Off-pump coronary surgery in selected patients: better early outcome but more recurrence of angina
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《血管的通路杂志》
a Cardiac Surgery Department, Timone University Hospital, Marseilles, France
b Anaesthesiology Department, Timone University Hospital, Marseilles, France
c Cardiology Department, Timone University Hospital, Marseilles, France
Presented at the 53rd International Congress of the European Society for Cardiovascular Surgery, Ljubljana, Slovenia, June 2–5, 2004.
1 Superficial vessels, not or moderately calcified; with a diameter >1.2 mm.
Abstract
This non-randomized retrospective study included all patients operated on for CABG through median sternotomy between January 2000 and December 2002 by the same surgeon trained to both techniques. Using risk-adjusted comparison where expected mortality was given by the EuroSCORE value assessed pre-operatively, and studying mid-term survival and functional results we aimed to evaluate our indications for OPCAB versus conventional CABG through a consecutive series of 308 patients. Selected indications for OPCAB (n=154) were isolated LAD coronary system lesions and multivessel diseases with suitable anatomy in high surgical risk patients (EuroSCORE5). The first 154 patients operated on conventionally during the time-study interval were included in the control group. Expected mortality was significantly higher in the OPCAB group: 4.29 [95% CI: 3.83–4.77] vs. 3.54 [95% CI: 3.17–3.91] (P=0.024). Observed mortality was 1.3% and 2.6% for patients treated OPCAB and with conventional technique, respectively. Survival at three years was 91.5 and 93.8% in the conventional and OPCAB groups, respectively. Angina-free survival at three years was 95.8% and 89.6% in the conventional and OPCAB groups, respectively (P=0.04). To promote OPCAB in selected patients results in decreasing operative risk to the price of worsening late functional results.
Key Words: Coronary disease; Minimally invasive surgery
1. Introduction
Conventional coronary artery bypass grafting (CABG) under cardiopulmonary bypass (CPB) and cardioplegic arrest remains the gold standard for surgical coronary revascularization. Conventional CABGs generally provide excellent survival and functional results. However, due to a significant morbidity and immobilization stay, conventional CABGs are constantly challenged by less invasive techniques including percutaneous coronary intervention (PCI) and off-pump coronary bypass (OPCAB). Avoiding the potential side effects of CPB, OPCAB exerted by well-trained surgeons is an attractive alternative technique to conventional CABG in almost all patient settings [1]. However, suggested by data from large retrospective studies [2,3], a superior survival with OPCAB has not, until now, been shown by prospective randomized studies [4] probably because of the methodological difficulties inherent to those trials [5].
Despite this it is clinically relevant to observe a facilitated recovery after OPCAB even in patients with important co-morbid conditions with a proven reduction of myocardial injuries, transfusion requirements, neurological impairment and maybe the need for dialysis in patients with preoperative renal insufficiency [6–8]. For the sake of patients and providing that they can achieve an equivalent quality of revascularization, surgeons should consider both techniques not as competitive but as complementary and decide whether or not to use the pump according to each case.
Our OPCAB program started in 1995 and, for ethical considerations, was initially reserved to patients contra-indicated for an aortic clamping. Subsequently, indications were progressively extended towards selected patients and OPCAB surgery was performed routinely in the late 1990s. The present report exposes a single surgeon's practice of CABG performed on or off-pump according to coronary lesions and patient's risk-profile and aims to evaluate our institutional indications for OPCAB vs. conventional CABG.
2. Patients and methods
2.1. Patients and decision criteria
Out of a consecutive series of 328 patients operated on for isolated CABG and who received complete revascularization [9] between January 2000 and January 2003 by a single surgeon trained to both techniques, we included a consecutive series of all 154 patients treated with OPCAB technique with tissue stabilizer and the first 154 patients operated on conventionally with CPB and cardioplegic arrest. Patients were assigned to either technique according to the coronary lesions (to assess feasibility of OPCAB) or to the estimation of risk factors for conventional CABG as assessed by the additive EuroSCORE risk-scale (to enhance potential benefits of OPCAB for the patient). Selected indications for OPCAB (n=154) were isolated LAD coronary system lesions and multivessel diseases with suitable anatomy1 in high surgical risk patients including: EuroSCORE5, age older than 70 years; left ventricular systolic dysfunction defined as left ventricular ejection fraction <50%; COPD; renal insufficiency defined by dialysis or creatinine before surgery >200 mmol/l; and disease of the ascending aorta. However, patients requiring more than 4 distal anastomoses were discarded from OPCAB technique.
