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Additional value of myocardial perfusion imaging during
dobutamine stress magnetic resonance for the assessment
of coronary artery disease
R. Gebker1, MD; C. Jahnke1, MD; R. Manka1, MD; A. Hamdan1, MD; B. Schnackenburg1,
PhD; E. Fleck1, MD; I. Paetsch1, MD
1 German Heart Institute Berlin, Germany
Corresponding author:
Dr. Rolf Gebker,
Deutsches Herzzentrum Berlin,
Augustenburger Platz 1
13353 Berlin
Germany
Tel: +49 30 45932457
Fax: +49 30 45932458
Email: [email protected]
word count: 6170
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Abstract
Background: Dobutamine stress magnetic resonance (DSMR) imaging has emerged as a
valuable tool for the detection of inducible wall motion abnormalities (WMA). The role of
perfusion imaging during DSMR is not well defined. We examined whether the addition of
myocardial perfusion imaging during DSMR provides incremental benefit for the evaluation
of coronary artery disease (CAD).
Methods and Results: DSMR was combined with perfusion imaging (DSMRP) in 455
consecutive patients who were scheduled for clinically indicated invasive coronary
angiography. Perfusion images were acquired in three standard short axis views at rest and
during maximum dobutamine-atropine stress. Wall motion and perfusion images were
interpreted sequentially, blinded to other data. Significant (≥70%) stenoses were present in
285 patients on invasive coronary angiography. The use of DSMRP vs. DSMR increased
sensitivity (91% vs. 85%, P=0.001), but not specificity (70% vs. 82%, P=0.001) resulting in
identical overall diagnostic accuracy (84% vs. 84%, P=n.s.; Youden index 0.61 vs. 0.67).
DSMRP enabled the correct diagnosis of CAD in an additional 13% of DSMR negative
patients at the cost of 11% more false positive cases.
Conclusion: The addition of perfusion imaging during DSMR improves sensitivity for the
diagnosis of CAD but does not enhance overall diagnostic accuracy due to a concomitant
decrease in specificity.
Key words: magnetic resonance; coronary disease; myocardium; perfusion; dobutamine; wall
motion analysis
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Introduction
Dobutamine stress magnetic resonance wall motion imaging (DSMR) is an established
clinical method with high diagnostic and prognostic value for the evaluation of coronary
artery disease (CAD) (1-4). Due to a high intrinsic contrast between intracavitary blood and
the endocardium DSMR allows an accurate delineation of the endocardial border and thus
compares favorably with stress echocardiography (5, 6). Nevertheless, wall motion studies
during dobutamine have a number of inherent limitations, e.g. interobserver variability of
qualitative wall-motion scoring (7). In addition, the presence of left ventricular hypertrophy
(LVH) (8) and resting WMAs (9) are known to reduce diagnostic accuracy and may impair
the ability of DSMR to detect CAD.
The capability of cardiovascular magnetic resonance (CMR) to evaluate myocardial perfusion
has been demonstrated in several studies as well (10-12). While vasodilators like adenosine
are usually applied to perform perfusion studies, dobutamine may cause enough myocardial
blood flow heterogeneity to detect perfusion deficits in myocardial territories supplied by a
coronary artery with a critical stenosis (13, 14). In nuclear and echocardiographic studies (15,
16) dobutamine proved to be a useful stress agent for the induction of myocardial perfusion
deficits. Recent advances in magnetic resonance gradient performance and innovative pulse
sequence design led to a substantial increase in acquisition speed of CMR first pass perfusion
imaging thereby allowing multislice imaging at higher heart rates (17).
Thus, we sought to determine whether CMR perfusion imaging during high dose dobutamine
stress (DSMRP) adds additional diagnostic value to DSMR for the detection of ischemia in
patients with known and suspected CAD, as defined by invasive coronary angiography.
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Materials and Methods
Patient population
The study was conducted in accordance with the standards of the Charité Ethics Committee.
Written informed consent was given by all patients. DSMRP was performed prospectively in
455 consecutive patients who were scheduled for a clinically indicated coronary angiography
with suspected and known CAD. Patients with contraindications to either MR imaging (non-
compatible biometallic implants or claustrophobia) or dobutamine (acute coronary syndrome,
severe hypertension, significant aortic stenosis, myocarditis, endocarditis, pericarditis), and
patients with arrhythmia were not considered for study inclusion. All patients were instructed
to refrain from any beta-blockers or nitrates 24 hours prior to the MR study.
