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Brown et al Surgery for Acquired Cardiovascular Disease

Conduit choice for coronary artery bypass grafting after


mediastinal radiation
Morgan L. Brown, MD, Hartzell V. Schaff, MD, and Thoralf M. Sundt, MD

Objective: Patients who have undergone prior mediastinal radiation might require coronary artery bypass graft-
ing. However, there is some concern regarding potential radiation damage to the internal thoracic artery. Our
objective was to assess the late patency of the internal thoracic artery and venous grafts in patients with prior
mediastinal radiation.

ACD
Methods: Patients undergoing coronary artery bypass grafting at our clinic after prior mediastinal radiation were
identified, and medical records, including operative reports, clinical notes, and coronary angiography, were reviewed.
Results: Between 1985 and 2005, 138 patients had coronary artery bypass grafting after mediastinal radiation. Of
these, 25 underwent clinically indicated postoperative angiography. The mean patient age was 56.1  13.8 years,
and 24% were female. All patients received between 3000 and 6000 rads in fractionated doses. Seventy-two per-
cent of patients had 3-vessel coronary artery disease. At late angiography (mean, 2.2 years), 6 (32%) of 19 in-
ternal thoracic arteries and 13 (27%) of 48 venous or radial arterial conduits showed stenosis of 70% or
greater (P ¼ .72). Assessing only grafts that were anastomosed to the left anterior descending coronary artery,
35% (6 of 17) of internal thoracic artery grafts and 60% (3 of 5) of non–internal thoracic artery grafts showed
narrowing of 70% or greater (P ¼ .61). Among patients who received a graft to the left anterior descending cor-
onary artery (n ¼ 113), however, age-adjusted survival at 5 years was superior among those receiving an internal
thoracic artery graft to the left anterior descending coronary artery.
Conclusions: Internal thoracic artery graft patency among patients with prior radiation was less than expected and
similar to that for venous grafts, although the effect of conduit disease versus distal target vessel runoff is
unknown. Despite this, late survival was superior among those receiving an internal thoracic artery graft to the
left anterior descending coronary artery. These data support use of an internal thoracic artery graft to the left
anterior descending coronary artery when it appears grossly to be an acceptable conduit.

Patients who have undergone prior mediastinal radiation are tween 1985 and 2005, 138 patients were identified with a history of previous
at risk for early development of coronary artery disease1 and mediastinal radiation and CABG. After review of clinical information from
the medical record, 25 (18%) patients underwent follow-up angiography. In
might require surgical revascularization. The preferred con- all cases angiography was performed for clinical indications, including
duit for coronary artery bypass grafting (CABG), particu- chest pain or shortness of breath.
larly to the left anterior descending coronary artery (LAD),
is the internal thoracic artery (ITA); however, the effect of Surgical Approach
therapeutic doses of radiation on the integrity of the ITA Although there is no policy at our institution regarding patients with me-
itself is unknown. Studies regarding the late patency of diastinal radiation therapy in general, the ITA is preferred as the conduit of
irradiated ITAs are small and conflicting.2-13 We therefore choice to the LAD. After median sternotomy, ITAs were harvested by using
a pedicled technique and grossly inspected for patency. If the ITA did not
retrospectively reviewed patients who had a history of medi- appear to have adequate blood flow or was fibrotic, the artery was ligated,
astinal radiation and underwent CABG at our institution and and venous or radial arterial conduits were used as bypass conduits. It has
subsequent graft angiography. not been the practice in our institution to assess the ITAs preoperatively
for patency during coronary artery catheterization. Intraoperative graft
flow measurements were not performed. At the time of the operation, con-
MATERIALS AND METHODS comitant procedures were performed as indicated.
Patients
Institutional review board approval was obtained. Patients who received Statistical Analysis
large doses of radiation (3000–6000 rads) to the mediastinum before cardiac Continuous variables are expressed as means and standard deviations or
operation were identified from institutional databases. Patients who received medians and ranges. Groups were compared by using t tests or c2 tests, as
only neck, spine, or tangential radiation for breast cancer were excluded. Be- appropriate. Vital status for all patients was attained through use of Accurint
(www.accurint.com) and the Social Security Death Index. Kaplan–Meier
From the Division of Cardiovascular Surgery, Mayo Clinic, Rochester, Minn. survival curves were created with SAS version 9.1 (SAS Institute, Inc,
Received for publication Nov 25, 2007; revisions received June 4, 2008; accepted for
Cary, NC) and compared with a log-rank test.
publication July 3, 2008.
Address for reprints: Thoralf M. Sundt, MD, Mayo Clinic, 200 1st St SW, Rochester,
MN 55905 (E-mail: [email protected]).
J Thorac Cardiovasc Surg 2008;136:1167-71 RESULTS
0022-5223/$34.00
Copyright Ó 2008 by The American Association for Thoracic Surgery Of the 138 patients undergoing CABG after mediastinal ra-
doi:10.1016/j.jtcvs.2008.07.005 diation, 51% were female, and the mean age was 63  13

