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Eur J Cardiothorac Surg 2005;28:120-126
© 2005 Elsevier Science NL
a Department of Cardiac Surgery, Cattedra e Scuola di Specializzazione in Cardiochirurgia, University of Florence, Viale Morgagni, 85, Careggi, 50134 Firenze, Italy
b Division of Cardiovascular Surgery, Toronto General Hospital, University of Toronto, Canada
c Division of Cardiac Surgery, Azienda Universitario-Ospedaliera ‘Careggi’, Firenze, Italy
d Brigham and Women's Hospital, Harvard University, Boston, USA
Received 5 October 2004; received in revised form 7 March 2005; accepted 30 March 2005.
* Corresponding author. Tel.: +39 338 9855782; fax: +39 055 4277458. (Email: mbonacchi{at}unifi.it).
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Abstract |
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 Top Abstract 1. Introduction2. Material and methods3. Results4. DiscussionReferences |
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Key Words: Unstable angina • Coronary artery bypass grafting • Emergency surgery • Double mammary arteries
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1. Introduction |
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TopAbstract1. Introduction2. Material and methods3. Results4. DiscussionReferences |
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However, despite improvements in anesthesia management, surgical procedures, and perioperative care, the risk of early death or acute myocardial infarction after surgery for unstable angina is higher than elective surgery for stable angina [3]. In addition, the timing of the surgery, and the use of arterial grafts are still debated. Recent reports have suggested a benefit in the use of the internal mammary artery compared to the use of venous conduits [5–8] in the setting of non-elective coronary artery bypass grafting (CABG). Conversely, other authors [9,10] have failed to identify a survival benefit after elective procedures for the use of more than a single arterial graft.
Given the increased number of patients undergoing urgent/emergent surgical revascularization for UA, it is important to clarify the surgical and myocardial protection techniques as well the role of arterial conduits. Accordingly, we undertook this retrospective study to evaluate the use, in-hospital and mid-term outcomes of bilateral skeletonized internal mammary arteries (BIMA) in non-elective CABG for unstable angina.
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2. Material and methods |
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TopAbstract1. Introduction2. Material and methods3. Results4. DiscussionReferences |
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All patients presented unstable angina pectoris, defined as prolonged (more than 15min) angina at rest, associated with usually reversible electrocardiographic alterations, but without enzymatic evidence of myocardial injury (creatine phosphokinase (CPK)-MB/CPK>10% and/or Troponine I>0.15ng/mL) and refractory or incomplete response to maximum medical treatment. The medical treatment was as follows: intravenous heparin infusion adjusted for activated partial thromboplastin time; initial dose of aspirin (300–600mg), but not followed by a maintenance dose because if at following coronary angiography they were considered suitable for CABG, and intravenous therapy with organic nitrates and ß-blockers unless contraindicated. Since 1999 clopidogrel was added to aspirin in 120 (15.8%) patients. All patients were treated in the intensive coronary unit.
According to Braundwald's classification [11], 102 (13%) patients were in class II (patients with unstable symptoms at rest despite medical treatment in the last 2–30 days) and 656 (87%) patients were in class III (presence of unstable symptoms in the previous 48h). 578 (76) patients had primary angina pectoris (subgroup B) and 180 (24%) patients had angina pectoris within 2 weeks following a myocardial infarction (subgroup C). According to the Canadian Cardiovascular Society classification 424/758 (56%) patients were in CCS IV and 334/758 (44%) in CCS III. At coronary angiography three-vessel disease was present in 619/758 (81%) and two-vessel disease in the remaining 139 patients. A left main coronary artery disease was present in 297/758 (39%) patients.
2.2. Operative techniques
2.2.1. Cardiopulmonary bypass and myocardial protection
Cardiopulmonary bypass was instituted using ascending aortic cannulation and two-stage venous cannulation in the right atrium. Heparin was given at a dose of 300IU/kg to achieve a target ACT of >450s. Moderate hemodilution (hematocrit 20–25%) and normothermia (range 38–35°C) were maintained during cardiopulmonary bypass. Myocardial protection was achieved with antegrade cold (4°C) blood cardioplegia (4:1 ratio). Following aortic clamping, cardioplegic arrest was achieved in all patients by antegrade coronary infusion of 400mL of high-potassium (15–30mEq/L) solution over a period of 2–3min at a perfusion pressure not exceeding 250mmHg in the infusion line and retrograde (successively or simultaneous) somministration over a period of 1–2min at a perfusion pressure not exceeding 50mmHg in the infusion line. Diastolic arrest was usually obtained before termination of the initial infusion. Thereafter, and for the remainder of the procedure, intermittent bolus infusion of 200–300mL of low-potassium solution (10–20mEq/L) was administered antegrade via the ascending aorta and/or retrogrades through the coronary sinus every 20–30min.
