The search for water: Is it so easy to diagnose acute myocarditis?
The search for water: Is it so easy to diagnose acute myocarditis?
G. Ross Farris 0 2
Steven G. Lloyd 0
0 Reprint requests: Steven G. Lloyd, MD, PhD , Division of Cardiovascular Disease, Department of Internal Medicine, University of Alabama at Birmingham , 1808 7th Avenue South, BDB 201, Birmingham, AL 35244 , USA
1 Birmingham VA Medical Center , Birmingham, AL , USA
2 Division of Cardiovascular Disease, Department of Internal Medicine, University of Alabama at Birmingham , Birmingham, AL , USA
Acute myocarditis (AM) is a common clinical
problem that affects approximately 1.5 million people
per year worldwide.1 However, the true incidence of
AM is unknown and likely underestimated due to low
sensitivity of diagnostic methods and low clinical
suspicion. The etiologies of AM are varied and include
autoimmune, drug reactions, and infection, the most
common cause.2,3 Diagnosis of AM is difficult to
ascertain because patients may range in symptoms from
asymptomatic to severe disturbances—including
malignant arrhythmias, cardiogenic shock, or even death.
Additionally, current World Health Organization
(WHO) and International Society and Federation of
Cardiology (ISFC) guidelines specify that the diagnosis
be made on the grounds of established histologic,
immunological, and immunohistochemical criteria.3
Because of this, many patients with suspected AM never
receive a formal diagnosis. Electrocardiography (ECG),
echocardiography, and cardiovascular magnetic
resonance (CMR) are all useful noninvasive aids in
increasing or decreasing suspicion of AM in a given
patient. Endomyocardial biopsy (EMB) is currently
considered the gold standard,4 but has limited use due to
its invasive nature and low sensitivity secondary to
sampling errors.5 CMR is now being used more
frequently as a first-line noninvasive diagnostic tool with
good sensitivity and specificity. The current
recommended CMR diagnostic criteria are based on
T2weighted imaging and two different contrast-enhanced
techniques, the early gadolinium enhancement (EGE)
and late gadolinium enhancement (LGE)—the so-called
‘‘Lake Louise Criteria’’ (LLC) requiring at least two of
three findings of abnormal T2 signal suggesting
myocardial edema, EGE suggesting hyperemia, and
LGE suggesting myocardial injury in a nonischemic
In this issue of JNC, Imbriaco et al. investigate the
above criteria, noting the marked variation of sensitivity
and negative predictive value in the literature.7 They
then seek to compare CMR qualitative and qualitative
analytical methods for the evaluation of patients with
suspected AM, including (after exclusions) 61 patients
with suspected AM with CMR within approximately
7 ± 4 days of admission. The size of the study is
consistent with other work published within this topic. 80%
of the patients studied were finally diagnosed with AM.
Troponin and CK levels were significantly higher in the
patients with AM, although only 43% of the patients
with AM had an abnormal troponin level. They found no
significant differences in diagnostic test performance
among qualitative measures—T2- weighted STIR
(Short-TI Inversion Recovery), EGE, and LGE
sequences, as well as overall LLC (i.e., two of three positive
features) for the diagnosis of AM. Among quantitative
measures, the Edema ratio (ER, defined as the ratio of
signal intensity on T2-weighted STIR images between
LV myocardium and pectoralis muscle) and global
relative enhancement (RE, defined as the increase in signal
intensity in myocardium following contrast infusion,
compared to pre-contrast signal intensity) were higher in
patients with AM compared to those without. As with
the qualitative measures, there were no significant
differences in diagnostic test performance among any of
the quantitative methods in the identification of patients
with AM. Because the addition of gadolinium
contrastenhanced images did not perform better than the
noncontrast, T2-weighted STIR alone, the authors
concluded that identification of edema (water) may be
the only necessary test in evaluating AM, and that use of
contrast may not be necessary.
