The Coronary Artery Bypass Graft (CABG) failure is a cause of major cardiac events. CABG to coronary arteries with low-grade stenosis resulting in competitive flow and graft failures is a controversial issue. Some studies refute this. All of these studies have been performed with Invasive Catheter Angiogram. This study is the first one to investigate the relationship between CABG failure and chronic competitive flow with Coronary CT Angiogram.
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Coronary artery bypass graft failure and its relationship to target artery percentage stenosis and competitive flow. A CT angiographic analysis
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Studies reveal that 1 in 10 patients undergoing CABG have
at least 1 occluded graft at 30 days and one in 20 of all grafts
are blocked.1 The 10-year patency rates of the Left Internal
Mammary (LIMA) graft are reported to be above 90%. However,
if and when the LIMA graft, which is the most robust conduit,
fails, the options of future revascularisation are significantly
handicapped. Early Saphenous Vein Graft (SVG) failure is
known to be associated with worse long term outcomes after
CABG.2 Despite good overall outcomes with CABG, 30% of
SVGs have been known to fail within 12e18 months. SVG
failure is also associated with a higher rate of perioperative MI
and a higher incidence of MI and revascularization at 1 year.3
Several causes of graft failure are known. Among these,
CABG to coronary arteries with low-grade proximal stenosis
continues to be a controversial issue. Some studies state that
anastomosis of grafts to coronary arteries with low grade
stenosis leads to reduced ante grade flow through the graft, a
condition known as chronic competitive flow, which may lead
to early graft failure. Other studies have refuted this fact and
recommend grafting to moderately stenosed coronary ar-teries.
Some canine experiments have demonstrated that
arterial grafts on arteries with no stenosis remained patent at
the end of a two-month follow up advocating CABG to
moderately stenosed coronary arteries.
SVGs are more prone to failure than arterial conduits.
Surgical factors, intimal hyperplasia and atherosclerosis are
thought to be the main reasons for SVG failure. No clear un-derstanding
is present on the effect of chronic flow competi-tion
on SVG.
64-slice CT technology has been proved to have a high
diagnostic accuracy in assessing CABGs as well as native
coronary artery stenosis.
Recent studies show that the 320 slice CT scanners are
more accurate than the 64 slice scanners. Percent diameter
stenosis determined with the use of 320-slice CT Angiography
(CTA) shows good correlation with Invasive Catheter Angio-gram
(ICA) (p < 0.0001).4 While competitive flow has been
addressed with ICA, it has not been evaluated before to our
knowledge with CTA. CTA gives the unique advantages of
simultaneously visualizing all the bypass grafts as well as
evaluating the target arteries for their luminal stenosis. Ma-jority
of the earlier studies have also addressed graft types
separately and near, intermediate and long term CABG failure
separately. This study, for the first time investigates the rela-tionship
between CABG failure and chronic competitive flow
across all terms and all graft types in a comprehensive and
panoramic manner with the help of CTA. The objective of the
study is to determine whether flow competition from border-line
stenotic coronary arteries can cause failure of the bypass
graft placed on such an artery. The study also highlights the
sign of competitive flow from target coronary artery on CTA.
2. Materials and methods
2.1. Study population
1445 grafts in 438 patients referred between 2007 and 2012 to
our department for Coronary CTA 4 months to 23 years after
CABG, were included in this retrospective study. These
patients had no other additional procedures like valve
replacement at the time of CABG. Average number of grafts
per patient was 3.2. Patients ranged in age from 37 to 84 and
had a mean age of 60.1 years with 401 men and 37 women. 236
patients were symptomatic. The remaining 202 were asymp-tomatic
and referred for checking graft patency. The average
left ventricular ejection fraction was 58%. 50% of patients were
diabetics, 57% hypertensives, 56% dyslipidemics, and 31%
were smokers. 41% had a family history of coronary artery
disease and 43% had no risk factors at all. 42% had an MI prior
to the CABG. In cases with sequential grafts, each segment
was counted as a separate graft.