2.2. Studied outcomes and statistical analyses
The primary study outcomes were 3-months operative death and perioperative major adverse cardiac and cerebrovascular events (MACCEs). Perioperative MACCEs included cardiac deaths, myocardial infarctions, strokes and repeat target vessel revascularizations (TVR). Estimated mortality was given by the mean value of the EuroSCORE for each considered group of patients. During follow-up, all survivors completed personal or telephone interviews at approximately 45 days and each year after surgery. These interviews assessed major adverse cardiac events (MACEs) including cardiac deaths, recurrence of angina, myocardial infarctions and any new coronary revascularization. All symptomatic patients during follow-up were controlled by coronary angiogram. For deceased patients, date and cause of death was obtained from hospitalization reports or interviews of the relatives and referees. We assessed normality or non-normality of distributions of continuous data by using Kolmogorov–Smirnov test and used Student t-test or Mann–Whitney test accordingly when performing comparison between groups. We compared proportion or percentages of nominal data with Chi-square test. Mid-term results study was based on actuarial analysis (Kaplan–Meier method). Log-rank test was used for comparison of survival curves. For all analyses, statistical significance was established at P<0.05.
2.3. Surgical techniques
All patients were operated on through a standard sternotomy with a small skin incision. Left internal thoracic artery was systematically harvested. Both squeletonized internal thoracic arteries were liberally used in no diabetic patients under 70 years. Arterial grafts were used preferentially to revascularize the left ventricle. Radial artery grafts being very few in this series, internal saphenous grafts were harvested whenever required and used to complete the revascularization. A saline humidified carbon dioxide blower (Medtronic DLP, Minneapolis, MN, USA) was used to facilitate the construction of distal anastomoses in both groups. Proximal anastomoses to the aorta were performed under side clamping. At the end of operation, heparin was completely reversed.
2.3.1. Conventional CABG
Heparin was given at 300 UI/kg. Conventional CABG with CPB was accomplished using slight hypothermic (34 °C) systemic perfusion. The typical circuit was uncoated and integrated a membrane oxygenator with a 40-μm arterial line filter. During aortic cross-clamp, myocardial arrest and protection was assured by cold crystalloid cardioplegia with maintenance doses given every 15 min via a retrograde catheter.
2.3.2. OPCAB technique
Heparin was given at 150 UI/kg. With respect of hemodynamic stability by optimized preload, small boluses of epinephrine and liberal use of IABP in case of depressed ventricular function, a LIMA stitch was used to allow a gentle and progressive dislocation of the heart, therefore presenting all target vessels. Coronary stabilization was obtained using various stabilizing suction devices. Most anastomoses were constructed under simple proximal coronary clamping. In case of excessive feedback bleeding, like in the case of hemodynamic instability or arrhythmia following coronary clamping, coronary shunts were used.
3. Results
During the time interval of this study 47% of patients were operated on with OPCAB technique. Table 1 shows the presentation of coronary disease for patients operated on with OPCAB or conventional techniques. Because of discrepancies in the distribution of coronary lesions and because we limited our OPCAB indications to patients requiring 4 distal anastomoses at maximum, the mean number of distal anastomoses was higher in the group of patients treated conventionally. Table 2 presents the prevalence of relevant risk factors of EuroSCORE in both groups. As a result of a higher EuroSCORE in the OPCAB group, expected operative mortality was also significantly higher: 4.29 [95% CI: 3.83–4.77] vs. 3.54 [95% CI: 3.17–3.91] (P=0.024). Despite this, for an overall 3-months operative mortality of 1.9%, the observed mortality was higher in the group of patients receiving conventional CABG (2.6% vs. 1.3%, non-significant). Four patients from the conventional CABG group died postoperatively. Causes of deaths were cardiac in two cases, respiratory failure and mediastinitis in one case each. Two patients from the OPCAB group died from cardiac causes during the same interval.
In this series, both techniques resulted in below-to-one observed-to-expected (O/E) mortality ratio. The O/E mortality ratio were 0.73 [95% CI: 0.66–0.82] and 0.30 [95% CI: 0.27–0.33] in the conventionally and OPCAB treated group of patients, respectively. Fig. 1 represents the performance across the spectrum of risk for both groups [10]. For the OPCAB group, whatever the cumulative expected mortality on x axis, the corresponding observed mortality was always below the standard of EuroSCORE as opposed to the conventional CABG group.
