Download Arterial Grafts Protect the Native Coronary Vessels From

Arterial Grafts Protect the Native Coronary Vessels From Atherosclerotic Disease
Progression
Kamellia R. Dimitrova, Darryl M. Hoffman, Charles M. Geller, Gabriela Dincheva,
Wilson Ko and Robert F. Tranbaugh
Ann Thorac Surg 2012;94:475-481
DOI: 10.1016/j.athoracsur.2012.04.035
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://ats.ctsnetjournals.org/cgi/content/full/94/2/475
The Annals of Thoracic Surgery is the official journal of The Society of Thoracic Surgeons and the
Southern Thoracic Surgical Association. Copyright © 2012 by The Society of Thoracic Surgeons.
Print ISSN: 0003-4975; eISSN: 1552-6259.
Downloaded from ats.ctsnetjournals.org by Robert Tranbaugh on September 21, 2012
Kamellia R. Dimitrova, MD, Darryl M. Hoffman, MD, Charles M. Geller, MD,
Gabriela Dincheva, Wilson Ko, MD, and Robert F. Tranbaugh, MD
Division of Cardiac Surgery, Beth Israel Medical Center, New York, New York
Background. We sought to examine the effect of different conduits on the progression of atherosclerosis in
previously revascularized coronary territories.
Methods. Between 1995 and 2010, 4,960 patients were
discharged alive after primary isolated coronary artery
bypass grafting (CABG) with a left internal thoracic
artery (LITA) conduit and additional conduits as needed:
radial artery (RA) or saphenous vein graft (SVG), or both.
Seven hundred seventy-two patients had coronary angiography for recurrent symptoms an average of 5.5 ⴞ 3.5
years after CABG (range, 0.1–16 years). Cumulative graft
patency and disease progression in the native vessels was
estimated by the Kaplan-Meier survival method. The
log-rank test was used to assess differences of disease
progression per territory between different types of
conduits.
Results. Kaplan-Meier– estimated 1-, 5-, and 10-year overall disease progression in territories with patent LITAs was
0.01%, 4%, and 8%, respectively; with patent RA grafts, it
was 0.01%, 6%, and 11%, respectively (log-rank test, p ⴝ
0.157); and with patent SVGs it was 3%, 19%, and 43%,
respectively (log-rank test; p < 0.0001). Disease progression
in grafted native coronary arteries in the anterior territory
with patent LITA-to–left anterior descending (LAD) artery
was 8%, and with patent RA grafts versus patent SVGs to
the diagonal branches of LAD artery was 10% and 40%,
respectively (log-rank test; p < 0.0001). Disease progression
in grafted native coronary arteries to the lateral territory
with a patent RA graft was 11% versus 50% with a patent
SVG (log-rank test; p < 0.0001).
Conclusions. RA and LITA grafting has a strong
protective effect against progression of native coronary
artery disease in previously grafted vessels. Multiple
arterial grafting may improve long-term survival by
preventing progression of atherosclerosis in the native
coronary vessels.
(Ann Thorac Surg 2012;94:475– 81)
© 2012 by The Society of Thoracic Surgeons
C
Our hypothesis is that arterial grafting prevents progression of disease in the grafted territories, which may help
explain the improved long-term survival in patients undergoing multiple arterial grafting.
oronary artery bypass grafting (CABG) results in
excellent long-term survival [1, 2]. However its
effectiveness is limited by recurrent symptoms caused by
failure of the conduits or progression of the atherosclerosis in the native vessels, estimated to affect more than
half of patients by 25 years postoperatively [3–5]. Longterm event-free survival after CABG is not only related to
the preoperative status of the patient and new atherosclerotic lesions in ungrafted coronary territories but also
to the progression of disease in the grafted native coronary arteries and the patency of the conduits used [6, 7].
Arterial conduits, including the left internal thoracic
artery (LITA) [8], bilateral internal thoracic arteries [9],
and the radial artery (RA) [10] have excellent patency,
resulting in better long-term survival in comparison with
CABG using the saphenous vein graft (SVG). However
Sergeant and colleagues [5] found that arterial grafting
did not prevent angina or improve survival after CABG.
Our study examines the effect of conduit type on the
progression of atherosclerosis in the revascularized coronary territories in symptomatic patients after CABG.
Accepted for publication April 5, 2012.
Presented at the Poster Session of the Forty-eighth Annual Meeting of
The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28 –Feb 1, 2012.
Address correspondence to Dr Dimitrova, Beth Israel Medical Center, 317
E 17th St, 11 Flr, New York, NY 10003; e-mail: [email protected].
