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Archives of cardiovascular diseases
Volume 110, n° 12
pages 646-658 (décembre 2017)
Doi : 10.1016/j.acvd.2016.12.019
Received : 17 November 2016 ;  accepted : 22 December 2016
Is bilateral internal thoracic artery grafting a safe option for chronic dialysis patients?
Intérêt des pontages tout artériel avec les deux artères mammaires internes chez les patients dialysés chroniques
 

Giuseppe Gatti a, , Andrea Perrotti b, Antonio Fiore c, Eric Bergoend c, Sidney Chocron b, Jean-Paul Couetil c, Gianfranco Sinagra a, Aniello Pappalardo a
a Cardiovascular department, Ospedali Riuniti and university of Trieste, Trieste, Italy 
b Department of thoracic and cardiovascular surgery, university hospital Jean-Minjoz, 25000 Besançon, France 
c Department of cardiac and thoracic surgery, university hospital Henri-Mondor, Assistance publique–Hôpitaux de Paris, 94000 Créteil, France 

Corresponding author at: Cardiovascular department, division of cardiac surgery, Ospedale di Cattinara, via Pietro Valdoni, 7, 34148 Trieste, Italy.
Summary
Background

The use of bilateral internal thoracic artery (BITA) grafting has been proposed for dialysis patients with multivessel coronary artery disease, primarily because of hypothetical long-term survival benefits.

Aims

To investigate the outcome of BITA grafting in dialysis patients.

Methods

This was a retrospective analysis of the use of BITA grafting in 105 consecutive patients with end-stage renal failure on chronic dialysis in three European centres with extensive experience in BITA. Baseline patient characteristics, operative data, early postoperative complications and late survival were reviewed. Outcomes of patients from one of the three centres who underwent either BITA (n =40) or single internal thoracic artery (SITA) grafting (n =19) were also analysed; a one-to-one propensity score (PS)-matched analysis was performed.

Results

There were 19 (18.1%) hospital deaths. Despite differences in preoperative patient characteristics and surgical features, in each centre, hospital mortality was greater than the 75th percentile of expected operative risk (EuroSCORE II). Diseased ascending aorta and extracardiac arteriopathy were found to be predictors of hospital death (odds ratio 9.7; P =0.006) and complicated hospital course (odds ratio 2.54; P =0.035), respectively. The 7-year non-parametric estimates of freedom from all-cause death and cardiac or cerebrovascular death were 59% (95% confidence interval: 52.3–65.7%) and 75.6% (95% confidence interval: 71.2–80%), respectively. There were no significant differences in early and late outcomes between BITA and SITA PS-matched groups.

Conclusions

BITA grafting remains a risky operation for chronic dialysis patients, even when performed routinely. No long-term survival benefits for the use of BITA versus SITA were proven.

The full text of this article is available in PDF format.
Résumé
Contexte

L’utilisation de deux artères mammaires interne (BITA) a été proposée pour revasculariser les patients dialysés atteints d’une maladie coronarienne avec atteinte bi- ou tri-tronculaire, principalement en raison des avantages supposés de survie à long terme.

Objectifs

Évaluer le résultat de l’utilisation des 2 artères mammaires internes chez les patients dialysés chronique.

Méthodes

Étude rétrospective de l’utilisation des deux artères mammaire internes chez 105 patients consécutifs dialysés chronique dans trois centres européens ayant une importante expérience des BITA. Les caractéristiques de base des patients, les données peropératoires, les complications postopératoires et la survie ont été examinées. Les résultats des patients provenant de l’un des trois centres qui ont bénéficié soit d’un BITA (n =40), soit des pontages avec une seule artère mammaire interne (SITA) (n =19) ont également été analysés ; une analyse de score de propension (SP) a été effectuée.

