Should Bilateral Internal Thoracic Artery Grafting Be Used in Elderly Patients Undergoing Coronary Artery Bypass Grafting?Clinical Perspective
Background—Although bilateral internal thoracic artery grafting is associated with improved survival, the use of this technique in the elderly is controversial because of their increased surgical risk and shorter life expectancy. The purpose of this study was to evaluate the effect of age on outcome of patients undergoing bilateral internal thoracic artery grafting.
Methods and Results—Between 1996 and 2001, 1714 consecutive patients underwent skeletonized bilateral internal thoracic artery grafting, of whom 748 were ≤65 years of age, 688 were between 65 and 75 years of age, and 278 were ≥75 years of age. Operative mortality of the 3 age groups (1.2%, 4.1%, and 5.8%, respectively) was lower than the logistic EuroSCORE predicted mortality (3.9%, 6.5%, and 9.3%, respectively; P<0.001). There were no significant differences among the groups in occurrence of sternal infection (1.3%, 2.6%, and 1.4%, respectively; P=0.171). Mean follow-up was 11.5 years. Kaplan–Meier 10-year survival for patients ≤65, 65 to 75, and >75 years of age was 85%, 65%, and 40%, respectively (P<0.001). These rates were better than the corresponding predicted Charlson Comorbidity Index survival rates (68%, 37%, and 20%, respectively; P<0.001 for all age groups), approaching survival of the sex- and age-matched general population (90%, 70%, and 41%, respectively). Age ≤65 years (hazard ratio, 0.232; 95% confidence interval, 0.188–0.288) and age 65 to 75 years (hazard ratio, 0.499; 95% confidence interval, 0.414–0.602) were independent predictors of improved survival (Cox model).
Conclusions—Bilateral internal thoracic artery grafting should be considered in patients >65 years of age because of the significant survival benefit obtained with this surgical technique with no additional risk of sternal wound infection related to age.
With the expansion in life expectancy, an increasing number of elderly patients are referred for coronary artery bypass grafting (CABG), and the current trend is to use the internal thoracic artery (ITA) in all patients who undergo surgery, including the older ones. The current conventional and most commonly used operative procedure for myocardial revascularization includes 1 pedicled ITA together with 1 or more vein grafts.1,2 Vein graft exhaustion is a major drawback of CABG, and surgical techniques of complete arterial myocardial revascularization without veins have been attempted. Two popular techniques for achieving this goal are bilateral and sequential ITA grafting.3
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When the ITA is dissected as a skeletonized artery,4 it becomes longer and its spontaneous blood flow is probably greater5,6 than that of the pedicled ITA, allowing the use of both ITAs to almost all coronary territories that require bypass. In many patients, no additional vein grafts are required.7 Another advantage of using the ITA as a skeletonized artery is the preservation of collateral blood supply to the sternum,8 which enables more rapid healing and decreases the risk of infection.9,10 The bilateral skeletonized ITA technique was adapted in our service as the preferred method for myocardial revascularization.11,12 The purpose of the present report is to analyze the impact of age on the outcome of the first 1714 consecutive patients in whom we used this surgical technique.
From 1996 to 2001, 1714 consecutive patients underwent myocardial revascularization with bilateral ITAs (BITAs) that were dissected as skeletonized arteries.12 They constituted 73% of the 2346 isolated CABG procedures for multivessel disease performed in the Tel Aviv Sourasky Medical Center during this period. Preoperative and operative patient data were collected from the hospital medical records after receipt of approval from the Institutional Review Board. To evaluate the effect of age on early and long-term outcome, patients were stratified into 3 age groups: ≤65 years of age, between 65 and 75 years of age, and ≥75 years of age. To evaluate the operative-period effect, patients were stratified according to their operative date into 2 groups, early (1996–1999) and late (2000–2001).
