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Ann Thorac Surg 2005;79:1895-1901
© 2005 The Society of Thoracic Surgeons
a Division of Cardiothoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA
b Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California, USA
c Division of Biostatistics, Cedars-Sinai Medical Center, Los Angeles, California, USA
d Departments of Medicine and Surgery, UCLA School of Medicine, Los Angeles, California
Accepted for publication November 10, 2004.
* Address reprint requests to Dr Czer, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Rm 6215, Los Angeles, CA 90048-1865 (E-mail: czer{at}csmc.edu).
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Abstract |
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METHODS: We studied 355 patients who underwent revascularization alone (n = 168) or revascularization combined with mitral valve repair (n = 187) for IMR from March 1994 to September 2003. Preoperative and operative characteristics, postoperative mitral regurgitation severity, operative mortality, and late survival were examined for each surgical group.
RESULTS: No differences were noted between the two groups in age, sex, history of diabetes or hypertension, and number of bypass grafts. The combined surgical group had a lower preoperative left ventricular ejection fraction (0.38 ± 0.14 versus 0.44 ± 0.15), greater severity of IMR, higher frequency of prior myocardial infarction, and longer cross-clamp and pump times (p < 0.01). The combined surgical group had a greater reduction in IMR grade (2.7 ± 0.1 grades versus 0.2 ± 0.1 grade), a lower postoperative IMR grade (0.9 ± 0.1 versus 2.3 ± 0.1), and a higher success with reduction of IMR by two or more grades (89% versus 11%) (p < 0.001). In patients with 3+ or 4+ IMR, both groups had similar operative mortality (11.0% in the combined group compared with 4.7% for revascularization alone, p = 0.11) and actuarial survival at 5 years (44% ± 5% versus 41% ± 7%, p = 0.53). Independently predictive of higher early mortality (
30 days) by Cox analysis were longer pump time (p < 0.001) and older age (p < 0.02). Predictive of late mortality (>30 days) were older age (p < 0.001), fewer bypass grafts (p < 0.01), and lower ejection fraction (p < 0.01). After adjustment for these variables, there was a trend (p = 0.08) toward a higher late survival with the combined surgical procedure.
CONCLUSIONS: In patients with IMR, combined mitral valve repair and revascularization resulted in less postoperative mitral regurgitation and similar 5-year survival when compared with revascularization alone. Attempts to reduce pump time by using off-pump techniques may reduce early mortality in these high-risk patients.
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Introduction |
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TopAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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75% stenosis), 19% had mitral regurgitation [1]. The management of ischemic mitral regurgitation represents a therapeutic challenge. Although most patients are treated medically, many patients are referred for surgery. Because the morbidity and operative mortality associated with combined revascularization and mitral valve replacement are high and long-term survival is poor [1–4], some authors have advocated revascularization alone [5, 6], whereas others have recommended revascularization combined with mitral valve repair [1–4, 7–9]. Uncorrected mitral regurgitation leads to reduced long-term survival after revascularization [1, 4, 10]; however, mitral valve surgery may add to the operative risk when combined with revascularization [4, 8, 9, 11, 12]. The optimal strategy for treatment of ischemic mitral regurgitation is not known.
Herein we report our center’s experience with 355 patients who underwent revascularization alone or combined with mitral valve repair for ischemic mitral regurgitation. We compared the effect of each surgical procedure on the severity of mitral regurgitation, on operative mortality, and on late survival. We also examined the influence of the repair method.
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Patients and Methods |
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Doppler Echocardiography
Real-time two-dimensional imaging of intracardiac structure and blood flow was performed using an HP Sonos (Hewlett-Packard Co, Andover, MA), ATL 5000 (Philips Medical Systems Co, Bothell, WA), or Acuson Sequoia (Acuson Corp, Mountain View, CA) color Doppler system, and images were recorded using 1/2-inch videotape. Imaging was performed within 1 year before the operation or before cardiopulmonary bypass using previously described methods [8, 9, 13, 14] and after cardiopulmonary bypass or up to 1 year after the operation, with appropriate attention to control of afterload and preload conditions [13, 14].
