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Ann Thorac Surg 2005;80:1719-1727
© 2005 The Society of Thoracic Surgeons

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Original article: Cardiovascular

Is Reoperation Still a Risk Factor in Coronary Artery Bypass Surgery?

^a Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio
^b Department of Quantitative Health Sciences, The Cleveland Clinic Foundation, Cleveland, Ohio

Accepted for publication April 25, 2005.

^_* Address correspondence to Dr Sabik, Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, 9500 Euclid Ave / Desk F24, Cleveland, OH 44195 (Email: sabikj{at}ccf.org).

Presented at the Poster Session of the Forty-first Annual Meeting of The Society of Thoracic Surgeons, Tampa, FL, Jan 24–26, 2005.

	Abstract

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Appendix 3 Appendix 4 Footnotes References

 
BACKGROUND: Hospital mortality for reoperative coronary artery bypass grafting (CABG) is approaching that of primary CABG. This raises two questions: (1) has experience neutralized the risk of reoperation attributable to its greater difficulty, or (2) has experience neutralized the risk attributable to the higher-risk profile of reoperative patients?

METHODS: From 1990 to 2003, 21,568 CABG procedures were performed, of which 4,518 (21%) were reoperations: 3,919 first, 552 second, 43 third, 3 fourth, and 1 fifth. Reoperative patients had a higher-risk profile than primary patients, with more vascular disease, left ventricular dysfunction, and coronary artery disease (all p < 0.0001). Logistic regression was used to identify factors associated with hospital death and to develop a propensity score for reoperation, which was used to (1) adjust multivariable analyses of death and (2) compare outcomes in matched patients.

RESULTS: Hospital mortality was 4.3% (168 of 3,919) for first reoperation, 5.1% (28 of 552) for second, and 6.4% (3 of 47) for third or more, compared with 1.5% (263 of 17,050) for primary operations. Risk of both primary and reoperative CABG decreased with experience (p > 0.0002); however, reoperative risk fell markedly in the mid-1990s. In both the overall and matched-pairs analyses, reoperation was a risk factor before 1997 (p 0.008), but not after (p = 0.2). Reoperation within 1 year of previous CABG increased risk (p < 0.0001). Risk attributable to left ventricular dysfunction decreased with experience (p = 0.05).

CONCLUSIONS: Hospital mortality for reoperative CABG has been consistently higher than for primary operation, but this difference has narrowed considerably. Patient characteristics, not reoperation itself, now have greater influence.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Appendix 3 Appendix 4 Footnotes References

 
Hospital mortality after reoperative coronary artery bypass grafting (CABG) is higher than after primary CABG [1–6]. The higher risk is attributable to (1) increased technical difficulty of reoperative CABG and (2) the higher-risk profile of reoperative CABG patients. In our clinical practice, we perceived that risk of reoperative CABG had declined to a level approaching that of primary coronary surgery. This raised two questions: (1) has risk attributable to the technical difficulty of reoperations been neutralized, or (2) has risk attributable to the higher-risk profile of reoperative CABG patients been neutralized? To answer these questions, we compared results of primary and reoperative CABG from 1990 to 2003.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Appendix 3 Appendix 4 Footnotes References

 
Patients
Using the computerized Cardiovascular Information Registry at The Cleveland Clinic Foundation, patients were identified and included in this study if they had isolated primary or reoperative CABG from January 1, 1990, to January 1, 2003. Patients with prior noncoronary heart surgery, such as valve, aortic, or ventricular aneurysm operations, were excluded. During this time, 21,302 patients underwent 21,568 isolated CABG procedures (Fig 1). There were 17,050 (79%) primary operations and 4,518 reoperations: 3,919 first, 552 second, 43 third, 3 fourth, and 1 fifth. Preoperative clinical characteristics, operative details (Table 1), and hospital outcomes were collected prospectively and entered into the Cardiovascular Information Registry. Use of these data for research was approved by the Institutional Review Board.

View larger version (46K): [in this window] [in a new window]   Fig 1. Number of isolated primary (black bars) and reoperative (gray bars) coronary artery bypass graft (CABG) operations by year.

