Innovations: Technology & Techniques in Cardiothoracic & Vascular Surgery:
Off-Pump Coronary Artery Bypass Grafting is Associated With Reduced Operative Mortality and In-Hospital Adverse Events in Patients With Left Main Coronary Artery Disease
Sarin, Eric L. MD*; Puskas, John D. MD*; Kilgo, Patrick D. MS†; Thourani, Vinod H. MD*; Guyton, Robert A. MD*; Lattouf, Omar M. MD, PhD*
From the *Division of Cardiothoracic Surgery, Joseph B. Whitehead Department of Surgery, Carlyle Fraser Heart Center, Cardiothoracic Surgery Clinical Research Unit; and †Department of Biostatistics, Rollins School of Public Health, Emory University School of Medicine, Atlanta, GA, USA.
Accepted for publication February 4, 2009.
Presented at the Annual Meeting of the International Society for Minimally Invasive Cardiothoracic Surgery, Boston, MA, June 11–14, 2008.
Address correspondence and reprint requests to Omar M. Lattouf, MD, PhD; 550 Peachtree Street, MOT, 6th Floor, Atlanta, GA 30308 USA; E-mail: email@example.com.
Disclosure: Robert Guyton has research relationships from Edwards Lifesciences, Medtronic, OnX Life technologies and a consulting relationship with Transcardiac Therapeutics.
John Puskas has research relationships with Medtronic, Maquet, OnX life technoliges, Cardica and consulting relationships with Medtronic, Maquet, Transcardiac therapeutics.
Vinod Thourani has research relationships with Maquet, Medtronic, Edwards Lifesciences, and consulting relationships with Cardiomems, Mitral Solutions. Omar Lattouf has research relationships with OnX life technologies and consulting relationships with Medtronic, Cardiogenesis and Baxter.
Objective: Left main coronary artery disease (LMD) is a known risk factor for perioperative complications. This study compares off-pump coronary artery bypass (OPCAB) versus on-pump coronary artery bypass (ONCAB) grafting, CABG, with respect to in-hospital death, stroke, myocardial infarction, and major adverse cardiac events (MACE) in CABG patients with and without LMD.
Methods: Among 13,108 consecutive isolated patients with CABG treated from 1997 to 2007, 2891 patients (22.1%) were preoperatively found to have LMD. Of 5917 patients with OPCAB, 1276 (21.6%) had LMD, whereas among patients with ONCAB, 1615 of 7191 (22.5%) had LMD. Surgery type, LMD, and their interaction were examined for their impact on operative mortality, stroke, myocardial infarction, and MACE via multiple logistic regression models and adjusted odds ratios (AOR).
Results: Utilization of OPCAB for coronary revascularization in patients with LMD disease gradually increased from an initial low of 1.3% of patients in 1997 to a peak of 80.8% in 2007. OPCAB was associated with reduced incidence of stroke (AOR = 0.51, P < 0.001) and MACE (AOR = 0.66, P = 0.002), whereas LMD was associated with an increased incidence of MACE (AOR = 1.24, P = 0.038). No interactions between surgery type and LMD existed, meaning that the 2 conditions did not combine in any way to modify outcomes.
Conclusions: Patients with LMD are more likely to suffer a MACE event than those without LMD. Off-pump coronary artery bypass grafting is marginally associated with lesser risk of operative mortality and significantly associated with less stroke and overall MACE when compared with ONCAB. This benefit of OPCAB is similar for patients with and without LMD.
Atherosclerotic disease of the left main coronary artery (LMD) has long been recognized as a significant risk factor with considerable associated morbidity and mortality.1 Revascularization using on-pump coronary artery bypass (ONCAB) grafting has been established as the standard of care for the treatment of these lesions.2 The application of coronary artery bypass grafting (CABG) without the use of off-pump coronary artery bypass (OPCAB) has grown substantially over the last 2 decades. Powered by favorable early results,3,4 the broad application of OPCAB has been facilitated by technical improvements in intraoperative stabilization devices as well as the increase in surgical expertise and improved management of hemodynamic fluctuations by the anesthesiologist This has been corroborated by multiple studies demonstrating improved outcomes associated with the OPCAB approach.5–9
Despite these technical improvements and the tangible benefits associated with the OPCAB approach, some surgeons have considered LMD has remained a relative contraindication to the performance of OPCAB. Concerns over the large amount of at-risk myocardium and the perceived inevitability of at least some hemodynamic instability during surgery have prompted many to forego the benefits of OPCAB for the ONCAB approach in that subset of patients with LMD.