© 2012 by The Society of Thoracic Surgeons
Published by Elsevier Inc
Patients and Methods
Patients
From January 1, 1995 to December 31, 2010, 4,960 patients
were discharged alive after primary isolated CABG with
the LITA, RA, or SVG (or a combination) as needed.
Seven hundred seventy-two patients underwent symptom-driven coronary angiography an average of 5.5 ⫾ 3.5
years (range, 0.1–16 years) after CABG. The study population was identified from prospectively collected databases of all patients undergoing CABG and subsequent
cardiac catheterization or percutaneous coronary interventions (PCIs), or both, in our institution as part of the
New York State Cardiac Surgery Reporting System, Cardiac Catheterization Reporting System and Percutaneous
Coronary Intervention Reporting System. This study was
approved by the institutional review board at our institution, which waived written informed consent. The
Cardiac Surgery Reporting System database was used to
identify patients discharged alive after isolated primary
CABG with 1 or more arterial conduits and the Percuta0003-4975/$36.00
http://dx.doi.org/10.1016/j.athoracsur.2012.04.035
Downloaded from ats.ctsnetjournals.org by Robert Tranbaugh on September 21, 2012
ADULT CARDIAC
Arterial Grafts Protect the Native Coronary Vessels
From Atherosclerotic Disease Progression
476
DIMITROVA ET AL
ARTERIAL GRAFTS PROTECT CORONARY ARTERIES
ADULT CARDIAC
neous Coronary Intervention Reporting System database
was used to identify those who underwent coronary
reintervention after CABG. All patients were discharged
on statin, aspirin, and beta-blockers unless contraindications were present.
Endpoint
The entire patient population was followed up to the first
coronary angiogram for recurrent symptoms, date of
death (using the US Social Security Death Index), or
December 31, 2010.
Angiographic Analysis
Conduits were evaluated on the first angiogram obtained
after CABG and were classified as functioning if open
and the native vessel was fully opacified by the graft, or
as malfunctioning when occluded, had greater than 50%
stenosis anywhere in the graft, or the flow from the native
vessel was dominant. Progression of disease was assessed
by comparison of the angiograms before and after CABG
using similar projections. Extent of disease was classified as
either no new disease or progression of disease if there
were new obstructive lesions distal to the anastomosis (Fig
1A) or new diffuse distal disease (Fig 1B).
Statistical Analysis
Continuous variables were expressed as mean and standard deviation. Categorical variables were expressed as
numbers and percentages. Dichotomous variables were
analyzed using the ␹2 test and Fisher’s exact test, and
continuous variables were analyzed using the Student’s t
test. Overall graft patency and disease progression in the
native vessels was estimated by the Kaplan-Meier
method. The log-rank test was used to assess differences
between groups. The Cox proportional hazards regression model was used to determine independent predictors of recurrent myocardial ischemia and disease progression after CABG. Modeling was done using
backward elimination. Variables with p values less than
0.05 were retained in the final model. Hazard ratios (HRs)
and 95% confidence intervals (CI) are presented. Statistical analysis was performed with statistical software
Zelig/CRAN 2.14.01 (available at: http://cran.r-project.
org) [11, 12].
Ann Thorac Surg
2012;94:475– 81
Results
Recurrent Symptoms After CABG
Table 1 summarizes the prospectively collected preoperative risk factors and the operative data from the 772 patients
who underwent symptom-driven coronary angiography an
average of 5.5 ⫾ 3.5 years (range, 0.1–16 years) after CABG.
Of the 772 recatheterized patients, 340 patients (44%) had
progression of disease in previously grafted coronary vessels with both patent and malfunctioning grafts, 149 patients (19%) had isolated malfunctioning grafts without
progression of disease, 212 patients (28%) had no new
disease and all grafts were patent, and 71 patients (9%) had
new disease in an ungrafted coronary territory.
Table 2 shows the results of multivariate Cox proportional regression modeling for recurrent symptoms in patients after CABG. Previous PCI, younger age at the time of
operation, female sex, emergency operation, hemodynamic
instability, and longer cross-clamp time were independent
predictors of recatheterization after CABG.
Disease Progression
Table 3 summarizes overall graft patency and progression of disease per conduit and per coronary territory.
Overall LITA graft, RA graft, and SVG patency were 87%,
82%, and 58%, respectively.
Table 4 shows the predictors of disease progression per
territory estimated by multivariate Cox proportional regression model. Left main stenosis greater than 50%,
history of peripheral vascular disease, previous stroke,
diabetes mellitus, hypertension, advanced atherosclerosis in the aorta, and stent placement before CABG were
independent predictors of increased risk of disease progression. Conversely, grafting with the RA and LITA was
found to have a highly significant protective effect on
disease progression compared with SVGs.
