Interact CardioVasc Thorac Surg 2008;7:111-115. doi:10.1510/icvts.2007.167734
© 2008 European Association of Cardio-Thoracic Surgery
Institutional report - Cardiac general |
Do beating heart techniques applied to combined valve and graft operations reduce myocardial damage?
John C.Y. Lua,
Matthew Shawb,
Antony D. Graysonb,
Michael Poullisa,
Mark Pullana and
Brian M. Fabria,*
a Department of Cardiothoracic Surgery, The Cardiothoracic Centre Liverpool, UK
b Department of Clinical Governance, The Cardiothoracic Centre Liverpool, UK
Received 18 September 2007;
received in revised form 6 November 2007;
accepted 6 November 2007
 Presented at the 21st Annual Meeting of the European Association for Cardio-thoracic Surgery, Geneva, Switzerland, September 16–19, 2007.
*Corresponding author. Cardiac Surgery, The Cardiothoracic Centre NHS Trust, Thomas Drive, Liverpool L14 3PE, UK. Tel.: +44 151 228 1616; fax: +44 151 288 2371.
E-mail address: brian.fabri{at}ctc.nhs.uk (B.M. Fabri).
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Abstract
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We examined the outcomes of combined beating heart CABG and valve surgery (hybrid) and compared these to conventional CABG and valve surgery (conventional). Between April 1997 and March 2006, 388 patients received combined CABG and valve surgery. Patient characteristics and cardiac enzyme release were collected prospectively. To account for differences in case-mix we used logistic regression to develop a propensity score for hybrid group membership and then performed a propensity-matched analysis. One hundred and forty patients underwent hybrid operation with a mean logistic EuroSCORE of 13.5%, compared to 248 who underwent conventional operation with a mean logistic EuroSCORE of 10.9% (P=0.006). Eighty-two patients from each group were successfully matched. The mean logistic EuroSCORE after matching was similar between the groups (11.3% vs. 12.9%; P=0.48). The median number of grafts per patient was also similar, three in each group (P=0.98). Post-op CK-MB levels were found to be significantly lower for hybrid patients (44 U/I vs. 29.5 U/I; P=0.037). In-hospital mortality was not statistically different (9.8% vs. 6.1%; P=0.39). Survival at 5 years was 74% for hybrid and 71% for conventional group (P=0.92). CK-MB levels in patients receiving hybrid CABG and valve surgery are reduced compared to conventional CABG and valve surgery.
Key Words: Hybrid CABG and valve surgery; CK-MB; Mortality
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1. Introduction
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Duration of cardiopulmonary bypass and aortic cross-clamp time (ischaemic time of myocardium) are two major intra-operative factors that influence morbidity and mortality after cardiac surgery. In the last few years, a number of different techniques have emerged which are directed towards minimising the deleterious effects of cardiopulmonary bypass and optimising myocardial protection. This includes mini-bypass and heparin bonded circuits to minimise the inflammatory response as well as a variety of myocardial protection strategies including cardioplegia solutions, temperature and mode of delivery. In recent years, off-pump coronary artery bypass surgery (OPCAB) has become well established as an alternative method to surgical revascularisation without the need for cardiopulmonary bypass.
Combining the use of beating heart techniques to the coronary artery bypass graft (CABG) part of combined CABG and valve procedures will reduce the global ischaemic time. There is very little published literature examining the effects of reducing cross-clamp time in the setting of combined CABG and valve surgery. Gersak and Sutlic [1], described the technique of performing CABG and valve procedure with beating heart supported with a cardiopulmonary bypass machine and cross-clamping the aorta. The metabolic requirement of the heart was met by continuous retrograde warm blood only.
Since 1999 we have adopted a ‘hybrid’ approach by performing CABG on the beating heart supported by cardiopulmonary bypass followed by aortic cross-clamping and cardiac arrest prior to the valve procedure being undertaken. This report seeks to quantify any differences in myocardial damage (enzyme release), other postoperative outcomes and mid-term survival.
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2. Methods
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2.1. Patient population and data
We conducted a cohort study using prospectively collected data on 388 consecutive patients undergoing combined CABG and valve surgery between 1 April 1997 and 31 March 2006 at the Cardiothoracic Centre-Liverpool. All operations (conventional and hybrid) were performed by two surgeons (DMP and BMF).
Preoperative data were collected prospectively during patient admission as part of routine clinical practice. Methods of data collection and definitions have been previously published [2] and are also available from www.nwheartaudit.nhs.uk. Preoperative and operative data collected are listed in Table 1. In-hospital outcomes collected included mortality, cardiac enzyme release, intensive care unit and postoperative length of stay. In-hospital mortality was defined as death within the same hospital admission regardless of cause.