Evaluation of perioperative morbidity assessed by the MACCEs composite endpoint is resumed in Table 3. It shows no significant differences between groups concerning cardiac deaths, myocardial infarctions, strokes and repeat TVRs. Noticeably, the two strokes in the OPCAB group occurred secondarily to surgery and during postoperative coronary angiography control. As opposed, strokes in the conventional CABG group, being directly imputable to the operative technique, occurred immediately after surgery.
All patients completed a complete follow-up at one year after surgery. Mean follow-up was 20.4±8.8 months. Fig. 2 shows a Kaplan–Meier representation of late survival in both groups with no significant difference in a Log-rank analysis. Fig. 3 shows a Kaplan–Meier representation of survival free from angina. Angina-free survival at three years was 95.8% and 89.6% in the conventional and OPCAB groups, respectively (P=0.04). All coronary angiography during follow up were clinically indicated and all symptomatic patients underwent control angiogram. Patency rate of controlled grafts was comparable for both techniques. Most recurrences of angina, being CCS I or II, were controlled by adjustment of medical therapy. Late percutaneous TVRs were performed in three patients from both groups. Two additional percutaneous non-TVRs were performed during follow-up in the OPCAB group.
4. Discussion
In this series, patients treated conventionally or with OPCAB techniques differed considering both the feature of coronary disease and the operative risk assessment. Therefore straight comparison of results between groups is necessarily inappropriate and we rather used risk-adjusted comparison. Observed-to-expected mortality ratio as compared to the standard of STS has been used previously to validate results of OPCAB surgery [2,12]. In the current series, we used the EuroSCORE risk-scale, the most rigorously evaluated scoring system in cardiac surgery [11]. O/E mortality ratio as compared to the standard of EuroSCORE was 30% in the OPCAB group vs. 73% in the conventional CABG group. Due to the fact that more low surgical risk patients were treated conventionally in the current study and since the EuroSCORE generally over-estimates mortality at lower values [11,13], difference in O/E mortality ratio is probably minimized. This result makes us confident in pursuing OPCAB surgery for selected cases in our CABG program especially since the surgical treatment of coronary disease is nowadays reserved to a declining number of patients who arrive sicker to surgery because of the constant pressure of PCI. With cases becoming sparser and more challenging, a tendency emerges in many centers to centralize indications for coronary surgery on expert surgeons to insure optimal surgical outcome. During the last four years, as a consequence of this evolution, indications for OPCAB increased in our center. Actually we assume that early survival is optimized with the adoption of OPCAB technique whenever possible in selected patients (especially those with a high surgical risk for conventional CABG).
Which patients could benefit the most by OPCAB is indeed a difficult question to be answered. Looking at the performance across the spectrum of risk obtained in both groups [10], we note that the observed mortality in the OPCAB group was always lower than the standard of EuroSCORE. However, when high surgical risk patients were progressively included in the stepwise cumulated analysis, the interval between expected and observed mortality in that group increased, clearly favoring the OPCAB approach in that setting. However, our criteria for OPCAB surgery are to be taken as more than an indication than an incitement. Indeed each surgeon should apply OPCAB technique by negotiating a safe learning curve approach [1]. We deliberately reserved OPCAB surgery for selected cases and performed 47% of our CABG cases off-pump during the period of this study.
Operative technique had no effect on late survival as opposed to late functional results. However, we could not exclude that the higher morbidity observed during follow-up in OPCAB patients might be because of some selection bias, or might be a result of the operation, like deciding not to bypass some arteries for anatomical considerations because the patient is off-pump. Noticeably most recurrences of angina were not related to graft dysfunction and were easily controlled by optimization of medical therapy. Because of the observed morbidity of coronary angiography early after surgery in OPCAB patients, we avoided elective indications of controls in both groups. As a consequence, every coronary angiography control in this series was clinically indicated. It is therefore possible that an unknown proportion of graft failure or evolving coronary lesions remains undiagnosed. However, previous studies have shown that the percentage of graft failure significantly increased in coronary angiographies clinically indicated as opposed to elective controls where 97% of anastomoses are patent [14].
Conventional CABG and OPCAB are both palliative treatments for coronary disease. To promote OPCAB in selected patients results in decreasing operative risk to the apparent price of worsening late functional results.