Disease Progression by Conduit
Table 3 also shows disease progression among the conduit types (LITA, RA, and SVG). Twenty-two percent of
the grafted vessels with a patent SVG had disease progression compared with 4.3% and 6.1% in the grafted
vessels with patent LITAs and RAs, respectively. KaplanMeier– estimated 1-, 5-, and 10-year overall disease pro-
Fig 1. (A) Angiographic image of a patent
saphenous vein graft (SVG) to OM2 with disease progression distal to the anastomosis (10degree right anterior 30-degree caudal view).
(B) Angiographic image of a patent SVG to
PDA with diffuse distal disease progression
(30-degree right anterior oblique view).
(CABG ⫽ coronary artery bypass grafting;
OM2 ⫽ second obtuse marginal branch of the
left circumflex artery; PDA ⫽ posterior descending artery.)
Downloaded from ats.ctsnetjournals.org by Robert Tranbaugh on September 21, 2012
Ann Thorac Surg
2012;94:475– 81
DIMITROVA ET AL
ARTERIAL GRAFTS PROTECT CORONARY ARTERIES
477
Variable
Age (y)
BMI
Ejection fraction
No. of grafts
Radial artery
Cross-clamp time (min)
CPB time
Sex (male) %
Elective
Urgent
Emergent
LMT 50%–69% stenosis
LMT 70%–89% stenosis
LMT 90%–100% stenosis
Proximal LAD artery 50%–69% stenosis
Proximal LAD artery 70%–100% stenosis
Mid/dist LAD artery 50%-69% stenosis
Mid/dist LAD artery 70%–100% stenosis
RCA 50%–69% stenosis
RCA 70%–100% stenosis
Circumflex artery 50%–69% stenosis
Circumflex artery 70%–100% stenosis
Triple-vessel disease
Previous MI
MI ⬍ 6 h previously
MI - 6–23 h previously
MI ⬎ 23 h previously
Previous stroke
Cerebrovascular disease
Aortoiliac PVD
Femoral/popliteal PVD
Hemodynamic instability
More than 1 MI
HTN
IV nitroglycerin 24 hours previously CABG
Current CHF
History of CHF
COPD
Calcified aorta
DM
Hepatic failure
Creatinine level ⬎ 2.5 mg/dL
Renal failure, HD
Immune system deficiency
PCI this admission
PCI before this admission
Patients With Angiography
After CABG (n ⫽ 772)
Patients Without Angiography
After CABG (n ⫽ 4,188)
p Value
62.5 (⫾ 9.7)
28.7 (⫾ 5.91)
48.6 (⫾ 12.0)
3.59 (⫾ 0.877)
278 (36%)
64.39 (⫾ 21.1)
87.9 (⫾ 26.9)
66.8%
138 (17.9%)
575 (74.5%)
59 (7.6%)
128 (16.6%)
88 (11.4%)
39 (5.05%)
72 (9.3%)
488 (63.2%)
24 (3.1%)
478 (61.9%)
44 (5.7%)
603 (78.1%)
41 (5.3%)
568 (73.6%)
601 (77.8%)
247 (32.0%)
2 (0.26%)
4 (0.52%)
392 (50.8%)
54 (7.0%)
67 (8.7%)
13 (1.7%)
45 (5.8%)
17 (2.2%)
104 (13.5%)
562 (72.8%)
97 (12.6%)
44 (5.6%)
42 (5.4%)
179 (23.2%)
43 (5.6%)
302 (39.1%)
2 (0.26%)
24 (3.1%)
15 (1.9%)
18 (2.3%)
16 (2.1%)
152 (19.7%)
65 (⫾ 10.4)
28.3 (⫾ 5.78)
47.3 (⫾ 12.5)
3.64 (⫾ 0.895)
1,573 (37.5%)
65.35 (⫾ 22)
89.1 (⫾ 28.5)
72.7%
899 (21.5%)
2,985 (71.3%)
304 (7.3%)
641 (15.3%)
546 (13.0%)
165 (3.9%)
331 (7.9%)
2,773 (66.2%)
183 (4.4%)
2,546 (60.8%)
217 (5.2%)
3312 (79.1%)
249 (5.9%)
3,349 (80.0%)
3,369 (80.4%)
1,418 (33.9%)
19 (0.45%)
32 (0.76%)
2,221 (53.0%)
289 (6.9%)
485 (11.6%)
159 (3.8%)
348 (8.3%)
62 (1.5%)
521 (12.4%)
2,967 (70.8%)
518 (12.4%)
316 (7.5%)
305 (7.3%)
1,116 (26.6%)
306 (7.3%)
1,590 (37.9%)
3 (0.07%)
147 (3.5%)
78 (1.9%)
124 (2.9%)
64 (1.5%)
621 (14.8%)
⬍0.0001
0.804
0.012
0.748
0.776
0.153
0.658
⬍0.001
0.125
0.543
0.912
0.861
0.273
0.156
0.056
0.049
0.204
0.488
0.491
0.603
0.004
⬍0.0001
0.974
0.932
0.467
0.297
0.175
0.502
0.129
0.057
0.201
0.040
0.086
0.325
0.910
0.171
0.198
0.063
0.528
0.945
0.105
0.941
0.897
0.490
0.998
0.008
BMI ⫽ body mass index;
CABG ⫽ coronary artery bypass grafting;
CHF ⫽ chronic heart failure;
COPD ⫽ chronic obstructive pulmonary
disease;
CPB ⫽ cardiopulmonary bypass;
DM ⫽ diabetes mellitus;
