Innovations: Technology & Techniques in Cardiothoracic & Vascular Surgery:
Outcomes and Predictors of Mortality and Stroke After On-Pump and Off-Pump Coronary Artery Bypass Surgery in Octogenarians
Raja, Shahzad G. MRCS, FRCS(C-Th)*; Shah, Jaymin MRCP†; Navaratnarajah, Manoraj MRCS*; Amin, Fouad MD‡; Amrani, Mohamed PhD, FRCS*
From the *Department of Cardiac Surgery, and †Department of Cardiology, Harefield Hospital, London, England; and ‡Department of Cardiology, Wexham Park Hospital, Slough, England.
Accepted for publication June 21, 2013.
Presented at the Annual Scientific Meeting of the International Society for Minimally Invasive Cardiothoracic Surgery, May 30 – June 3, 2012, Los Angeles, CA USA.
Disclosure: The authors declare no conflicts of interest.
Address correspondence and reprint requests to Shahzad G. Raja, MRCS, FRCS(C-Th), Department of Cardiac Surgery, Harefield Hospital, Hill End Road, UB9 6JH, London, England. E-mail: firstname.lastname@example.org.
Objective: Octogenarians, as the fastest growing stratum of the population and with the highest prevalence of coronary artery disease, are being increasingly referred for coronary artery bypass grafting (CABG). The general perception is that the presence of comorbidities and the propensity for neurological injury expose them to a higher risk for mortality and morbidity after conventional on-pump CABG, and therefore, off-pump CABG should be preferentially offered to octogenarians to improve outcomes. This study evaluates the in-hospital outcomes and predictors of mortality and stroke in octogenarians undergoing on- and off-pump CABG at our institution.
Methods: From January 2000 to December 2010, a total of 290 octogenarians underwent off-pump (n = 217) and on-pump (n = 73) CABG. Their data were prospectively entered into the cardiac surgery database (Patients Analysis & Tracking System; Dendrite Clinical Systems, Ltd, Oxford, England, United Kingdom) and analyzed retrospectively. Outcome measures included in-hospital mortality, major complications, and length of stay. Multivariate analysis was performed to identify predictors of combined outcome of in-hospital mortality and stroke.
Results: The mean ± SD age of the patients was 82 ± 2.0 years. Preoperative demographics were similar for the on-pump and off-pump groups. The patients who underwent off-pump CABG had a lower number of distal anastomoses performed compared with the patients who underwent on-pump CABG [mean difference, 0.2; 95% confidence interval (CI), 0.02-0.4; P = 0.03]. However, the ratio of grafts (received/needed) was the same in both groups. In-hospital mortality for the entire cohort was 7.2%, with no significant difference between the groups for death (6.0% vs 11.0%; P = 0.08), stroke (2.8% vs 2.8%; P = 1.0), other major complications, and length of hospital stay. Independent predictors of combined outcome identified from the multiple logistic model included heart failure [odds ratio (OR), 4.4; 95% CI, 1.5–13.0; P = 0.008], diabetes (OR, 2.6; 95% CI, 1.0–6.0; P = 0.046), nitrate infusion (OR, 2.9; 95% CI, 1.1–8.0; P = 0.04), postoperative renal failure requiring hemofiltration (OR, 8.6; 95% CI, 3.5–21.1; P < 0.001), and postoperative ventricular arrhythmias (OR, 7.3; 95% CI, 1.9–27.8; P = 0.009).
Conclusions: Both on-pump and off-pump CABG are reasonable revascularization strategies in octogenarians. Careful patient selection and individualized treatment decisions can minimize postoperative mortality and morbidity in octogenarians undergoing on- and off-pump CABG.