Appendix A. ICVTS on-line discussion
Author: Shazad G. Raja (Royal Hospital for Sick Children, Glasgow, UK)
eComment: The article by Caus et al. raises important concerns about the quality of anastomoses performed off-pump (OPCAB). As an alternative to conventional coronary artery surgery (CABG), OPCAB can only be adopted if it achieves graft patency rates equal or superior to those of conventional CABG. Interestingly, the study by Caus et al. suggests that OPCAB fails in achieving this most important objective. However, a number of confounding factors not considered by the authors could very well explain the worsening late functional results observed by the authors.
In my opinion, apart from selection bias as accepted by the authors, several other factors that could have negatively affected patency in those who underwent OPCAB include the relatively low dose of intraoperative heparin (150 IU/kg) and its complete reversal at the end, the use of proximal coronary clamping at the time of anastomoses construction, technique of saphenous vein graft harvesting and preservation, the severity of target vessel stenosis (impact of competitive flow), and the absence of aggressive antiplatelet therapy with clopidogrel postoperatively in high risk patients. It would be interesting to know whether the authors took into consideration all of these confounding factors before reaching a conclusion which has far reaching implications for the practice of off-pump coronary artery bypass surgery.
Author: Thierry Caus (University Hospital Timone, Marseille, France)
eResponse: Confounding factors are an important well known limitation of non prospective randomized studies. We published our series, a retrospective analysis of our practice report aiming at addressing two messages to the readers of the Interactive CardioVascular and Thoracic Surgery: i) we observed a mortality for patients operated OPCAB much below the expected mortality predicted by the Euroscore (as opposed to patients operated on-pump for which the predicted mortality was only slightly higher than the observed one) and ii) patients operated with OPCAB technique experienced more often a recurrence of angina during follow-up essentially due to initial biases of selection since all symptomatic patients were controlled by coronary angiogram with similar patency rate of anastomoses performed with either technique. We respect the opinion of Shahzad G. Raja concerning the possibility of an increased coagulation state in patients operated OPCAB, though still controversial to our knowledge [A1]. However, at this point, we do not routinely prescribe aggressive antiplatelet therapy after OPCAB procedures. We totally agree with Shahzad G. Raja in that the functional outcome may be improved by avoiding as much as possible vein grafts and we did significantly increase our use of arterial grafts in patients operated OPCAB during the past two years.
References
A1 Quigley RL, Fried DW, Pym J, Highbloom RY. Off-pump coronary artery bypass surgery may produce a hypercoagulable patient. Heart Surgery Forum 2003;6:94–98.
References
Song H, Petersen R, Sharoni E, Guyton G, Puskas J. Safe evolution towards routine off-pump coronary artery bypass: Negotiating the learning curve. Eur J Cardiothorac Surg 2003;24:947–952.
Cleveland J, Shroyer A, Chen A, Peterson E, Grover F. Off-pump coronary artery bypass grafting decreases risk-adjusted mortality and morbidity. Ann Thorac Surg 2001;72:1282–1289.
Mack M, Bachand D, Acuff T, Edgerton J, Prince S, Dewey T, Magee M. Improved outcomes in coronary artery bypass grafting with beating heart techniques. J Thorac Cardiovasc Surg 2002;124:598–607.
van der Heijden G, Nathoe H, Jansen E, Grobbee D. Meta-analysis on the effect of off-pump coronary bypass surgery. Eur J Cardiothorac Surg 2004;26:81–84.
Anyanwu A, Treasure T. Surgical research revisited: Clinical trials in the cardiothoracic surgical literature. Eur J Cardiothorac Surg 2004;25:299–303.
Puskas J, Williams W, Duke P, Staples J, Glas K, Marshall J, Leimbach M, Huber P, Garas S, Sammons B, McCall S, Petersen R, Bailey D, Chu H, Mahoney E, Weintraub W, Guyton R. Off-pump coronary artery bypass grafting provides complete revascularization with reduced myocardial injury, transfusion requirements, and length of stay: a prospective randomized comparison of two hundred unselected patients undergoing off-pump vs. conventional coronary artery bypass grafting. J Thorac Cardiovasc Surg 2003;125:797–808.