2.2. Angiographic data
The degree of preoperative stenosis of the grafted coronary
artery was obtained from the preoperative ICA. The post-
CABG CTA was performed on the Aquilion 64 and Aquilion
One 320, Toshiba Japan, scanners. 46% of the patients under-went
the study on the 64 slice CT and the remaining under-went
a 320 slice CT. IV contrast used was Optiray 350 mg,
Mallinckrodt USA. ECG gated scans were performed through
the heart after 65 ml of intravenous contrast injection at the
rate of 4.5 ml/s with a pressure injector chased by a bolus of
30 ml of normal saline at the same rate. The images were
interpreted on curved reconstructions through the vessel
lumen as well as the cross sections on a dedicated worksta-tion.
A senior and a junior radiologist interpreted the scans
separately. Consensus was arrived at by discussion prior to
final report generation. The percentage of stenosis on the CT
Angiograms was calculated with calipers on cross sections of
the minimum luminal diameter of the stenotic segment and
the reference vessel diameter of the adjacent normal
segment.
The study group was divided according to graft types into
LIMA þ Right internal mammary artery (RIMA), SVG and left
radial artery (LRA). Each type was further divided into “Patent”
and “Failed” groups. The failed group consisted of occluded,
diffusely narrowed, and grafts with more than 70% stenosis.
The two groups were compared for target artery percentage
stenosis below and above 75%.
Each graft type was further divided into subgroups ac-cording
to years after CABG as follows: less than 2, 2e5, 5e7,
7e10, 10e15 and more than 15 years post CABG. These sub-groups
were again compared for the percent stenosis of the
target artery.
2.3. Statistical analysis
The statistical analysis was performed per conduit and not per
patient. Chi Square Test, p Values, Odds ratio, CI and z statistic
were calculated. In all tests, differences were considered not
significant when p > 0.05.
3. Results
In our study, of the total 1445 grafts 8.6% failed within 2 years,
13.8% failed within 5 years and 23.5% failed within 10 years.
72% of total grafts including LIMA, RIMA, SVG and LRA when
Please cite this article in press as: Ramanan RV, Ramalingam A, Coronary artery bypass graft failure and its relationship to
target artery percentage stenosis and competitive flow. A CT angiographic analysis, Apollo Medicine (2014), http://dx.doi.org/
10.1016/j.apme.2014.09.001
4. a p o l l o me d i c i n e xxx ( 2 0 1 4 ) 1e1 0 3
Fig. 1 e The left panel of the bar chart shows patency of total grafts (IMA, LRA and SVG together) when placed on target
arteries with less than or more than 75% stenosis. Majority of grafts fail when placed on arteries with less than 75%
stenosis. The right panel shows a breakup of specific graft types. IMA, SVG and LRA all respond to competitive flow similarly
with majority failing below 75% target artery stenosis.
placed on coronary arteries with less than 75% stenosis failed
as compared to 22.8% grafts failing when placed on coronary
arteries with more than 75% stenosis with a p < 0.0001, Odds
ratio of 1.14, 95% CI of 0.60e2.15 and z statistic of 0.398 (Fig. 1
left panel).
When placed on target arteries with less than 75% stenosis,
67% of the internal mammary arteries (IMAs), 73.3% of the
SVGs and 75% of the LRA failed revealing no statistical dif-ference
in failure rates (p ¼ 0.4) (Fig. 1 right panel upper half).
This suggests that when faced with competitive flow all graft
types fail equally. In grafts placed on target vessels with more
than 75% stenosis, 86.8% of IMA and 83.5% of LRA were patent
as compared to70.7% of the SVGs. This suggests that the
arterial grafts are better conduits as compared to the SVG,
with IMAs being the champion (Fig. 1 right panel lower half).
In the subgroups broken down as years after CABG (<2,
2e5, 5e7, 7e10, 10e15 and >15 years) significant number of
grafts regardless of graft type (IMA, SVG or LRA) failed when
placed on target arteries with less than 75% stenosis and
majority survived when placed on arteries with more than
75% stenosis. (Figs. 2e4) SVG showed higher failure rates as
graft age progressed.
4. Discussion
4.1. Competitive flow from moderately stenosed target
coronary arteries causing graft failure
The issue of whether to graft coronary arteries with moderate
stenosis and what effect this has on the graft as well as native
coronary arteries has been discussed over the past two de-cades.