2.2.2. Surgery
All patients underwent median sternotomy. The internal mammary arteries were harvested contemporary to the saphenous vein and/or radial artery. In all patients the IMAs were harvested in a skeletonized fashion as previously described [14,15]. The mediastinal pleura were dissected gently from the endothoracic fascia, and then the endothoracic fascia was incised medially. The IMA was separated from the chest wall and isolated from the fascia; the collateral branches were legated with small-sized hemostatic clips frequently only by the IMA' side. Following systemic heparinization, the IMA was clipped distally, cut, clamped proximally with a bulldog, and covered with gauze impregnated with papaverine solution (4mg/mL). The duration of the IMA's harvesting was reduced from initially 42±18min in 1997 to 18.2±14.6min in 2003. In both sides of the superior mediastinum the pleurae-pericardial tissues were dissected and the ‘IMA-beds’ were created maintaining the pleura integrity. The IMAs were mobilized through this ‘beds’ anterior to the phrenic nerve. This route allows the IMAs to lie medially and posteriorly to the lungs, so that the inflation of the lungs does not produce stretch or distortion of the arteries. The RIMA eventually was routed retrocavally and superiorly to the azygous vein. All the IMAs used as conduits were over 1.5mm in size and had a free flow >50ml/min.
The RA was harvested simultaneously to the IMAs' preparation at the non-dominant arm. Preoperative assessment of the palmar arch was done with an Allen test and in questionable cases by digital plethysmography. The RA was excised bilaterally, cannulated with a 1-mm elastic needle through which 10ml of a solution containing dilzene (5mg/ml) and nitroprussiate (10mg/ml) in warm Ringer solution was gently injected.
On-pump/beating heart, the coronary arteries were explored. The length of the LIMA was measured and, if necessary, the remaining segment was used as a composite graft. All the IMAs' anastomoses were performed using 8-0 polypropylene continuing sutures. The LIMA was anastomosed to the LAD in all patients. In Group B the RIMA, passed through the transverse sinus and, eventually, retrocaval (n=136, 42.4%), was grafted to an obtuse marginal artery in 230 patients (72%), and postero-lateral branches (Cx) in 26 (28%).
The left ventricle was lifted and rotated to the right side for exposing its lateral wall. Sewing the RIMA in this position is easier than when the heart is not rotated but, on the other hand, requires additional length. The RIMA may be tight during this part of the operation; however, the release of the heart after the anastomosis' completion restores adequate length of the graft. All the anastomoses, distal and proximal, were performed with the aorta clamped.
Intravenous nitrates therapy was initiated immediately after removal of the aorta clamp and continued during the postoperative course in the intensive care unit. In patients with the radial artery anastomosis, intravenous diltiazem was added.
If present at the time of the surgery, intra-aortic balloon pump was discontinued with CPB initiation and was restarted after releasing the aortic clamp. 32 (12%) patients and 48 (11%) patients in Group B and M, respectively, necessitated preoperative IABP. In Group B, 6 (18.7%) from 32 preoperatively contrapulsated patients presented unstable hemodynamic status and ischemic electrocardiographic alterations persistent during the initial phase of the operation. In this subgroup of 6 patients, the CPB was initiated immediately and on-pump, the BIMAs were harvested. In Group M, 10 (21%) from 48 patients with preoperative IABP required immediate institution of CPB, due to unstable hemodynamic status.
2.2.2.1. Study design
The data for analysis were obtained by review of medical records. Survival status was determined by contacting all patients and or the primary care physician/or cardiologist.
2.2.3. Definitions
Hospital mortality was defined as death for any reason occurring within 30 days after the initial surgery. New peri-operative myocardial infarction was defined as the appearance of new Q-waves or significant loss of R-wave, forces peak creatine phosphokinase (CPK) MB fractions greater than 10% of total CK or Troponine I>0.15ng/ml. Low cardiac output syndrome was defined as a cardiac index <2.0L/min/m2, the requirement of triple inotropic support to maintain a systolic pressure >90mmHg for at least 30min, and/or the requirement of an intra-aortic balloon pump. Neurological complications were defined as a new central neurologic deficit; transient persisting less than 24h or permanent persisting for >24h. Postoperative renal insufficiency was defined as an increment of creatinine 
1mg/dl compared to the preoperative baseline value. Gastrointestinal complications included upper or lower gastrointestinal hemorrhage requiring blood transfusion, or the presence of acute cholecystitis, acute pancreatitis or clinical mesenteric ischemia.