Zamvar V, Williams D, Hall J, Payne N, Cann C, Young K, Karthikeyan S, Dunne J. Assessment of neurocognitive impairment after off-pump and on-pump techniques for coronary artery bypass graft surgery: prospective randomised controlled trial. BMJ 2002;325:1268–1271.
Sabik J, Gillinov M, Blackstone E, Vacha C, Houghtaling P, Navia J, Smedira N, McCarthy P, Cosgrove D, Lytle B. Does off-pump coronary surgery reduce morbidity and mortality J Thorac Cardiovasc Surg 2002;124:698–707.
Vander Salm TJ, Kip KE, Jones RH, Schaff HV, Shemin RJ, Aldea GS, Detre KM. What constitutes optimal surgical revascularization Answers from the Bypass Angioplasty Revascularization Investigation (BARI). J Am Coll Cardiol 2002;39:565–572.
Sergeant P, de Worm E, Meyns B, Wouters P. The challenge of departmental quality control in the reengineering towards off-pump coronary artery bypass grafting. Eur J Cardiothorac Surg 2001;20:538–543.
Gogbashian A, Sedrakyan A, Treasure T. EuroSCORE: a systematic review of international performance. Eur J Cardiothorac Surg 2004;25:695–700.
Plomondon M, Cleveland J, Ludwig S, Grunwald G, Kiefe C, Grover F, Shroyer A. Off-pump coronary artery bypass is associated with improved risk-adjusted outcomes. Ann Thorac Surg 2001;72:114–119.
Sergeant P, de Worm E, Meyns B. Single centre, single domain validation of the EuroSCORE on a consecutive sample of primary and repeat CABG. Eur J Cardiothorac Surg 2001;20:1176–1182.
Weigang E, Royl J, Dencker A, Schoellhorn J, van de Loo A, Beyersdorf F. Results after MIDCAB and OPCAB surgeries: problems and consequences of incomplete angiographic follow-up in the mid-term course. Interact CardioVasc and Thorac Surg 2004;3:302–308.(Thierry Caus, Yves Seree,)
b Anaesthesiology Department, Timone University Hospital, Marseilles, France
c Cardiology Department, Timone University Hospital, Marseilles, France
Presented at the 53rd International Congress of the European Society for Cardiovascular Surgery, Ljubljana, Slovenia, June 2–5, 2004.
1 Superficial vessels, not or moderately calcified; with a diameter >1.2 mm.
Abstract
This non-randomized retrospective study included all patients operated on for CABG through median sternotomy between January 2000 and December 2002 by the same surgeon trained to both techniques. Using risk-adjusted comparison where expected mortality was given by the EuroSCORE value assessed pre-operatively, and studying mid-term survival and functional results we aimed to evaluate our indications for OPCAB versus conventional CABG through a consecutive series of 308 patients. Selected indications for OPCAB (n=154) were isolated LAD coronary system lesions and multivessel diseases with suitable anatomy in high surgical risk patients (EuroSCORE5). The first 154 patients operated on conventionally during the time-study interval were included in the control group. Expected mortality was significantly higher in the OPCAB group: 4.29 [95% CI: 3.83–4.77] vs. 3.54 [95% CI: 3.17–3.91] (P=0.024). Observed mortality was 1.3% and 2.6% for patients treated OPCAB and with conventional technique, respectively. Survival at three years was 91.5 and 93.8% in the conventional and OPCAB groups, respectively. Angina-free survival at three years was 95.8% and 89.6% in the conventional and OPCAB groups, respectively (P=0.04). To promote OPCAB in selected patients results in decreasing operative risk to the price of worsening late functional results.
Key Words: Coronary disease; Minimally invasive surgery
1. Introduction
Conventional coronary artery bypass grafting (CABG) under cardiopulmonary bypass (CPB) and cardioplegic arrest remains the gold standard for surgical coronary revascularization. Conventional CABGs generally provide excellent survival and functional results. However, due to a significant morbidity and immobilization stay, conventional CABGs are constantly challenged by less invasive techniques including percutaneous coronary intervention (PCI) and off-pump coronary bypass (OPCAB). Avoiding the potential side effects of CPB, OPCAB exerted by well-trained surgeons is an attractive alternative technique to conventional CABG in almost all patient settings [1]. However, suggested by data from large retrospective studies [2,3], a superior survival with OPCAB has not, until now, been shown by prospective randomized studies [4] probably because of the methodological difficulties inherent to those trials [5].
