Impact of Syntax Score On The Early Outcome of Cabg Surgery in Low Ejection Fraction Patients

IMPACT OF SYNTAX SCORE ON THE EARLY
OUTCOME OF CABG SURGERY IN LOW

EJECTION FRACTION PATIENTS
Thesis
Submitted in Partial Fulfillment of the MD Degree in Cardiothoracic
Surgery
RESULTS
Whole sample data
Demographic data
Our study included 100 patients; 29 females (29%) and 71 males (71%).The
mean and standard deviation values of age were 55.40 ± 8.10 years with
aminimum of 31 and a maximum of 69 years. The mean and standard deviation
values of body mass index were 28.27 ± 3.70 with aminimum of 22 and a
maximum of 35 .
Table (2): Descriptive statistics of demographic data in the study sample

Total no. 100
Mean ± SD 55.40 ± 8.10
Age
Range 31 – 69
Female 29 (29.0%)
Sex
Male 71 (71.0%)
Mean ± SD 28.27 ± 3.70
BMI
Range 22 – 35
percentage
Male
Female
Figure (12): Pie chart representing gender distribution in the whole sample
Risks factors
The most prevalent risk factors were hypertension (69% of the cases) and
Dyslipidemia (69% of the cases) followed by DM (65% of cases).
Table (3): Risk factors in the study sample
Total no. 100

No 41 (41.0%)
Smoking
Yes 59 (59.0%)
No 31 (31.0%)
HTN
Yes 69 (69.0%)
No 35 (35.0%)
DM
Yes 65 (65.0%)
No 31 (31.0%)
Hypercholesterolemia
Yes 69 (69.0%)
Figure (13): Bar chart representing risk factors in the whole sample
Clinical characteristics
Study including four patients with peripheral vascular diseases (4%),

twenty-seven cases with previous MI (27%) and no patient with history of
cerebrovascular accident or present chronic renal failure.
Table (4): Clinical characteristics in the study sample
Total no. 100

No 100 (100.0%)
CRF
Yes 0 (0.0%)
No 96 (96.0%)
PVD
Yes 4 (4.0%)
No 100 (100.0%)
Prior CVA
Yes 0 (0.0%)
No 73 (73.0%)
Prior MI
Yes 27 (27.0%)
Echocardiography
Table (5): Descriptive statistics of ejection fraction
Total no. 100

Mean ± SD 35.20 ± 3.17
LVEF
Range 25 – 39
SYNTAX score
Table (6): Descriptive statistics of SYNTAX score
Total no. 100

Mean ± SD 32.03 ± 9.62
SYNTAX score
Range 10 – 58
Low 16 (16.0%)
SYNTAX score subgroups Intermediate 40 (40.0%)
High 44 (44.0%)
Intra-operative findings
Table (7): Descriptive statistics of intra-operative findings
Mean ± SD Range
TOTAL CPB 108.83 ± 32.23 45 – 230
Cross clamp 65.38 ± 20.56 20 – 160
Total no. 100

Mean ± SD 2.95 ± 0.85
No of grafts
Range 1–5
Incomplete 23 (23.0%)
Revascularization
Complete 77 (77.0%)
Post-operative findings
Table (8): Descriptive statistics of post-operative findings
Total no. 100

Mean ± SD 3.17 ± 1.12
ICU Stay
Range 2–7
Mean ± SD 11.75 ± 4.93
Mechanical ventilation
Range 4 – 34
No 91 (91.0%)
IABP
Yes 9 (9.0%)
No 86 (86.0%)
ARRHYTHMIAS
Yes 14 (14.0%)
No 25 (25.0%)
INOTROPES
Yes 75 (75.0%)
No 97 (97.0%)
acute RF
Yes 3 (3.0%)
No 32 (32.0%)
BLOOD T
Yes 68 (68.0%)
No 97 (97.0%)
REOPENING
Yes 3 (3.0%)
Early Outcome
Table (9): Descriptive statistics of the Early outcome
No. %
No 86 86.0%
MACCE
Yes 14 14.0%
No 91 91.0%
MI
Yes 9 9.0%
No 100 100.0%
CVA
Yes 0 0.0%
No 94 94.0%
DEATH
Yes 6 6.0%
Figure (14): Bar chart representing Early Outcome in the whole sample
Association between SYNTAX score and different variables
Demographic data
There was no statistically significant correlation between syntax score and

age. No statistically significant correlation between syntax score and BMI .There
was also no statistically significant association between syntax score and gender.
Table (10): Results of association between SYNTAX score and demographic

data
Syntax score
r P-value
Age 0.058 0.568
BMI 0.038 0.708
Independent t-
Syntax score
test
Mean ± SD Range t P-value
Female 30.90 ± 9.79 10 – 58
Sex 0.751 0.454
Male 32.49 ± 9.58 14 – 57
r: Pearson’s correlation coefficient
Significant at P ≤ 0.05
t: Independent t-test
Risks factors
There was no statistically significant association between syntax score and

different risk factors.
Table (11): Results of association between SYNTAX score and Risks factors
Syntax score Independent t-test

No 32.48 ± 10.15 19 – 58
Smoker -0.384 0.701
Yes 31.72 ± 9.31 10 – 54
No 31.55 ± 10.16 14 – 58
HTN 0.334 0.739
Yes 32.25 ± 9.44 10 – 55
No 32.06 ± 8.49 16 – 51
DM 0.021 0.984
Yes 32.02 ± 10.24 10 – 58
No 31.56 ± 9.28 16 – 54.5
Hypercholesterolemia 0.323 0.748
Yes 32.24 ± 9.83 10 – 58

any of the clinical characteristics.
Correlations could not be computed for CRF and Prior CVA because there were no
cases.
Table (12): Results of association between SYNTAX score and Clinical

characteristics
Independent t-
Syntax score
test
CRF No 32.03 ± 9.62 10 – 58 NA NA
No 31.70 ± 9.14 10 – 58
PVD 0.323 0.748
Yes 39.88 ± 17.99 17 – 54.5
Prior CVA No 32.03 ± 9.62 10 – 58 NA NA
No 31.51 ± 9.31 10 – 57
Prior MI 0.893 0.374
Yes 33.44 ± 10.48 16 – 58
t: Independent t-test
Ejection Fraction
All cases in our study having EF < 40%. There was no statistically
significant correlation between syntax score and ejection fraction.
Table (13): Results of association between SYNTAX score and ejection

fraction
Syntax score
r P-value
LVEF -0.026 0.800
There was a statistically significant positive (direct) correlation between

SYNTAX score and number of grafts. An increase in SYNTAX score is associated
with an increase in number of grafts and vice versa.
There was a statistically high significant positive (direct) correlation

between SYNTAX score and cross-clamp time. An increase in SYNTAX score is
associated with an increase in cross-clamp time and vice versa.

between SYNTAX score and total CPB. An increase in SYNTAX score is
associated with an increase in total CPB and vice versa.
Table (14): Results of association between SYNTAX score and intraoperative
findings
Syntax score
r P-value
Number of grafts r = 0.213 0.030
Total CPB 0.458** 0.000
Cross clamp 0.490** 0.000
High significant at P ≤ 0.01
Figure (15): Scatter diagram representing positive correlation between SYNTAX score and
number of grafts
Total CPB
Figure (17): Scatter diagram representing positive correlation Between SYNTAX score and
cross-clamp time
There was statistically significant correlation between syntax score and

blood transfusion and use of Inotropes where patients who received blood
transfusion showed statistically significantly higher mean syntax score than those
who didn’t had transfusion.
Patients who received Inotropes also showed statistically significantly higher

mean syntax score than those who didn’t receive Inotropes.

other post-operative findings.
Table (15): Results of association between SYNTAX score and Post-operative

findings

Yes 38.67 ± 11.11 29 – 54.5
No 31.85 ± 9.57 10 – 58
IABP 0.606 0.546
Yes 33.89 ± 10.50 24 – 51
No 31.60 ± 9.49 10 – 57
ARRHYTHMIAS 1.112 0.269
Yes 34.68 ± 10.37 14 – 58
No 28.48 ± 12.07 10 – 58
INOTROPES 2.170 0.032
Yes 33.21 ± 8.42 14 – 57
No 31.88 ± 9.55 10 – 58
Acute RF 0.877 0.383
Yes 36.83 ± 12.83 26 – 51
No 26.41 ± 8.78 10 – 52
BLOOD TRANSF 4.359 0.000
Yes 34.68 ± 8.88 21 – 58
No 32.05 ± 9.62 10 – 58
REOPENING -0.096 0.923
Yes 31.50 ± 11.63 21 – 44
There was statistically significant correlation between syntax score and ICU
stay and duration of Mechanical ventilation .

Syntax score
r P-value
ICU Stay 0.246* 0.014
Mechanical ventilation 0.399** 0.000
Total ICU stay
Figure (19): Scatter diagram representing positive correlation between syntax score and
Mechanical ventilation
Early Outcome
There was no statistically significant correlation between SYNTAX score and

MACCE. Also There was no statistically significant correlation between syntax
score and MI and Death.
Correlations could not be computed for cerebro-vascular accidents because

there were no cases.
Table (16): Results of association between SYNTAX score and Early Outcome

No 32.21 ± 9.47 10 – 58
MACCE 1.300 0.199
Yes 36.07 ± 9.3 26 – 54.5
No 31.55 ± 9.49 10 – 58
MI 1.601 0.113
Yes 36.89 ± 10.19 26 – 54.5
CVA No 32.03 ± 9.62 10 – 58 NA NA
No 31.61 ± 9.43 10 – 58
DEATH 1.761 0.081
Yes 38.67 ± 11.11 29 – 54.5
Association between Subgroups SYNTAX score and different
variables
Demographic data
No significant colleration between Age , Sex and BMI with all subgroups of
syntax score.
Table (17): Results of association between SYNTAX score subgroups and

Demographic data
One Way
Low Syntax Intermediate High Syntax
ANOVA
score Syntax score score
test
No = 16 No = 40 No = 44 F/X²* P-value
Mean ± SD 54.56 ± 10.37 54.73 ± 8.29 56.32 ± 7.05
Age 0.502 0.607
Range 31 – 68 36 – 69 36 – 69
Female 5 (31.2%) 14 (35.0%) 10 (22.7%)
Sex 1.580 0.454*
Male 11 (68.8%) 26 (65.0%) 34 (77.3%)
BM Mean ± SD 27.19 ± 3.90 28.70 ± 3.67 28.27 ± 3.66
0.955 0.388
I Range 22 – 34 22 – 35 22 – 35
*: Chi-square test
P > 0.05: NS
P < 0.05: S
P < 0.01: HS
Risks factors
There was no statistically significant association between subgroups of

syntax score and different risk factors.
Table (18): Results of association between syntax score subgroups and Risks
factors
Intermediat
Low Syntax e High Syntax Chi-square
score Syntax score test
score
No = 16 No = 40 No = 44 X²/F* P-value
No 5 (31.2%) 22 (55.0%) 14 (31.8%)
Smoker 5.403 0.067
Yes 11 (68.8%) 18 (45.0%) 30 (68.2%)
No 5 (31.2%) 12 (30.0%) 14 (31.8%)
HTN 0.033 0.984
Yes 11 (68.8%) 28 (70.0%) 30 (68.2%)
No 4 (25.0%) 14 (35.0%) 17 (38.6%)
DM 0.959 0.619
Yes 12 (75.0%) 26 (65.0%) 27 (61.4%)
Hypercholesterolem No 6 (37.5%) 12 (30.0%) 13 (29.5%)
0.378 0.828
ia Yes 10 (62.5%) 28 (70.0%) 31 (70.5%)
There was no statistically significant correlation between syntax score

subgroups and any of the clinical characteristics.
Correlations could not be computed for CRF and Prior CVA because there
were no cases.
Table (19): Results of association between syntax scoresubgroups and
Intermediate
Low Syntax score High Syntax score Chi-square test
Syntax score
No = 16 No = 40 No = 44 X²/F* P-value
No 16 (100.0%) 40 (100.0%) 44 (100.0%)
CRF NA NA
Yes 0 (0.0%) 0 (0.0%) 0 (0.0%)
No 15 (93.8%) 40 (100.0%) 41 (93.2%)
PVD 2.788 0.248
Yes 1 (6.2%) 0 (0.0%) 3 (6.8%)
No 16 (100.0%) 40 (100.0%) 44 (100.0%)
Prior CVA NA NA
Yes 0 (0.0%) 0 (0.0%) 0 (0.0%)
No 12 (75.0%) 31 (77.5%) 30 (68.2%)
Prior MI 0.962 0.618
Yes 4 (25.0%) 9 (22.5%) 14 (31.8%)
*: One Way ANOVA test
P < 0.05: S
Ejection Fraction
There was no statistically significant correlation between SYNTAX score

subgroups and ejection fraction.
Table (19): Results of association between SYNTAX score Subgroups and
ejection fraction
Low Syntax Intermediate High Syntax Chi-square

score Syntax score score test
No = 16 No = 40 No = 44 X²/F* P-value
Mean ±
35.75 ± 3.49 35.15 ± 3.33 35.05 ± 2.95
LVEF SD 0.293 0.746*
Range 29 – 39 25 – 39 29 – 39
There was a statistically significant positive (direct) correlation between

syntax score subgroups and number of grafts. An increase in syntax score is
associated with an increase in number of grafts and vice versa.

between syntax score subgroups and cross-clamp time. An increase in syntax score
is associated with an increase in cross-clamp time and vice versa.

between syntax score subgroups and total CPB. An increase in syntax score is
associated with an increase in total CPB and vice versa.
Table (20): Results of association between syntax score Subgroup and
intraoperative findings
Low Syntax Intermediate

High Syntax score Chi-square test
score Syntax score
No = 16 No = 40 No = 44 X²/f* P-value
Mean ± SD 2.06 ± 0.57 2.88 ± 0.79 3.34 ± 0.71
No of grafts 18.521 0.000
Range 1–3 2–5 2–5
P < 0.05: S
Low Syntax Intermediate High Syntax One Way

score Syntax score score ANOVA test
No = 16 No = 40 No = 44 F P-value
73.38 ± 122.84 ±
TOTAL Mean ± SD 107.60 ± 33.60
14.63 24.95 18.879 0.000
CPB
Range 45 – 110 63 – 230 75 – 220
43.00 ±
Mean ± SD 63.00 ± 15.84 75.68 ± 19.35
Cross clamp 14.25 21.632 0.000
Range 20 – 80 35 – 100 50 – 160
P < 0.05: S
No of grafts
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
Low Syntax score Intermediate Syntax High Syntax score
score
Figure (20): Bar Chart representing positive correlation between SYNTAX score subgroup
and number of grafts
TOTAL CPB
140
120
100
80
60
40
20
0
Low Syntax score Intermediate Syntax score High Syntax score
Figure (21): Bar Chart representing positive correlation between SYNTAX score Subgroup
and Total CPB
cross clamp
80
70
60
50
40
30
20
10
0
Low Syntax score Intermediate Syntax score High Syntax score
There was statistically high significant correlation between SYNTAX score

subgroups and blood transfusion and use of Inotropes where patients who received
blood transfusion showed statistically significantly higher mean SYNTAX score
than those who didn’t had transfusion.
Patients who received Inotropes also showed statistically significantly

higher mean SYNTAX score than those who didn’t receive Inotropes.
There was statistically high significant correlation between SYNTAX score

subgroups and ICU stay and Mechanical ventilation.

Table (21): Results of association between syntax score subgroups and Post-
operative findings
Intermediate
High Syntax One Way
Low Syntax score
score ANOVA test
Syntax score
No = 16 No = 40 No = 44 F/X²* P-value
Mean ± SD 2.44 ± 0.89 3.23 ± 1.07 3.39 ± 1.15
ICU Stay 13.135 0.000
Range 2–5 2–6 2–7
Mechanical Mean ± SD 6.69 ± 1.66 12.15 ± 4.52 13.23 ± 4.95
13.135 0.000
ventilation Range 4 – 11 7 – 24 5 – 34
No 16 (100.0%) 35 (87.5%) 40 (90.9%)
IABP 2.181 0.336*
Yes 0 (0.0%) 5 (12.5%) 4 (9.1%)
No 15 (93.8%) 36 (90.0%) 35 (79.5%)
Arrhythmias 2.852 0.240*
Yes 1 (6.2%) 4 (10.0%) 9 (20.5%)
No 10 (62.5%) 8 (20.0%) 7 (15.9%)
Inotropes 14.473 0.001*
Yes 6 (37.5%) 32 (80.0%) 37 (84.1%)
No 16 (100.0%) 39 (97.5%) 42 (95.5%)
acute RF 0.890 0.641*
Yes 0 (0.0%) 1 (2.5%) 2 (4.5%)
No 13 (81.2% 14 (35.0%) 5 (11.4%)
BLOOD T 26.612 0.000*
Yes 3 (18.8%) 26 (65.0%) 39 (88.6%)
No 15 (93.8%) 39 (97.5%) 43 (97.7%)
Reopening 0.695 0.706*
Yes 1 (6.2%) 1 (2.5%) 1 (2.3%)
*: Chi-square test
P < 0.05: S
Early Outcome
There was no statistically significant correlation between syntax score

subgroups and MACCE. Also There was no statistically significant correlation
between syntax score and MI and Death.
Correlations could not be computed for cerebro-vascular events because there were
no cases.
Table (22): Results of association between SYNTAX score Subgroups and

Early Outcome
Intermediate
Low Syntax score High Syntax score Chi-square test
Syntax score
No. % No. % No. % X² P-value
No 16 100.0% 35 87.5% 35 79.5%
MACCE 4.202 0.122
Yes 0 0.0% 5 12.5% 9 20.5%
No 16 100.0% 36 90.0% 39 88.6%
MI 1.931 0.381
Yes 0 0.0% 4 10.0% 5 11.4%
No 16 100.0% 40 100.0% 44 100.0%
CVA NA NA
Yes 0 0.0% 0 0.0% 0 0.0%
No 16 100.0% 38 95.0% 40 90.9%
DEATH 1.838 0.399
Yes 0 0.0% 2 5.0% 4 9.1%
Chi-square test
P < 0.05: S
SUMMARY
Despite tremendous medical progress over the last 20 years in the fields of
conservative, interventional and surgical treatment, the selection of therapy in
stable coronary artery disease (CAD) remains a challenge, Specifically, the optimal
revascularization. (Hahalis and Alexopoulos., 2014).
Coronary artery bypass graft surgery (CABG) has been considered the
optimum revascularization treatment for patients with de novo left main (LM)
disease and/or three-vessel disease (3VD) (Kappetein et al., 2011).
Prior to the development of the SS, several coronary angiographic-based

scores were created to risk-stratify patients with CAD. Most of these early scores
were elaborated around the concept of quantification of myocardium at risk and/or
severity of coronary artery stenosis.(Yadavet al., 2013)
The awareness of the risk of feasible complications before treatment may

lower these complications. The SYNTAX score (SS) is a scoring system to
indicate the complexity of coronary artery disease (CAD), to select the optimal
technique of revascularization and to distinguish patients at risk for major adverse
events. Recently, the reproducibility of angiographic SSs has been shown to be
clinically acceptable. Angiographic SSs are based on lesions and include
parameters such as dominancy, number, location and length of the lesion, vessel
tortuosity, grade of calcification, presence of thrombus and branching. The total SS
is obtained by multiplying the score for each separate lesion. (Stahli et al., 2012)
In real-life patients undergoing CABG, the Syntax score does not

independently predict short-term outcome. Intermediate and high Syntax scores do
identify high risk patients with increased crude mortality rates (Gannotet al., 2014)
The SYNTAX score can not predict the outcome of CABG patients.
SYNTAX suffers from lack of clinical risk factors. (Serruyset al., 2009)
This study aims to clarify whether SYNTAX score affects the outcome of
bypass grafting in CABG patients with low ejection fraction as defined by major
adverse cerebrovascular and cardiac events (MACCE) and its components over 30
days postoperative follow-up period.
Methods: 100 patients who underwent primary CABG for left main
coronary artery disease or one, two, three vessel disease were studied all diagnostic
angiograms were scored by one experienced investigator who was blinded as to
procedural data and clinical outcome.
Data were collected, revised, coded and entered to the Statistical Package
for Social Science (IBM SPSS) version 20. Qualitative data were presented as
number and percentages while quantitative data with parametric distribution were
presented as mean, standard deviations and ranges.
The comparison between two groups with qualitative data were done by
using Chi-square test and/or Fisher exact test was used instead of Chi-square test
when the expected count in any cell was found less than 5.
Comparison between two independent groups regarding quantitative data

with parametric distribution were done by using Independent t-test.
Comparison between more than two independent groups regarding

quantitative data with parametric distribution were done by using One Way
ANOVA.
Spearman correlation coefficients were used to assess the correlation
between syntax score and the studied parameters.
The confidence interval was set to 95% and the margin of error accepted
was set to 5%. So, the p-value was considered significant as the following:
 P > 0.05: Non significant
 P < 0.05: Significant
 P < 0.01: Highly significant.
RESULLTS: The present study was conducted on 100 patients; 29 females

