Download Evaluation of myocardial ischemia in coronary artery disease with

ORIGINAL ARTICLE
Evaluation of myocardial ischemia in coronary artery disease
with cardiac MR perfusion method: comparison with the results
of catheter or CT angiography
Mehmet Sait Doğan1, Erkan Yılmaz2, Sümeyra Doğan3, Bahri Akdeniz4, Nezihi Barış4, Uygar Teomete5,
Leyla İyilikçi6
Radiology Clinic, Mardin State Hospital, Mardin, 2Department of Radiology, Dokuz Eylül University School of Medicine, İzmir, 3Radiology Clinic, Mardin Women’s and Children’s Hospital, Mardin, 4Department of Cardiology, Dokuz Eylül University School of Medicine,
İzmir, Turkey, 5Department of Radiology, University of Miami Miller School of Medicine, Miami/Florida, USA, 6Department of Anesthesi-
1
ology and Reanimation, Dokuz Eylül University School of Medicine, İzmir, Turkey
ABSTRACT
Aim To evaluate the eficacy of the Cardiac Magnetic Resonance
Perfusion (CMRP) method in detection of Coronary Artery Disease (CAD) by comparing CMRP indings with the results of Coronary Computed Tomography Angiography (CCTA) or Catheter
Coronary Angiography (CCA).
Corresponding author:
Mehmet Sait Doğan
Radiology Clinic, Mardin State Hospital,
Mardin
Nur Mahallesi, Diyarbakır Bulvarı Yan
Yolu, 47200, Mardin, Turkey
Phone: +90-480-2121048 ;
Fax: +90-480-2125865 ;
Email: [email protected]
Original submission:
21 August 2012;
Accepted:
19 September 2012.
Methods Thirty one patients in whom CMRP was performed
along with CCTA or CCA within a month after CMRP between
December 2009 and November 2010 were selected for the study.
In CMRP, after adenosine administration as a stress agent Balanced
TFE sequences were used to gather dynamic images that include
the myocardial irst pass of contrast media. Image analysis was performed visually. CMRP indings were compared to CCTA or CCA
results for each coronary artery territories and for all territories.
Results Sensitivity, speciicity, accuracy, positive predictive value, and negative predictive value of CMRP test in the identiication of patients with signiicant (≥70%) coronary artery stenosis
were 94.7%, 83%, 90.3%, 90%, and 90.9% for all coronary arteries, respectively; 94.4%, 84.6%, 90.3%, 89.4%, and 91.6% for left
anterior descending artery, respectively; and 100%, 100%, 100%,
100%, and 100% for circumlex and right coronary artery, respectively. There was no statistically signiicant difference between angiography methods (CCTA/CCA) and CMRP (p>0.05). Methods
had good to perfect consistency (ĸ = 0.79-1.00).
Conclusion CMRP test seems to be a reasonable alternative for
catheter angiography, which is considered the gold standard for
evaluation of CAD and exclusion of signiicant coronary artery
obstruction.
Key words cardiac catheterization, computed tomography, coronary angiography, perfusion magnetic resonance imaging
Med Glas Ljek komore Zenicko-doboj kantona 2013; 10(1):63-69
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Medicinski Glasnik, Volume 10, Number 1, February 2013
INTRODUCTION
The major cause of Ischemic Heart Disease (IHD)
is reduction of blood low through coronary arteries due to atherosclerosis. Detection of coronary
atherosclerosis and evaluation of myocardial hypoperfusion is important for decisions regarding
an appropriate and effective therapeutic approach, including catheter based interventions or surgical options (1).
Myocardial perfusion, deined as blood volume
lowing through a given myocardial area in a determined time, is one of the irst steps of the ischemic cascade and may be detected prior to electrocardiogram (ECG) alterations, clinical symptoms,
or myocardial wall motion abnormalities (2). The
most common clinical method performed for detecting perfusion abnormalities is single photon
emission computerized tomography (SPECT) (2).
