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Interact CardioVasc Thorac Surg 2009;9:630-634. doi:10.1510/icvts.2009.206078 © 2009 European Association of Cardio-Thoracic Surgery
Is the aortic valve pathology type different for early and late mortality in concomitant aortic valve replacement and coronary artery bypass surgery?Department of Cardiovascular Surgery, Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Center, Istanbul, Turkey Received 24 February 2009; received in revised form 30 June 2009; accepted 6 July 2009
*Corresponding author. M.Akif Cad. Sakl
We assessed the effects of aortic valve pathology type on the long-term outcomes of patients who underwent concomitant aortic valve replacement (AVR) and coronary artery bypass grafting (CABG) surgery. We retrospectively reviewed 150 patients who underwent AVR-CABG at our institution between January 1997 and December 2006. We divided patients into aortic stenosis (AS), aortic regurgitation (AR), and mixed-type groups consisting of 98 (65.3%), 20 (13.3%) and 32 (21.3%) patients, respectively. The AS group had more female patients, a higher mean angina class, older mean patient age, increased history of previous myocardial infarction (MI), and smaller valve size compared to other groups. No significant differences were observed among groups in the operative mortality for five or ten-year survival rates. Significant early mortality risk factors included cross-clamp and cardiopulmonary bypass (CBP) time, number of blood transfusion units, chronic obstructive pulmonary disease (COPD), intra-aortic balloon pump (IABP), inotropic drugs, and pacemaker use. Significant late mortality risk factors included intensive care unit (ICU) stay, IABP, stroke, and dialysis. The aortic valve pathology type in patients undergoing concomitant AVR-CABG does not adversely affect survival.
Key Words: Coronary artery bypass grafting; Aortic valve replacement; Aortic valve pathology; Early and late mortality
The incidence of coronary artery and degenerative valve diseases is increasing as the population ages, with the most common of these disorders being aortic stenosis (AS). Aortic regurgitation (AR) is an etiologic factor in 10–25% of patients with coronary artery disease (CAD), and is an early risk factor for mortality [1]. Combined procedures are markers for increased operative mortality and decreased survival [2]. However, patients undergoing combined operations are generally older, have more functional disabilities, are more likely to suffer from angina, have a higher rate of previous myocardial infarction (MI), and a higher prevalence of hemodynamic instability than patients with isolated aortic valve disease. These patients also have longer cross-clamp and cardiopulmonary bypass (CBP) times. Many of these factors have been shown to increase the mortality risk after a combined operation. Previous studies have analyzed the impact of sex [3], age [4–7], number of bypass grafts [8], valve prosthesis type [9, 10], primary cardiac pathology (i.e. CAD vs. aortic valve disease) [2], and severity of valve pathology [11] on long-term survival following combined operation. However, to our knowledge no reported study has investigated the impact of the aortic valve pathology type on survival of patients undergoing concomitant aortic valve replacement (AVR) and coronary artery bypass grafting (CABG) surgery. Therefore, the purpose of this study was to compare the impact of the aortic valve pathology type on early and long-term outcomes in AVR-CABG patients.
2.1. Patients Preoperative, perioperative, and postoperative data for all patients undergoing cardiac surgery at our institution were collected retrospectively. A total of 150 consecutive patients undergoing combined CABG and AVR surgery between January 1997 and December 2006 were identified. Patients were grouped into AS, AR, and mixed aortic valve lesion groups, according to aortic valve pathology. The AS group consisted of patients with symptomatic severe AS (mean transvalvular aortic gradient [TVAG] of >50 mmHg). The AR group consisted of patients with 3–4+ pure aortic insufficiencies. The mixed group consisted of patients with at least moderate AS (mean TVAG >30 mmHg), and with 2+ or more aortic insufficiencies. Selection of the aortic valve prosthesis was made on an individual basis, taking into consideration patients' wishes as well as the surgeon preference. Long-term follow-up, including survival data, was obtained from the clinical database (e.g. hospital re-admission data), by telephone interview, or from the governmental death registry. The closing date for follow-up data was January 31, 2007. This study was approved by our Institutional Research Ethics Board. 