(29%) and 71 males (71%). The mean and standard deviation values of age were
55.40 ± 8.10years with a minimum of 31 and a maximum of 69 years. The overall
EURO score below 5.The syntax score ranged from 10 to 58 with mean
32.03.There was no statistically significant correlation between syntax score and
age. There was also no statistically significant association between syntax score
and gender.
There was statistically significant positive correlation between syntax

score and number of grafts done, cardiopulmonary bypass time , ischemic time,
blood transfusion, inotropic support, ICU stay and Mechanical ventilation.
Correlations could not be computed for cerebro-vascular accidents because

there were no cases because of small sample size.
Our study group subdivided into 3 subgroups which showed the same
results of the whole sample.
Conclusion: This study showing that, the Syntax score seems not to be the
predictor of major adverse cardiac and cerebrovascular events such as death, MI,
or stroke.
NORMAL CORONARY ANATOMY
The aortic root represents the outflow tract from the left ventricle and extends
between the aortic valve and the sinotubular junction which demarcates the aortic
root from the ascending aorta. Aortic root has three small dilatations called the
coronary sinuses (Fig. 1a). More anteriorly located right coronary sinus (RCS)
gives rise to the right coronary artery (RCA) and the left main coronary artery
(LMCA) arises from more cephaladly located the left coronary sinus (LCS) (Fig.
1b). The posteriorly located aortic sinus normally does not give rise to a coronary
artery and named as the noncoronary sinus (Erol et al., 2013).
A B
Figure 1: Normal anatomy of the aortic root and coronary arteries. Short- axis coronary
computed tomography angiography image (a) shows that the aortic root has 3 aortic
sinuses which are the right coronary sinus (RCS), left coronary sinus (LCS) and
noncoronary sinus (NCS). Maximum intensity projection reformatted coronary CT
angiography image (b) at the level of the coronary sinuses demonstrates that the right
coronary artery (RCA) originates from anteriorly located the RCS and the left main
coronary artery (LMCA) arises from posteriorly located the LCS. The LMCA divides into
the left anterior descending artery (LAD) and the circumflex artery (LCx) (Erol et al.,
2013).
Right coronary artery
The right coronary artery arises from the right anterior part of the aortic sinus and
runs forward to join the right coronary sulcus. After originated from the RCS, the
RCA runs downwards in the right atrioventricular groove to reach the cardiac crux.
The first branch of the RCA is the conus artery in most of the cases which supply
the right ventricular outflow tract (Figure 2). In as mall proportion (11.6 to 22%),
the conus artery has an origin directly from the aorta which sometimes causes
problems during ventriculostomy used to treat ventricular septal defect or
pulmonary stenosis (Cademartiri et al., 2008).
Figure 2: Diagram illustrating the right coronary artery [RCA] and the course of the
sinoatrial [SA] node artery.(A) Right coronary artery with the SA nodal artery in the left
anterior oblique view with a corresponding angiogram and (B) right coronary artery with
the SA node artery in aright anterior oblique view with corresponding angiogram. (Images
reprinted from: Netter FH.Colacino S (ed). Atlas of Human Anatomy.Summit, NJ: Ciba-
Geigy Corp.; 1989.1.)
The sinoatrial node artery originates from the RCA as the second branch in 55 to
65% ofpatients (Figure 2) and from the proximal left circumflex artery (LCx) in 35
to 45% of the population (Erol and Şeker., 2012). It can also originate directly
from the LCS, RCS, LMCA, or from the ascending aorta in a small percentage of
patients (0.7%) (Erol and Şeker, 2012). It courses dorsally towards lateromedial
aspect ofthe right atrium. The middle RCA gives rise to several right ventricular
branches which supply the anterior free wall of the right ventricle. The largest of
them called as the acute marginal branch that runs along the acute margin from
base to apex (Figure 2). The atrioventricular node artery generally originates
fromthe dominant coronary artery (Erol and Şeker, 2012). In right coronary
dominancy, the RCA gives off the posterior descending artery(PDA) and the
posterolateral branch artery (PLB) which perfuse the posterior interventricular
septum and the inferior left ventricular wall, respectively . The RCA is divided into
3 segments. The proximal segment runs between the ostium and the right
ventricular branch. The middle segment is from this point to the acute marginal
branch and after, the distal segment courses towards the crux of the heart (Erol et
al., 2013).
Coronary dominance
Coronary dominance is determined by observing which coronary artery passes

over the crux of the heart and gives off the PDA. Mainly, the co-dominance is a
state where branches from both the distal RCA and the distal LCx supply the
posterior interventricular septum (Schlesinger, 1940). However, some authors
define co-dominance as a state where the PDA originates from the RCA and the
PLB from the LCx (Kini et al., 2007). Because of these different definitions, the
incidence of coronary artery dominance varies in the literature (Koşar et al., 2009).
The reported incidence of right dominance is 70%to 89% (Figure 3), left
dominance 7% to 13% and co-dominance 2.5% to20% (Koşar et al., 2009). In case
of left dominance, the RCA remains in small caliber and terminates before
reaching the cardiac crux.
A B
Figure 3: (A) Diagram of the normal right-dominant coronary artery anatomy. (B) Normal
coronary Anatomy viewed from the sternocostal (anterior) surface. (C) Right-dominant
circulation viewed from the diaphragmatic surface of the heart. Note how the right
coronary artery travels in the posterior interventricular sulcus, giving rise to the posterior
descending artery. [LM = left main artery; LAD = left anterior descending artery; Cx =
circumflex; RCA = right coronary artery; S = septal; D = diagonal;OM = obtuse marginal;
RM = right marginal;RPDA = right posterior descending artery;RPL = right
posterolateral; RI = ramus intermediate.]
Left main coronary artery
The LMCA arises from the aorta, close to the level of the sinotubular junction and
slightly cephalad from the origin of the RCA. It than takes a short course between
the main pulmonary artery and left atrium. The LMCA divides, beneath the left
atrial appendix, into the left anterior descending artery (LAD)and the LCx (Figure
4) (Cademartiri et al., 2008).
Figure 4: Diagram showing the left coronary artery. The left main courses around the
pulmonary artery to bifurcate into the left anterior descending and left circumflex.
In approximately 30% of the cases, the LMCA gives rise to the third vessel
between the LAD and LCx, called as the intermediate artery analogous to a
diagonal branch and usually supplies anterolateral wall of the left ventricle (Kini et
al., 2007). The LMCA length usually varies in between 1-2cm. Short LMCA (<5
mm) is accepted as a normal variant without clinical significance and found in
4.7% of the cases (Erol and Şeker., 2012).
Left anterior descending artery
The LAD courses downward in the anterior interventricular groove towards the
cardiac apex. It gives rise to diagonal branches laterally and septal branches
medially which supply to anterolateral free wall of the left ventricle and anterior
two thirds of the septum, respectively. The LAD has three segments like the RCA.
The proximal and middle segments of LAD is separated from each other by the
first septal branch and halfway point from the first septal branch to the apex
determines the boundary between the middle and distal segments.
Left circumflex artery
The LCx turns backwards after its origin from the LMCA and runs downwards in
the left atrioventricular groove. The proximal portion of the LCx passes under the
left atrial auricle that makes the visualization difficult. The LCx gives rise to a
variable number of marginal branches and supply the lateral wall of the left
ventricle. The LCx is divided into proximal and distal portions in relation to the
major obtuse marginal branch origin.
Normal diameter of coronary arteries
Diameter of coronary arteries is influenced by gender, body size, coronary

dominancy and left ventricular mass, and greatly differs person to person (Dodge
et al., 1992). One of the main advantages of CCTA over CCA is its ability to
provide visualization of the vessel wall and surrounding soft tissues together with
the vessel lumen. So, CCTA can give much more correct measurements about
vessel sizes than CCA which gives information only about vessel lumen. Coronary
artery lumen diameter and area studies are mainly CCA based and there is need
studies with CCTA to define range of normality for coronary artery diameters.
PATHOGENESIS OF THEROSCLEROSIS
(CORONARY ATHEROSCLEROSIS)
Introduction
Atherosclerosis is a progressive disease of medium and large sized arteries

characterized by focal intimal lesions called atheromas or atherosclerotic plaques
that protrude into vessel lumen and eventually leading to various complications.
‘Athero’ in Greek means gruel and ‘sklerose’ means hard. Coronary arteries are
particularly susceptible to atheromas. In developed countries atherosclerosis causes
more than half of total mortality, Coronary Artery Disease (CAD) is responsible
for a major proportion of these deaths (Kralova et al., 2014). The most dreaded
sequel of atherosclerosis, such as myocardial infarction and stroke, are caused by
superimposed thrombosis in a ruptured plaque. Therefore, the intriguing question
is not why atheroma develops but rather why atherosclerosis, after years of
indolent growth, suddenly becomes complicated with luminal thrombosis. If such
vulnerable plaques, which are prone to rupture could be detected beforehand, it
would contribute towards decreasing the morbidity and mortality due to
atherosclerosis. In this respect,current advances in understanding the pathogenesis
of atherosclerosis has given some major targets for the functional imaging of
atheromatous plaques. Once these rupture prone plaques are detected their critical
assessment and observation by the physician can avert their risk of disruption and
subsequent death causing potential. Besides this, the type of plaque also guides the
therapy that will benefit the patient in alleviating his symptoms (Singh et al.,
2012).
Endothelial cells, leukocytes, and intimal smooth muscle cells are the major
players in the development of this disease. Approximately 76% of all fatal
coronary thrombi are precipitated by plaque rupture. Plaque rupture is a more
frequent cause of coronary thrombosis in men (80%) than in women (60%).
Ruptured plaques are characterized by a large lipid-rich core, a thin fibrous cap
that contains few smooth muscle cells and many macrophages, angiogenesis,
adventitial inflammation, and outward remodeling. Plaque rupture is the most
common cause of coronary thrombosis. Ruptured plaques and, by inference,
rupture-prone plaques have characteristic pathoanatomical features that might be
useful for their detection in vivo by imaging (Falk et al., 2006).
Therefore, the vital question is not why atherosclerosis develops but rather why
none or only few among many plaques within a given person apparently pass
through a thrombosis-prone and dangerous phase during a lifetime (Casscells et
al., 2003). That is what it is all about; preventing the development of thrombosis-
prone plaques and, if they already are there, finding and treating those who harbor
them and are at high risk of losing myocardium, brain, and/or life. This viewpoint
describes the pathogenesis of atherosclerosis with this ambitious goal in mind.
Risk Factors in Atherosclerosis
Various prospective epidemiological trials have shown that the risk of developing
the manifestations of coronary atherosclerosis is increased by smoking,
hyperlipidemia, hypertension and diabetes. These risk factors can be prevented by
lifestyle modification measures. The non modifiable risk factors are increased age,
male gender and genetics and most importantly a positive family history. Still there
are 20% of cardiovascular events that take place in the absence of the above
mentioned risk factors. Few other factors have been implicated to explain it like
increased levels of C Reactive Protein (CRP), an acute phase reactant synthesized
primarily by liver, hyperhomocysteinemia, metabolic syndrome, increased
lipoprotein A levels, elevated plasminogen activator inhibitor 1 levels. Last but not
the least, competitive and stressful lifestyle, better known as Type A personality, is
another very important risk factor for developing atherosclerosis (Singh et al.,
2012).
Theories of atherogenesis pathology
Atherosclerosis pathology research began more than 100 years ago with pioneering
German and Russian studies recognizing lipid and inflammatory theories. Further
development of atherosclerosis patholology started in the 1950s by Keys
documenting a crucial role of cholesterol concentration. In 1985 Brown and
Goldstein discovered that human cells have low-density lipoprotein (LDL)
receptors on cell surfaces that remove cholesterol from the blood. If LDL receptors
are not present in sufficient numbers or if genetic defects in LDL receptor structure
occur, individuals develop hypercholesterolemia and become at risk for cholesterol
related diseases (Goldstein and Brown., 1973).
In the 1990s, Virchow’s hypothesis was rediscovered by Russell Ross. He

formulated the “response to injury” hypothesis (Ross, 1999), which proposed that
endothelial damage is the first step in the development of atherosclerotic lesions
followed by monocyte and T-cell infiltration into the arterial wall (Figure 5)
(Jonassonet al., 1986). Although this protective effect of the intact endothelium to
modify LDL atherogenic lipoprotein and monocyte influx into arterial wall has
been questioned, the pioneer papers of Ross are still frequently referenced, and so-
called endothelial dysfunction is supposedly the first sign of preclinical
atherosclerosis development. It should be emphasized that under physiological
conditions, transcellular LDL particle transport occurs through the endothelium
(Rosengrenet al., 2002).
Because it is perceived that the main function of monocytes and T cells is

connected to local or systemic infection, several theories that proposed infectious
disease as the cause of atherosclerosis appeared in the 1970s (Epstein et al., 2009).
This concept is also supported by experiments performed by Fabricant et al.
(1978), who found the presence of arterial lesions in chickens that had been
infected with avian herpes virus. These lesions were similar to atherosclerotic
changes in humans. Later, several other infectious agents, which might be
responsible for atherosclerotic changes in humans, began to appear gradually.
These included Chlamydia pneumoniae, Cytomegalovirus, Helicobacter pylori,
hepatitis A virus, Porphyromonas gingivalis, Herpes simplex virus and others,
which most likely reflect a synergy of multiple infectious agents in the
development of atherosclerosis. Antibodies against various pathogens were
detected in atherosclerotic plaques. It was observed that in the case of Chlamydia
pneumonia, the DNA of which was found in atherosclerotic plaques by polymerase
chain reaction (PCR) (Farsaket al., 2000), there is invasion and damage in the
arterial wall, increased LDL uptake by macrophages and foam cell formation in the
neointima (Kalayoglu and Byrne., 1998).
Cytomegalovirus infection increased adhesion molecule expression, particularly

intercellular adhesion molecule 1 (ICAM-1), on the endothelial surface
(Altannavch et al., 2002). The animal model demonstrated cross immune response
against heat shock protein 60 (HSP-60) – antigen located on the surface of
Helicobacter pylori and on the endothelial cell surface (Ayada et al., 2009).
It is quite clear that viral and bacterial infections likely do not play a direct role in
the process of atherosclerosis, as a sharp decrease of myocardial infarction
mortality was not related to incidence of different infectious diseases (Dvořáková
and Poledne., 2004). Concurrently, a certain proinflammatory state, which is
genetically determined, determines different monocyte behavior (Hubáčeket al.,
1999). The proinflammatory state marker could be C-reactive protein (CRP), as a
number of studies have revealed that inflammatory markers including CRP and
proinflammatory cytokines are strong predictors of atherosclerosis and other
cardiovascular diseases (Ridkeret al., 1998). The importance of the
proinflammatory state in atherogenesis was highlighted by findings that increased
CRP concentration in the “normal” range represents a significant marker of
cardiovascular disease risk (de Maat and Trion, 2004). It has been documented
that in healthy men who later suffered a myocardial infarction (MI), the
concentrations of IgA, IgE and IgG antibodies were significantly higher than in
control (Kovannenet al., 1998).
The level of subclinical inflammation might be affected by several genetic and

environmental factors including the effect of individual diet. There is considerable
evidence that visceral fat in obesity plays a crucial role in the inflammatory process
as a chronic inflammatory disease with dysregulation of pro- and anti-
inflammatory cytokine production (Lyon et al., 2003). It was also documented that
a switch from a saturated fatty acid diet to a polyunsaturated fatty acid diet reduced
CRP concentration (Lesná et al., 2013). CRP concentration increased with
increasing body weight and is related to visceral fat volume (Tintěra et al., 2004).
A positive relation of CRP to body mass index (BMI), waist circumference and
triglyceride concentration was also documented. Substantial sex differences were
observed in the relationship of CRP to age. Whereas it is continuously increasing
in men, this increase appears in women only after menopause. A decrease in body
weight and visceral fat volume by increased physical activity was accompanied by
a significant decrease of CRP levels in young obese women (Poledne et al., 2009).
Figure 5: The role of monocytes in the initiation and progression of atherosclerosis.

Following initial injury, endothelial cells become activated and facilitate the rolling,
attachment and transmigration of monocytes into the subendothelial space. Monocytes can
differentiate into macrophages, which secrete proinflammatory cytokines. Engulfment of
lipoprotein particles by macrophages can lead to fatty streak formation, which is the
earliest ultrastructural alteration in atherogenesis. The migration of smooth muscle cells
from the tunica media into the tunica intima further promotes atherogenic processes.
Monocyte-derived cells turn this early lesion into an advanced atherosclerotic plaque that
is comprised of a lipid-and macrophage-rich necrotic core that is finally destabilized,
leading to plaque rupture (Heine et al., 2012).
1- Atherogenic Stimuli
Elevated plasma cholesterol level (normally <150 mg/dl) is probably unique in

being sufficient to drive the development of atherosclerosis, even in the absence of
other known risk factors . The other risk factors, such as hypertension, diabetes,
smoking, male gender, and possibly inflammatory markers (e.g., C reactive
protein, cytokines, and so on), appear to accelerate a disease driven by atherogenic
lipoproteins, the first of which being low-density lipoprotein (LDL). Mechanism is
uncertain which is individually and clinically different with the same plasma
cholesterol level (Glass et al., 2001).
2- Protective Factors
Alcohol, exercise, and high-density lipoprotein (HDL) and its major

apolipoprotein, apoA-I, confer protection against diseases caused by
atherothrombosis. Among other things, HDL/apoA-I prevents the atherogenic
modifications of LDL and promotes “reverse cholesterol transport,” which slows
plaque progression and may induce rapid regression, documented in experimental
studies and suggested by serial intravascular ultrasound examinations of patients
with acute coronary syndrome (Lewis et al ., 2005).
3- Susceptibility
Based on risk factor scores our ability to predict clinical disease is limited and our
knowledge about the individual susceptibility to atherogenic stimuli is inadequate
(Wang et al., 2005). Inactivation of genes coding for monocyte chemotactic
protein-1 (MCP-1), its receptor on monocyte/macrophages (CCR2),and
macrophage colony-stimulating factor indicates profound impact on the
development of atherosclerosis in experimental studies in identical mice (Glass et
al., 2001).
However, with similar risk factor scores there is individual and arterial
susceptibility difference to atherothrombosis (Cunningham et al., 2005).
4- Cellular Components Of Atherosclerosis
Atherosclerosis is achronic immunoinflammatory, fibro proliferative disease of

large and medium-sized arteries fuelled by lipid (Hansson et al., 2005).
Endothelial cells, leukocytes, and intimal smooth muscle cells are the major
players in the development of this disease.
I- Endothelial cells:
In atherosclerosis-prone areas, the lesion begins to develop under an intact but

leaky, activated, and dysfunctional endothelium. Later, endothelial cells may
vanish and de-endothelialized (denuded) areas appear over advanced lesions, with
or without platelets adhering to the exposed subendothelial tissue.
Plasma molecules and lipoprotein particles extravasate through the leaky and
defective endothelium into the sub endothelial space depending on there size and
concentration, where potentially atherogenic lipoproteins are retained and modified
(e.g., oxidized) and become cytotoxic, proinflammatory, chemotaxic, and
proatherogenic.The mechanisms responsible for the atherogenic modification of
LDL are unknown but could include oxidation mediated by myeloperoxidase, 15-
lipoxygenase, and/or nitric oxide synthase (NOS). Nitric oxide is a potent oxidant
produced by both endothelial cells and macrophages. Nitric oxide produced by
endothelial NOS has vasodilator function and is potentially atheroprotective. In
contrast, nitric oxide produced via the much higher capacity inducible NOS in
macrophages, serving antimicrobial functions based on its potent oxidative
properties, is potentially pro atherogenic. So NOS exerts both protective and
atherogenic effects according to the source of production. The endothelium
becomes activated by atherogenic and pro inflammatory stimuli, and the
expression of adhesion molecules, primarily vascular cell adhesion molecule-1
(VCAM-1), are up-regulated, and monocytes and T-cells are recruited. Besides
VCAM-1, other adhesion molecules, such as intercellular adhesion molecule-1, E
selection, and P selection, probably contribute to the recruitment of blood borne
cells to the atherosclerotic lesion (Hansson et al., 2005) .
Endothelial dysfunctionis the key for atherosclerosis specially in the presence of

risk factors where the anti-inflammatory and antithrombotic properties of the
endothelium lost (Willerson et al., 2003).
II- Leukocytes:
The focal recruitment of circulating monocytes is considered one of the earliest

cellular responses in atherogenesis and, to a lesser extent, T lymphocytes
(Hansson et al., 2005).
The persistence of this cellular response seems to underlie disease progression. B

lymphocytes and plasma cells are rare in the intimal plaque but may be abundantly
present in adventitia next to advanced intimal disease (Houtkamp et al., 2001).
Activated mast cells may be found both in plaque and adventitia, particularly in
culprit lesions causing acute ischemic events (Kaartinen et al., 1998). Neutrophils
are rare in uncomplicated atherosclerosis but have been described in thrombosed
coronary plaques, probably recruited as a response to plaque rupture (Narukoet al.,
2002).
The mere adhesion to the endothelium is, of course, not enough for blood-borne
cells to arrive in the lesion, transendothelial migration also is required. As to that,
one or more chemokines (chemotactic cytokines) are necessary. Experimental
studies indicate that the most important atherogenic chemoattractants are oxidized
LDL and MCP-1.Monocyte chemotacticprotein-1 is a powerful chemokine and its
receptor on monocyte/macrophages (CCR2) may be up-regulated enormously
during plaque development, from 3,000/cell in the resting state to 60,000/cell when
stimulated. Monocyte chemotactic protein-1 attracts potently both monocytes and
T cells (but not neutrophils and B cells) and most likely plays a fundamental role in
the recruitment of these cells. Endothelial cells, smooth muscle cells, and
macrophages all contribute to over expression of MCP-1 in atherosclerosis. Thus,
once within the intima, monocyte-derived macrophages may recruit themselves by
secreting MCP-1. Cytokines (e.g, interleukin-8) also may play a role in monocyte-
macrophage trafficking (Glass et al., 2001).
Within intima, the monocytes differentiate into macrophages and internalize the
atherogenic lipoproteins via so-called scavenger receptors, of which SR-A and
CD36 have been demonstrated to play quantitatively significant roles in
experimental atherosclerosis. The development of lipid loaded macrophages
containing massive amounts of cholesteryl esters (foam cells) is a hallmark of both
early and late atherosclerotic lesions. With continuing supply of atherogenic
lipoproteins, the macrophages eat until they die because, in contrast to the native
LDL receptor, scavenger receptors are not down regulated by cellular cholesterol
accumulation. The death of macrophages by apoptosis and necrosis contributes to
the formation of a soft and destabilizing lipid-rich core within the plaque.
On the other hand, macrophages may under appropriate conditions (low LDL and
high HDL) shrink by effluxing cellular cholesterol to extracellular HDL via
membrane transporters, the initial step in “reverse cholesterol transport” (Glass et
al., 2001).
Aside from their scavenger function, macrophages also possess destabilizing and
thrombogenic properties by expressing matrix-degrading proteolytic enzymes (e.g.,
matrix metalloproteinases) and tissue factor Thus, these innate protective cells
initially recruited to combat cytotoxic lipids, turn into devastating friendly fire
during the progression of atherothrombosis. Immune activation is ongoing in
atherosclerotic lesions (Hansson et al., 2005).
Although lymphocytes are not required for the development of atherosclerosis, the
immune system modulates the progression of the disease. There are a number of
candidate antigens in the lesion that could be responsible for immune activation,
including modified LDL, heat-shock proteins, beta-2-glycoprotein I, and microbial
antigens. Of these, the most extensive data support an important role for oxidized
LDL, which is abundantly present in atherosclerotic plaques, where it is recognized
by T-cells. The up-regulated expression of the immune mediator CD40 and its
ligand CD154 by all cell types present in advanced atherosclerotic lesions
promotes lesion formation in atherosclerosis-prone mice (Hansson et al., 2005).
III- Smooth muscle cells:
Macrophages, endothelial cells, and a few T cells are the only cells participating in
the development of the early and asymptomatic foam-cell lesion, the fatty streak.
The immunoinflammatory response during the disease progression is joined by a
fibro proliferative response mediated by intimal smooth muscle cells. These cells
are responsible for healing and repair after arterial injury (Kragel et al., 1989).
Nevertheless, plaque stability and protection from rupture and thrombosis is the
role of smooth muscle cells and the collagen-rich matrix. The smooth muscle cell
is the principal connective tissue producing cell in the normal and diseased intima
(Schwartz et al., 2000). Smooth muscle cells having a recruitment, proliferation,
and synthetic activities which is responsible for repairing and protecting the
plaques, For unknown reason smooth muscle cells are lacking at rupture sites, but
apoptotic cell death could play an important role (Geng et al., 2002).
Special Features Of Atherosclerotic Plaques
I- Lipid-rich core:
The scavenging macrophages clearing the atherogenic lipoproteins from the intima
in the early in atherogenesis, giving rise to intracellular lipid accumulation (foam
cell formation). These cells die and leave the lipid behind as a soft, destabilizing,
and inert necrotic (atheromatous) core within the plaque so the protective function
may be overwhelmed and turned into a detrimental disease. Atherogenic
lipoproteins also accumulate within intima without first passing through foam
cells. The lipid-rich atheromatous core is avascular, hypocellular, soft, and totally
devoid of supporting collagen. Its size is critical for the stability of a plaque
(Guyton et al., 2001).
II- Cell death:
Endothelial cells, macrophages, and smooth muscle cells die by apoptosis or

necrosis during the disease progression. Disintegration of foam cells and loss of
smooth muscle cells leads to formation of a destabilizing lipid-rich core and a
fragile and rupture prone fibrous cap. Furthermore, apoptosis contributes
dramatically to the high tissue factor activity and thrombogenicity of the lipid-rich
core (Tedgui et al., 2001).
Plaques may grow inspite of cell death exceeds local cells proliferation is due to
new cell recruitment rather than local cell division.(Llodrá et al., 2004).
III- Calcification:
The total amount of calcification-the coronary artery calcium score is a marker of

coronary plaque burden and provides prognostic information beyond that provided
by traditional risk factor scoring (Pletcher et al., 2004). Focal calcification in
atherosclerotic plaques is very common and increases with age (Hoffmann et al.,
2003). Its active and controlled process, resembling calcification in bone, and both
lipid and connective tissue may calcify. (Beckman et al., 2001).
IV- Neovascularization and intraplaque hemorrhage:
Plaque neovascularization is amarker for high risk and active disease . Endothelial
proliferation originates from vasa vasorum in adventitia and extends through media
into the base of the plaque. The new micro vessels are fragile, are leaky, and
express cellular adhesion molecules (VCAM-1,intercellular adhesion molecule-1),
resulting in local extravasation of plasmaproteins, erythrocytes (bleeding), and
inflammatory. So, angiogenesis and inflammation often coexist and could mediate
rapid plaque progression (Barger et al., 1984).
No evidence that extravasated erythrocytes in the neovascularized areas (low-

