.
mendations. J Am Coll Cardiol 2018;72:3158–76. 52. Felker GM, Thompson RE, Hare JM, et al. Un-
39. Fallah-Rad N, Walker JR, Wassef A, et al. The derlying causes and long-term survival in patients
26. Galán-Arriola C, Lobo M, Vílchez- utility of cardiac biomarkers, tissue velocity and with initially unexplained cardiomyopathy. N Engl
Tschischke JP, et al. Serial cardiac magnetic reso- strain imaging, and cardiac magnetic resonance in J Med 2000;342:1077–84.
nance to identify early stages of anthracycline- predicting early left ventricular dysfunction in
induced cardiotoxicity. J Am Coll Cardiol 2019; 53. Meléndez GC, Sukpraphrute B, D’Agostino RB,
patients with human epidermal growth factor re-
73:779–91. et al. Frequency of left ventricular end-diastolic
ceptor II-positive breast cancer treated with
volume-mediated declines in ejection fraction in
27. Haslbauer JD, Lindner S, Valbuena-Lopez S, adjuvant trastuzumab therapy. J Am Coll Cardiol
patients receiving potentially cardiotoxic cancer
et al. CMR imaging biosignature of cardiac 2011;57:2263–70.
treatment. Am J Cardiol 2017;119:1637–42.
involvement due to cancer-related treatment by 40. Lunning MA, Kutty S, Rome ET, et al. Cardiac
T1 and T2 mapping. Int J Cardiol 2019;275:179–86. 54. Jordan JH, Todd RM, Vasu S, Hundley WG.
magnetic resonance for the assessment of the
Cardiovascular magnetic resonance in the
28. Motwani M, Kidambi A, Herzog BA, Uddin A, myocardium after doxorubicin-based chemo-
oncology patient. J Am Coll Cardiol Img 2018;1:
Greenwood JP, Plein S. MR imaging of cardiac therapy. Am J Clin Oncol 2015;38:377–81.
1150–72.
tumors and masses: a review of methods and 41. Neilan TG, Coelho-Filho OR, Pena-Herrera D,
clinical applications. Radiology 2013;268:26–43. et al. Left ventricular mass in patients with a car- 55. Armstrong GT, Plana JC, Zhang N, et al.
diomyopathy after treatment with anthracyclines. Screening adult survivors of childhood cancer for
29. Wassmuth R, Lentzsch S, Erdbruegger U, et al.
Am J Cardiol 2012;110:1679–86. cardiomyopathy: comparison of echocardiography
Subclinical cardiotoxic effects of anthracyclines as
and cardiac magnetic resonance. J Clin Oncol
assessed by cardiac magnetic resonance-a pilot 42. Lawley C, Wainwright C, Segelov E, Lynch J,
2012;30:2876–84.
study. Am Heart J 2001;141:1007–13. Beith J, McCrohon J. Pilot study evaluating the
role of cardiac magnetic resonance in monitoring 56. Zamorano J. An ESC position paper on cardio-
30. Kwong RY, Chan AK, Brown KA, et al. Impact
adjuvant trastuzumab therapy for breast cancer. oncology. Eur Heart J 2016;37:2739–40.
of unrecognized myocardial scar detected by car-
Asia Pac J Clin Oncol 2012;8:95–100. 57. Ganatra S, Carver JR, Hayek SS, et al. Chimeric
diac magnetic resonance on event-free survival in
patients presenting with signs or symptoms of 43. Harries I, Biglino G, Baritussio A, et al. Long antigen receptor T-cell therapy for cancer and
coronary artery disease. Circulation 2006;113: term cardiovascular magnetic resonance pheno- heart: JACC Council Perspectives. J Am Coll Car-
2733–43. typing of anthracycline cardiomyopathy. Int J diol 2019;74:3153–63.
Cardiol 2019;292:248–52.
31. Wu KC, Weiss RG, Thiemann DR, et al. Late 58. Kochenderfer JN, Somerville RPT, Lu T, et al.
gadolinium enhancement by cardiovascular mag- 44. Messroghli DR, Moon JC, Ferreira VM, et al. Lymphoma remissions caused by anti-CD19
netic resonance heralds an adverse prognosis in Clinical recommendations for cardiovascular chimeric antigen receptor T Cells are associated
nonischemic cardiomyopathy. J Am Coll Cardiol magnetic resonance mapping of T1, T2, T2* and with high serum interleukin-15 levels. J Clin Oncol
2008;51:2414–21. extracellular volume: a consensus statement by 2017;35:1803–13.
JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020 Harries et al. 291
JUNE 2020:270–92 MRI to Detect Cardiovascular Effects

59. Burstein DS, Maude S, Grupp S, Griffis H, 73. Cammann VL, Sarcon A, Ding KJ, et al. Clinical survivors of Hodgkin lymphoma treated with ra-
Rossano J, Lin K. Cardiac profile of chimeric anti- features and outcomes of patients with malig- diation therapy. JAMA 2003;290:2831–7.
gen receptor T cell therapy in children: a single- nancy and takotsubo syndrome: observations from
87. Maraldo MV, Ng AK. Minimizing cardiac risks
institution experience. Biol Blood Marrow the International Takotsubo Registry. J Am Heart
with contemporary radiation therapy for Hodgkin
Transplant 2018;2:1590–5. Assoc 2019;8:e010881.
lymphoma. J Clin Oncol 2016;34:208–10.
60. Ghosh A, Chen D, Guha A, Mackenzie S, 74. Eitel I, von Knobelsdorff-Brenkenhoff F,
88. Caruthers SD, Lin SJ, Brown P, et al. Practical
Walker JM, Claire R. CAR T cell therapy–related Bernhardt P, et al. Clinical characteristics and
value of cardiac magnetic resonance for clinical
cardiovascular outcomes and management: sys- cardiovascular magnetic resonance findings in
quantification of aortic valve stenosis: comparison
temic disease or direct cardiotoxicity? J Am Coll stress (takotsubo) cardiomyopathy. JAMA 2011;
with echocardiography. Circulation 2003;108:
Cardiol CardioOnc 2020;2:97–109. 306:277–86.
2236–43.
61. Ylänen K, Poutanen T, Savikurki-Heikkilä P, 75. Montalescot G, Sechtem U, Achenbach S, et al.
89. Søndergaard L, Hildebrandt P, Lindvig K, et al.
Rinta-Kiikka I, Eerola A, Vettenranta K. Cardiac 2013 ESC guidelines on the management of stable
Valve area and cardiac output in aortic stenosis:
magnetic resonance in the evaluation of the late coronary artery disease: the task force on the
quantification by magnetic resonance velocity
effects of anthracyclines among long-term survi- management of stable coronary artery disease of
mapping. Am Heart J 1993;126:1156–64.
vors of childhood cancer. J Am Coll Cardiol 2013; the European Society of Cardiology. Eur Heart J
61:1539–47. 2013;34:2949–3003. 90. Piccirillo JF, Tierney RM, Costas I, Grove L,
62. Ylänen K, Eerola A, Vettenranta K, Poutanen T. 76. Ibanez B, James S, Agewall S, et al. 2017 ESC Spitznagel EL. Prognostic importance of comor-
Three-dimensional echocardiography and cardiac Guidelines for the management of acute myocar- bidity in a hospital-based cancer registry. JAMA
magnetic resonance in the screening of long-term dial infarction in patients presenting with ST- 2004;291:2441–7.
survivors of childhood cancer after cardiotoxic segment elevation: the task force for the man- 91. Wu S, Chen JJ, Kudelka A, Lu J, Zhu X. Inci-
therapy. Am J Cardiol 2014;113:1886–92. agement of acute myocardial infarction in patients dence and risk of hypertension with sorafenib in
presenting with ST-segment elevation of the Eu- patients with cancer: a systematic review and
63. Chamsi-Pasha MA, Zhan Y, Debs D, Shah DJ.
ropean Society of Cardiology (ESC). Eur Heart J meta-analysis. Lancet Oncol 2008;9:117–23.
CMR in the evaluation of diastolic dysfunction and
2018;39:119–77.
phenotyping of HFpEF: current role and future 92. Maceira AM, Mohiaddin RH. Cardiovascular
perspectives. J Am Coll Cardiol Img 2020;13 1 Pt 2: 77. Dastidar AG, Rodrigues JC, Baritussio A, Buc- magnetic resonance in systemic hypertension.
283–96. ciarelli-Ducci C. MRI in the assessment of ischae- J Cardiovasc Magn Reson 2012;14:28.
mic heart disease. Heart 2016;102:239–52.
64. Saiki H, Petersen IA, Scott CG, et al. Risk of
93. Valent P, Hadzijusufovic E, Schernthaner GH,
heart failure with preserved ejection fraction in 78. Nagel E, Greenwood JP, McCann GP, et al.
Wolf D, Rea D, le Coutre P. Vascular safety issues
older women after contemporary radiotherapy for Magnetic resonance perfusion or fractional flow
in CML patients treated with BCR/ABL1 kinase in-
breast cancer. Circulation 2017;135:1388–96. reserve in coronary disease. N Engl J Med 2019;
hibitors. Blood 2015;125:901–6.
380:2418–28.