The validity of this method is evident in a number of multi-center trials, however, low spatial and
temporal resolution, exposure to ionising radiation,
and attenuation artifacts are its signiicant limitations (2). In contrast, stress Cardiac Magnetic Resonance Perfusion (CMRP) does not emit ionising
radiation, has high spatial and temporal resolution,
is able to evaluate subendocardial perfusion, and
is a non-invasive modality; therefore it is the preferred method for myocardial perfusion evaluation
(2,3). In 2006, a consensus panel from the American College of Cardiology Foundation (ACCF)
deemed the following indications as appropriate
uses of stress perfusion MRI: evaluating chest pain
syndromes in patients who have intermediate probability of coronary artery disease (CAD) and ascertaining the physiologic signiicance of indeterminate coronary artery lesions (4). Recent studies
have shown that stress CMRP has high sensitivity
and speciicity for IHD diagnosis, and negative
stress CMRP was considered a perfect test for ruling out a major cardiac event (2,3,5).
In light of this information, the present study aims
to compare the indings of CMRP with the results
of CCTA or CCA and to evaluate the eficacy of
CMRP in detection of CAD.
PATIENTS AND METHODS
Patients
Thirty one patients were selected at the Department of Radiology, Dokuz Eylül University
Hospital between December 2009 and November
64
2010 in whom CMRP, as well as CCA or CCTA,
were performed within one month after CMRP.
All patients were investigated for the criteria that
are contraindicated for the Magnetic Resonance
Imaging (MRI) including claustrophobia, cardiac
pacemaker, and inappropriate surgical and prosthetic materials for MRI. Perfusion MRI was
performed after 12-hour fasting. For maximum
response to vasodilatory effect of adenosine, if
patients were using calcium channel blockers, beta-blockers and nitrates these were discontinued
24 hours before the procedure. Also consumption
of foods and beverages containing caffeine was
discontinued 12 hours prior to the procedure. Patients with conditions that are contraindicated for
adenosine administration including signiicant
valvular stenosis, unstable angina, obstructive
pulmonary disease, severe arterial hypertension, and history of myocardial infarction within
3 days prior to the procedure were excluded. An
anesthesia team was ready during the procedure
in order to address any potential adverse effects of
adenosine. All patients provided written informed
consents before the procedure. This retrospective
study was approved by the Ethics Committee of
Dokuz Eylül University School of Medicine.
Cardiac MR perfusion techniques
Although the present study was retrospective, the
standard sequences of adenosine-stress CMRP
imaging were used in each patient.
Cardiac Magnetic Resonance Perfusion imaging
was performed with 1.5 Tesla MRI device (Philips Intera Achieva; Philips Medical Systems,
Holland) with ECG, respiratory pad and 5-phased
array cardiac coil that was applied to the anterior
chest of the patient in the supine position.
In stress perfusion imaging, 140 microgram/kg/
min dosing of adenosine was administered for 4
minutes via IV infusion as a vasodilator (Adenosin-L.M., Apoteket AB, Sweden). At the end of the
4th minute, 0.08 mmol/kg gadobutrol (Gadovist,
Bayer Schering, Germany) followed by 20-50 ml
saline (4-5 ml/sec) IV bolus was administered. In
the mean time, through the short axis perpendicular
to the long axis of left ventricle, 3-4 slices with slice thickness of 10 mm and interval of 10 mm from
the left ventricle basal, midventricular layer, and
apex were displayed at each heart beat. From these slices, 60 heart beat long dynamic images were
gathered that included myocardial irst pass of con-
Doğan et al. MR perfusion in coronary artery disease
trast media with Balanced Turbo Field Echo (TFE)
sequence. Imaging parameters for Balanced TFE
sequences were as follows TR: 2.4 msec; TE: 1.2
msec, Flip Angle: 50 degrees, FOV: 350-400 mm;
matrix: 128x256, Sense factor: 2, Slice width: 10
mm and Slice Interval: 10 mm. For higher quality
images, patients were asked to hold breath at the
end of the expirium during dynamic assessment.