Mitral regurgitation was graded semiquantitatively on a scale of 0 to 4+ using a visual estimation of the regurgitation jet area in relation to the left atrial area, modified from Nanda’s criteria [13]. A successful valve repair was defined as a two-grade or greater reduction in mitral regurgitation when compared with the preoperative or prepump study. Doppler echocardiography was performed at a mean (±SD) of 3 ± 29 days (range 0 to 12 months) before the operation and 4 ± 25 days (range 0 to 10 months) after the operation in the combined mitral valve repair and revascularization group, and at a mean of 14 ± 42 days (range 0 to 8 months) before the operation and 34 ± 129 days (range 0 to 40 months) after the operation in the revascularization-alone group.
Surgical Procedure
The etiology of valve disease was determined from direct visual inspection of the mitral valve leaflets, annulus, chordae tendineae, and papillary muscles. If the valve was not repaired, the etiology was determined from the echocardiographic findings. An ischemic etiology was concluded if the mitral leaflets and chordae appeared normal, but there were findings of papillary muscle infarction or thinning, papillary muscle ischemia, or mitral annular dilation associated with left ventricular dilation and healed infarction [8, 9].
Ischemic mitral regurgitation was repaired by one of several annuloplasty techniques at the discretion of the operating surgeon. No specific criteria were used in selecting a particular annuloplasty technique for an individual patient. Ring annuloplasty was performed as described by Carpentier and colleagues [15], and included 70 Carpentier-Edwards, 36 Dacron (C.R. Bard, Covington, GA), 26 pericardial, and 48 other rings (34 St. Jude Tailor and 14 Duran or other type of ring). Suture annuloplasty was performed as described by Kay and associates [3] in 7 patients with placement of encircling mattress or figure-of-eight sutures at one or both commissures of the mitral valve. No ancillary leaflet repair or chordal shortening procedures were required in any patient.
Postoperative Follow-Up
After the operation, we followed up with a mailed questionnaire, telephone interview, or examination in our offices. Follow-up was continued yearly, unless death occurred.
Statistical Methods
For comparing the surgical groups with regard to preoperative characteristics and measures of operative success we used two-sample t tests (for continuous or ordinal data) and 
2 analysis or Fisher’s exact test for categorical data. Analysis of variance (with the Bonferroni correction) was used for the change in the mitral regurgitation grade. The significance level was set at p = 0.05. Actuarial survival was calculated by the life-table method. All mortalities (including operative deaths) were included. For analysis of survival data, a Wilcoxon test was used to test for equality among the surgical groups. A multivariate stepwise Cox model was used to determine predictors of early (30 days) and late (>30 days) survival.
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Results |
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Doppler Echocardiography
The preoperative mitral regurgitation grade was significantly greater in the combined group than in the revascularization-alone group (p < 0.001, Table 1). Despite this difference, the postoperative mitral regurgitation grade in the combined group (0.9 ± 0.1, mean ± SD) was significantly lower when compared with the revascularization-alone group (2.3 ± 0.1, p < 0.001). As a result, the preoperative to postoperative change in mitral regurgitation grade was greater in the combined group (Fig 1, p < 0.001). Defined as a two-grade or greater reduction in mitral regurgitation, a successful outcome occurred significantly more often in the combined group than in the revascularization-alone group, as shown in Figure 2 (89% versus 11%, p < 0.001). When comparing different types of valve repair (Fig 2), the success rate after repair was significantly lower with a pericardial ring (73% success rate) than with the Carpentier-Edwards ring (94% success rate; p = 0.008). Other comparisons among different ring repair techniques did not reach statistical significance after adjustment for multiple comparisons (Bonferroni correction).