MR Imaging
Imaging Protocol
MR was performed with the patient in supine position with a 1.5 T MR scanner (Philips Intera
CV, Best, The Netherlands) equipped with a Nova gradient system (33mT/m; 160 mT/m/ms)
based on Philips release 11. A five-element cardiac synergy coil was used for signal
reception. Cardiac synchronization was performed by using four electrodes placed on the left
anterior hemithorax (vector electrocardiography), and scans were triggered on the R wave of
the ECG.
Figure 1 shows the course of the examination. The patients underwent a standardized CMR
examination including the following steps: First, fast survey images were acquired in three
standard planes (transversal, sagittal and coronal) for localization of the heart. Second, single-
angulated, single slice cine scan of the left ventricle was performed on a transverse view.
Third, a double-angulated, single slice cine scan of the left ventricle was planned on the
previous view. Fourth, cine-imaging of three short axis views and three long axis views (four-
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chamber, two-chamber and three-chamber view) were acquired. The three short axis views
were distributed to cover the heart at the basal, equatorial and apical position by adjusting the
gap between the sections. The distance between the apical slice and the apex on the one hand
and the basal slice and the mitral valve on the other hand were identical. Fifth, perfusion test
scans using an identical geometry as the three short axis cine views were conducted to
carefully exclude any wrap around or trigger artifacts before starting the actual index test.
Sixth, rest perfusion imaging was performed using 60 dynamic acquisitions during the
administration of an intravenous bolus of 0.1 mmol/kg Gd-DTPA (Magnevist®, Bayer,
Berlin, Germany) at an injection rate of 4 ml/s followed by a flush of 20 ml of saline solution
at the same rate. Patients were instructed to hold their breath as long as possible during
imaging and to continue breathing shallowly when they could no longer hold their breath.
Seventh, a standard DSMR examination (18) was carried out following a high-dose regimen
(up to 40 µg/kg/min) plus atropine (up to 2 mg) if needed to reach target heart rate defined as
age-predicted submaximal heart rate [(220-age) x 0.85]. Eighth, during maximum dobutamine
stress perfusion imaging was performed using the same geometry and giving an identical
bolus of contrast agent as during rest imaging. Blood pressure and heart rate were monitored
continuously during the administration of dobutamine and the contrast agent. Termination
criteria were severe chest pain, significant arrhythmia, hypertension (blood pressure ≥
240/120 mm Hg), systolic blood pressure drop of > 40 mm Hg, and any intolerable side effect
regarded as associated with dobutamine (6). If chest pain or arrhythmias did not resolve after
termination of dobutamine infusion esmolol (50-100 mg) was given intravenously. Ninth,
standard delayed enhancement imaging was carried out 10 minutes after termination of
dobutamine infusion.
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MR Sequence Design
For cine imaging, a balanced steady-state free precession (bSSFP) sequence in combination
with parallel imaging (SENSitivity Encoding, SENSE-factor 2.0) and retrospective gating (50
phases per cardiac cycle) was used during an end-expiratory breath hold of 9 seconds
(repetition time (TR), 3.4 ms; echo time (TE), 1.7 ms; flip angle (FA), 60°). In-plane spatial
resolution was 1.8 x 1.8 mm with a slice thickness of 8 mm.
For perfusion imaging the bSSFP sequence parameters were: TR/TE/FA = 2.8 ms/ 1.4 ms/
50°, SENSE-factor 3.0, raw data matrix of 160 x 143, rectangular field of view 450 x 428
cm2, and voxel size: 2.8 x 3 x 10 mm3. Three short axis views (one basal, mid-ventricular and
apical slice) were acquired every second heart beat during dobutamine stress with 2 slices
being acquired during the first heart beat and the remaining slice being acquired during the
second heart beat. A separate saturation pulse was applied to each slice (delay 100 ms). A half
alpha/half TR startup mode with additional 8 startup echoes had been applied before real data
acquisition started in order for the SSFP magnetization to reach equilibrium. The acquisition
time per image was 145 ms.