Barner and others found as early as the 1970s, a diffuse
reduction in the caliber of the Internal mammary artery (IMA)
graft which was called “disuse atrophy” because the native
coronary arteries to which the IMAs were anastomosed
Please cite this article in press as: Ramanan RV, Ramalingam A, Coronary artery bypass graft failure and its relationship to
target artery percentage stenosis and competitive flow. A CT angiographic analysis, Apollo Medicine (2014), http://dx.doi.org/
10.1016/j.apme.2014.09.001
5. 4 a p o l l o me d i c i n e x x x ( 2 0 1 4 ) 1e1 0
Fig. 2 e The bar chart with breakup of the IMA grafts according to years after the CABG shows that significant numbers fail
when placed on target arteries with less than 75% stenosis irrespective of the time interval after CABG. The 7e10 and
10e15 years bars showing grafts patent on less than 75% target artery stenosis can be explained by factors such as
erroneous %stenosis on the ICA or graft supplying adjacent arteries with critical stenosis.
appeared to be patent and to have good flow thereby
rendering the graft useless.5,6 This phenomenon is now
commonly known as the “String Phenomenon” (Fig. 5).
Though other studies have shown that competitive flow
causes graft failure7,8 and does not increase the blood supply
to the myocardium in the region of the grafted coronary ar-tery,
9 there have been opponents of the competitive flow
theory who recommended grafting to moderately stenosed
coronary arteries. Canine experiments have shown that
arterial conduits grafted on fully patent native arteries
remained patent. However, patency was assessed at a
maximum of 2 months, which is not enough to predict the
long-term effect of competitive flow.10,11
In some of the earlier studies on potential predictive fac-tors
of IMA occlusion, control angiograms were obtained
relatively soon after CABG. Grafts on moderate stenosis were
found to be patent and recommended. However these studies
too did not address the long-term effect of flow
competition.12,13
In a large long term study between 1982 and 2002 Shah
et al. showed that target artery stenosis did not affect IMA
graft patency.14 This could be because only two broad cate-gories
of 60e79% and 80e99% stenosis of target arteries were
considered. If majority of grafts in the 60e79% group were on
79% stenosis it would not reflect the effect of a 60% target
artery stenosis on the grafts. In our study majority of grafts on
Please cite this article in press as: Ramanan RV, Ramalingam A, Coronary artery bypass graft failure and its relationship to
target artery percentage stenosis and competitive flow. A CT angiographic analysis, Apollo Medicine (2014), http://dx.doi.org/
10.1016/j.apme.2014.09.001
6. a p o l l o me d i c i n e xxx ( 2 0 1 4 ) 1e1 0 5
Fig. 3 e Bar chart with breakup of the LRA grafts according to years after the CABG shows that significant numbers fail when
placed on target arteries with less than 75% stenosis irrespective of the time interval after CABG.
a target artery stenosis of 79% survived whereas on 60% ste-nosis
did not.
Glineur et al. have also divided patients into very broad
groups of native vessel percent stenosis, clubbing 65%e99%
stenosis together. It is not clear whether the grafts, which
survived, were closer to 65% or 99%.15
Sabik et al. found that internal thoracic artery graft patency
does decrease as coronary artery competitive flow increases.
