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Ann Thorac Surg 2004;77:549-556
© 2004 The Society of Thoracic Surgeons

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Original article: cardiovascular

Comparison of short-term mortality risk factors for valve replacement versus coronary artery bypass graft surgery

^a Department of Veterans Affairs Medical Center, Denver, Colorado, USA
^b University of Colorado Health Sciences Center, Denver, Colorado, USA
^c Office of Patient Care Services, Veterans Affairs Central Office, Washington, DC, USA

Accepted for publication August 6, 2003.

^* Address reprint requests to Dr Shroyer, Cardiac Research, Denver Department of Veterans Affairs Medical Center, 1055 Clermont St. (112R), Denver, CO 80220, USA.
e-mail: laurie.shroyer{at}med.va.gov

	Abstract

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
BACKGROUND: Risk factors for 30-day operative (short-term) mortality following coronary artery bypass graft (CABG only) procedures are well established. However, little is known about how the risk factors for short-term mortality following valve replacement procedures (with or without a CABG procedure performed) compare with CABG only risk factors.

METHODS: Department of Veterans Affairs (VA) records (65,585 records) were collected from October 1991 through March 2001 and analyzed. Risk factors for short-term mortality were compared across three subgroups of patients: CABG only surgery (n = 56,318), aortic valve replacement (AVR) with or without CABG (n = 7450), and mitral valve replacement (MVR) with or without CABG (n = 1817). Multivariable logistic regression analyses were used to compare the relative magnitude of risk for 19 candidate predictor variables across subgroups.

RESULTS: Only three patient baseline characteristics differed significantly in magnitude of risk between the procedure groups. Partially or totally dependent functional status significantly increased the risk of short-term mortality for AVR patients (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.29–2.09) and MVR patients (OR 2.21, 95% CI 1.48–3.30), but not for CABG only patients (OR 1.04, 95% CI 0.93–1.16). Conversely, previous heart surgery and New York Heart Association functional class III or IV symptoms conferred greater magnitude of risk for CABG only patients compared with the valve subgroups.

CONCLUSIONS: Overall, the risk factors for short-term mortality following valve replacement and CABG surgery appear to be relatively consistent. However, clinicians should be aware of the importance of preoperative functional status as a unique predictor of mortality following valve surgery.

	Introduction

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Coronary artery bypass graft (CABG) surgery and valve surgery represent more than 10% of all cardiac procedures in the United States [1]. Since the mid-1980s the identification of risk factors for short-term mortality has been an emphasis in the field of cardiac surgery [2]. Factors predictive of operative death following CABG only surgery are well described and include age, previous heart surgery, prior myocardial infarction, priority of operation, and the extent of noncardiac comorbidity [3–9]. These factors are used by clinicians to identify which patients are at increased risk for short-term mortality following surgery, and to counsel patients on their risk before surgery.

Risk factors for short-term mortality following valve procedures with or without CABG have received less attention and are less well established than risk factors for CABG only procedures. Advanced age, salvage and emergent surgical status, renal failure, New York Heart Association (NYHA) class IV, female gender, reoperation, and several other factors have been reported to predict operative mortality for valve procedures alone as well as for valve procedures in combination with CABG [3, 10–12]. However, many studies have been limited by small sample size and have not compared valve procedures with CABG only procedures. The aim of the current study was to compare factors predictive of short-term mortality for three subgroups of procedures (CABG only, aortic valve replacement (AVR) with or without concurrent CABG, and mitral valve replacement (MVR) with or without concurrent CABG) in a large cohort of Department of Veterans Affairs (VA) patients.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Study population
Since April 1987 the VA Continuous Improvement in Cardiac Surgery Program (CICSP) has maintained an ongoing database of individual patient risk variables (collected prospectively), procedural details, and outcomes on all patients having cardiac surgery in the VA system [3, 4]. The present study included a cohort of all patients who received a CABG procedure and no other cardiac procedure (CABG only), an AVR with or without concurrent CABG procedure and no other cardiac procedure (AVR ± CABG), or a MVR with or without concurrent CABG procedure and no other cardiac procedure (MVR ± CABG) between October 1, 1991 and March 30, 2001 at one of the 43 cardiac surgery programs of the Department of Veterans Affairs. Seven patients were omitted due to missing procedure information, and 1 patient was omitted due to incorrect patient identification information, giving a total study population of 65,585 patients.