Delayed enhancement imaging was performed using an inversion prepared 3D-spoiled-
Gradient-Echo-Sequence (TR/TE/FA = 3.6 ms/ 1.7 ms/ 15°, voxel size: 1.5 x 1.7 x 10 mm³,
interpolated to 1.5 x 1.7 x 5 mm³) with an individually adapted IR-delay (200-250 ms).
MR Image Analysis
Measurements of left ventricular wall thickness were performed immediately basal to the tips
of the papillary muscles during end-diastole on the basal short axis view. LVH was defined as
an interventricular septum thickness ≥ 12 mm (19). Isolated basal septal hypertrophy was
accounted for by carefully double-checking our measurements in the short axis view with the
four- and three-chamber long axis views. Left ventricular ejection fraction was determined
with the combined triplane model (20).
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Segmental analysis of wall motion was performed in consensus by two observers blinded to
patients´ identities and results of the perfusion study and coronary angiography using a
synchronized quad-screen image display and applying a standard 16-segment scoring system
(1 = normal, 2 = hypokinetic, 3 = akinetic, or 4 = dyskinetic). A positive DSMR was defined
as a new or worsening WMA in ≥ 1 segments.
Perfusion scans were interpreted in consensus by two observers blinded to the results of
DSMR and invasive coronary angiography. The readers were presented with anonymized
MRI studies including perfusion at stress and rest and delayed enhancement. For visual
grading of perfusion deficits, stress and rest perfusion scans were magnified 2-fold and
displayed simultaneously. Ischemia was considered present when segments without delayed
enhancement showed a perfusion deficit of ≥ 25% of the transmural extent during stress
perfusion but not at rest (stress-inducible deficit) for ≥ 3 consecutive image frames or when
segments with non-transmural delayed enhancement demonstrated additional stress-inducible
perfusion deficits.
For the overall assessment, patients were judged to have CAD if there were inducible WMAs
or inducible perfusion deficits evident. These overall results were compared with those from
DSMR assessment.
To assess interobserver variability for interpretation of DSMRP, two independent observers
scored perfusion imaging qualitatively based on the reading criteria mentioned above in a
randomly selected sample of 50 studies. The interobserver agreement in our laboratory is 91
% for DSMR (21).
The authors had full access to and take full responsibility for the integrity of the data. All
authors have read and agree to the manuscript as written.
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Coronary angiography
All 455 patients underwent coronary x-ray angiography within 1 month after MR imaging.
Conventional coronary x-ray angiography was performed using the transfemoral Judkins
approach with selective catheterization of the left and right coronary artery system in multiple
projections. The classification of patients into those with and without obstructive CAD was
based on their current coronary status as assessed by invasive angiography. The angiograms
were evaluated visually for the presence of significant stenoses (i.e. ≥ 50% and ≥ 70% luminal
diameter reduction) in major epicardial coronary arteries and their branches (vessel diameter
≥ 2.0 mm) by highly experienced interventionalists; all readers were blinded to the MR data.
In patients with bypass grafts, significant arterial or vein graft stenoses were assigned to the
recipient native coronary vessel. The angiographic results were then classified as 1-, 2- and 3-
vessel disease or exclusion of significant obstructive coronary artery disease.
Statistical analysis:
Statistical analysis was performed using the SPSS software package release 15.0.1 (Chicago,
USA). For all continuous parameters, mean ± standard deviation is given. Comparisons were
made with two sample t tests for continuous data and chi-square tests for discrete. McNemar´s
test was used to compare the diagnostic accuracy of techniques. Sensitivity, specificity and
diagnostic accuracy were calculated according to standard definitions. The Youden index,
defined as sensitivity plus specificity minus 1, was also applied to compare the two tests (22).
The Wilcoxon test was applied to paired samples. Agreement between the two methods and
between observers was assessed with kappa statistics (23). Statistical tests were two-tailed;
significance was considered if p < 0.05.
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Results
Dobutamine Stress Test
Assessment of wall motion at rest was feasible in all patients. Table 1 summarizes the reasons
for non-diagnostic tests. Technical difficulties like poor ECG-triggering and insufficient
image quality during stress precluded interpretation of wall motion and perfusion images in
12 (3%) patients. In 29 (6%) patients target heart rate was not achieved either due to a
maximum infusion of dobutamine/atropine (13 patients) without reaching target heart rate or
because of early termination of the examination as a result of limiting side effects (16
patients); thus, DSMRP was feasible in 414 patients (91%). The clinical data of the final
population of the study is presented in Table 2.