pressure bleedings) may precipitates rupture of the plaque surface and/or acute
luminal thrombosis (Davies et al., 1984).
VI- Vascular remodeling and luminal stenosis:
During plaque development, remodeling of the artery takes place, in which the
flow-limiting potential of the intimal plaque may be attenuated (expansive
remodeling) or accentuated (constrictive remodeling) by reactive changes in the
underlying vessel wall. Plaques assumed to be rupture-prone (so-called inflamed
thin-cap fibroatheroma) and those responsible for acute coronary syndromes
usually are relatively large and associated with expansive remodeling, which tends
to preserve a normal lumen. In contrast, plaques responsible for stable angina
usually are smaller but, nevertheless, often are associated with more severe luminal
narrowing because of concomitant constrictive remodeling (Vink et al., 2001).
The reason for these different modes of remodeling is unknown. Experimental

studies indicate that processes in adventitia could play a decisive role in
remodeling.
V- Plaque rupture:
Plaque rupture is exposure of the thrombogenic core of the plaque due to deep
injury with areal defect or gap in the fibrous cap (Figure 6 ) that had separated its
lipid-rich atheromatous core from the flowing blood. This is the most common
cause of coronary artery thrombosis (Schaar et al., 2004).
Figure 6: Molecular and structural targets for imaging. Cross section of coronary artery
containing plaque assumed to be rupture-prone. Potential targets for imaging are
highlighted. They comprise: 1) the large lipid-rich necrotic core (orange asterisk), 2) thin
fibrous cap (blue arrows), 3)expansive remodeling (green arrow), and 4) vasa vasorum and
neovascularization (red open circles)( Falk., 2006).
I- Nonfatal thrombosis:
Plaque rupture is acommon and frequent event and often multiple in acute
coronary syndromes (Falk et al., 2000).Rupture of the plaque surface is followed
by variable amounts of hemorrhage into the plaque and luminal thrombosis,
causing sudden and rapid but often clinically silent progression of the lesion. It is
probably the most important mechanism underlying the episodic (versus linear)
progression of coronary lesions observed by serial angiography (Mann et al.,
1999).
II- Fatal thrombosis:
Plaque rupture is amore frequent cause of coronary thrombosis in men (80%) than
in women (60%). A recent extensive review of the literature revealed that plaque
rupture is responsible for 76% of all fatal heart attacks caused by coronary
thrombosis worldwide (Shah et al., 2011).The remaining 24% are caused by
plaque erosion and other less well-defined mechanisms.
III- Fibrin and platelets:
Multiple sites of endothelial denudation and plaque rupture developed and heal
during atherogenesis where platelets adhere and fibrin adhere to subendothelial
tissue. plaque rupture probably is much more thrombogenic than plaque erosion. In
the pathogenesis of arterial thrombosis, platelet aggregation is responsible for the
initial flow obstruction but fibrin formation is necessary for the subsequent
stabilization of the platelet-rich thrombosis. Thus, both platelets and fibrin may
accumulate over ruptured and eroded plaques.
IV- Contribution of bone marrow-derived cells:
Macrophages derived from bone marrow play a critical role in the initiation and
progression of atherosclerosis. However, endothelial cells and intimal smooth
muscle cells reside within the arterial wall and proliferate, migrate, and secrete
what might be needed for expedient healing and repair after injury. Smooth muscle
cells originated in the bone marrow were brought to the injured vessel wall with
the circulating blood (Sata et al., 2003).
The new trends nowdays is towards stabilization of the atherosclerotic plaques

against thrombosis and its devastating consequences. (Caplice et al., 2003).
THE SYNTAX TRIAL
Several randomized control studies and registries have previously shown

that coronary artery bypass surgery (CABG) is the preferred mode of
revascularization in patients with multi vessel and/or left main coronary
artery disease . The most recent large randomized study, Synergy
between percutaneous coronary intervention (PCI) with TAXUS and
cardiac surgery (SYNTAX), also confirmed this observation even when
percutaneous revascularization was performed using drug-eluting stents .
However, the SYNTAX trial was able to show that in patients with low
anatomic risk for PCI, e.g., lowest tertile of Syntax score (SS) , PCI may
be comparable to CABG in all aspects including target vessel
revascularization. The SYNTAX study confirmed that the Syntax score
is correlated with outcome only in patients undergoing PCI but failed to
show the same correlation in patients undergoing CABG . The
SYNTAX trial selected patients who were suitable for both PCI and
CABG according to the heart team and therefore may not represent
“real-world” patients who are routinely referred to CABG (Gannot et
al., 2014).
Current guidelines recommend coronary artery bypass graft surgery
(CABG) when treating significant de novo LM stenosis; however,
percutaneous coronary intervention (PCI) has a Class IIa indication for
unprotected LM disease in selected patients.
Scince first introduction of Coronary Artery Bypass Grafting (CABG) in 1968, it
rapidly became the standard of care for symptomatic patients with coronary artery
disease (Buxton et al., 1998). Advances in coronary surgery (e.g., off-pump
CABG, enhanced myocardial preservation , smaller incisions, use of arterial
conduits, and improved postoperative care) have reduced morbidity, mortality
(Barner et al., 2008). Percutaneous Coronary Intervention (PCI) was introduced in
1977 (Grüntzig., 1978). Experience with this approach, coupled with improved
technology, has made it possible to adopt PCI as viable treatment option for patient
complex coronary disease who would have been referred for CABG (Serruys et
al., 2006).
Despite this advances, the ideal revascularization treatment that is durable,

less invasive, carries insignificant morbidity and mortality is yet to be determined.
This has lead to the development of the so called Appropriateness Criteria for
Coronary Revascularization (Patel et al., 2009a,b), in general, PCI was rated as
appropriate for acute myocardial injury and most scenarios where there was
significant CAD associated with demonstrable ischemia and symptoms despite
adequate medical therapy. The degree of appropriateness generally increased as the
extent of myocardium at risk increased until the 3-vessel disease threshold of
CAD extent was reached. For these patients, PCI was rated as uncertain regardless
of the presence of diabetes or left ventricular dysfunction. PCI for left main CAD
was scored as inappropriate in all described settings. CABG was rated as
appropriate for 3-vessel and for left main CAD in all settings. Although CABG
remains the standard of care for patients with >50% stenosis of the three coronary
arteries and/or left main stem stenosis (Taggart., 2009).
Percutaneous coronary intervention (PCI) has progressed through simple balloon

angioplasty, to bare metal stents, and drug-eluting stents, and has become a rival to
CABG in patients with multivessel coronary artery disease (CAD) or left main
disease. However, the need for repeat revascularization, in-stent stenosis, and
thrombosis remain the achilis heal of PCI. The introduction of coronary artery
bypass surgery (CABG) in 1968 resulted in a paradigm shift in the management of
coronary artery disease. Subsequent randomized studies in patients with chronic
stable angina established the superiority of CABG over medical therapy in patients
with left main coronary artery disease and multivessel disease with left ventricular
dysfunction, especially if the proximal left anterior descending artery was
involved. The beneficial effect of CABG on the relief of angina was noted in all
trials (Gulati et al., 2009).
Various studies in recent years have compared CABG with PCI including BMS &
DES. The PCI without stents trials (e.g. BARI, CAPRI, RITA, EAST, GABI,
ERACI) (Bravata et al., 2007) and with bare metal stent (BMS) (ARTS I, SOS,
ERACIII, MASS II, AWESOME) (Takagi et al., 2008). Data from the majority of
the randomized clinical trials showed that CABG provides more effective angina
relief and less need for repeat revascularization, but offered no short term survival
benefit over PCI, except in patients with diabetes. However, the rate of strokes was
significantly increased in CABG patients (Bravata et al., 2007 and Takagi et al.,
2008).
Interestingly, the recently published meta-analysis of the BMS vs. CABG trials
which was the first to include long-term follow-up data, did not show any
significant differences in the rates of death, cardiovascular death, myocardial
infarction, cerebrovascular events and angina. Yet, again, higher rates of target
lesion revascularizations were observed in the PCI group (Bravata et al., 2007).
Two randomized studies (ARTSII and ERACI III) determined the efficacy of DES
compared to CABG in the setting of stable multivessel disease. Target vessel
revascularization was comparable to CABG in the
ARTS II (Serruys et al., 2005) and ERACI III, (Alfredo R., 2006) studies.
Recently published 3-year data from the ERACI III, group reveals a major adverse
cardiac and cerebrovascular events (MACCE) rate of 22.7%, equal to that of
CABG (Rodriguez et al., 2007). Data showing mortality benefit for CABG in
multivessel CAD compared to PCI are mainly derived from registries, with the
New York registry data (Hannan and Wu., 2008) showing a mortality rate
reduction of at least 25% across all anatomic subgroups infavor of CABG. The
SOS was a randomized trial that also reported a mortality benefit for surgery over
1 year, but with an exceedingly low death rate in the CABG arm (2% vs. 5%; P
=0.01). Meta-analysis of 13 randomized clinical trials (Hoffman et al., 2003) also
demonstrated a 1.9% survival advantage for CABG over PCI.
Randomized, controlled trials enrolled smaller numbers of patients, and many of

true trials were underpowered to detect survival benefit. Registries do have the
advantage of analyzing large number of real-life patients, but they provide
observational data usually affected by selection bias. Therefore, large scale
prospective randomized trials (such SYNTAX and FREEDOM) comparing PCI to
CABG in the today’s practice are poised to improve our understanding of how to
manage CAD in the ERA of DES. In this manuscript we discuss the SYNTAX trial
in some details.
Study design
The Synergy between percutaneous coronary intervention with TAXus and cardiac
surgery (SYNTAX) compared PCI with DES and CABG in patients with untreated
3VD and/or LMS disease (Serruys et al., 2009b). SYNTAX is the first randomized
prospective, multicenter, multinational, randomized, and controlled all comers’
trial to compare PCI using drug-eluting stents (DES) to CABG in patients with left
main disease and three vessel disease.
Study Participants
A total of 4337 patients with untreated 3VD or LMD or both initially screened.
About 3075 patients were found eligible for the trial 1800 patients deemed suitable
for the trial were randomized at 85 sites and of the remaining 1077 patients,198
patients were enrolled in the PCI registry and 1077 in the CABG registry. Patients
followed up at 30 days post procedure and at 1, 6 12, 30 and 60 months (Serruys et
al., 2009).
The primary end point and outcome of the study:
The compound clinical outcome constituted of death by any cause, strokes,

myocardial infarction, the necessity of repeated revascularization by PCI and/or
CABG (defined as MACCE – Major Cardiovascular or Cerebrovascular Events) at
12 months of follow-up I an attempt to assess the non-inferiority of PCI compared
to CABG. After 1 year follow, the study failed to meet its primary endpoint, with a
relative hazard of 1.44 for excess MACE with PCI. The primary endpoint of
SYNTAX, 12-month binary MACCE was significantly higher in the PCI arm
(12.4%CABG vs. 17.8% P = 0.002) due, in large part, to increased repeat
revascularization (CABG 5.9% vs. PCI 13.5%). The rate of repeat
revascularization was significantly higher among patients in the PCI group than
among those in the CABG group (13.5% vs. 5.9%, P <0.001). Most patients who
underwent repeat revascularization were treated with PCI rather than CABG. The
rate of stroke was significantly higher with CABG than with PCI at 12 months,
even though the two groups were well balanced with regard to carotid artery
disease and other risk factors for stroke (2.2% vs. 0.6% P0.003).
The two groups had similar rates of death from any cause or myocardial infarction
and of the combined end point of death from any cause, stroke, or myocardial
infarction. About 3.5% in the CABG group versus 4.4% in the PCI group (P
=0.37). The rate of death from cardiac causes was greater with PCI than with
CABG (3.7% vs. 2.1%, P = 0.05); the rate of death from non cardiac causes,
although not significant, was higher with CABG (1.4% vs. 0.7%, P = 0.13). Other
data showed that the rate of symptomatic graft occlusion was 3.4% in the CABG
group, and the rate of stent thrombosis in the PCI group 3.3% (P =0.89). Analysis
of secondary end points showed that the two treatment groups had similar rates of
death from any cause, stroke, or myocardial infarction (7.6% for PCI and 7.7% for
CABG).
After 2 years follow-up; MACCE was significantly increased in PCI patients

(CABG 16.3% vs. PCI 23.4%;P = 0.0002); mainly attributable to an increased rate
of repeat revascularization in PCI-treated patients (CABG 8.6% vs. PCI17.4%; P
<0.0001). The composite safety endpoint of death/stroke/MI was comparable
between the two groups (CABG9.6% vs. PCI 10.8%; P = 0.44). The rate of MI was
significantly increased in PCI patients (CABG 3.3% vs. PCI 5.9%; P =0.01),
whereas stroke remained significantly higher in CABG patients (CABG 2.8% vs.
PCI 1.4%; P= 0.03) after 2 years of follow-up, due to early increase in stoke rate.
Stroke rate over the second year was indistinguishable between the two arms (0.6%
for CABG versus 0.7% for PCI;P =0.82).
The flattening of the difference in stroke was replaced by an uptake in the MI rate
during the same period. Repeat revascularization rate, had narrowed to 3.7% for
CABG versus 5.6% for patients treated with stents after 1year, and was no longer
significant (P = 0.06).Serruys (ESC, 2009a) reported a statistically significant
decrease in the 2-year rate of major adverse cerebrovascular and cardiac events
(MACCE) in patients with a Syntax score =33who were treated with CABG vs.
those treated with PCI using aTaxus stent. For patients with a Syntax score <33,
the 2-year MACCE rate was similar between groups (Dalton K., 2009).
In the LM subgroup: at 2 years (Rodriguez et al., 2007) MACCE rates were

comparable between CABG and PCI-treated patients (CABG 19.3% vs. PCI
22.9%; P = 0.27). The impact of lesion complexity on 2-year clinical outcomes
was estimated by examining patient outcomes relative to SYNTAX Score tercile
(Serruys et al., 2009b). Low SYNTAX Scores: the rates of MACCE were not
significantly different between PCI and CABG (CABG 17.4% vs. PCI 19.4%, P =
0.63). Intermediate SYNTAX Scores, there was a trend towards increased MACCE
with PCI (CABG 16.4% vs. PCI 22.8%, P = 0.06). In the most complex patients
(SYNTAX Scores >33), MACCE was significantly increased in patients treated
with PCI (CABG 15.4% vs. PCI 28.2%; P = 0.0001).
The CABG registry patients who are technically unsuitable for PCI have the most
complex lesion anatomy as expressed by a higher SYNTAX score. In the CABG
registry the 12 month outcomes are: All Cause Death 2.5%, CVA 2.2%, MI
2.5%,repeat revascularization 3.0%, and MACCE 8.8%.Strengths of SYNTAX:
(Serruys et al., 2009b) the study is aprospective, multicenter trial in which a large
number of patients were enrolled at 85 centres in Europe and the United States. It
attempted to include ‘‘all comers’’, with 71% of screened patients enrolled in the
randomized or registry cohorts. While in previous less than 10% of screened
patients were included. The study used state-of-the-art CABG and PCI (with
arterial grafts and drug-eluting stents, respectively).
A ‘‘heart team’’ consisting of an interventional cardiologist and cardiac surgeon

reviewed each subject’s data to decide on the appropriate treatment. A very useful
part of the SYNTAX trial was not only reinforcing a multi-disciplinary team
approach but the introduction of the SYNTAX score. Limitations of SYNTAX:
(Serruys et al., 2009b) The follow-up period was only 12–24 months; the
outcomes of PCI and CABG over a longer period of follow-up in patients with
severe coronary artery disease are unknown. Since most of the patients (78%) were
men, it is unknown whether these findings are applicable to women. The patients
who underwent CABG were less likely to receive optimal medical therapy (i.e.,
statins, aspirin or other antiplatelet agents, and angiotensin-converting-enzyme
[ACE] inhibitors or angiotensin II-receptor antagonists), which may have
contributed to their increased risk of stroke.
The investigators did not discuss whether the strokes were related to the procedure
or influenced by differences in the occurrence of atrial fibrillation, use of
antiplatelet agents, or presence of risk factors for atherosclerosis. The statistical
power is reduced by short duration and early reporting. The trial design, which
may not reflect real-world clinical treatment and may not effectively isolate the
treatment effect to the primary outcome of the procedure being studied. In
SYNTAX, for example, a large difference in secondary prevention medical therapy
resulted from the trial design.
CABG patients were significantly under treated with aspirin (84% vs. 91%),
thienopyridine (15% vs. 71%), and statin drugs (75% vs. 87%) compared with PCI
patients. These factors may be relevant to the50%ofCABGstrokes that occurred
more than 30 days after operation. Extensive post hoc subgroup analysis was
undertaken to establish a role for the SYNTAX score, which is a risk stratification
score based entirely on coronary anatomy and lesion characteristics. This score is
not yet externally validated or published in detail, but it is known to contain risk
adjustors that are not significant for CABG (in which coronary and lesion anatomy
is largely irrelevant, as evidenced by registry results).The anatomic bias of the
SYNTAX score may skew decisions toward the use of PCI despite other patient
risk factors that support an advantage for CABG.
Opinion regarding the meaning and potential effect of the SYNTAX trial has been
largely one-sided and aligned with the paradigm that as long as PCI has no
demonstrable mortality disadvantage, it remains the treatment of choice. As
described, however, absolutely no justification exists for even implying that PCI is
equivalent to CABG for safety outcomes in this trial. In fact, the evidence supports
the opposite conclusion. The trial was underpowered to demonstrate safety other
than MACE (where CABG was shown to be significantly superior), and the
mortality trend favors CABG, with 26% excess death at 1 year for PCI. Finally, the
trial design actually stacked the cards against PCI intervention by combining both
the hard end points of death, MI, and stroke, and the soft endpoint, he need for
revascularization, into a combined primary end point. If the trial design had
separated those end points, the primary end point would have been equivalent.
Selection and Randomization of Patients

A multi-disciplinary team approach should be the standard of care when
recommending treatment in more complex coronary artery disease. SYNTAX
makes interventionists and surgeons come together, it may set the benchmark for
MVD revascularization. PCI and CABG should be considered complementary
rather than competitive revascularization strategies. There is no substitute for
sound clinical judgment that takes into account the patient’s overall clinical profile,
functionality, comorbidities, as well as the patient’s coronary anatomy. The
SYNTAX Score, which is now available free online, should be utilized to decide
on treatment of patients with LM/MVD (Feldman et al., 2009). IT represents a
great tool for abetter analysis of the angiogram, helps the interventional
cardiologist in decision-making and prognostication but also and is predictive for
postoperative outcome. The Score will be useful in directly to the heart surgeon
when deciding for a surgical option. Using the same score in order to keep track of
indications with either PCI or CABG will be helpful during later follow-up.
Patients with low and intermediate score can be treated with PCI or CABG with
equal results. Those with high score do better with CABG. Increasing SYNTAX
Scores (and lesion complexity) are related to increased adverse outcomes in PCI,
where as outcomes of CABG are independent of SYNTAX Score. Among patients
in the PCI group with high SYNTAX scores (=33), not only was the overall rate of
MACCE significantly increased, but also the rate of the composite components of
death, stroke, and MI (11.9% vs. 7.6%, respectively, in the PCI and CABG
groups). This finding suggests that a percutaneous approach should be avoided in
patients with high SYNTAX score. Therefore, patients with a high SYNTAX
Score need an ‘‘individualized’’ approach, especially in the presence of diabetes
and/or with bifurcation lesions. Based on a non-significant difference in MACCE
at 1 year, the SYNTAX results suggest that 66% of all patients with 3VD or LM
coronary artery disease are still best treated with CABG. For the remaining 1/3 of
such patients with a low SYNTAX Score (0–22), PCI may be considered as an
alternative to surgery (with the exception of insulin-dependent diabetic patients).
The mortality rate at 12 months was 4.3% in the PCI Group and 3.5% in the
Surgical Group. Even though the study was not designed and did not have
statistical power to analyze differences in isolated outcomes, surgery showed a
strong tendency of improved survival over 1 year, with a 23% benefit in respect to
death compared to PCI. Mortality is directly related to syntax score. As with
previous trials and registries, the
safety in terms of death, MI and stroke remained the same for PCI and CABG in
the SYNTAX trial. Furthermore, the increase in repeat revascularization for PCI is
much lower than in any prior trials, despite a much more complex coronary
anatomy of patients studied. The excess of early graft occlusion is offset by
increase in late stent thrombosis: the stent thrombosis risk should be considered
when taking a decision. Stent thrombosis lead to AMI in 100% of patients and
death in 30% of them (Lancet et al., 2007).
On the other hand, the occlusion rate of symptomatic grafts was 3.4% over 12
months. This number is lower than that classically reported of 10% of occlusion of
venous grafts over 1 year. Better surgical techniques allied to the intensive use of
statins and antiplatelet agents may be responsible for the difference in these results.
The prognosis of these complications is also different. In drug-eluting stent
thrombosis, the mortality rate varies between 30% and 45% and the occurrence of
myocardial infarction is greater than 80% of patients affected (Wenaweser et al.,
2008).
Stroke occurs mostly within the first 30 post operative days (Stettler, 2008). The
incidence of strokes after CABG is mainly related to the age of the patient and the
presence of atherosclerotic plaque in the ascending and transverse aorta. Peri-
operative atheroembolism from the aorta is responsible for at least one-third of the
cases of strokes after CABG due to the handling of the ascending aorta or aortic
arch during cannulation, aortic clamping, and preparation of proximal anastomoses
or of the arterial cannula flow. Recent more rigorous methods to detect advanced
atherosclerosis of the ascending aorta, as well as surgical strategies, such as routine
ultrasound assessment of carotid arteries in patients above the 65 years, the use of
no touch technique of off-pump surgery, may reduce the mobilization of aortic
atheroma and prevent the occurrence of this event (Vallely et al., 2008).
Stroke can be prevented and/or minimized by better management of the antiplatelet

therapy. The patients who underwent CABG were less likely to receive optimal
medical therapy (i.e., statins, aspirin or other antiplatelet agents, Angiotensin-
converting enzyme (ACE) inhibitors or angiotensin II-receptor antagonists).Angina
and Quality of life: While CABG is effective in reducing angina. Among patients
undergoing revascularization for left main or 3-vessel CAD, angina relief was
better with CABG than DES at 6 and 12 months. The magnitude of benefit was
smaller than in previous CABG vs. PCI comparisons, however, and below the
threshold that most patients would find clinically meaningful. All other QOL
endpoints favored PCI at 1 month, although these differences were transient and
largely resolved by 6 months. Complete revascularization was performed in only
63% of the patients submitted to CABG against 57% in PCI; the goal should be
complete revascularization. Arterial graft: More use of arterial graft should be
encouraged; LIMA was used in 97% but BIMA artery in 27% and all arterial grafts
in only 19%.While the saphenous vein has been considered as the predominant
graft, venous graft atherosclerosis continues to be the major cause of late failure of
CABG. Diabetics with CAD had worse prognosis than non-diabetics regardless of
treatment option (Kapur et al., 2009 and Lange and Hillis, 2009).
Compared with non-diabetic patients, those with diabetes had more complex
lesions and a higher incidence of co-morbidities. The 1-year MACCE rate was
significantly higher with PES due to an increase in repeat revascularizations. Other
endpoints were similar between the DES and CABG groups, although there were
trends toward higher cardiac death rates with DES and more strokes with CABG.
Looking only at patients with the greatest anatomical complexity (Syntax scores =
33), the mortality advantage with CABG compared with PES was statistically
significant for both diabetics (4.1% vs. 13.5%; P =0.04) and non-diabetics (2.2%
vs.6.1%; P = 0.04). Insulin-treated diabetes who received DES showed a trend
toward higher mortality (12.5%) than similar patients who underwent CABG
(5.7%; P =0.12). Also had higher mortality than patients with non-insulin-
dependent diabetes who received PES (5.8%; P = 0.07).Patient with DM
(especially IDDM), with intermediate or high syntax score better treated with
CABG. CARDIA trial, in pre-specified subgroup analyses, including DES vs.
BMS, 2-vessel vs. 3-vesseldisease, insulin-treated vs. not insulin-treated, female
vs. male, and age <65 years vs. P65 years, outcomes showed no significant
differences. Only DES and 2-vessel disease appeared to favor PCI over CABG for
the primary endpoint (11.6% vs. 12.4% for BMS and 8.9% vs. 9.8% for 3-vessel
disease, respectively).
However, all subgroup analyses were underpowered, according to the authors