The increase in life expectancy has confronted cardiac surgery with a rapidly growing population of elderly patients requiring surgical myocardial revascularization. The age group defined as “elderly” in the literature has gradually increased from 65 years or older to 80 years or older. A total of 80% of patients older than 80 years have identifiable cardiovascular disease.1 This increasing octogenarian population, not unexpectedly, has a relatively greater prevalence of cerebrovascular disease, left ventricular dysfunction, diabetes mellitus, chronic obstructive pulmonary disease, renal impairment, and peripheral arterial disease.2–4 An increasingly greater number of these high-risk octogenarians affected with symptomatic and surgically correctable coronary artery disease have become candidates for coronary artery bypass grafting (CABG) because of recent advances in the perioperative care of cardiac surgical patients and the techniques of surgical myocardial revascularization. Surgical myocardial revascularization in such patients, however, remains associated with morbidity and mortality substantially higher than those observed in the younger patient population.5
Off-pump coronary artery bypass (OPCAB) grafting, in recent years, has emerged as an effective surgical technique and may be of particular benefit in high-risk populations including the octogenarians. Conventional CABG using cardiopulmonary bypass (CPB) and cardioplegic arrest has, for many years, represented the “gold standard” in coronary revascularization. However, during the past decade, OPCAB has gained increasing popularity. Resurgence of interest in OPCAB is associated with the expectation that avoiding deleterious effects of the CPB pump leads to better outcomes and possibly decreased costs and resource use.6 Off-pump coronary artery bypass is clearly associated with blunting of systemic inflammatory response syndrome.7 Systemic inflammatory response syndrome results from a cascade of events generated by the contact of plasma proteases and blood cells with the gaseous interface and bioincompatible surfaces of the CPB machine. High-risk patients including the elderly are particularly susceptible to damage by these inflammatory mediators.8,9 There is overwhelming evidence from randomized controlled trials, propensity score analyses, and observational studies that OPCAB is associated with reductions in the risks for stroke, atrial fibrillation, wound infection, and acute kidney injury.10–12 Off-pump coronary artery bypass also reduces transfusion and inotrope requirements, ventilation time, intensive care unit and hospital stays, and in-hospital and 1-year direct costs.12 Because atrial fibrillation, decline of neurocognitive functions, delirium, stroke, increased length of stay, and renal failure are common complications more frequently encountered in the octogenarians,13 it is logical to offer OPCAB surgery to this patient population.
This study evaluates the in-hospital outcomes and predictors of mortality and stroke in octogenarians undergoing on- and off-pump CABG at our institution.
This study comprised a retrospective analysis of a prospectively collected cardiac surgery database (PATS; Dendrite Clinical Systems, Ltd, Oxford, UK). Because of its retrospective nature, informed consent was waived for this study. The PATS database captures detailed information on a wide range of preoperative, intraoperative, and hospital postoperative variables (including complications and mortality) for all patients undergoing cardiac surgery in our institution. The database was collected and reported in accordance with the Society for Cardiothoracic Surgery in Great Britain & Ireland database criteria. In addition, the medical notes and charts of all the study patients were reviewed.
From January 2000 to December 2010, a total of 290 consecutive octogenarians underwent isolated multivessel CABG at our institution. Two hundred seventeen of these patients undergoing off-pump CABG were compared with a control group undergoing on-pump CABG (n = 73). The patient characteristics of both groups are shown in Table 1. Indications for surgical intervention were determined at a weekly review involving cardiologists, cardiac surgeons, and cardiac radiologists. The patients were placed on a specific waiting list according to the urgency of their procedure.
Eight surgeons performed the 290 operations during the study period. All interventions were performed via a midline sternotomy. The choice of on- or off-pump strategy was based on the surgeon’s preference. The left and the right internal mammary artery were harvested with minimal trauma as pedicled or skeletonized grafts, based on the surgeon’s preference, and treated with papaverine solution before use. The great saphenous vein was harvested using open or endoscopic technique.
Conventional CABG on CPB was performed at 34°C. Cardiopulmonary bypass was instituted with single two-stage right atrial cannulation and an ascending aorta perfusion cannula. Standard bypass management included membrane oxygenators, arterial line filters, and nonpulsatile flow of 2.4 L · min−1 · m−2, with a mean arterial pressure of greater than 50 mm Hg. The myocardium was protected by using intermittent antegrade cold blood cardioplegia (blood-crystalloid ratio, 4:1). Anticoagulation was achieved using 300 U/kg of heparin. If required, heparin was supplemented to maintain the activated clotting time of more than 480 seconds and was reversed by protamine at the end of the procedure.
All patients underwent conventional multivessel CABG using varying combinations of left and/or right internal mammary artery and saphenous vein grafts. All distal and proximal anastomoses on CPB were performed during a period of single aortic cross-clamping.
For off-pump CABG, the heart was stabilized using the suction-irrigation tissue stabilization system. A deep pericardial retraction suture helped position the heart for grafting. Anticoagulation was achieved with 150 U/kg of heparin. If required, heparin was supplemented to maintain the activated clotting time of more than 250 seconds and was reversed by protamine at the end of the procedure. Blood pressure was continually optimized during the procedure, and the mean arterial pressure was maintained higher than 50 mm Hg by repositioning the heart and by intravenous fluids or selective use of vasoconstrictors or both. Proximal graft anastomoses to the aorta were performed with partial cross-clamping of the ascending aorta. Each distal anastomosis was followed by construction of the corresponding proximal anastomosis.