2.2. Preoperative investigations Cardiac catheterization was performed on all patients over 40 years of age to assess the extent of CAD. Coronary arteries with narrowing of >50% were considered stenosed, and were treated with CABG. The left ventricular (LV) ejection fraction (EF) was quantified by echocardiography or single-plane ventriculography. The extent and location of valvular disease was determined by echocardiography and/or cardiac catheterization. Severe AS was defined by a mean TVAG of >50 mmHg. If the mean TVAG was <30 mmHg, it was categorized as mild AS. CBP was established with mild systemic hypothermia (28 °C). Myocardial protection was achieved using cold, intermittent potassium blood cardioplegia. The left internal thoracic artery and saphenous veins were used as conduits for bypass grafting. Distal coronary bypass anastomoses were constructed first, followed by valve replacement. Proximal coronary bypass anastomoses were performed after closure of the cardiac chambers, using a single aortic cross-clamp technique. Pharmacologic or mechanical support was initiated during weaning from CPB as required. All patients were admitted to the intensive care unit (ICU) postoperatively, and then transferred to the ward when their hemodynamic and respiratory functions were stable. Preoperative data that were obtained in all patients included age, sex, body surface area, EF, and associated comorbidities including diabetes mellitus, hypertension, previous MI, chronic obstructive pulmonary disease (COPD), renal failure, New York Heart Association (NYHA) functional class, Canadian Cardiovascular Society angina class, LV EF, and valvular pathology.Perioperative variables included the valve prosthesis type, coronary bypass conduit type, number of coronary bypass grafts, and aortic cross-clamp and CPB times. Postoperative variables included the amount of drainage, revision for bleeding, stroke, prolonged mechanical ventilation, inotropic agent use, intra-aortic balloon pump (IABP) placement, duration of intensive care and hospital stay, number of blood transfusion units, infection, acute renal failure, dialysis requirement, postoperative arrhythmia, and pacemaker use. Renal insufficiency was defined as new onset renal insufficiency requiring dialysis postoperatively, or a serum creatinine level >2.5 mg/dl. Pulmonary complication was defined as pneumonia, adult respiratory distress syndrome, or reintubation. Stroke was defined as a neurologic deficit lasting through the time of hospital discharge. Prolonged intubation was defined as an intubation lasting >24 h postoperatively. Postoperative arrhythmia was defined as any rhythm disturbance that required pacemaker use, or any tachyarrhythmia. Operative mortality was defined as any death occurring in the hospital or within 30 postoperative days. Continuous variables are reported as the mean±S.D., and categorical variables are reported as percentages. Descriptive statistics were used to describe patient characteristics. Differences were assessed with one-way analysis of variance (ANOVA) and Tukey's HSD test for post-hoc analysis for normally distributed continuous data. The Kruskal–Wallis test was used for skewed data and Mann–Whitney U-test for post-hoc analysis. Categorical variables were compared with a 2 or Fisher's exact test. Univariate comparisons of long-term outcomes were performed using the Kaplan–Meier method. The independent predictors of each outcome of interest were determined by Cox regression analysis. Survival curves were constructed directly from the data, and were compared by the log-rank test. Statistical significance was defined as P<0.05. For all statistical analyses, SPSS for Windows version 10.0 (SPSS Inc, Chicago, IL) was used.
The preoperative clinical features of the patients are shown in Table 1. The overall mean age of patients was 67.21±9.28, and 75% were men. Patients with AS were significantly older and had significant preoperative risk factors compared to the other groups, including previous MI, higher angina class, female gender, and smaller aortic valve size. The preoperative EuroSCORE of the AS group was significantly higher than that of the other groups. Furthermore, the logistic EuroSCORE was significantly higher in the AS group than in the AR group. History of previous MI was significantly lower in AR than in the other groups.
Perioperative and postoperative clinical variables are shown in Table 2. The overall percentage of patients to undergo revision for bleeding was 7.3%, and for prolonged intubation was 4.6%. For AVR, 84% of patients received mechanical and 16% biological valve replacements. The overall operative mortality was 10%. When we stratified the operative mortality rate by the aortic valve pathology, we did not find any significant differences. The percentage of operative deaths were 11.2%, 5%, and 9.4% in the AS, AR, and mixed groups, respectively. The overall mortality percentages were 26.5%, 20%, and 28.1%, respectively.
The Kaplan–Meier survival did not differ with the log-rank test among the three groups (P=0.83) (Fig. 1). The survival at five years for patients in the AS, AR, and mixed groups were 78.15±3.0%, 87.93±8.03%, 75.38±15.27%, and at 10 years were 42.90±18.84%, 66.32±20.01%, and 58.75±14.56%, respectively. The cumulative survival for the entire population sample was 75.37±5.33% and 52.79±11.68% at five and ten years, respectively.
Significant risk factors by univariate analysis of early mortality included preoperative COPD, the number of blood transfusion units, cross-clamp and CPB times, inotropic agent use, perioperative or postoperative IABP placement, and pacemaker use (Table 3). Cox regression analysis revealed the following independent predictors for early mortality (odds ratio, 95% confidence interval, P-value): COPD (11.84, 2.26–61.99, P<0.01), CPB time (1.02, 1.00–1.03, P<0.05), and inotropic agent use (13.31, 2.48–71.36, P<0.01) (Table 4).