Presentation
Continuous variables are presented as mean ± standard deviation. Categorical or ordinal variables are presented as number and percentage. Event data are presented as percentages with asymmetric 68% confidence limits (CL; comparable to ± 1 standard error), as are odds ratios.

	Results

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Appendix 3 Appendix 4 Footnotes References

 
Unadjusted Hospital Mortality
Overall hospital mortality was 2.1% (462 of 21,568; CL, 2.0% to 2.2%); however, for patients undergoing isolated primary CABG it was 1.5% (263 of 17,050; CL, 1.4% to 1.5%), and for patients having reoperative CABG, 4.4% (199 of 4,518; CL, 4.1% to 4.7%). Hospital risk increased with number of previous operations. For patients having a first reoperation, hospital mortality was 4.3% (168 of 3,919; CL, 4.0% to 4.6%), for second reoperations, 5.1% (28 of 552; CL, 4.1% to 6.2%), and for three or more reoperations, 6.4% (3 of 47; CL, 2.9% to 12.2%). Hospital mortality decreased in both primary and reoperative CABG patients as surgical experience grew, and by late 1997, reoperative risk approached that of primary CABG (Fig 2).

View larger version (12K): [in this window] [in a new window]   Fig 2. Hospital mortality after primary and reoperative coronary artery bypass grafting according to year of operation.

View larger version (23K): [in this window] [in a new window]   Fig 3. Hospital mortality. Graphs are for a 65-year-old man with a previous myocardial infarction, peripheral vascular disease, chronic obstructive pulmonary disease, and an internal thoracic artery graft. (A) By year of operation for primary coronary artery bypass grafting (CABG) according to left ventricular (LV) function. (B) By year of operation for reoperative CABG according to LV function.

Propensity-Matched Comparison
Patients undergoing reoperative CABG had a different risk profile from those undergoing primary CABG (Table 1, Appendix 3). Propensity matching yielded well-matched groups of primary and reoperative CABG patients, and the risk profile of the two groups was similar to that of the reoperative CABG patients (Table 3, Appendix 4). Among propensity-matched patients, hospital mortality was higher after reoperative CABG (93 of 1,966, 4.7%; CL, 4.2% to 5.3%) than after primary CABG (44 of 1,966; 2.2%; CL, 1.9% to 2.6%; Table 3).

	Comment

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Appendix 3 Appendix 4 Footnotes References

 
Hospital mortality among patients undergoing reoperative CABG is higher than among patients undergoing primary CABG [1–6]. There are two reasons for this. First, reoperations are technically more demanding. Sternal reentry, pericardial adhesions, in situ arterial grafts, and patent but diseased saphenous vein bypass grafts all increase the complexity and risk of coronary reoperations. Second, patients undergoing reoperation have a higher preoperative risk profile. They are older and more likely to have vascular disease, left ventricular dysfunction, and extensive coronary artery disease [4].

Despite these factors, hospital mortality associated with coronary reoperation has decreased with greater surgical experience, and in our as well as others' experience [4, 9–11], it now approaches that of primary CABG. Whether this improvement is attributable to operative experience and better surgical techniques or to improved management of patient comorbidities is unknown. To answer this question, we analyzed our patients undergoing both primary and reoperative CABG and specifically analyzed our data to determine whether the risk attributable to the complexity of coronary reoperations or to patient preoperative risk factors decreased with greater surgical experience.

Principal Findings
Reoperation is no longer a risk factor for increased hospital mortality in patients undergoing CABG. Although hospital mortality of patients undergoing coronary reoperation is higher than that of patients undergoing primary coronary surgery, this is attributable to the higher-risk profile of reoperative patients, not the increased technical complexity of coronary reoperation.

Reoperative CABG presents many technical challenges not present in primary operations. These challenges are due to both the nature of reoperations and patient characteristics. With careful preoperative planning and surgical technique, they can be managed safely.

The first challenge is sternal reentry. The pericardium is usually not closed after heart surgery, and the aorta, right ventricle, and bypass grafts may adhere to the underside of the sternum. At reoperation, these structures can be easily injured when the sternum is opened. Although using an oscillating saw decreases this risk, it does not eliminate it. Knowing the proximity of mediastinal structures to the sternum is necessary, and if preoperative imaging suggests that they may be in jeopardy, extra measures before reopening the sternum, such as peripheral cannulation and cardiopulmonary bypass (with or without hypothermic circulatory arrest), may be necessary to avoid catastrophe.