Expected operative mortality was calculated with the logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation)13 and compared with the observed early mortality. Expected mid- and long-term mortality without operation was calculated with the Charlson Comorbidity Index14–16 (Table 1) and compared with the expected survival of the Israeli population of the same age and sex17 and with the Kaplan–Meier actuarial survival. Follow-up was obtained by use of the Israeli National Registry database and a telephone questionnaire.
Operations were performed with standard cardiopulmonary bypass or off-pump coronary artery bypass. Myocardial preservation during cardiopulmonary bypass involved intermittent, antegrade, or retrograde blood cardioplegia (30°C-32°C). Coronary stabilization during off-pump coronary artery bypass was facilitated with CTS stabilizers (CardioThoracic Systems, Cupertino, CA) or the Octopus system (Medtronic, Minneapolis, MN). ITAs were mobilized from the chest wall as skeletonized vessels. In 1515 of the cases,3 BITAs were used to graft the left coronary system, that is, the myocardial territory supplied by the left anterior descending and circumflex arteries. Left-sided revascularization was achieved with 2 basic arrangements: A free ITA (in most cases the right ITA [RITA]) attached proximally end-to-side on the in situ ITA (primarily the left ITA) in a T-graft configuration (composite T-graft) and an in situ BITA with an ante-aortic crossover RITA. The choice of configuration was determined by previously detailed technical considerations.18 The type of conduit selected for right coronary artery grafting was not related to the configuration of the ITAs. Our strategy was to use RITAs, right gastroepiploic arteries, and radial arteries as grafts to the right coronary artery branches only in the presence of a significant stenosis (ie, >80%).19 When the right coronary artery system was unsuitable for arterial grafting, such as in cases with a potential for high competitive flow in the right coronary artery, we selected saphenous vein grafts as the conduit for revascularization of the right coronary artery. To decrease the risk of spasm of the arterial grafts, all patients were treated with a high-dose intravenous infusion of isosorbide dinitrate (Isoket, 4–20 mg/h) during the first 48 hours postoperatively. Calcium channel blockers (diltiazem; 90–180 mg/d orally) were given to patients operated on with right gastroepiploic arteries or radial arteries from the second postoperative day for at least 3 months.12
Definition of Terms and Data Collection
Patient data were analyzed according to American College of Cardiology/American Heart Association clinical data standards.20 Chronic renal failure was diagnosed if the creatinine level exceeded 1.8 mg/dL. Peripheral vascular disease included all symptomatic and asymptomatic extracoronary arteriopathy. Cerebrovascular disease included past history of any cerebrovascular event with or without permanent neurological damage. Our definition of emergency operation is based on the Society of Thoracic Surgeons guidelines and includes patients operated on within 24 hours of cardiac catheterization, with ongoing angina, acute evolving myocardial infarction, pulmonary edema, or cardiogenic shock.21 Patients who needed emergency surgery and were not stabilized after intra-aortic balloon counterpulsation were usually operated on with 1 ITA combined with saphenous vein grafts and therefore were not included (Table 2). A perioperative myocardial infarction was defined by the appearance of new Q waves in the ECG associated with elevated levels of creatine phosphokinase-MB fraction >50 mU/mL. A cerebrovascular accident was defined as a new permanent neurological deficit and computed tomographic evidence of cerebral infarction. Deep sternal infection was defined as the sum of deep infection and late dehiscence that required sternectomy.
Data are expressed as mean±SD or as a proportion. The χ2 test and 2-sample t tests were used to compare discrete and continuous variables, respectively. Multivariable logistic regression analysis was used to predict early mortality and early morbidity events by various risk factors. Odds ratios (ORs) and 95% confidence intervals (CIs) are provided. Postoperative survival of each age group was expressed by the Kaplan–Meier method, and survival curves were compared by the log-rank test. Cox proportional hazard model was used to evaluate the influence of preoperative variables (sex, period of surgery, age group, diabetes mellitus, chronic obstructive pulmonary disease [COPD], congestive heart failure, chronic renal failure, peripheral vascular disease, recent myocardial infarction, old myocardial infarction, acute myocardial infarction, unstable angina, preoperative intra-aortic balloon pump support, emergency operation, ejection fraction ≤25%, number of vessels diseased, left main disease), and operative data (repeat operation, off-pump coronary artery bypass, number of grafts, bypass time, aortic cross-clamp time, composite T-graft), on late and overall mortality. A Cox model was used to compare adjusted survival between the various age groups after controlling for differences between groups in preoperative and operative characteristics. Results of Cox analysis were expressed as hazard ratios (HRs) and 95% CIs.