Résultats

Il y a eu 19 décès intrahospitaliers (18,1 %). Malgré les différences dans les caractéristiques préopératoires des patients et les différentes techniques chirurgicales utilisées dans chaque centre, la mortalité hospitalière était supérieure au 75e percentile du risque opérationnel attendu (EuroSCORE II). La présence d’une aorte ascendante calcifiée et l’artériopathie périphérique étaient des prédicteurs de la mortalité hospitalière (Odds Ratio 9,7 ; p =0,006) et des complications postopératoire (Odds Ratio 2,54; p =0,035). Les estimations non paramétriques à 7 ans de l’absence de toutes causes de décès, et des décès cardiaques ou cérébrovasculaires étaient de 59 % (52,3–65,7 %) et de 75,6 % (71,2–80 %), respectivement. Il n’y avait pas de différence significative entre les résultats à court et à long termes entre les groupes BITA et SITA SP-appariés.

Conclusions

L’utilisation de BITA reste une option risquée pour les patients atteints de dialyse chronique, même lorsqu’ils sont exécutés de façon routinière. Aucun bénéfice de survie à long terme pour l’utilisation de BITA par rapport à SITA n’a été prouvé.

The full text of this article is available in PDF format.

Keywords : Arterial graft, Coronary artery bypass graft, Dialysis, Quality improvement, Renal failure, Survival

Mots clés : Greffons artériels, Pontage aorto-coronaire, Dialyse

Abbreviations : BITA, CI, EuroSCORE II, HR, ITA, OR, PS, SITA


Background

The use of arterial grafts, primarily the internal thoracic artery (ITA), has been recommended for patients with end-stage renal failure on chronic dialysis [1, 2, 3, 4]. At least on a speculative basis, higher long-term patency rates of arterial versus venous coronary grafts could give survival benefits to these patients with high early operative risk and poor late outcomes. To date, however, there is no clear evidence that the use of two or more arterial grafts might improve survival in dialysis patients, despite a number of authors having shown best outcomes, with respect to the use of venous grafts alone, when an in situ ITA was adopted to bypass the left anterior descending coronary artery [1].

Over the past few years, several investigators have emphasized that the use of bilateral ITA (BITA) grafting for coronary revascularization may give survival benefits even in difficult subsets of patients, such as insulin-dependent patients with diabetes [5, 6], octogenarians [7] and patients with severe renal impairment [3]. There are only a few reports on the use of BITA grafting in dialysis patients [2, 3, 4]. Consequently, any hypothetical benefit from BITA use remains a controversial issue.

In the present study, we reviewed the results of BITA grafting in chronic dialysis patients in three European surgical institutions with extensive experience of BITA use. The primary endpoints were early (hospital) and late survival.

Methods

A total of 105 consecutive patients with multivessel coronary artery disease and end-stage renal failure on chronic dialysis were operated on in three European centres — the department of thoracic and cardiovascular surgery of the university hospital Jean-Minjoz of Besançon, France (23 patients, group A); the department of cardiac and thoracic surgery of the university hospital Henri-Mondor of Créteil, France (42 patients, group B); the cardiovascular department of the Azienda Ospedaliero-Universitaria Ospedali Riuniti of Trieste, Italy (40 patients, group C) — during three different periods, 2006–2015, 2011–2015 and 1999–2015, respectively. Baseline characteristics of patients, operative data, early postoperative complications and late survival were analysed retrospectively.

In addition, in the cardiovascular department of Trieste, the outcomes of patients who underwent BITA grafting (group C) were compared with a consecutive series of 19 dialysis patients with multivessel coronary artery disease who underwent single ITA (SITA) grafting (group D) during the same period. No dialysis patients underwent SITA grafting in the two French centres during the corresponding study periods.

Unless otherwise stated, definitions of preoperative clinical variables and postoperative complications were those used for the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) [8] and for the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG registry) [9], respectively. The risk profile for each patient was calculated according to EuroSCORE II.

To evaluate the suitability of both ITAs to be used as coronary grafts, all patients underwent bilateral selective angiography of the subclavian artery during preoperative coronary angiography. Atherosclerosis of the ascending aorta was demonstrated, preoperatively, with a computed tomography scan; in groups C and D, it was confirmed using an epiaortic ultrasonography scan, which was performed intraoperatively in every patient [10]. All diabetics were treated during the operation, and then in intensive care unit, with a continuous intravenous insulin infusion. Prophylactic antibiotics were administered before surgical incision; either a first- or second-generation cephalosporin was chosen. Vancomycin was used if there was a severe allergy to β-lactam antibiotics.