In patients requiring limited revascularization, risk of sternal reentry can be avoided by using alternative incisions. Anterior thoracotomy has been advocated for anterior coronary artery revascularization, lateral thoracotomy for circumflex revascularization, and an epigastric approach for distal right coronary artery revascularization [12].

A second challenge at reoperation is managing patent atherosclerotic vein grafts. Embolization of atherosclerotic debris, resulting in coronary ischemia or myocardial infarction, may occur if these grafts are manipulated during dissection of pericardial adhesions [13]. Our approach has been to avoid atherosclerotic vein grafts before aortic clamping and arresting the heart. We dissect out only enough of the heart and aorta to cannulate and clamp the aorta. After the heart is arrested and protected with cardioplegia, dissection of adhesions between the heart and pericardium is completed. If it is not possible to expose enough of the heart to cannulate safely without touching a patent atherosclerotic vein graft, peripheral cannulation is used. This is often necessary when an atherosclerotic patent vein graft to the right coronary artery is adherent to the right atrium.

We routinely replace atherosclerotic vein grafts with another vein graft. Myocardial hypoperfusion and infarction may occur if a patent vein graft is replaced with an arterial graft [14]. We do not routinely divide all old vein grafts. If dividing an old vein graft could compromise coronary perfusion, we leave it in place.

Patients undergoing reoperation are more likely to have vascular disease, and a common challenge at reoperation is dealing with an atherosclerotic ascending aorta. If aortic atherosclerosis is detected by palpation or imaging studies, alternative cannulation sites and hypothermic circulatory arrest with or without ascending aortic replacement may be necessary. We prefer cannulating the axillary artery when it is unsafe to cannulate the ascending aorta, because these patients usually have aortoiliac and femoral atherosclerosis as well [15, 16]. Off-pump revascularization with no manipulation of the ascending aorta may also be used.

Patients undergoing coronary reoperation may have multiple sources of coronary perfusion, making myocardial protection a challenge. Because antegrade cardioplegia will not reach areas of the myocardium whose coronary blood flow is supplied by in situ grafts or occluded coronary arteries, retrograde cardioplegia is extremely useful. Borger and colleagues [17] reported retrograde cardioplegia significantly decreased hospital mortality in patients undergoing reoperative CABG. We first use antegrade cardioplegia to arrest the heart, then retrograde cardioplegia is administered and given every 15 to 20 minutes during myocardial ischemia. Antegrade cardioplegia is not repeated, to reduce risk of vein graft atheroembolism. Because retrograde cardioplegia might not perfuse the right ventricle, if a vein graft is performed to the right coronary artery, we administer antegrade cardioplegia through the graft. Patent in situ grafts are clamped while the aorta is clamped to avoid washing out the cardioplegia and warming the heart. If in situ grafts cannot be clamped, the patient is systemically cooled.

We also use retrograde cardioplegia to remove vein graft atherosclerotic debris that inadvertently embolizes to a coronary artery. After the coronary arteriotomy is made, retrograde cardioplegia is administered, and the atherosclerotic debris is flushed out of the artery.

Careful myocardial protection, we believe, is one of the reasons that left ventricular dysfunction is no longer a risk factor for patients undergoing primary and reoperative CABG. Davierwala and colleagues [9] have also reported the decreasing importance of left ventricular dysfunction as a predictor of hospital mortality in patients undergoing CABG. In addition to better myocardial protection, improved perioperative management and revascularization of patients with hibernating (viable but dysfunctional) myocardium have contributed to decreased risk in patients with left ventricular dysfunction.

Secondary Findings
Patient characteristics identified as risk factors for hospital death included those previously reported for CABG [1, 3, 6, 10, 11, 17, 18], and for the most part, they were equally important for both primary and reoperative surgery. Except for left ventricular dysfunction, we did not find that the risk attributable to patient factors decreased with greater surgical experience.