Outcomes
The primary outcome was short-term mortality, defined as death between 0 and 30 days inclusive following index CABG only, AVR ± CABG, or MVR ± CABG procedure, death within the index hospitalization, or death occurring after 30 days that could be attributed directly to the index procedure (eg, death associated with readmission for mediastinitis beyond 30 days). This short-term outcome is collected within the CICSP program using follow-up VA personnel (surgical clinical nurse reviewers at each local center). Moreover, the occurrence of death and death dates are reconciled with the VA beneficiary identification and record locator system, which has been reported to be comparable with the National Death Index for mortality assessment in a VA population [13].

Risk variables
Predictor variables included a wide range of demographic, cardiac, and noncardiac (comorbid) risk variables that are captured routinely for the CICSP (Table 1). In the CICSP database, NYHA functional class is specifically defined to reflect symptom burden from dyspnea or fatigue before surgery, including class I (no limitation due to dyspnea or fatigue), class II (slight limitation due to dyspnea or fatigue), class III (marked limitation due to dyspnea or fatigue), or class IV (symptoms at rest).

Statistical analyses
Missing values were imputed using the median for continuous variables and the most frequent category for categorical variables. No variables had more than 0.1% missing values, except for left ventricular ejection fraction (6.2% missing), left main coronary artery stenosis (2.8% missing), and serum creatinine (0.3% missing). An independent sample t test or a ² test of association was used to compare the mean or the proportion of each risk variable between pairs of the three procedure groups.

Multivariable logistic regression analysis was first used to model the probability of short-term mortality for each of the three procedure groups separately. Backward selection with a removal criterion of p value more than 0.05 was used to determine a set of significant risk factors for each separate procedure group. For each significant risk factor, the odds ratio and 95% confidence interval for short-term mortality were determined. To control for changes in mortality over the 9.5-year period, all analyses included a linear term for the time in years since October 1, 1991 during which the patient had their index procedure.

It is important to note that deriving separate models for each procedure group does not provide significance tests for the equality of risk factor effects across the procedure groups. Rough comparisons across separate models can be difficult, especially with different sample sizes for each of the procedure groups. For example, if a risk variable is found to be significant for one procedure group but not for another, this does not necessarily indicate that the variable represents a greater risk for one group than the other. The difference in statistical significance could be due to unequal sample sizes between the two groups and, therefore, reflect a difference in power (or the statistical ability to detect a significant odds ratio) between the two groups.

Therefore, in order to compare the relative effect of the risk factors on short-term mortality across the three different procedure groups (CABG only, AVR ± CABG, and MVR ± CABG), all risk factors and interactions between each risk factor and each procedure group were included simultaneously in a multivariable model. An interaction between a risk factor and the procedure group variable provides a test of equality of the risk effect across the procedure groups. When the effect of a risk factor was found to differ significantly across procedure groups (p 0.05 for the interaction), the p value for the significance test of equality across procedure groups was reported, and linear contrasts were used to determine which of the three procedure groups differed significantly. The main effects of all risk factors, as well as interactions of each risk factor by procedure group, were retained in the model, regardless of statistical significance. Thus, the effect of each risk factor is interpreted as adjusted for all other risk factors listed in Table 1. All statistical analyses were conducted using SAS version 8.2 (SAS Institute, Cary, NC [14]).

	Results

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Study population
Descriptive statistics for the study population are illustrated in Table 1. There were 56,318 patients in the CABG only group (85.9%), 7450 in the AVR ± CABG group (11.3%), and 1817 in the MVR ± CABG group (2.8%). Table 1 demonstrates significant differences in patient characteristics across the procedure groups. As expected, compared with CABG only patients, patients in both of the valve groups were more likely to have conditions related to heart failure (eg, higher NYHA class and active endocarditis) and less likely to have conditions related to coronary artery disease (eg, Canadian Cardiovascular Society [CCS] anginal class III or IV, prior myocardial infarction, preoperative ST-segment depression on electrocardiogram, urgent or emergent surgical priority, and left main coronary artery stenosis 50%).

Compared with AVR patients, MVR patients were younger, more likely to be NYHA class IIII or IV, and more likely to have active endocarditis or elevated serum creatinine. Also, MVR patients were less likely to be CCS anginal class III or IV, which is not surprising because angina is a primary symptom of aortic stenosis but not mitral valve disease.

Outcomes
Overall there were 2747 deaths (mortality rate 4.2%) for the study period, with 2127 in the CABG only group (mortality rate 3.8%), 458 in the AVR ± CABG group (mortality rate 6.1%), and 162 in the MVR ± CABG group (mortality rate 8.9%).