In rest perfusion imaging, after waiting 10 minutes
for clearance of gadolinium from the blood pool,
dynamic images were taken with the same parameters that were used before without adenosine
infusion. During this 10-minute waiting period,
dynamic images including the entire left ventricle
through the short axis with Steady-state Free Precession (SSFP) sequence were taken (functional
imaging). The myocardial perfusion MRI protocol
used in our study is summarized in Figure 1.
Image analysis
For each coronary artery territory, CMRP indings
were evaluated retrospectively by two radiologists
separately (one of them was experienced on cardiac imaging) and they were blinded to the results of
CCTA and CCA assessment of perfusion defect.
Perfusion defect is deined as hypointense subendocardial regions in comparison with the normal myocardium at early myocardial signal enhancement. If
discordance occurred in the results, the radiologists
re-examined the indings and reached a consensus.
Then, CMRP results were compared to that of angiography techniques (CCTA or CCA). Obstructions of 70% or greater detected at angiography were
considered positive for signiicant stenosis.
between analyses. For the Kappa test, ≤ 0.20, 0.21
- 0.40, 0.41 - 0.60, 0.61 - 0.80 and 0.81 - 1.00 values were considered bad, weak, moderate, good and
perfect harmonization, respectively.
RESULTS
Twenty ive of 31 patients were males (80.6%)
and six of 31 (19.4%) were females (age range,
22-88 years). All patients had chest pain. The interval between CMRP imaging and angiography
methods varied 0 to 18 days (mean 4.2 days). Two
patients had a history of coronary artery bypass
surgery, nine had coronary artery stents. Five patients with stent had obstruction or occlusion.
Figure 1. Illustration of study protocol
A total of 93 coronary artery territories consisting
of left anterior descending artery (LAD), circumlex artery (Cx) and right coronary artery (RCA)
territories were evaluated and it was revealed that
32 of these included perfusion defects.
Twenty of 31 patients had perfusion defect in at
least one of the coronary artery territories. Five
patients had perfusion defects at all three LAD,
Cx and RCA territories (Figure 2), one patient
A)
B)
C)
D)
E)
F)
Statistical analysis
Cardiac Magnetic Resonance Perfusion imaging
results of 31 patients were compared to those of
angiography (CCTA or CCA) according to the
coronary artery territories.
Angiography indings were considered as gold
standard, and then CMRP indings were compared
to angiography with respect to perfusion defects
for each case and also each coronary artery perfusion territory. Then sensitivity, speciicity, accuracy, positive predictive value and negative predictive value were calculated. Analysis of diagnostic
differences for all comparisons mentioned above
was performed using the McNemar test. P<0.05
value was considered signiicant for the McNemar
test. The Kappa test was used for harmonization
G)
H)
Figure 2. A) wide perfusion defects at each of three coronary artery territories of the left ventricle (stress-CMRP test images,) A-C)
no perfusion defect was detected in rest perfusion images, D-F), an
obstruction of 95% at Cx artery (long arrow) and occlusions at LAD
artery (short arrow) and G,H) at RCA (thick arrow) (CCA)
65
Medicinski Glasnik, Volume 10, Number 1, February 2013
A)
B)
C)
D)
had perfusion defects at LAD and RCA territories, one had perfusion defects at LAD and CX
territories. One patient had a perfusion defect at
the Cx artery territory and the remainder (12 patients) had perfusion defect at LAD artery territory (Figures 3, 4).
Angiography studies (CCTA or CCA) revealed
that 18 of 20 patients with perfusion defects had
70% or greater obstruction in at least one of the
three coronary arteries (LAD, Cx or RCA) or
their branches. One patient had no coronary artery obstruction in CCA, the other patient had no
coronary artery obstruction in CCTA, however,
there was myocardial bridging at the middle segment of LAD artery (Figure 4).