2.2.3.1. Follow-up
End-points of this study were: survival, angina-free survival, infarction-free survival reoperation-free survival and event-free survival defined as freedom from any cardiac event (recurrence of angina, new myocardial infarction, coronary reinterventions, repeated CABG or percutaneous transluminal coronary angioplasty) and cardiac death. Outpatients' information were collected from patients' cardiologist and home physicians and by telephone interview. Follow-up was 99.7% complete.
2.2.4. Statistical analysis
Group statistics were expressed as mean±SD. The generalized Wilcoxon test was performed for the statistical analysis between groups. Fisher's exact test was used for the non-continuous variables. The relationship between preoperative and postoperative variables within the same group was assessed by the McNemar test. The Cox proportional analysis was used to identify the independent predictors for early and late deaths. Variables with P-value less than 0.25 in the univariate analysis were entered in the Cox's model. Long-term survival rates were calculated using the Kaplan–Meier method and differences between groups were assessed with the long rank test. Significance between data was considered achieved when P<0.05. Statistical analysis was performed with the use of Statsoft 6.0 (Tulsa, OK) software package.
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3. Results |
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TopAbstract1. Introduction2. Material and methods3. Results4. DiscussionReferences |
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4. Discussion |
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TopAbstract1. Introduction2. Material and methods3. Results4. DiscussionReferences |
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4.1. Operative mortality and morbidity
The operative mortality (OM), in this series (5.4%), despite been higher than that for elective revascularization (in our institution <2%) confirms that CABG for UA may be performed with acceptable operative mortality. Recently, Bjessmo and co-authors [6] have reported a 3.4% OM in unstable patients with a significant decline of early OM and/or early myocardial infarction during a 6-year period. It should be noted, however, that the OM reported is for patients without congestive heart failure and not operated on emergency. As demonstrated by this and previous reports, depressed left ventricular function, older age and more extensive CAD are predictors for increased mortality [7]. Furthermore, operative mortality is increased in reoperative surgery and by long aortic cross-clamp time, which often reflects the presence of diffuse CAD and necessity of multiple distal anastomoses [6,7].
The incidence of perioperative MI was 4.5% in our series (15 non-fatal and 19 fatal myocardial infarction), which is lower to that in other reports [5,6]. These encouraging results may be related to several reasons. Cold blood cardioplegia has been shown to offer better myocardial protection for coronary revascularization for unstable angina than crystalloid cardioplegia [11]. Thus, we adopted this myocardial strategy in all the patients. Bjessmo and co-authors [6], reported a peri-operative MI rate of 17.2%, however, only half of their patients received a combination of both, antegrade and retrograde cold blood cardioplegia. In a similar study, Louagie et al. [5] also administrated cold blood cardioplegia only in a part of their patients, namely those high-risks, reporting an incidence of new postoperative myocardial infarction of 7.2%.
The fact that global ischemic time plays such an important role in OM in patients with UA raises the question of the good timing elapsing between the onset of the symptoms and the surgery. Same authors recognize that early reperfusion following the onset of symptoms should be obtained as quickly as possible [12]. We concur with those groups, and none of our patients underwent surgery more than 3h after the onset of symptoms.
A key role in the timing of the surgery is represented by the medical protocol for UA adopted in our institutions. We favor the early aggressive approach [1,2] which consists in routine coronary angiography within 48 of UA symptoms for two reasons: (1) as shown by recent trials an aggressive approach is justified and can reduce death, myocardial reinfarction or rehospitalization (2) patients with suitable coronary anatomy for CABG may be treated with IV heparin, nitrates, and ß-blockers, while those not deemed to be suitable for CABG are treated with combined aspirin and clopidogrel. This clinical algorithm reduces significantly the proportion of patients undergoing CABG under the treatment of antiplatelets agents. The addition of clopidogrel to aspirin increases significantly the risk of bleeding [13]. In this study, all patients, with significant bleeding, were on a combination of the above mentioned drugs. The risk of bleeding may be mitigated by temporary discontinuation of the medication before the surgery, however, in the presence of UA symptoms it is not possible to wait until the effects of the medication disappear.
