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Ann Thorac Surg 2005;80:136-142
© 2005 The Society of Thoracic Surgeons

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Original article: Cardiovascular

On-Pump Versus Off-Pump Surgical Revascularization for Left Main Stem Stenosis: Risk Adjusted Outcomes

^a Department of Cardiothoracic Surgery, The Cardiothoracic Centre, Liverpool, United Kingdom
^b Department of Research and Development, The Cardiothoracic Centre, Liverpool, United Kingdom

Accepted for publication February 1, 2005.

^_* Address reprint requests to Mr Grayson, The Cardiothoracic Centre-Liverpool, Thomas Dr, Liverpool, L14 3PE, UK (Email: tony.grayson{at}ctc.nhs.uk).

	Abstract

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
BACKGROUND: Recent publications have shown coronary surgery is safe and effective in patients with critical left main stem stenosis when using off-pump coronary surgery techniques. However, these studies were small and did not adjust for differences in case mix.

METHODS: Between April 1997 and March 2003, 1,197 consecutive patients with critical left main stem stenosis (> 50%) underwent coronary surgery. Two hundred and fifty-nine (21.6%) of these patients had off-pump coronary surgery, while 938 (78.4%) received on-pump coronary surgery. Multivariate logistic regression and Cox proportional hazards analysis were used to assess the effect of off-pump coronary surgery on outcomes, while adjusting for patient characteristics (treatment selection bias). Treatment selection bias was controlled by constructing a propensity score from core patient characteristics. The propensity score was the probability of receiving off-pump coronary surgery and was included along with the comparison variable in the multivariable analyses of outcome.

RESULTS: After adjusting for the propensity score, the requirement for inotropic support (22.4% versus 35.3%; p < 0.001) or a prolonged length of stay (5.3% versus 9.3%; p = 0.034) were significantly reduced after receiving off-pump coronary surgery. There was a trend to suggest that off-pump patients had a lower incidence of stroke and chest infection. The adjusted freedom from death in off-pump patients at 2 years was 94.6% compared with 93.6% for on-pump patients (p = 0.54).

CONCLUSIONS: After risk adjustment, patients with critical left main stem stenosis can undergo off-pump coronary surgery safely, with results comparable with on-pump coronary surgery.

	Introduction

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Patients with significant left main stem (LMS) disease, ie, greater than 50% stenosis of the left main coronary artery, are considered by many as being at high risk of mortality after coronary artery bypass grafting (CABG) [1, 2]. The Society of Cardiothoracic Surgeons of Great Britain and Ireland recently identified that patients with significant LMS disease are almost twice as likely to die after their CABG [2]; even though proven risk models, such as the European System for Cardiac Operative Risk Evaluation (EuroSCORE), have not identified LMS disease as an independent risk factor for mortality [3]. However, the prognostic benefits of surgical intervention over medical therapy are well proven [4] and the use of percutaneous coronary interventions is still not clear [5]. The growing evidence supporting the use of off-pump CABG, especially in high-risk patients [6–10], has turned attention for this technique toward patients with LMS disease in the hope of improving prognosis.

In recent years, there have been data published from a few institutions [11–14] suggesting that the risks of undergoing off-pump CABG in patients with LMS disease are similar, if not better, than receiving conventional on-pump CABG, particularly with respect to lower mortality, inotrope use, chest infection, and postoperative length of stay. However, these results are unclear due to the small number of off-pump CABG patients studied and lack of adjustments for differences in case mix. We therefore aimed to study the effect of off-pump CABG, compared with conventional on-pump CABG, in patients with LMS disease on risk-adjusted mortality and morbidity.

	Material and Methods

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Patient Population
Between 1 April 1997 and 31 March 2003, 1,197 consecutive patients with LMS disease underwent isolated CABG at the Cardiothoracic Centre in Liverpool. Critical LMS disease was defined as LMS with stenosis greater than 50%, in line with the definition used by the Society of Cardiothoracic Surgeons of Great Britain and Ireland [2]. Patients undergoing CABG that was combined with heart valve repair or replacement, resection of a ventricular aneurysm, or other surgical procedures were not included.

Surgical Techniques
Off-pump CABG was performed consecutively by three of the seven surgeons at our institution who have switched their entire coronary revascularization practice to off-pump surgery. Any conversions to cardiopulmonary bypass (CPB) were classified as off-pump cases on the basis of "intention to treat" analysis (8 cases were converted to CPB).

All off-pump patients were operated through a median sternotomy approach. Target coronary arteries were stabilized using the Octopus II+ tissue stabilization system Medtronic, Minneapolis, MN). Appropriate size intracoronary shunts (Medtronic Clearview Shunt; Medtronic) were used in all cases to maintain distal perfusion and to achieve a bloodless operative field. Visualization was aided with a humidified carbon dioxide blower (CTS Aires CO2 Blower; Cardiothoracic Systems, Cupertino, CA). Hypothermia was prevented by application of an air warming blanket to the lower half of the body.

