Long-term results of bilateral internal thoracic artery grafting

Long-Term Results of Bilateral Internal Thoracic Artery Grafting Masashi Ura, MD, Ryuzo Sakata, MD, Yoshihiro Nakayama, MD, Yoshio Arai, MD, and Taro Saito, MD Departments of Cardiovascular Surgery and Cardiology, Kumamoto Central Hospital, Kumamoto City, Japan

Background. Little is known about the long-term results of the uniform group of patients who had bilateral internal thoracic artery (ITA) grafting with the method of left ITA-to-left anterior descending coronary artery and right ITA-to-circumflex artery. Methods. Late follow-up study was performed in the first consecutive 203 patients (mean age, 62.6 ⴞ 9.1 years) who underwent isolated coronary artery bypass grafting with the left ITA anastomosed to the left anterior descending coronary artery and the right ITA to major branches of the circumflex artery. The patients were grouped according to the patency of ITA grafts demonstrated by early postoperative angiography (Both patent (BP) group, 168 patients: both ITAs showed complete patency; Not patent (NP) group, 23 patients: at least one ITA was dysfunctional). Results. Actuarial 7-year survival in all patients was 89.3% ⴞ 3.1%. The cumulative probability of event-free

survival for cardiac death, myocardial infarction, intervention, and angina at 7 years was 96.6% ⴞ 1.8%, 98.0% ⴞ 1.5%, 86.7% ⴞ 3.2%, and 90.7% ⴞ 2.9%, respectively. NP group had more myocardial infarction and angina than the BP group, but was not statistically significant. Because of failed grafts at the early angiography, intervention was performed more frequently in NP group (p < 0.01). Conclusions. Our results of actuarial 7-year survival and the cumulative probability of event-free survival were at least comparable to the results of other similar studies using bilateral ITA. The freedom from angina appeared to be better than in the previous study. Overall our study supports the continued use of this method of ITA grafting.

I

nary artery in 39.6% of patients; the right ITA was anastomosed to the LAD in 37.7%, to the circumflex artery in 30.4%, and to the right coronary artery in 31.9% of patients. Excellent long-term (10 years) patency rates (about 90%) have been reported in cases of the left ITA anastomosed to the LAD [1–3], but few reports exist concerning the patency rate of the left or right ITA when directed to vessels other than the LAD [17–19]. We and other investigators [20 –24] have recently reported good long-term patency of in situ right ITA bypass through the transverse sinus for revascularization of the circumflex and diagonal arteries. The present series reports the intermediate-term results of the patients who underwent bilateral ITA grafting using the left ITA-to-LAD and right ITA-to-circumflex artery method.

mproved long-term survival and a reduction in late cardiac events have been documented in patients receiving a left internal thoracic artery (ITA) graft to the left anterior descending coronary artery (LAD) compared with patients revascularized with saphenous veins [1–3]. Controversy exists, however, about whether the use of bilateral ITA provides additional survival benefits [4 –12]. Long-term survival and freedom from angina and infarction after coronary artery bypass grafting (CABG) are related to the preoperative status of the patient, progression of the native coronary artery arteriosclerosis, the completeness of revascularization, technical factors during the operation, and subsequent early and late closure of the bypass grafts [13–16]. Studies of late results after bilateral ITA grafting are often confounded by the use of different grafting methods in both ITA grafts. In previous investigations, the bilateral ITA groups often included patients who had undergone different grafting methods [4, 5, 10]. In the report by Berreklouw and colleagues [10], although the left ITA was anastomosed to the LAD in the single ITA group, in the double ITA group, the left ITA was anastomosed to the LAD in 60.4% and to the circumflex coro-

Accepted for publication May 3, 2000. Address reprint requests to Dr Ura, Department of Cardiothoracic Surgery, St. George Hospital, Gray St, Kogarah NSW 2217 Australia; e-mail: [email protected].