The mean dosages of dobutamine and atropine given were 34 ± 7.4 µg/kg/min and 0.3 ± 0.4
mg, respectively. Atropine was administered in 217 (52%) patients. Table 3 summarizes the
hemodynamic data. Most patients (62%) experienced side effects during the infusion like
chest pain (54%) or dyspnea (32%). One patient had self-limiting ventricular tachycardia
during dobutamine infusion. No death, MI or ventricular fibrillation occurred. Target heart
rate was achieved in 388 (94%) patients and 26 patients (6%) developed new WMAs before
reaching target heart rate; in these cases stress perfusion imaging was performed at this stress
level and the dobutamine infusion was terminated.
Coronary Angiography
Coronary artery disease (≥ 70% stenosis) was present in 285 (69%) patients. Among these
patients, 167 (59%) had single-vessel, 99 (35%) had two-vessel, and 19 (7%) had three-vessel
CAD. The remaining 129 (31%) patients had no significant CAD.
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Results of DSMR and DSMRP
New or worsening WMAs occurred in 264 (64%) patients. DSMR had a sensitivity of 85%
for the detection of CAD, as defined by ≥ 70% stenosis by coronary angiography and a
specificity of 82%. Stress inducible perfusion deficits were detected in 269 (65%) patients. A
stress inducible WMA or perfusion deficit occurred in 299 patients (72%). Perfusion deficits
occurred in the presence of inducible WMAs in 234 of 264 patients (89%) and in the absence
of inducible WMAs in 35 of 150 patients (13%).
The use of DSMRP vs. DSMR to detect CAD as defined by ≥ 70% luminal narrowing
increased sensitivity (91% vs. 85%, P=0.001, Table 4), while specificity decreased (70% vs.
82%, P=0.001) resulting in identical overall diagnostic accuracy (84% vs. 84%, P n.s.). When
defining CAD as ≥ 50% luminal narrowing, diagnostic accuracy increased significantly for
DSMR vs. DSMRP from 82% to 85%, respectively (P<0.001). The Youden index suggested
that DSMRP did not provide a measurable diagnostic advantage in the overall study cohort
(Table 4). However, in those 150 patients without inducible WMAs, we found that adding
DSMRP enabled the correct diagnosis in an additional 13% (19/150, ≥ 70% stenosis) or 15%
(23/150, for ≥ 50% stenosis) of patients, respectively. In 68% (13/19) of these patients the
number of ischemic segments was ≥ 3; 42% (8/19) had multivessel CAD (i.e. 2- or 3-vessel
CAD). This advantage in sensitivity came at the cost of 11% (16/150, ≥ 70% stenosis) or 8%
(12/150, for ≥ 50% stenosis) more false positive cases, respectively.
Subgroup analysis
DSMRP led to a significant increase in sensitivity and diagnostic accuracy in patients with
LVH from 79% to 91% (P<0.001) and from 80% to 87% (P<0.001, Table 4), respectively,
without significant reduction in specificity from 85% to 74% (P=0.25). The Youden index
was similar for DSMRP vs. DSMR (0.65 vs. 0.64) when defining CAD as ≥ 70% stenosis.
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With DSMR alone sensitivity decreased in patients with LVH vs. patients without LVH (79%
vs. 88%, P=0.52), while specificity increased (85% vs. 81%, P=0.63).
In patients with resting WMAs, the use of DSMRP compared to DSMR also led to a
significant increment in sensitivity from 82% to 89% (P=0.002) with a nonsignificant
reduction in specificity from 73% to 61% (P=0.125) and a significant increase in diagnostic
accuracy from 80% to 84% (P<0.001). However, the Youden index implied that DSMR was
superior to DSMRP in patients with resting WMAs (see Table 4). With DSMR alone
sensitivity and specificity decreased for patients with resting WMAs vs. patients without
resting WMAs (82% vs. 88% (P=0.53) and 73% vs. 85% (P<0.001), respectively). The results
for using ≥ 50% luminal narrowing for the definition of CAD can be found in Table 4.
Representative imaging examples are given in Figures 2 and 3.