HD ⫽ hemodialysis;
HTN ⫽ hypertension;
IV ⫽
intravenous;
LAD ⫽ left anterior descending;
LMT ⫽ left main trunk;
MI ⫽ myocardial infarction;
Mid/dist ⫽ middle and distal;
PCI ⫽
percutaneous transluminal coronary intervention;
PVD ⫽ peripheral vascular disease;
RCA ⫽ right coronary artery.
gression in territories with a patent LITA was 0.01%, 4%,
and 8%, respectively; with a patent RA it was 0.01%, 6%,
and 11%, respectively (LITA versus RA log-rank test; p ⫽
0.157); and with a patent SVG, it was 3%, 19%, and 43%,
respectively (RA versus SVG log-rank test, p ⬍ 0.0001)
(Fig 2).
Downloaded from ats.ctsnetjournals.org by Robert Tranbaugh on September 21, 2012
ADULT CARDIAC
Table 1. Patient Characteristics
478
DIMITROVA ET AL
ARTERIAL GRAFTS PROTECT CORONARY ARTERIES
Table 2. Multivariate Cox Proportional Regression Model for
Recatheterization After CABG
Hazard
Ratio
Risk Factor
ADULT CARDIAC
Age
Previous stent
Emergency CABG
Female sex
Hemodynamic instability
Cross-clamp time
0.976
1.383
1.262
1.274
1.901
1.006
CABG ⫽ coronary artery bypass grafting;
CI 95%
0.968–0.984
1.141–1.675
1.088–1.462
1.049–1.547
1.138–3.174
0.987–1.001
Ann Thorac Surg
2012;94:475– 81
Table 4. Multivariate Cox Proportional Regression Model for
Native Coronary Artery Disease Progression in Previously
Revascularized Territories
p Value
⬍0.0001
0.0009
0.0022
0.0143
0.0332
0.0795
CI ⫽ confidence interval.
Disease Progression by Territory
Table 3 shows that the inferior territory had the highest
overall disease progression rate (46%) compared with the
lateral territory (36%) and the anterior territory (18%).
The LITA (783 grafts) was used to bypass only the left
anterior descending (LAD) artery in the anterior territory. RA (86 grafts) and SV (377 grafts) were used to
bypass diagonal branches in the anterior territory. Kaplan-Meier– estimated 10-year disease progression rate
in LAD artery with a patent LITA was 8%, and in the
diagonal branches disease progression with a patent RA
was 10% versus 40% for a patent SVG (log-rank test, p ⬍
0.0001). Cox proportional regression modeling found that
the use of the RA was associated with an HR of 0.277 (95%
CI, 0.114 – 0.673; p ⫽ 0.005) for native coronary artery
disease progression in previously grafted diagonal arteries with patent conduits compared with the progression
of disease in the diagonal arteries with a patent SVG.
The left circumflex system and ramus intermedius (lateral territory) were bypassed with 312 RA grafts and 599
SVGs. Fig 3 shows the Kaplan-Meier– estimated 10-year
disease progression rate, with a patent RA graft of 11%
Risk Factor
Left main stenosis ⬎ 50%
Peripheral vascular disease
Stroke
DM
Hypertension
Advanced atherosclerosis in
aorta
Stenting before CABG
RA
LITA
Hazard
Ratio
95% CI
p Values
1.201
4.079
1.645
1.423
1.494
1.401
1.028–1.404
1.859–8.951
1.008–2.683
1.085–1.865
1.138–1.961
1.029–1.907
0.0213
0.0005
0.0464
0.0107
0.0030
0.0325
1.208
0.254
0.280
1.105–1.352
0.188–0.344
0.224–0.349
0.0001
0.0001
0.0001
CI ⫽ confidence interval;
DM ⫽ diabetes mellitus;
CABG ⫽
coronary artery bypass grafting;
LITA ⫽ left internal thoracic artery;
RA ⫽ radial artery.
versus 48% with a patent SVG (log-rank test, p ⬍ 0.0001)
(Fig 3). Cox proportional regression modeling found that
use of the RA was associated with an HR of 0.254 (95% CI,
0.188 – 0.344; p ⬍ 0.0001) for native coronary artery disease
progression in the previously grafted lateral territories with
a patent conduit compared with the progression of disease
in the lateral territories with a patent SVG.