During the evaluation of both coronary arteries
and perfusion territories, angiography detected
signiicant luminal narrowing (≥70%) or occlusion in LAD arteries of 17 of 19 patients who had
perfusion defect in LAD artery territory, and in
all RCA and/or Cx arteries who had a perfusion
defect in RCA and/or Cx artery territories. Stenosis of 90% was detected at the D1 branch of LAD
artery in one of 11 patients who did not have perB)
66
Figure 5. Normal findings in stress-cardiac MR perfusion study
(A-D) in a patient, with obstructive CAD. There was no perfusion
defect at short axis views obtained from the apex of left ventricule
(A) to the basal layer (D). CCA (E) revealed a high-grade (90%)
stenosis of the diagonal 1 branch of LAD artery (It was also reported as a thin vessel at CCA).
fusion defects (Figure 5). In this case, stenosis of
60% at the distal LAD artery and 30% obstruction at the RCA were also observed. No signiicant
stenosis (≥70%) was detected in the coronary
arteries of 10 patients who did not have perfusion defect. Similarly, coronary arteries associated
with normal perfusion areas of the patients with
perfusion defect were not signiicantly narrowed.
Only ive patients had stenosis with up to 50%
obstruction in coronary arteries or branches.
The overall sensitivity, speciicity, accuracy, positive predictive value and negative predictive
value of CMRP imaging in detecting signiicant
coronary artery stenosis (≥70%) at angiography were 94.7%, 83%, 90.3%, 90% and 90.9%,
respectively. There was no statistical difference
between the two methods (p>0.05). Harmonization between the two groups was “good”
(ĸ=0.79).
When evaluating each separate coronary artery
territory; sensitivity, speciicity, accuracy, positive
Table 1. Sensitivity, specificity, accuracy, positive predictive
value and negative predictive value of Cardiac MR perfusion
test in detecting significant (70% or greater) obstruction at
CCA-CCTA
Diagnostic
Sensi- Speci- Accu- Positive Negative
difference Consitivity icity racy predictive predictive
between stency
(%)
(%) (%) value (%) value (%)
methods
C)
Figure 4. In stress perfusion test (A), short axis image through
left ventricular basal layer showed hypointensitiy at anteroseptal wall in concordance with subendocardial perfusion defect,
whereas, there was no perfusion defect at the same level at rest
perfusion image (B). In CCTA (C), no stenosis was detected in
coronary arteries. However, it was revealed that there was myocardial bridging at the middle segment of LAD artery (arrow).
E)
D)
C)
Figure 3. In stress perfusion test, short axis images obtained
from apical (A) and midventricular (B) layer of the left ventricule
showed hypointensities at inferoseptal wall in concordance with
perfusion defects, whereas, there was no perfusion defect at the
same levels at rest perfusion images (C,D). In CCA (E), RCA was
reported to be non-dominant and an obstruction of 80% at the
origin of diagonal 1 branch of LAD artery was detected (arrow).
Because of non-dominant RCA, perfusion defects at inferoseptal
wall were thought to be at LAD artery territory and to be associated with the obstruction of LAD artery
A)
B)
A)
E)
LAD
AT
94.4
84.6
90.3
89.4
91.6
none
good
CX
AT
100
100
100
100
100
none
perfect
RCA
AT
100
100
100
100
100
none
perfect
All
ATs
94.7
83
90.3
90
90.9
none
good
CCA, catheter coronary angiography; CCTA, coronary computed
tomography angiography; LAD, left anterior descending artery; CX,
circumlex artery; RCA, right coronary artery; AT, artery territory.