Significant risk factors by univariate analysis of late mortality included duration of ICU stay, perioperative or postoperative IABP placement, postoperative stroke, and dialysis (Table 3). Cox regression did not reveal any independent predictors for late mortality. There were ten late deaths related to cardiac etiology. The two most common causes were congestive heart failure in five patients and MI in four patients. One patient died during reoperation for CABG. Other causes of late mortality included valve related in three patients and non-cardiac cause in six patients. The cause of death in five patients could not be determined.
In this study, the aortic valve pathology type did not appear to affect the mortality rate at five and ten years in patients undergoing concomitant AVR and CABG surgery. The AS group displayed a number of significant postoperative risk factors compared to the other groups. We also identified significant risk factors of early and late mortality. The overall operative mortality in our study was 10%, similar to that found in previous studies (4–13.5%) [8]. Previously, survival has been reported in a range of 62–78% at five years [2, 3, 8] and 42–56% at 10 years [3, 9], also consistent with our results. It is difficult to determine which variables are responsible for the wide range of mortalities observed; however, patient selection for surgery may play a role. Selection of patients with more functional disabilities, in particular, a higher mean EuroSCORE in the AS group, and referral to surgery could have caused worse outcomes. Reported preoperative MI rates range 7.9–30% [3, 8, 9]. We observed a preoperative MI rate of 24.2%. Previous multivariate analyses have identified age, sex, NYHA class III–IV, DM, bioprosthetic valve replacement, IABP use, preoperative MI, urgency, stroke, renal failure, EF <30%, COPD, PAD, AR, congestive heart failure, and CAD severity as risk factors for early and late mortality in patients with combined AVR-CABG [2, 3, 8, 9, 12, 13]. In this study, cross-clamp and CBP times, number of blood transfusion units, COPD, IABP, inotropic agent use, and pacemaker use were identified as significant risk factors of early mortality. ICU stay, IABP, stroke, and dialysis were significant risk factors for late mortality. Age was not a predictor for early or late mortality. Each of these complications significantly decreased long-term survival, and thus could be used to predict prognosis. Inotropic agent use, COPD, and CPB time were significant independent predictors for early mortality. However, we did not identify any independent predictors for late mortality. Melby et al. [12] previously indicated that AR is a risk factor for long-term survival. However, their sample size for AR was very small, and it is unclear how many patients had undergone concomitant AVR-CABG. These deficits make it difficult to truly conclude a relationship between AR and survival from their study. However, we found similar risk factors for late survival, including postoperative renal failure, stroke, and IABP use. Kobayashi et al. [8] have suggested that neither AR nor AS is a predictor of late mortality. They found that 20% of patients had AR in each group according to the graft number, but did not separate patients as stenotic, regurgitation, or mixed-type, making identification of patients with AR alone without AS unclear. Our analyses indicate that patients in the AR group showed similar survivals during short- and long-term follow-up. A variety of variables may have contributed to the insignificant increase in mortality observed in the AS group compared to other groups. The AS group had a smaller aortic valve size than the other two groups, which may have caused a residual aortic valve gradient that affected the early mortality rates. The mean age and percentage of female patients in the AS group, which are important risk factors for mortality, were significantly higher than those in other groups [3]. Furthermore, although we did not identify patients according to their primary pathology (i.e. CAD vs. aortic valve disease), this distinction is important, since severe CAD is associated with increased mortality. Indeed, the higher preoperative MI rates and higher angina class of the AS group may indicate a primary pathology of severe CAD, although the number of bypass grafts was similar across all groups and with previous studies [4, 8, 13]. Patients in the AS group may have exhibited increased subendomyocardial ischemia rates, given their more advanced age, higher rate of previous MI, and angina class rate, which are related to CAD with LV hypertrophy. The rate of left internal mammary artery (LIMA) use was previously reported as 30–80% [6, 8–11, 13], while that in our study was 62%. These rates may be associated with the extent of vessel disease, especially of the left anterior descending coronary artery. Thus, AS group patients may have undergone AVR and CABG surgery to resolve more serious CADs rather than valvular disease. The complete revascularization of AR patients may account for their similarly late survival, although incomplete revascularization is not a predictor of late mortality [8]. Retrospective studies have inherent limitations, such as small sample sizes. We may observe different results and outcomes with comprehensive studies using a larger sample size. However, our results indicate that AR patients have similar survivals as those with other types of aortic valve pathology.
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Abstract
1. Introduction