The aim of this study was to evaluate and compare the clinical outcomes for patients with LMD who underwent either ONCAB or OPCAB for coronary artery disease.
MATERIALS AND METHODS
The Society of Thoracic Surgeons (STS) Adult Cardiac Database was searched for all patients who underwent primary isolated CABG at Emory Health Care Hospitals Emory University Hospital (Atlanta, GA), Emory Crawford Long Hospital (Atlanta, GA), and Wellstar Kennestone Hospital (Marietta, GA) between January 1, 1997 and April 30, 2007. This time frame was chosen to coincide with the entire period during which OPCAB was performed. The study cohort consisted of 13,108 consecutive patients including urgent and emergent patients. Extracted records from this retrospective study included demographic data, preexisting comorbidities, surgeon identity, operative strategy, and clinical outcomes. The study was approved by the Emory University Institutional Review Board in compliance with HIPAA regulations and the Declaration of Helsinki. The Institutional Review Board waived individual patient consent.
Interventions, Surgeons, and Surgical Technique
Each patient underwent a single surgical session consisting of either OPCAB or ONCAB, performed at the discretion of any of 17 faculty surgeons during this time period. OPCAB was performed with 1 of several commercially available cardiac positioning and coronary artery stabilizing devices, using techniques that have been previously described.10 Conventional ONCAB was performed with standard techniques, using roller head pumps, membrane oxygenator, cardiotomy suction, arterial filter, cold antegrade and retrograde blood cardioplegia, and moderate systemic hypothermia (30°C–34°C). Patients who were converted intraoperatively from OPCAB to ONCAB or from ONCAB to OPCAB were entered into the database and analyzed according to the operation they ultimately received. Intraoperative conversion began to be recorded as part of the institutional database in 2004, when a data field for conversion was introduced into the STS national adult cardiac database.
Variables of Interest
Before analysis, preoperative risk factors for the outcomes of interest were identified and harvested from the STS database (Table 1). Standard STS definitions of each risk factor and outcome were used. LMD is defined as left main disease greater than or equal to 50% stenosis. Race was dichotomized as either white or non-white. The outcomes examined in this study were in-hospital mortality, permanent stroke, myocardial infarction, and the composite end point for any of these major adverse cardiac events (MACE).
The institutional medical records database was populated by trained personnel devoted exclusively to this task; consequently, missing data were scarce. Data were 100% complete for the critical risk factors of interest (surgery type and LMD) and for each major postoperative hospital outcome. Data were missing for the following variables: body mass index (n = 834, 6.4%), body surface area (n = 834, 6.4%), height (n = 753, 5.7%), weight (n = 799, <6.1%), ejection fraction (n = 1702; 13.0%), STS predicted risk of mortality (n = 4, <0.1%), number of diseased vessels (n = 976, 7.5%), white race (n = 598, 4.6%), and last creatinine level (n = 2640, 20.1%).
Data Management and Statistical Analysis
All data for consecutive patients were entered into a computerized cardiac surgical database, using the data fields and definitions of the STS National Adult Cardiac Database. Checks for data quality are employed both at the institutional level and before final entry into the STS national adult cardiac database.
A multiple imputation algorithm was used to impute values that reflect the uncertainty surrounding the missing data. This was not performed in an effort to recreate the truth; rather, the goal of the imputation was to avoid selection bias that can occur by deleting cases with missing variables of interest. Five datasets were imputed, and parameter estimates from the 5 datasets were combined using methods originally described by Molenberghs.11 Data were assumed to be missing at random.
