Download S1936878X14001363_mmc1 - JACC: Cardiovascular Imaging

SUPPLEMENTARY METHODS
Dobutamine-stress CMR (DSCMR)
Dobutamine CMR was performed with a 1.5T system (Avanto Magnetom, Siemens,
Erlangen, Germany) using an 8-element cardiac phased-array receiver coil. An antecubital
intravenous cannula of 20-gauge or larger was used for the delivery of gadolinium-DOTA.
Non-invasive monitoring and gating for image acquisition (MedRad 9500 Monitor, PA) were
performed continuously in all cases. Dobutamine was infused at progressive 3-minute stages
of 10, 20, 30, and 40 mcg/kg/min via a separate intravenous cannula. Intravenous boluses of
atropine sulfate (0.25-0.5 mg aliquots up to a maximum total dose of 2 mg) were used at 30 or
40 mcg/kg/min stages to augment the heart rate response. Dobutamine infusion was
terminated before the end of the infusion protocol if there was an achievement of 85% of
maximum predicted heart rate response for age, worsened wall motion score in any
myocardial segment by >1 grade, severe angina, systolic hypotension (<90 mm Hg) or
hypertension (>230 mm Hg), complex ventricular arrhythmias. All dobutamine-CMR image
acquisitions were performed ECG-gated and during breath-holding. Cine images were
obtained in 3 parallel short-axis and 3 radial views at baseline and at each stress stage as
follows. The basal plane was taken at 1.5 cm below the mitral valves apparatus and the midventricular and apical short-axis views were divided equally over the remaining part of the
left ventricle (base, mid and apex). Steady-state free precession segmental gradient-echo
pulse sequence was used for all CMR cine imaging (TrueFisp: TR 57.64, ms; TE, 1.2 ms; α,
59°; FOV, 284 × 350 mm; slice-thickness 8 mm; and matrix 125 × 192 and iPAT 2). With
progressive heart rate increase, the views per segment were lowered (from 16 at rest to lowest
6 at high heart rates) to improve the temporal resolution (50 to 29 ms). During dobutamine
stress, commercially available display software (CardioVue, Prova Images, Winston-Salem,
NC) permitted on-the-fly viewing of LV regional function, either by infusion stage or by slice
location, on an adjacent computer workstation.
A single lead ECG display provided cardiac gating as well as continuous rhythm monitoring
throughout the CMR study. A nurse controlled the dobutamine infusion and monitored the
patient symptoms continuously in the scanner room while a physician monitored the progress
of dobutamine stress and the acquired images at the imaging console. Vital signs were
checked at least once at each dobutamine infusion stage.
CMR Myocardial First Pass Perfusion
At the stage of 20 μg/kg/min dobutamine stress (henceforth defined as intermediate dose),
intravenous gadolinium-DOTA (0.1 mmol/kg) was injected using a power injector (MedRad
Inc., PA) while first-pass myocardial MR perfusion imaging (MPI) was acquired. This dose
was selected due to our previous clinical experience suggesting that at higher doses of
dobutamine the increase in contractility and heart rate makes it difficult to qualitatively
interpret the first pass perfusion images. Furthermore, there is also some evidence that
myocardial perfusion can be accurately assessed at 20 μg/kg/min with a similar increase in
myocardial blood flow to adenosine at this dose (14-16). Multi-slice MPI was acquired using
an ECG triggered TurboFLASH sequence (echo time, 0.99 ms; repetition time, 173 ms; time
for inversion, 90 ms; flip angle, 8°; slice thickness, 8 mm; field of view, 213 × 340 mm;
matrix, 80 × 128 mm; spatial resolution, 2.7 × 2.7 mm2; bandwidth, 780 Hz per pixel). One
image per slice location was acquired every 1-3 cardiac cycles at peak heart rates (average
121 + 13 beats/minute) while gadolinium-DOTA 0.1 mmol/kg of patient’s body weight was
injected at 5 ml/sec followed by 15-20 ml of saline flush at 5 ml/sec. To minimize respiratory
motion during the first-pass transit of the gadolinium bolus, patients were instructed to
maintain breath-holding for at least the first 20 seconds of the acquisition and allowed to free
breathe afterwards.
Late Gadolinium Enhancement (LGE)
Late gadolinium enhancement imaging for myocardial infarction was acquired 10 minutes
after intravenous contrast administration (after a total cumulative gadolinium-DOTA dose of
0.2 mmol/kg) by an inversion recovery fast gradient-echo sequence as previously reported
(17). Infarcted myocardium was quantified by semiautomatic detection of any region with
signal intensity 2 standard deviations above the mean signal intensity of the remote
myocardium as previously validated (17). LGE was counted as positive only if it was in a
sub-endocardial or transmural distribution typical of CAD. The complete DSCMR protocol is
summarized in the main manuscript Figure 2.
Dobutamine Stress CMR Analysis
Two experienced readers blinded to patients’ clinical history and outcome interpreted the
dobutamine-CMR images. A third observer was called upon for adjudication in cases of
disagreement between the first two readers. Segmental wall motion and thickening at each
stage was analyzed according to the standardized 17-segment nomenclature (18). Each of the
17 myocardial segments was graded at each dobutamine stage as 1 = normal, 2 = hypokinesia,
3 = akinesia, and 4 = dyskinesia. An ischemic wall motion abnormality was defined as the
presence of segmental wall motion grade >1 and absence of wall thickening during
progressive dobutamine stress, apart from the progression of segmental akinesia to dyskinesia
which was considered non-specific. Excepting the left ventricular apex, a myocardial segment
was considered ischemic only if concordant findings were observed on both the short-axis
and the matching long-axis views. MPI data acquired during intermediate dobutamine dose
(20 mg/kg/min) was viewed and visually analyzed off-line with dedicated software
(CardioVue). The left ventricular myocardium was segmented into 6 sectors at the basal and
mid ventricular levels and 4 sectors at the apical level using the anterior insertion of the right
ventricle as an anatomic landmark. Each myocardial segment was qualitatively interpreted as
having normal perfusion or abnormal hypoperfusion based on the consensus of the same
readers blinded to the wall motion results and the patient’s identity. Ischemia by myocardial
perfusion imaging was defined by any persistent segmental hypo-enhancement in absence of
delayed hyper-enhancement by delayed imaging. Additionally, in patients who had evidence
of prior myocardial infarction by LGE, the presence of peri-infarct ischemia (a perfusion
defect on stress larger than but corresponding to the area of LGE) was also counted as
positive for ischemia. Interpretations of the wall motion, MPI and late gadolinium
enhancement imaging were blinded to the results of coronary angiography. In detecting
coronary stenosis, myocardial ischemia by wall motion or MPI was only considered true
positive if the myocardial segment was in the same territory of a significant stenosis. Using
CMR cine imaging alone, CMR was judged to be positive if an inducible regional wall
motion abnormality (RWMA) was seen. In the comprehensive DSCMR examination, the test
was adjudged to be positive if either there was LGE present in a distribution typical of
infarction (subendocardial or transmural) with evidence of peri-infarct ischemia; or if there
was no LGE, if there was an inducible perfusion defect which corresponded to an inducible
RWMA.