In the on-pump group, standard CPB techniques were used with a median sternotomy approach. Membrane oxygenators and roller pump heads were used for the CPB. Normothermia or mild hypothermia (34–36°C) was maintained and myocardial protection was achieved with antegrade induction of blood cardioplegia followed by intermittent antegrade or continuous retrograde warm blood cardioplegia.

Data Collection
Preoperative definitions and data collection methods have been previously published [15]. Data were collected prospectively during the patient’s admission as part of routine clinical practice and entered into our cardiac surgery registry (Tables 1 and 2).

Follow-Up Mortality
Patient records were linked to the National Strategic Tracing Service (NSTS), which records all deaths in the United Kingdom. To establish current vital status, patients were matched to the NSTS based on patient name, National Health Service unique number, date of birth, gender, and postcode.

Statistical Analysis
Continuous variables are shown as median with 25th and 75th percentiles and categorical variables are shown as a percentage. Comparisons were made with Wilcoxon rank sum and ² tests as appropriate. Standard statistical tests were used to calculate odds ratios (OR) with 95% confidence intervals (CI). Logistic regression was used to adjust in-hospital outcomes for differences in patient and disease characteristics (treatment selection bias) [17]. Deaths occurring as a function of time were described using the product limit methodology of Kaplan and Meier [18]. To control for treatment selection bias, we used Cox proportional hazards analyses to calculate adjusted hazard ratios (HR) and to risk adjust the Kaplan-Meier survival curves [19].

Treatment selection bias was controlled for by constructing a propensity score [20]. The propensity score was the probability that a patient would receive off-pump CABG, and was constructed from all the variables listed in Table 1. The C statistic for this model was 0.74 [21]. Once the propensity score is constructed for each patient, there are three ways of using the score for comparisons: matching, stratification, and multivariable adjustment. Due to the small sample size available to us for this study, we have decided to use multivariable adjustment because matching would have reduced the study size even further and stratification can be difficult to interpret. The propensity score is then included along with the comparison variable (off-pump or on-pump) in multivariable analyses of outcome producing adjusted OR with 95% CI as shown in Table 3 and adjusted Kaplan-Meier survival curves. The propensity score adjusts for the treatment selection bias, which is evident in Table 1, between one group and the other. Using a propensity score as the sole means for adjusting outcomes was preferable due to the low number of events in our study and provides better adjustment for those factors driving treatment selection; the overall effect is more complete risk adjustment [20]. Due to concerns of a potential time effect on our results, we repeated our analyses with year of operation included as a covariate in the multivariate models. All results remained consistent with our conclusions and therefore are not shown in this report. In all cases a p value less than 0.05 was considered significant. All statistical analysis was performed retrospectively with SAS for Windows Version 8.2 (SAS, Cary, NC).

	Results

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View larger version (35K): [in this window] [in a new window]   Fig 1. Distribution of off-pump and on-pump coronary artery bypass grafting (CABG) undertaken during the study period.

Crude In-Hospital Outcomes
Table 2 shows that off-pump patients were less likely to require inotropic support or a prolonged length of stay. Off-pump patients also had significantly less incidence of postoperative stroke and chest infections.

Crude Two-Year Mortality
Seventy-two (6.0%) deaths occurred during the study with a total follow-up period of 24,044 patient-months (mean follow-up of 20.1 months). The number of patients at risk of death during the follow-up period for both study groups is shown in Figure 2. The crude HR of two-year mortality for off-pump patients was 1.11 (95% CI 0.64 to 1.93; p = 0.71). Freedom from death in off-pump patients at 30 days, 1 year, and 2 years was 96.5%, 94.5%, and 93.1%, respectively, compared with 97.4%, 95.2%, and 93.7% for on-pump patients (Fig 2).

View larger version (16K): [in this window] [in a new window]   Fig 2. Observed survival after coronary artery bypass surgery. p = 0.71; -·-·- = on-pump; — = off-pump.

View larger version (13K): [in this window] [in a new window]   Fig 3. Adjusted survival after coronary artery bypass surgery, adjusted for the propensity score, p = 0.54; -·-·- = on-pump; — = off-pump.

	Comment

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

Although these patients are high-risk, the long-term prognosis is vastly improved when receiving CABG compared with medical therapy alone [4]. However, the desire to improve the results of CABG surgery in patients with significant LMS stenosis is of great interest to cardiac surgeons. With the growing number of institutions showing improved results in off-pump CABG compared with on-pump CABG [6–10], interest has now turned to examining the potential benefits of off-pump CABG in this high-risk group.

A small number of reports [11–14] have examined the results of off-pump CABG in patients with LMS disease; all of which have concluded that this technique is feasible and safe compared to conventional on-pump CABG. These reports have all been carried out on around 100 patients or less and in some cases were limited by not attempting to risk-adjust for selection bias.