Doğan et al. MR perfusion in coronary artery disease
and negative predictive value of CMRP imaging
for detecting signiicant obstruction in associated
coronary artery indicated at angiography (CCTA
or CCA) were 94.4%, 84.6%, 90.3%, 89,4%
and 91.6% respectively for LAD; 100%, 100%,
100%, 100% and 100% respectively for Cx; and
100%, 100%, 100%, 100% and 100% respectively for RCA. There was no diagnostic difference
between methods (p>0.05). Harmonization of
two methods resulted in ĸ values of 0.80, 1.00
and 1.00 for LAD artery, Cx and RCA territories, respectively and harmonization was “good”,
“perfect” and “perfect”, respectively (Table 1).
DISCUSSION
This study evaluates the eficacy of CMRP imaging in detecting CAD in comparison to CCTA or
CCA results, revealing high sensitivity and speciicity. This is the irst adenosine-stress CMRP
study on this subject in Turkey.
Hamon et al. (6) completed a meta-analysis of
articles that had been published up to July 2009.
This analysis included 20 trials and a total of 1678
patients in whom CMRP imaging was performed
with adenosine as the pharmacological stress
agent and another 5 trials with a total of 417 patients in whom dipiridamol was used as the pharmacologic stress agent in CMRP imaging. Sensitivity and speciicity for detecting CAD were
90% and 81% respectively in the irst group and
86% and 76% respectively in the latter. We used
adenosine as the stress agent and found both high
sensitivity (94.7%) and high speciicity (83%).
Semi-quantitative analysis requires additional
time; it is not appropriate for daily practice and
there is no consensus in post-processing protocol.
Therefore, we preferred the visual method.
It is stated that as a stress test, CMRP imaging
should be avoided in patients with signiicant
valvular stenosis, unstable angina, obstructive
pulmonary disease, recent myocardial infarction, and severe arterial hypertension because of
the hemodynamic disruption and possible side
effects of adenosine (7), whereas, Greenwood et
al (8) suggest that adenosine-stress CMRP imaging is a safe method in early after ST elevated
myocardial infarction (STEMI) patients. In our
study, the patients in whom adenosine usage may
be hazardous were excluded from MRI perfusion
examination.
Plein et al. (9) evaluated cardiac MRI tests that
include 4 parameters: perfusion imaging, myocardial function, late enhancement, and coronary
artery anatomy. In this study, CMRP imaging itself is suficient for detecting coronary artery stenosis with high sensitivity and speciicity (88%
and 83%, respectively). But in cases of equivocal
results or cases with insuficient evaluation resulting from artifacts (motion artifact, respiratory
artifact, ring artifact) other cardiac MRI methods
may be combined to increase sensitivity.
Klem et al. (10,11) stated that the combination
of CMRP imaging with late enhancement would increase speciicity and accuracy. Moreover,
according to the results of another study this
combination did not seem to affect sensitivity and
speciicity. (12). We evaluate only the eficacy of
CMRP in detecting signiicant coronary artery
stenosis at angiography and found high sensitivity, speciicity and accuracy. These results are
similar to that of literature, with the exception of
the studies by Klem et al. (10,11).
Merkle et al. (13) stated that CMRP imaging had
low positive predictive value (59%) in the primary diagnosis of CAD. They thought that the
higher rate of risk factors in these patients supported the idea that those patients more frequently
had non-vascular conditions like hypertensive heart disease, syndrome X, or coronary endothelial
dysfunction, which might be the cause of false
positive results and ischemic pain. Burgstahler et
al. (14) found severe myocardial hypertrophy in
2 patients with false positivity. Hamon et al. (6)
stated that the reason for higher sensitivity than
speciicity was the high rate of false positives. We
also found that sensitivity was higher than speciicity. Our two cases had MR perfusion defects in
the LAD artery territory, but there were no signiicant coronary artery stenosis. One had LIMALAD and AO-OM-SVG bypass grafts with patent
vascular lumen and suficient low on CCA. In
this case, perfusion defect is considered to be due
to microvascular disease or persistent microvascular obstruction. The other case was not observed to have signiicant coronary artery stenosis in
CCTA, however, there was myocardial bridging
at the middle segment of LAD artery and this is
thought to explain the perfusion defect.