Postoperative intensive care unit management was standardized for all patients. All patients received intravenous nitroglycerin (0.1–8 μg · kg−1 · min−1) infusions for the first 24 hours unless hypotensive (systolic blood pressure, <90 mm Hg). Choice of inotropic agents was dictated by the hemodynamic data. Other routine medications included daily aspirin and resumption of cholesterol-lowering agents and β-blockers. Diuretics, angiotensin-converting enzyme inhibitors, and warfarin were gradually introduced when indicated clinically.
Variables and Data Collection
Preoperative variables of interest included age, sex, body mass index, smoking history, chronic obstructive pulmonary disease, diabetes, hypercholesterolemia, renal insufficiency (preoperative serum creatinine, ≥200 μM · L−1), hypertension, peripheral vascular disease, cerebrovascular disease, left ventricular ejection fraction, urgency (operation performed <24 hours vs >24 hours from time of referral), previous myocardial infarction, previous percutaneous coronary interventions, preoperative intravenous nitrates, preoperative intravenous inotropes, number of diseased vessels, preoperative intra-aortic balloon pump, and logistic EuroSCORE. Intraoperative variables of interest included types of grafts used, grafts/patient, CPB time, aortic cross-clamp time, conversion to CPB, and index of completeness of revascularization (ICOR). The ICOR was defined as the total number of distal grafts constructed divided by the number of the affected coronary vessels reported on the preoperative coronary angiogram.14 Complete revascularization was assumed when the ICOR was 1 or greater.
Postoperative variables of interest included in-hospital mortality, postoperative intra-aortic balloon pump, stroke or transient ischemic attack, prolonged ventilation of more than 24 hours, atrial fibrillation, deep sternal infection, superficial sternal infection, mediastinitis, vein harvest site infection, blood products use, hemofiltration, inotropes after leaving operating room, chest infection, return to operating room for bleeding, gastrointestinal complications, postoperative ventricular arrhythmias, postoperative bradycardia needing pacing, and length of intensive care unit and hospital stay.
Statistical analysis was performed using the SAS for Windows version 9.2 (SAS, Cary, NC USA). The summary results for numeric variables were presented as mean ± SD. The summary results for categorical variables were presented as frequency and percentage. The χ2 test was used to compare the categorical variables. The numeric variables were tested for normality, and the Mann-Whitney U test or the two-tailed, independent-samples Student t test was used accordingly. All values are expressed as mean ± SD. Statistical significance was defined as P < 0.05.
To account for differences in case mix, we developed a propensity score for the receipt of an on-pump procedure.15 The propensity for the receipt of an on-pump procedure was determined without regard to outcome, using multivariate logistic regression analysis.16 A full nonparsimonious model was developed that included all variables listed in Table 1. This gave a C-statistic of 0.8, indicating a good discriminatory power. The goal was to balance patient characteristics by incorporating everything recorded that may relate to either systematic bias or simply bad luck. We then used a macro (available at: http://www2.sas.com/proceedings/sugi29/165–29.pdf) to perform propensity matching. In all cases, P < 0.05 was considered significant.
A forward stepwise binary logistic regression analysis approach with entry to the model set at P = 0.1 and the criterion for remaining in the model set at P < 0.05 were used to identify predictors of the combined outcome of in-hospital mortality and stroke. Variables entered into the model were identified from univariate analysis. The Hosmer-Lemeshow goodness-of-fit test was used to assess the performance of the analysis.16 The odds ratio, the corresponding 95% confidence interval (CI), and the P value are reported for each independent factor.
The authors had full access to the data and take responsibility for integrity of the data. All authors have read and agree to the manuscript as written.
From January 2000 to December 2010, a total of 290 patients older than 80 years (mean ± SD age, 82 ± 2.0 years; range, 80–89 years) underwent CABG at our institution. Two hundred seventeen patients (74.8%) underwent off-pump CABG, and 73 patients (25.2%) underwent on-pump CABG. The two groups had similar preoperative demographics and EuroSCORE risk stratification (Table 1).
No statistical difference was found between the two groups in terms of intraoperative data except that the patients who underwent off-pump CABG had, on average, a lower number of distal anastomoses performed as compared with the patients who underwent on-pump CABG (mean difference, 0.2; 95% CI, 0.02–0.4; P = 0.03). Figure 1 demonstrates that this is driven by a higher proportion of the patients who underwent on-pump CABG having triple-vessel grafting as compared with those who underwent off-pump CABG. However, it is important to mention that the ICOR was similar for the two groups (P = 0.8). The overall conversion to CPB rate for the OPCAB cohort was 0.9%. Intraoperative data are summarized in Table 2.
