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Limited Flow Reserve in Non-Obstructed Bypass Grafts Supplying Infarcted Myocardium: Implications for Cardiovascular Magnetic Resonance Imaging Protocols

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We evaluated flow reserve in non-obstructed bypass grafts supplying infarcted and noninfarcted myocardium. Bypass grafts were examined by phase-contrast flow measurements and myocardial viability was assessed with late enhancement technique. Flow reserve was higher in bypasses supplying normal myocardium compared to those supplying infarcted myocardium (2.9 vs. 1.5, p<.0001). This difference remained significant after adjusting for co-variables. Bypass grafts supplying infarcted myocardium were more likely to have lower flow reserve than those supplying normal myocardium (flow reserve < or =2, 84% vs 18%, p = .0003). Flow reserve is reduced in non-stenosed bypasses supplying infarcted myocardium, likely due to altered microcirculation. Thus, cardiovascular magnetic resonance based bypass assessment must include myocardial viability testing.
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Journal of Cardiovascular Magnetic Resonance (2006) 8, 373–379
Copyright
c
2006 Taylor & Francis Group, LLC
ISSN: 1097-6647 print / 1532-429X online
DOI: 10.1080/10976640500452067
CORONARY ARTERIES
Limited Flow Reserve in Non-Obstructed Bypass
Grafts Supplying Infarcted Myocardium: Implications
for Cardiovascular Magnetic Resonance
Imaging Protocols
Christian Spies, MD,
1
Oliver K. Mohrs, MD,
2
James R. Madison, DO,
3
Andreas Fach, MD,
2
Bernd Nowak, MD, FESC,
2
and Thomas Voigtl¨ander, MD
2
Rush University Medical Center, Section of Cardiology, Chicago, Illinois, USA,
1
Cardioangiologisches Centrum Bethanien (CCB),
Frankfurt/Main, Germany,
2
University of California Davis, Division of Nephrology, Sacramento, California, USA
3
ABSTRACT
We evaluated flow reserve in non-obstructed bypass grafts supplying infarcted and non-
infarcted myocardium. Bypass grafts were examined by phase-contrast flow measurements and
myocardial viability was assessed with late enhancement technique. Flow reserve was higher in
bypasses supplying normal myocardium compared to those supplying infarcted myocardium
(2.9 vs. 1.5, p < .0001). This difference remained significant after adjusting for co-variables.
Bypass grafts supplying infarcted myocardium were more likely to have lower flow reserve than
those supplying normal myocardium (flow reserve 2, 84% vs 18%, p = .0003). Flow reserve
is reduced in non-stenosed bypasses supplying infarcted myocardium, likely due to altered
microcirculation. Thus, cardiovascular magnetic resonance based bypass assessment must
include myocardial viability testing.
INTRODUCTION
Coronary artery bypass grafting (CABG) is one of the main-
stays of coronary revascularization with 515,000 performed pro-
cedures in the US annually (1, 2). With bypass patency rates of
61–85% at 10 years follow-up recurrent angina in post-CABG
patients is a frequently encountered clinical scenario (3, 4). Con-
ventional coronary angiography is considered the gold standard
for evaluation of subsequent graft disease. However, its inva-
siveness, X-ray exposure, and risk for complications make an
Keywords: Coronary Artery Bypass, Magnetic Resonance
Imaging, Coronary Flow Reserve, Late Enhancement.
Correspondence to:
Christian Spies, MD
Rush University Medical Center
Section of Cardiology
1653 West Congress Parkway
Chicago, IL 60612
USA
phone: 312.942.5338 fax: 312.942.5829
email: christian
spies@rush.edu
alternative non-invasive diagnostic modality desirable (5). Car-
diovascular magnetic resonance (CMR) is a promising alterna-
tive surveillance tool for patients with suspected graft disease
following CABG. Several reports demonstrated the ability of
CMR to discriminate between grafts with significant stenosis
(50% or 70% luminal diameter by cine conventional angiog-
raphy) from those without stenosis by combining CMR derived,
anatomic information of 2D-angiography, and physiologic char-
acteristics with flow reserve (FR) estimates using phase-contrast
flow mapping (6–9).
However, since FR is a function of epicardial blood flow
and coronary microcirculation, not only bypass or native coro-
nary artery stenosis can cause reduced FR. Among several fac-
tors known to reduce coronary microcirculation is the presence
of left ventricular hypertrophy, hypertension, diabetes melli-
tus, left ventricular dysfunction, prior myocardial infarction,
smoking, hyperlipidemia, and obesity (10–15). To which ex-
tent these factors influence the FR in bypass grafts is unknown.
Prior studies have either not addressed this potential limitation of
CMR based FR measurement, or patients with these conditions
were excluded from the studies. This would seemingly create
an artificially selected subgroup, since the majority of patients
373
undergoing CABG likely have at least one of the aforementioned
co-factors (6–9, 16).