Patients were classified according to LMD and the surgery type (OPCAB or ONCAB) they received. To control for potential selection bias, propensity scores (PSs), described by Blackstone12 and D’Agostino,13 were calculated for each patient based on 51 risk factors available preoperatively (including surgeon identity, year of surgery, and 9 indicators of missingness, Table 1). For the PS calculation, a multiple logistic regression model was used nonparsimoniously to model OPCAB (yes or no) as a function of all 51 risk factors (Table 1). The resulting conditional probability of a patient receiving OPCAB is the PS. The goal of the PS adjustment is to “postrandomize” or “balance” the groups with respect to their preoperative risk factors so that nonconfounded comparisons of group effects can be estimated in an unbiased fashion. The PS was then used as a regression covariate in the logistic regression models. The assumption of a linear relationship between the PS and the logit of the predicted probabilities of each outcome was verified by plotting these quantities in deciles.
To statistically evaluate the effects of LMD and surgery type, multivariable logistic regression models were constructed for each outcome of interest. Each model consisted of dichotomous LMD (presence or absence), surgery type (OPCAB or ONCAB) and their interaction, adjusted for the PS. If the interaction was statistically insignificant then that term was removed from the model and the main effects alone were evaluated. This model was primarily designed to evaluate the effects of LMD and surgery type in unison and to determine whether OPCAB lessened or worsened outcomes in the presence of LMD. Adjusted odds ratios (AOR) associated with OPCAB and LMD, along with 95% confidence intervals, were computed for each of the 4 adverse outcome endpoints. All logistic models were adjusted with the PS.
The data were managed and analyzed using SAS Version 9.1 (Cary, NC) and STATA 9.0. Unadjusted comparisons were performed with χ2 tests and 2-sample t-tests for categorical and continuous predictors, respectively. All statistical tests were 2-sided using a P ≤0.05 level of significance. No adjustments for multiple tests were made.
The preoperative demographics of all patients are presented in Table 1. A total of 2891 (22.1%) patients were identified as having LMD consisting of stenosis ≥50%. Of these, 1276 (44.1%) underwent OPCAB and 1615 (55.9%) underwent ONCAB. Over the course of the study period, and as surgeons became more comfortable with OPCAB techniques, OPCAB for LMD increased dramatically from a low of 1.3% in 1997 to a peak of 80.8% in 2007 (Fig. 1).
The subset of patients with LMD who underwent ONCAB were more likely to have Canadian Cardiovascular Society Class 5 angina (34.5% vs. 29.2%, P < 0.001) or a preoperative intraaortic balloon pump (8.4% vs. 4.7%, P < 0.001) when compared with patients who underwent OPCAB. Conversely, the patients in the OPCAB group had a significantly higher mean body mass index (30.4 vs. 28.8, P = 0.017), almost triple the incidence of COPD (12.5% vs. 4.2%, P < 0.001), and double the incidence of smoking (54.3% vs. 22%, P < 0.001).
Unadjusted postoperative outcomes are summarized in Table 2. Patients with LMD and undergoing OPCAB had a statistically significant decrease in in-hospital mortality compared with those undergoing ONCAB (1.4% vs. 3%, P = 0.004). This significant decrease in operative mortality was also seen in those patients without LMD (1.3% vs. 2.2%, P < 0.001, respectively). Furthermore, the incidence of MACE among LMD patients was significantly lower among those patients undergoing OPCAB compared with ONCAB (3.6% vs. 5.2%, P = 0.04). This reduced incidence was also significant among non-LMD patients in the OPCAB versus ONCAB groups (2.6% vs. 4.5%, P < 0.001).
Adjusted multivariable logistic regression analysis is presented in Table 3. The use of OPCAB was associated with a decreased incidence of permanent stroke (AOR = 0.51, P < 0.001) and MACE (AOR = 0.66, P = 0.002). The presence of LMD was associated with an increased incidence of MACE (AOR = 1.24, P = 0.038). No interactions existed between LMD and surgery type (ONCAB vs. OPCAB) for any of the outcomes.