Despite this it is clinically relevant to observe a facilitated recovery after OPCAB even in patients with important co-morbid conditions with a proven reduction of myocardial injuries, transfusion requirements, neurological impairment and maybe the need for dialysis in patients with preoperative renal insufficiency [6–8]. For the sake of patients and providing that they can achieve an equivalent quality of revascularization, surgeons should consider both techniques not as competitive but as complementary and decide whether or not to use the pump according to each case.
Our OPCAB program started in 1995 and, for ethical considerations, was initially reserved to patients contra-indicated for an aortic clamping. Subsequently, indications were progressively extended towards selected patients and OPCAB surgery was performed routinely in the late 1990s. The present report exposes a single surgeon's practice of CABG performed on or off-pump according to coronary lesions and patient's risk-profile and aims to evaluate our institutional indications for OPCAB vs. conventional CABG.
2. Patients and methods
2.1. Patients and decision criteria
Out of a consecutive series of 328 patients operated on for isolated CABG and who received complete revascularization [9] between January 2000 and January 2003 by a single surgeon trained to both techniques, we included a consecutive series of all 154 patients treated with OPCAB technique with tissue stabilizer and the first 154 patients operated on conventionally with CPB and cardioplegic arrest. Patients were assigned to either technique according to the coronary lesions (to assess feasibility of OPCAB) or to the estimation of risk factors for conventional CABG as assessed by the additive EuroSCORE risk-scale (to enhance potential benefits of OPCAB for the patient). Selected indications for OPCAB (n=154) were isolated LAD coronary system lesions and multivessel diseases with suitable anatomy1 in high surgical risk patients including: EuroSCORE5, age older than 70 years; left ventricular systolic dysfunction defined as left ventricular ejection fraction <50%; COPD; renal insufficiency defined by dialysis or creatinine before surgery >200 mmol/l; and disease of the ascending aorta. However, patients requiring more than 4 distal anastomoses were discarded from OPCAB technique.
2.2. Studied outcomes and statistical analyses
The primary study outcomes were 3-months operative death and perioperative major adverse cardiac and cerebrovascular events (MACCEs). Perioperative MACCEs included cardiac deaths, myocardial infarctions, strokes and repeat target vessel revascularizations (TVR). Estimated mortality was given by the mean value of the EuroSCORE for each considered group of patients. During follow-up, all survivors completed personal or telephone interviews at approximately 45 days and each year after surgery. These interviews assessed major adverse cardiac events (MACEs) including cardiac deaths, recurrence of angina, myocardial infarctions and any new coronary revascularization. All symptomatic patients during follow-up were controlled by coronary angiogram. For deceased patients, date and cause of death was obtained from hospitalization reports or interviews of the relatives and referees. We assessed normality or non-normality of distributions of continuous data by using Kolmogorov–Smirnov test and used Student t-test or Mann–Whitney test accordingly when performing comparison between groups. We compared proportion or percentages of nominal data with Chi-square test. Mid-term results study was based on actuarial analysis (Kaplan–Meier method). Log-rank test was used for comparison of survival curves. For all analyses, statistical significance was established at P<0.05.
2.3. Surgical techniques
All patients were operated on through a standard sternotomy with a small skin incision. Left internal thoracic artery was systematically harvested. Both squeletonized internal thoracic arteries were liberally used in no diabetic patients under 70 years. Arterial grafts were used preferentially to revascularize the left ventricle. Radial artery grafts being very few in this series, internal saphenous grafts were harvested whenever required and used to complete the revascularization. A saline humidified carbon dioxide blower (Medtronic DLP, Minneapolis, MN, USA) was used to facilitate the construction of distal anastomoses in both groups. Proximal anastomoses to the aorta were performed under side clamping. At the end of operation, heparin was completely reversed.
2.3.1. Conventional CABG
Heparin was given at 300 UI/kg. Conventional CABG with CPB was accomplished using slight hypothermic (34 °C) systemic perfusion. The typical circuit was uncoated and integrated a membrane oxygenator with a 40-μm arterial line filter. During aortic cross-clamp, myocardial arrest and protection was assured by cold crystalloid cardioplegia with maintenance doses given every 15 min via a retrograde catheter.