The goal of the present study was to evaluate the role of
myocardial scarring on FR measured with CMR phase contrast
flow mapping in bypass grafts without significant stenosis.
METHODS
Study population
We retrospectively identified patients with a history of CABG
who underwent a complete CMR based bypass graft evaluation
between December 2002 and August 2004. Patients were re-
quired to have a recent conventional coronary angiogram within
3 months of the time of CMR bypass evaluation, which showed
no evidence for significant stenosis in the bypass graft evaluated
with CMR. No change in the patients’ clinical status or med-
ication regimen could occur between procedures. All patients
were in sinus rhythm. We excluded patients with irregular heart
rhythms or unstable angina. Written informed consent was ob-
tained from all participants. Initial screening of our database
revealed 45 potential bypass grafts in 29 patients (Fig. 1). After
reviewing the CMR and conventional angiography data files and
images, 15 bypass grafts had to be excluded because either the
bypass graft or runoff vessels had significant stenosis (n = 9),
as defined in the following paragraph or were occluded (n = 3),
the CMR image quality was inadequate due to artifact from vas-
cular clips (n = 1), or the vascular territory of the bypass grafts
was supplied by large collateral flow (n = 2). The remaining 30
bypass grafts in 19 patients were included in the present analysis.
Figure 1. Flow chart of included bypass grafts. Initial database
search revealed 45 potential bypass grafts. After review of the CMR
and conventional angiography images 15 grafts had to be excluded.
Thirty bypass grafts remained which underwent complete CMR
evaluation and which were found to have at most 20% stenosis on
conventional angiography. Grafts were separated into two groups
based on presence or absence of prior myocardial infarction in the
vascular territory of the bypass as determined by late enhancement
CMR imaging.
Conventional coronary angiography
Selective X-ray angiography was performed using the Jud-
kins technique with standard 4–6F catheters. All native vessels,
saphenous vein grafts, internal mammary grafts and stumps were
visualized in 2 orthogonal views. Grafts with a stenosis more
than 20% in diameter of the bypass or run-off vessel as well as
grafts supplying vascular territory receiving significant collat-
eral blood flow by cine angiography were excluded. Collateral
blood flow was analyzed subjectively as present or absent.
Cardiovascular magnetic resonance imaging
Prior to CMR evaluation the surgical report was reviewed
to identify number of proximal anastomoses and their corre-
sponding sites of distal anastomoses in all patients. CMR was
performed on a 1.5-T MRI system (Magnetom Sonata Mae-
stro Class, Siemens Medical Solutions, Erlangen, Germany).
For signal detection the combination of a six-channel body
phased-array coil and a two-channel spine phased-array coil was
used. ECG-signal was received from an external system (Mag-
nitude 3150, InVivo Research Inc., Orlando, FL, USA). Patients
were monitored throughout the procedure with non-invasive
blood pressure, heart rate and continuous electrocardiographic
measurements.
First, for visualization of the graft origin and course, a
multi-slice two-dimensional breath-hold, ECG-gated, double
inversion, black blood turbo spin-echo sequence (echo time
44 ms; acquisition window 800 ms, field of view 230 to
350 mm; matrix 176 × 256, slice thickness 5 mm) was ap-
plied in axial and individual planes. ECG-gated, breath-hold,
contrast-enhanced 3D-gradient-echo angiography was applied
using gadolinium–diethylene triamine pentaacetic acid (DTPA,
dosage 0.1 mmol/kg body weight) to evaluate patency and course
of each graft. Typical sequence parameters for MR angiogra-
phy were the following: TR 3.1 ms, TE 1.2 ms; voxel-size
1.2 × 0.9 × 2.0 mm
3
, flip angle 20
, matrix 240 × 384, parti-
tions 52, slab-thickness 104 mm.
Second, ECG-gated, breath-hold, phase-contrast flow map-
ping was performed based on different localizer planes (typ-
ical sequence parameters: TE 4.2 ms, temporal resolution 70
ms, segmentation 7, breath-hold of approximately 20–30 sec-
onds, flip angle 30
,velocity encoding 75 cm/s, voxel-size
1.4 × 0.8 × 6.0 mm
3
) (Fig. 2). Flow data of each visible graft
were acquired at rest and during adenosine-induced hyperemia
(dosage: 140 µg/min/kg body weight, first measurement 3 min-
utes after start of infusion). Flow mapping was performed in
the proximal third of saphenous vein grafts (SVG) to minimize
motion due to cardiac pulsations, while left internal mammary
artery (LIMA) grafts were evaluated in the mid third as more
proximal measurements would be inaccurate due to a larger
proximity to the isocenter.
Third, an ECG-gated, breath-hold, segmented inversion-
recovery-turboFLASH-sequence “TrueFISP-cine-sequence”
(TE 4.4 ms; acquisition window 800 ms, segmentation 25,
TI optimized to null the myocardium, typical at 200 to 300
ms; flip angle 30
,voxel-size 1.7 × 1.3 × 6.0 mm
3
) served for
374 C. Spies et al.
Figure 2. Flow measurement with phase-contrast flow mapping in the left internal mammary artery (arrow). (A) The anatomic image.