However, they included diffusely narrowed grafts into the
patent category instead of the failed and therefore found that
the effect of competitive flow on ITA graft patency is mild, and
at no degree of proximal coronary stenosis is there a severe
decline in ITA patency. They therefore recommended
bypassing coronary arteries with moderate degrees of
stenoses.16
Manninen et al. found in their study that vein grafts were
more likely to fail on moderately stenosed target arteries
rather than arterial grafts. Contrary to this, we found that both
arterial and venous grafts shut down equally if placed on
insignificant stenosis. The string sign was not included in
graft failure by above workers. However, in the conclusion
they agree that if it were included then arterial and venous
grafts would appear to fail equally on insignificant percent
stenosis.17
4.2. Competitive flow from a graft placed on an adjacent
artery or an adjacent ungrafted native artery causing graft
failure
We found that 0.01% of the LIMA, 0.02% of the SVG and 0.01%
of the LRA grafts failed because of competitive flow from
patent grafts to adjacent vessels or an ungrafted largely open
native coronary artery. In one of our cases with significant
proximal LAD stenosis, a LIMA placed on the LAD downstream
Please cite this article in press as: Ramanan RV, Ramalingam A, Coronary artery bypass graft failure and its relationship to
target artery percentage stenosis and competitive flow. A CT angiographic analysis, Apollo Medicine (2014), http://dx.doi.org/
10.1016/j.apme.2014.09.001
7. 6 a p o l l o me d i c i n e x x x ( 2 0 1 4 ) 1e1 0
Fig. 4 e Bar chart with breakup of the SVG grafts according to years after the CABG shows that significant numbers fail when
placed on target arteries with less than 75% stenosis irrespective of the time interval after CABG. The 2 grafts, which appear
to survive on target arteries with less than 75% stenosis in the 2e5 year group, can be explained by factors such as
erroneous %stenosis on the ICA.
(at a level more distal) to a grafted diagonal branch failed, due
to flow competition when the diagonal ostium was not
significantly stenosed. Due to a relatively more proximal
positioning of the diagonal graft, there occurred a free
competitive flow through the diagonal graft into the diagonal
and thence to the LAD (Fig. 6).
A similar phenomenon was observed in one of our patients
with critical Left main stenosis, where a LIMA to distal LAD
failed due to free flow from a graft on the early OM branch
located upstream, through the widely patent LCx ostium into
the LAD.
This is consistent with observations of Achouh et al.18
4.3. Graft failure when placed on occluded or critically
stenosed arteries
0.02% of LIMA and 0.1% [32/339] of SVGs in our study failed
despite landing on target arteries, which were occluded, or
more than 90% stenosed. Here the distal target segments
beyond occlusions or very tight stenosis were poorly opacified
on ICA and graft worthiness could not be assessed. Grafts
probably landed on diffusely diseased segments and occluded.
We found this phenomenon more commonly with the RCA
territory grafts. Myers et al. found, similarly that though pre-operative
ICA showed otherwise, coronary arteries could not
Please cite this article in press as: Ramanan RV, Ramalingam A, Coronary artery bypass graft failure and its relationship to
target artery percentage stenosis and competitive flow. A CT angiographic analysis, Apollo Medicine (2014), http://dx.doi.org/
10.1016/j.apme.2014.09.001
8. a p o l l o me d i c i n e xxx ( 2 0 1 4 ) 1e1 0 7
Fig. 5 e 3D volume rendered CTA shows a composite graft arrangement with the LIMA anastomosed to the Diagonal and
then to distal Left anterior descending (LAD). The LRA to Obtuse marginal branch of the left circumflex is anastomosed
proximally to the LIMA. The proximal LIMA segment connecting to the LRA is large calibered as it supplies a critical stenosis
in the circumflex. However the mid LIMA segment to the Diagonal is diffusely small calibered due to competitive flow from
the insignificant stenosis in the proximal LAD and the diagonal branch. The distal segment of the LIMA to LAD is once again
large caliber being supplied by the patent diagonal branch.
be revascularized often with a plain CABG procedure after
making an arteriotomy due to extensive plaques.19
4.4. Graft survival on less than 75% target artery
stenosis due to adjacent territory supply
0.1% of LIMA, 0.05% of SVG and 0.04% of LRA grafts in our
study survived on less than 75% target artery stenosis as they
were supplying the adjacent un-grafted but critically stenosed
artery. For example grafts on distal LAD that supplied the
critically stenosed but un-grafted Posterior descending artery
via collaterals around the cardiac apex survived even when
they were grafted on less than 75% LAD stenosis. A similar
phenomenon could be seen when Obtuse marginal grafts
supplied the Posterolateral branches of the Right coronary
artery or vice versa.
4.5. Graft survival on less than 75% target artery
stenosis in chronic heavy smokers
In two of our patients who were chronic heavy smokers grafts
survived on less than 75% stenosis. This could be attributed to
severe micro-vascular disease in the myocardium upgrading
the need for revascularization.