The right coronary artery (RCA) and its branches
(inferior territory) were bypassed with 586 SVGs and 22
RA grafts. The cumulative rate of disease progression
with a patent SVG at 10 years was 45%.
Conduit Patency
Of the 783 LITA conduits, 96 conduits (12%) were found
to be malfunctioning at the time of the first symptomdriven angiogram. The Kaplan-Meier– estimated cumu-
Table 3. Graft Patency and Progression of Disease Per Coronary Territory in 772 Symptomatic Patients After CABG
Graft Patency/Disease Progression
Total Grafts
(n ⫽ 2765)
Anterior
(n ⫽ 1246)
Lateral
(n ⫽ 911)
Inferior
(n ⫽ 608)
LITA
Patent/no new disease
Patent ⫹ disease progression
Malfunctioning graft
Malfunctioning graft ⫹ disease progression
(n ⫽ 783)
653 (83.1%)
34 (4.3%)
43 (5.5%)
53 (6.8%)
(n ⫽ 783)
653 (83.1%)
34 (4.3%)
43 (5.5%)
53 (6.8%)
(n ⫽ 0)
...
...
...
...
(n ⫽ 0)
...
...
...
...
RA graft
Patent/no new disease
Patent ⫹ disease progression
Malfunctioning graft
Malfunctioning graft ⫹ disease progression
(n ⫽ 420)
319 (76%)
26 (6.1%)
54 (12.8%)
21 (5%)
(n ⫽ 86)
70 (81.4%)
4 (4.7%)
11 (12.8%)
1 (1.2%)
(n ⫽ 312)
232 (74.5%)
21 (6.7%)
40 (12.8%)
19 (6%)
(n ⫽ 22)
17 (78%)
1 (4.5%)
3 (13%)
1 (4.5%)
SVG
Patent/no new disease
Patent ⫹ disease progression
Malfunctioning graft
Malfunctioning graft ⫹ disease progression
(n ⫽ 1562)
560 (35.8%)
352 (22.5%)
292 (19%)
358 (23%)
(n ⫽ 377)
163 (43.2%)
50 (13.3%)
76 (20.2%)
88 (23.3%)
(n ⫽ 599)
203 (34%)
154 (25.7%)
104 (17.4%)
138 (23%)
(n ⫽ 586)
194 (33%)
148 (25.3%)
112 (19%)
132 (22.5%)
CABG ⫽ coronary artery bypass grafting;
LITA ⫽ left internal thoracic artery;
RA ⫽ radial artery;
SVG ⫽ saphenous vein graft.
Downloaded from ats.ctsnetjournals.org by Robert Tranbaugh on September 21, 2012
DIMITROVA ET AL
ARTERIAL GRAFTS PROTECT CORONARY ARTERIES
479
ADULT CARDIAC
Ann Thorac Surg
2012;94:475– 81
Fig 2. Kaplan-Meier– estimated disease progression rates in all territories with patent conduits. (LITA ⫽ left internal thoracic artery;
RA ⫽ radial artery; SVG ⫽ saphenous vein graft.)
lative LITA patency rate in all coronary territories (with
and without disease progression) at 1, 5, and 10 years was
97%, 91%, and 80%, respectively (Fig 4).
Four hundred twenty RA conduits were used in 278
patients to bypass the second-best target vessel with
greater than 70% stenosis in the lateral territory (n ⫽ 312),
the diagonal branches of the LAD artery (n ⫽ 86), or the
inferior territory (n ⫽ 22). There were a total of 75
malfunctioning RA conduits (18%). The Kaplan-Meier–
estimated cumulative RA patency rate for all coronary
territories at 1, 5, and 10 years was 96%, 90%, and 76%,
respectively (RA versus LITA log-rank test, p ⫽ 0.092)
(Fig 4).
SVGs were used to bypass the second-best target
vessel in the lateral territory (n ⫽ 599) in patients who did
not receive RA grafts and for diagonal branches of the
LAD (n ⫽ 377). Also, the majority of the inferior territory
Fig 3. Kaplan-Meier– estimated disease progression rates with patent
conduits in the lateral territory. (RA ⫽ radial artery; SVG ⫽ saphenous vein graft.)