2.3.2. OPCAB technique
Heparin was given at 150 UI/kg. With respect of hemodynamic stability by optimized preload, small boluses of epinephrine and liberal use of IABP in case of depressed ventricular function, a LIMA stitch was used to allow a gentle and progressive dislocation of the heart, therefore presenting all target vessels. Coronary stabilization was obtained using various stabilizing suction devices. Most anastomoses were constructed under simple proximal coronary clamping. In case of excessive feedback bleeding, like in the case of hemodynamic instability or arrhythmia following coronary clamping, coronary shunts were used.
3. Results
During the time interval of this study 47% of patients were operated on with OPCAB technique. Table 1 shows the presentation of coronary disease for patients operated on with OPCAB or conventional techniques. Because of discrepancies in the distribution of coronary lesions and because we limited our OPCAB indications to patients requiring 4 distal anastomoses at maximum, the mean number of distal anastomoses was higher in the group of patients treated conventionally. Table 2 presents the prevalence of relevant risk factors of EuroSCORE in both groups. As a result of a higher EuroSCORE in the OPCAB group, expected operative mortality was also significantly higher: 4.29 [95% CI: 3.83–4.77] vs. 3.54 [95% CI: 3.17–3.91] (P=0.024). Despite this, for an overall 3-months operative mortality of 1.9%, the observed mortality was higher in the group of patients receiving conventional CABG (2.6% vs. 1.3%, non-significant). Four patients from the conventional CABG group died postoperatively. Causes of deaths were cardiac in two cases, respiratory failure and mediastinitis in one case each. Two patients from the OPCAB group died from cardiac causes during the same interval.
In this series, both techniques resulted in below-to-one observed-to-expected (O/E) mortality ratio. The O/E mortality ratio were 0.73 [95% CI: 0.66–0.82] and 0.30 [95% CI: 0.27–0.33] in the conventionally and OPCAB treated group of patients, respectively. Fig. 1 represents the performance across the spectrum of risk for both groups [10]. For the OPCAB group, whatever the cumulative expected mortality on x axis, the corresponding observed mortality was always below the standard of EuroSCORE as opposed to the conventional CABG group.
Evaluation of perioperative morbidity assessed by the MACCEs composite endpoint is resumed in Table 3. It shows no significant differences between groups concerning cardiac deaths, myocardial infarctions, strokes and repeat TVRs. Noticeably, the two strokes in the OPCAB group occurred secondarily to surgery and during postoperative coronary angiography control. As opposed, strokes in the conventional CABG group, being directly imputable to the operative technique, occurred immediately after surgery.
All patients completed a complete follow-up at one year after surgery. Mean follow-up was 20.4±8.8 months. Fig. 2 shows a Kaplan–Meier representation of late survival in both groups with no significant difference in a Log-rank analysis. Fig. 3 shows a Kaplan–Meier representation of survival free from angina. Angina-free survival at three years was 95.8% and 89.6% in the conventional and OPCAB groups, respectively (P=0.04). All coronary angiography during follow up were clinically indicated and all symptomatic patients underwent control angiogram. Patency rate of controlled grafts was comparable for both techniques. Most recurrences of angina, being CCS I or II, were controlled by adjustment of medical therapy. Late percutaneous TVRs were performed in three patients from both groups. Two additional percutaneous non-TVRs were performed during follow-up in the OPCAB group.
4. Discussion
In this series, patients treated conventionally or with OPCAB techniques differed considering both the feature of coronary disease and the operative risk assessment. Therefore straight comparison of results between groups is necessarily inappropriate and we rather used risk-adjusted comparison. Observed-to-expected mortality ratio as compared to the standard of STS has been used previously to validate results of OPCAB surgery [2,12]. In the current series, we used the EuroSCORE risk-scale, the most rigorously evaluated scoring system in cardiac surgery [11]. O/E mortality ratio as compared to the standard of EuroSCORE was 30% in the OPCAB group vs. 73% in the conventional CABG group. Due to the fact that more low surgical risk patients were treated conventionally in the current study and since the EuroSCORE generally over-estimates mortality at lower values [11,13], difference in O/E mortality ratio is probably minimized. This result makes us confident in pursuing OPCAB surgery for selected cases in our CABG program especially since the surgical treatment of coronary disease is nowadays reserved to a declining number of patients who arrive sicker to surgery because of the constant pressure of PCI. With cases becoming sparser and more challenging, a tendency emerges in many centers to centralize indications for coronary surgery on expert surgeons to insure optimal surgical outcome. During the last four years, as a consequence of this evolution, indications for OPCAB increased in our center. Actually we assume that early survival is optimized with the adoption of OPCAB technique whenever possible in selected patients (especially those with a high surgical risk for conventional CABG).