(B) The corresponding velocity map.
detection of non-viable myocardium in a stack of contiguous
long axis views and short axis planes (Fig. 3). Images were
acquired approximately 15 minutes after administration of a
second bolus of 0.1 mmol/kg gadolinium-DTPA (total dosage
0.2 mmol/kg).
Data analysis
Conventional angiography and CMR bypass data were re-
viewed separately by two experienced readers (C.S. and O.K.M.)
at different time points. The readers were blinded to the results
of the other imaging modality. Flow velocity analysis and quan-
tification of left ventricular mass and ejection fraction was per-
formed using an analytic software package (Argus Software,
Siemens Medical Solutions, Erlangen, Germany). FR was cal-
culated as the ratio between flow velocity at maximal hyperemia
and baseline. Vascular territory supplied by the bypass graft and
area of myocardial scarring on late enhancement were catego-
rized following the AHA 17-segment model (17).
To allow analysis of regional myocardial function, percent
myocardial thickening (PMT) was analyzed in segments 1 to
16 of the AHA 17-segment model. PMT was calculated as end-
systolic myocardial thickness (ESMT) minus end-diastolic my-
ocardial thickness (EDMT) divided by EDMT × 100. Further,
as a surrogate marker for regional myocardial mass, EDMT
was evaluated separately. Measurements in the 16 segments
were taken in three representative short axis views (basal, mid-
ventricular, and apical), thus excluding the apical segment 17
from the analysis. According to the vascular territory supplied
by the bypass graft as determined on conventional angiography,
PMT and EDMT was calculated as the mean of all segments
within this territory. Further, PMT and EDMT was calculated
for the entire heart (segments 1 to 16) as a reference value.
According to the presence of myocardial scarring in the by-
pass distribution as seen on late enhancement imaging, grafts
were categorized into 2 groups: 1) grafts supplying normal,
completely viable myocardium, and 2) grafts supplying either
partially or completely non-viable myocardium due to prior my-
ocardial infarction (Fig. 1). Bypass grafts supplying normal my-
ocardium were required to have no segmental overlap between
the vascular territory served by the bypass graft and abnormal
Figure 3. Late contrast-enhanced gadolinium-DTPA infarct images. (A) Four-chamber view with non-transmural hyperenhancement of the left
ventricular apex, consistent with subendocardial infarction. (B) Mid-ventricular short axis image with hyperenhancement of the entire anterior
and anterior-septal wall with non-transmural involvement of the lateral wall, consistent with transmural infarction.
Flow Reserve in Bypass Grafts 375
Table 1. Characteristics of bypass grafts according to the presence/absence of infarcted myocardium in the graft distribution
Normal myocardium
(n = 19)
Infarcted myocardium
(n = 11) p value
Age (years) 64 (54–82) 69 (60–72) .72
Male gender 16 (84%) 11 (100%) .17
Height (cm) 175 (162–184) 172 (162–184) .85
Weight (kg) 82 (60-100) 82 (70–100) .77
Body mass index (kg/m
2
) 26.5 (19.6–33.8) 25.7 (24.2–33.8) .80
Hypertension 15 (79%) 10 (91%) .4
Diabetes mellitus 4 (21%) 5 (45%) .16
Beta blocker 12 (63%) 5 (45%) .35
Calcium channel blocker 6 (32%) 3 (27%) .80
Nitrate 1 (5%) 3 (27%) .09
Renin-angiotensin system inhibitor 15 (79%) 5 (45%) .06
Statin 13 (68%) 7 (64%) .79
Antiplatelet 14 (74%) 9 (82%) .61
Diuretic 3 (16%) 2 (18%) .87
Digoxin 2 (11%) 3 (27%) .24
Sequential grafts 6 (32%) 2 (18%) .42
LIMA bypass 7 (37%) 4 (36%) .98
Ejection fraction (%) 67 (24–78) 45 (24–75) .035
Left ventricular mass (g/m
2
)78(40–110) 90 (64–110) .22
EDMT
- graft area (mm) 8.3 (4–12) 6.3 (5–15) .343
EDMT - all segments (mm) 8.7 (5.5–13.5) 8.4 (5.6–13.5) .95
PMT
+
- graft area (%) 96 ([18]200) 55 ([15]143) .11
PMT - all segments (%) 87 (21–123) 53 (15–105) .03
Values are numbers of patients (percentages) or medians and range.
EDMT - end-diastolic myocardial thickness,
+
PMT - percent myocardial thickening.
late enhancement in the same territory, whereas grafts supplying
infarcted myocardium had at least one segmental overlap.
