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Ann Thorac Surg 2005;80:2132-2140
© 2005 The Society of Thoracic Surgeons
Cardiac Surgery Unit, Magna Graecia University of Catanzaro, Catanzaro, Italy
Accepted for publication May 17, 2005.
* Address correspondence to Dr Onorati, Viale dei Pini 28, Napoli, 80131 Italy (Email: frankono{at}libero.it).
| Abstract |
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METHODS: Transit-time flowmetric results and clinical, enzymatic, and echocardiographic findings from 201 consecutive isolated on-pump coronary artery bypass graft cases (cardiopulmonary bypass coronary artery bypass grafting; group A) were compared with 96 consecutive OPCAB (group B) cases performed at our institution between January 2003 and December 2004. Maximum, mean, minimum flow, and pulsatility index were compared, stratifying the two groups according to graft type and coronaries revascularized. Graft flow reserve was evaluated in patients undergoing preoperative intraaortic balloon pump during baseline conditions and at a 1 to 1 ratio of intraaortic balloon pump augmentation.
RESULTS: No differences were recorded between the two groups in hospital mortality, perioperative myocardial infarction, postoperative enzymatic leakage, echocardiographic recovery, or hospital stay (p = not significant). Off-pump coronary artery bypass and cardiopulmonary bypass coronary artery bypass grafting demonstrated similar intraoperative maximum (75.8 ± 10.4 mL/min vs 82.3 ± 15.8; p = 0.190), mean (50.1 ± 13.3 vs 46.3 ± 7.7; p = 0.420), minimum flow (12.7 ± 5.3 vs 11.9 ± 5.4; p = 0.811), and pulsatility index (2.9 ± 0.2 vs 2.6 ± 0.8; p = 0.360). After stratifying the population according to graft type, no differences were detected between the two groups in transit-time flowmetric results of left internal mammary artery, radial artery, and single and sequential saphenous vein grafts. A one to one ratio of intraaortic balloon pump augmentation did not result in any difference in graft flow reserve when left internal mammary artery (p = 0.699), radial artery (p = 0.066), and saphenous vein graft anastomoses (p = 0.772) were considered.
CONCLUSIONS: Off-pump coronary artery bypass grafting and cardiopulmonary bypass coronary artery bypass grafting demonstrated similar clinical, biochemical, and transit-time flowmetric results, as well as comparable graft flow reserve. These data exclude a lower anastomotic quality in off-pump coronary artery bypass grafting.
| Introduction |
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Assessment of coronary blood flow is critical in determining perfusion abnormalities, and is of particular importance after coronary artery bypass grafting (CABG). The transit time flow (TTF) method has been used with increasing frequency during recent years. It is fast and easy, even under surgical conditions. It is also predictive of graft occlusion at short-term angiographic follow-up, and is less affected by artifacts than are other techniques [35]. In particular, not only the absolute flow values, but also the flow curve patterns and the pulsatile index (PI) are needed to correctly use this technology in both OPCAB and traditional CABG [6].
Finally, some series comparing OPCAB with conventional on-pump CABG lack homogeneity because of incomplete revascularization in the OPCAB populations, especially in the circumflex territory [79].
Therefore, our aim in this study was to evaluate the TTF results and in-hospital findings of a consecutive series of patients who had undergone complete myocardial revascularization, comparing off-pump with on-pump isolated CABG performed during the last 2 years at a single academic institution.
| Material and Methods |
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Exclusion criteria were as follows: additional cardiac or vascular surgical procedures, severe systemic comorbidities (dyalisis, hepatic failure, cancer, autoimmune disease), and coronary revascularization with "Y"-graft or "T"-graft construction.
Angiography
Preoperative coronary angiography of each patient was reviewed by two cardiologists, blinded to the study, and thrombolysis in myocardial infarction scores were calculated for each vessel.
Surgery
A standard anaesthetic protocol was used throughout the study period. This consisted of intravenous anesthesia with a propofol infusion at 3 mg/kg per hour combined with fentanyl administration at 0.10 mg each 20 minutes. Neuromuscular blockade was achieved by pancuronium bromide (4 mg/h), and the lungs were ventilated to normocapnia with air and oxygen (45% to 50%).
All surgical procedures were performed by the same three senior surgeons (AR, PM, AdV). We started to perform off-pump surgery 6 years before the study began, and it is institutional practice to perform about 30% of all coronary surgical procedures without cardiopulmonary bypass.