(Kapur et al., 2009). Medical treatment: should be optimized in all patients, it is
surprising to see that in the SYNTAX trial, only 74.5% of patients in the CABG
group received statin therapy, whereas in the PCI group, 86.7% of patients
received statin therapy (P< 0.001). How patient should be treated according to
SYNTAX? If safe and complete revascularization is feasible with either PCI or
CABG – as was true in roughly 60% of the patients in the SYNTAX study – an
assessment of coronary anatomical characteristics should be performed, and a
SYNTAX score assigned. The presence of complex coronary anatomical features
(assigned a high SYNTAX score) identifies patients with an increased risk of a
suboptimal outcome with PCI; they should been couraged to undergo CABG.
Conversely, patients with less complex coronary anatomical features (i.e., a low
SYNTAX score) should be presented with the advantages and disadvantages of
each procedure and allowed to choose between them. Irrespective of which
procedure is performed, the patient should receive optimal medical therapy
involving an antiplateletagent (or agents), a statin, and an ACE inhibitor, if
appropriate. The patient has the right to know: that PCI treats the culprit
lesion whereas CABG bypasses the lesion therefore treating not only the culprit
but also future lesions (Eagle et al., 2004).
PCI associated with higher need of repeat revascularization, a trend toward higher
likelihood of cardiac death (PCI3.7% vs. CABG 2.1%, P =0.05); and (MI (CABG
3.3% vs. PCI 5.9%; P = 0.01). CABG associated with higher rate of CVA (CABG
2.8% vs. PCI 1.4%; P = 0.03). The results of SYNTAX study have a number of
implications to medical management of CAD; (Serruys et al., 2009a) when
designing the study, interventional cardiologists had proposed using intensive post-
procedural medications such as antiplatelets, angiotensin-converting (ACE)
inhibitors, statins and beta-blocker. These are frequently administered following
PCI, with well established benefits (Serruys et al., 2005).
While this practice was upheld in the SYNTAX study, the same degree of
intensive therapy was not practiced in the CABG arm of the study. This minor
variation in the standard of care between the two groups is not anew occurrence; in
practice, this presents only a small difference as patients soon return to the care of
a cardiologist after surgical intervention. The lower rate of stroke observed among
the PCI group is attributed to the higher use of antiplatelet therapy in this cohort of
patients following the medical procedure and its protective effects against
thromboembolic events (Goldstein, 2007). It is therefore possible that this benefit
could be extended to patients undergoing CABG if the use of additional
antiplatelet drugs were adopted as the norm in practice (Eagle et al., 2004).
Conclusion
CABG remains the standard of care for these complex patients; however, an
assessment of worldwide clinical practice in 2004 indicated that 29% of patients
with complex disease were already having PCI, despite the absence of any
supportive evidence and against all guidelines. The SYNTAX study, which was
specifically designed to reflect real-world practice, has indicated that in 2009, for
two-thirds of patients with complex coronary disease, cardiac surgery is still the
optimal method of revascularization. In the remaining one-third, PCI offers a
suitable alternative. However, a full and frank discussion between doctor and
patient is required to ensure that a completely informed decision is made.
Historically, these patients were already being selected by intervention lists for
PCI; these decisions are now justified by clinical evidence, and, by utilizing the
SYNTAX score, these patients can be identified more systematically.
One important take-home message from the study is that the method of
revascularization must be individualized taking into account not only coronary
anatomy but also the patient’s co morbidities and personal preference. The
editorial associated with the SYNTAX trial publication (Lange and Hillis., 2009)
was generally balanced and calls for separating CAD diagnosis and treatment to
allow for multi-disciplinary decision-making regarding treatment selection.
Recommendations must be guided by a patient-centric process that results in
reasoned agreement between colleagues rather than procedural advocacy. It is
incumbent upon cardiac surgeons to own this disease through knowledge and
experience and not own the patient or the procedure. This paradigm includes a
responsibility to ensure that CABG patients receive optimal medical management
for the rest of their lives. Although the evidence supports the appropriateness of
CABG for virtually all scenarios of significant CAD, it is no more the treatment of
choice for all patients than is PCI ( Serruys et al., 2009).
Five particular strengths of the SYNTAX study are worthy of note:
 Size. With 1800 patients randomized from 85 centers in the Europe and
the United States, this has been the largest randomized controlled study
of PCI versus CABG.
 Design as an “all-comers” study. With the only exclusion criteria being

previous revascularization, acute MI, or need for concomitant cardiac
surgery, a full 71% of screened patients were enrolled into one of the
randomized or registry cohorts. In this regard, although accepting that
certain clinical subgroups encountered in routing clinical practice were
excluded, it can be argued that the results are more applicable to the
clinical setting than any previous comparison of revascularization
strategies.
 Heart-team concept. Each clinical case and angiogram was reviewed by

a team consisting of an interventionist and a surgeon. After review,
consensus agreement was obtained as to which procedure or procedures
the patient may be eligible for.
 Inclusion of nested registries of either PCI or surgery in the study design

has allowed for detailed characterization and outcome analysis of groups
felt to be ineligible for one of the strategies.
 Use of state-of-the-art technology, with arterial grafts for CABG where
possible, DES for all PCI, and aggressive secondary prevention in both
groups (Gulati et al .,2009).
SYNTAX SCORE
Accurate characterization of coronary disease anatomy based on the diagnostic

angiogram is essential to select the optimal strategy of revascularization. Recently,
the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac
Surgery (SYNTAX) score has generated agreat amount of interest because of its
capacity to risk stratify and discriminate outcomes of patients with complex
coronary disease undergoing percutaneous coronary intervention (PCI) compared
with coronary artery bypass graft surgery(CABG). However, assessment of the
SYNTAX score relies on visual interpretation of lesion severity by clinical
operators (Généreux et al., 2011)
Risk stratification is an important and essential component in appropriately

informing patients electing to undergo coronary artery bypass graft (CABG)
surgery or percutaneous coronary intervention (PCI).This process is an integral
part of the SYNTAX trial pioneered Heart Team approach in selecting the most
appropriate revascularization modality in patients with complex (three-vessel or
left main stem[LMS] disease) coronary artery disease and has recently been
incorporated as a class I recommendation in recent myocardial revascularization
guidelines (Wijns et al., 2010).
Pre-existing classifications
The SYNTAX score has been developed based on the following:
1. The AHA classification of the coronary tree segments modified for the ARTS
study
2. The Leaman score

3. The ACC/AHA lesions classification system
4. The total occlusion classification system
5. The Duke and ICPS classification systems for bifurcation lesions
6. Consultation of experts
Each of these classifications has been focusing on specific functional and

anatomical parameters of the lesions. Thus, the development of a global
classification system that would take into account all the variables was necessary
(Valgimigli et al., 2007).
Leaman score:
The 'Leaman score' is based on the severity of luminal diameter narrowing and
weighed according to the usual blood flow to the left ventricle in each vessel or
vessel segment. In a right dominant system, the right coronary artery (RCA)
supplies approximately 16% and the left coronary artery (LCA) 84% of the flow to
the left ventricle (LV). This 84% is normally directed for 66% to the left anterior
descending artery (LAD), and for 33% into the left circumflex coronary artery
(LCX). Thus, the Left Main (LM) supplies approximately 5 times, the LAD
approximately 3.5 times (84/16 x 0.66) and the circumflex 1.5 times as much blood
as the RCA to the left ventricle.
In a left dominant system the RCA does not contribute to the blood supply of the
ventricle. Thus the LM supplies 100% of the flow to the LV. The RCA
contribution of blood flow to the LV is now supplied by the LCX. Hence the LAD
provides 58% (weighing factor 3.5) andthe LCX 42% (weighing factor 2.5) of the
total flow to the LV. Using the same principle of relative blood supply to the LV
all coronary segments has been given a weighing factor (Sianos et al ., 2005).
The contribution of each coronary segment to the blood flow to the LV is used as a
multiplication factor for the calculation of the Leaman score and as such has been
transferred to the SYNTAX score. A lesion is defined as significant when it causes
(50% reduction in luminal diameter by visual assessment in vessels (1.5mm. Less
severe lesions should not be included in the SYNTAX score. The percent diameter
stenosis is not considered in the algorithm. Distinction has been made only
between occlusive (100% diameter stenosis) and non occlusive (50-99% diameter
stenosis) disease. A multiplication factor of 2 is used for non-occlusive lesions and
5 for occlusive lesions reflecting the difficulty of the percutaneous treatment.
Multiple-tandem lesions:
If multiple lesions are less than 3 vessel reference diameters apart (tandem lesion),
these lesions are scored as one lesion. However, lesions at a greater distance from
each other (more than 3 vessel reference diameters), are considered as separate
lesions.
ACC/AHA lesion classification system:
This lesion classification system is based on parameters, such as length,

eccentricity, angulation, calcification, involvement of side branches, thrombus and
severity of stenosis. Lesions are classified as Type A, (high success and low risk),
Type B (moderate success and moderate risk) or Type C (low success and high
risk).
The majority of these individual parameters have been incorporated in the

SYNTAX score. Although the ACC/AHA system takes into account the total
occlusions and the bifurcation lesions classifying them as a high-risk, it is not
considered as detailed enough to adequately quantify their complexity.
Total occlusion classification system:
A lesion is characterized as a total occlusion when no antegrade flow is visible

distally (Valgimigli et al., 2007 and Sianos et al., 2005).
SYNTAX score calculation:
Scoring to each coronary lesion with a Diameter Stenosis ≥50% in vessels ≥1.5
mm must be done. Each lesion can involve ≥1 diseased segments. If serial stenoses
are less than 3 vessel reference diameters apart, they should be scored as one
lesion. However, stenoses at a greater distance from each other (more than 3 vessel
reference diameters), are considered as separate lesions.
* ≥3 vessel reference diameters.
This case should be described as two lesions:

-one lesion involving segments 5, 6, and 11 and
-one lesion involving segment 6.
* <3 vessel reference diameters.
This case should be described as one lesion:
- one lesion involving segments 5, 6, and 11.
The SYNTAX scoring system including the following components (Figure 7).
Figure 7: Component of SYNTAX score.

Dominance
A. Right dominance: the posterior descending coronary artery is a branch of the
right coronary artery (segment 4)
Figure 8: Right dominance (Généreux et al., 2012).
B. Left dominance: the posterior descending artery is a branch of the left

coronary artery (segment 15). Co-dominance does not exist as an option in the
SYNTAX score.
Figure 9: Left dominance (Généreux et al ., 2012).

I- Total occlusion
No intra-luminal ante grade flow (TIMI 0) beyond the point of occlusion.

However, ante grade flow beyond the total occlusion might be maintained by
bridging collaterals and/or ipsicollaterals. At the question ‘Specify which segments
are diseased for lesion X' one should only fill out the segment number of the start
of the Total Occlusion.
- Blunt stump
- Bridging collaterals:
Small channels running in parallel to the vessel and connecting proximal vessel to
distal and being responsible for the ipsilateral collateralization.
II- Trifurcation
A trifurcation is a division of a main branch into three branches of at least 1.5mm.

Trifurcations are only scored for the following segment junctions: 3/4/16/16a,
5/6/11/12, 11/12a/12b/13, 6/7/9/9a and 7/8/10/10a. ‘Specify which segments are
diseased for lesion X’: one should only fill out those segment numbers of the
trifurcation that have a Diameter Stenosis ≥50%in direct contact with the
trifurcation.
-One lesion-
Trifurcation: ‘Yes’
III- Bifurcation
A bifurcation is a division of a main, parent, branch into two daughter branches of

at least 1.5mm. Bifurcation lesions may involve the proximal main vessel, the
distal main vessel and the side branch according to the Medina classification. The
smaller of the two daughter branches should be designated as the ‘side branch’. In
case of the main stem either the LCX or the LAD can be designated as the side
branch depending on their respective calibres. Bifurcations are only scored for the
following segment junctions: 5/6/11, 6/7/9,7/8/10, 11/13/12a, 13/14/14a, 3/4/16
and 13/14/15. ‘Specify which segments are diseased for lesion X’: one should fill
out only those segment numbers of thebifurcation that have a Diameter Stenosis
≥50% in direct contact with the bifurcation.
Example 1
-One lesion - one segment number involved/diseased (= segment: 7).
- Bifurcation ‘Yes’- Medina class: 0, 1, 0
Example 2
One lesion - three segment numbers involved/diseased (= segments: 6, 7 and 9).
- Bifurcation ‘Yes’ - Medina class: 1, 1, 1.
IV- Aorto-ostial
A lesion is classified as aorto-ostial when it is located immediately at the origin of

the coronary vessels from the aorta (applies only to segments 1 and 5or to 6 and 11
in case of double ostium of the LCA).
VI- Severe tortuosity

One or more bends of 90° or more, or three or more bends of 45° to 90° proximal
of the diseased segment.
VII- Length >20mm
Estimation of the length of that portion of the stenosis that has ≥50% reduction in
luminal diameter in the projection where the lesion appears to bethe longest. (In
case of a bifurcation lesion at least one of the branches has alesion length of
>20mm).
VIII- Heavy calcification
Multiple persisting opacifications of the coronary wall visible in more than one
projection surrounding the complete lumen of the coronary artery at the site of the
lesion.
IX- Thrombus
Spheric, ovoid or irregular intraluminal filling defect or lucency surrounded on
three sides by contrast medium seen just distal or within the coronary stenosis in
multiple projections or a visible embolization of intraluminal material downstream.
Diffuse disease
Present when at least 75% of the length of any segment(s) proximal to the lesion,at
the site of the lesion or distal to the lesion has a vessel diameter of <2mm.
Definition of the coronary tree segments

1. RCA proximal: From the ostium to one half the distance to the acute margin of
the heart.
2. RCA mid: From the end of first segment to acute margin of heart.
3. RCA distal: From the acute margin of the heart to the origin of the posterior
descending artery.
4. Posterior descending artery: Running in the posterior interventricular groove.
16. Posterolateral branch from RCA: Posterolateral branch originating from the
distal coronary artery distal to the crux.
16a. Posterolateral branch from RCA: First posterolateral branch from segment 16.
16b. Posterolateral branch from RCA: Second posterolateral branch from segment
16.
16c. Posterolateral branch from RCA: Third posterolateral branch from segment
16.
5. Left main: From the ostium of the LCA through bifurcation into left anterior
descending and left circumflex branches.
6. LAD proximal: Proximal to and including first major septal branch.
7. LAD mid: LAD immediately distal to origin of first septal branch and extending
to the point where LAD forms an angle (RAO view). If this
angle is not identifiable this segment ends at one half the distance from the first
septal to the apex of the heart.
8. LAD apical: Terminal portion of LAD, beginning at the end of previous segment
and extending to or beyond the apex.
9. First diagonal: The first diagonal originating from segment 6 or 7.
9a. First diagonal a: Additional first diagonal originating from segment 6 or 7,

before segment 8.
10. Second diagonal: Originating from segment 8 or the transition between

segment 7 and 8.
10a. Second diagonal a: Additional second diagonal originating from segment 8.
11. Proximal circumflex artery: Main stem of circumflex from its origin of left
main and including origin of first obtuse marginal branch.
12. Intermediate/anterolateral artery: Branch from trifurcating left main other than
proximal LAD or LCX. It belongs to the circumflex territory.
12a. Obtuse marginal a: First side branch of circumflex running in general to the
area of obtuse margin of the heart.
12b. Obtuse marginal b: Second additional branch of circumflex running in the

same direction as 12.
13. Distal circumflex artery: The stem of the circumflex distal to the origin of the
most distal obtuse marginal branch, and running along the posterior
leftatrioventricular groove. Caliber may be small or artery absent.
14. Left posterolateral: Running to the posterolateral surface of the left ventricle.
May be absent or a division of obtuse marginal branch.
14a. Left posterolateral a: Distal from 14 and running in the same direction.
14b. Left posterolateral b: Distal from 14 and 14 a and running in the same
direction.
15. Posterior descending: Most distal part of dominant left circumflex when
present. It gives origin to septal branches. When this artery is present, segment 4 is
usually absent (Sianos et al., 2005).
SYNTAX-DERIVED RISK SCORES
One important limitation of SS is that it does not integrate clinical variables in the
scoring algorithm. Patients with equivalent scores may have different short- and
long-term outcomes, depending on the presence of comorbidities (Romagnoli et
al., 2009). To overcome these limitations, attempts have been made to combine
clinical-based scores with SS (Figure 10).
2 Figure 10 : Scores evolving from SYNTAX score(Yadav et al., 2013 ).
Global risk classification.
The global risk classification (GRC), a combination of SS and EuroSCORE

(European System for Cardiac Operative Risk Evaluation), was developed to
improve the predictive ability of SS (Capodanno et al., 2010).
Capodanno et al., (2010) were the first to demonstrate that the GRC had
significantly better discriminative power for risk prediction of cardiac mortality
than did SS alone in patients with multivessel CAD. Indeed, among patients with
LMCAD undergoing PCI, the GRC had a net reclassification improvement of 26%.
In contrast to SS alone, GRC had abetter ability for discriminating patients at
intermediate risk of cardiac mortality.
Similar results were reported by Serruys et al., (2012), who showed that GRC has
a better predictive ability than either SS alone or EuroSCORE both in patients with
unprotected LM CAD and in those with multivessel CAD. Additionally, GRC
identified a low-risk cohort of patients that could be safely treated with PCI.
Clinical SYNTAX score.
The clinical SYNTAX score (CSS) integrates SS with the modified ACEF (Age,
Creatinine clearance and Ejection Fraction) score. Using only 3 clinical variables,
the ACEF score has been shown to predict outcomes with comparable accuracy as
that of EuroSCORE in patients undergoing CABG (Ranucci et al., 2009). CSS is
determined by multiplying the SS and modified ACEF score values. In the study
by Garg et al. (Garg et al.,2010) the CSS hada better discriminatory power for 5-
year mortality and MACE than either SS alone or modified ACEF score did.
Patients in the highest tertile of CSS had significantly higher rates of mortality,
MACE, and repeat revascularization than did those in the lower 2 tertiles.
Moreover, CSS was an independent predictor of MACE at 5 years.
Girasis et al., (2011) reported that CSS had a better discriminatory power and at
least equivalent calibration than SS for all-cause mortality and cardiac mortality.
However, the main limitations of CSS is represented by the fact that it has a poor
discriminative power for ischemic outcomes in the lower 2tertiles and that its
prognostic performance is poorer forpooled patients with double- and triple-vessel
CAD than for patients with only triple-vessel CAD (Garg et al., 2010).
Logistic clinical SYNTAX score.
In order to overcome the above-mentioned limitations of the SS and CSS, the

logistic CSS was developed. SS and consequently CSS were not developed by
selecting variables in multivariable logistic models, but rather on an arbitrary
ranking of lesion site and complexity. The logistic CSS variables were selected on
the basis of logistic regression coefficients, thus developing score charts for
individual risk assessment. This score demonstrated a substantial improvement in
the predictive ability for 1-year all-cause death compared with SS, but not for
MACE. The predominant role of angiographic variables over clinical factors in
determining the risk of TVR is apossible explanation (Farooq et al., 2012).
The logistic CSS has recently been externally-validated in a different population of

patients with acute coronary syndrome (Farooq et al., 2013). Functional SYNTAX
score. The rationale of integrating fractional flow reserve (FFR) measurements to
SS is supported by 2 concepts highlighted by recent studies: 1) there is a
significant discrepancy between lesion severity assessed by visual estimation and
their functional correlates as determined by FFR (Novara et al., 2012). FFR-
guided PCI is associated with lower rates of adverse ischemic events in patients
with multivessel CAD compared with angiography guided PCI (Pijls et al., 2010).
In a recent study, the functional SS(FSS) reclassified 39% of patients from the
highest tertile to the lower 2 tertiles, resulting in an improvement in the
discrimination power for 1-year adverse cardiovascular events (MI, TVR, and
MACE) (Nam et al., 2011). FSS was also associated with a better inter- and
intraobserver reproducibility than SS was. Whereas FSS has the potential to be an
important tool in risk-stratification and selection of revascularization strategy, the
lack of prospective validation, especially in LM and multivessel CAD, the limited
discrimination power, and the fact that it may be time-consuming to perform, limit
the broad applicability of this score in daily clinical practice.
Residual SYNTAX score.

Some studies have suggested that incomplete revascularization is among the main
factors associated with an increased risk of adverse ischemic outcomes after PCI in
patients with high SS (Capodanno et al., 2009). The residual SYNTAX score
(rSS) was recently proposed as amethod to systemically characterize and quantify
residual CAD after PCI (Généreux et al., 2012). The rSS calculation is similar to
the SS calculation in every respect, except that it is computed after PCI. Among
the patients presenting with acute coronary syndrome undergoing PCI, rSS was
found to be an independent predictor of mortality, cardiac mortality, MI,
unplanned revascularization, and MACE at 1 year (Généreux et al., 2012).
The predictive and discriminative abilities of rSS were similar to the baseline SS
for all outcomes except MI, forwhich the baseline SS was superior. In an all-
comers population undergoing LM CAD revascularization, rSS was also shown to
be an independent predictor of mortality at 1 year (Malkin et al., 2013). Recently,
the rSS was also validated in the randomized SYNTAX trial, where the rSS was
shown to be a strong independent predictor of 5-year mortality, with similar effects
among different subgroups (unprotected left main, diabetes, poor ejection fraction)
(Farooq et al., 2013).
In this analysis, the rSS demonstrated greater discrimination and predictive value
for adverse events including death, cardiac death, stent thrombosis, andmajor
adverse cardiac and cerebrovascular events, compared tobaseline SS. Similar to the
baseline SS, rSS aims to offer uniform and standardized characterization of
residual CAD to help patient risk stratification, appropriate groups comparison,
and potential revascularization strategy selection (Malkin et al., 2013).
CABG SYNTAX score.