65. Ferreira de Souza T, Quinaglia A C Silva T,
94. Fajardo LF. Is the pathology of radiation injury
Osorio Costa F, et al. Anthracycline therapy is 79. Kristensen SD, Knuuti J, Saraste A, et al. 2014
different in small vs large blood vessels? Car-
associated with cardiomyocyte atrophy and pre- ESC/ESA Guidelines on non-cardiac surgery: car-
diovasc Radiat Med 1999;1:108–10.
clinical manifestations of heart disease. J Am Coll diovascular assessment and management [in Pol-
Cardiol Img 2018;11:1045–55. ish]. Kardiol Pol 2014;72:857–918. 95. Plana JC, Galderisi M, Barac A, et al. Expert
consensus for multimodality imaging evaluation
66. Mahmood SS, Fradley MG, Cohen JV, et al. 80. van Nimwegen FA, Schaapveld M, Janus CP,
of adult patients during and after cancer ther-
Myocarditis in patients treated with immune et al. Cardiovascular disease after Hodgkin lym-
apy: a report from the American Society of
checkpoint inhibitors. J Am Coll Cardiol 2018;71: phoma treatment: 40-year disease risk. JAMA
Echocardiography and the European Association
1755–64. Intern Med 2015;175:1007–17.
of Cardiovascular Imaging. J Am Soc Echo-
67. Puzanov I, Diab A, Abdallah K, et al. Managing 81. Darby SC, Ewertz M, McGale P, et al. Risk of cardiogr 2014;27:911–39.
toxicities associated with immune checkpoint in- ischemic heart disease in women after radio-
96. Rhodes M, Lautz T, Kavanaugh-Mchugh A,
hibitors: consensus recommendations from the therapy for breast cancer. N Engl J Med 2013;368:
et al. Pericardial effusion and cardiac tamponade
Society for Immunotherapy of Cancer (SITC) 987–98.
in pediatric stem cell transplant recipients. Bone
Toxicity Management Working Group.
82. Correa CR, Litt HI, Hwang WT, Ferrari VA, Marrow Transplant 2005;36:139–44.
J Immunother Cancer 2017;5:95.
Solin LJ, Harris EE. Coronary artery findings after
97. Bogaert J, Francone M. Cardiovascular mag-
68. Haanen JBAG, Carbonnel F, Robert C, et al. left-sided compared with right-sided radiation
netic resonance in pericardial diseases.
Management of toxicities from immunotherapy: treatment for early-stage breast cancer. J Clin
J Cardiovasc Magn Reson 2009;11:14.
ESMO Clinical Practice Guidelines for diagnosis, Oncol 2007;25:3031–7.
treatment and follow-up. Ann Oncol 2018;29 98. Kramer CM, Barkhausen J, Flamm SD, Kim RJ,
83. Machann W, Beer M, Breunig M, et al. Cardiac
suppl 4:iv264–6. Nagel E. Standardized cardiovascular magnetic
magnetic resonance findings in 20-year survivors
69. Bonaca MP, Olenchock BA, Salem JE, et al. of mediastinal radiotherapy for Hodgkin’s disease. resonance (CMR) protocols 2013 update.
Myocarditis in the setting of cancer therapeutics: Int J Radiat Oncol Biol Phys 2011;79:1117–23. J Cardiovasc Magn Reson 2013;15:91.
proposed case definitions for emerging clinical 99. Hoey ET, Gulati GS, Ganeshan A, Watkin RW,
84. Tichelli A, Bucher C, Rovó A, et al. Premature
syndromes in cardio-oncology. Circulation 2019; Simpson H, Sharma S. Cardiovascular MRI for
cardiovascular disease after allogeneic hemato-
140:80–91. assessment of infectious and inflammatory con-
poietic stem-cell transplantation. Blood 2007;11:
70. Zhang L, Awadalla M, Mahmood SS, et al. 3463–71. ditions of the heart. AJR Am J Roentgenol 2011;
Cardiovascular magnetic resonance in immune 197:103–12.
85. Lancellotti P, Nkomo VT, Badano LP, et al.
checkpoint inhibitor-associated myocarditis. Eur 100. Taunk NK, Haffty BG, Kostis JB, Goyal S.
Expert consensus for multi-modality imaging
Heart J 2020;41:1733–43. Radiation-induced heart disease: pathologic ab-
evaluation of cardiovascular complications of
71. Ganatra S, Neilan TG. Immune checkpoint radiotherapy in adults: a report from the European normalities and putative mechanisms. Front Oncol
inhibitor-associated myocarditis. Oncologist 2018; Association of Cardiovascular Imaging and the 2015;5:39.
23:879–86. American Society of Echocardiography. Eur Heart J
101. Flett AS, Hayward MP, Ashworth MT, et al.
Cardiovasc Imaging 2013;14:721–40.