In patients with prior CAD the use of DSMRP led to a significant increment in sensitivity
from 83% to 90% (P<0.001) with a significant decline in specificity from 75% to 65%
(P=0.03) and a significant increase in diagnostic accuracy from 82% to 85% (P<0.001). In
patients without prior CAD DSMRP was associated with a significant increase in sensitivity
from 87% to 95% (P<0.001) as well. However, the decrease in specificity from 88% to 74%
(P<0.001) led to a decrease in overall diagnostic accuracy from 87% to 84% compared to
DSMR alone when CAD was defined as ≥ 70% luminal narrowing.
In patients with single-vessel CAD the use of DSMRP significantly improved sensitivity from
84% to 91% (P=0.001).
In patients with no LVH, no resting WMAs, no prior CAD and no single-vessel CAD the use
of DSMRP compared to DSMR led to a non-significant increase in sensitivity from 88% to
94% (P=0.125) and a significant decrease in specificity from 87% to 72% (P=0.02) resulting
in a significant decrease in diagnostic accuracy from 87% to 78% (P=0.008, Table 4).
The application of the Youden index suggested that DSMRP was not associated with a
measurable diagnostic advantage in most patient subgroups (table 4).
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Segmental Analysis
The number of segments exhibiting inducible WMAs in the absence of perfusion deficits was
318 (4.8%). The number of segments experiencing perfusion deficits in the absence of
inducible WMAs was 516 (7.8%). The total number of mismatched segments was thus 12.6%.
In 132 patients perfusion deficits involved more segments, in 83 patients less segments than
WMAs, and in 84 patients the number of ischemic segments was identical. The mean number
of ischemic segments in patients with perfusion deficits vs. patients with inducible WMAs
was 3.6 ± 1.9 vs. 2.9 ± 1.5, P<0.001, respectively.
Delayed enhancement was present in 197 patients with a mean number of 3.1 ± 1.8 segments.
In 162 out of these 197 patients perfusion deficits or inducible WMAs were present. In 64
patients perfusion deficits were more extensive than WMAs, in 60 patients WMAs were less
extensive than perfusion deficits, and in 38 patients identical. The mean number of ischemic
segments in patients with perfusion deficits vs. patients with inducible WMAs was 3.1 ± 2.1
vs. 2.8 ± 1.5, P=0.12.
Interobserver agreement
In 50 randomly selected patients from the study population, the interobserver agreement (i.e.
agreement on test positivity or negativity) of DSMRP was 88% (κ 0.67).
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Discussion
We found that DSMRP provided good diagnostic accuracy for the detection of CAD.
However, though DSMRP improved sensitivity compared to DSMR, no gain in overall
diagnostic accuracy was detectable due to a concomitant decrease in specificity for the overall
population and all subgroups.
Cardiac Stress Testing with CMR
CMR has been shown to be a clinically useful and versatile technique for the detection of
myocardial ischemia (24). Both the detection of stress inducible WMAs as well as the
depiction of inducible perfusion deficits have been established as independent techniques to
diagnose myocardial ischemia (6, 11). However, the clinical usefulness of combined wall
motion and perfusion assessment during application of dobutamine is less well defined and it
is unknown whether high dose dobutamine/atropine perfusion imaging provides incremental
diagnostic information. Several clinical studies applying echocardiography (16) or nuclear
imaging techniques (25) provided evidence that dobutamine can effectively induce perfusion
deficits. The induction of myocardial ischemia during dobutamine stress testing is largely
attributed to an increase in myocardial oxygen demand with subsequent worsening of left
ventricular wall motion in areas subtended by coronary arteries with relevant stenoses.
Besides an increase in contractility and rate-pressure product, dobutamine may also exert a
direct vasodilatative effect on coronary vessels (14, 26). Recent studies have shown that the
extent of hyperemia with standard dobutamine–atropine stress testing is not less than that
observed with dipyridamole (27).
CMR is regarded the standard of reference for the assessment of left ventricular function and
regional wall motion at rest (24). Compared to echocardiography CMR has been shown to be
diagnostically superior for the detection of WMAs due to a consistently high endocardial
border delineation (5, 6). Although additional diagnostic value was ascribed to dobutamine
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perfusion imaging with echocardiography (28), it is unclear whether the same applies to
CMR. Furthermore, diagnostic accuracy of dobutamine stress wall motion studies for the
detection of CAD is impaired in patients with LVH (8) and resting WMAs (9).