As the SS was initially validated for patients with native CAD (Serruys et al.,
2009), it cannot be implementedin patients with CABG. To help address this issue,
the CABG SS was developed (Farooq et al., 2013) This score can be calculated by
computing first the baseline SS of native vessels and then subtracting points on the
basis of graft functionality. The score was evaluated in a pilot study of 115 patients
with acceptable reproducibility (k ¼ 0.74; 95% confidence interval: 0.53 to 0.95, p
< 0.001) (Farooq et al., 2013).
Despite the limited power of the study, it suggested a trend toward higher all cause
death and MACE in patients with high CABG SS. One major limitation of this
score is that it does not take into consideration the type of graft used. At this infant
stage, the score still requires external validation in larger studies to prove its
prognostic capabilities SYNTAX score II. The SS II was recently developed to
better guide decision-making between CABG and PCI compared to the anatomical
SS in patients with complex CAD (Farooq et al., 2013).
The SS II combines the anatomical SS with anatomical and clinical variables that
were shown to alter the threshold value of the anatomical SS so that equipoise was
achieved between CABG and PCI for long-term mortality. These included the
presence of age, creatinine clearance, left ventricular ejection fraction, presence of
unprotected LMCAD, peripheral vascular disease, female sex, and chronic
obstructive pulmonary disease. In addition the SS II allowed for the individualized
assessment of long-term mortality in patients with LM/multivessel CAD
undergoing either PCI or CABG, compared to the grouping of risk(low,
intermediate, high) with the anatomical SS. The SS II was developed in the
randomized SYNTAX Trial and validated in the DELTA (Drug-eluting stent for
left main coronary artery disease) registry. The proposed nomogram for bedside
application of the SS II. Use of SS in daily practice and clinical research. The SS
has many potential applications both in daily clinical practice and for research
purposes. First, it provides the interventional cardiology community a powerful
stratification tool, allowing uniform, standardized assessment of CAD extent and
severity. Second, the SS may guide clinicians who are deciding upon the most
appropriate revascularization modality, especially in complex CAD, and this fact
has been recently endorsed in both American and European coronary
revascularization guidelines (Class IIa recommendation) (Hillis et al., 2011).
This clearly justifies the score’s integration in the routine clinical practice when
facing a complex CAD dilemma. Third, as in the multinational EXCEL trial, it
may be used as a standardized tool in identifying and stratifying patients to be
enrolled in randomized controlled trials. Finally, its ability to predict post-
procedural outcomes has important clinical implications, especially when
informing patients and family regarding potential adverse outcomes associated
with a given revascularization strategy (Singh et al., 2007).
Comparison of SS and Derived SS Systems:
Table 1: Comparion between SS and its derived score
Score Type Anatomical Clinical Predictor Predictor Discrimination

Variables Variables of Death of MACE Between Lower
and Intermediate
Tertiles
SYNTAX score yes no yes yes no
Global risk yes yes yes yes yes
classification
Clinical SYNTAX yes yes yes yes no
score
Logistic clinical yes yes yes yes yes
SYNTAX
Functional yes no N/A yes no
SYNTAX score
SYNTAX score II yes yes yes yes yes
N/A = not applicable
)Yadav et al., 2013(
Current Limitations
As one would expect with any scoring system, the angiographic SS does have
limitations. First, the SS is a purely angiographic score and it does not integrate
clinical variables that may be relevant for risk stratification of patients undergoing
PCI. Nonetheless, by focusing precisely on angiographic characteristics, the SS
score can adequately summarize in a quantitative manner the complexity of
coronary anatomies that may exist across different patients. Additionally, SS can
be combined with other clinical parameters, thereby improving its discriminatory
power.
Second, SS suffers interobserver variability inherent to visual estimation of vessel

stenosis. Online quantitative coronary angiography measurement or physiological
assessment using FFR may overcome this issue. Third, the SS score bears other
limitations inherent to angiographic characterization of coronary lesions, such as
the inability to estimate precisely coronary plaque burden or to identify vulnerable
plaques. Whether other modalities, such as intravascular ultrasound, optical
coherence tomography, or near-infrared spectroscopy may improve the prognostic
power of SS deserves further investigation. Fourth, SS, or any other derived scores,
lacks the capacity to take into consideration variation in patient coronary anatomy
(vessel diameter, presence and localization of major side branches, myocardium
area perfused, etc.) or the impact of presence or absence of viability beyond
stenosis.
Fifth, these scores suffer from the incapacity to appropriately weigh major
differences in operator skills, experience in realization of complex procedures, and
the impact of novel revascularization techniques or improvement in device
technology. Finally, whereas SS seems to successfully predict several ischemic
adverse events in different clinical settings, the predictive power of individual SS
components is not known. Indeed, SS integrates heterogeneous angiographic
variables that may have a different weight in relation to different ischemic
outcomes. For example, it is possible that calcifications or lesion length are
associated with TVR more than with other ischemic outcomes, whereas the amount
of jeopardized myocardium may be a better predictor of cardiac death. By
integrating all-important angiographic variables together with the amount of
myocardium at risk, SS represents the most powerful angiographic tool to predict
any relevant cardiac endpoints.
Conclusions
The introduction of SS represented a substantial advancement in the quest for

better risk stratification and prognostication of patients with CAD undergoing PCI.
Although further prospective studies are needed to better determine SS cutoff
values for risk-stratifying patients in different clinical scenarios, the possibility of
combining clinical and anatomic variables, such as in SS II, represents amajor
improvement. The role of FSS, with the possibility of determining FFR in a
noninvasive fashion using computed tomography angiography (Koo et al., 2011),
may help to overcome current limitations of SS, but this possibility warrants
further investigation.
PATIENTS WITH LOW EJECTION FRACTION
UNDERGOING CORONARY ARTERY BYPASS
GRAFTING
Traditionally impaired ventricular function has been arisk factor for mortality
associated with coronary artery bypass grafting (Ascioneet al., 2003). Left
ventricular function is important predictor of hospital mortality following coronary
artery bypass grafting. Despite improvement in surgical technique, myocardial
protection and postoperative care, surgical risk remains high (Lam et al., 2011).
Many studies show that patients have better quality of life and ejection fraction
after coronary surgery than with continuous medical therapy (Paterson et al.,
2011). Patients with coronary artery disease and poor left ventricular function have
a poor outlook despite maximum medical therapy with a two year survival rate of
only 20-30% (De Rose et al ., 2005).
Numerous controlled trials of coronary artery bypass grafting in patients with

depressed left ventricular ejection fraction, have shown that these are the patients
that benefit most from revascularization, especially if symptoms of angina or
ischemia are present(Kunadian et al ., 2011). This benefit is not only for
symptoms, but in this selected patient group also on longevity. It is important to
determine first if any condition exist that may preclude intervention or that could
raise the risk of revascularization above any potential benefit (Detre et al., 2000).
Some authors correctly note that coronary artery bypass grafting (CABG) carries
increased risk in this patient group. Indeed, several authors have suggested that
recruitable contractile reserve is an important determinant of improvement after
CABG in ischemic heart disease patients who undergo surgery (primary for heart
failure) (Shah et al., 2011). Patients without such reserve are less likely to benefit
simptomatically from CABG whereas those with reserve are. Further, studies have
shown that ischemic heart disease patient with a low left ventricle EF who undergo
surgery primarily for angina are more likely to obtain symptomatic benefit than are
those who undergosurgery primarily for heart failure (Wijns et al., 2010).
Mickleborough LL et al., (2000) reported no difference in longtime survival

between patients who underwent surgery primarily for angina and patients who
underwent surgery for heart failure (Mickleborough et al., 2000). Although one
can define a subset of ischemic cardiomyopathy patients who are likely to have an
increase in left ventricle EF with CABG, this information often has not proven
useful in predicting improvement in functional class. Moreover, improvement in
mortality after revascularization of viable myocardium may have little to do with
change in either ejection fraction or functional class. Instead, improvement may be
result of other factors, such as electric stabilization or reduction of ischemic events
(Cleland et al., 2011).
Indeed, existing data from observational studies indicate no difference in survival

after CABG between patients with left ventricle EF improvement and patients
without, again suggesting that changes in contractile function may not be the most
helpful surrogate endpoint (Kurki et al., 2003).
The magnitude of improvement in left ventricle EF is directly related to the extent

of dysfunctional but viable issue. The presence and extent of viability is predictive
of the improvement in heart failure symptoms after revascularization. Patients with
angina as the main symptom were significantly more likely to improve their left
ventricular ejection fraction after surgery. These findings are consistent with the
conceptthat the preoperative angina predicts a good result, but its absence is not
necessarily associated with a poor result. Ischemic dysfunction may be reversible
or not, the degree of reversibility probably determining which patients will respond
favourably to CABG. Potentially reversible dysfunction should be assessed when
considering CABG for patients with poor left ventricular function (ischemic or
hibernating myocardium).
Chapter Four
COMBINED RISK SCORES
R isk stratification is an integral and increasingly important aspect of the

assessment of patients with complex coronary artery disease who are
candidates for coronary revascularization.
Although the landmark SYNTAX trial established that surgery was the
standard of care for patients with left main stem (LMS) and/or multivessel disease,
an important finding from this study was that patients with less complex disease
were found to have equivalent outcomes to surgery at 1 and 3 years' follow-up
(Serruys et al., 2009).
The “Heart Team” approach in managing these complex patients was

pioneered within the SYNTAX trial, and has recently been incorporated as a class I
recommendation in recent myocardial revascularization guidelines (Kolh et al., 2010).
As part of this approach, risk models to appropriately stratify patients are

crucial to aid in the decision-making process regarding the choice of
revascularization modality. Within cardiothoracic practice, the use of risk scores
are well established and are predominantly related to clinical variables alone, with
the Euro SCORE (European System for Cardiac Operative Risk Evaluation) being
in widespread contemporary use (Roques et al., 2003).
With percutaneous coronary intervention (PCI) of complex coronary artery

disease, the risk models are still evolving, with models consisting of clinical or
anatomical variables alone or combinations of the two variable types.
Whereas anatomical variables have been shown to be less important for
surgical outcomes, the SYNTAX trial and subsequent studies have confirmed these
to be of significant importance for multivessel PCI (Serruys et al., 2009),
However, there is recognition that both anatomical and clinical variables are
required to appropriately risk stratify patients contemplating percutaneous
revascularization.
The purpose of this review article is to explore the numerous types of risk
scores that are available that take into account either anatomical or clinical
variables alone or a combination. We also aim to highlight areas of potential
further developments of contemporary risk models—in particular, the emerging
concept of a risk/ benefit tradeoff—all of which may ultimately allow the
individual patient and the Heart Team to best determine the most appropriate
revascularization strategy.
 Anatomical and Functional Based Risk Scores
In 1981, our group developed a coronary scoring system that assessed the
severity and extent of the underlying coronary artery disease (Serruys et al., 2009);
this system was based on the severity of luminal diameter narrowing and weighted
according to the usual flow to the left ventricle in each coronary vessel.
Consequently the most weight was given to the LMS, followed by the left anterior
descending, circumflex, and right coronary arteries. This early pioneering work
ultimately formed the basis of the SYNTAX score (SX score) (Sianos et al., 2005),
since then, numerous angiographic-based risk scores have been developed several
of which are described below.
American College of Cardiology/American Heart Association Lesion

Classification System The American College of Cardiology/American Heart
Association (ACC/AHA) lesion classification system was one of the first
angiographic scoring systems developed, comprising of 11 angiographic variables
with all lesions categorized into types (A, B1, B2, and C).This system was predictive
of the angiographic success of PCI with a subsequent prognostic effect on the early
and late clinical outcomes in the pre drug-eluting stent era.
However, registry data from the drug-eluting stent era have had conflicting
results. The German Cypher registry (n=6755) failed to show any significant
association with clinical outcomes at 6 months; conversely, data from the ARTS II
registry suggested an association with clinical outcomes for two and three-vessel
disease (3VD) (Valgimigli et al., 2007).
Furthermore, a small registry (n=255) demonstrated this classification system to be

potentially predictive of mortality in unprotected LMS PCI at 1-year follow-up
(Capodanno et al., 2009).
 SYNTAX Score
The SXscore is a well-described anatomical risk-based score that takes into

account features such as bifurcations, total occlusions, thrombus, calcification,
small vessels, and so forth.
Each coronary lesion with a greater than 50% luminal obstruction lumen in
vessels≥1.5 mm are separately scored and summated to provide the overall
SXscore. This is calculated using dedicated software that integrates the number of
lesions with their specific weighting factors, based on the amount of myocardium
distal to the lesion and morphologic features of each single lesion (Sianos et al.,
2005).
Within the SYNTAX trial, the distribution of the SXscore was found to be
Gaussian in the randomized PCI and coronary artery bypass grafting (CABG)
populations with the curves almost being super imposable. When the scores of the
randomized SYNTAX population were divided into tertiles, the upper boundary of
the lowest tertile was 22 (low risk), the second tertile ranged from 23 to 32
(intermediate risk), and the lower boundary for the highest tertile is≥33 (high risk).
The SXscore has since been consistently shown to demonstrate poorer outcomes
and to be an independent predictor of major adverse cardiac events (MACE) in the high
tertile group of risk for PCI with both multivessel and LMS disease at up to 5 years of
follow-up (Garg et al., 2010).
This is maintained even with next-generation drug-eluting stents

(Wykrzykowska et al., 2010) demonstrated in the LEADERS all-comers trial a
higher rate of myocardial infarction (MI), target vessel revascularization, and
MACE in highest tertile of the SXscore.
Of note is that within this study approximately 30% of the high SX score
risk tertile had 3VD compared with only 10% in the low SX score risk tertile.
Within the CABG population, the SX score however appears to have little
predictive value for outcome. This is likely due to the simple fact that the bypass is
anastomosed distal to the severe coronary disease, regardless of the complexity,
provided there are suitable graftable targets (Mohr et al., 2011).
Functional SYNTAX Score The FAME study first established that by utilizing
fractional flow reserve (FFR) measurements to determine the functional significance
of individual coronary lesions and guide subsequent coronary intervention, that this
leads to a potential prognostic impact when compared with angiographic guidance
alone (Tonino et al., 2010).
Consequently, by incorporating FFR measurements into the SX score to

form the recently dubbed, Functional SYNTAX score, it was shown in a
retrospective sub analysis of almost 500 patients with multivessel disease from the
FFR-guided arm of FAME, that this improved the risk stratification of patients
when compared with the conventional angiographic-based SX score (Fearon et al.,
2011).
The primary benefit appeared in reclassifying a significant proportion of the

higher-risk groups into lower-risk categories while still maintaining a significantly
higher event rate (death/MI and MACE at 1 year) in the high-risk groups.
However, the study did not include LMS disease, and from a practical
perspective, even if validated in larger prospective populations, is limited by the
more invasive nature of the procedure. One of the criticisms of the FAME study
was that quantitative coronary angiography (QCA) was not used to assess vessel
size and instead was reliant on visual estimation (Cutlip et al., 2011).
Visual assessment is well known to be associated with poor reproducibility and

often overestimates lesion significance. If QCA had been used to assess vessel size,
then the potential benefit seen in favor of FFR may have been less. The practice of
visual assessment of vessel/lesion size is however representative of real-life practice
and was also the basis of how the SX scores were calculated within the SYNTAX
study.
Novel techniques to potentially simplify the generation of the newly

developed Functional SYNTAX score include the use of noninvasive computed
tomographic angiography that allows for the simultaneous assessment of anatomy
and the measurement of the hemodynamic significance of lesions (Vasim et al.,
2011).
 Limitations
The progressive development of anatomical-based risk scores culminating in

the Functional SYNTAX score has undoubtedly improved the performance of
these risk models in terms of stratification for the individual patient.
However, the limiting factors are the inevitable variability in coronary

angiogram assessment if visual assessment is used to assess the vessel/lesion size
(Garg et al., 2010).
With the potential use of the Functional SYNTAX score this problem may
be circumvented, especially if a noninvasive assessment of the Functional
SYNTAX score is developed as mentioned.
The other limiting factors are that no clinical variables are used, which in
themselves are less subjective than some angiographic variables; consequently,
important prognostic information may potentially be missing that may aid in risk
stratifying these patients further.
 Clinical-Based Risk Scores
The main advantages of clinical-based scores are that they are potentially
easier to perform and less subjective compared with purely anatomical-based
scores that require interpretation of the coronary angiogram. They can also be
performed relatively quickly and often at bedside if necessary.
1. EuroSCORE
The EuroSCORE is an established risk model, which utilizes 17 clinical
variables within cardiothoracic practice for predicting operative mortality. In use
since 1999, the model was derived from almost 20,000 consecutive patients from
128 hospitals in eight European countries. The additive model assigns an
individual score to 17 clinical variables and has been validated in many
populations around the world.
These studies have consistently demonstrated that among cardiothoracic

surgery patients, a low EuroSCORE risk tertile ranges from 1 to 2, intermediate-risk
tertile from 3 to 5, and a high-risk tertile of 6+.
The subsequently developed logistic EuroSCORE allows for a more accurate

risk prediction within the CABG cohort, in particular for the high-risk patient in
which the additive model was found to lead to a potential underestimation of risk.
Kim et al. (2006) demonstrated that the high-risk tertile of the EuroSCORE
was an independent predictor of death/MI after unprotected LMS intervention with
sirolimuseluting stents.
Subsequently, Romagnoli et al. (2009) applied the additive EuroSCORE to

predict in-hospital mortality in 1173 consecutive patients undergoing PCI in a single
high-volume center and correlated the higher-risk tertiles of the EuroSCORE with in-
hospital mortality. This included patients who had undergone unprotected LMS PCI.
In addition, several studies have since all identified the additive EuroSCORE as an
independent predictor of major adverse cardiac and cerebrovascular events (MACCE)
among patients with unprotected LMS PCI at up to 4 years of follow-up (Onuma et
al., 2010).
Only one study has examined the logistic EuroSCORE in PCI patients;
however, little differences were found in stratifying risk when compared with the
additive EuroSCORE.
2. ACEF Score
Ranucci et al. (2009) demonstrated in a relatively simple risk model

consisting of only three clinical variables:
1. Age.
2. Preoperative serum creatinine value.
3. Left ventricular ejection fraction—a risk model for assessing operative

mortality risk in elective cardiac operations.
Of note is that despite the simplicity of the model, its clinical performance
appeared to be equivalent to either the additive or the logistic EuroSCOREs.
The ACEF score is calculated using the formula: ACEF=Age/Ejection

fraction % +1if creatinine > 2mg=dL]_: From this score, a mortality risk can be
calculated from a graphical relationship of the score with an operative risk or an
equation (Ranucci et al., 2000).
The ACEF model was recently applied to PCI patients from the all-comers
LEADERS population at 1-year follow-up (Wykrzykowska et al., 2011).
Despite the ACEF score being demonstrated to be superior to the SX score

alone as a predictor of cardiac death and MI after PCI, the ACEF score was found to
be inferior to the SX score at predicting overall MACE and the risk of repeat
revascularization. This reflects the observation that anatomical and clinical variables
appear to be a necessary requirement for a comprehensive risk model in predicting
clinical outcomes with PCI.
Limitations
The main limitations of the clinical-based risk scores alone are predominantly
related to the lack of anatomical variables which in themselves may carry additional
prognostic information, such as the SYNTAX score as previously discussed.
3. Combined (Anatomical and Clinical) Based Risk Scores
SYNTAX Score and the Parsonnet Score. By combining the Parsonnet

score, an operative risk score published in 1989 consisting of 14 clinical variables.
Parsonnet et al. (1989) with the SXscore, it has been shown that this may
potentially improve the performance of the SXscore alone.
In 2005, Valgimigli et al. (2005) demonstated that the Parsonnet score was
an independent predictor of MACE after LMS intervention from the Rotterdam
RESEARCH and T-SEARCH registries. More recently, (Chakravarty et al. 2011)
demonstrated that by adding the Parsonnet score as a covariate to the SX score, this
improved the ability of the score in predicting MACCE after LMS PCI.
4. Clinical SYNTAX Score
The underlying rationale for the Clinical SYNTAX Score was to combine,
by multiplication, the Syntax score and a variant of the ACEF score (modified
ACEF score), of which the latter had proven to be comparable to the EuroSCORE
in elective CABG patients as previously described (Ranucci et al., 2009).
The modified ACEF score was used instead of ACEF score in this model as
it allowed for a more accurate assessment of the underlying renal function and had
subsequently improved the accuracy of cardiac prediction models such as the
EuroSCORE (Chakravarty et al., 2011).
The modified ACEF score is calculated by using the formula: age/ejection
fraction+1 point for every 10-ml/min reduction in creatinine clearance below 60
ml/min/1.73 m2 (up to a maximum of 6 points).
This model was applied to the ARTS II population treated with sirolimus-
eluting stents for multi vessel coronary artery disease by our group (Walter et al.,
2003). By dividing the calculated Clinical SYNTAX scores into tertiles of risk, it
was demonstrated that the risk model for predicting outcomes for MACCE and
death at 5 years was superior to the Syntax score or modified ACEF scores alone.
One of the limiting factors of the Clinical SYNTAX score was that despite
being able to predict events accurately in the high risk tertile, the risk model was
unable to discriminate between the end points for the low and intermediate-risk
tertiles. This was also recently demonstrated within a registry of patients
undergoing left main PCI (Garg et al., 2010).
5. New Risk Classification Score
The New Risk Classification Score (NERS) (Chen et al., 2010) is a risk
model developed to predict outcomes for unprotected LMS PCI from four centers
in China (n=260).
Reflecting the long period over which this registry was performed (~ 10
years), the patients included had either bare-metal or drug-eluting stent
implantation. The model was subsequently validated in a different consecutive
group of patients within the same registry all treated with drug-eluting stents
(n=337). This risk model consists of 54 variables (17 clinical, 4 procedural, and 33
angiographic features). A substantially higher c-statistic was evident for the NERS
compared with the SXscore (NERS: 0.89 vs SXscore: 0.69), indicating that it had
an excellent discriminatory ability.
When the NERS score was separated into two groups of risk (high and low)
and clinical outcomes assessed, the high-risk group was demonstrated to be
significantly more predictive of MACCE compared with the intermediate or high SX
score tertiles.
In the low-risk NERS group, outcomes were similar to the low SXscore group,
suggesting at least from this study that anatomical variables alone may be sufficient to
predict outcomes in the low-risk group. However, patient co morbidity was
significantly less prevalent in the NERS patient population compared with the all-
comers SYNTAX population (Serruys et al., 2009) the latter of which was
designed to overcome many of the limitations/bias selections inherent in small
registries. Validation of the NERS risk model in a much larger, randomized
population of patients is therefore required.
6. Global Risk: The SYNTAX trial established a complex interaction between the
EuroSCORE and the SXscore. The need to combine the angiographic and clinical
scores into a single approach consequently became evident (Serruys et al., 2010).
The Global Risk approach aims to potentially combine established

historically accepted clinical variables from the EuroSCORE with anatomical
variables from the SXscore to allow for a Global Risk assessment for patients
proposing undergoing revascularization with PCI (Serruys et al., 2010).
By adopting this approach, the same risk model could potentially be used by
the Heart Team to appropriately risk stratify patients proposing to undergo PCI or
CABG. This may potentially increase the number of patients who could safely and
efficaciously be treated with PCI compared to the use of the SYNTAX score alone.
In variants of this model, one group has previously demonstrated the

potential of the Global Risk model to enhance risk stratification among patients
who underwent LMS PCI from a single-center registry (Capodanno et al., 2010).
A major criticism of their approach has been the lack of consistency in their
application of the Global Risk model. The range of scores within each tertile of
risk for the Euro SCORE and SXscores has been established as described earlier.
Yet in the two publications using the Global Risk approach by the same group
(Capodanno et al., 2009) a different range of scores for the tertiles of risk for the
EuroSCORE and SXscores has been used (Federspiel et al., 2011).
It is the authors’ opinions that the established range of scores for the tertiles
of risk for the EuroSCORE and SXscore should be maintained to allow the
application of the Global Risk model across surgical and PCI populations, and
importantly allow for a consistency in the ranges of scores that will make
application of the model by other groups possible and ultimately may allow
validation of this risk model in the future, should this risk model prove feasible.
Further study into the concept of a Global Risk approach utilizing the
EuroSCORE and SXscores with ranges of risks based on consistently defined
values for the EuroSCORE and SXscore tertiles are forthcoming.
 Risk/Benefit Analysis
Undoubtedly, both PCI and CABG allow for an improvement in the quality of
life for patients. However, one of the main drawbacks of using contemporary risk
models for both PCI and CABG is that the role of the individual patient, their personal
preferences, and perception of risk may be underestimated. To address this issue, the
novel concept of a clinical model that balances the risks and benefits of the proposed
revascularization procedure has recently emerged (Federspiel et al., 2011).
Individual patients may value this risk/benefit tradeoff differently. For some,
exchanging the increased risk of repeat PCI or CABG to obtain short-term pain
relief and a rapid return to full mobility will be acceptable, whereas others may
prefer to endure short-term pain to obtain a higher probability of avoiding a
subsequent revascularization.
Patients may also prefer to risk undergoing multiple PCI procedures rather than
a single CABG, or they may prefer to avoid the risk of requiring CABG subsequent to
PCI and instead have CABG initially.
Consequently, from the patient’s perspective, the balance between these

conflicting considerations appears to play a crucial role in the identification of the
preferred revascularization strategy (Federspiel et al., 2011).
Thus, It would appear that a combination of clinical and anatomical

variables are required for an effective, clinically useful risk model for patients with
complex coronary artery disease proposing to undergo multivessel PCI.
Ideally this model would be simple to calculate and could be rapidly

performed at the bedside. However, the need to include detailed anatomical
assessments appears evident, such as the incorporation of the SXscore. The
pragmatic approach appears in developing and refining a risk model that
incorporates both elements in as simple a way as possible.
Concepts such as the noninvasive calculation of the Functional SYNTAX score

may serve to streamline this process and the concept of patient-empowered
risk/benefit tradeoff are potential further areas for research (Vasim et al., 2011).
Influence of gender , diabetes & PVDs on SVGs

In a study conducted by (Garland et al, 2003), Female gender, peripheral
vascular disease, and postoperative intra-aortic balloon pump use were identified
as significant independent predictors of major leg wound complications. Unlike the
multiple logistic analysis, performed by Crouch et al., which showed that open
harvesting (p ≤ 0.0007) and diabetes (p ≤ 0.0001) were independent risk factors for
wound infection (Crouch et al, 1999).
Wilson et al, 2003 documented many factors that he believed to be the most
important in the pathology of wound infection, among these factors were the
patient side: age, nutritional status, obesity and altered immune response (Wilson
et al, 2003).Other operative factors as: duration of surgery, skin antiseptic/shaving,
instrument sterilization and antimicrobial prophylaxis. Wilson also suggested
another procedure which may add another dimension to surgical prophylaxis, a
new method of delivering topical antibiotics in the wound and the use of antiseptic-
impregnated suture (Wilson et al., 2003).
Other risk factors identified for wound infection in lower limb include
female gender, chronic steroid therapy, and diabetes mellitus, and malnutrition,
post-operative use of blood products, lymph leak, post-operative edema, low pre-
operative hematocrit, high pre-operative urea, and low serum albumin (Wilson et
al., 1990).
Idiopathic etiology
Recent evidence suggested that two-thirds of wound infections occur in

clean wounds following discharge and that these infections are not predicted by the
recognized risk factors (Wilson et al., 1990).
Intraoperative data:
Harvesting time
The time spent during the process of vein harvesting until skin closure (mean of
70.8 ±31.8 min SD) in group A; versus in group B (P value was statistically-
insignificant) and 69.7± 39.8 min for group B. The operative time was (mean of
201.1± 51 minSD) and (mean of 199.4± 40.8 min SD) for A and B group
respectively.
In our study there was no significant difference in time spent in harvesting

the saphenous vein between the two groups of patients, unlike the study which was
conducted by Enoch et al. 2006 that document significant longer time in the group
of patients in which vein harvesting was extended above the knee.
ANATOMY OF THE GREAT SAPHENOUS

VEIN
It is generally believed that the term saphenous derives from the Greek
word" Safaina", which means "evident".
However, some researchers have disproved this assumption as intenable. It

seems that the origin of the word saphenous is the Arabic word "el Safin", which
means "hidden" or "concealed".
This is in harmony with the deep location of the saphenous veins below the
superficial fascia (Caggiati &Bergon, 2002).
The great saphenous vein starts inferiorly (below) as a continuation of the

medial marginal vein and ends in the femoral vein a short distance distal to the
inguinal ligament, being thus the body's longest vein, the GSV begins just anterior
to the medial ankle, crosses in front of the tibia, and ascends medial to the knee
(Figure 3).
Proximal to the knee, the GSV ascends on the medial side of the thigh and
enters the fossa ovalis 3cm inferior and 3cm lateral to the pubic tubercle, the GSV
is doubled in the calf in 25% of the population, in the thigh in 8%, the saphenous
nerve runs in close proximity to the GSV in the distal two-thirds of the calf
(Scultetus et al., 2001).
Figure 14: Surface anatomy of great saphenous vein (Grants et al , 2005).