Fig 4. Kaplan-Meier– estimated conduit patency rates. (LITA ⫽ left
internal thoracic artery; RA ⫽ radial artery; SVG ⫽ saphenous vein
graft.)
vessels (96%) were grafted with SVGs (n ⫽ 586). Overall,
650 (41.6%) of all SVGs were found to be malfunctioning.
The Kaplan-Meier– estimated cumulative SVG patency
rate for all coronary territories at 1, 5, and 10 years was
93%, 69%, and 43%, respectively (SVG versus RA and
LITA log-rank test, p ⬍ 0.0001) (Fig 4).
Disease Progression and Conduit Patency
Kaplan-Meier estimated overall freedom from disease
progression after CABG with a patent conduit at 1, 5, and
10 years for territories grafted with the LITA was 95%,
86%, and 72%, respectively; for territories grafted with
the RA, it was 91%, 81%, and 60%, respectively (LITA
versus RA log-rank test, p ⫽ 0.034); and for territories
grafted with SVGs it was 91%, 56%, and 21%, respectively
(RA versus SVG log-rank test, p ⬍ 0.0001) (Fig 5).
Fig 5. Kaplan-Meier– estimated overall freedom of disease progression and graft failure. (LITA ⫽ left internal thoracic artery; RA ⫽
radial artery; SVG ⫽ saphenous vein graft.)
Downloaded from ats.ctsnetjournals.org by Robert Tranbaugh on September 21, 2012
480
DIMITROVA ET AL
ARTERIAL GRAFTS PROTECT CORONARY ARTERIES
Comment
ADULT CARDIAC
Our study suggests that patent RA grafts are associated
with a decreased risk of disease progression in the native
coronary arteries compared with patent SVGs. Overall,
RA use resulted in a 75% decrease in disease progression
in all coronary territories (Table 4). RA conduits were
associated with a 74% decreased risk of disease progression in the diagonal arteries and a 75% decreased risk of
disease progression in the lateral territory compared with
patent SVGs (Fig 3).
SVGs were more likely to be found malfunctioning in
symptomatic patients compared with RA grafts. Malfunctioning conduit with disease progression was also found
in 23% of the territories treated with SVGs versus 5% in
the RA territories. However it is unclear if there is an
interaction between the slow process of atherosclerosis
and the patency of the conduit. The overall freedom from
disease progression and treatment failure (malfunctioning graft) was significantly better for the coronary territories treated with RA grafts compared with those bypassed with SVGs (Fig 5).
Older age, chronic pulmonary obstructive disease, and
worse left ventricular function were all associated with
decreased occurrence of recatheterization (Table 1). A
possible explanation is that these factors increase the risk
associated with reintervention and therefore treatment
may be biased in favor of medical therapy. Table 4 shows
that patients with hypertension, diabetes, and advanced
atherosclerosis (peripheral vascular disease, advance
aortic disease, and previous stroke) are at higher risk for
coronary artery disease progression. In addition to these
factors, PCI before CABG was associated with a 20%
greater risk of disease progression in previously stented
territories, which may be a contributing factor for the
worse outcomes reported by Rao and associates [13] in
patients undergoing CABG after previous PCI.
Patients who are symptomatic after CABG have been
previously studied with a main focus on the conduit
patency. The impact of the type of conduit and its status
(patent versus malfunctioning) on disease progression
has been reported less often. Our study confirms earlier
studies (10, 14 –16) of generally superior long-term RA
patency compared with SVG patency but also found a
significant difference in disease progression rates between territories revascularized with patent SVGs and
patent RA grafts.
We found that only 9% of the recatheterized patients
had new disease in ungrafted territories. The BARI (Bypass Angioplasty Revascularization Investigation) study
[17] reported that native coronary disease progression
exceeds failed revascularization in patients with anginal
symptoms after CABG but was most likely to occur in
untreated vessels (55%). However the patients who underwent CABG in that study received an average of 2.9
grafts per patient, whereas our patients who underwent
CABG received an average of 3.6 grafts, suggesting that
more complete initial revascularization would result in
less disease progression in untreated vessels.
Ann Thorac Surg
2012;94:475– 81
Isolated graft failure was identified as the cause for
recurrent symptoms in 19% of our patients versus 44%
who had disease progression with patent or malfunctioning grafts in previously grafted vessels; only 9% presented with disease progression in ungrafted territory.