© 2000 by The Society of Thoracic Surgeons Published by Elsevier Science Inc

(Ann Thorac Surg 2000;70:1991– 6) © 2000 by The Society of Thoracic Surgeons

Patients and Methods After gaining approval by the Ethics Committee and the Internal Review Board, the first consecutive 203 patients were studied who had undergone isolated CABG with left ITA anastomosed to the LAD and right ITA to major branches of the circumflex artery at Kumamoto Central Hospital. There were 164 men and 39 women with a mean age of 62.6 ⫾ 9.1 years (13 to 78 years). Operations were performed between September 1989 and December 1997. Patients with free ITAs, combined procedures, 0003-4975/00/$20.00 PII S0003-4975(00)01697-0

1992

URA ET AL LATE RESULTS OF LEFT ITA–LAD AND RIGHT ITA–CX

Ann Thorac Surg 2000;70:1991– 6

Postoperative Angiography

Table 1. Preoperative Characteristics Characteristics

Data 62.6 ⫾ 9.1 (13–78)

Mean age Age ⬍ 60 ⬍ 60 to ⬍ 70 ⬍ 70 Gender (male:female) Hypertension Diabetes mellitus Hyperlipidemia Chronic renal failure (dialysis) No. of diseased vessels 2 3 LMT LMT ⫹ 1 LMT ⫹ 2 LMT ⫹ 3 Old myocardial infarction EF ⬍40 LMT ⫽ left main trunk disease;

62 94 47 164:39 93 (45.8%) 44 (21.7%) 56 (27.6%) 1 (0.5%)

To evaluate the early patency rate, postoperative angiography was performed 2 to 3 weeks after operation. All ITA grafts were evaluated for occlusion, development of string sign, or presence of significant stenosis (flow limiting or stenosis of more than 50% of the vessel diameter at any point along the body of the graft or at any anastomoses). Only grafts of good caliber, with no occlusion, string sign, or significant stenosis were considered patent.

Late Follow-up Late follow-up information was collected from the patients’ most recent clinical visits, supported by telephone interviews with family physicians or patients. If patients had suffered late ischemic-related events, meticulous inquiry into angiographic data and hospital records was carried out to gain detailed information. Follow-up was performed between November 1998 and March 1999. Completeness of the follow-up was 100%.

32 93 21 7 21 29 96 (47.3%) 7 (3.4%)

Statistical Methods

EF ⫽ ejection fraction.

other arterial grafts including gastroepiploic arteries (GEAs), or reoperations were excluded from the present study. Patients who had received a right ITA-to-diagonal artery graft were also excluded. Patients’ characteristics are summarized in Table 1.

Operative Procedures This group underwent a uniform operative technique, in which the left ITA was singly or sequentially anastomosed to the LAD. The in situ right ITA was routed through the transverse sinus and anastomosed to the major branches of the circumflex artery as previously described [24]. The ITAs were dissected conventionally as a musculofascial pedicle in this group. Semiskeletonizing or skeletonizing techniques were not used. As can be seen in Table 2, the in situ right ITA through the transverse sinus was used to revascularize mostly the posterolateral wall and the left ITA, the anterolateral wall of the left ventricle. In 192 patients (94.6%) the in situ left ITA was anastomosed to the LAD alone, using standard methods. Supplemental saphenous vein grafts were used in 176 patients (86.7%) mainly to the diagonal and right coronary arteries.

Data are presented as mean and 95% confidence intervals. Survival curves were estimated using the KaplanMeier method. Differences in survival rates between the two groups were analyzed using the log rank test. Analyzed late results included all late deaths, late cardiac deaths, recurrences of angina, myocardial infarction, percutaneous transluminal coronary angioplasties, and reoperations. Univariate testing of variables was performed with the Fisher’s exact test for discrete variable comparisons between two groups. The Mann-Whitney U test was used for continuous variable comparisons. All analyses were performed using commercial statistical software (SAS version 6.12, Cary, NC).

Results Early Results There were two noncardiac hospital deaths (0.99%). A 70-year-old man who suffered a stroke and had mediastinitis, died postoperatively of sepsis. The other death occurred in a 69-year-old woman with a history of bronchial asthma: on the 49th postoperative day, a local anesthetic used during the treatment of a leg wound induced a severe asthmatic attack necessitating ventilator support, which was subsequently complicated by pneu-

Table 2. ITA Destination

RITA LITA

Intermediate Branch

Obtuse Marginal Branch

Posterolateral Artery

39 0

79 0

85 0

ITA ⫽ internal thoracic artery;

LAD ⫽ left anterior descending artery.