Reoperative CABG less than 1 year after previous operation was associated with significantly increased hospital mortality. Shapira and colleagues [11] reported 10% mortality in patients undergoing first-time reoperative coronary surgery less than 1 year after primary surgery, versus only 2.6% in those undergoing reoperation at a later time (p < 0.05). Similar findings were reported by Christenson and colleagues [2]. Early coronary reoperations are due to failure to completely revascularize or to failure of revascularization. Both of these, as well as dense mediastinal adhesions encountered soon after the last operation, would be expected to increase hospital risk of the subsequent operation.

Limitations
This study represents many operations performed by many surgeons over many years. Although we currently all use the reoperative techniques discussed in this summary, during the 13 years of this study, each surgeon adopted these methods at different times. Because we did not record many of these techniques in our database and there is no specific date of uniform adoption, we could not determine the individual contribution of these methods to reducing technical risk of coronary reoperations.

Although many variables were included in the multivariable analysis, important variables might have been excluded. This could explain why some factors found to be significant are difficult to understand. For example, it is hard to understand how saphenous vein grafting to the diagonal increased hospital mortality. One possibility is that it is a surrogate for a factor we did not analyze. Another is that it was found to be significant by chance alone.

Summary
Risk of hospital death for both reoperative and primary CABG has decreased with increasing surgical experience. Although risk of reoperative CABG has been consistently greater than that of primary CABG, the difference has narrowed considerably, and risk of reoperative CABG now approaches that of primary CABG. Increased surgical experience has neutralized the risk of reoperation attributable to greater technical difficulty, and the increased risk of reoperative CABG now appears to be related to the higher-risk profile of reoperative CABG patients.

	Appendix 1

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Appendix 3 Appendix 4 Footnotes References

 
Detailed Statistical Methods
Overall multivariable analysis
Multivariable logistic regression analysis was used to identify factors associated with hospital death (see Appendix 2 for variables considered in the analyses), including clinical risk profile, number of reoperations, interval between reoperation and previous operation, graft type and location of distal anastomoses, completeness of revascularization, and surgical experience (expressed as date of operation). To evaluate whether greater surgical experience decreased the risk of hospital death attributable to increased technical difficulty of reoperative CABG or to patient risk profile, we searched for interactions of date of operation with preoperative patient characteristics and reoperation. This analysis used a directed stepwise technique [19], bootstrap bagging for validation [20], and a model retention criterion of p 0.05. The final model was further adjusted by propensity score (see Matched Analyses).

Stratified multivariable analysis
Because risk of hospital death for patients undergoing reoperative CABG approached that of primary CABG by 1997, patients were stratified into two groups—those operated on before January 1, 1997, and those operated on after that date. Analytic techniques were similar to those used in the overall multivariable analysis, except a variable for all reoperations before or after January 1, 1997, was added.

Matched analysis
To adjust for differences in the preoperative profile of patients undergoing primary and reoperative CABG, multivariable logistic regression analysis was used to model the probability of any reoperation, using only preoperative and surgical experience variables (see Appendix 2). After establishing a parsimonious model (see Appendix 3), a saturated propensity model was developed by adding other preoperative patient characteristics that were not found to be significantly associated with reoperation but that might represent unrecorded patient characteristics. The c-statistic was 0.86.

A propensity score was calculated for both primary and reoperative CABG patients by solving the saturated model for the probability of having a reoperation. In addition to using this score to adjust all multivariable analyses, it was used to match reoperative patients with primary CABG patients using greedy matching [21]. Reoperative patients whose propensity scores deviated more than 0.10 from those of primary CABG patients were unmatched. This yielded 1,966 propensity-matched pairs. Risk of hospital death was compared between these two groups.

Stratified matched analysis
Multivariable analysis of these 1,966 matched pairs was performed to compare risk of reoperations performed before and after January 1, 1997, adjusted for continuous date of operation.

	Appendix 2

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Appendix 3 Appendix 4 Footnotes References

 
Variables Considered in the Analyses _^*
Demography
Sex, age (years), weight (kg), height (cm), body surface area (m²), body mass index (kg/m²).

Symptoms
New York Heart Association functional class (I–IV), Canadian Angina class (0–4), emergency operation.