The unadjusted in-hospital mortality was 6.0% for the OPCAB group and 11% (P = 0.08) for the on-pump group, and the overall mortality for the entire cohort was 7.2%. The causes of in-hospital death were acute myocardial infarction in two patients, ischemic bowel in three patients, respiratory failure/acute respiratory distress syndrome in three patients, suspected hypoperfusion syndrome/low cardiac output syndrome in two patients, resistant vasoplegia in two patients, overwhelming sepsis in two patients, retroperitoneal hematoma in one patient, and multiorgan failure in six patients.
The incidence of stroke for the entire cohort was 2.8%, with similar incidence after OPCAB and on-pump CABG (2.8% vs 2.8%; P = 1.0). Stroke with documented neurological deficit was experienced by five patients in the off-pump group and 2 patients in on-pump group. Five of these patients made full recovery before discharge, whereas two patients required long-term stroke rehabilitation and repatriation to a specialist stroke unit. One patient who underwent OPCAB had a transient ischemic attack with slurring of speech but made full recovery before brain imaging. Computed tomography of the brain was obtained in all these patients. The results were positive for stroke in seven (87.5%) of eight patients, showing large embolic stroke in two patients (25%), watershed in three patients (37.5%), hemorrhagic in one patient (12.5%), and mixed pattern in one patient (12.5%).
The remaining in-hospital outcomes including length of hospital stay (Fig. 2) were similar as well. Table 3 summarizes the in-hospital outcomes for the unmatched groups.
We were able to successfully match 73 on-pump patients to a similar number of OPCAB patients. The preoperative characteristics of the propensity-matched off-pump and OPCAB patients are shown in Table 4. Table 5 also shows the operative data of the matched groups. The number of distal anastomoses was comparable in both groups. In the matched groups, there were no significant differences between the on-pump and OPCAB patients with regard to in-hospital mortality rate or morbidity (Table 6).
The stepwise multivariate logistic regression analysis revealed preoperative congestive heart failure, diabetes, nitrate infusion, postoperative renal failure requiring hemofiltration, and postoperative ventricular arrhythmias as independent predictors for the occurrence of composite endpoint of death and stroke (Table 7). The Hosmer-Lemeshow goodness-of-fit test was not statistically significant (P = 0.41), indicating accuracy of the analysis.
This study was conducted to analyze the in-hospital outcomes as well as the independent risk factors of death and the occurrence of stroke in octogenarians undergoing on-pump and off-pump CABG. In our study, in-hospital mortality for the entire cohort was 7.2%, with no significant difference between the groups for death (6.0% vs 11.0%; P = 0.08). This is similar to the in-hospital mortality rates for octogenarians undergoing on-pump CABG and OPCAB reported in the literature5,17–23 (Table 8).
Surgical myocardial revascularization is associated with adverse neurological complications, of which stroke is the most debilitating. Despite the improvement in surgical techniques, along with the introduction of membrane oxygenators and in-line filtration, there is a persistent stroke rate associated with CABG ranging from 1% to 5%.24,25 It is estimated that 3,000 to 15,000 patients each year have a stroke in the perioperative period after CABG.24,25 Age is identified as an independent predictor of stroke.26 During the last decade, prevalence of stroke after CABG surgery has significantly decreased in octogenarians, and recent reports quote a risk of 2% (Table 8).5,17–23 Athanasiou et al,27 in their meta-analysis of all observational studies, published in MEDLINE between 1999 and 2002, showed that the OPCAB technique was associated with significantly lower incidence of stroke in elderly patients compared with the CPB technique (1% vs 3%), with an odds ratio of 0.38% to 95% (CI, 0.22–0.65). Similar results have been reported by Panesar et al.28 Their meta-analysis showed a significant reduction of stroke in OPCAB patients older than 70 years compared with conventional CABG surgery (0.9% vs 3.9%, P = 0.05). The strongest benefit was observed in the octogenarians. Although history of stroke was more frequent in OPCAB surgery octogenarian patients (15.4 vs 8.9%), occurrence of new postoperative stroke was significantly higher with conventional surgery (P = 0.002). The general perception is that the less invasive nature of OPCAB with minimal manipulation of the atheromatous aorta could account for the reduction of postoperative stroke in octogenarians.