LAD 0 192 (LAD–LAD sequential 3)

Diagonal LAD (sequential)

Total

0 11

203 203

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URA ET AL LATE RESULTS OF LEFT ITA–LAD AND RIGHT ITA–CX

Table 3. Late Results Late Events Myocardial infarction (2)

PTCA (20) Before hospital discharge

After discharge

Recurrent angina (13)a

Cause

Lesion

New stenosis in the native artery New stenosis distal to the patent graft

RCA (1)

Graft failure (4)

LITA (3) SVG (1) RCA (1)

LAD (1)

Redisual stenosis distal to the 1 patent graft New stenosis in the native artery (9) Graft failure (6)

New stenosis in the native artery (6) Graft failure (5)

RCA (8) OM (1) LITA (1) RITA (3) SVG (2) RCA (5) OM (1) RITA (3) SVG (2)

a

Of 13 patients with recurrent angina, 11 patients underwent coronary angiography. ITA ⫽ internal thoracic artery; OM ⫽ obtuse marginal artery; RCA ⫽ right coronary artery; SVG ⫽ saphenous vein graft.

monia. She died of septic shock 61 days after the operation. Postoperative intraaortic balloon pumps were required in 3 patients (1.5%) and sustained ventricular tachycardia or fibrillation occurred in 3 patients (1.5%). There were 7 patients sustained a stroke (3.4%). In spite of the relatively higher frequency of diabetes mellitus in this group (44 patients; 21.7%), there were only three cases of mediastinitis (1.5%)

Late Results Twelve patients died during the follow-up period (mean, 52 months): 3 from heart failure (ischemic cardiomyopathy), 2 from malignancy, 2 from pneumonia, 3 from cerebrovascular accidents, and 1 each from motor vehicle accident and sudden death. No late deaths were related to postoperative in-hospital complications. All 3 patients who died from heart failure had been suffering from ischemic heart failure with ejection fraction of less than 30%. Early and late angiography revealed all grafts, including bilateral ITA, to have been patent in these patients. Two patients suffered myocardial infarction during the

1993

follow-up period and of 13 patients with recurrent angina, 11 patients underwent coronary angiography. The detail is summarized in Table 3. Twenty patients underwent percutaneous transluminal coronary angioplasty (PTCA) after the operation during the follow-up period, with 5 requiring the procedure before hospital discharge, and 15 afterward. Of three dysfunctional right ITA, which were related to late PTCA, angiography on discharge revealed two right ITAs to be already dysfunctional (1 occluded and 1 stringlike artery), and the other patient, a 13-year-old girl with aortitis, suffered recurrent angina caused by newly developed 90% stenosis in the midportion of the right ITA. This patient underwent CABG for a second time after unsuccessful PTCA, and was the only individual to undergo reintervention due to right ITA failure, which occurred after discharge. In the remaining 1 patient, PTCA was performed on the significant stenosis in the LAD distal to the anastomotic site of the left ITA, which angiography at discharge had revealed to be patent (Table 3.). Only 1 patient underwent repeat CABG: the above mentioned 13-year-old girl with aortitis.

Actuarial Curves According to the Kaplan-Meier Method Actuarial 7-year survival in all patients was 89.3% ⫾ 3.1% (including hospital deaths). The cumulative probability of event-free survival at 7 years was 98.0% ⫾ 1.5% for cardiac death, 96.6% ⫾ 1.8% for myocardial infarction, 86.7% ⫾ 3.2% for intervention (angioplasty), and 90.7% ⫾ 2.9% for angina pectoris (Table 4 and Figs 1 to 5).

Actuarial Curves in the Groups According to the Patency of Internal Thoracic Artery Grafts To further analyze the true effect of bilateral ITA grafting, the patients were grouped according to the patency of ITA grafts as demonstrated by early postoperative angiography. Early postoperative angiography was performed 2 to 3 weeks after operation in 197 patients. The study was not performed in 6 patients due to severe arteriosclerosis of the ascending aorta in 3, chronic renal failure in 1, and poor postoperative course (hospital death) in 2 patients. Of 197 patients who underwent early examination, data were not available in 6 individuals. Thus, finally, among the remaining 191 patients, there were 10 patients with dysfunctional right ITA (3 oc-

Table 4. Overall Patient Survival and Freedom From Ischemia-Related Events at 7 Years After Operation

Survival Cardiac death Myocardial infarction Intervention Angina

All Patients (n ⫽ 203)

BP Group (n ⫽ 168)

NP Group (n ⫽ 23)

89.3 ⫾ 3.1 96.6 ⫾ 1.8 98.0 ⫾ 1.5 86.7 ⫾ 3.2 90.7 ⫾ 2.9

89.9 ⫾ 3.1 95.9 ⫾ 2.1 99.3 ⫾ 0.7 89.5 ⫾ 3.2 92.6 ⫾ 2.9

87.5 ⫾ 11.7 100.0 90.9 ⫾ 8.7 69.6 ⫾ 11.2 82.1 ⫾ 9.8

BP ⫽ both patent group, NP ⫽ not patent group.