In all patients CABG was performed through a median sternotomy and the left anterior descending artery always grafted using pedicled left internal mammary artery. The radial artery (RA) was always used in a pedicled fashion. The Allen test was considered negative when hand vascularization became normal in less than 6 seconds. In all patients the RA was harvested by the aid of harmonic scalpel (Ethicon Endo-Surgery, Cincinnati, OH) with the hook blade, using the variable mode at moderate intensity. Major collateral branches were controlled with small clips. The arterial graft pedicles were always secured with two epicardial stitches using 6-0 polypropylene on both sides after completion of distal anstomoses. Internal saphenous vein was always harvested from the best side, as detected by preoperative Doppler scanning.
Blood recovery with autotransfusion device (Autotrans Dideco, Mirandola, Modena, Italy) was performed intraoperatively and routinely in all cases. A level of haemoglobin lower than 8 g/dL was used as an indication for blood transfusion.
Of 297 patients admitted to our institution, 201 (67.7%) underwent standard CABG under cardiopulmonary bypass (group A) and 96 patients (32.3%) underwent OPCAB (group B).
In group A, cardiopulmonary bypass was started by cannulating the ascending aorta and the right atrium with a two-stage venous cannula. A standard cardiopulmonary bypass circuit was used (ie, a Dideco [Mirandola, Modena, Italy]) tubing set that included a 40-micron filter, a Stockert roller pump (Stockert Instrumente, Munich, Germany) and a hollow fiber membrane oxygenator (Dideco D903 Avant, [Mirandola, Modena, Italy]). Nonpulsatile flow with an output of 2.4 L/m2 per minute was used. Systemic temperature was kept between 32°C and 34°C. Myocardial protection was achieved by using warm blood cardioplegia [10]. On completion of all distal anastomoses, the aortic cross clamp was removed, and proximal anastomoses were performed with partial clamping.
In group B, the exposure and stabilization was achieved with the Octopus-III tissue stabilizer (Medtronic Inc, Minneapolis, MN). Exposure of the lateral wall vessels was obtained with the aid of the Starfish system (Medtronic Inc, Minneapolis, MN) Visualization was enhanced by using a surgical blowerhumidifier device (model SSVW-002, Surgical Site Visualization Wand [Research Medical, Midvale, UT]) connected to a regulated CO2-gas source. Intracoronary shunts were routinely used with a success rate of 100% in all coronaries, except for the obtuse marginal branches. In 11 patients (11.4%) of the latter group we were unable to introduce the shunt. On the other hand, we never did OPCAB with the aid of coronary snaring.
The first grafted vessel was always the left anterior descending artery, followed by proximal anastomoses with the saphenous vein or RA, and finally, distal anastomoses.
Anticoagulation Protocol
A heparinization protocol of 300 international units per kilogram was used in patients undergoing cardiopulmonary bypass coronary artery bypass grafting (CPBCABG) to maintain an activated clotting time of 480 seconds. On the other side, a heparinization protocol of 150 international units per kilogram was used in OPCAB to obtain an activated clotting time greater than 300 seconds. Protamine was always used when hemodynamic stability was achieved at a dose of 1 mg of protamine for each 100 international units of heparin to achieve complete heparin neutralization, which was confirmed by an activated clotting time below 120 seconds.
In both groups 4,000 international units nadroparin/die was started 8 hours after surgery and was maintained until the fourth postoperative day. Oral antiplatlet therapy (150 mg/die of salicilic acid) was started immediately after removal of chest drains, or at least 48 hours after surgery.
Flowmetric Analysis
Assessment of each graft was performed under stable hemodynamic conditions in both groups, generally 30 minutes after protamine administration. Flowmetry of the grafts was performed with a transit-time flowmeter (HT313, Transonic [Transonic Systems Inc, Ithaca, NY]). Different probe sizes (2-mm, 2.5-mm, or 3-mm) were available to avoid distortion or compression of the graft. Skeletonization of a small segment of the RA and of the left internal mammary artery was necessary to reduce the quantity of tissue interposed between the vessel and the probe. Maximum, mean and minimum flows, flow curve, and PI were obtained directly from the flowmeter. The curves were always coupled with the electrocardiogram tracing to correctly differentiate the systolic from the diastolic flow. Transit time flow measurements were interpreted as previously suggested by D'Ancona and associates [6]. The maximum, minimum, and mean flows were reported as mL per minute, and PI was reported as an absolute number [6]. Data from single or sequential grafts and from arterial or venous conduits were recorded and compared between the 2 groups.