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Postoperative Survival
Early mortality (30 days) was lower in the group with revascularization alone than in the combined valve repair and revascularization group (4.2% [7 of 168 patients] compared with 11.2% [21 of 187 patients], respectively; p = 0.02, Fisher’s exact test). When only patients with 3+ or 4+ preoperative mitral regurgitation were included, the early mortality with revascularization alone (4.7% [4 of 85 patients]) was not significantly different from the combined group (11.0% [20 of 182 patients]; p = 0.11, Fisher’s exact test). In a Cox stepwise model, neither the preoperative grade of mitral regurgitation nor the surgical group (revascularization alone, versus combined valve repair and revascularization) were predictive of early survival. Of the variables listed in Table 1, only pump time (p < 0.001) and age (p < 0.02) were predictors of early survival in a multivariate Cox model. Shorter pump time and younger age predicted higher early survival.
No significant difference was noted for survival up to 5 years after the operation between the revascularization-alone group and the mitral valve repair plus revascularization group (Fig 3; p = 0.30). At 5 years, survival was 52% ± 5% with revascularization alone compared with 44% ± 5% with combined mitral valve repair and revascularization. Mitral valve reoperation was required for no patient in the revascularization-alone group and for 4 patients (2.1%) in the combined group (p = 0.13 by Fisher’s exact test). In patients with 3+ or 4+ mitral regurgitation, no significant difference was noted in survival up to 5 years after the operation between the groups (Fig 4; p = 0.53). At 5 years, survival was 41% ± 7% with revascularization alone compared with 44% ± 5% with combined mitral valve repair and revascularization. There was a trend toward a higher survival in the combined surgical group after the first postoperative year (Fig 4). A multivariate stepwise Cox regression analysis was performed to determine which preoperative or operative variables were predictive of late survival (>30 days) in the overall patient population. Independently predictive of higher late survival were younger age (p < 0.001), larger number of bypass grafts (p < 0.01), and higher ejection fraction (p < 0.01). There was a trend favoring a higher late survival in the combined (valve repair and revascularization) surgery group after adjustment for age, number of bypass grafts, and ejection fraction (p = 0.08). The specific annuloplasty repair method had no significant effect on late survival. Tricuspid valve repair was not a predictor of late survival.
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30 days) for the revascularization-alone group (n = 7) were cardiac in 4 (57%), and noncardiac in 3 (43%). Causes of early death for the combined valve repair and revascularization group (n = 21) were cardiac in 13 (62%) and noncardiac in 8 (38%) (p = 0.99 for comparison between surgical groups). Causes of late death (>30 days) for the revascularization-alone group (n = 54) were cardiac in 23 (43%), noncardiac in 24 (44%), and indeterminate in 7 (13%); causes of late death for the combined valve repair and revascularization group (n = 56) were cardiac in 34 (61%), noncardiac in 20 (36%), and indeterminate in 2 (4%) (p = 0.08 for comparison between surgical groups).
Functional Class
The New York Heart Association (NYHA) functional class was assessed before and at a mean of 12 and 24 months after the operation in survivors. In 1-year survivors, the preoperative NYHA class was 3.11 ± 1.01 (mean ± SD) and decreased at 1 year to 1.28 ± 0.74 (change of 1.83 ± 1.22) in the revascularization group (n = 71), compared with 3.27 ± 0.84 before the operation and decreasing at 1 year to 1.33 ± 0.69 (change of 1.94 ± 1.07) in the combined mitral valve repair and revascularization group (n = 64). Despite strong evidence of overall improvement (p < 0.001), no difference was noted between the two surgical groups in the magnitude of improvement (p = 0.77). In 2-year survivors, the preoperative NYHA class was 3.12 ± 1.02 and decreased at 2 years to 1.12 ± 0.38 (change of 2.00 ± 1.08) in the revascularization group (n = 65), compared with 3.22 ± 0.82 before the operation and decreasing at 2 years to 1.29 ± 0.63 (change of 1.92 ± 1.00) in the combined mitral valve repair and revascularization group (n = 65). There was overall improvement (p < 0.001), but no difference was noted between the two surgical groups in the magnitude of improvement (p = 0.49).