The post-hoc analysis of the second Medical, Angioplasty, or Surgery Study (MASS II) [18] showed that a
LITA graft resulted in less disease progression in the
LAD artery than did SVG grafts. In our series, the LAD
artery was always bypassed with the LITA, whereas the
SVG and RA conduits were used to bypass the diagonal
branches, and therefore we are not able to compare the
LITA with the SVG or RA to the LAD artery.
We observed the highest overall disease progression
rate in the inferior coronary territory, revascularized
mainly with SVGs. It remains unclear whether the highest rate of atherosclerosis development is caused by SVG
failure or accelerated progression of disease specifically
in the RCA territory. Only 22 (22/608) or 4% of all grafts
applied to the RCA were RAs. The INTACT (International Nifedipine Trial on Antiatherosclerotic Therapy)
study [19] also indicated that the inferior territory had
more disease progression after revascularization, but it
remains unclear if this is a consequence of using mainly
SVGs (which have higher failure rates) or is a result of
generally incomplete inferior territory revascularization.
Berreklouw and associates (6) observed that grafting
with 2 internal thoracic arteries has a protective effect
against recurrent angina but they did not report angiographic findings related to their finding. However Sergeant and associates [5] showed no or trivial benefit of
bilateral internal thoracic artery grafts on recurrent anginal symptoms and survival. Our findings suggest that
RA grafting decreases native coronary artery disease
progression and may explain the documented survival
benefit of RA grafting compared with SVGs [10, 15].
The mechanism of the protective effect of the arterial
grafts on disease progression in patients after CABG yet
needs to be clarified. There may be a benefit from the
active endothelium of the RA and LITA conduits. These
are metabolically active grafts, producing vasoactive and
endothelial progenitor substances that may defend the
native vessels from progression of atherosclerosis with a
mechanism similar to that of their own protection against
disease [20]. The presence of a smooth muscle layer in
the arterial wall helps the conduit to adjust its caliber to
the coronary flow in the native vessels, creating less
turbulence at the distal anastomosis [21].
Recurrent symptoms after CABG is a clinical event
based on interpretation of medical history and therefore
subject to possible bias selection. Symptom-driven coronary angiograms were obtained based on the clinical
presentation and were not always confirmed by stress
testing. Our 772 patients included only those patients
returning to our hospitals, resulting in a likely underestimation of the incidence of recatheterization after
CABG. The lipid profile and statin treatment were not
included in our study because the data for these variables
was not collected prospectively. However our patients
who underwent CABG had a homogeneous characteris-
Downloaded from ats.ctsnetjournals.org by Robert Tranbaugh on September 21, 2012
DIMITROVA ET AL
ARTERIAL GRAFTS PROTECT CORONARY ARTERIES
tic profile, and their postoperative medical management
was uniform, including administration of statins, aspirin,
beta-blockers, and anti-hypertensive medications.
RA and LITA grafting showed a strong protective effect
against native coronary artery disease progression and
excellent cumulative patency rates in symptomatic patients after CABG. This benefit of arterial grafting may
contribute to the better survival of the patients who
underwent revascularization with more than 1 arterial
graft. Arterial grafting should be used more widely in
CABG.
We would like to thank Lillia Dincheva, Dana Faleck, Adam
Fink, and Samantha Ni for gathering the angiographic data.
References
1. Wu C, Zhao S, Wechsler AS, et al. Long-term mortality of
coronary artery bypass grafting and bare-metal stenting.
Ann Thorac Surg 2011;92:2132– 8.
2. Buxton BF, Komeda M, Fuller JA, Gordon I. Bilateral internal
thoracic grafting may improve outcome of coronary artery
surgery. Risk-adjusted survival. Circulation 1998;(19 Suppl):
II1– 6.
3. Sergeant P, Blackstone E, Meyns B. Is return of angina after
coronary artery bypass grafting immutable, can it be delayed, and is it important? J Thorac Cardiovasc Surg 1998;
116:440 –53.
4. Sergeant P, Lesaffre E, Flameng W, Suy R, Blackstone E. The
return of clinically evident ischemia after coronary artery
bypass grafting. Eur J Cardiothorac Surg 1991;5:447–57.
5. Sergeant P, Blackstone E, Meyns B, Stockman B, Jashari R.
First cardiological or cardiosurgical reintervention for ischemic heart disease after primary coronary artery bypass
grafting. Eur J Cardiothorac Surg 1998;14:480 –7.
6. Berreklouw E, Rademakers P, Koster J, Leur L, Wielen B,
Westers P. Better ischemic event-free survival after two
internal thoracic artery grafts: 13 years of follow-up. Ann
Thorac Surg 2001;72:1535– 41.