2.2. Cardiac enzyme release
Cardiac enzyme release (CK-MB fraction) within the first 24 h post-op was abstracted from a routinely recorded electronic clinical biochemistry archive, blind to clinical data. The cardiac enzymes were measured on the morning after the operation, approximately 12–18 h after the patient's arrival in the intensive care unit. The assay used was CK-MB measured by the immuno-inhibition method performed on the Roche 917 Analyser (reference range 5–24 U/l at 37 °C).
2.3. Patient follow-up
Patient records were linked to the National Strategic Tracing Service (NSTS), which records all deaths in the UK. To establish vital status at one year after operation, patients were matched to the NSTS based on patient name, National Health Service number, date of birth, gender, and postcode.
2.4. Surgical technique
In all operations normothermic (37 °C) cardiopulmonary bypass was used. In the hybrid group, the CABG procedure was done on the beating heart supported by cardiopulmonary bypass. The Octopus IV (Medtronic Inc.) stabilisation device and intracoronary shunts (Medtronic Inc.) were used during construction of distal anastomoses. Thereafter, the heart was arrested with antegrade cold blood cardioplegia and maintained in an arrested state with continuous retrograde cold blood cardioplegia. With the heart arrested, the concomitant aortic or mitral valve procedure was performed. All the graft top ends to the ascending aorta were performed with the cross-clamp applied. Upon completion of the procedure, a terminal hot shot of blood cardioplegia was given via the coronary sinus and the cross-clamp released.
In the conventional group, CABG and valve surgery were done with the cross-clamp on and the heart arrested and maintained in the arrested state with the above technique. Upon completion of the procedure, a terminal hot shot of blood cardioplegia was given via the coronary sinus and the cross-clamp released.
2.5. Statistical methods
Continuous variables not normally distributed are shown as median with 25th and 75th percentiles. Categorical data are shown as percentages. Univariate comparisons were made with Wilcoxon rank sum tests and  2-tests as appropriate. Deaths occurring over time were described using Kaplan–Meier survival curves [3].
To account for differences in case-mix we developed a propensity score for hybrid group membership [4]. The propensity for hybrid group membership was determined without regard to outcome, using multivariable logistic regression analysis [5]. A full non-parsimonious model was developed that included all variables listed in Table 1 and the year of surgery. The goal is to balance patient characteristics by incorporating everything recorded that may relate to either systematic bias or simply bad luck. This model yielded a C statistic of 0.82, indicating a good ability to differentiate between patients with or without hybrid CABG and valve surgery. We then used a macro (available at: http://www2.sas.com/proceedings/sugi29/165-29.pdf) to perform propensity-matching.
In all cases a P-value <0.05 was considered significant. All statistical analysis was performed retrospectively using SAS for Windows Version 8.2.
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3. Results
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3.1. Un-matched patients
Patient characteristics based on the operation received are shown in Table 1. One hundred and forty patients underwent hybrid approach with a mean logistic EuroSCORE of 13.5%, compared to 248 who underwent conventional surgery with a mean logistic EuroSCORE of 10.9% (P=0.006). Patients who received hybrid CABG and valve surgery were more likely to have triple-vessel disease, left main stem disease and poor ejection fraction. The hybrid group was also more likely to undergo non-elective surgery and received significantly more grafts during the procedure.
In-hospital mortality and cardiac enzyme release were not statistically significant between the hybrid and conventional groups as shown in Table 2. However, intensive care and postoperative length of stay were different. No difference existed in follow-up mortality between the groups. Freedom from death for patients receiving hybrid CABG and valve surgery at 30 and 60 months was 78.8% and 74.0%, respectively, compared to 80.0% and 71.3% for patients receiving conventional CABG and valve surgery (Fig. 1).
3.2. Propensity-matched patients
Eighty-two patients from each group were successfully matched. The mean logistic EuroSCORE after matching was similar between the groups (11.3% vs. 12.9%; P=0.48). Patient characteristics were well matched as shown in Table 3. The proportion of patients in each group with triple-vessel disease, left main stem disease, poor ejection fraction and received non-elective surgery was no longer statistically significant. The median number of grafts per patient was also similar, three in each group (P=0.98).