The authors undertake an important qualitative and
quantitative analysis for AM. They build on prior
knowledge of utility of MRI in AM, and most
importantly their findings may lead to further, larger studies of
the relative utility of the various CMR measures of
The most important limitation of this study is the
lack of validation of CMR findings with pathology, as
recognized by the authors. There are limited data
comparing CMR to endomyocardial biopsy (EMB), and the
authors also acknowledge the drawbacks of EMB. This
includes an overall complication rate of 6% and a
serious complication rate of 0.1–0.5%.8 Additionally,
sensitivity of EMB is low due to the heterogeneous
nature of AM.5 As noted in the consensus JACC White
Paper,6 many CMR studies use clinical diagnosis to
validate, which has inherent limitations.
Other potential pitfalls of the study include the fact
that CMR was not obtained until around 7 ± 4 days after
admission for the average patient. While this is in line
with the current guidelines, AM improves with time;
therefore, a delay in imaging may reduce the sensitivity
of the test. With regard to the patient population, ECG
abnormalities were only present in 26% of patients
studied, and evident viral syndrome was present in only
25%. Furthermore, the incidence of positive troponin
was low for a group with suspected AM (although in
patients with troponin elevation, the degree of elevation
was quite high compared to their normal range). While
several studies considered in formulation of the LLC
used clinical diagnosis as the gold standard,9–12 these
studies were fairly stringent in clinically diagnosing
AM, requiring either ECG changes or troponin elevation
to enroll, and some required serologic evidence of viral
infection that could cause AM or a recent flu-like or
diarrheal illness.9,10 Imbriaco et al. employed the
European Society of Cardiology guidelines for
management of acute coronary syndromes in patients
presenting without persistent ST-segment elevation to
support the diagnosis of AM,13 potentially reducing the
pre-test probability for AM. Lastly, despite presumably
normal coronary angiography, some patients were
excluded post angiography due to an ischemic pattern on
the CMR LGE imaging. It is unclear whether the authors
dismissed these patients because they thought the
ischemic pattern was due to vasospasm, embolic MI, or
other reasons in the setting of normal coronary arteries.
Myocardial infarction with no obstructive coronary
atherosclerosis (MINOCA) is a syndrome defined as
evidence of a myocardial infarction (MI) including
elevated troponin or other cardiac biomarkers and at
least two of ischemic symptoms, new ST or T wave
changes, and/or new left bundle branch block and
coronary angiography with no epicardial vessel with
greater than 50% stenosis.14 The primary differential
diagnosis for MINOCA includes AM, Tako-tsubo
cardiomyopathy, and coronary artery spasm. Other causes
include hypertrophic cardiomyopathy, pericarditis, and
amyloidosis, but these are much less frequent. CMR is
useful in diagnosing AM and Tako-tsubo
cardiomyopathy, but is less useful in diagnosing spasm. While the
authors excluded patients with coronary artery disease
by angiography, it is unclear if and how the authors
excluded spasm as a cause of the abnormalities on CMR,
as less prolonged spasm might not result in the
characteristic LGE pattern of a Type I myocardial infarction
(following a vascular distribution corresponding to that
of a major epicardial coronary artery).
The authors suggest that current guidelines (i.e., use
of LLC) may need to be revised given the results of this
study and suggest that patients may not need to undergo
contrast administration as the accuracy of qualitative
and quantitative methods is similar. This could expand
the application of CMR since a distinct subset of
patients may have contraindications to contrast
administration. At the very least, omission of the contrast
administration would certainly make test performance
considerably faster and better tolerated for the patient.
Will the current study change practice in diagnosing
AM? Probably not at this moment—important technical
details needed to implement the clinical CMR protocol
are not specified in this paper, including whether a
surface coil proximity correction method was applied
(critical in understanding the effects of signal intensity
changes in pectoralis muscle compared to myocardium),
and the specific values for CMR acquisition parameters
such as repetition, echo, and inversion times which have
major impact on the image signal intensity. However, it
is certainly likely that this paper could lead to changes in
the priority of imaging acquisition. T2-weighted STIR
could be obtained early in the imaging protocol, so that
if the imaging session has to be terminated early for any
reason, a diagnosis still could be made. And, most
importantly, it is quite likely that the findings presented
here will lead to further comparative effectiveness
research among the various CMR and other techniques
for diagnosis of this common and clinically important
disorder. Imbriaco et al. have suggested that looking for
water (edema) is the way to diagnose AM. Now that we
have been led to the water, will we drink?
G. Ross Farris and Steven G. Lloyd have no conflicts of
interest related to the topic of this manuscript.
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