4.6. Competitive flow due to inaccurate percentage
stenosis on ICA causing graft failure
In our study, 21% (22/101) of the occluded IMA grafts, 11% (36/
339) of the occluded SVGs and 29% (15/51) of the occluded LRA
grafts that failed on target arteries with more than 75% ste-nosis
as seen on the preoperative ICA, revealed that on the
Fig. 6 e 3D volume rendered CTA. The LIMA to LAD is
occluded due to competitive flow from the SVG to the
diagonal branch located upstream from the point of LIMA
anastomosis to the LAD giving it a hemodynamic
advantage over the LIMA graft. The Distal LAD is now
supplied from free flow through the SVG to the diagonal via
a patent diagonal osmium (arrows).
Please cite this article in press as: Ramanan RV, Ramalingam A, Coronary artery bypass graft failure and its relationship to
target artery percentage stenosis and competitive flow. A CT angiographic analysis, Apollo Medicine (2014), http://dx.doi.org/
10.1016/j.apme.2014.09.001
9. 8 a p o l l o me d i c i n e x x x ( 2 0 1 4 ) 1e1 0
Fig. 7 e The left panel shows a volume rendered 3D CTA where the LIMA is anastomosed to the LAD. A composite LRA graft
is anastomosed proximally to the LIMA and distally sequentially to the two OM branches. The LIMA segment connecting to
the LRA is largely patent as it supplies the critical stenosis in mid circumflex. However the LIMA segment to the LAD
becomes string like and occludes distally due to the flow competition from the LAD. The right panel shows a curved
reconstruction through the LAD. The two calcified plaques cause only 40% stenosis of the LAD. On review of the ICA this
segment appeared 70% stenosed due to foreshortening of the artery.
post-CABG CTA the percentage stenosis of the target coronary
artery was in fact less than 75%. This inaccurate percent ste-nosis
on ICA caused competitive flow and subsequent graft
failure.
Several authors have questioned the accuracy and repro-ducibility
of ICA. Visual interpretation of the ICA exhibited
clinically significant intra-observer and inter-observer vari-ability,
with differences in the estimation of stenosis severity
approaching 50%.
Studies also reported major discrepancies between the
apparent angiographic severity of lesions and postmortem
histology.20
Due to tortuosity and foreshortening of arteries, moderate
coronary artery stenosis can sometimes appear severe on ICA
and grafts placed on such stenosis appear to fail due to “no
apparent reason” (Fig. 7). Similarly very significant stenosis
may appear moderate on ICA because of the morphology of
the lesion within the coronary arterial lumen. When such
arteries are grafted, the graft appears to survive on a moder-ately
stenosed artery whereas in fact it has survived on a
critically stenosed one.20
4.7. Accelerated atherosclerosis after CABG
When grafts occlude the native coronary arteries do not
remain as they were prior to grafting. CABG is associated with
accelerated atherosclerosis in the target artery segments
proximal to graft anastomosis with several proceeding to oc-clusion.
21,22 In fact, the site of PCI in post CABG patients is
significantly more in the native coronary artery proximal to an
occluded graft as compared to a stenosed graft, coronary
stenosis distal to a patent graft or on a non-grafted vessel.18
Because of the diffuse nature of this accelerated disease, PCI
becomes challenging and even impossible in some cases.23 It
would therefore be judicious to not graft borderline stenotic
coronary arteries where a competitive flow would result in
graft occlusion and the native artery borderline stenosis
would progress to diffuse critical stenosis defeating the very
purpose of revascularisation.
4.8. Sign of competitive flow on CT
Competitive flow on ICA has been defined as a phenomenon
where the target coronary branch and anastomotic site are
clearly opacified in the native coronary injection, but not on
injection of the in situ graft.24 An adaptation of the same sign
can be seen on CTA. Grafts that are occluded from the prox-imal
anastomotic site upto the distal segment with only the
distal anastomotic site patent and opacified through the flow
in the borderline stenotic native coronary artery backing up
retrograde into the graft are a clear indicator of competitive
flow (Fig. 8).