For each centre, all perioperative data were prospectively recorded for every patient in a computerized data registry. An up-to-date clinical follow-up was obtained by a telephone interview with the patients or their families. For this study, follow-up closed on 1st March 2016. Approval to conduct the study was acquired from the Hospital Ethics Committee of each centre, based on retrospective data retrieval; the need for patients to provide their individual written consent was waived.

Surgical techniques

Surgery was carried out via a median sternotomy either with cardiopulmonary bypass, with or without cross-clamping of the aorta, or with the off-pump technique. When a period of myocardial ischaemia was used, myocardial protection was achieved with multidose warm blood cardioplegia delivered in antegrade mode (groups A and B), or with multidose cold blood cardioplegia delivered in both antegrade and retrograde mode (groups C and D). In group A, the use of either the off-pump or the on-pump technique depended on the surgeon's choice, except for diseased ascending aorta, where the off-pump (or beating heart on-pump) technique was used to avoid the risk of cracking atherosclerotic plaques with the aortic cross-clamp. In group B, only the on-pump technique was used, the off-pump and beating heart on-pump techniques being reserved for an unclampable ascending aorta because of extensive circumferential calcifications. In groups C and D, off-pump and beating heart on-pump techniques were adopted only in the presence of a diseased ascending aorta.

Both ITAs were harvested as skeletonized conduits. In all the patients of group A and in almost all the patients of group B, the right ITA was taken down and used as the second branch of a Y-graft with the in situ left ITA; the BITA grafting alone technique was used. In group C, both ITAs were used as in situ grafts when possible; the right ITA was preferentially directed to the left anterior descending coronary artery and the left ITA to the posterolateral cardiac wall (left-sided BITA grafting). Sometimes, the right ITA was taken down and used as a free graft from either the in situ left ITA (Y-graft) or (rarely) the roof of the proximal (aortic) end of a saphenous vein graft. In group D, the in situ left ITA was invariably directed to the left anterior descending coronary artery. In both groups (C and D), additional coronary bypasses, usually for the right coronary artery, were performed with saphenous vein grafts. The aortic anastomosis of every venous graft was performed during cross-clamping of the ascending aorta in the on-pump technique, and during aortic side-clamping in the off-pump technique.

Fluid management

The fluid management protocol for chronic dialysis patients undergoing coronary surgery was the same in the three centres: isovolemic dialysis the day immediately before surgery for stable patients; perioperative fluid containment; ultrafiltration during cardiopulmonary bypass for unstable and plethoric patients; and hypovolemic dialysis at the second or third postoperative day.

Statistical analysis

Data are expressed as numbers of patients and percentages or means±standard deviations with the range between the 25th and the 75th percentile. Study patients were divided into three groups (A, B and C) according to the centre where they were operated on. Perioperative clinical variables were compared using the χ 2-test or Fisher's exact test for dichotomous variables and Student's t -test or the Mann-Whitney U test for continuous variables, as appropriate. The Bonferroni method was used to correct for multiple comparisons. To find the predictors of early (hospital) death and a complicated hospital course, variables from the univariate analysis with a P -value<0.1 were entered into a multivariable analysis (binary logistic regression model). An odds ratio (OR) with a 95% confidence interval (CI) was given for each variable. The Cox proportional hazards model was used to determine the influence of patient characteristics and operative findings on survival. The hazard ratio (HR) and 95% CI were calculated for each variable. Non-parametric estimates and curves of freedom from all-cause death and cardiac or cerebrovascular death (including hospital mortality) were generated with the Kaplan-Meier method. Comparisons between survival curves were made using the Log-Rank test. As groups C and D differed significantly in the number of diseased coronary artery vessels, a multivariable analysis was performed using logistic regression, and a propensity score (PS) was calculated to estimate the probability of being assigned to either group. The area under the receiver-operating characteristic curve, with 95% CI, was used to represent the regression probabilities. This PS was calculated in a non-parsimonious way, including preoperative variables. The obtained PS was used for one-to-one PS matching. The calliper width chosen was 0.2 times the standard deviation of the PS. Adjusted risk estimates of all-cause death and cardiac or cerebrovascular death after surgery according to the use of BITA/SITA grafting were calculated with the Cox proportional hazards regression method. Estimates of 1- and 2-year survival were calculated with the Charlson Comorbidity Scoring System estimating prognosis for dialysis patients [11]. A P -value<0.05 was considered to be significant. Analyses were performed with SPSS for Windows, version 13.0 (SPSS Inc., Chicago, IL, USA).