Delayed enhancement imaging has been demonstrated to be a highly sensitive and specific
technique to diagnose myocardial scar tissue and has become part of a routine CMR
examination today. Since the administration of an extracellular contrast agent is mandatory
for delayed enhancement, total examination duration with additional perfusion imaging during
dobutamine stress is only marginally prolonged (< 3 minutes).
Diagnostic accuracy of DSMRP
DSMRP yielded a high number of diagnostic examinations as 91% were either positive for
ischemia or negative after reaching target heart rate. Main reasons for early termination of the
examination were insufficient hemodynamic response to dobutamine-atropine administration
or limiting cardiac side-effects like chest pain, dyspnea, hypertension and atrial fibrillation,
and were comparable to studies using dobutamine stress perfusion scintigraphy (29) and
echocardiography (30). Non-cardiac side-effects like nausea, headache and anxiety were not
uncommon but usually well tolerated without the need to terminate the examination. Only a
minority of patients had to be excluded due to insufficient image quality or technical failure of
DSMRP. In addition, the interobserver agreement for DSMRP is good despite the
heterogeneity of our patient population.
Our study showed that inducible myocardial perfusion deficits could be detected by DSMRP.
Furthermore, DSMRP is significantly more sensitive than DSMR for the detection of CAD in
the overall population of our study. This finding is in line with the ischemic cascade theory,
which states that perfusion deficits precede WMAs and electrocardiographic changes (31).
Our study also showed that the sensitivity in identifying patients with single-vessel CAD is
significantly higher for DSMRP compared to DSMR, which further supports the
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aforementioned theory. Animal studies have confirmed this phenomenon by demonstrating
that dobutamine causes a reduction in coronary flow distal to a noncritical coronary stenosis
while wall thickening remains normal (32). Our results regarding diagnostic accuracy of
DSMR were within the range of previously published data (3, 6, 7) thereby reflecting its
reliability in detecting significant CAD. However, the observed increase in sensitivity for
DSMRP in our study did not translate into an improved diagnostic accuracy due to a
significant decrease in specificity. Other studies using dobutamine perfusion imaging have
reported lower values for specificity either (28, 33). This might be explained by several
factors. Half of the patients responsible for false positives during DSMRP were diabetics and
75% of them had arterial hypertension. Both of these risk factors are known to cause impaired
coronary vasoreactivity even in the absence of a significant epicardial coronary arterial
narrowing (34, 35). In addition, the decline in specificity of DSMRP might be attributed to
CMR specific artifacts (mainly susceptibility), which arise from gadolinium bolus
administration, motion, or limited spatial resolution, and are known to reduce specificity in
CMR perfusion studies (36).
Our study showed that DSMRP exhibited a higher sensitivity for the detection of CAD in
patients with LVH. A possible explanation for this might be inherent to the perfusion imaging
approach, since it depicts inducible regional inhomogeneities of myocardial blood flow rather
than their functional consequences. Moreover, in patients with LVH left ventricular
obliteration during dobutamine stress and diastolic dysfunction associated with increased
myocardial stiffness are known phenomena, which can interfere with the identification of
WMAs (37, 38). However, the recognition of a perfusion deficit in a largely obliterated left
ventricle should be less demanding and might further serve as an explanation as to why
DSMRP might be a better test than DSMR to detect ischemia in patients with LVH. The fact
that in our study the differences in specificity did not reach statistical significance in patients
with LVH was somewhat surprising taking into account that patients with hypertrophy have a
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high probability of microvascular coronary disease and impaired coronary flow reserve (39)
and was most likely due to the small number of patients with negative invasive angiograms.
In patients with prior CAD the use of DSMRP also led to a significant increase in sensitivity.
Conversely, in patients with no LVH, no resting WMAs, no prior CAD and no single-vessel
CAD, DSMRP was associated with a lower diagnostic accuracy due to a significant decrease
in specificity. Thus, our results indicate that DSMRP is not necessarily justified in all patients
but may be advantageous in those in whom a high sensitivity is desirable.