Figure 15: Surface anatomy of great saphenous vein (Grants et al , 2005).
Figure 16: The medial part of the dorsal vein loop of the right foot ( blue arrow ) and its
junction with the great saphenous vein. It is visible in front of the medial malleolus
(white arrow) (Mendoza et al. 2014).
Figure 17: Course of the great saphenous vein in right lower leg and knee (Mendoza et
al. 2014).
Figure 18: The fascial compartment of the great saphenous vein. The course of the great
saphenous vein is drawn on the inner side of the leg. The green hatching shows the
width of the saphenous compartment starting on the dorsal foot. It is very narrow
along the lower leg, grows broader in the thigh and ends at the inguinal ligament
where the two fasciae (muscle fascia and saphenous fascia) are joined ( Mendoza
et al. 2014).
Figure 19: Arch veins with a view of the inner side of the right calf. The course of the great
saphenous vein is marked green . The anterior arch vein, marked in orange , enters just
after it crosses the tibia. The dotted line is a frequent alternative and/or additional course of
the arch vein. The posterior arch vein is marked medially, also in orange , along Linton’s
line (Mendoza et al. 2014).
Figure 20: Postero-medial view of the calf demonstrating the inter-saphenous vein between the small and
great saphenous veins in the calf ( arrow ). The posterior arch vein arises behind the medial
malleolus and travels straight up to the great saphenous vein. The black dots represent the
locations of the perforating veins. The numbers by the perforating veins show their distance in cm
from the ground in a standing patient ( 4 medial ankle perforating vein, formerly Kuster
perforating vein; 7 lower posterior tibial perforating vein, formerly Cockett 1, C1; 14 middle
posterior tibial perforating vein, formerly Cockett 2, C2; 18 upper posterior tibial perforating vein,
formerly Cockett 3, C3; 24 medial paratibial perforating vein in the mid lower leg, formerly
Sherman perforating vein (Mendoza et al. 2014).
Figure 21:Anterior and posterior accessory saphenous veins ( orange ) demonstrating variations in their
termination with the great saphenous vein ( green ). The dotted line marks the alternative course of
the posterior accessory saphenous vein into the confluence of superficial inguinal veins. The black
mark indicates where the anterior accessory saphenous vein leaves the fascial compartment of the
great saphenous vein and becomes epifascial. Distal of this point, there is very often a connecting
vein between the anterior accessory saphenous vein and the great saphenous vein (Mendoza
et al. 2014).
Figure 22: Location of the perforating veins of the adductor canal (formerly Dodd and Hunter) in the above-
knee great saphenous vein. Location of the paratibial perforating veins (formerly Boyd) in the below-
knee great saphenous vein (Mendoza et al. 2014).
Figure 23: Location of the perforating veins on the front and inner sides of the calf ( Blue , perforating veins
of the anterior arch vein; light blue , outfl ow into the arch vein lateral of the edge of the tibia and
drainage into the anterior tibial veins; dark blue , outfl ow into the arch vein medial of the edge of
the tibia and drainage into the posterior tibial veins; green, perforating veins of the great saphenous
vein; dark green , Boyd perforating vein; light green, paratibial perforating veins with drainage into
the posterior tibial veins; black , perforating veins of the posterior arch vein ) (Mendoza et al.
2014).
The relationship between the GSV and these subcutaneous tributaries
may be classified as three anatomical patterns, each with a specific ultrasound
appearance
 Type ‘I’: the saphenous trunk is present with a normal diameter throughout
the length of the saphenous compartment and there are no large parallel
tributaries.
 Type ‘h’: the saphenous trunk is present throughout the saphenous

compartment, and there is also a tributary vein that may be even larger than
the GSV.
 Type ‘S’: a superficial tributary ascends and pierces the superficial fascia
continuing as the GSV within its compartment, while distal to this point the
GSV is absent or only barely visible on ultrasound imaging (absent or
hypoplastic). (Cronenwett and Wayne, 2010)
Figure 24: Anatomic types of the great saphenous vein (GSV) with respect to the fascial
envelope. A, “I” type. The GSV is present within the fascial envelope along its
entire length.B, “H” type. There is a subcutaneous collateral running parallel and
superficial to the mainsaphenous trunk (left). C, “S” type. The caudal portion of
the GSV in the thigh is atretic and the extrafascial tributary is dominant.
(Cronenwett and Wayne, 2010).
Accessory great saphenous veins are frequently present and they run parallel
to the GSV both in the thigh and in the leg; they lie anterior, posterior, or
superficial to the main trunk. The posterior accessory GSV of the leg (Leonardo’s
vein or posterior arch vein) is a common tributary, it begins posterior to the medial
malleolus, ascends on the posteromedial aspect of the calf, and joins the GSV
distal to the knee (Bergan, 2007).
The anterior accessory GSV of the leg drains the anterior aspect of the leg
below the knee. The posterior accessory GSV of the thigh, if present, drains the
medial and posterior thigh. The anterior accessory GSV of the thigh collects blood
from the anterior and lateral side of the thigh (Figure 4).
The anterior and posterior accessory GSVs join the GSV just before it ends at
the confluence of superficial inguinal veins (saphenofemoral junction). The
superficial circumflex iliac, superficial epigastric, and external pudendal veins join
each other and the distal GSV to form the confluence of superficial inguinal veins
(saphenofemoral junction) (Figure 5).
Rarely, the GSV terminates high on the lower abdomen or joins the femoral
vein very low and the superficial inguinal veins empty individually into the
femoral vein. Other occasional tributaries of the GSV in the groin include the
posterior and anterior thigh circumflex veins (Bergan, 2007).
Figure 25: Common variations (a. -33%, b. -15%, c. -15%, d.-13%) in the anatomy
of the confluence of inguinal veins (saphenofemoral junction) (Bergan, 2007).
Proximal veins drain venous blood from the abdominal wall and pudendal
areas, and from lateral to medial. These are the superficial circumflex iliac,
superficial epigastric and superficial external pudendal veins. Proximal veins may
be single or multiple and are of clinical importance because they may transmit
retrograde flow into the GSV even with a competent terminal valve, reported in
28–59% of cases (Cavezzi et al., 2000).
Distal merging veins at the SFJ are often relatively large and are typically
the lateral AASV which is present in 41% of subjects12 joining the GSV within 1
cm of the SFJ, and the medial PASV which may represent the proximal end of the
Giacomini vein at a variable distance from the SFJ, often distal to the pre- terminal
valve. In most cases, there is a quite constant lymph node in the angle between the
GSV and AASV before they merge and the vein net of lymphatic node(s) that
surrounds the AASV may be sometimes large and incompetent, forming a source
for reflux into thigh and leg varicose veins (Cavezzi et al.,2006).
Surface Marking of Great or Long Saphenous Vein
It can be marked by joining the following points, although it is may easily

visible in living subjects.
(a) First point on the dorsum of the foot at the medial end of the dorsal venous
arch.
(b) Second point on the anterior surface of the medial malleolus. It ascends about
2.5-3 cm anterior to the tibial malleolus.
(c) Third point on the medial border of the tibia at the junction of the upper two-
thirds and lower one-third of the leg. crosses the distal third of the medial
surface of the tibia obliquely to its medial border.
(d) Fourth point at the adductor tubercle, ascends a little behind the border to the
knee; proximally it is posteromedial to the medial tibial and femoral condyles
then ascends the medial aspect of the thigh; after traversing the saphenous
opening it finally opens into the femoral vein.
(e) Fifth point just below the centre of the saphenous opening(Its centre lies 4 cm
below and 4 cm lateral to the pubic tubercle, It is about 2.5 cm long and 2 cm
broad, with its long axis directed downwards and laterally) . The so-called
"centre" of the opening is often said to be 2.5-3.5 cm inferolateral to the pubic
tubercle; and the vein is then, held to be represented by a line drawn from this
to the femoral adductor tubercle. However, the saphenous opening, as noted
elsewhere, varies greatly in size and disposition and its imagined centre has
proved a poor indicator of the saphenofemoral junction (Gabella et al., 1995).
The long saphenous vein has from 10 to 20 valves, which are more
numerous in the leg than the thigh.
One is present just before it pierces the cribriform fascia, another at its
junction with the femoral vein (Peter, 1995).
The valves in the saphenous vein are classically bicuspid, although on

occasion they may have only one cusp, the valves cusps are oriented parallel to the
surface of the skin (Edwards, 1986).
Physiology of the Great Saphenous Vein
Careful study of the macroscopic as well as the microscopic anatomy of the

veins especially, the long saphenous vein led us to better understanding of its
function and hence directed us to choosing it as a conduit (Nehler et al., 1991).
When the body is erect, the zero level of venous pressure is in the right
atrium. The hydrostatic pressure in a vein on the dorsum of the foot is equal to the
distance from the right atrium to the foot i.e about 100 cm H2O, so that the more
dependent the vein, the higher the hydrostatic pressure and the thicker the vein
wall. This is why the long saphenous vein can be used so readily as an arterial
substitute (Clarke et al., 1992).
According to the microscopic and biochemical aspects, the autogenous vein

(long saphenous vein as an example) serves as a superior conduit because it is a
living structure that actively participates in keeping the flowing stream of blood
liquid as it crosses its surface. A variety of molecules secreted by the vein wall
have been identified, including: -
 Glycosaminolgycans, which serve as cofactors for antithrombin III.

 Heparin cofactors II (Ratnoff et al., 1991).
Thrombomodulin, protein C, and protein S are also secreted and together

participate in inactivation of coagulant antihemophilic factor (factor VIII) and
proaccelerin (factor V). (Marlar, 1985).
Endothelial cells play an important role in the balance of coagulation and

fibrinolysis (Fig. 3); regulate platelet function and vascular growth. In addition, the
vascular endothelium plays a critical role in regulation of vascular tone through the
release of a variety of biological substances (Luscher, 1991).
Fig. 26: Schematic representation of the fibrinolytic system (O’Reilly, 1995)

For example, nitric oxide, which is formed from L-arginine, is both a potent
vasodilator and an inhibitor of platelet adhesion and aggregation (Fig. 4) (Palmer
et al., 1988) and (Radomski et al., 1987).
Nitric oxide acts by activating the soluble guanylate cyclase in vascular

smooth muscle raising cGMP levels which then mediates relaxation by reducing
intracellular levels of calcium (Rapoport et al., 1983).
Again, the endothelial cells also synthesize prostacyclin, a potent inhibitor of

platelet aggregation and a stimulus for platelet disaggregation (Eldor et al., 1981)
and (Bush et al., 1984).
Ratnoff and his group have demonstrated that endothelial cells secrete in
addition a substance that inactivates hageman factor (factor XII), which prevents
the first steps of the intrinsic pathway of thrombus formation (fig. 5) (Ratnoff et
al., 1991).
Endothelial cells are also a source of growth regulatos that stimulate or

inhibit proliferation of vascular cells (Luscher, 1990) and (Fox, 1988).
Another important growth inhibitors secreted by endothelial cells are heparin

and heparin sulfate (Castello et al., 1981).
Fig. 27: Diagram showing formation in an endothelial cell of nitric oxide (NO) from
arginine in a reaction catalyzed by NO synthase.(Murray, 1993).
Interaction of an agonist (eg, aceytlcholine) with a receptor (R) probably

leads to intracellular release of Ca2+ via inositol triphosphate generated by the
phosphoinositide pathway, resulting in activation of NO synthase.
The NO subsequently diffuses into adjacent smooth muscle, where it leads

to activation of gaunylate cyclase, formation of cGMP, stimulation of cGMP-
protein kinases, and subsequent relaxation. The vasodilator glyceryl trinitrate is
shown entering the smooth muscle cell, where is metabolism also leads to
formation of NO (Murray, 1993).
Fig. 28: The pathways of blood coagulation. The intrinsic and extrinsic pathways are
indicated (Roberts et al., 1992).
Heparin in concentrations (100μg/mL) normally found in the extracellular

matrix and vascular smooth muscle cells of the vessel wall has been shown to
inhibit vascular smooth muscle cell proliferation (Yla- Herttuala al., 1989).
In a recent report, it was found that cells from patients with restenosis, both
restenotic lesions and undistended veins, showed much lower sensitivity to growth
inhibition by heparin than controls. Thus, it has been suggested that heparin
resistance in normal vascular tissue may indicate a propensity for the development
of restenosis (Chan et al., 1993).
Additional work has identified another potent, locally vasoactive substances

collectively known as endothelium – derived relaxing factors (EDRFs) (Lawrie et
al., 1990).
EDRFs mediate vascular relaxation tonically in response to increased flow

and to a variety of agonists (adenosine triphosphate [ATP], 5 – hydroxytryptamine
[5 – HT ] ) that may be released by activated platelets. EDRFs are also potent
inhibitors of platelet aggregation and adhesion.
The chief function of EDRFs is to restrict vasoconstriction and thrombus

propagation at sites of vascular injury (Angelini et al., 1989).
Endothelial cells can synthesize polypeptide growth factors, collectively

named endothelium-derived growth factors (EDGFs), they include:
 Basic fibroblast growth factor (bFGF) (Klagsburn, 1989).
 Platelet-derived growth factor (PDGF)-like substance (Raines et al., 1990).
 Vascular endothelial cell growth factor/vascular permeability factor

(VEGF/VPF) (Ferrara and Henzel, 1989).
EDGFs are potent angiogenic factors, which promote endothelial cell regrowth
following vascular injury via a NO dependent mechanism (Hariwala et al., 1996).
Iba and associates have evaluated the ability of the vein’s endothelium to
secrete tissue plasminogen activator (t – pa), which triggers the fibrinolytic cascade
to maintain blood in a fluid state (Iba et al., 1991).
2011/AMERICAN COLLEGE OF CARDIOLOGY (ACC)
AND AMERICAN HEART ASSOCIATION (AHA)
GUIDELINE FOR CABG
Asymptomatic/mild angina
Class I
1. Left main stenosis
2. Left main equivalent (proximal LAD and proximal circumflex)
3. Triple-vessel disease
Class lla
1. Proximal LAD stenosis and one- or two-vessel disease
Class IIb
1. One- or two-vessel disease not involving proximal
LAD
If a large territory at risk on noninvasive studies or LVEF> 50%, IIa and IIb
become class I indications
Stable angina
Class I
2. Left main equivalent (proximal LAD and proximal circumflex)

3. Triple-vessel disease
4. Two-vessel disease with proximal LAD stenosis and EF > 50% or demonstrable
ischemia
5. One- or two-vessel disease without proximal LAD stenosis but with a large
territory at risk and high risk criteria on noninvasive testing
6. Disabling angina refractory to medical therapy
Class IIa
1. Proximal LAD stenosis with one vessel disease
2. One- or two-vessel disease without proximal LAD stenosis, but with a moderate
territory at risk and demonstrable ischemia.
If a large territory at risk on noninvasive studies and meets high risk criteria on
noninvasive testing becomes a class I indication
Unstable angina/non-ST-segment elevation MI (NSTEMI)
Class I
1. Left main
2. Left main equivalent
3. Ongoing ischemia not responsive to maximal nonsurgical therapy
Class IIa
1. Proximal LAD stenosis with one- or two-vessel disease
Class IIb
1. One- or two-vessel disease without proximal LAD stenosis when PCI not
possible (becomes class I if high risk criteria on noninvasive testing)
ST-segment Elevation (Q-wave) MI
Class I
1. Failed PCI with persistent pain or hemodynamic instability and anatomically

feasible
2. Persistent or recurrent ischemia refractory to medical treatment with acceptable

anatomy who have a significant territory at risk and not a candidate for PCI
3. Requires surgical repair of postinfarction ventricular septal rupture or mitral

valve insufficiency
4. Cardiogenic shock in patients less than 75 years of age who have ST-segment
elevation, LBBB, or a posterior MI within 18 hours of onset
5. Life-threatening ventricular arrhythmias in the presence of ≥ 50% left main

stenosis or triple-vessel disease
Class IIa
1. Primary reperfusion in patients who have failed fibrinolytics or PCI and are in
the early stages (6–12 hours) of an evolving STEMI
2. Mortality with CABG is elevated the first 3–7 days after STEMI/NSTEMI.
After 7 days, criteria for revascularization in previous sections apply
Poor LV function
Class I
2. Left main equivalent

3. Proximal LAD stenosis and two- to three-vessel disease
Class IIa
1. Significant viable territory and noncontractile myocardium
Life-threatening ventricular arrhythmias
Class I
1. Left main disease
2. three-vessel disease
Class IIa
1. Bypassable one- or two-vessel disease
2. Proximal LAD disease and one- or two-vessel disease
These become class I indications if arrhythmia is resuscitated cardiac death or

sustained ventricular tachycardia
Failed PCI
Class I
1. Ongoing ischemia with significant territory at risk
2. Hemodynamic instability
Class IIa
1. Foreign body in critical position
2. Hemodynamic instability with coagulopathy and no previous sternotomy

Class IIb
1. Hemodynamic instability with coagulopathy and previous sternotomy
Previous CABG
Class I
1. Disabling angina refractory to medical therapy
2. Nonpatent previous bypass grafts, but with class I indications for native CAD
Class IIa
1. Large territory at risk
2. Vein grafts supplying LAD or large territory are greater than 50% stenosed.
Class I: conditions for which there is evidence and/ or general agreement that a
given procedure or treatment is useful and effective.
Class II: conditions for which there is confilicting evidence and/ or a divergence
of opinion about the usefulness or effcany of a procedure
Class IIa: weight of evidence/ opinion is in favor of usefulness/ efficacy.
Class III: conditions for which there is evidence and/or general agreement that the
procedure/ treatment is not useful/ effective and in some cases may be harmful.
GREATER SAPHENOUS VEIN GRAFT
CONDUIT IN CABG
Saphenous vein was the conduit used in the first series of coronary surgery,
and, with the exception of revascularization of the left anterior descending
coronary artery, it remains the most commonly used conduit (Favaloro et al , 1969
).
In spite of its shortcomings the saphenous vein continues to be one of the

most commonly used conduits in coronary bypass grafting. Characteristics that
have solidified the greater saphenous vein as a coronary conduit include its ease of
harvest, ready availability, resistance to spasm, and thoroughly studied long-term
results.
There are several reasons for this. First, because of its relatively large diameter
and wall characteristics, it is technically easy to use; second, it is plentiful, and
therefore can be used to perform multiple grafts; third, it is long and can reach any
coronary artery; and fourth, it is easily harvested.
Patency rates for vein grafts gave one year graft patency rates of 93,4%, five
year rates of 74.0%, and ten year rates of 41.0%. (Barner et al., 1985).
Szylagyi and colleagues (1990) believed the most important factor in

success of the coronary revascularization to be the quality of the vein itself.
Experiments demonstrated that vein grafts were more vulnerable to atherosclerosis
than pedicled IMA grafts. It was thought that early failure of saphenous vein grafts
were caused by subintimal hyperplasia.
As efforts were made toward more suitable matching of the size of the vein graft
to the size of the artery, the incidence of hyperplasia in vein grafts diminished.
There was a continued trend toward the recurrence of angina one year post-
operatively, which was shown angiographically to be due to vein grafts failure.
Failure of vein grafts increased in frequency beyond five years post-operatively
secondary to accelerated atherosclerosis (Doty and Donald, 1997).
Impairment of vasa vasorum in vein grafts creates atherosclerotic lesions.

The disruption of the vasa vasorum leaves the walls of the veins without capillary
flow for 72 hours. Approximately six weeks are needed for maximal return of
arteriolar flow. This flow, regardless of placement does not come from it’s own
lumen; it comes from neighboring arteries (Green, George, 1986).
Deficiencies of vasa vasorum preclude the development of atherosclerosis.

Grondin reported at 10 years, only 21% of SVG’s showed no adverse changes,
whereas 95% of IMA pedicled grafts showed no adverse changes (Fiore et al.,
1990).
In pharmacologic strategies to maximize early and late venous graft patency.

Prospective randomized trials have shown that early aspirin administration reduces
vein graft occlusion in the first year after CABG. Administration of aspirin within
48 hours after CABG also reduces early postoperative complications including
mortality, MI, stroke, renal failure, and bowel infarction (Mangano et al, 2002).
More recently it has been recognized that lipid-lowering agents reduce the
progression of both native coronary artery and graft atherosclerosis, as well as
subsequent cardiovascular events (Anonymous, 1997).
Aggressive use of statins to achieve a low-density lipoprotein cholesterol
<100mg/dL decreased by one-third the number of grafts affected with
atherosclerosis at angiographic follow-up, and also decreased the need for repeat
revascularization in The Post Coronary Artery Bypass Graft Trial Investigation.
Despite clear documentation of improved outcomes with these two

pharmacologic strategies, there is evidence of underutilization of these therapies
after CABG (Brophy et al., 2003 & Foody et al., 2003).
Systemic approaches to ensure their universal application are needed.