Statistical analysis
Continues data is presented as median and range, except
for the unadjusted and adjusted variables in the analysis of
variance (ANOVA), which is presented as mean with standard
deviation (SD) and mean with 95% confidence interval (CI),
respectively. Differences in baseline characteristics between the
two groups were compared with Mann-Whitney U-test for con-
tinues data and chi-square test for dichotomous variables. We
used ANOVA to compare the mean flow reserve adjusting for
variables that were associated with FR (at p < .15) and for vari-
ables known to affect FR (diabetes mellitus, hypertension, and
obesity).
To determine an independent association of the presence or
absence of myocardial scarring with FR, we used binary logistic
regression analysis. FR was divided in two groups, either 2, or
>2. The same confounders were entered in a sequential analysis
as described above for the ANOVA. Analyses were performed
with SPSS software (Version 13.0, SPSS Inc., Chicago, IL).
RESULTS
Of 30 grafts included in the present analysis, 12 were LIMAs
and 18 SVGs. Nineteen bypass grafts were found to sup-
ply normal, non-infarcted myocardium, while 11 grafts had a
vascular distribution which had at least one segment overlap with
an infarcted territory as seen on late enhancement. Median age
of the predominantly male patient population was 67 (range 54–
82) years (Table 1). Patients with bypass grafts supplying nor-
mal myocardium were more likely to have diabetes mellitus and
were more frequently prescribed nitrates and renin-angiotensin
system inhibitors, although these differences did not meet sta-
tistical significance. Further, patients with grafts supplying nor-
mal myocardium had a higher ejection fraction (67% [24–78] vs
45% [24–75], p = .035) and a higher PMT in both the graft area
(96% [18–200] vs 54.5% [15–143], p = .11) and in all my-
ocardial segments combined (87% [21–123] vs 53% [15–105],
p = .03).
Flow reserve in bypass grafts supplying normal myocardium
was almost twice as high (2.9 ± 0.9 vs. 1.5 ± 0.7; p < .0001)
compared to the group of bypasses with myocardial scar for-
mation in its vascular distribution (Table 2). The difference in
FR between the two groups remained significant even after ad-
justing for potential confounders (2.6 [2.0–3.1] vs 2.2 [1.3–3.2],
p = .03), including usage of nitrates and renin-angiotensin sys-
tem inhibitors, presence of diabetes mellitus, hypertension, and
obesity, left ventricular ejection fraction, and PMT in the graft
area and in all myocardial segments.
Bypass grafts supplying infarcted myocardium were more
likely to have a FR 2 than those supplying normal myocardium
(84% vs 18%, p = .0003; Fig. 4). In logistic regression analysis,
the presence of infarcted myocardium in the graft distribution
was associated with a lower FR (OR 24, 95% CI 3.4–171.5,
p = .002), although this association weakened after adjusting for
376 C. Spies et al.
Table 2. Flow reserve by presence/absence of infarcted myocardium
in graft distr ibution
Normal
myocardium
(n = 19)
Infarcted
myocardium
(n=11) p value
Unadjusted mean ± SD 2.9 ± 0.9 1.5 ± 0.7 <.0001
Adjusted mean (A) [95% CI] 2.9 [2.5–3.4] 1.6 [0.9–2.2] .008
Adjusted mean (B) [95% CI] 2.5 [2.1–3.0] 2.3 [1.5–3.1] .002
Adjusted Mean (C) [95% CI] 2.6 [2.0–3.1] 2.2 [1.3–3.2] .03
A = Adjusted for nitrate and renin-angiotensin system inhibitor use,
B = Adjusted for nitrate and renin-angiotensin system inhibitor use,
diabetes mellitus, hyper tension, and body mass index; C = Adjusted for
nitrate and renin-angiotensin system inhibitor use, diabetes mellitus,
hypertension, body mass index, ejection fraction, PMT in graft area,
and PMT in all segments.
potential confounders and became statistically non-significant
(Table 3).
DISCUSSION
The present study finds that FR in non-obstructed bypass
grafts supplying normal myocardial tissue was almost twice
as high compared to non-obstructed bypasses supplying par-
tially infarcted myocardium. Our finding has significant impact
on the strategy of CMR-based bypass evaluation, as infarcted
myocardium in the distal territory of the normal bypass graft
might lead to falsely low FR values. This would lead to the false
assumption that an “epicardial” bypass stenosis is present. A
concept prior described in an animal model evaluating regional
perfusion with magnetic resonance first-pass measurements af-
ter selective administration of adenosine and microspheres in
the left circumflex territory (18).
However, an ideal non-invasive surveillance test, used to
evaluate bypass grafts demands the precise distinction between
stenosed and not-stenosed bypass grafts. Hence, a comprehen-
sive bypass evaluation is warranted when using CMR technolo-
gies, which not only evaluates patency and FR of the bypass
Figure 4. Proportion of bypass grafts with flow reserve greater
than 2 by presence/absence of infarcted myocardium in graft
distribution.