Graft Flow Reserve
It has been demonstrated that the intraaortic balloon pump (IABP) recruits graft flow reserve during assistance [11]. To evaluate graft flow reserve, mean flow and PI were recorded in all patients undergoing preoperative intraaortic balloon pumping, both during IABP support and during temporary cessation. Graft flow reserve was calculated from the mean flow assessed during a 1 to 1 ratio of IABP support divided by mean flow at baseline (IABP off).
Postoperative Care
According to an institutional policy, inotropes were started immediately after aortic cross-clamp removal with enoximone at a dosage of 5 µg/Kg/min [12]. The need for a further increase in inotropes was recorded. Inotropic support was defined as low dose when enoximone was administered at a dosage lower than or equal to 5 µg/Kg/min; medium dose was defined when enoximone was employed at a dosage between 6 and 10 µg/Kg/min, or dobutamine was added at a dosage between 5 and 10 µg/Kg/min; and high dose was defined when enoximone or dobutamine infusion was > 10 µg/Kg/min, or epinephrine was added at any dose.
Biochemical Analysis
Blood samples were always collected from a central venous line with the tip of the cannula in the lower part of the right atrium, as confirmed by postoperative chest roentgenogram. Determinations of blood concentration of cardiac troponin I, creatine-phosphokinase (CPK), and MB-CPK were conducted preoperatively before anaesthetic induction, and postoperatively at 12, 24, 48, and 72 hours. The assays were carried out using diagnostic kits provided by Beckman Coulter, Inc (Fullerton, CA) for troponin I (Access Immunoassay System, AccuTnI), CK-MB (Synchron CX system), by Beckman Instruments for CK (Synchron CX system). Biochemical diagnostic criteria for perioperative myocardial infarction were peak troponin I greater than 3.7 µg/L and a troponin I concentration greater than 3.1 µg/L at 12 hours or greater than 2.5 µg/L at 24 hours as determined by Mair and colleagues [13].
Echocardiography
All studies were performed using a transthoracic Acuson Sequoia C256 echocardiography system (Acuson Corp, Mountain View, CA) with probe 3V2C, and always by the same 2 physicians in a blind manner at the time of hospital admission and before discharge. Left ventricle ejection fraction and wall motion score index were recorded.
Statistical Analysis
Statistical analysis was performed by using the SPSS program for Windows, version 10.1 (SPSS Inc, Chicago, IL). Continuous variables are presented as mean ± standard deviation and categorical variables are presented as either absolute numbers or percentages. Data were checked for normality before statistical analysis. Normally distributed continuous variables were compared using the unpaired t test, whereas the MannWhitney U test was used for those variables that were not normally distributed. Categorical variables were analyzed using either the
2 test or Fischer's exact test. Comparisons were considered significant if p < 0.05.
Limitations of the Study
Off-pump coronary artery bypass grafting practice was started 6 years before the study began, and about 30% of all coronary cases of our institution were done off-pump. Moreover OPCAB procedures were always performed by the same 3 surgeons, so that no biases of the learning curve could be advocated in comparing results.
An ideal comparison between two treatments should be performed on the basis of a prospective randomized study. Although the data were prospectively collected, no real randomization has been performed, and the option to avoid cardiopulmonary bypass was conditioned by the patient as to who preferentially underwent OPCAB (ie, patients who were preoperatively considered easy, which includes young age, good ventricular function, or small number of planned distal anastomoses, or patients who were preoperatively considered difficult for preexisting comorbidities, potentially threatened by cardiopulmonary bypass, which includes mild renal or hepatic insufficiency, neurologic dysfunction, chronic obstructive pulmonary disease, unstable patients, or the elderly). Angiographic coronary anatomy was never represented as an indication for OPCAB.
However, the aim of this study was not to define which was the best surgical strategy (ie, on-pump or off-pump surgery), but to analyze, with the aid of TTF and in-hospital results, the potential for a lower technical accuracy and a poorer quality of off-pump anastomoses, responsible for the recently reported lower graft patency in OPCAB [1].
Finally, it has to be kept in mind that not only the quality of the grafts and the distal anastomoses, but it is also the run-off bed of the grafted coronaries that determine the TTF values. However, the thrombolysis in myocardial infarction angiographic score was similar between the two groups (see Table 1), as was the harvesting techniques of the grafts.