Finally, in the future gene therapy may allow modification of the venous vascular
endothelium to avert development of intimal hyperplasia (Mann et al., 1997).
Unfortunately, the PREVENT IV trial, testing whether short-term

angiographic vein graft failure could be diminished with treatment of saphenous
vein prior to grafting with edifoligide (an oligonucleotide decoy that binds to and
inhibits E2F transcription factors) demonstrated no impact of the treatment
(Alexander et al., 2005).
The concept remains a valid one, however, and gene therapy will continue to
be an exciting area of investigation in the future.
SURGICAL TECHNIQUES REDUCING VEIN
GRAFT FAILURE
Routinely, graft preparation includes dissection of the vein from its bed,
ligation of side branches, flushing and distension of the lumen to overcome spasm
and to identify leaks (Gundry et al., 1980).
Endothelial injury results from direct mechanical trauma and stretching as a

result of luminal distension (Haudenschild et al., 1981).
Impaired fibrinolytic activity, caused by uncontrolled distension of

saphenous vein prior to its use as a vascular conduit, may contribute to early vein
graft thrombosis, and can be avoided by using controlled distension to <120 mmHg
(Underwood, 1993).
In 1977, an endothelium preserving technique without touching the vein

during the anastomosis was described (Gottlob, 1977).
In 1980 it was recommended that the vein should be harvested by a "no-

touch" technique to minimize manipulation, side branch ties should be placed away
from the SV wall, veins should be immersed in cold blood and distension above
100mmHg was to be avoided (Gundry, 1980).
Prevention of endothelial damage in veins was demonstrated by applying

pharmacologic relaxation of the vessel that allows a gentle dilatation with low,
controlled pressure (Haudenschild et al., 1981).
Based on this principle, it was suggested that the SV preparation should

incorporate subcutaneous and perivenous infiltration with papaverine, atraumatic
dissection, controlled gradual distension, and storage of the vein in cold
heparinized blood (Adcock et al., 1984).
The use of glyceryl trinitrate-verapamil solution both topically and

intraluminally was introduced in 1993 as a very effective and safe combination to
promote relaxation of the vein during preparation (Rosendfeldt et al., 1993).
Thus, various atraumatic techniques have been described to reduce vein

damage during harvesting and implantation. All these techniques avoid high-
pressure distension, but mechanical distension is still generally required, and
adventitial damage still occurs due to stripping of the perivascular tissue (Gundry,
1980).
No-touch technique consists of retaining the cushion of surrounding tissue

that both prevents venospasm, thereby obviating the need for distension, and
protects the vein from direct handling by surgical instruments even during
performing the anastomoses (Souza et al., 2001).
III. The Conventional Saphenous Venous Grafts.
The Surgical Anatomy of Saphenous Venous Grafts (SVGs)
1- The greater saphenous vein:

The term saphenous is derived from the Greek word for "visible”. The great saphenous vein
drains the medial end of the dorsal venous arch of the foot and passes upward directly in front of
the medial malleolus. It then ascends in company with the saphenous nerve in the superficial
fascia over the medial side of the leg. The vein passes behind the knee and curves forward
around the medial side of the thigh. It passes through the lower part of the saphenous opening in
the deep fascia and joins the femoral vein about 1 ½ inches (4 cm) below and lateral to the pubic
tubercle. (Snel, 198l).
The great saphenous vein possesses numerous valves; it is connected to the small saphenous
vein by one or two branches that pass behind the knee.A number of Perforating veins connect the
saphenous vein with the deep veins along the medial side of the calf. The great saphenous vein
pierces the saphenous opening in the deep fascia (fascia lata) of the thigh and joins the femoral
vein 1½ inches (4 cm) below and lateral to the pubic tubercle.
At the saphenous opening in the deep fascia, great saphenous vein usually receives three
tributaries which are variable in size: (1) the superficial circumflex vein, (2) the superficial
epigastric vein, and (3) superficial external pudendal vein. These veins correspond with the three
branches of the femoral artery found in this region. An additional vein, known as the lateral
accessory vein, usually joins the main vein about the middle the thigh or higher up at the
saphenous opening (Snell, 1981).
II- The lesser saphenous vein.

The short saphenous vein, also called the small or internal saphenous vein, originates from the
junction of the lateral marginal vein of the foot with small veins from the lateral side of the heel
behind the lateral malleolus. (Skandalakis, 2000).
Unlike the greater saphenous vein, the lesser saphenous vein may penetrate the deep fascia at
any point from the middle third of the calf upward. This fact explains the segmental rather than
total nature of reflux found in the lesser saphenous vein. (Bergan, 2000). It passes between the
Achilles tendon and the posterior border of the lateral malleolus to ascend in the center of the
calf up to the popliteal fossa about 1.25 cm below the posterior transverse skin crease of the
knee. From this level to about 10 cm above the crease, the lesser saphenous vein joins the
popliteal vein. The small saphenous vein has numerous valves along its course. (Skandalakis,
2000).
Fig 6: The Superficial and the Deep Venous Systems of the Lower Limb (Snell, 1981).
* Tributaries:
1. Numerous small veins from the back of the leg.

2. Communicating veins with the deep veins of the foot.
3. Important anastomotic branches that run upward and medially to join great saphenous vein.
The small saphenous vein terminates by either joining the popliteal vein; the great saphenous
vein; or by splitting in two, one division to popliteal and the other the great saphenous vein.
There are five perforating veins between the two venous systems of the leg:
1) A vein, just distal to the knee, from great saphenous into the posterior tibial vein.
2) The external or lateral perforating vein at the junction of middle and lower thirds of the leg.
3) The upper ankle perforating vein halfway up the leg at the posterior tibial margin.
4) The middle ankle perforating vein is 7.5-10 cm above the medial malleolus.
5) The lowest ankle perforating vein behind and below the medial malleolus (Snel, 198l).
Variations of Saphenous Veins:
Variation in the level of the short saphenous termination by: ending in midthigh to join great
saphenous rather than the popliteal vein (13 %), dividing in the popliteal space, with one branch
entering the popliteal vein and the other branch continuing upward in the superficial fascia to
join great saphenous vein (15%). Rarely, may join great saphenous vein at Knee level. The great
saphenous may enter the femoral vein as far as 5 cm below the saphenous opening. Accessory
saphenous vein may occur at the medial aspect of the inner thigh, or the great saphenous vein
may be duplicated below the knee (Skandalakis, 2000).
Fig. 7: The Free Aorto-Coronary Saphenous Vein Graft (Skandalakis, 2000).

The following surgical factors are possibly responsible for graft occlusion
1. Handling the vein with surgical instruments, stripping of the adventitial layer, and hydrostatic
dilatation (>150 mm Hg) to overcome spasm may cause prominent endothelial cell loss and
medial damage (Qvist et al, 1992).
2. Site of Insertion: Occlusion occurrs in diagonal branches > circumflex > right coronary.
3. Size of artery bypassed graft: Occlusion occurs in grafts sutured to arteries < 2 mm with a
flow rate of 20 ml/min or less (Cataldo et al, 1993)..
4. Quality of the recipient arteries.
5. Length of Graft: kinking will occur if the graft is too lung. (Ramos et al, 1976)..
6. The quality of the vein before its harvesting.
7. Clinical factors: age, New York heart Association functional class, preioperative infarctions,
cholesterol level, smoking, hypertension, or use of antiplatelet drugs (Souza et al, 2001).
Strategies that prevent early graft occlusion and improve the early patency rate
1. Pharmacologic interventions.
2. Gene transfer before grafting.
3. External stenting of the vein graft.
4. Refined SV harvesting technique (non-touch) (Souza et al, 2001).
* Early graft closure (1 month):

Grondin and associates in 1974 found that 10 to 15 % of saphenous vein grafts occlude by
the first month after surgery (Grondin et al, 1974).
At this early stage, the principal underlying mechanism of vein graft occlusion is graft
thrombosis by alteration in the vessel wall, changes in blood rheology, altered flow dynamics, or
focal endothelial disruption (related to irrigating solution, storage solution, storage temperature,
and distending pressure). Additional endothelial loss occurs when the vein is placed within the
arterial system or in physiologic saline (acidic pH, causes endothelial cell loss). Storage at room
temperature (20 to 230C) or 370C within lactated Ringer's solution better preserves endothelial
cells. (Lawne et al, 1990), (Solberg et al, 1987).
Fitzgibbon and associates found in 1996 that 3 to 12 % of saphenous vein grafts occlude,
with or without symptoms by the first month after surgery secondary to reduced graft flow,
limited outflow (coronary diameter of 1.5 mm or less) (Cataldo et al, 1993) (Ramos et al, 1976).
Loss of endothelial monolayer results in the accumulation of fibrin on the luminal surface
(which starts 24 hours after grafting), the adherence of platelets and neutrophils, and a reduction
in tissue plasminogen activator production. Endothelial loss also activates the extrinsic
coagulation cascade by tissue factor that is expressed in the exposed subendothelium.
Additionally, the inherent antithrombotic properties of veins are comparatively week. Heparin
sulfate, a proteoglycan molecule with anticoagulant properties mediated by potentiation of
antithrombin III, is less prominent in the media and in the poorly developed internal elastic
lamina of veins as compared with arteries. Production of nitric oxide and prostacycline, both
potent inhibitors of platelet activation, is lower in veins than in arteries, and nitric oxide
production is further reduced by bypass grafting. The low fluid shear stress in grafted venous
conduits, as compared with arteries, reduces the shear-dependent release of tissue plasminogen
activator, nitric oxide, and prostacycline (Joseph et al, 1998) .
The propensity for early graft occlusion resulting from these prothrombotic effects may, on
occasion, be amplified by technical factors that reduce graft flow, and failure at the aortic
anastomosis can be due to: Large suture bites in the vein, or angulation at the neck due to
improper alignment of the anastomotic axis with the vein course. (Grondin et al, 1974).
Failure of the distal anastomosis may be due to: Suture placement in the coronary artery using
large bites in the coronary artery at the heel and toe; Linear tension due to insufficient graft
length; redundancy of the graft (Griffith et al, 1977).
* Graft failure from 1 to 12 months:
Intimal hyperplasia, defined as the accumulation of smooth muscle cells and extracellular
matrix in the intimal compartment, is the major disease process in venous grafts within 4 to 6
weeks hence reducing the lumen by up to 25%. (Joseph et al, 1998).
Medial smooth muscle cells proliferate, migrate, and synthesize extracellular matrix in
response to a number of growth factors and cytokines released from activated endothelial cells,
platelets and macrophages (Verrier and Boyle, 1996). The transient "ischemia-reperfusion" after
grafting reduces endothelial production of antiproliferative mediators (eg: NO), and induces
marked superoxide radical formation with direct promotion of smooth muscle cell proliferation.
The acute, pronounced increase in wall stress incurred by saphenous veins on exposure to
arterial pressures furtherly promotes intimal fibrosis, fibroblast growth factor (bFGF), increases
vein diameter, reduces mean blood velocity, and shear stress. This increases the shear-regulated
production of potent mitogens thus shifting the balance toward smooth muscle cell proliferation
and intimal hyperplasia. (Allaire and Clowes, 1997).
* Graft failure from 1 to 5 years:
This interval has a failure rate of 2 to 3 % per year due to vein atherosclerosis often with
superimposed late graft thrombosis, and rupture of atheromatous plaques (Joseph et al, 1998).
* Graft failure beyond 5 years:
Graft failure after the fifth year occurs at a rate of 5% per year, with a 10- year-patency rate
varying between 41% and 56% while 25% of vein grafts have significant atherosclerotic lesions.
Graft closure in this interval is almost always secondary to atherosclerosis and its complications
(Campeau et at, 1983).
Harvesting Technique of Venous Grafts
After preoperative examination of both legs erect, and with ultrasonic imaging, the GSV is
chosen if no multiple large varicosities are present (Kirklin, 2003), orelse other veins eg:
cephalic vein can be taken. (Wijinberg, 1990).
Leg is abducted, knee flexed (45°), supported with initial skin incision made just anterior to the
medial malleolus, or the groin. The desired plane is accessed by blunt dissection with scissors
down to the vein. Skin and subcutaneous fat are undermined with the scissors, staying just
superficial to it. and spreading the tips of the scissors over it.
Fig (8): Harvesting of the Greater Saphenous vein.

A, Location of greater saphenous vein and line of incision.
B, Continuous incision over the entire length.
C, Multiple small incisions along its route. ,(Boyle et al,
1997).
Continuous or multiple small incisions over the vein may be used avoiding creation of
flaps divide just above the knee, and just below it till just before it penetrates the fascia lata to
join the femoral vein. (Kirklin, 2003) (Figure 8). A single long segment (50- 65cm) is removed:
12-15cm (for diagonals), 20-24 cm for marginal Cx, and 18-22 for RCA as long as external
diameter of the vein is > 3.0-3.5 mms (Simon, 1982). When exposed and length measured, the
proximal (femoral) end is isolated and divided between ligatures, and a vascular clamp is placed
on the vein to mark its distal end prior to removal and ligating its branches using fine silk sutures
or between hemostatic clips (being not too close) and after flushing it to prevent any nidus for
thrombus formation. (Kirklin, 2003) (Figure 9).
Figure (9): Division of side branches of saphenous vein using fine ligatures or hemostatic clips. A,
Venous branches should be secured just flush with the saphenous vein to avoid narrowing (upper inset) or
creating diverticula aower inset), which can be a nidus for thrombus formation. K, Avulsed branches are
secured with a double loop suture of No. 7-0 polypropylene (Kirklin, 2003).
Lesser saphenous vein can be removed posterior to the lateral malleolus and extended
superiorly toward the popliteal fossa to divide the vein where it penetrates the deep fascia to join
the GSV protecting sural nerve parallel to the vein. (Kirklin, 2003). Leg incisions are closed in
layers over a small drainage catheter. Branches that have been avulsed are secured with No.7-0
polypropylene sutures. (Chester, 1998).
.
IV. Arterial Grafts: Surgical Anatomy, Histology/Histopathology,

History of Use, Harvesting Technique, Biological Characteristics,
Functional Classification & Criteria for Selection.
The Internal Mammary Artery (IMA)
Introduction:
The left internal thoracic artery (LITA) is used in nearly every coronary artery reconstruction, either
alone or in conjunction with the right internal thoracic artery or other arterial or venous grafts.
Bilateral ITA grafting is believed to confer survival benefit. Bilateral internal thoracic artery usage in
everyday practice is increasing. The anatomy, physiology, harvesting and grafting techniques therefore
assume enormous relevance to the surgeon .
Anatomy:
The internal thoracic artery (ITA) arises from the first part of the subclavian artery behind the head of the
clavicle.
It passes medially and anteriorly to descend behind the first six intercostal cartilages and the intercostal
spaces approximately 1 cm lateral to the border of the sternum. The ITA and veins lie in the plane
between the internal intercostal and transverse thoracis muscle layers.
The ITA divides into the mus-culophrenic and superior epigastric arteries usually at the level of the sixth
intercostal space. Variations of the terminal branches and the level of termin-tion are common. There are
variable numbers of perforating , sternal and anterior intercostal branches; they normally arise singly but
can arise as common trunks(sternal/perforating and sternal/intercostal). In some patients, a persisting
posterior intercostal artery does not connect with the ITA and may represent an important collateral
blood supply to the sternum
a) anatomy of the internal mammary artery

b) Transverse section of the anterior end of a typical interspace between the first and six ribs.The internal
thoracic artery and veins lie between the transversus thoracis and internal intercostal muscles about 1 cm
lateral to the sternal edge. (He , 1999).
Branches:
1-Pericardiacophrenic artery. long, slender, accompanies the phrenic nerve to the diaphragm.
2-Mediastinal arteries. Distributed to the areolar tissue/lymph nodes of anterior mediastinum
3-Pericardial branches. These supply the upper anterior region of the pericardium.
4-Sternal branches. Distributed to transversus thoracis, periosteum of posterior sternal surface
and the sternal red bone marrow.
5-Anterior intercostal branches. Distributed to the upper six intercostal spaces, two in each
space passing laterally along the borders of the space to anastomose with the posterior intercostal
arteries supplying the intercostal muscles and pectoral muscles, breast and skin.
6-Perforating branches. They traverse the upper 5-6 spaces with anterior cutaneous branches of
the corresponding intercostal nerves. In the female the 2-4 branches supply the breast (Giorgio
Gabella, 1995).
7-Musculophrenic artery. Passes inferolaterally behind 7-9 costal cartilages, traverses the
diaphragm near the ninth and ends near the last intercostal space anastomosing with the inferior
phrenic and the lower two posterior intercostal and ascending branches of the deep circumflex
iliac arteries. It also supplies the lower part of the pericardium and the abdominal muscles.
8- Superior epigastric artery (Giorgio Gabella, 1995).
III. The Conventional Saphenous Venous Grafts.
The Surgical Anatomy of Saphenous Venous Grafts (SVGs)
1- The greater saphenous vein:

The term saphenous is derived from the Greek word for "visible”. The great saphenous vein
drains the medial end of the dorsal venous arch of the foot and passes upward directly in front of
the medial malleolus. It then ascends in company with the saphenous nerve in the superficial
fascia over the medial side of the leg. The vein passes behind the knee and curves forward
around the medial side of the thigh. It passes through the lower part of the saphenous opening in
the deep fascia and joins the femoral vein about 1 ½ inches (4 cm) below and lateral to the pubic
tubercle. (Snel, 198l).
The great saphenous vein possesses numerous valves; it is connected to the small saphenous
vein by one or two branches that pass behind the knee.A number of Perforating veins connect the
saphenous vein with the deep veins along the medial side of the calf. The great saphenous vein
pierces the saphenous opening in the deep fascia (fascia lata) of the thigh and joins the femoral
vein 1½ inches (4 cm) below and lateral to the pubic tubercle.
At the saphenous opening in the deep fascia, great saphenous vein usually receives three
tributaries which are variable in size: (1) the superficial circumflex vein, (2) the superficial
epigastric vein, and (3) superficial external pudendal vein. These veins correspond with the three
branches of the femoral artery found in this region. An additional vein, known as the lateral
accessory vein, usually joins the main vein about the middle the thigh or higher up at the
saphenous opening (Snell, 1981).
II- The lesser saphenous vein.

The short saphenous vein, also called the small or internal saphenous vein, originates from the
junction of the lateral marginal vein of the foot with small veins from the lateral side of the heel
behind the lateral malleolus. (Skandalakis, 2000).
Unlike the greater saphenous vein, the lesser saphenous vein may penetrate the deep fascia at
any point from the middle third of the calf upward. This fact explains the segmental rather than
total nature of reflux found in the lesser saphenous vein. (Bergan, 2000). It passes between the
Achilles tendon and the posterior border of the lateral malleolus to ascend in the center of the
calf up to the popliteal fossa about 1.25 cm below the posterior transverse skin crease of the
knee. From this level to about 10 cm above the crease, the lesser saphenous vein joins the
popliteal vein. The small saphenous vein has numerous valves along its course. (Skandalakis,
2000).
Fig 6: The Superficial and the Deep Venous Systems of the Lower Limb (Snell, 1981).
* Tributaries:
1. Numerous small veins from the back of the leg.

2. Communicating veins with the deep veins of the foot.
3. Important anastomotic branches that run upward and medially to join great saphenous vein.
The small saphenous vein terminates by either joining the popliteal vein; the great saphenous
vein; or by splitting in two, one division to popliteal and the other the great saphenous vein.
There are five perforating veins between the two venous systems of the leg:
6) A vein, just distal to the knee, from great saphenous into the posterior tibial vein.
7) The external or lateral perforating vein at the junction of middle and lower thirds of the leg.
8) The upper ankle perforating vein halfway up the leg at the posterior tibial margin.
9) The middle ankle perforating vein is 7.5-10 cm above the medial malleolus.
10) The lowest ankle perforating vein behind and below the medial malleolus (Snel, 198l).
Variations of Saphenous Veins:
Variation in the level of the short saphenous termination by: ending in midthigh to join great
saphenous rather than the popliteal vein (13 %), dividing in the popliteal space, with one branch
entering the popliteal vein and the other branch continuing upward in the superficial fascia to
join great saphenous vein (15%). Rarely, may join great saphenous vein at Knee level. The great
saphenous may enter the femoral vein as far as 5 cm below the saphenous opening. Accessory
saphenous vein may occur at the medial aspect of the inner thigh, or the great saphenous vein
may be duplicated below the knee (Skandalakis, 2000).
Fig. 7: The Free Aorto-Coronary Saphenous Vein Graft (Skandalakis, 2000).

The following surgical factors are possibly responsible for graft occlusion
8. Handling the vein with surgical instruments, stripping of the adventitial layer, and hydrostatic
dilatation (>150 mm Hg) to overcome spasm may cause prominent endothelial cell loss and
medial damage (Qvist et al, 1992).
9. Site of Insertion: Occlusion occurrs in diagonal branches > circumflex > right coronary.
10. Size of artery bypassed graft: Occlusion occurs in grafts sutured to arteries < 2 mm with a
flow rate of 20 ml/min or less (Cataldo et al, 1993)..
11. Quality of the recipient arteries.
12. Length of Graft: kinking will occur if the graft is too lung. (Ramos et al, 1976)..
13. The quality of the vein before its harvesting.
14. Clinical factors: age, New York heart Association functional class, preioperative infarctions,
cholesterol level, smoking, hypertension, or use of antiplatelet drugs (Souza et al, 2001).
Strategies that prevent early graft occlusion and improve the early patency rate
5. Pharmacologic interventions.
6. Gene transfer before grafting.
7. External stenting of the vein graft.
8. Refined SV harvesting technique (non-touch) (Souza et al, 2001).
* Early graft closure (1 month):

Grondin and associates in 1974 found that 10 to 15 % of saphenous vein grafts occlude by
the first month after surgery (Grondin et al, 1974).
At this early stage, the principal underlying mechanism of vein graft occlusion is graft
thrombosis by alteration in the vessel wall, changes in blood rheology, altered flow dynamics, or
focal endothelial disruption (related to irrigating solution, storage solution, storage temperature,
and distending pressure). Additional endothelial loss occurs when the vein is placed within the
arterial system or in physiologic saline (acidic pH, causes endothelial cell loss). Storage at room
temperature (20 to 230C) or 370C within lactated Ringer's solution better preserves endothelial
cells. (Lawne et al, 1990), (Solberg et al, 1987).
Fitzgibbon and associates found in 1996 that 3 to 12 % of saphenous vein grafts occlude,
with or without symptoms by the first month after surgery secondary to reduced graft flow,
limited outflow (coronary diameter of 1.5 mm or less) (Cataldo et al, 1993) (Ramos et al, 1976).
Loss of endothelial monolayer results in the accumulation of fibrin on the luminal surface
(which starts 24 hours after grafting), the adherence of platelets and neutrophils, and a reduction
in tissue plasminogen activator production. Endothelial loss also activates the extrinsic
coagulation cascade by tissue factor that is expressed in the exposed subendothelium.
Additionally, the inherent antithrombotic properties of veins are comparatively week. Heparin
sulfate, a proteoglycan molecule with anticoagulant properties mediated by potentiation of
antithrombin III, is less prominent in the media and in the poorly developed internal elastic
lamina of veins as compared with arteries. Production of nitric oxide and prostacycline, both
potent inhibitors of platelet activation, is lower in veins than in arteries, and nitric oxide
production is further reduced by bypass grafting. The low fluid shear stress in grafted venous
conduits, as compared with arteries, reduces the shear-dependent release of tissue plasminogen
activator, nitric oxide, and prostacycline (Joseph et al, 1998) .
The propensity for early graft occlusion resulting from these prothrombotic effects may, on
occasion, be amplified by technical factors that reduce graft flow, and failure at the aortic
anastomosis can be due to: Large suture bites in the vein, or angulation at the neck due to
improper alignment of the anastomotic axis with the vein course. (Grondin et al, 1974).
Failure of the distal anastomosis may be due to: Suture placement in the coronary artery using
large bites in the coronary artery at the heel and toe; Linear tension due to insufficient graft
length; redundancy of the graft (Griffith et al, 1977).
* Graft failure from 1 to 12 months:
Intimal hyperplasia, defined as the accumulation of smooth muscle cells and extracellular
matrix in the intimal compartment, is the major disease process in venous grafts within 4 to 6
weeks hence reducing the lumen by up to 25%. (Joseph et al, 1998).
Medial smooth muscle cells proliferate, migrate, and synthesize extracellular matrix in
response to a number of growth factors and cytokines released from activated endothelial cells,
platelets and macrophages (Verrier and Boyle, 1996). The transient "ischemia-reperfusion" after
grafting reduces endothelial production of antiproliferative mediators (eg: NO), and induces
marked superoxide radical formation with direct promotion of smooth muscle cell proliferation.
The acute, pronounced increase in wall stress incurred by saphenous veins on exposure to
arterial pressures furtherly promotes intimal fibrosis, fibroblast growth factor (bFGF), increases
vein diameter, reduces mean blood velocity, and shear stress. This increases the shear-regulated
production of potent mitogens thus shifting the balance toward smooth muscle cell proliferation
and intimal hyperplasia. (Allaire and Clowes, 1997).
* Graft failure from 1 to 5 years:
This interval has a failure rate of 2 to 3 % per year due to vein atherosclerosis often with
superimposed late graft thrombosis, and rupture of atheromatous plaques (Joseph et al, 1998).
* Graft failure beyond 5 years:
Graft failure after the fifth year occurs at a rate of 5% per year, with a 10- year-patency rate
varying between 41% and 56% while 25% of vein grafts have significant atherosclerotic lesions.
Graft closure in this interval is almost always secondary to atherosclerosis and its complications
(Campeau et at, 1983).
Harvesting Technique of Venous Grafts
After preoperative examination of both legs erect, and with ultrasonic imaging, the GSV is
chosen if no multiple large varicosities are present (Kirklin, 2003), orelse other veins eg:
cephalic vein can be taken. (Wijinberg, 1990).
Leg is abducted, knee flexed (45°), supported with initial skin incision made just anterior to the
medial malleolus, or the groin. The desired plane is accessed by blunt dissection with scissors
down to the vein. Skin and subcutaneous fat are undermined with the scissors, staying just
superficial to it. and spreading the tips of the scissors over it.
Fig (8): Harvesting of the Greater Saphenous vein.