Dewey and colleagues original work [13] involved 100 LMS patients who received off-pump CABG. They performed a multivariate logistic regression analysis which concluded that the use of cardiopulmonary bypass was a significant risk factor for in-hospital mortality, with an OR of 7.3. It is important to note that the confidence limits around this estimate were rather large (95% CI 1.3 to 138.4) due to the small sample size and that vast differences between off-pump and on-pump patients, such as extent of disease and renal dysfunction, were not adjusted for. Dewey did note in the discussion, however, that since performing the original analysis their series of off-pump CABG had grown to 273 patients and showed a strong significant difference between the groups with respect to in-hospital mortality in favor of the off-pump technique.

Yeatman and colleagues [14] had a slightly smaller cohort of only 75 off-pump CABG with significant LMS stenosis and made no attempt at risk adjustment for differences in case mix. The preoperative characteristics were relatively well-matched between off-pump and on-pump patients; however, a significant difference with respect to extent of disease was present. Off-pump patients had a lower incidence of inotropic support, temporary pacing, blood transfusion, and chest infection, plus a shorter postoperative length of stay. Unlike Dewey and colleagues [13], Yeatman and colleagues could not demonstrate a survival advantage even up to 24 months after the surgery.

In our retrospective series of 259 off-pump CABG in patients with significant LMS disease, we have risk-adjusted for differences in case mix by using a propensity score. Adjusting for a propensity score or "balancing score," as we have done by including all the variables listed in Table 1, not only adjusts for significant factors but augments them with other variables, even if not significant. The aim is to balance the patient characteristics in both study groups by incorporating "everything" that may relate to potential systematic bias [20].

After risk-adjusting for differences in case mix, our findings are very similar to the findings of Yeatman and colleagues [14] backing up the inferences made from their report. Off-pump CABG was associated with lower inotrope support and less prolonged postoperative length of stay. Chest infections were also less likely, but just failed to reach statistical significance (adjusted OR 0.49; p = 0.057). We also could not find a significant difference between in-hospital and 24-month mortality.

The incidence of stroke also demonstrated a significant trend toward being reduced by off-pump CABG with an adjusted OR of 0.17 (95% CI 0.02 to1.31; p = 0.088). The low occurrence of stroke led to the significantly wide confidence intervals. Several reports have demonstrated a lower incidence of stroke when receiving off-pump CABG [6, 7, 10, 22]. Calafiore and colleagues [22] have concluded that off-pump cases using side-clamping provide the same risk of stroke as in patients in whom CPB, aortic cannulation, and cross-clamping were used. Previous work involving this institution has, however, shown that off-pump CABG significantly lowers stroke rates compared with conventional on-pump CABG, irrespective of aortic manipulation [7]. We believe the mechanism for this apparent advantage is through a reduction in the embolic load caused by the bypass circuit generating microgaseous and microparticulate emboli during the procedure.

There are some limitations which may affect the conclusions drawn from our study. First, this is an observational study and by its retrospective nature cannot account for the unknown variables affecting the outcomes that are not correlated strongly with the variables used in the risk adjustment. Second, the study is spread over a period of five years with most patients on CPB being from the early part of the study period, and with most belonging to the off-pump group from the later part of the study period. Also, the off-pump patients include the period during the "learning curve," maybe indicating a degree of selection bias. Perhaps one of the most important limitations is inextricable confounding [20] caused by the off-pump procedures being performed completely by three of the seven surgeons. Even after careful application of multivariate analyses and propensity scores, it remains difficult to distinguish between surgeon and treatment differences. However, historical results of the three surgeons when they performed on-pump CABG, with regard to postoperative outcomes in LMS patients, were similar to their colleagues (Table 4). A final limitation is that we have only assessed survival in the follow-up period as data on cardiac events (recurrent angina, reoperation, myocardial infarction, etc) are not currently recorded.

In conclusion, off-pump CABG is feasible and safe to perform in patients with significant LMS stenosis. There is no difference between the groups with respect to mortality, but the incidence of postoperative morbidity can be significantly reduced when performing off-pump CABG in this high-risk group of patients.

	Acknowledgments

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We would like to acknowledge the cooperation given to us by all the Consultant Cardiac Surgeons at the Cardiothoracic Centre-Liverpool: John A. C. Chalmers, Walid C. Dihmis, Brian M. Fabri, Elaine M. Griffiths, Neeraj K. Mediratta, D. Mark Pullan, and Abbas Rashid. We would also like to thank Janet Deane, who maintains the quality and ensures completeness of data collected in our Cardiac Surgery Registry.

	References

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): John C.Y. Lu Antony D. Grayson Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lu, J. C.Y. Articles by Pullan, D. M. Search for Related Content PubMed PubMed Citation Articles by Lu, J. C.Y. Articles by Pullan, D. M. Related Collections Coronary disease Related Article