Log-rank Test BP Group versus NP Group p p p p p

⫽ ⫽ ⫽ ⬍ ⫽

0.81 0.45 0.09 0.01 0.21

Results by Bergsma and associates [11] 91.1 ... 97.3 95.4 85.4

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Fig 1. Actuarial survival curve including hospital deaths in all patients, BP group and NP group up to 7 years after operation.

cluded, 6 stringlike, 1 stenosis), 12 with dysfunctional left ITA (7 occluded, 2 stringlike, 3 stenotic), and 1 patient with both ITAs stringlike. These patients were classified as the Not patent (NP) group and the remaining 168 whose both ITAs showed complete patency were classified as the Both patent (BP) group. Although not demonstrated, there were no significant difference between two groups in frequency of various preoperative risk factors such as gender, diabetes, and age Actuarial 7-year survival and freedom from cardiac death, myocardial infarction, intervention, and angina pectoris at 7 years are summarized in Table 4. The patient survival rate is illustrated in Figure 1. The 7-year survival figures show no differences between the groups. Freedom from cardiac death did not reveal any differences between the groups: 95.9% ⫾ 2.1% for the BP group and

Fig 2. Actuarial freedom from cardiac death in all patients, BP group and NP group up to 7 years after operation.

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Fig 3. Actuarial freedom from myocardial infarction in all patients, BP group and NP group up to 7 years after operation. A trend toward reduced freedom from myocardial infarction in the NP group was noted, but was not statistically significant (p ⫽ 0.09).

100% for NP group (Fig 2). The NP group had more myocardial infarction and angina than the NP group, but was not statistically significant (p ⫽ 0.09, p ⫽ 0.21) (Figs. 3 and 4). Because of failed graft revealed by early angiography, intervention was performed more frequently in the NP group (p ⬍ 0.01) (Fig 5).

Ischemic-Related Events in the Left Coronary Artery System in Patients With Both Internal Thoracic Artery Grafts Patent Of the 168 patients with both ITAs patent, ischemicrelated events in the left coronary artery system occurred in 8 patients during the follow-up period. Five patients had recurrent angina, and in 2 angina was

Fig 4. Actuarial freedom from angina pectoris in all patients, BP group and NP group up to 7 years after operation. A trend toward reduced freedom from angina pectoris in the NP group was noted, but was not statistically significant (p ⫽ 0.21).

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Fig 5. Actuarial freedom from intervention in all patients, BP group and NP group up to 7 years after operation. Because of failed graft revealed by early angiography, intervention was performed more frequently in the NP group (p ⬍ 0.01).

related to a new lesion developed in the coronary artery distal to the patent graft (left ITA to LAD in 1, and saphenous vein to circumflex artery in 1). In the remaining 3 patients, angina was caused by late graft closure or stenosis (saphenous vein to diagonal artery in 2 and right ITA to circumflex artery in 1). Thus, late right ITA closure was the lesion responsible in only 1 patient in this group. Myocardial infarction occurred in 1 of these patients, but was not fatal. There were three cardiac deaths in this group. All 3 patients had been suffering from ischemic heart failure in spite of the presence of all grafts being patent, including bilateral ITA as mentioned above.

Comment Controversy exists about whether the use of the bilateral ITA provides additional survival benefits [4 –12]. In a large scale prospective study comparing single to multiple ITA grafts, routine multiple ITA grafting was revealed to result in negligible survival benefits beyond that attributable to a single ITA during an average 4-year follow-up [4]. Recently published data suggest that bilateral ITA grafting is an independent predictor of lower rates of recurrence of angina, late myocardial infarction, and the composite end point of any cardiac-related event [12]. Long-term survival and freedom from angina and infarction after CABG are related to many variables, such as the preoperative status of the patient, the progression of disease in the native coronary artery, the completeness of revascularization, and late closure of bypass grafts [13–16]. We speculated that the method of grafting bilateral ITA could be a strong confounding factor in a study of late results. In previous investigations, the bilateral ITA group had often undergone a range of different grafting methods. In the report by Berreklouw and colleagues 10, although the left ITA was anastomosed to the LAD in the