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Comment |
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TopAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Several mechanisms may explain the incomplete leaflet coaptation in ischemic mitral regurgitation, including mitral annular dilation [8, 9] due to thinning and stretching of the adjacent left ventricular myocardium after myocardial infarction [16], abnormal mitral valve tethering by displaced papillary muscles [16] resulting from dyskinesis of the left ventricular wall after myocardial infarction or ischemia, papillary muscle elongation due to myocardial infarction [15], early systolic mitral leaflet "loitering" effect [17], and a reduced ventricular force acting to close the leaflets [18]. Given the central role of myocardial infarction (or ischemia) and the lack of mitral valve or chordal pathology, ischemic mitral regurgitation may more appropriately be termed "left ventricular" regurgitation.
The management of ischemic mitral regurgitation remains controversial. Therapeutic options have included mitral valve replacement and coronary artery revascularization, mitral valve repair and coronary artery revascularization, and revascularization alone. Previous studies have reported that the patients with mitral valve replacement and coronary artery revascularization have high early and late mortality and low long-term survival [1–4]. In comparison with mitral valve replacement, mitral valve repair has been associated with a lower rate complications, especially thromboembolism and warfarin-related hemorrhage, and a higher survival rate [3]. A previous study has reported that 40% of patients continued to have significant residual mitral regurgitation and only 9% had resolution of mitral regurgitation with revascularization alone for ischemic mitral regurgitation [7]. Similarly, in the present study, revascularization alone did not result in a significant change in mitral regurgitation grade (Fig 1), and only 19 (11%) of 168 patients achieved a two-grade or greater reduction in mitral regurgitation (Fig 2). In other words, reduction or elimination of mitral regurgitation can be expected in only about 10% of patients after revascularization alone. In these patients, improvement in mitral regurgitation probably occurs as a result of restoration of blood flow to an area of hibernating myocardium; that is, ischemic but viable myocardium that does not function properly at rest, but does function with adequate blood flow. Notwithstanding these observations, reported mortality rates have been low after revascularization alone [5, 6]. The optimal treatment strategy, therefore, is not known.
Previous studies have shown that mitral valve repair (especially mitral annuloplasty) can decrease or eliminate mitral regurgitation in most cases [8, 9, 11, 12, 19]. In the present study, the repair patients had a significantly greater reduction in mitral regurgitation (Fig 1) than patients who underwent revascularization alone. The responsible mechanisms may include a more favorable subvalvular three-dimensional dynamic geometry [20], a reduction in annulus diameter [8], and an increased leaflet coaptation area [8]. Although mitral annuloplasty is an important aspect of mitral valve repair, the preferred technique remains controversial. The flexible pericardial and Dacron rings may be superior to the rigid Carpentier-Edwards ring for mitral valve annuloplasty in the view of more favorable mitral annulus dynamics and preservation of left ventricular function during stress conditions [21]. Based on the present report, however, success (reduction of mitral regurgitation by two grades or more) was achieved in 94% of patients with the Carpentier-Edwards ring, 86% with the Dacron ring, and 73% with the pericardial ring (Fig 2). The pericardial ring had a significantly lower success rate than the Carpentier-Edwards (classic) ring, but the other comparisons did not reach statistical significance. A larger study is needed to detect any difference among ring annuloplasty techniques for the successful reduction of ischemic mitral regurgitation.
Most series have reported operative mortalities ranging from 9.5% to 15% when mitral valve repair is added to revascularization, [11, 12] in comparison with 3% to 4% for revascularization alone [5–7]. In the present series, early mortality (30 days) after the combined procedure was higher than after revascularization alone, but the difference was not statistically significant in patients with 3+ or 4+ mitral regurgitation. A somewhat higher early mortality after the combined procedure may be attributable to the longer pump time (Table 1), which may be poorly tolerated in patients with reduced ventricular function and an already high "ischemic burden" due to the coronary artery disease. In support of this hypothesis, independent predictors of higher early mortality (30 days) by Cox analysis were longer pump time (p < 0.001) and older age (p < 0.02). A possible strategy to shorten ischemic time (and thus operative mortality) in these patients would be to perform bypass grafting on the beating heart (off-pump). The inclusion of a small number of tricuspid valve repair procedures in patients with combined revascularization and mitral valve repair in the current study did not adversely affect survival.