The surgical approach to coronary revascularization using off-pump techniques (OPCAB) has experienced a true renaissance over the last decade and a half. Although coronary artery bypass (CABG) without the benefit of cardiopulmonary bypass (CPB) had been described half a century ago,14,15 it was not until recently that technological advances, coupled with the dedicated efforts of OPCAB surgeons, established the technique as not just viable, but indeed a preferable option to conventional ONCAB. The early work of Buffolo et al3 and Benetti et al,4 a combined experience of nearly 1300 patients, established OPCAB as a safe, effective technique with tangible benefits when compared with traditional ONCAB. These early observations were reinforced by several subsequent studies which demonstrated decreased neurologic events, lower incidence of blood transfusion, and shorter hospital stay associated with the OPCAB approach.5–8
The introduction of modern stabilizing devices coupled with the increasing expertise of cardiac anesthetists in the off-pump setting has greatly facilitated the development of this procedure. Although OPCAB represented 10% of all CABG procedures performed from 1998 to 1999,9 this proportion doubled by 2001. As the collective experience with OPCAB has grown, it has been increasingly applied in various clinical settings.
Significant (>50%) atherosclerotic disease of the left main coronary artery is a clinical entity long recognized for its associated operative risks and associated comorbidities. Surgical revascularization in LMD is associated with a distinct survival advantage when compared with medical therapy.16–18 Furthermore, long-term follow-up provided by the Coronary Artery Surgery Study (CASS) trial and the VA Cooperative study demonstrate these benefits persist for more than a decade from the time of intervention.19,20 The wealth of evidence supporting surgical revascularization for LMD is reflected in the current practice guidelines from the American College of Cardiology and the American Heart Association.1 Although the advent of drug-eluting stents has prompted a renewed interest in percutaneous interventions for LMD disease for some interventionalists,21,22 CABG remains the standard of care with percutaneous coronary intervention (PCI) used only in the absence of other viable revascularization options.23
Previously described hemodynamic variations associated with cardiac positioning during OPCAB coupled with the large amount of at-risk myocardium with LMD caused early trepidation and the consideration that these lesions represented a relative contraindication to the off-pump approach. However, review of our experience does not demonstrate any increased risk of complications when LMD is treated using OPCAB. This finding is consistent with conclusions from several smaller reviews of OPCAB in LMD.24–29
This study has several limitations. It is retrospective in nature and does not permit for complete accounting for all sources of bias, despite advanced statistical methodology designed to correct for both treatment selection bias and potential confounders of outcomes in preplanned analyses. In addition, the database used for this study reports surgical cases according to the ultimate surgery type performed. This means that patients whose coronary revascularization was initially attempted without cardiopulmonary bypass and who required conversion to cardiopulmonary bypass (typically because of hemodynamic instability) were included in the ONCAB group. This may potentially disadvantage ONCAB in comparison of outcomes with OPCAB. Additionally, our data analysis did not address the extent of coronary calcification and the utilization of coronary endarterectomy in each group or the incidence of conversion from OPCAB to ONCAB in the occasional cases of severe calcified coronary arteries. Such patients’ can potentially disadvantage 1 method of revascularization in comparison with the other. The database does not allow reconciliation of these data to an intention to treat analysis.
Our review represents a decade of experience from an academic division of cardiac surgery that encompasses the work of 14 attending surgeons. To our knowledge, this series represents the largest evaluation of the interaction between LMD in OPCAB to date in the literature. Our series confirms the clinical severity of LMD, as it was associated with an increased incidence of MACE in all patients. Additionally, it once again demonstrates the deceased incidence of neurologic events associated with OPCAB as well as a lower incidence of operative mortality and MACE when OPCAB is used. Finally, in a review of nearly 3000 patients with LMD, it demonstrates that OPCAB use is safe and associated with a significant clinical benefit. The presence of LMD should no longer be considered a contraindication to the OPCAB approach.
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This retrospective review from Emory University examines the role of off-pump versus on-pump coronary bypass grafting in patients with left main disease. They examine the 2 techniques with respect to in-hospital death, stroke, myocardial infarction, and major adverse cardiac events. Their experience showed that the utilization of off-pump coronary bypass grafting increased from 1.3% in 1997 to 81% in 2007. Off-pump surgery was associated with a reduced incidence of stroke and major adverse cardiac events in patients with left main disease. Interestingly, the benefit of OPCAB was similar in patients with and without left main disease. This report is another of a number of important publications from this group emphasizing the advantages of off-pump coronary bypass grafting in various patient cohorts.
Left main disease; OPCAB; Mortality; MACE
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