The Journal of Thoracic and Cardiovascular Surgery c Volume 136, Number 5 1167
Surgery for Acquired Cardiovascular Disease Brown et al

TABLE 1. Preoperative and operative characteristics of the entire


Abbreviations and Acronyms cohort of patients with prior mediastinal radiation
CABG ¼ coronary artery bypass grafting Patients
ITA ¼ internal thoracic artery Patients with without
LAD ¼ left anterior descending coronary artery follow-up follow-up
angiography angiography
Patient characteristics (n ¼ 25) (n ¼ 113) P value
Mean age (y) 56  13 64  13 .007
ACD

years. The most common reasons for mediastinal radiation Female sex (%) 6 (24) 65 (58) .002
History of smoking (%) 12 (48) 61 (54) .588
included breast cancer (40%), lymphomas (including
History of diabetes (%) 4 (16) 24 (21) .556
Hodgkin’s and non-Hodgkin’s lymphoma: 34%), germ
History of 17 (68) 74 (65) .810
cell tumors (9%), lung cancers (8%), and others (thymic, hypercholesterolemia (%)
esophageal, and laryngeal: 9%). History of hypertension 15 (52) 63 (58) .698
New York Heart Association 21 (84) 88 (78) .288
Patients With Follow-up Angiography class III/IV (%)
Of the 25 patients who had follow-up angiography, Mean ejection fraction (%) 56  12 57  13 .212
a lower percentage were female (24%), and the patients Isolated bypass procedure (%) 17 (68) 63 (56) .262
were younger when compared with the entire cohort (Table Mean no. of distal 2.6  1.2 2.4  1.0 .333
1). The most common reasons for radiation therapy were anastomoses
similar (52% lymphoma, 24% germ cell cancer, and 20% ITA use (no. of patients, %) 18 (72) 65 (58)
Left ITA 15 59 .731
breast cancer). The median time from radiation exposure
Right ITA 2 4 .298
to CABG was 23.1 years (range, 2.1–40.3 years) for the
Bilateral ITA 1 2 .454
angiography group. Fifteen patients had a history of hyper- Radial artery use (no. of 2 (8) 4 (4) .298
tension, 17 patients had hyperlipidemia, 12 patients were patients, %)
previous or current smokers, and 4 patients had diabetes Venous distal anastomoses
(Table 2). Twenty-one (84%) of the patients were in New 1 4 27 .392
York Heart Association class III or IV, and the mean ejection 2 9 44 .237
fraction was 56%  12%. 3 8 26 .345
Among those patients undergoing postoperative angiog- 4 0 1 1.000
raphy, the majority (72%) had 3-vessel disease, and the av- ITA, Internal thoracic artery.
erage number of distal anastomoses per patient was 2.6
versus 2.4 (P ¼ .33) in those patients who did not have fol- grafts (P ¼ .44). Assessing only grafts that were anastomosed
low-up angiography. Conduit selection was similar between to the LAD, 32% of ITA grafts and 60% of the non-ITA
grafts showed stenosis of 70% or greater (P ¼ .61).
the angiography group and the whole group. Among the an-
giography group (n ¼ 25), there were 19 ITAs used (16 left
and 3 right), 2 radial arteries, and 46 vein grafts. Sixteen ITA Patients With Grafts to the LAD
grafts and 5 vein grafts were anastomosed to the LAD. Con- We selected all patients who had a graft to the LAD (n ¼
comitant procedures were performed in 9 patients, including 113, 82%). Patients did not receive an ITA graft to the LAD
aortic valve replacement (n ¼ 6), mitral valve replacement (n ¼ 34) for several reasons: 10 were fibrotic or scarred, 4
(n ¼ 1), mitral valve repair (n ¼ 1), pericardiectomy (n ¼ 1), were not used because the patient’s condition was unstable,
and septal myectomy (n ¼ 1). 2 had prior injury to the ITA, 2 had a known ITA stenosis on
The median time from operation to angiography was 2.2 angiography, 1 had poor pulsations, 1 was of inadequate
years (range, 0.5–10.3 years). Angiograms were performed length, and 1 had tumor-positive tissue around the ITA. In
for clinical indications, including symptoms or positive non- 13 patients there was inadequate documentation to deter-
invasive test results. In the ITA grafts, 4 were completely oc- mine the reason why the ITA was not used.
cluded, leaving 15 (79%) of 19 patent. Of these, 9 ITA grafts Late survival was compared between patients who had an
were perfectly patent, 4 had narrowing of less than 70%, and ITA graft (n ¼ 79) and those who had a venous graft (n ¼
2 were narrowed by 70% or more. Analysis of other con- 34) to the LAD. At 1 and 5 years, the age-adjusted survivals
duits, both radial arteries and vein grafts, revealed that 13 of patients with an ITA graft to the LAD were 89% and 67%
grafts were completely occluded, resulting in 36 (73%) of compared with 80% and 51% in patients with a venous graft
48 patent grafts. This included 12 that were perfectly patent, to the LAD, respectively (P ¼ .16, Figure 1). When all pa-
19 that showed less than 70% stenosis, and 5 that showed tients who received a graft to the LAD (n ¼ 113) were com-
70% or greater stenosis. Late patency on angiography was pared with an age- and sex-matched population, the overall
not significantly different between ITA grafts and venous survival was decreased (P < .001, Figure 2).