Table 3. Association of flow reserve with the presence/absence of
infarcted myocardium in graft distribution
Odds ratio
[95% CI] p value
Unadjusted model 24 [3.4–171.5] .002
Adjusted model (A) 19.3 [1.7–222] .02
Adjusted model (B) 2.4 [0.07–86] .63
Adjusted model (C) 2.6 [0.06–122.6] .63
Odds ratio from binary logistic regression representing the
independent association between the predictor variable (presence of
infarcted myocardium in the distribution of the bypass graft) and the
outcome variable (flow reserve) divided into two groups (2 and >2).
A = Adjusted for nitrate and renin-angiotensin system inhibitor use,
B = Adjusted for nitrate and renin-angiotensin system inhibitor use,
diabetes mellitus, hyper tension, and body mass index; C = Adjusted for
nitrate and renin-angiotensin system inhibitor use, diabetes mellitus,
hypertension, body mass index, ejection fraction, PMT in graft area,
and PMT in all segments.
graft but also localizes myocardial scar tissue in relation to the
bypass graft distribution. This becomes imperative since prior
myocardial infarction is a common finding in patients with prior
CABG.
The difference in FR between grafts supplying normal and
infarcted myocardium remained statistically significant, even
after adjusting for several confounders including left ventricu-
lar ejection fraction and PMT. The latter parameter, as well as
EDMT, was included in the analysis as they are surrogate mark-
ers for regional function and mass. Bypass grafts supply only a
portion of the left ventricle, but left ventricular ejection fraction
and mass are parameters representing the entire left chamber.
The observed loss of statistical significance of the association
of presence of myocardial scarring with low FR after adjusting
for confounders is not surprising, given the small sample size
of the study, also leading to a wide confidence interval in the
regression analysis.
Prior studies evaluating bypass grafts with CMR flow map-
ping have not adequately addressed the importance of myocar-
dial scar formation and the role of microcirculation. Bedaux
et al (7) addresses the impact of stenosis in the native coronary
vascular structure by dividing groups based on bypass grafts
with normal or abnormal runoff; however, the influence of the
vascular bed distal to the epicardial vascular structure is not con-
sidered. Although Langerak et al (8) discuss the importance of
the microcirculation in FR, they conclude that there is a good
correlation between CMR flow characteristics and conventional
angiography, minimizing the role of microcirculation in the es-
timation of FR. Consequently, FR alone was unable to differ-
entiate more than 50% stenosed from non-stenosed sequential
grafts. Perhaps, because sequential bypass grafts usually supply
larger areas of myocardium, the influence of altered microcir-
culation contributes in a greater manner to these FR estima-
tions. Additionally, Ishida et al (6) were unable to differentiate
stenosed from non-stenosed grafts with CMR based coronary
flow reserve measurements in internal mammary artery grafts
with distal anastomosis to the left anterior descending artery
Flow Reserve in Bypass Grafts 377
or diagonal branches. It is possible that this finding is related
to the fact that mammary arteries commonly are used regard-
less of myocardial viability in the vascular distribution of the
grafts, but simply because their patency rates are excellent and a
CABG is being done regardless. This might as well increase the
importance of an altered microcirculation on the flow pattern un-
der rest and stress in these bypasses. Finally, Nagel’s approach
of excluding all patients with myocardial infarction, left ven-
tricular hypertrophy, micro-vessel disease, cardiomyopathy, or
severe valvular disease in the evaluation of native coronary ves-
sels following stent placement does not appear to be practical,
since several patients following CABG would be excluded from
CMR bypass evaluation as most of them have at least on of the
above listed factors potentially influencing FR (17).
The mechanism by which scared myocardium in the territory
of a non-obstructed bypass graft causes reduced FR is obvious.
It is well accepted that destruction of the morphologic integrity
and scar formation of the myocardium as caused by myocar-
dial infarction negatively affects the coronary microcirculation
(17, 19). Increased vascular resistance and abnormal viscosity
are the purposed pathomechnisms by which hypertrophy or dys-
function of the left ventricle, hypertension, diabetes mellitus and
hyperlipidemia reduces microcirculatory blood flow, secondar-
ily leading to a reduction of FR as well (11–13, 20, 21).
In addition to describing the association between myocardial
infarction and reduced FR, our study has further implications
on CMR based protocols evaluating bypass grafts. It appears
crucial to identify the localization of myocardial scar formation
in order to reliably calculate FR, which should translate into
less false-positive test results potentially further improving the
specificity of CMR based bypass evaluation. A score system to
calculate FR, weighting the pertinent variables FR, presence of
myocardial scarring, left ventricular ejection fraction, PMT, and
various comorbidities such as diabetes mellitus or hypertension,
would be optimal. However, our sample size is not sufficient to
develop such a model. Further, redefining the cut off value for
FR in CMR based flow mapping seems warranted. However, the
presented data does not allow such a modification as we have
excluded stenosed bypass grafts as a comparative group. Future
studies should be able to clarify these uncertainties.
Nevertheless, CMR based bypass evaluation is an intrigu-
ing approach as it provides anatomic and functional informa-
tion from CMR-angiography, bypass flow characteristics and
myocardial properties, by visualizing reduced microcirculation
and myocardial scarring via wash-in and wash-out characteris-
tics of a single bolus of intravenous contrast agent (Gadolinium-
DTPA) during early and late enhancement, respectively (22–27).