Separate multivariable models
Significant predictors of short-term mortality for the CABG only group are illustrated in Table 2. Significant noncardiac predictors included older age, chronic obstructive pulmonary disease, peripheral vascular disease, cerebral vascular disease, and serum creatinine level of 1.5 mg/dL or higher. Significant cardiac predictors included previous heart operation, CCS angina class III or IV, previous myocardial infarction, preoperative ST-segment depression on the electrocardiogram, urgent or emergent surgical priority, NYHA class III or IV, left main coronary artery stenosis 50%, and left ventricular ejection fraction less than 0.45. There was a significant decrease in risk across the 9.5-year study period (p = 0.0006).

New York Heart Association class III or IV symptoms were a stronger risk factor for the CABG only patients (OR 1.75, 95% CI 1.58–1.94) than for the AVR ± CABG patients (OR 1.34, 95% CI 1.09–1.66) or the MVR ± CABG (OR 1.06, 95% CI 0.72–1.55) patients.

Table 6 is included to compare the results of this study to literature previously published by the Society of Thoracic Surgeons, which developed models across different categories of procedural groups [10]. The results concerning differences in key risk factors (functional status, prior heart surgery, and NYHA class) between treatment groups were largely retained.

	Comment

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

Impaired functional status has been demonstrated to be an independent risk factor for mortality in several clinical settings [15–19]. However, the explanation for the finding that patients with impaired functional status in either of the valve groups had a significantly higher increase in risk for short-term mortality than patients with impaired functional status in the CABG only group is unclear. Certainly the reasons for referral and timing of valve surgery differ from those for CABG only surgery. Patients with coronary artery disease may have dependent functional status based on angina alone, which may be relieved by a CABG only procedure [20].

The CICSP dataset does not capture the severity of valve stenosis or regurgitation at baseline. It is possible that patients with valve disease may present with a more advanced disease process, and have functional disability in direct relation to the extent of valve and associated cardiomyopathic disease [21]. One may speculate that valve patients who become functionally impaired have a more advanced cardiomyopathic status at the time of surgery. The reserve of these patients may be very limited, and their ability to tolerate the superimposed pathophysiologic changes associated with cardiac surgery is likely to be minimal.

The results of this study support that functional impairment is an independent risk factor for valve patients above and beyond their symptom burden and other patient characteristics. Indeed, for mitral valvular disease the OR of 2.5 in patients with partial or totally dependent functional status was the strongest magnitude of risk of all the identified risk factors for short-term mortality following MVR. Clearly, elucidating the mechanisms responsible for the increased mortality in valve patients with functional impairment deserves further investigation. In the meantime, however, clinicians should be aware of the importance of functional status as a mortality risk factor, and treatment strategies should be considered to avoid functional impairment before surgery. For example, given that patients with mitral insufficiency in particular may progress to advanced degrees of left ventricular dysfunction before presenting for health care, the philosophy of proactive surgical mitral valve repair/replacement before functional disability occurs may be justified. This strategy may be important for aortic valve disease and mitral stenosis as well. Given timing of valve surgery in relationship to patient functional status may be important, future studies are needed to determine whether impaired functional status in valve patients can be modified preoperatively in order to reduce mortality risk.

Previous heart operation remains a robust predictor of increased short-term mortality following CABG only procedures [8]. In patients undergoing reoperative CABG in the setting of a prior CABG, several technical issues could be responsible for increased short-term mortality. These issues include surgical adhesions with entry into the right ventricle during sternal reopening, injury to patent arterial and venous grafts, embolic debris with the handling of diseased grafts causing myocardial necrosis, and the quality of the remaining native vessels for bypass. Prior cardiac surgery carries a less ominous risk for patients undergoing AVR and did not emerge as a risk factor for patients undergoing MVR. Reasons why prior heart surgery is a risk factor for AVR, but not MVR, are not readily apparent, but this differential observation is intriguing and is deserving of future research.

Other than the three key risk factors noted, it is important to emphasize that we have not noted substantial differences in the risk factor sets for valve versus CABG only. General statements about statistical power to determine the differences in OR between procedure groups that could have been detected in our study are difficult due to the complex statistical models as well as differences in sample sizes, mortality rates, and risk factor incidences between the three procedure groups. However, we can note from Table 5 that differences in OR of 0.6 to 0.7 were seen to be significant for risk variables that had relatively low incidences (8.4% to 25.0% for impaired functional status and previous heart operation). Thus, other than the three risk variables previously noted, as well as active endocarditis, which had very low incidence rates and therefore low power to detect differences, our results indicate there are not large differences in effects of risk factors between procedure groups. Therefore, it appears that preoperative mortality risk assessment can be accomplished with a fairly uniform set of risk factors.