1168 The Journal of Thoracic and Cardiovascular Surgery c November 2008


Brown et al Surgery for Acquired Cardiovascular Disease

TABLE 2. Characteristics of patients who had follow-up angiography available


Patient no. Age at operation (y) M/F Year of radiation Cancer type [ BP Smoking Hx DM [ Lipids NYHA class
1 57 M 1968 Sarcoma No No No No 2
2 62 M 1986 Hodgkin’s No Yes No No 3
3 61 M 1986 Hodgkin’s No No Yes No 3
4 39 M 1980 Non-Hodgkin’s Yes No No No 3
5 71 F 1955 Breast (L) Yes No No No 3
6 76 F 1984 Breast (L) No No No Yes 4

ACD
7 39 M 1969 Hodgkin’s No No No Yes 3
8 45 M 1976 Hodgkin’s No No No No 2
9 48 M 1964 Hodgkin’s Yes Yes Yes Yes 2
10 49 M 1976 Germ cell Yes Yes No Yes 4
11 39 M 1974 Hodgkin’s Yes No No No 4
12 46 M 1967 Hodgkin’s No Yes No Yes 3
13 57 M 1986 Germ cell No Yes No Yes 3
14 47 M 1970 Hodgkin’s No Yes No Yes 4
15 67 F 1969 Breast (R) Yes No Yes Yes 3
16 37 M 1976 Hodgkin’s Yes Yes No Yes 3
17 58 M 1975 Germ cell Yes No No Yes 4
18 64 M 1967 Hodgkin’s Yes Yes No Yes 2
19 60 F 1960 Germ Cell Yes Yes No Mo 4
20 46 M 1970 Non-Hodgkin’s No No No Yes 4
21 89 F 1992 Breast (R) No No No Yes 3
22 53 M 1965 Non-Hodgkin’s No Yes No Yes 3
23 63 M 1963 Seminoma Yes No No Yes 4
24 76 F 2002 Breast (L) Yes Yes Yes Yes 4
25 62 M 1980 Seminoma Yes Yes No Yes 4
M, Male; F, female; BP, blood pressure; Hx, history; DM, diabetes mellitus; NYHA, New York Heart Association; L, left; R, right.

DISCUSSION vascular system, such as hypertension or diabetes, radiation


Patients with prior mediastinal radiation can present with damage to vessels can be greater in severity.2 When CABG
myocardial, pericardial, valvular, and coronary artery dis- surgery is required, the choice of bypass conduit presents an
ease. Radiation can cause damage to the vasculature through additional challenge. The ITA is the preferred conduit in
direct damage to the endothelial cells.1 Fibrous proliferation most circumstances, with 5-year patency rates in contempo-
can then occur, resulting in a loss of parenchymal cells.2 In rary series for nonirradiated ITA grafts as high as 96% to
patients who have medical conditions that also affect the 98% in comparison with venous grafts as low as 83% to

FIGURE 1. Age-adjusted survival compared between patients with prior


mediastinal radiation therapy who received an internal thoracic artery FIGURE 2. Survival of patients who had prior mediastinal radiation ther-
(ITA) graft compared with a venous graft to the left anterior artery. This apy and had either an internal thoracic artery or vein grafted to the left an-
age-adjusted comparison demonstrates superior survival in patients who re- terior descending coronary artery (LAD; n ¼ 113). When compared with an
ceived an internal thoracic artery graft, but overall, it was not statistically age- and sex-matched Minnesota population, patients who had prior medi-
significant. astinal radiation therapy had a significantly reduced late survival.