Results
Intergroup differences

As expected, there were many intergroup differences in patients’ baseline characteristics, risk profiles and operative data (Table 1, Table 2). The prevalence of dialysis patients in group B (4.7%) was higher than in group A (1.3%) and group C (1.2%; P <0.0001).

Early (hospital) outcomes

There were 19 (18.1%) hospital deaths. Hospital mortality was twice that expected (mean EuroSCORE II 9.1±9.7%); in each centre, it was greater than the 75th percentile of the expected operative risk (Table 1, Table 3). The causes of death were: stroke (n =1), respiratory insufficiency (n =1), pneumonia (n =6), low cardiac output (n =4), intestinal necrosis (n =1), multiorgan failure (n =3) and sepsis (n =3). According to the multivariable analysis, the presence of a diseased ascending aorta was a predictor of early death (OR 9.7; P =0.006; Table 4). Prolonged invasive ventilation, pneumonia, low cardiac output, multiple blood transfusion and deep sternal wound infection were the most frequent major postoperative complications. In 54.3% of cases, the postoperative hospital course was complicated by one or more major complications (Table 3). Extracardiac arteriopathy was a predictor of a complicated hospital course according to the multivariable analysis (OR 2.54; P =0.035; Table 5). There were no intergroup differences in the rates of complications, except for more frequent use of blood transfusion and multiple blood transfusions in groups A and C (Table 3).

Late survival

A total of 86 patients were discharged home from the hospital. For these patients, the mean follow-up period was of 3.8±2.9 years (median 3.2 years). Overall, 325.5 patient-years were reviewed. The follow-up periods in group A (4.9±3.4 years) and group C (4.7±3.2 years) were longer than in group B (2.4±1.3 years; P =0.014 and 0.0013, respectively). During the follow-up period, there were 15 deaths: five (5.8%) cardiac or cerebrovascular deaths; and 10 (11.8%) non-cardiac or non-cerebrovascular deaths. The causes of death were: myocardial infarction (n =1), congestive heart failure (n =2), sudden death (n =2), pneumonia (n =3), sepsis (n =2), malignancy (n =2), multiorgan failure (n =2) and car accident (n =1). The non-parametric estimates of the 1-, 2-, 5- and 7-year freedom from all-cause death were 78.9% (95% CI: 74.9–82.9%), 76.4% (95% CI: 72.0–80.8%), 68.1% (95% CI: 62.9–73.3%) and 59% (95% CI: 52.3–65.7%), respectively (Figure 1A). Non-elective operative priority was a predictor of all-cause death during the follow-up period (HR 3.34; P =0.036; Table 6). The non-parametric estimates of 1-, 5- and 7-year freedom from cardiac or cerebrovascular death were 84.8% (95% CI: 81.3–88.3%), 75.6% (95% CI: 71.2–80.0%) and 75.6% (95% CI: 71.2–80.0%), respectively (Figure 1B). There were no intergroup differences in freedom from all-cause death and from cardiac or cerebrovascular deaths (Figure 1C and D).



Figure 1


Figure 1. 