Interestingly, contrary to these meta-analyses27,28 as well as several previously published studies5,22,23 and the general perception, our study failed to show the superiority of OPCAB in reducing the incidence of stroke in octogenarians compared with conventional on-pump CABG. The most plausible explanation for this discrepancy could be the use of the single cross-clamp technique for constructing proximal anastomoses during on-pump CABG and repetitive tangential clamping of the aorta during OPCAB for the same purpose in this study. The use of the single cross-clamp technique by avoiding repeated aortic manipulation seems a rational strategy to avoid neurological complications especially in high-risk patients with atheromatous aorta29 including octogenarians. Perhaps OPCAB “no-touch aorta” total arterial revascularization could be the ideal technique for avoiding postoperative stroke because it would theoretically avoid generation of microemboli and macroemboli resulting from the use of CPB, aortic manipulation, and inadequate de-airing.29
The predictors of the composite endpoint of death and stroke in this study are similar to those previously identified.2,5,26 These predictors reflect the increasing morbid state of individuals referred for surgery and should be taken into account during the decision-making process. Although age alone must not be a barrier to access to surgery, careful patient selection and individualized treatment decisions can minimize postoperative morbidity and reduce burden on increasingly limited resources of healthcare systems worldwide.
Cardiac surgery has been increasingly offered to elderly patients particularly octogenarians during the past decade. Increasing age is a well-established independent predictor of postoperative morbidity and mortality among patients undergoing CABG. In such patients, minimizing the invasiveness of the surgical procedure by avoiding the use of CPB seems a reasonable strategy to improve outcomes. Off-pump coronary artery bypass, because of its less invasive nature, seems an attractive option to reduce the mortality and the morbidity in high-risk elderly patients.
At present, the evidence comparing the impact of OPCAB on postoperative complications in octogenarians fails to show a convincing benefit of avoiding CPB. At our institution, with a significant bias for OPCAB revascularization in the elderly, particularly octogenarians, outcomes of OPCAB are comparable with outcomes for CABG on CPB (Table 3). These comparable outcomes are a reflection of the careful selection and decision-making process involved in managing octogenarians referred for surgical myocardial revascularization to our institution. We preferentially offer CABG on CPB to patients with poor ventricular function; patients with diffusely diseased, calcified, and poor-quality target vessels; and those requiring emergency surgical revascularization. On the other hand, OPCAB grafting is the procedure of choice for patients with a higher risk for complications from CPB and aortic manipulation, particularly those with advanced ascending aortic disease. Overall, our institutional approach is that technical precision, anastomotic quality, and completeness of revascularization should not be compromised in an effort to avoid CPB unless the short-term risks outweigh any potential long-term benefit. Finally, it is important to mention that lengthy rehabilitation was needed in most of the octogenarians postoperatively, irrespective of the surgical strategy used.
The results of our study should be interpreted with caution in light of the fact that our investigation has several limitations. These include, and are not limited to, the small sample size, the retrospective nonrandomized nature of this study, and the selection bias related to the fact that the patients received one of the two treatments solely on the basis of different referral patterns and preference of the operating surgeons. In addition, it is important that the patients in the two groups were operated on by different surgeons, and this should be taken into account. Furthermore, our study lacks intermediate or long-term follow-up, and we were able to comment only on short-term outcomes. Finally, the relatively low incidence of operative mortality and stroke after the on-pump and off-pump CABG operations limited modeling efforts. Nevertheless, the results of this study provide an important context on which to base future prospective studies.
In conclusion, this study shows that both on-pump and off-pump CABG are reasonable revascularization strategies octogenarians. Careful patient selection and individualized treatment decisions can minimize postoperative mortality and morbidity in octogenarians undergoing on- and off-pump CABG.
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This retrospective study analyzed predictors of in-hospital mortality and stroke in octogenarians undergoing either off-pump (n = 217) or on-pump (n = 73) coronary artery bypass grafting (CABG). There were no differences between the two cohorts in death, stroke, other major complications, or length of hospital stay. Independent predictors of the combined outcome of mortality or stroke included heart failure, diabetes, nitrate infusion, postoperative renal failure, and postoperative ventricular arrhythmias. The authors concluded that both on-pump and off-pump CABG are reasonable strategies in octogenarians, but careful patient selection is necessary.
This is an interesting study, and the authors are to be congratulated for both their propensity analysis and a thorough examination of their data. More and more octogenarians are undergoing CABG, and outcomes data are sorely needed. The limitations of the study, acknowledged by the authors, are its small sample size and its retrospective, nonrandomized nature, leaving it open to selection bias. Moreover, the patients in the two groups were operated on by different surgeons, and this makes the outcomes difficult to interpret. There was also a lack of long-term follow-up. However, even in light of these shortcomings, the study provides useful information that may help guide patient selection and preoperative counseling in these patients.
Octogenarians; On-pump coronary artery bypass grafting; Off-pump coronary artery bypass grafting; Stroke; Outcomes
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