72. Ederhy S, Cautela J, Ancedy Y, Escudier M, Equilibrium contrast cardiovascular magnetic
Thuny F, Cohen A. Takotsubo-like syndrome in 86. Hull MC, Morris CG, Pepine CJ, resonance for the measurement of diffuse
cancer patients treated with immune checkpoint Mendenhall NP, et al. Valvular dysfunction and myocardial fibrosis: preliminary validation in
inhibitors. J Am Coll Cardiol Img 2018;11:1187–90. carotid, subclavian, and coronary artery disease in humans. Circulation 2010;122:138–44.
292 Harries et al. JACC: CARDIOONCOLOGY, VOL. 2, NO. 2, 2020

MRI to Detect Cardiovascular Effects JUNE 2020:270–92

102. Karamitsos TD, Piechnik SK, Banypersad SM, ment systems: understanding the past and present vational study. J Cardiovasc Magn Reson 2017;
et al. Noncontrast T1 mapping for the diagnosis of in order to guide the future. J Am Coll Cardiol Img 19:44.
cardiac amyloidosis. J Am Coll Cardiol Img 2013;6: 2014;7:324–32.
115. Nazarian S, Hansford R, Rahsepar AA, et al.
488–97.
109. Garg R, Sevilla A, Garberich R, Fleishman CE. Safety of cardiac magnetic resonance in patients
103. Banypersad SM, Sado DM, Flett AS, et al. Remote delivery of congenital cardiac cardiac with cardiac devices. N Engl J Med 2017;377:
Quantification of myocardial extracellular vol- magnetic resonance services: a unique telemedi- 2555–64.
ume fraction in systemic AL amyloidosis: an cine model. Pediatr Cardiol 2015;36:226–32. 116. Marano AA, Henderson PW, Prince MR,
equilibrium contrast cardiovascular magnetic Dashnaw SM, Rohde CH. Effect of MRI on breast
110. Cardinale D, Colombo A, Bacchiani G, et al.
resonance study. Circ Cardiovasc Imaging 2013; tissue expanders and recommendations for safe
Early detection of anthracycline cardiotoxicity
6:34–9. use. J Plast Reconstr Aesthet Surg 2017;70:1702–7.
and improvement with heart failure therapy.
104. Maceira AM, Joshi J, Prasad SK, et al. Car- Circulation 2015;131:1981–8. 117. Woolen SA, Shankar PR, Gagnier JJ,
diovascular magnetic resonance in cardiac MacEachern MP, Singer L, Davenport MS. Risk of
111. Yeh ET, Bickford CL. Cardiovascular compli-
amyloidosis. Circulation 2005;111:186–93. nephrogenic systemic fibrosis in patients with
cations of cancer therapy: incidence, pathogen-
stage 4 or 5 chronic kidney disease receiving a
105. Falk RH, Quarta CC, Dorbala S. How to image esis, diagnosis, and management. J Am Coll
group ii gadolinium-based contrast agent: a sys-
cardiac amyloidosis. Circ Cardiovasc Imaging 2014; Cardiol 2009;53:2231–47.
tematic review and meta-analysis. JAMA Intern
7:552–62.
112. Khakoo AY, Kassiotis CM, Tannir N, et al. Med 2019;180:223–30.
106. Armenian SH, Lacchetti C, Barac A, et al. Heart failure associated with sunitinib malate: a
Prevention and monitoring of cardiac dysfunction multitargeted receptor tyrosine kinase inhibitor.
in survivors of adult cancers: American Society of Cancer 2008;112:2500–8. KEY WORDS cardio-oncology,
Clinical Oncology Clinical Practice Guideline. J Clin cardiotoxicity, cardiovascular magnetic
113. Cornell RF, Ky B, Weiss BM, et al. Prospective resonance, chemotherapy, left ventricular
Oncol 2017;35:893–911.
study of cardiac events during proteasome inhib- dysfunction, tissue characterization
107. Vermersch M, Longere B, Coisne A, et al. itor therapy for relapsed multiple myeloma. J Clin
Compressed sensing real-time cine imaging for Oncol 2019;37:1946–55.
assessment of ventricular function, volumes and Go to http://www.acc.org/
114. Barthur A, rezden-Masley C, Connelly KA,
mass in clinical practice. Eur Radiol 2020;30: jacc-journals-cme to take
et al. Longitudinal assessment of right ventric-
609–19. the CME/MOC/ECME quiz
ular structure and function by cardiovascular
108. Ferrari VA, Whitman B, Blankenship JC, et al. magnetic resonance in breast cancer patients for this article.
Cardiovascular imaging payment and reimburse- treated with trastuzumab: a prospective obser-