Non-parametric curves of freedom from: all-cause death during the follow-up period in the overall series (A); cardiac or cerebrovascular (CV) death (including hospital mortality) during the follow-up period in the overall series (B); all-cause death during the follow-up period in the three groups separately (C); cardiac or cerebrovascular (CV) death (including hospital mortality) during the follow-up period in the three groups separately (C).

Zoom

BITA versus SITA grafting, unmatched and PS-matched patients

As expected, according to the policy of the Cardiovascular Department of Trieste (see Discussion), patients who underwent BITA grafting (group C) and those who underwent SITA grafting (group D) differed in the number of diseased coronary arteries (Appendix A). Consequently, the number of coronary anastomoses was higher and surgical times were longer in BITA patients compared with SITA patients (Appendix A). Postoperative bleeding and a complicated hospital course were more frequent after BITA grafting than after SITA grafting. However, these differences were not confirmed after PS-matched analysis (Appendix A). In group D, the non-parametric estimates of 1-, 5- and 7-year freedom from all-cause death were 89.5% (95% CI: 82.5–96.5%), 59.6% (95% CI: 47.7–71.5%) and 39.8% (95% CI: 27.5–52.1%), respectively (Figure 2A); the non-parametric estimates of 1-, 5- and 7-year freedom from cardiac or cerebrovascular deaths were 89.5% (95% CI: 82.5–96.5%), 59.6% (95% CI: 47.7–71.5%) and 44.7% (95% CI: 32.0–57.4%), respectively (Figure 2C). Between the BITA and SITA patients, no differences were found in the crude rates and the risk-adjusted estimates of all-cause death and cardiac or cerebrovascular deaths; in addition, no differences in late survival were found in PS-matched patients (Table 7, Figure 2B and D).



Figure 2


Figure 2. 

Bilateral internal thoracic artery (BITA) grafting (group C) versus single internal thoracic artery (SITA) grafting (group D). Non-parametric curves of freedom from: all-cause death during the follow-up period in unmatched patients (A); all-cause death during the follow-up period in propensity score-matched patients (B); cardiac or cerebrovascular (CV) death (including hospital mortality) during the follow-up period in unmatched patients (C); cardiac or cerebrovascular (CV) death (including hospital mortality) during the follow-up period in propensity score-matched patients (D).

Zoom

Discussion

To date only a few studies have specifically reported outcomes of BITA grafting in chronic dialysis patients [2, 4]. Generally, these clinical reports support BITA use, being perioperative results of BITA grafting in dialysis patients that do not differ from those of SITA grafting, but with better long-term outcomes. However, these studies usually involved limited series of patients from single centres where BITA grafting is not a routine surgical practice. As no propensity analysis was performed, a selection bias could be present.

Actually, there are good reasons to support and not to support the use of BITA grafting in dialysis patients. In addition to probable (but not yet certain) long-term survival benefits [2, 12], by reducing aortic manipulation, BITA grafting may broaden surgical options in the presence of atherosclerotic disease of the ascending aorta [4, 7], which is a frequent finding when there is severe and long-standing renal impairment. Besides, arteries could be more compliant conduits than veins for calcific coronary vessels, another common finding in chronic renal failure. On the other hand, some sceptics are opposed to BITA use in such frail patients because of the longer cross-clamping times, the potential for maldistribution of cardioplegia and the initial inadequacy of flow, not to mention exposing the patient to an increased risk of bleeding from the corresponding vascular beds by harvesting both ITAs. In addition, there is an increased risk of sternal wound infection [13]. Last, but not least, there might be a coronary steal in the presence of an upper limb dialysis fistula, ipsilateral to a simple or composite in situ ITA graft [14]. Consequently, the use of BITA grafting in chronic dialysis patients could be an unnecessarily risky operation.

We reviewed the results of BITA grafting in chronic dialysis patients from three European surgical institutions with extensive experience in BITA use (a total of ∼6000 operations during the period covered in the present study). In two centres, BITA grafting is performed on 95–100% of cases. In the Cardiovascular Department of Trieste, the rate of BITA use has increased from about 60% in 1999 to>95% in the last 3 years (every patient with multivessel coronary disease needing left-sided myocardial revascularization is a potential candidate for BITA grafting; the sole exceptions are the rare cases where one or both ITAs are unsuitable as coronary grafts, when there is an unexpected operative finding of severe cardiac dysfunction or when a rapid ischaemic worsening of haemodynamics needs immediate institution of cardiopulmonary bypass) [5, 7, 13].