To present the expected annual survival of the general population based on our sample of patients, we used the 2005–2009 complete life tables published by the National Central Bureau of Statistics17 to calculate the annual survival for each patient according to age and sex for 15 years. In addition, we used the Charlson index formulation to calculate the expected 10-year survival of patients in the present study assuming no surgery was performed. The Charlson index formulation estimates survival of people according to their age and certain comorbidities (Charlson index). It was validated for 10-year survival.14 For presentation purposes only, we extended the Charlson index formulation principle to calculate the estimated annual survival of each patient according to age and Charlson index to 15 years. The Charlson index formulation uses a 10-year survival of a 40-year-old person with no comorbidities (98%) as the baseline survival for its calculations. We used the relative annual survival of a 40-year-old person taken from the Israeli complete life tables17 as the baseline survival to calculate the annual estimated survival of each patient without surgery. However, because the Charlson index formulation was validated for 10-year survival only, we performed a formal statistical comparison of survival between the expected general population survival, observed actuarial survival, and estimated survival of the patients if no operation had been performed, at 10 years only, using a 1-sample t test.
Statistical analysis was performed with SPSS for Windows version 19. Statistical significance was considered at P<0.05.
Table 2 compares patients’ preoperative and operative characteristics with those of atients with multivessel disease operated on during the study period with a single ITA. Patients’ preoperative characteristics by age groups are presented in Table 3. Patients’ characteristics by operative period are presented in Table 4. Operative mortality of the 3 age groups (1.2%, 4.1%, and 5.8%) was lower than the logistic EuroSCORE-predicted mortality (3.9%, 6.5%, and 9.3%, respectively; P<0.001). COPD (OR, 3.145; 95% CI, 1.402–7.042; P=0.005), preoperative old myocardial infarction (OR, 1.990; 95% CI, 1.089–3.603; P=0.025) or acute myocardial infarction (OR, 2.915; 95% CI, 1.570–5.405; P=0.001), emergency operation (OR, 3.39; 95% CI, 1.855–6.211; P<0.001), and ejection fraction ≤25% (OR, 3.47; 95% CI, 1.036–11.627; P=0.044) were independent predictors of increased operative mortality. Age ≤65 years was associated with reduced operative mortality (OR, 0.236; 95% CI, 0.098–0.566; P=0.001). Sternal infection occurred in 32 patients (1.9%; Table 5). Increased prevalence of sternal complications was observed in patients with COPD (11.3%, P<0.001), repeat operation (9.5%, P<0.001), peripheral vascular disease (3.5%, P=0.004), diabetes mellitus (3.4%; P=0.001) and patients operated on between 1996 and 1999 (early period, 2.4%; P=0.001). Repeat operation (OR, 6.289; 95% CI, 1.945–20.408; P=0.002), COPD (OR, 9.524; 95% CI, 4.255–20.276; P<0.001), peripheral vascular disease (OR, 2.155; 95% CI, 1.036–4.484; P=0.04), diabetes mellitus (OR, 3.472; 95% CI, 1.645–7.299; P=0.001), and early (1996–1999) operative period (OR, 8.835; 95% CI, 1.184–65.910; P=0.034) were identified as independent predictors of sternal wound infection.