In a long-term study of more than 2,000 patients who underwent revascularization alone, uncorrected mitral regurgitation nearly doubled the risk of late death, and risk of death increased with greater severity of uncorrected regurgitation [10]. Additionally, with valve surgery performed late after revascularization, in-hospital mortality has been reported to be 8.8% [22]. If a significant reduction or elimination of the mitral regurgitation can be achieved in a patient with moderately severe (3+) or severe (4+) regurgitation, performing the combined procedure is justifiable and prudent, even though the combined group may have a somewhat increased operative risk. In a multivariate Cox regression analysis, factors that were independently predictive of lower late survival (>30 days) were older age (p < 0.001), fewer bypass grafts (p < 0.01), and lower ejection fraction (p < 0.01). A trend was found (p = 0.08) toward a higher late survival with the combined surgical procedure in the multivariate Cox analysis. A trend toward lower survival after the first postoperative year in the revascularization-alone group for 3+ or 4+ mitral regurgitation (Fig 4) implies an adverse effect from uncorrected ischemic mitral regurgitation, but longer follow-up of these patients will be required to confirm this observation. In the current study, 5-year actuarial survival in patients with 3+ or 4+ mitral regurgitation was 44% ± 5% after the combined procedure and 41% ± 7% after revascularization alone (Fig 4). The high mortality in both groups at 5 years suggests that the major determinant of late survival in patients with ischemic mitral regurgitation is the presence of coronary artery disease and reduced left ventricular function, characteristics which both surgical groups shared. Previous studies have demonstrated a 5-year survival of 31% to 48% after revascularization combined with mitral valve repair [6, 23].
Little attention has been paid to the issue of sudden death in patients with ischemic mitral regurgitation. Because causes of late death include sudden cardiac death, myocardial infarction, and heart failure, strategies directed at reducing or preventing these occurrences should improve late survival. The use of an automatic implantable cardioverter defibrillator may be indicated in many patients with ischemic mitral regurgitation, and a clinical trial is probably warranted. A possible additional benefit of the combined procedure is a reduction in symptoms of heart failure, but in the present study no beneficial effect on the postoperative NYHA functional class was found, possibly due to the lower preoperative left ventricular ejection fraction in this group.
We have previously shown that the grade of mitral regurgitation remains unchanged in the early postoperative period (in the absence of a new ischemic event) if the afterload conditions are carefully monitored and controlled [8, 9, 13]. Thus, the early postoperative (or intraoperative) echocardiographic evaluation provides an accurate assessment of the adequacy of repair [8, 9, 13, 14]. A small but significant change in the grade of mitral regurgitation from the first to the second postoperative examination occurred in the combined surgical group (mitral regurgitation grade from 1.2 ± 1.2 to 1.8 ± 1.3, p = 0.005; mean interval 195 ± 408 days), but was not observed in the revascularization-alone group (from 2.5 ± 1.0 to 2.5 ± 0.9; mean interval 412 ± 636 days). This change in postoperative mitral regurgitation grade in the combined surgical group may reflect differing afterload conditions, left ventricular remodeling due to a lower ejection fraction, or possibly the occurrence of an ischemic event during the interval. A postoperative ischemic event may affect left ventricular function and thus the magnitude of ischemic mitral regurgitation [8, 9, 15–18]. Further studies are needed to determine whether left ventricular remodeling differs with the two surgical approaches.
In patients with ischemic mitral regurgitation and severely reduced left ventricular function (ejection fraction <0.30), heart transplantation is a therapeutic option with an estimated median survival of 8.5 to 10 years. This survival after heart transplantation is approximately twice as long as the nearly 5-year median survival after revascularization alone or combined with mitral valve repair. However, not all patients with ischemic mitral regurgitation are heart transplant candidates. Alternative strategies in patients with ischemic mitral regurgitation require further investigation, such as passive epicardial containment with the Acorn device [24] as an adjunct to revascularization, or coronary artery bypass grafting on the beating heart using off-pump techniques to reduce ischemic time. Development of off-pump techniques may be especially important in this high-risk group of patients with ischemic mitral regurgitation.
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Acknowledgments |
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TopAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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