A, Location of greater saphenous vein and line of incision.
B, Continuous incision over the entire length.
C, Multiple small incisions along its route. ,(Boyle et al,
1997).
Continuous or multiple small incisions over the vein may be used avoiding creation of
flaps divide just above the knee, and just below it till just before it penetrates the fascia lata to
join the femoral vein. (Kirklin, 2003) (Figure 8). A single long segment (50- 65cm) is removed:
12-15cm (for diagonals), 20-24 cm for marginal Cx, and 18-22 for RCA as long as external
diameter of the vein is > 3.0-3.5 mms (Simon, 1982). When exposed and length measured, the
proximal (femoral) end is isolated and divided between ligatures, and a vascular clamp is placed
on the vein to mark its distal end prior to removal and ligating its branches using fine silk sutures
or between hemostatic clips (being not too close) and after flushing it to prevent any nidus for
thrombus formation. (Kirklin, 2003) (Figure 9).
Figure (9): Division of side branches of saphenous vein using fine ligatures or hemostatic clips. A,
Venous branches should be secured just flush with the saphenous vein to avoid narrowing (upper inset) or
creating diverticula aower inset), which can be a nidus for thrombus formation. K, Avulsed branches are
secured with a double loop suture of No. 7-0 polypropylene (Kirklin, 2003).
Lesser saphenous vein can be removed posterior to the lateral malleolus and extended
superiorly toward the popliteal fossa to divide the vein where it penetrates the deep fascia to join
the GSV protecting sural nerve parallel to the vein. (Kirklin, 2003). Leg incisions are closed in
layers over a small drainage catheter. Branches that have been avulsed are secured with No.7-0
polypropylene sutures. (Chester, 1998).
.
IV. Arterial Grafts: Surgical Anatomy, Histology/Histopathology,

History of Use, Harvesting Technique, Biological Characteristics,
Functional Classification & Criteria for Selection.
The Internal Mammary Artery (IMA)
Introduction:
The left internal thoracic artery (LITA) is used in nearly every coronary artery reconstruction, either
alone or in conjunction with the right internal thoracic artery or other arterial or venous grafts.
Bilateral ITA grafting is believed to confer survival benefit. Bilateral internal thoracic artery usage in
everyday practice is increasing. The anatomy, physiology, harvesting and grafting techniques therefore
assume enormous relevance to the surgeon .
Anatomy:
The internal thoracic artery (ITA) arises from the first part of the subclavian artery behind the head of the
clavicle.
It passes medially and anteriorly to descend behind the first six intercostal cartilages and the intercostal
spaces approximately 1 cm lateral to the border of the sternum. The ITA and veins lie in the plane
between the internal intercostal and transverse thoracis muscle layers.
The ITA divides into the mus-culophrenic and superior epigastric arteries usually at the level of the sixth
intercostal space. Variations of the terminal branches and the level of termin-tion are common. There are
variable numbers of perforating , sternal and anterior intercostal branches; they normally arise singly but
can arise as common trunks(sternal/perforating and sternal/intercostal). In some patients, a persisting
posterior intercostal artery does not connect with the ITA and may represent an important collateral
blood supply to the sternum
a) anatomy of the internal mammary artery

b) Transverse section of the anterior end of a typical interspace between the first and six ribs.The internal
thoracic artery and veins lie between the transversus thoracis and internal intercostal muscles about 1 cm
lateral to the sternal edge. (He , 1999).
Branches:
1-Pericardiacophrenic artery. long, slender, accompanies the phrenic nerve to the diaphragm.
2-Mediastinal arteries. Distributed to the areolar tissue/lymph nodes of anterior mediastinum
3-Pericardial branches. These supply the upper anterior region of the pericardium.
4-Sternal branches. Distributed to transversus thoracis, periosteum of posterior sternal surface
and the sternal red bone marrow.
5-Anterior intercostal branches. Distributed to the upper six intercostal spaces, two in each
space passing laterally along the borders of the space to anastomose with the posterior intercostal
arteries supplying the intercostal muscles and pectoral muscles, breast and skin.
6-Perforating branches. They traverse the upper 5-6 spaces with anterior cutaneous branches of
the corresponding intercostal nerves. In the female the 2-4 branches supply the breast (Giorgio
Gabella, 1995).
7-Musculophrenic artery. Passes inferolaterally behind 7-9 costal cartilages, traverses the
diaphragm near the ninth and ends near the last intercostal space anastomosing with the inferior
phrenic and the lower two posterior intercostal and ascending branches of the deep circumflex
iliac arteries. It also supplies the lower part of the pericardium and the abdominal muscles.
9- Superior epigastric artery (Giorgio Gabella, 1995).
Fig. 11: The intact Internal Thoracic (Mammary) Artery with Pedicle.
Histology and Histopathology of the Internal Mammary Artery
The first 20-30 % of the IMA length is elastomuscular with smooth muscle content in the media
prevails > 5-7 elastic lamellae. Downstream, there is an abrupt transition into the elastic pattern
for 70-80 % of the entire length followed by a second elastomuscular segment, analogous to the
proximal one. The mean cross sectional area of the proximal elastomuscular and elastic segments
of the IMA (both 1.9 mm2) is significantly > its distal elastomuscular segment (1.2 mm2). The
intima is significantly thicker in the purely muscular segment (25.6% degree of intimal
hyperplasia) than in the elastic segment (15.3%) (Van son et al, 1993).
IMA has proved relatively resistant to intimal hyperplasia and atherosclerosis, with incidence of
atherosclerosis of only 0.7% (Permyos et al, 1999). The occurrence of discontinuities in the
internal elastic lamina provokes early and progressive intimal thickening/hyperplasia (Sims,
1983), by invasion of smooth muscle cells from the media through these fenestrations. Elastic
arteries are less prone to intimal hyperplasia than muscular arteries, as intimal hyperplasia
develops slower because proliferative smooth muscle cells are present only to a moderate extent.
Moreover, multiple elastic lamellae and the internal elastic lamina form barriers to their invasion.
(Van son et al, 1990).
Moreover, elastin the basic component of the elastic tissue of the media is a relatively inert tissue
with a low metabolic rate, and lower intrinsic demand for oxygen and substrates, either by
diffusion from the main lumen or by perfusion by vasa vasora, than the compact media of the
muscular artery. The vasa vasora is confined to the adventitia and the artery is nourished entirely
from the lumen, which offers a good explanation of the proximity of the patency rate between in
situ and free internal mammary artery grafts. (Van Son et al, 1990).
History of Using Internal Mammary (Thoracic) Artery

Arthur Vineberg, a Canadian surgeon, in 1946 reported implanting the IMA through a
myocardial tunnel, and showed that communications developed between it and the coronary
arteries. (Vineberg, 1946). By 1962 Vineberg had reported 140 operations with an initial
mortality of 33% that subsequently fell to 2% in the decade between 1954 and 1963. These
patients had no, or only slight angina and showed marked clinical improvement. (Vineberg,
1962).
It may have been Longmire who first used IMA to a lesion in the RCA, who (during an
endarterectomy) found that it was not possible to repair the coronary artery> In desperation, he
performed IMA-RCA anastomosis beyond the endarterectomized segment. (Longmire et al,
1958).
Recognition of the IMA value as a conduit came slowly as Vassili Kolessov, working in
the 1960s at the Pavlov Institute in Leningrad, described IMA use for coronary revascularization
without routine arteriography or CPB (Kolessov, 1967).
Bailey and Hirose reported attachment of RIMA to RCA on beating heart. (Bailey &
Hirose, 1968). In the same year, Green grafted IMAs to mid-LAD in 18 patients using CPB with
no early operative deaths, ⅓ of patients died prior to leaving hospital (Green, 1972).
Since then, a report by Loop and colleagues from the Cleveland Clinic disclosed a
superiority of the LIMA to the LAD on postoperative survival. In the early 1980s, LIMA use for
grafting of the (LAD) became the standard of care based on reports of superior graft patency,
reduced cardiac events, and enhanced survival when compared with patients receiving only
venous conduits. This led to more widespread use of both internal mammary arteries (BIMA)
with development of different surgical techniques including free grafting, sequential
anastomosis, and the use of composite grafts. (Loop et al, 1986).
Free Mammary Artery Grafts
Detachment of the internal mammary artery pedicle from the subclavian vessels for use as
a free graft has greatly expanded the use of the right mammary artery (RIMA) by extending its
use to distal branches of the right and left systems. Early results showed 77 % patency which is
similar to, but not as good as the results of pedicled mammary artery grafting. (Loop et al, 1973).
Alternative techniques using a vein patch on the aorta for the proximal anastomosis were
described in 1987 by Kanter & Barner.
In 1996, Verhelst and associates, reported an early patency of 86.4% for the free RIMA
and 100% for the pedicled LIMA. Their surgical strategy was to frequently use a venous hood
for the proximal anastomosis with patency rates not significantly different from direct aortic
anastomosis (89% versus 82.8%).
In 1997, Tatoulis and associates reported the routine use of the right internal mammary
artery as a free graft in 1,454 patients. They showed that the patency rate for the free RIMA was
89% versus 96% for the pedicled LIMA at 5 years. (Verhelst et al, 1996).
Sequential Mammary Artery Grafts
Use of sequential ITA graft started in 1983 because of the insufficiency of venous grafts
and aortic wall disease and as a way to extend the use of arterial conduits. Following this,
sequential mammary grafting became well established (Kabbani et al, 1983). In 1989, Dion and
associates reported sequential grafting for both right and left mammary arteries in 231 patients
with patency rate was 95% at 6 months. In 1993, Palatino and colleagues, confirmed the
efficacy of this technique. Over 145 patients, the operative mortality was 2.8% and a very low
incidence of perioperative myocardial infarction was observed (0.7%). A follow up report by
Dion and associates (2000), showed that these excellent results were maintained at 10 years. The
patency of sequential anastomoses directed to the LAD, the circumflex, and the RCA was 96%,
92%, and 82 % respectively, with need for redo intervention of only 3.1 %.
Failure of sequential ITA anastomoses in some patients was attributed to several factors eg:
luminal diameter, quality of the coronary artery, angulation, or competitive flow caused by a
low-grade stenosis in the native coronary artery. (Bakay et al, 2002). However, some authors
stated that graft failure caused by competition is a reversible phenomenon and the graft may
reopen with worsening of native vessel stenosis as time progresses.
Sequential ITA anastomoses yield excellent patency rates to all coronary vessels except the very
distal Cx and the distal branches of RCA. Therefore, for this area, it is recommended nowadays
to use either GEA or the free RITA in a `T' connection with the pedicled LIMA (Dinçer et al,
1983).
Bilateral Internal Mammary Artery Grafts

While bilateral IMA (BIMA) grafting was a logical alternative, its introduction was slow,
with only sporadic publications of the results and the benefits of using BIMA compared with
single IMA grafting remain unproven due to differences in patient selection and insufficient
follow up (Pick et al, 1997). This idea changed after Grondin and colleagues (1984) compared
survival and patency of IMA grafts vs. SVGs at 10 years. 10-year survival for IMA was 84%
compared to 70 % for SVGs. The patency at 1 year was 89 % and 76 % and at 10 years was 84%
and 53% respectively, for IMAs vs. SVGs (Grondin et al, 1984).
Controversy still surrounds the optimal surgical strategy for the simultaneous use of both
IMAs (Lytle et al, 1999). These include choices of pedicled or free grafts (aorto-coronary or
composite), the site of proximal anastomosis (if used as a free graft), and the alternate strategies
of positioning the pedicle of (RIMA) when used in combination with the LIMA. (Barner, 1983).
In 1990, Fiore and associates compared retrospectively 100 CABG patients using both
IMAs and SVGs between 1972 and 1975 with a series of 100 patients operated on during the
same period who had one IMA along with SVG. Single IMA operative mortality was 2% vs. 9 %
for double IMA. At 13 years, the patency rate of RIMAs was 85 % and the patency rate of
LIMAs was 82 %. Patients receiving BIMA grafts had a significant freedom from subsequent MI
(75% versus 59%), and recurrent angina (36% versus 27%), hence supporting use of BIMA in
selected patients.
Harvesting:
The in-situ ITA conduit may be harvested as a pedicle with its adjacent veins and pleura
attached, or it may be skeletonized. The ITA should be mobilized fully, especially at the superior
aspect, to prevent any tethering of the conduit to the chest wall and consequent angulation or
tension from the medial part of the inflating lung .
During harvesting, the pleura may be opened widely, allowing the fully mobilized ITA pedicle to
lie near the phrenic nerve, anterior to the hilum of the lung.
Alternatively, an extra pleural technique can be employed however, in this case the ITA conduit
needs to be routed in a plane posterior to the thymic fat pad to prevent the pedicle lying in the
retrosternal space with consequent risk of injury during later re-sternotomy
The sternum is opened and the appropriate side elevated by a retractor. The endothoracic fascia
is divided to expose the pleura and extrapleural fat. The pleura is then entered medial to the ITA
pedicle .The pleural incision extends from the first to the sixth inter-costal space. Alternatively,
in the extrapleural technique aimed to preserve the pleura, it may be carefully peeled back far
enough laterally to expose the internal thoracic vessels. It is important to enter the correct plane
by reflecting the transversus thoracis muscle behind the sternum, commencing in one of the
lower intercostal spaces. Retraction of the pedicle displays the venae comitantes and the internal
thoracic artery itself.
The perforating and anterior intercostal branches are clipped near the ITA and divided with
electrocautery close to the chest wall to avoid damaging the ITA. The first and second
perforating branches are particularly large and often require division by scissors between metal
clips. Mobilization is continued proximally to the inferior border of the subclavian vein.
Complete mobilization of the ITA allows it to lie free medial to the lung, thus avoiding tension
on the conduit by the medial edge of the lung during ventilation .
Dissection is continued beyond the bifurcation of the ITA into the superior epigastric and
musculophrenic branches .
Skeletonization of the ITA is achieved by carefully clipping the branches close to the ITA and
involves the additional step of separating the ITA from the underlying transverses thoracis
muscle and the venae comitantes.
This allows the artery to be free of any other attachments resulting in extraavailable length. It
preserves sternal vascularity better than the standard pedicle technique and may reduce the
incidence of sternal wound complications.
A variation of this technique is semi-skeletonization, where the venae comitantes are harvested
along with the ITA leaving behind the attachment to the transversus thoracis muscle.
In the full pedicle form of harvesting, the transversus thoracis muscle, endothoracic fascia and
pleura are divided lateral to the internal thoracic vessels, leaving a pedicle approximately 1.5 cm
in width
The terminal branches of the ITA are double Clipped beyond the bifurcation and the conduit
sprayed with papaverine hydrochloride solution 80 mg ml(2mmo1/l)./
The papaverine solution is mixed with an equal volume of blood [final concentration
(1 mmo1/l)] and injected into the lumen of the ITA, which is clipped and allowed to dilate
passively
Fig (12): Mode of Dissection during harvesting of the Internal Mammary Artery using Electrocautery and
Metal Clips. NB: A Transverse section of the anterior end of a typical interspace between the first and six ribs shows that the
internal thoracic artery and veins lie between the transversus thoracis and internal intercostal muscles about 1 cm lateral to the
sternal edge. (He, 1999).
Harvesting OF RITAs:
Opening the right pleura and dissecting the entire length of the RITA provides two advantages: first,
provides more length to RITA; second, provides space for e rotated/verticalized heart to minimize
hemodynamic compromise during OPCABG (Bonacchi et al, 2000).
RITA, harvested as wide pedicle including artery, vein, muscle, fascia, and adipose tissue or by the
skeletonization technique, is brought to the left side through a right pericardial incision crossing over the
aorta and pulmonary trunk, as far cranial as possible, passing wrapped behind the thymus gland which
separates it from the sternum (Bonacchi et al, 2000). If the distal segment of the LAD needs to be
reached, a longitudinal and transverse fasciotomy of the pedicle is performed (Al-Ruzzeh et al, 2002).
RIMA through the transverse sinus:

The harvested RIMA is passed through a wide pericardial incision anterolateral to SVC behind
the aorta, through the transverse sinus. Mobilization of the pedicle with adjacent tissues helps
positioning via this route and avoids possible stretch during marginals and first diagonal. The
possibility of overstretching and rotating RIMA and the difficulty to control bleeding represent
the major disadvantages of this technique. (Gerola et al, 1996).
4. Respiratory problems:
Several factors can cause lung injury, independent of whether arterial conduits have been used, eg:
1- CPB: Decrease of surfactant production, hypoxic damage, and systemic inflammatory reaction.
2- Pleural opening produces accumulation of effusion, minor atelectasis of the lower lobes.
3-Pain related to chest drainage tubes can induce hypoventilation.
4- Phrenic neuropathy with IMA dissection/grafting. is probably associated with the technique of
IMA harvesting. Phrenic nerve palsy (most of the time reversible) occurs in 3% of patients
benefiting from complex arterial grafting (O ’Brien et al, 1992), (Dion, 1996).
1. Sternal Wound Complications:
Sternal ischemia is influenced by several factors, including the technique of harvesting, the position
of the sternal wires, diabetes, obesity, advanced age, chronic obstructive pulmonary disease, the need
for early resternotomy, chronic dialysis, and multiorgan failure. Bilateral ITA grafting (2.5%)
increases sternal complications by two-folds in the presence of insulin-dependent diabetes and four-
fold in patients undergoing chronic renal replacement therapy (Dion, 1996).
2. Postoperative Bleeding
Bilateral ITA grafting has been reported to be accompanied with greater incidence of bleeding (up to
6%) when compared to SVG (Kouchoukos et al, 1990). Some factors seem to decrease
postoperative blood loss eg: Systemic intraoperative normothermia, active intraoperative
hemodilution, shorter extracorporeal circuit and low prime oxygenators, tranexamic acid or
aprotinin, acceptance of lower hematocrit values in the immediate postoperative period (28%) and at
discharge (33%) (Dion, 1996).
VII. Assessment of the quality of the distal anastomosis of the

coronary artery bypass conduit
The outcome of coronary artery bypass grafting procedures is highly dependent on the
technical adequacy of the distal anastomosis. Various methodologies, including flow
measurement and imaging techniques, have been used by the cardiothoracic surgeon to assess the
adequacy of the distal anastomosis. (Wolf, 2001) eg: IMA flow patterns are highly dependant
on: The degree of LAD stenosis; integrity of the anastomosis; and the resistance of the distal
runoff bed as related to coronary blood flow demands (Barnen, et al 1997).
Methods of assessment of distal anastomosis performed:
A. Electromagnetic versus Doppler techniques .
B. Transit time flow .
C. Calibrated pump flow .
D. Thermal coronary angiography .
E. Coronary angiography––the "gold standard".
F. Metabolic assessment .

Impact of Syntax Score On The Early Outcome of Cabg Surgery in Low Ejection Fraction Patients

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Impact of Syntax Score On The Early Outcome of Cabg Surgery in Low Ejection Fraction Patients

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IMPACT OF SYNTAX SCORE ON THE EARLY

OUTCOME OF CABG SURGERY IN LOW

Whole sample data

Table (2): Descriptive statistics of demographic data in the study sample

Table (3): Risk factors in the study sample

Total no. 100

Study including four patients with peripheral vascular diseases (4%),

Table (4): Clinical characteristics in the study sample

Total no. 100

Table (5): Descriptive statistics of ejection fraction

Total no. 100

Table (6): Descriptive statistics of SYNTAX score

Total no. 100

Table (7): Descriptive statistics of intra-operative findings

Total no. 100

Table (8): Descriptive statistics of post-operative findings

Total no. 100

Table (9): Descriptive statistics of the Early outcome

There was no statistically significant correlation between syntax score and

Table (10): Results of association between SYNTAX score and demographic

r: Pearson’s correlation coefficient

There was no statistically significant association between syntax score and

Syntax score Independent t-test

There was no statistically significant correlation between syntax score and

Table (12): Results of association between SYNTAX score and Clinical

Table (13): Results of association between SYNTAX score and ejection

There was a statistically significant positive (direct) correlation between

There was a statistically high significant positive (direct) correlation

There was a statistically high significant positive (direct) correlation

There was statistically significant correlation between syntax score and

Patients who received Inotropes also showed statistically significantly higher

There was no statistically significant correlation between syntax score and

Table (15): Results of association between SYNTAX score and Post-operative

Syntax score Independent t-test

There was no statistically significant correlation between syntax score and

There was no statistically significant correlation between SYNTAX score and

Correlations could not be computed for cerebro-vascular accidents because

Syntax score Independent t-test

Table (17): Results of association between SYNTAX score subgroups and

There was no statistically significant association between subgroups of

There was no statistically significant correlation between syntax score

There was no statistically significant correlation between SYNTAX score

Low Syntax Intermediate High Syntax Chi-square

There was a statistically significant positive (direct) correlation between

There was a statistically high significant positive (direct) correlation

There was a statistically high significant positive (direct) correlation

Low Syntax Intermediate

Low Syntax Intermediate High Syntax One Way

There was statistically high significant correlation between SYNTAX score

Patients who received Inotropes also showed statistically significantly

There was statistically high significant correlation between SYNTAX score

There was no statistically significant correlation between syntax score and

There was no statistically significant correlation between syntax score

Table (22): Results of association between SYNTAX score Subgroups and

Prior to the development of the SS, several coronary angiographic-based

The awareness of the risk of feasible complications before treatment may

In real-life patients undergoing CABG, the Syntax score does not

Comparison between two independent groups regarding quantitative data

Comparison between more than two independent groups regarding

 P > 0.05: Non significant

 P < 0.05: Significant

 P < 0.01: Highly significant.