The Youden index gives equal weight to sensitivity and specificity without reflecting CAD
prevalence. Although it is generally desirable to choose a test that has high values for both,
sensitivity and specificity may not be equally important in clinical practice. Patients who are
at high risk for future cardiac events may benefit from a test with high sensitivity. In the
present study DSMRP enabled the correct diagnosis in an additional 13% of DSMR negative
patients: 68% (13/19) demonstrated ischemia in ≥ 3 segments with multivessel CAD in 42%
(8/19) and thus, these patients are at considerable risk for future cardiac events (2, 40). In
addition, more accurate detection of disease extent with DSRMP may facilitate better risk
stratification.
Study Limitations:
Catheterization results were based on visual analysis and not on quantitative coronary
angiography. A common problem in validating non-invasive techniques for the detection of
myocardial ischemia is the lack of an optimal standard of reference (41). The present study
documents the diagnostic accuracy of DSMRP in patient population typically referred to a
tertiary care hospital and many patients had prior CAD and myocardial infarctions. Thus, our
results may be applicable only to a similar clinical setting. Multicenter studies are required
before the clinical role of DSMRP for the assessment of myocardial perfusion can be
determined. The perfusion sequence, contrast agent (gadolinium-DTPA), and its dosage were
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optimized for visual evaluation of MR perfusion. Previous publications reporting on
(semi)quantitative analysis mainly used lower doses of gadolinium-DTPA because
quantification but not visual assessment suffers from nonlinearity between contrast agent
concentration and signal intensity. Thus, the present data set does not allow for quantification,
and we cannot assure whether it would produce similar results.
Summary and Conclusions
DSMRP is a safe non-invasive stress modality and is useful to assess patients with suspected
and known CAD. Compared to DSMR the addition of perfusion imaging during high dose
dobutamine stress is associated with a significant increase in sensitivity which is offset by a
decrease in specificity for the overall population and the subgroups of our study. In patients
with a negative DSMR result, DSMRP enabled the correct diagnosis of CAD in an additional
13% (≥ 70% stenosis) of patients at the cost of 11% more false positive cases. The findings of
our study suggest that DSMRP might be helpful in identifying patients in whom the benefit of
very high sensitivity outweighs the disadvantage of lower specificity. Future studies are
needed to determine whether DSMRP may provide incremental prognostic value.
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Tables
1. Reasons for non-diagnostic tests
2. Clinical characteristics of final patient population
3. Hemodynamic data
4. Diagnostic performance of DSMR and DSMRP
Figures
1. Time course of stress testing and corresponding MRI (cine and perfusion scans).
2. False-negative DSMR but true-positive results for DSMRP in a patient with multiple
stenoses of LAD, LCX and distal occlusion of RCA. DSMR: inferior hypokinesia at
rest with no improvement during low dose dobutamine and no stress inducible WMA
during maximum dobutamine stress (black arrows); DSMRP: small inferior
subendocardial perfusion deficit at rest (white arrow) and stress inducible perfusion
deficit during maximum dobutamine stress (white arrows).
3. False-negative DSMR but true-positive DSMRP in patient with LVH, proximal
occlusion of the RCA and retrograde filling by collaterals from LAD. DSMRP clearly
demonstrates a stress inducible perfusion deficit of the apical inferior wall.
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Table 1. Reasons for non-diagnostic tests Reasons for non-diagnostic tests n (%) Non-diagnostic tests 41 (9) Technical reasons (insufficient ECG-triggering) 5 (1) Insufficient image quality 7 (2) Maximum pharmacologic infusion in submaximal negative 13 (3) Limiting side effects 16 (3) Patient request 2 Severe chest pain 4 Severe dyspnea 3 Severe increase in blood pressure (> 240/120 mmHg) 2 Paroxysmal atrial fibrillation 4 Ventricular tachycardia (self limiting) 1 Values are n (%) unless otherwise noted
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Table 2. Patient Demographics
Patient characteristics Age, y 63 ± 9 Range 32 - 85 Gender, M/F 297/117 BMI, kg/m2 27 ± 4 Risk factors and patient history, n (%) Hypertension 290 (70) Hypercholesterolemia 276 (67) Smoking 121 (29) Diabetes mellitus 114 (28) Family history 94 (23) LVEF, % 56 ± 8 patients with LVH 126 (30) resting wall motion abnormalities 190 (46) Prior CAD 267 (64) Prior Myocardial infarction 197 (48) Prior PCI 232 (56) Prior CABG 92 (22) Serum Creatinine, mg/dl 0.99 ± 0.25 GFR, ml/min 89 ± 27 Vessel disease (coronary stenosis ≥ 70%), n (%) 1-CAD 167 (40) 2-CAD 99 (24) 3-CAD 19 (5) BMI indicates body mass index; LVEF left ventricular ejection fraction; LVH left ventricular hypertrophy (septum ≥ 12 mm); CABG coronary artery bypass graft surgery; GFR glomerular filtration rate estimated using Cockroft equation; Values are n (%) unless otherwise noted and expressed as mean ± SD.