Mean follow-up was 11.5 years. Kaplan–Meier 10-year survival for patients ≤65, 65 to 75, and >75 years of age was 85%, 65%, and 41%, respectively (P<0.001). These rates were better than the corresponding predicted Charlson Comorbidity Index survival rates (68%, 37%, and 20%, respectively,; P<0.001) for all age groups, approaching survival of sex- and age-matched general population (90%, 70%, and 40%, respectively; Figures 1 and 2). Predictors of decreased survival (Cox model; Table 6) were older age (Figure 3; P<0.001), congestive heart failure, diabetes mellitus, COPD, chronic renal failure, ejection fraction ≤25%, repeat operation, peripheral vascular disease, preoperative intra-aortic balloon pump support, and early operative period (Figure 4; P=0.004).
Surgical revascularization of the left anterior descending artery with the ITA in patients with multivessel disease is still the only proven method of improving event-free survival.22,23 ITA grafts, because of their resistance to atherosclerosis, have better long-term patency than saphenous vein grafts, and this improved patency of ITA grafts is believed to be responsible for the better survival and decreased recurrence of angina and need for reintervention when they are used to bypass the left anterior descending coronary artery.24
BITA grafting is associated with improved survival than single ITA and saphenous vein grafting.25 Besides improved survival, BITA patients had better event-free survival and reduced occurrence of reinterventions.25 Despite the improved long-term outcome, the application of this technique in the elderly remains controversial because of their shorter life expectancy and in view of the excellent survival benefit obtained with single ITA. In addition, BITA grafting was associated with increased risk of sternal dehiscence and sternal infection26–28 associated with the more extensive devascularization caused by harvesting 2 ITAs.29,30 In a later study by Lytle and associates,2 the number of patients >60 years of age who were operated on with BITA grafts was relatively small; however, BITA grafting improved survival of this subset of older patients compared with patients >60 years of age who underwent operation with a single ITA graft.
In the above and other series,31,32 extensive arterial grafting with BITAs was used preferentially in a selected group of young male nonobese, nondiabetic patients. Patients were preselected for BITA grafting according to their life expectancy, and only a few of the patients >70 years of age were offered the option of BITA grafting. The only large series (1467 patients) comparing BITA with single ITA grafting in elderly patients was reported by Galbut and associates.33,34 In their study, patients with BITAs had a lower hospital mortality rate (3.1%) than patients with a single ITA (6.4%), and the late survival (mean 43 months) was better as well (69.7% versus 60.7%, respectively).
Unlike the above reports, in the present series and that of Galbut and coworkers,33 old age was not a contraindication for BITA grafting. In the present study, complete arterial grafting with BITAs was the preferred method of myocardial revascularization for all age groups. During the study period, BITA grafting was performed in 61% of the patients referred for CABG, and 41% of them were ≥70 years of age.
Although the present cohort was a selected group of patients (Table 2), mortality and morbidity of patients ≥70 years of age in the present study (3.7%) compared favorably with mortality described in procedures in which a single ITA was used.1 In the report by Lytle and colleagues,2 the only morbid event that differed between the bilateral and single ITA groups was the difference in sternal wound complications (2.5% and 1.4%, respectively). Harvesting the ITA as a wide musculofascial pedicle with the aid of electrocautery was shown to devascularize sternal collateral blood supply and expose the sternum to increased risk of poor healing, dehiscence, and infection.30 The problem of poor healing caused by insufficient collateral blood supply may be more important in the elderly patient. The sternum of elderly patients is sometimes more fragile because of osteoporosis and suboptimal blood supply.
Collateral blood flow to the sternum can be significantly improved by using the skeletonization technique when harvesting ITAs for BITA grafting.4,5 This new technique of ITA harvesting was used in patients in the recently published Arterial Revascularisation Trial (ART).35 ART is an ongoing randomized, multicenter trial in which 3102 patients were randomized to receive either BITA or a single ITA during CABG, with a primary outcome of survival at 10 years. Currently, only 1-year follow-up is available.35 Perioperative mortality was similar between groups (1.2%), and 1-year survival was not significantly different between groups. Sternal wound reconstruction was higher in the BITA group (1.9%) than the single-ITA group (0.6%). The authors concluded that BITA grafting is feasible. They also stressed that these are only early data from a long-term trial, and follow-up will, in time, provide more definitive evidence on survival and morbidity.