Our imaging protocol omitted early imaging after contrast ad-
ministration; thus, we have no direct evidence of “pure” dimin-
ished microcirculation. However, it is reasonable to assume that
with documented late enhancement limited microcirculation is
present.
Since CMR is the only technology which evaluates bypass
flow reserve and microcirculation, it appears superior to other
tests. It provides data which otherwise can only be obtained by
combining different invasive tests, as in the case for FR with
transcatheter technique using Doppler or thermodilution tipped
catheters, with non-invasive modalities used for assessment of
myocardial perfusion or viability, such as contrast echocardio-
graphy or PET imaging (28–31). Further, adding late enhance-
ment imaging to the regular CMR based bypass evaluation pro-
tocol, barely prolongs the scanner time if timed optimally. At
our institution, gadolinium was given immediately before the
flow measurements at rest and following a 6 minute adenosine
infusion, a process taking about 15 minutes after which late
enhancement can be documented without delay.
Several limitations apply to our study. First, as outlined above,
myocardial perfusion was not measured directly, enabling us
only to assume an altered microcirculation if myocardial scar-
ring was present. Second, our sample size was not sufficient to
evaluate the importance of the transmural extent of myocardial
scar tissue. It is intuitive to assume that subendocardial scarring
would influence FR to a lesser extent than transmural infarcts;
however, this remains to be proven. Third, a history of hyper-
tension and diabetes mellitus is a crude estimate of the actual
blood pressure and glycemic control at the time examination.
Although actual values of blood pressure and serum glucose
would have been superior for data analysis, these data were un-
available. Further, despite being potential confounders for FR,
lipid levels and smoking status were unavailable and thus not
included in the analysis. Fourth, inclusion of the left ventricular
ejection fraction prior to bypass surgery would have been desir-
able; however, this value was frequently unavailable or obtained
by other modalities than CMR, preventing direct comparison.
In summary, FR in bypass grafts evaluated by CMR phase
contrast flow mapping is influenced by the presence of scarring
in the supplied myocardium. Thus, myocardial viability testing
with late enhancement technique appears to be crucial in order to
obtain a comprehensive and reliable coronary bypass evaluation
with CMR.
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Flow Reserve in Bypass Grafts 379
... The flow rates in the grafts are much higher in the "R3" group, probably because the microvascular resistances are smaller. As demonstrated by many authors [14][15][16][17][18], the status of the distal supplied territory influences the flow in the graft. (0G) and (2G). ...
... this could be related to the fact that the resistances of the distal perfused territories, R LCxc and R RCAc , are lower for this group of patients. Spies et al. [15] also found that flow reserve is reduced in bypasses supplying infarcted myocardium, likely due to altered microcirculation. ...
Article
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We study patients with stenoses of the left main coronary artery (LMCA), left anterior descending artery (LAD), and left circumflex branch (LCx) and with chronic occlusion of the right coronary artery (RCA), undergoing off-pump coronary surgery. An analog electrical model is used to provide quantitative estimations of the distribution of flows and pressures across the coronary network (in the stenosed native arteries, the collateral branches, the capillary areas, and so forth). The present paper demonstrates that the clinical information collected for the 10 patients included in the study (Rentrop score, history of myocardial infarction, left ventricular ejection fraction (LVEF)) are well correlated with the predicted hydrodynamic data. Patients with a good collaterality (Rentrop score = 3) or patients without anterior myocardial infarction have (i) less severe stenoses on the LMCA, (ii) lower microvascular resistances, (iii) higher grafts flow rates when the revascularization is performed, (iv) higher collateral flow rates towards the territory of the occluded artery, (v) better perfusion of this area, and (vi) better total perfusion of the heart.
... Adenosine has been validated as a safe pharmacological agent for myocardial scintigraphy and stress echocardiography (7,8). However, its use in the context of MRI has to be analysed separately since the MRI environment could induce additional effects such as claustrophobia. ...
... ECG-gated MR angiography and ECG-gated, breath-hold, phase-contrast flow mapping were performed to assess the flow in coronary bypass grafts (8). The typical sequence parameters were a TE of 4.2 ms, temporal resolution of 70 ms, segmentation: 7, a breath-hold of approximately 2030 seconds, a flip angle of 30°, velocity encoding at 75 cm/s and a voxel size of 1.4 x 0.8 x 6.0 mm 3. First, a flow measurement of each graft was done with the patient at rest followed by a second measurement during a continuous adenosine infusion after a run-in period of 3 minutes at a body weight-adapted infusion rate of 140 µg/kg/min. ...