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| Results |
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No diffferences were recorded between the two groups either in terms of postoperative acute myocardial infarction (group A: 3 of 201 [1.5%] vs group B: 1 of 96 [1.0%]; p = 0.611) or the need for postoperative IABP (group A: 6 of 201 [3.0% vs group B: 3 of 96 [3.1%]; p = 0.600). However, mechanical assistance was discontinued in all cases within 72 hours of the operation.
As far as inotropic support was concerned, the number of patients requiring medium doses of inotropes was similar in both groups (group A: 15 of 201 [7.5%] vs group B: 9 of 96 [9.4%]; p = 0.360), as was the number needing high doses of inotropes (group A: 5 of 201[2.5%] vs group B: 3 of 96 [3.1%]; p = 0.508).
No differences were recorded between the two groups in postoperative troponin I, CPK, or MB-CPK (Fig 1).
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According to graft flowmetry, 1 patient in group B (1 of 96 [1%]), but no one in group A (p = 0.323) required graft revison: the patient demonstrated a systolic pattern of the curve with low mean flow value (9 mL/min) and high PI [8] of the left internal mammary artery to left anterior descending coronary artery anastomosis. Graft revision demonstrated the recovery of the diastolic pattern of the curve together with the improvement of either mean flow (34 mL/min) and PI (2.1). Then the postoperative course was uneventful. On the other hand, 4 patients (2.0%) in group A and 3 OPCAB patients (3.1%; p = 0.406) demonstrated low mean flow (OPCAB: 10.1 ± 0.3 mL/min; CPBCABG: 15.3 ± 2.5 mL/min), and high PI (OPCAB: 5.8 ± 0.5; CPBCABG: 5.6 ± 0.9) without a systolic "spiky" pattern of the curves. The preserved diastolic flow pattern together with the angiographic findings of poor quality target vessels, because of severe and diffuse atherosclerosis, did not lead to graft revision. All but 1 patient, who had a perioperative myocardial infarction develop, had an uncomplicated postoperative course, and was asymptomatic at the last ambulatory follow-up.
As far as TTF values were concerned, the maximum, mean, and minimum flows, and the PI of the two groups were similar, as shown in Table 2.
Stratifying the two populations according to graft type, no differences existed in maximum, mean, nor minimum flow of left internal mammary artery to left anterior decending coronary artery anastomoses, RA to obtuse marginal branches (OM) anastomoses, or RA to right coronary territory anastomoses (Fig 2). Similarly, no differences were detected in single vein grafting on the right coronary artery, diagonal branches, or obtuse marginal artery, or in sequential vein grafting (Fig 3). Similarly, PI of these grafts was comparable between the two groups (Table 3).
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| Comment |
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It should be kept in mind that long-term patency is critically affected by the evolving atherosclerotic process and fibrointimal hyperplasia, which are both genetically modulated [14], but that short-term patency critically depends on technical accuracy, which is investigated by TTF [4, 5]. Intraoperative flow measurements together with postoperative angiographic follow-up are important methods aimed at documenting the efficacy of CABG. Although coronary angiography remains the gold standard method to assess graft patency, several techniques have been used in the past to test coronary graft flow intraoperatively. Of these, electromagnetic flowmeters, initially adopted in coronary surgery, have been recently replaced by ultrasonic technology (Doppler and transit-time flowmeter) because of the demonstration of the superiority of transit-time flowmeter over Doppler systems in direct real time detection of flow, independently of vessel diameter and Doppler angle [15]. Moreover, it has been demonstrated that this technology is predictive for graft occlusion at short-term angiographic follow-up [4, 5]. Since the first reports on coronary surgery, many authors have demonstrated that the long-term patency of the grafts critically depends on the flow rate throughout the graft itself, and that there is a reverse relationship between the flow rate and degree of intimal proliferation [1618]. However, the sensitivity of transit-time flowmeter in detecting less than critical stenoses remains to be defined. Jaber and colleagues [19] demonstrated that more than 70% of surgeons accepted anastomoses with severe stenoses, but all of them were able to detect highly stenotic anastomoses (> 90% stenosis). Cerrito and coworkers [20] showed that a complex mathematical analysis of the flow curves can detect stenoses causing a 50% or greater narrowing of the anastomoses, but that again, less than critical stenoses could not be detected by transit-time analysis due to the fact that no modifications in the hemodynamic performances of the grafts occur at this level. However, patent grafts have a mainly diastolic pattern with a small component of negative systolic flow, whereas stenotic anastomoses show spiky and mainly systolic flow patterns [6]. On the other hand, the quality of the target vessel has to be in mind, because severe and diffuse coronary atherosclerosis anticipated a poor run-off bed, and therefore poor TTF results. Seven patients in our experience demonstrated low flow values and almost acceptable PIs, although the diastolic pattern of the curves was preserved; these patients did not undergo graft revision and all but 1 had an uncomplicated course. According to these data, we take down and redo the anastomoses in which systolic spiky patterns of the curves, very low flow values, and high PIs are reported. On the other hand, low flow and normal PI preserved diastolic patterns without major electrocardiographic changes associated with intraoperative findings of the small and severely diseased vessel does not indicate graft revision.