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28
Table 3. Hemodynamic data
Rest Stress Heart rate (bpm) 72 ± 14 137 ± 15* Systolic blood pressure (mmHg) 132 ± 23 142 ± 31* Diastolic blood pressure (mmHg) 71 ± 12 70 ± 15 Pulse pressure product (bpm x mmHg) 9539 ± 2773 19463 ± 4737* Note: Values are expressed as mean ± SD. *p < 0.001
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Table 4. Diagnostic performance of DSMRP and DSMR
DSMR DSMRP p DSMR DSMRP p DSMR DSMRP p DSMR DSMRPCoronary Stenosis ≥ 70%
All patients 241/285 (85) 260/285 (91) 0.001 106/129 (82) 90/129 (70) 0.001 347/414 (84) 350/414 (84) n.s. 0.67 0.61
Patients with LVH* 78/99 (79) 90/99 (91) < 0.001 23/27 (85) 20/27 (74) 0.25 101/126 (80) 110/126 (87) < 0.001 0.64 0.65resting WMAs 128/157 (82) 139/157 (89) 0.001 24/33 (73) 20/33 (61) 0.125 152/190 (80) 159/190 (84) < 0.001 0.55 0.5prior CAD 176/210 (83) 189/210 (90) < 0.001 43/57 (75) 37/57 (65) 0.03 219/267 (82) 226/267 (85) < 0.001 0.58 0.55no prior CAD 65/75 (87) 71/75 (95) < 0.001 63/72 (88) 53/72 (74) < 0.001 128/147 (87) 124/147 (84) < 0.001 0.75 0.69single-vessel CAD 141/167 (84) 152/167 (91) 0.001
no LVH, no resting WMAs, no prior CAD, no single-vessel CAD
14/16 (88) 15/16 (94) 0.125 41/47 (87) 34/47 (72) 0.02 55/63 (87) 49/63 (78) 0.008 0.75 0.66
Coronary Stenosis ≥ 50%
All patients 252/315 (80) 275/315 (87) < 0.001 87/99 (88) 75/99 (76) < 0.001 339/414 (82) 350/414 (85) < 0.001 0.68 0.63
Patients with LVH* 80/106 (76) 92/106 (87) < 0.001 18/20 (90) 15/20 (75) 0.05 98/126 (78) 107/126 (85) < 0.001 0.66 0.62resting WMAs 134/170 (79) 146/170 (86) < 0.001 17/20 (85) 14/20 (70) 0.018 151/190 (79) 160/190 (84) < 0.001 0.64 0.56prior CAD 184/234 (79) 199/234 (85) < 0.001 27/33 (82) 23/33 (70) < 0.001 211/267 (79) 222/267 (83) < 0.001 0.61 0.55no prior CAD 68/81 (84) 76/81 (94) 0.008 60/66 (91) 52/66 (79) 0.008 128/147 (87) 128/147 (87) n.s. 0.75 0.73single-vessel CAD 100/126 (79) 106/126 (84) 0.03
no LVH, no resting WMAs, no prior CAD, no single-vessel CAD
15/21 (71) 18/21 (86) 0.02 37/42 (88) 32/42 (76) < 0.001 52/63 (83) 50/63 (79) 0.008 0.59 0.62
values are n (%) unless otherwise notedabbreviations are as defined in text* end-diastolic wall-thickness of interventricular septum ≥ 12 mm
Sensitivity Specificity Accuracy Youden-Index
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Fleck and Ingo PaetschRolf Gebker, Cosima Jahnke, Robert Manka, Ashraf Hamdan, Bernhard Schnackenburg, Eckart
resonance for the assessment of coronary artery diseaseAdditional value of myocardial perfusion imaging during dobutamine stress magnetic
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