Article
Full-text available
We wanted to prospectively assess the adverse events and hemodynamic effects associated with an intravenous adenosine infusion in patients with suspected or known coronary artery disease and who were undergoing cardiac MRI. One hundred and sixty-eight patients (64 ± 9 years) received adenosine (140 µg/kg/min) during cardiac MRI. Before and during the administration, the heart rate, systemic blood pressure, and oxygen saturation were monitored using a MRI-compatible system. We documented any signs and symptoms of potential adverse events. In total, 47 out of 168 patients (28%) experienced adverse effects, which were mostly mild or moderate. In 13 patients (8%), the adenosine infusion was discontinued due to intolerable dyspnea or chest pain. No high grade atrioventricular block, bronchospasm or other life-threatening adverse events occurred. The hemodynamic measurements showed a significant increase in the heart rate during adenosine infusion (69.3 ± 11.7 versus 82.4 ± 13.0 beats/min, respectively; p < 0.001). A significant but clinically irrelevant increase in oxygen saturation occurred during adenosine infusion (96 ± 1.9% versus 97 ± 1.3%, respectively; p < 0.001). The blood pressure did not significantly change during adenosine infusion (systolic: 142.8 ± 24.0 versus 140.9 ± 25.7 mmHg; diastolic: 80.2 ± 12.5 mmHg versus 78.9 ± 15.6, respectively). This study confirms the safety of adenosine infusion during cardiac MRI. A considerable proportion of all patients will experience minor adverse effects and some patients will not tolerate adenosine infusion. However, all adverse events can be successfully managed by a radiologist. The increased heart rate during adenosine infusion highlights the need to individually adjust the settings according to the patient, e.g., the number of slices of myocardial perfusion imaging.
... VI.2 -Microvascular damages of the targeted territory In many cases, a poor graft outcome is related to the microvascular status of the target territory [59,67,68,69]; however, the assessment of the status of the microvascular beds remains challenging. ...
Chapter
In this chapter, we recall the role of the coronary collateral circulation in severe obstructive coronary diseases, and, based on the literature review, we try to provide an answer to the question: When patients undergo aorto-coronary bypass graft surgery, does good collateral fl ow reduce the risk of graft disease or, on the contrary, does it increase the risk of graft disease? In order to get additional arguments, a review of the numerical models and simulations addressing this problem is also included in the chapter.
... The mechanism by which scarred myocardium, even in the territory of a nonobstructed epicardial coronary artery, causes a reduction of flow and flow reserve is obvious: Destruction of the morphologic integrity and scar formation of the myocardium as caused by myocardial infarction negatively affect the coronary microcirculation [29]. Using MRI, Spies et al. described that flow reserve after adenosine-induced hyperemia is not only influenced by the lumen of the bypass graft and the degree of stenosis, but strongly depends on whether the bypass supplies normal myocardium or scar [30]. These findings very much match our results. ...
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The aim of the study was to relate the extent of myocardial late gadolinium enhancement (LGE) in cardiac MRI to intraoperative graft flow in patients undergoing coronary artery bypass graft (CABG) surgery. Thirty-three CAD patients underwent LGE MRI before surgery using an inversion-recovery GRE sequence (turboFLASH). Intraoperative graft flow in Doppler ultrasonography was compared with the scar extent in each coronary vessel territory. One hundred and fourteen grafts were established supplying 86 of the 99 vessel territories. A significant negative correlation was found between scar extent and graft flow (r = -0.4, p < 0.0001). Flow in grafts to territories with no or small subendocardial scar was significantly higher than in grafts to territories with broad nontransmural or transmural scar (75 +/- 39 vs. 38 +/- 26 cc min(-1); p < 0.0001). In summary, the extent of myocardial scar as defined by contrast-enhanced MRI predicts coronary bypass graft flow. Beyond the probability of functional recovery, preoperative MRI might add value to surgery planning by predicting midterm bypass graft patency.
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The role played by glucose and/or insulin in local vascular regulation of tissue glucose uptake is largely unknown. Thus, the aim of this study was to examine microvascular changes induced either by hyperinsulinaemia alone or in combination with hyperglycaemia. The effects of insulin or glucose on the diameter and periodic vasomotion of precapillary arterioles (diameter < 20 microm) were determined by using the spinotrapezius muscle preparation in fasted, anaesthetized rats. Ten minutes after s.c. insulin administration, the blood insulin level was greatly increased whereas plasma glucose remained unchanged. This was associated with a marked and durable vasodilation of terminal arterioles without significant changes in vasomotion. When similar plasma insulin levels were attained by glucose infusion, tissue glucose uptake was increased in spite of a partial constriction and increased vasomotion of precapillary arterioles. Importantly, local tissue blood flow was not reduced despite the diminution in microvascular diameters. These results indicate that hyperinsulinaemia alone produces an increase in the diameter of terminal arterioles. This effect seems to be offset when the same level of hyperinsulinaemia is associated with hyperglycaemia (such as occurs postprandially), as illustrated by vasoconstriction of the muscle terminal arterioles. Our data suggest that the vasoconstriction of precapillary arterioles may be part of an active regulation for optimal glucose supply to the tissue in acute hyperglycaemic episodes. These data provide the first direct evidence that insulin and glucose can act as regulators of microflow in the skeletal muscle, as illustrated by changes in precapillary haemodynamics.