Cheng et al. (15) reported that 3 T CMRP imaging
was superior to 1,5 T CMRP imaging. Meyer et
67
Medicinski Glasnik, Volume 10, Number 1, February 2013
al. (16) used 3 T MR device and performed adenosine-stress CMRP test. When they compared
the results to those in the literature at 1.5 T based
on a visual analysis, they found that their protocol was at least as eficacious as those at 1.5 T.
Our results are similar to the study by Meyer et
al. with 3 T MR Devices.
Merkle et al. (13) found that the sensitivity of
CMRP imaging for diagnosis of coronary artery
stenosis was higher in LAD artery territory than
that of Cx and RCA territories. They stated that
a possible explanation might be the use of surface
coil leading to lower signal intensities at lateral and
inferior segments in especially obese population.
In our study, we evaluated eficacy of CMPR
method for detection of signiicant coronary artery stenosis in each coronary artery territory
separately. Sensitivity, speciicity, and accuracy
were higher than the values in literature. These
higher values, especially for Cx artery and RCA
territories, are thought to be due to fewer perfusion defects in these territories in comparison to
LAD artery territory, and relatively low number
of patients with Cx artery and RCA obstruction.
In our study, one of the patients without perfusion defects in CMRP imaging had an obstruction
of 90% at D1 branch of LAD in CCA and it was
noted as a thin vessel (Fig. 5). Lack of perfusion
defect in this patient may be explained because
of thin structure of obstructed artery and possible
collateral blood low.
One of the major limitations of our study is that
we did not compare the CMRP method with an
accepted test for evaluating perfusion defects such
as SPECT. Another limitation was the use of angiography methods for comparison in a perfusion
study. CCA is the standard diagnostic method for
detecting signiicant coronary artery obstruction
in daily practice. However, it is not appropriate to
evaluate the hemodynamic signiicance of coronary artery obstruction and the functional signiicance of obstruction is more important than morphological obstruction in the prognosis of CAD.
The invasive gold standard method in detecting
functional signiicance of obstruction is measurement of pressure dependent fractional low
reserve (FFR) (17). Rieber et al. (18) compared
CMRP imaging to CCA and FFR in accordance
68
with detecting functional status of CAD and found a strong correlation between CMRP method
and FFR measurement. FFR was not measured in
patients included in our retrospective study. We
considered angiography as the reference method,
similar to most studies in the literature. Another
limitation of our study was the absence of a single
angiography method. Coronary artery evaluation
was performed with CCA in 21 patients and CCTA
in 10 patients in our study. However, recent advances in CCTA with the development of Multi-Detector Computed Tomography technology provide
high sensitivity, speciicity, and accuracy for detection of CAD (19). Because of its high negative
predictive value, we used CCTA as an alternative
method to catheter angiography, especially in patients without perfusion defects. Small study sample
and retrospective design are two additional factors
that decrease statistical power. Further prospective
studies with larger sample size are needed.
Cardiac MR Perfusion test has high sensitivity
and speciicity in detecting signiicant coronary
artery stenosis when compared to catheter coronary angiography. We used adenosine as a pharmacologic stress agent in this technique. Sensitivity, speciicity, accuracy, positive predictive
value, and negative predictive value in detecting
70% or greater obstructions of coronary arteries in catheter coronary angiography or coronary
CT angiography were high, similar to literature.
There was no signiicant diagnostic difference
between these methods and the harmonization
was good-to-perfect.
In conclusion, cardiac MR perfusion test seems
to be a reasonable alternative for catheter angiography, which is considered the gold standard for
evaluation of CAD and exclusion of signiicant
coronary artery obstruction. We suggest that as
a non-invasive method, CMRP imaging could be
used more commonly in clinical practice in order
to decrease the use of invasive procedures like
catheter angiography.
FUNDING
No speciic funding was received for this study.
TRANSPARENCY DECLARATIONS
Competing interests: none to declare.
Doğan et al. MR perfusion in coronary artery disease
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