The median duration on cardiopulmonary bypass was 144 min (25th and 75th percentiles: 123–173) for patients receiving hybrid CABG and valve surgery compared to 154 min (25th and 75th percentiles: 134–168), which just failed to reach statistical significance (P=0.058). The median duration of aortic cross-clamp time was significantly reduced when using the hybrid approach compared to conventional CABG and valve surgery [66 min (25th and 75th percentiles: 59–75) vs. 106 min (25th and 75th percentiles: 96–119); P<0.001].
Table 4 shows that after propensity-matching, postoperative CK-MB levels were found to be significantly lower for hybrid patients (29.5 U/I vs. 44 U/I; P=0.037). No differences in outcomes existed between the groups with respect to in-hospital mortality and intensive care and postoperative length of stay. Follow-up mortality was also still not significantly different. Freedom from death for patients receiving hybrid CABG and valve surgery at 30 and 60 months was 78.4% and 70.2%, respectively, compared to 81.3% and 72.7% for patients receiving conventional CABG and valve surgery (Fig. 2).
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Fig. 2. Observed survival following hybrid and conventional CABG and valve surgery in propensity-matched groups.
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4. Discussion
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The primary aim of this study was to determine whether there was any significant difference in myocardial damage between the hybrid and conventional groups of combined CABG and valve surgery. We found that the hybrid group had significantly lower CK-MB release in the first twenty-four hours post surgery compared with the conventional group.
The initial analysis of the un-matched data found that there was no difference in postoperative CK-MB levels, and patients receiving the hybrid technique for combined CABG and valve surgery had longer intensive and postoperative stays. However, the hybrid patients were sicker patients with poorer left ventricular ejection fraction and more extensive coronary disease; receiving on average two more bypass grafts than the group treated with conventional CABG and valve surgery. After performing propensity-matching, which aims to balance out differences between the two groups, the CK-MB levels in the hybrid group were significantly lower compared to the conventional group (29.5 U/I vs. 44 U/I; P=0.037).
This evidence for decreased myocardial necrosis did not, however, translate to a decreased intensive care and total in-hospital stay or mortality. Although the cardiac enzyme release is significantly different between the two groups, the average enzyme rise for both groups is less than three times the upper limit of reference range (ULR). Previous work from this institution has shown that intermediate (3–6 times ULR) and high (>6 times ULR) perioperative cardiac enzyme release are independently associated with increased one-year mortality following isolated CABG [6].
Further work from our centre has also shown that cardiac enzyme release is reduced with OPCAB compared to CABG done on cardiopulmonary bypass but this was not associated with better 30-day and one-year survival [7]. Thus, in this report although we have shown a significantly lower cardiac enzyme release in the hybrid group, the cardiac enzyme release in both groups is actually ‘low’ and probably reflects adequate myocardial protection. It is therefore not surprising that both peri-operative and mid-term results are not significantly different.
The major limitation of the present study is its retrospective nature and the non-randomised allocation of the surgical intervention technique. The treatment groups do have differing baseline characteristics and even though we used propensity-matching to balance out these differences, this cannot categorically exclude subtle selective influences on our measured outcomes. As such we can only demonstrate association and not causality for our observations. Other limitations to the current study include the low numbers of cases for individual aortic and mitral valve pathologies, which preclude us from sub-analysing the CK-MB values and outcomes of these individual groups of patients. It should be noted that the low number of patients in the propensity-matched analysis could also have a risk of type II error. The long time period covered by the study could also have an impact on our findings. However, we attempted to minimise the impact this would have by incorporating the year of surgery into the propensity-matching. It could also be argued that a single measure of cardiac enzyme release on the morning after their operation may not reflect the peak CE levels which might have been reached. However, in this study, the emphasis is not on a specific value of cardiac enzyme release, rather it is a comparison of cardiac enzyme release between two techniques. The cardiac enzyme levels were measured at around the same duration after the operation (12–18 h) for both patient groups; hence, comparison of the measured values between the two groups should be possible. Another limitation is that we did not use more cardio-specific markers of cardiac myocyte injury such as troponin T or I, which although less widely accepted and used as markers of myocardial injury following cardiac surgery, are less likely to be raised by non-cardiac injury and may have additional prognostic value over CK-MB measurements [8]. A final limitation is the fact that we do not have data available regarding cause of death.
In conclusion, we have showed that hybrid CABG and valve surgery does result in lower CK-MB release compared with conventional CABG and valve surgery. Although significant, the difference in CK-MB levels between the two groups is weak (P=0.037) and therefore a randomised controlled trial may be warranted to confirm our findings. In this experience in-hospital outcomes and mid-term survival were similar between the two groups.
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References
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Abstract
1. Introduction