The sternal wound reconstruction rate of the BITA group in ART is identical to the occurrence of sternal complications in our previous publication describing the routine use of skeletonized BITA grafting in a cohort of 1515 patients.3 Occurrence of sternal complications (deep infection and dehiscence) in that study in patients >70 years of age was not significantly different from that of younger patients, and old age was not found to be an independent predictor of sternal complications.
A larger cohort of patients with longer follow-up is described in the present report. Occurrence of sternal complications in the 3 age groups was similar (1.3%, 2.4%, and 1.4%, respectively, for ages ≤65, 66–75, and >75 years). The observed hospital mortality increased with increase in age (1.2%, 4.1%, and 5.8%, respectively, for the 3 age groups in the present report); however, it was significantly lower than the EuroSCORE-calculated mortality (3.7%, 8.1%, and 17.2%; P<0.001). Moreover, the actual 10-year survival (Kaplan–Meier) and risk-adjusted (Cox) survival estimates were significantly better than the calculated Charlson index 10-year survival for all age groups, which suggests a significant survival benefit with BITA grafting, especially in the older age groups (Figures 1 and 2), despite the fact that older age was associated with significantly decreased long-term survival.
In an effort to reduce the risk of sternal complications, we analyzed our long-term survival results and became more careful, in the later period, with patient selection for BITA grafting, especially with regard to diabetic patients with COPD, repeat operations, female sex, and obesity.3,12,18,36,37 The decreased prevalence of COPD and obese diabetic females in the later period may be an explanation for the decreased occurrence of sternal complications in that period.
This was a retrospective study, and potential long-term benefits of BITA for elderly patients cannot be demonstrated without comparing its outcome with that of CABG procedures that incorporated 1 ITA and other conduits, such as saphenous vein grafts or radial arteries. Postoperative angiograms and coronary computed tomography angiograms were available only for a small number of patients, mostly in symptomatic patients; therefore, they could not be included in this report.
In conclusion, the present study suggests that the survival benefit of BITA grafting for all age groups outweighs the early adverse effect of sternal wound complications. Occurrence of these complications can be reduced by selective use of BITA grafting in patients undergoing CABG procedures. Further studies are required to compare long-term outcomes of BITA versus single ITAs in elderly patients.
- Received July 15, 2012.
- Accepted April 26, 2013.
- © 2013 American Heart Association, Inc.
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Our study shows that long-term survival after bilateral internal thoracic artery (BITA) grafting with the skeletonization technique is good for all age groups (≤65, 65–75, >75 years), approaching survival of the sex- and age-matched general population. Despite significantly lower long-term survival in the older age group (>75 years), their survival benefit, compared with Charlson Comorbidity Index–predicted survival without surgery, was not lower than that of the younger age groups. In our opinion, BITA grafting should be considered in patients >65 years of age because of the significant survival benefit, with no increased risk of sternal infection. This observation supports increased adoption of BITA grafting in the elderly, who are beginning to constitute a large proportion of the patients referred today for coronary artery bypass grafting. A major concern of surgeons that discourages them from the use of BITA is postoperative sternal infection, especially in elderly patients, who have poor sternal blood supply. The present study showed that the risk of sternal infection was not increased in the older age group; thus, age alone should not preclude the use of BITA. This observation is probably related to better preservation of sternal collateral blood flow with the skeletonization technique. The reduction of sternal infection occurrence in the later period of our study (2000–2001) suggests that the use of BITA grafting should be selective and that this technique should not be used in patients with chronic obstructive pulmonary disease or in obese females who have diabetes mellitus.