In the present series of chronic dialysis patients undergoing routine BITA grafting, hospital mortality was high–twice that expected according to EuroSCORE II, and higher than that in other (more limited) series of dialysis patients undergoing either BITA or SITA grafting [1, 2, 3, 4, 12]. In each of the centres in this study, hospital mortality was greater than the 75th percentile of expected operative risk, despite intergroup differences in the prevalence of dialysis patients, baseline characteristics, risk profiles, surgical techniques and operative data. Diffusely atherosclerotic ascending aorta was confirmed to be a predictor of early death after surgery [3, 12]. Extracardiac arteriopathy was found to be an independent risk factor for complicated hospital course, which occurred in more than half of the patients. Rates of survival and survival free from cardiac or cerebrovascular deaths (also including hospital death) during a mean follow-up period of about 4 years were both good, and compared favourably with other series of chronic dialysis patients who had coronary bypass surgery with at least one ITA graft [2, 12, 15]. However, while the 2-year survival of these patients who underwent BITA grafting was better than expected according to the estimates of survival derived from the Charlson Comorbidity Scoring System for dialysis patients (76.4% vs 58.1%), the 1-year survival was equivalent (78.9% vs 78.2%) because of the increased risk of hospital death early after surgery. No intergroup differences in late survival were found. Because of the limited number of deaths during the follow-up period, only a few variables could be tested as predictors of all-cause death during the follow-up period. However, non-elective surgical priority emerged as an independent risk factor for death during follow-up. In our opinion, this result may reflect both the negative impact on outcomes of recent ischaemic worsening of haemodynamics and the positive impact of careful preparation of these frail patients for surgery.

In the two French centres in this study, no dialysis patients underwent SITA grafting during the corresponding study periods. Thus, a comparison between BITA and SITA dialysis patients was obtained only from the Cardiovascular Department of Trieste. A PS-matched analysis was also performed. Between the BITA and SITA patients, there were no significant differences in early postoperative outcomes, although almost every postoperative complication in BITA patients occurred more frequently than in SITA patients. Between the BITA and SITA patients, there were no differences in late survival, in both unmatched and PS-matched patients.

Study limitations

The primary limitations of the present study were the retrospective nature of the analysis and the evaluation of patients at different times after surgery. As data from three European centres were analysed, some (minor) differences in the results could derive from inevitable differences in the characteristics and perioperative management of patients. Because of the limited number of patients and events during the follow-up period, freedom from major adverse cardiac and cerebrovascular events could not be explored, and only a survival analysis was performed. A comparison between BITA and SITA patients was made on a very limited series of cases. In addition, this comparison is questionable because the follow-up extends to 7 years, while it is usually beyond this timepoint that the reported superiority of BITA grafting becomes manifest. Finally, no direct information about patency of coronary grafts with coronary angiography was reported. Consequently, the results obtained can in no way be considered as conclusive, and should be verified in a larger patient population by means of prospective controlled trials that include angiographic evaluations [16].

Conclusions

The 2014 European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines on myocardial revascularization state that the selection of the most appropriate revascularization strategy must take into account the general condition and life expectancy of the patient (with end-stage renal disease or) in haemodialysis, the least invasive approach being more appropriate in the most fragile and compromised patients [17]. According to these recommendations, the results of the present analysis do not support the routine use of BITA grafting for chronic dialysis patients. Because of the high risk of death and major complications after surgery, BITA grafting should be discouraged in these too frail patients, except when the presence of pathological findings, such as an unclampable ascending aorta, requires less invasive techniques. No long-term survival benefits of BITA versus SITA grafting were proven.

Sources of funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Disclosure of interest

The authors declare that they have no competing interest.


Appendix A. Supplementary data

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