7. Sabik J, Blackstone E, Gillinov M, Smedira N, Lytle B.
Occurrence and risk factors for reintervention after coronary
artery bypass grafting. Circulation 2006;114(Suppl I):454 – 60.
8. Loop F, Lytle B, Cosgrove D, et al. Influence of the internal
mammary-artery graft on 10-year survival and other cardiac
events. N Engl J Med 1986;314:1– 6.
481
9. Lytle BW, Blackstone EH, Sabik JF, Houghtaling P, Loop FD,
Cosgrove DM. The effect of bilateral internal thoracic artery
grafting on survival during 20 postoperative years. Ann
Thorac Surg 2004;78:2005–14.
10. Zacharias A, Habib RH, Schwann TA, Riordan CJ, Durham
SJ, Shah A. Improved survival with radial artery versus vein
conduits in coronary bypass surgery with left internal thoracic artery to left anterior descending artery grafting. Circulation 2004;109:1489 –96.
11. Imai K, King G, Lau O. Zelig: Everyone’s Statistical Software.
2007. Available at: http://GKing.harvard.edu/zelig. Accessed
April 19, 2012.
12. Imai K, King G, Lau O. Toward a common framework for
statistical analysis and development. J Comp Graph Stat
2008;17:892–913.
13. Rao C, Stanbridge R, Chikwe J, et al. Does previous percutaneous coronary stenting compromise the long-term efficacy of subsequent coronary artery bypass surgery? A microsimulation study. Ann Thorac Surg 2008;85:501–7.
14. Tatoulis J, Royse AG, Buxton BF, et al. The radial artery in
coronary surgery: a 5-year experience— clinical and angiographic results. Ann Thorac Surg 2002;73:143– 8.
15. Tranbaugh RF, Dimitrova KR, Friedmann P, et al. Radial
artery conduits improve long-term survival after coronary
artery bypass grafting. Ann Thorac Surg 2010;90:1165–72.
16. Tatoulis J, Buxton BF, Fuller JA, et al. Long-term patency of
1108 radial arterial-coronary angiograms over 10 years. Ann
Thorac Surg 2009;88:23–30.
17. Alderman EL, Kip KE, Whitlow PL, et al. Native coronary
disease progression exceeds failed revascularization as
cause of angina after five years in the Bypass Angioplasty
Revascularization Investigation (BARI). J Am Coll Cardiol
2004;44:766 –74.
18. Borges J, Lopes N, Soares P, et al. Five-year follow-up of
angiographic disease progression after medicine, angioplasty, or surgery. J Cardiothorac Surg 2010;5:91–9.
19. Lichtlen PR, Nikutta P, Jost S, Deckers J, Wiese B, Raffembeul W. Anatomical progression of coronary artery disease in humans as seen by prospective, repeated, quantitative coronary angiography. Relation to clinical events
and risk factors. The INTACT Study Group. Circulation
1992;86:828 –38.
20. Briguori C, Testa U, Riccioni R, et al. Correlation between
progression of coronary artery disease and circulating endothelial progenitor cells. FASEB 2010;24:1981– 8.
21. Verhoeff B-J, Siebes M, Meuwissen M, et al. Influence of
percutaneous coronary intervention on coronary microvascular resistance index. Circulation 2005;111:76 – 82.
Downloaded from ats.ctsnetjournals.org by Robert Tranbaugh on September 21, 2012
ADULT CARDIAC
Ann Thorac Surg
2012;94:475– 81
Arterial Grafts Protect the Native Coronary Vessels From Atherosclerotic Disease
Progression
Kamellia R. Dimitrova, Darryl M. Hoffman, Charles M. Geller, Gabriela Dincheva,
Wilson Ko and Robert F. Tranbaugh
Ann Thorac Surg 2012;94:475-481
DOI: 10.1016/j.athoracsur.2012.04.035
Updated Information
& Services
including high-resolution figures, can be found at:
http://ats.ctsnetjournals.org/cgi/content/full/94/2/475
References
This article cites 19 articles, 14 of which you can access for free at:
http://ats.ctsnetjournals.org/cgi/content/full/94/2/475#BIBL
Subspecialty Collections
This article, along with others on similar topics, appears in the
following collection(s):
Coronary disease
http://ats.ctsnetjournals.org/cgi/collection/coronary_disease
Permissions & Licensing
Requests about reproducing this article in parts (figures, tables) or
in its entirety should be submitted to:
http://www.us.elsevierhealth.com/Licensing/permissions.jsp or
email: [email protected].
Reprints
For information about ordering reprints, please email:
[email protected]
Downloaded from ats.ctsnetjournals.org by Robert Tranbaugh on September 21, 2012