Left ventricular function
Grade of left ventricular dysfunction (grade 1 or normal: ejection fraction [EF] > 0.55; grade 2 or mild dysfunction: EF = 0.40–0.54; grade 3 or moderate dysfunction: EF = 0.25–0.39; grade 4 or severe dysfunction: EF <0.25), previous myocardial infarction, left ventricular EF from catheterization.

Valve pathology
Aortic valve regurgitation, aortic valve stenosis, mitral valve regurgitation, mitral valve stenosis, pulmonary valve regurgitation, pulmonary valve stenosis, tricuspid valve regurgitation, tricuspid valve stenosis.

Cardiac comorbidity
Family history of coronary artery disease, preoperative atrial fibrillation, ventricular arrhythmia, complete heart block or pacer, history of endocarditis.

Noncardiac comorbidity
History of smoking, peripheral vascular disease, chronic obstructive pulmonary disease, carotid disease, popliteal disease, medically treated diabetes, insulin-treated diabetes, hypertension, renal disease, creatinine (mg/dL), cholesterol (mg/dL), high-density lipoprotein (mg/dL), low-density lipoprotein (mg/dL), triglycerides (mg/dL), blood urea nitrogen (mg/dL), bilirubin (mg/dL), hematocrit (%).

Coronary anatomy (graft or native)
Lesser of the maximum degree of stenosis in graft or native vessel for following systems: left anterior descending coronary artery, left circumflex coronary artery, right coronary artery, diagonal (variables used were presence of 50% diameter stenosis, presence of 70% diameter stenosis, and percent diameter stenosis for each territory); number of diseased systems (50% diameter stenosis criteria).

Coronary anatomy (native vessels)
Left main trunk disease (percent diameter stenosis, presence of 50% diameter stenosis), left anterior descending coronary system disease (percent maximal diameter stenosis, presence of 50% and 70% diameter stenosis), circumflex coronary artery system disease (percent maximal diameter stenosis, presence of 50% and 70% diameter stenosis), right coronary artery system disease (percent maximal diameter stenosis, presence of 50% and 70% diameter stenosis), diagonal system disease (percent maximal diameter stenosis, presence of 50% and 70% diameter stenosis), number of diseased systems (50% diameter stenosis criteria).

Reoperation variables
Reoperation, operation number, first reoperation, second reoperation, third reoperation or more, reoperation within 1 year, reoperation in 1–5 years, reoperation beyond 5 years, time from previous operation, propensity score.

Coronary operation
Off-pump versus on-pump, internal thoracic artery (ITA) grafting (left, right, both, any, free, in situ), ITA to left anterior descending coronary artery (LAD), ITA to right coronary artery (RCA), ITA to circumflex coronary artery (Cx), ITA to diagonal, saphenous vein graft (SVG), SVG to LAD, SVG to RCA, SVG to Cx, SVG to diagonal, radial graft, radial to LAD, radial to RCA, radial to Cx, radial to diagonal, other conduit, LAD grafted, RCA grafted, Cx grafted, diagonal grafted, complete versus incomplete revascularization.

Experience
Date of operation (years since January 1990).

Interactions
Age with diabetes; operation date with reoperation; operation date with emergency operation; reoperation with emergency operation, age, female, complete heart block, medically treated diabetes, insulin-treated diabetes, ITA graft, and SVG graft; date of operation with age, female, emergency operation, myocardial infarction, heart block, left ventricular dysfunction, peripheral vascular disease, popliteal disease, insulin-treated diabetes mellitus, chronic obstructive pulmonary disease, renal disease, creatinine (2 mg/dL), bilirubin (mg/dL), left main trunk disease, any ITA grafting, and SVG to diagonal grafting.

	Appendix 3

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Appendix 3 Appendix 4 Footnotes References

 
Patient Characteristics Associated With Reoperation

	Appendix 4

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Appendix 3 Appendix 4 Footnotes References

	Footnotes

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Appendix 3 Appendix 4 Footnotes References

 
^_* These are the primary variables considered; however, several derived variables were investigated and used in the analyses as well (ie, transformations and groupings of primary variables).

	References

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Appendix 3 Appendix 4 Footnotes References

 

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