4.9. Advantage of studying CABG failure by CTA vs. ICA
In ICA each graft and the native coronary arteries are injected
individually giving separate images, which then have to be
collated in the mind of the investigator to form the total pic-ture.
On the other hand CTA simultaneously demonstrates all
grafts and native arteries in a 3D format, which gives a
Please cite this article in press as: Ramanan RV, Ramalingam A, Coronary artery bypass graft failure and its relationship to
target artery percentage stenosis and competitive flow. A CT angiographic analysis, Apollo Medicine (2014), http://dx.doi.org/
10.1016/j.apme.2014.09.001
10. a p o l l o me d i c i n e xxx ( 2 0 1 4 ) 1e1 0 9
Fig. 8 e A, B, C: Panel A demonstrates competitive flow to the LIMA. In this 3D volume rendered image the heart and several
grafts have been faded into the background in order to bring attention to the Left main artery, LAD and the diagonal branch
together with its LIMA graft. The LIMA placed on the diagonal branch is occluded proximally. The distal segment of the
LIMA is opacified through flow from the insignificantly stenosed LAD and diagonal backing up retrogradely into the graft.
This may be considered a sign of competitive flow on CTA. Panel B and C demonstrate competitive flow to a vein graft. Panel
B shows a curved reconstruction through the thrombosed SVG graft and demonstrates the distal anastomotic site that
remains patent due to retrograde competitive flow from the OM branch (arrow). Panel C shows a 3D volume rendered image
with patent LIMA graft to LAD, patent SVG to Diagonal and an occluded SVG to OM. The distal anastomosis and the distal
most bit of the SVG graft to OM is opacified by the retrograde flow through the insignificantly stenosed OM branch.
panoramic and global view of the heart and its conduits. The
diffuse critical narrowing of one graft in comparison with a
largely patent adjacent graft clearly demonstrates graft fail-ure.
A widely patent native artery with its failed graft seen
simultaneously leaves no doubt as to the cause of the graft
failure.
4.10. Recommendations for future research
Large prospective trials may be conducted with CABG based
on percentage stenosis measured by cross sectional preoper-ative
CTA image with the help of calipers and using minimum
luminal diameter and adjacent normal reference vessel
diameter. Graft failure can then be assessed on follow up CTA
to ascertain the cutoff value of percent stenosis or minimum
luminal diameter below which competitive flow would occur
causing graft failure. CABG recommendations should ideally
be based on cross sectional imaging like CTA.
In conclusion, ours is the first study that assesses CABG
failure due to competitive flow by CTA. It proves that CABG to
coronary arteries that have less than 75% stenosis causes
chronic competitive flow to the graft from the target coronary
artery resulting in reduced flow through the graft. This slow
flow causes reduction in graft caliber and eventual graft oc-clusion.
Arterial as well as venous grafts succumb to
competitive flow equally and fail. To add to this dilemma,
inaccurate percentage stenosis on ICA caused by myriad fac-tors
may cause arteries with insignificant stenosis seem sig-nificant
enough to be grafted resulting in graft failure. Hence
pre CABG assessment of coronary arteries with CTA and true
stenosis measured with calipers on cross section images
would be worthwhile to decide which arteries need grafting.
Arteries with moderate stenosis may be left ungrafted and
medically managed till they do need intervention in the form
of stenting.
Funding received
We received no support from any organization for the sub-mitted
work, have no financial relationships with any orga-nizations
that might have an interest in the submitted work
and no other relationships or activities that could appear to
have influenced the submitted work.
Conflicts of interest
All authors have none to declare (Ref.JSS).
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Please cite this article in press as: Ramanan RV, Ramalingam A, Coronary artery bypass graft failure and its relationship to
target artery percentage stenosis and competitive flow. A CT angiographic analysis, Apollo Medicine (2014), http://dx.doi.org/
10.1016/j.apme.2014.09.001
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Please cite this article in press as: Ramanan RV, Ramalingam A, Coronary artery bypass graft failure and its relationship to
target artery percentage stenosis and competitive flow. A CT angiographic analysis, Apollo Medicine (2014), http://dx.doi.org/
10.1016/j.apme.2014.09.001