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single ITA group, in the double ITA group, the left ITA was anastomosed to the LAD in 60.4% and to the circumflex coronary artery in 39.6% of patients. The right ITA was anastomosed to the LAD in 37.7%, to the circumflex artery in 30.4%, and to the right coronary artery in 31.9% of patients [10]. Dietl [17] and Chow [18] and their colleagues reported an increased rate of right ITA graft failure when it was used to bypass the right coronary and posterior descending arteries. Including such patients using right ITA on the diagonal branches or right coronary artery in studies of this nature might detract from results that would otherwise demonstrate the beneficial long-term effect of bilateral ITA grafting. Recently, Schmidt and associates [9] demonstrated a significant improvement in the survival rates of patients receiving both ITA bypass grafts to left-sided arteries compared to patients with left ITA grafts to the LAD and right ITA grafts to the right coronary artery. The method of ITA grafting as well as the use of bilateral ITA appeared to influence the long-term outcomes in patients after CABG. In contrast to the abundant reports describing the excellent long-term patency rates of the left ITA anastomosed to the LAD [1–3], few reports exist concerning the patency rate of the left or right ITA directed to vessels other than the LAD [17–19]. Recently, we and other investigators [20 –22] have reported the good long-term patency of in situ right ITA bypass through the transverse sinus for revascularization of the circumflex and diagonal arteries. Contrary to the common supposition that long-term patency rate would be compromised by routing the right ITA through the transverse sinus [19], our study demonstrates that cumulative patency rates at 6 years were 89.3% for right and 94.5% for left ITAs, the difference not reaching statistical significance [22]. A better survival benefit would be expected by locating both ITA grafts in areas with proven long-term patency. Our results of actuarial 7-year survival and the cumulative probability of event-free survival for ischemicrelated events at 7 years were at least comparable to the results of other similar studies using bilateral ITA [4 –12], including the very successful results recently published by Bergsma and colleagues [11]. The event-free survival rate for intervention in our study population was relatively lower than the results of other studies. This may be because aggressive and prophylactic PTCA was performed on significant lesions detected by early postoperative angiography, which was performed in almost all patients whether or not they had symptoms. On the other hand, freedom from angina appeared to be better than reported in previous studies. The completeness of revascularization (patency of the conduit) has been shown to be related to long-term survival and relief from angina and infarction [13, 14]. The frequency with which angina returned correlated significantly with the degree of patency of the grafts [15]. To clarify the true influence of bilateral ITA grafting, we included early angiographic data in the analysis of late results. Patients with both ITAs patent had low recurrence of all ischemic-related events and good long-term

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survival even when compared to the excellent results of Bergsma and associates [11], demonstrating the effectiveness of our method of bilateral ITA grafting. Late follow-up revealed that late right ITA closure was the lesion responsible for ischemic events in the left coronary artery system in only 1 patient with aortitis among 168 patients whose ITAs showed complete patency. Because we performed strict selection of patent graft (categorizing all stringlike ITAs as dysfunctional ITAs), similar good longterm results can be expected in patients with grafts categorized in this study as dysfunctional. Not all ischemic events would be avoidable even if multiple arterial grafts with superior patency were used. Some ischemic events can occur due to progression of native coronary artery disease in areas distal to the graft anastomotic site, or other nonbypassed branches of the coronary artery [16]. Most of the survival benefits resulting from ITA grafting may be provided by a single ITA, especially in the case of ITA grafts to the LAD; further use of the right ITA may be associated with relatively smaller changes in long-term survival [12]. However, when combined with the standard method of grafting the LAD with the left ITA, directing the right ITA to the most important branches of the circumflex artery is likely to be most beneficial [22]. Although Tatoulis and colleagues [25] noted they often found that the pedicled right ITA graft was limiting in not being able to reach the more distal circumflex marginal arteries, in our experience, in situ right ITA is, in most cases, able to reach most branches of the major circumflex artery if the right ITA is harvested as proximally as possible and by arranging the shortest route. Reduced recurrence of ischemic events would be expected by directing both ITA grafts to the left ventricle using methods with proven superior long-term patency. In conclusion, long-term outcomes in patients with in situ double ITA grafts using a method with proven good long-term patency (left ITA to LAD and right ITA to circumflex artery) were good, with low recurrence of all ischemic-related events and good long-term survival. Our results support the continued use of this method of ITA grafting.

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