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Nuclear cardiology, echocardiography, cardiovascular magnetic resonance (CMR), cardiac computed tomography (CT), positron emission computed tomography (PET), and coronary angiography are imaging modalities that have been used to measure myocardial perfusion, left ventricular function, and coronary anatomy for clinical management and research. Although there are technical differences between these modalities, all of them image the myocardium and the adjacent cavity. However, the orientation of the heart, angle selection for cardiac planes, number of segments, slice display and thickness, nomenclature for segments, and assignment of segments to coronary arterial territories have evolved independently within each field. This evolution has been based on the inherent strengths and weaknesses of the technique and the practical clinical application of these modalities as they are used for patient management. This independent evolution has resulted in a lack of standardization and has made accurate intra- and cross-modality comparisons for clinical patient management and research very difficult, if not, at times, impossible. Attempts to standardize these options for all cardiac imaging modalities should be based on the sound principles that have evolved from cardiac anatomy and clinical needs.1–3⇓⇓ Selection of standardized methods must be based on the following criteria: An earlier special report from the American Heart Association, American College of Cardiology, and Society of Nuclear Medicine4 defined standards for plane selection and display orientation for serial …
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Aortocoronary saphenous vein graft disease, with its increasing clinical sequelae, presents an important and unresolved dilemma in cardiological practice. During the 1st month after bypass surgery, vein graft attrition results from thrombotic occlusion, while later the dominant process is atherosclerotic obstruction occurring on a foundation of neointimal hyperplasia. Although the risk factors predisposing to vein graft atherosclerosis are broadly similar to those recognized for native coronary disease, the pathogenic effects of these risk factors are amplified by inherent deficiencies of the vein as a conduit when transposed into the coronary arterial circulation. A multifaceted strategy aimed at prevention of vein graft disease is emerging, elements of which include: continued improvements in surgical technique; more effective antiplatelet drugs; increasingly intensive risk factor modification, in particular early and aggressive lipid-lowering drug therapy; and a number of evolving therapies, such as gene transfer and nitric oxide donor administration, which target vein graft disease at an early and fundamental level. At present, a key measure is to circumvent the problem of vein graft disease by preferential selection of arterial conduits, in particular the internal mammary arteries, for coronary bypass surgery whenever possible.
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The clinical syndrome "coronary insufficiency with normal coronary arteriogram" is found in approximately 10% to 20% of patients with exercise-induced coronary insufficiency. In most of these cases, disturbances of the coronary microcirculation are present. They can appear in vascular diseases (arterial hypertension, systemic immunopathies, immune complex vasculitis), in rheologic diseases (paraproteinemia, hyperlipoproteinemia, polyglobulia) and in disturbances of transport and diffusion of oxygen (carbon monoxide intoxication, methemoglobinemia). The clinical diagnosis is based on the usual diagnostic procedures (electrocardiogram, exercise electrocardiogram, responsiveness to nitroglycerin), as well as on newer functionally oriented diagnostic procedures (determinations of coronary blood flow and coronary vascular reserve, production of lactate, serologic findings, histology and immune histology of peripheral arteries, measurements of viscosities in both plasma and blood). Many clinically relevant disturbances in the coronary microcirculation can thus be detected and treated on a rational basis by management of the underlying main disease, that is, by treatment of the vascular, rheologic and metabolic disorders. Persistent angina pectoris in the presence of a normal coronary arteriogram does not represent an end to coronary diagnostic procedures, but introduces the clinical task of using all diagnostic possibilities to enable functional and therapeutic assessment of the coronary microcirculation.
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The measurement of coronary vascular reserve by the reactive hyperemic response to ischemia has been advocated as a practical method of assessing the physiologic significance of coronary stenoses. Because the concept of measuring coronary blood flow during maximal vasodilation assumes a normal arteriolar network and viable myocardium, the presence of previous myocardial infarction may cause a significant decrease in the coronary reserve unrelated to the severity of a coronary stenosis itself. To determine the potential importance of this effect, rest and hyperemic coronary blood flow were measured in 14 dogs in the regions subtended by the left anterior descending and left circumflex coronary arteries. One hour occlusion of the left anterior descending artery followed by reperfusion was performed in 10 dogs; the 4 remaining dogs in which no occlusion was performed served as control animals (group 3). One week later, rest and hyperemic blood flow measurements were repeated in all 14 dogs. Of the 10 dogs undergoing left anterior descending artery occlusion, 5 had a large infarct (group 1) and 5 had a small infarct (group 2). In group 1 in the 1 week study, both the coronary reserve in the left anterior descending artery zone and the ratio of the coronary reserve in this zone and the left circumflex artery zone decreased compared with values before occlusion (from 425 +/- 134 to 150 +/- 34% and from 1.56 +/- 0.40 to 0.68 +/- 0.31, respectively; both p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)