An important message is that noncardiac comorbidity has a major impact on risk with cardiac surgery. Furthermore, the impact of comorbidities on the outcomes of cardiac surgery patients is likely to increase over time as the population ages and as the prevalence of comorbid diseases in cardiac populations continues to rise [1, 22].

This study has a number of strengths, including a large sample size (N = 65,585), which allowed the consideration of a large number of risk factors for short-term mortality in a single statistical model, as well as the use of significance tests explicitly comparing the risk effects among procedure groups. In addition, the completeness of the data, with no more than 0.1% missing for all but three risk factors, allowed the study to make more comprehensive conclusions regarding effects of clearly defined risk factors for short-term 30-day operative mortality. Finally, data were collected prospectively from operations conducted over nearly a 10-year period with almost complete short-term follow-up (99.9%) of all patients during that interval.

There is one other reported statistical comparison of risk factors for CABG and valve surgeries. Edwards and coworkers [10] recently described and compared risk factors for operative mortality for AVR versus MVR and for CABG/AVR versus CABG/MVR. However, the intention of that study was not the comparison of the risk factors for operative mortality for each of the valve replacement surgeries versus CABG only surgeries, as was the primary goal of the present study.

In order to address the similarities and differences in the analysis of the current study (which combines valve replacements and valve replacement plus CABG procedures in a single group for the purpose of analyses), we repeated our study analyses separately with five groups: CABG only, MVR only, AVR only, MVR plus concurrent CABG, and AVR plus concurrent CABG. The results of the analyses with these five groups were consistent with the analyses of the present study with three groups (CABG only, AVR ± CABG, and MVR ± CABG).

Potential limitations of the study should be acknowledged. First, the results using the VA CICSP dataset (predominantly male veterans with complex comorbid disease) may not be able to be generalized to nonveteran populations. Second, studies with large sample sizes such as the current study have the potential for finding differences that are statistically significant, but that are not large enough to be clinically meaningful. To the best of our knowledge, however, this problem was not apparent in the current study given the magnitude of associations found and that these same three risk factors were identified using different procedural classification approaches. Third, there may be other risk factors for CABG or for valve surgery (eg, baseline degree of valve stenosis) that are important, but were not available in the CICSP data. A limited set of 19 demographic, cardiac, and noncardiac variables was available in CICSP for this analysis. The CICSP database was not specifically designed to answer this particular study question (eg, details on valve regurgitation and stenosis were not available). Finally, in the current study, the effect of risk factors on only 30-day operative mortality was evaluated. An expanded focus on longer-term mortality or other clinically important outcomes such as health-related quality of life may yield other risk factors that should be differentially evaluated between procedural subgroups.

In summary, a few preoperative risk factors (previous heart surgery, impaired functional status, and higher NYHA classification) were found to have different OR and, therefore, contribute different risk for patients undergoing CABG only, CABG ± AVR, and CABG ± MVR procedures. Further research is needed to understand the reasons behind these differences in risk. Nonetheless, surgeons can consider these differential effects during preoperative counseling and postoperative follow-up so that patients receive appropriate advice and care for the procedure planned.

In contrast, differential effects were not demonstrated for most of the standard preoperative risk variables known to be associated with increased 30-day operative mortality following CABG only or valve or valve/CABG combination surgery. Therefore, most aspects of the "high-risk" profile typically associated with increased 30-day operative mortality following heart surgery appear to be similar for both CABG and valve procedures.

	Acknowledgments

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Funding for this study was provided in part by VA Health Services Research and Development Grant #IHY 99214–1 (Dr Shroyer, principal investigator), and by the Office of Patient Care Services at the Department of Veterans Affairs Headquarters. Doctor Rumsfeld is supported by a VA Health Services Research Career Development Award (RCD-98–341–1).

	References

Top Abstract Introduction Patients 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): Joseph C. Cleveland, Jr Frederick L. Grover Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gardner, S. C. Articles by Shroyer, A. L. Search for Related Content PubMed PubMed Citation Articles by Gardner, S. C. Articles by Shroyer, A. L. Related Collections Coronary disease