The Journal of Thoracic and Cardiovascular Surgery c Volume 136, Number 5 1169
Surgery for Acquired Cardiovascular Disease Brown et al

95%.14,15 The effect of radiation vasculopathy on the ITA, published on graft patency in patients with prior mediastinal
however, is uncertain. radiation because prior studies used both clinical and nonin-
Prior literature on the subject is divided. A study from vasive follow-up.3,4
Nasso and colleagues3 suggested that irradiated skeletonized Age-adjusted survival was superior among patients who
ITAs have equal patency as saphenous veins and other arte- had an ITA graft to the LAD when compared with those
rial conduits. Other authors have also supported the use of who had a venous graft, although this was not statistically
the ITA in these patients with prior mediastinal radiation ex- significant. This is likely highly susceptible to selection
posure4-9; however, others have suggested that mediastinal bias because in most cases the ITA was considered for use
ACD

radiation might damage the ITA, causing either fragility or unless it appeared fibrotic or had poor flow. In addition, it
leading to early graft failure if it is used as a conduit.10-13 is also possible that surgeons have a preference for placing
Several of these studies10-12 are case reports, but in the study ITA grafts in healthier patients. Our study reports a some-
by Hicks,13 the ITA was only usable as a graft in 3 of 14 pa- what lower survival than our previously reported 5-year sur-
tients with previous mediastinal radiation exposure because vival of 73% for patients undergoing CABG after previous
of friability and fibrosis. mediastinal radiation.16 In the current series, however, we
A previous study from our institution16 suggested that included patients who had concomitant valvular heart dis-
because of the unknown quality of the ITA graft and the in- ease that might indicate a poorer prognosis.19
creased risk of mediastinal wound complications in patients Finally, it must be acknowledged that our study might
with previous mediastinal radiation therapy, alternative con- simply be underpowered to detect a difference between the
duits should be considered. Despite these concerns, because patency of an ITA or venous conduit. In addition, we did
of the well-documented effect of an ITA graft to the LAD on not have adequate patient numbers to assess the effect of
late survival,17 it has been our strong institutional bias to use the radial artery in this cohort.
the ITA conduit when possible. Indeed, in this series 79
(70%) of 113 patients with significant LAD disease received CONCLUSION
an ITA graft. The argument to use the ITA is particularly Irradiated ITA grafts had similar patency rates to venous
compelling because these patients are often young. Further- or radial arterial conduits. Either ITA grafts or venous con-
more, with concerns about small-vessel disease and the ad- duits can be used in patients who have received previous
equacy of distal runoff, the ITA is an appealing conduit. mediastinal radiation. However, when patent, these data
This provided us with a sizeable population from which to suggest the ITA graft remains the conduit choice for grafting
draw survival data. Unfortunately, only a small minority un- to the LAD in patients with prior mediastinal radiation
derwent postoperative coronary angiography. therapy.
Preoperative assessment of the ITA might be a consider-
ation, although it has not been our practice up to now. Van References
Son and coworkers4 and others6,7 suggest that if the patency 1. Schultz-Hector S, Trott KR. Radiation-induced cardiovascular diseases: is the
is ascertained preoperatively, the ITA can be safely used. In epidemiologic evidence compatible with the radiobiologic data? Int J Radiat
Oncol Biol Phys. 2007;67:10-8.
general, patients in this study did not have examination of 2. Baker DG, Krochak RJ. The response of the microvascular system to radiation:
the ITA on angiography before surgical revascularization a review. Cancer Invest. 1989;7:287-94.
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Thoracic radiation therapy and suitability of internal thoracic arteries for myocar-
grossly inspected at time of surgical intervention for dial revascularization. Chest. 2005;128:1587-92.
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1992;104:1539-44.
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might include greater severity of native coronary artery dis- disease. Mayo Clin Proc. 1992;67:1081-4.
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8. Gansera B, Haschemi A, Angelis I, Eichinger W, Breuer M, Keiditsch E, et al.
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9. Gansera B, Schmidtler F, Angelis I, Botzenhardt F, Schuster T, Kiask T, et al.
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vs 9% in the ITA at 5 years, P ¼ .002). There are few data mastectomy and radiotherapy. Am J Cardiol. 1990;65:1044-5.

1170 The Journal of Thoracic and Cardiovascular Surgery c November 2008


Brown et al Surgery for Acquired Cardiovascular Disease

12. Renner S, Massel D, Moon BC. Mediastinal irradiation: a risk factor for mediastinal radiation therapy. J Thorac Cardiovasc Surg. 1999;117:
atherosclerosis of the internal thoracic arteries. Can J Cardiol. 1999;15: 1136-43.
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13. Hicks GL Jr. Coronary artery operation in radiation-associated atherosclerosis: et al. Influence of the internal-mammary-artery graft on 10-year survival and other
long-term follow-up. Ann Thorac Surg. 1992;53:670-4. cardiac events. N Engl J Med. 1986;314:1-6.
14. Tatoulis J, Buxton BF, Fuller JA. Patencies of 2127 arterial to coronary conduits 18. Buxton BF, Durairaj M, Hare DL, Gordon I, Moten S, Orford V, et al. Do angio-
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ACD
Daly RC, et al. Coronary artery bypass grafting in patients with previous Ann Thorac Surg. 2001;71:1880-4.

The Journal of Thoracic and Cardiovascular Surgery c Volume 136, Number 5 1171

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