Which patients could benefit the most by OPCAB is indeed a difficult question to be answered. Looking at the performance across the spectrum of risk obtained in both groups [10], we note that the observed mortality in the OPCAB group was always lower than the standard of EuroSCORE. However, when high surgical risk patients were progressively included in the stepwise cumulated analysis, the interval between expected and observed mortality in that group increased, clearly favoring the OPCAB approach in that setting. However, our criteria for OPCAB surgery are to be taken as more than an indication than an incitement. Indeed each surgeon should apply OPCAB technique by negotiating a safe learning curve approach [1]. We deliberately reserved OPCAB surgery for selected cases and performed 47% of our CABG cases off-pump during the period of this study.
Operative technique had no effect on late survival as opposed to late functional results. However, we could not exclude that the higher morbidity observed during follow-up in OPCAB patients might be because of some selection bias, or might be a result of the operation, like deciding not to bypass some arteries for anatomical considerations because the patient is off-pump. Noticeably most recurrences of angina were not related to graft dysfunction and were easily controlled by optimization of medical therapy. Because of the observed morbidity of coronary angiography early after surgery in OPCAB patients, we avoided elective indications of controls in both groups. As a consequence, every coronary angiography control in this series was clinically indicated. It is therefore possible that an unknown proportion of graft failure or evolving coronary lesions remains undiagnosed. However, previous studies have shown that the percentage of graft failure significantly increased in coronary angiographies clinically indicated as opposed to elective controls where 97% of anastomoses are patent [14].
Conventional CABG and OPCAB are both palliative treatments for coronary disease. To promote OPCAB in selected patients results in decreasing operative risk to the apparent price of worsening late functional results.
Appendix A. ICVTS on-line discussion
Author: Shazad G. Raja (Royal Hospital for Sick Children, Glasgow, UK)
eComment: The article by Caus et al. raises important concerns about the quality of anastomoses performed off-pump (OPCAB). As an alternative to conventional coronary artery surgery (CABG), OPCAB can only be adopted if it achieves graft patency rates equal or superior to those of conventional CABG. Interestingly, the study by Caus et al. suggests that OPCAB fails in achieving this most important objective. However, a number of confounding factors not considered by the authors could very well explain the worsening late functional results observed by the authors.
In my opinion, apart from selection bias as accepted by the authors, several other factors that could have negatively affected patency in those who underwent OPCAB include the relatively low dose of intraoperative heparin (150 IU/kg) and its complete reversal at the end, the use of proximal coronary clamping at the time of anastomoses construction, technique of saphenous vein graft harvesting and preservation, the severity of target vessel stenosis (impact of competitive flow), and the absence of aggressive antiplatelet therapy with clopidogrel postoperatively in high risk patients. It would be interesting to know whether the authors took into consideration all of these confounding factors before reaching a conclusion which has far reaching implications for the practice of off-pump coronary artery bypass surgery.
Author: Thierry Caus (University Hospital Timone, Marseille, France)
eResponse: Confounding factors are an important well known limitation of non prospective randomized studies. We published our series, a retrospective analysis of our practice report aiming at addressing two messages to the readers of the Interactive CardioVascular and Thoracic Surgery: i) we observed a mortality for patients operated OPCAB much below the expected mortality predicted by the Euroscore (as opposed to patients operated on-pump for which the predicted mortality was only slightly higher than the observed one) and ii) patients operated with OPCAB technique experienced more often a recurrence of angina during follow-up essentially due to initial biases of selection since all symptomatic patients were controlled by coronary angiogram with similar patency rate of anastomoses performed with either technique. We respect the opinion of Shahzad G. Raja concerning the possibility of an increased coagulation state in patients operated OPCAB, though still controversial to our knowledge [A1]. However, at this point, we do not routinely prescribe aggressive antiplatelet therapy after OPCAB procedures. We totally agree with Shahzad G. Raja in that the functional outcome may be improved by avoiding as much as possible vein grafts and we did significantly increase our use of arterial grafts in patients operated OPCAB during the past two years.
References
A1 Quigley RL, Fried DW, Pym J, Highbloom RY. Off-pump coronary artery bypass surgery may produce a hypercoagulable patient. Heart Surgery Forum 2003;6:94–98.
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