Finally, good TTF results can be helpful in the decision-making process whenever complications, such as minor electrocardiographic changes, hypotension, or arrythmias occur during the sternal wiring, and TTF confirms unchanged findings.
A recent report by Kjaergard and colleagues [21] clearly pointed out that off-pump and on-pump surgery achieved similar flowmetric results, without gender-related differences, although only on-pump CABG could restore approximately half of the normal resting coronary artery blood flow. However there is evidence that flow values per se are not a good indicator of the quality of the anastomosis. Absolute flow is influenced by too many variables including type and size of the graft, and quality of the coronary artery distal territory [6]. We similarly found comparable flowmetric results between CPBCABG and OPCAB. However, if mean flow values are not good predictors of the quality of the grafts, on the contrary PI values are, per se, very suggestive of the actual status of the anastomoses [6, 22]. Our study demonstrated that OPCAB and CPBCABG showed not only comparable mean, maximum, and minimum flow values, but also similar PI. Moreover, the analysis of either arterial, single venous or sequential venous grafts similarly did not demonstrate any difference between the two groups, either in terms of absolute flow values, or in PI. Such results can be due to a so-called "no touch" technique employed in OPCAB. We avoid coronary snaring, and routinary use intracoronary shunts; it has been demonstrated that coronary snaring is associated with focal endothelial denudation, microthrombosis, atherosclerotic plaque rupture and distal embolization, and injury to target vessel branches [23, 24]. All these complications may explain the lower patency rate reported in some off-pump series, and their avoidance can be responsible for our results in the early perioperative time. Moreover, intracoronary shunting protects against back wall suturing, another cause of early graft failure.
Although the sensitivity of transit-time flometer in detecting less than critical stenoses remains to be defined, it has been shown that the study of flow reserve is a valid tool to diagnose anastomotic imperfections, as described by Walpoth et al., improving the accuracy of TTF measurements [4]. On the other hand, it has been demonstrated that IABP recruits graft flow reserve during assistance [11]. Again, our subset of patients undergoing preoperative IABP insertion and transit-time flow measurements with both 1:1 IABP and IABP off demonstrated a significant improvement of graft flows and PI of both the off-pump and on-pump groups, without differences comparing the two techniques. According to these data, postoperative enzymatic leakage, as well as clinical end-points were comparable between the two groups. Therefore the potential for the evaluation of graft flow reserve is another tool to be kept in mind in patients undergoing IABP assistance, because it can further explore the accuracy of the anastomosis and the quality of the graft: we now routinely assess flowmetric values during IABP assistance, and compared to those values obtained during temporary IABP discontinuance, whenever issues on the quality of the surgical result are argued.
Finally, it has to be considered that few data exist about differences in TTF measurements in different grafts [6, 22]. Kjaergard and colleagues [21] reported similar graft flow values of left internal mammary artery to LAD anastomoses, and those of single and sequential vein grafts, either in conventional CABG on CPB and off-pump surgery. Our data are consistent with those reported by Kjaergard and colleagues [21], also when the RA is considered. Moreover, we were able to demonstrate a similar graft flow reserve in the left internal mammary artery, RA, and saphenous vein grafts of both groups. However, we do not have actual nominal flow and PI values to suggest a correct interpretation of flowmetric findings.
In conclusion, our study, although not randomized, demonstrated that intraoperative flowmetric results and graft flow reserve of OPCAB are as good as those achieved with conventional CABG on CPB. These data were confirmed by similar early troponin release and later echocardiographic controls. Transit time flowmetry is a valid tool to intraoperatively explore the efficacy of myocardial revascularization, with the possibility to study the graft flow reserve whenever issues on the quality of coronary artery bypass grafting, sometimes important after OPCAB are argued. Although our data clash with the recently reported lower graft patency of off-pump CABG, they seem to exclude the potential of a lower quality graft anastomotic accuracy, secondary to a more technically demanding procedure. However the long-term significance of such results needs to be further investigated.
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