4.2. Arterial revascularization and mid-term outcomes
Very few reports have focused on the use of arterial grafts in the setting of UA [4–6]. The principal objections to their use in non-elective surgery are the longer dissection time, the potential for cardioplegia maldistribution and initial inadequacy of flow. Since 1996, we decided to adopt bilateral skeletonized IMAs technique as our standard method for myocardial revascularization for grafting the left coronary system [14–16] and, later on, after 1997, we have expanded their use for non-elective revascularization. Our current approach, in patients with UA, refractory to maximal medical therapy, is to put an intra-aortic balloon pump and to start the surgical procedure. If electrocardiographic alterations are still present during the IMAs' harvesting, we immediately institute CPB and, on pump-beating heart, the IMAs' harvesting is completed. We believe that this operative strategies reduces the overall time on cardiopulmonary bypass and enhances coronary perfusion following the period of clamp ischemia, thus reducing CPB time, due to the few proximal anastomoses performed. Skeletonized mammary arteries have similar immediate flow compared to the vein grafts as opposed to the pedicled mammaries arteries, which have an immediate flow inferior to that of the saphenous vein grafts [15,16]. Better initial patency of the IMA may explain its ‘protective’ effect on early mortality [5], while its non-use is a predictor for OM [6] and low cardiac output syndrome [4].
The use of BIMA in UA patients is safe with no increased operative risk and with in-hospital outcome similar to that for the use of a single IMA. Though, the benefits of BIMA become evident at mid-term follow-up (7 years). We demonstrated that the overall survival for hospital survivors after 7 years was better for the BIMA group (96%) compared to the LIMA (88.4%) (P<0.05). Fiore [8], Berreklouw [9] and their co-workers have failed to identify additional benefit in survival for patients in whom two mammary arteries were used, either at mid-term follow-up (8 years) or over a15-year period. However, Fiore et al. [8], always grafts the LIMA to the LAD and the RIMA to the right coronary artery, while Berreklouw and co-authors [9] have grafted the RIMA to the circumflex system in only 30% of the patients. We believe that the improved survival is related to the complete arterial revascularization of the left heart. In addition to the type of surgical revascularization performed, age, severe impaired left ventricular function, and the presence of diffuse (> than one area) of irreversible ischemic are predictors for late death.
Angina-free cardiac survival after 7 years in our BIMA (98%) group is also better than that for the LIMA (96%) alone. Recurrent symptoms following CABG may be a sign of slow grafts deterioration. Due to the superior long-term patency rate, the use of a second IMA diminished the recurrency of angina symptoms [8,17]. Thus, improving freedom from coronary reinterventions.
After 7 years, we demonstrated an infarction-free cardiac survival for BIMA patients of 98.7% and for LIMA patients 96%, P=0.05. Fiore and co-workers [8] observed a significant reduction of late myocardial infarctions (from 59 to 75% freedom) with the use of two mammary arteries at mean of 15 years follow-up, but not in the first 10 years. It is likely that, there is no difference in recurrence of MI in elective CABG during the first 10 years due to the low incidence of this event. In unstable coronary artery disease the recurrence of late myocardial infarction is higher and the risk of having a fatal MI within 6 months is 9.4% (FRISC) II trial [1]. This increased risk is consistent with possible persistent plaque instability after an acute rupture.
4.3. Limitations of the study
The principle limitation of this study lies in its retrospective nature. Over the past decade the treatment for UA has greatly evolved with the introduction of new drugs. Though, our treatment for UA was consistent over the time period, except for the introduction of clopidogrel after 1997, used in a small proportion of our patients.
The dissection of the IMA, as a skeletonized vessel, has remained the same over the study period, but the dexterity of the surgeons has improved over time. We did not find, however, any difference between the initial phase of the study and the later.
In summary, routine use of bilateral skeletonized mammary arteries for surgical revascularization in the setting of UA is safe with comparable in-hospital mortality and morbidity as single skeletonized IMA. The benefit of using both arterial grafts are evident at 7 years follow-up with significantly better event- and angina-free survival, free-reoperation survival and lower reinfarction rate. These encouraging results, justify continuing this surgical approach for myocardial revascularization in UA.
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References |
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TopAbstract1. Introduction2. Material and methods3. Results4. DiscussionReferences |
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This article has been cited by other articles:
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  M. Bonacchi, M. Maiani, and M. Leacche Reply to Raja: Why skeletonized BIMA for unstable angina? Eur. J. Cardiothorac. Surg., November 1, 2005; 28(5): 781 - 781. [Full Text] [PDF]
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S. G. Raja Skeletonized bilateral internal mammary arteries in unstable angina: a paradigm shift Eur. J. Cardiothorac. Surg., November 1, 2005; 28(5): 780 - 781. [Full Text] [PDF]
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