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Ann Thorac Surg 2003;76:1094-1100
© 2003 The Society of Thoracic Surgeons

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Original article: cardiovascular

Mild to moderate mitral regurgitation in patients undergoing coronary bypass grafting: effects on operative mortality and long-term significance

^a University of Toronto, Toronto, Ontario, Canada

Accepted for publication April 8, 2003.

^* Address reprint requests to Dr Mickleborough, Division of Cardiovascular Surgery, Toronto General Hospital, 200 Elizabeth St, Toronto, Ontario, Canada M5G 2C4, Canada.
e-mail: l.mickleborough{at}on.aibn.com

	Abstract

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
BACKGROUND: Patients undergoing bypass grafting (CABG) often present with mitral regurgitation (MR). While surgical strategy for patients with either trace or severe MR is well established, the need for a valve procedure with mild (2) to moderate (3+) mitral regurgitation is controversial.

METHODS: We reviewed 1,939 consecutive CABG patients (1987 to 1999). A preoperative echocardiogram performed when clinically indicated graded MR from 1 to 4+. Patient characteristics, hospital mortality, and long-term survival were compared between 167 patients with grade 2 to 3+ MR and controls. A multivariate analysis identified independent predictors for long-term mortality.

RESULTS: The MR patients were more often female and older; had increased comorbities including hypertension, diabetes, and heart failure; had more extensive coronary disease and worse left ventricular (LV) function; and required urgent surgery more often. Operative mortality was 0.8% in no MR patients and 1.8% in MR patients (p not significant). Long-term survival for MR patients with poor LV function (LV grade 3 to 4) was significantly lower (53% versus 75% at 10 years, p = 0.001). Independent predictors of poor long-term survival were advanced age, LV dysfunction, heart failure, diabetes, prior cerebrovascular accident, peripheral vascular disease, and no left internal mammary artery use.

CONCLUSIONS: Coronary artery bypass graft patients with mild or moderate MR have worse baseline characteristics but operative mortality with CABG alone is not significantly increased. Long-term prognosis for MR patients with poor LV function is worse compared with patients with no MR but MR was not an independent predictor of long-term mortality. To determine whether surgical correction of MR would improve results, a prospective randomized trial seems warranted.

	Introduction

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Patients undergoing coronary artery bypass grafting (CABG) can present with associated mitral regurgitation that may be extremely variable in degree and etiology. Left ventricular (LV) wall motion abnormalities consequent to ischemic heart disease with or without ventricular dilatation or papillary muscle elongation may lead to altered geometry of the entire valve apparatus responsible for mitral incompetence [1–3]. Conversely degenerative mitral valve disease with leaflet prolapse or mitral dilatation can be associated with ischemic heart disease and can be responsible for mitral regurgitation.

Assessing the presence of mitral regurgitation, its etiology, and severity by an LV angiogram or echocardiogram are important components of the preoperative patient evaluation. Given this information surgeons have to decide whether some kind of valve procedure is required together with revascularization. The decision is relatively easy in patients with only trace (1+) mitral regurgitation that does not require any correction and in patients with severe (4+) mitral regurgitation that obviously requires a valve procedure. For patients with mild (2+) and moderate (3+) mitral regurgitation the decision is more difficult. Surgeons must weigh the potentially higher operative risk of a combined valve and bypass procedure with possible improvement in long-term outcome.

To assist surgeons in this decision process this study was undertaken to evaluate the operative and long-term outcome of patients with mild to moderate mitral regurgitation who were treated with revascularization alone. These results have been compared with those achieved in a control group with 0 or 1+ MR.

	Material and methods

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Between 1987 and 1999, 1,939 patients with significant coronary artery disease underwent isolated CABG by a single surgeon (LLM) at Toronto General Hospital. Data were prospectively collected by trained chart reviewers using a standard data collection form. All patients had a preoperative left ventriculogram. Patients in whom significant MR was suspected underwent a preoperative echocardiography assessment using color flow imaging. Preoperative evaluation identified 142 patients (7.3%) with 2+ MR who underwent revascularization alone. Patients with 3+ MR were reevaluated intraoperatively by transesophageal echocardiography. If this study downgraded the MR to 2 to 3+, revascularization alone was performed (25 patients, 1.3%). Therefore 167 patients (8.6%) comprise the MR group. Patients with 0 or 1+ MR form the control group (no MR group). During the same time frame 45 patients with more severe mitral regurgitation, 4+ on preoperative echocardiography or 3+ or greater on intraoperative echocardiography, underwent a combined procedure with revascularization plus mitral valve repair or replacement and were excluded from this analysis.

Preoperative clinical variables are given in Table 1. Catheterization data including extent of coronary artery disease and left ventricular function graded as previously described [4] are shown in Table 2.

Based on these criteria, etiology of MR was ischemic in 120 patients and valvular in 24 patients. In the remaining 23 patients the etiology could not be determined because of technically inadequate studies.

Operative technique
Fentanyl citrate was used for induction and maintenance of anesthesia. Between 1987 and 1989 moderate systemic hypothermia (25°C) was used. Since 1989 body temperature has been allowed to drift spontaneously without active cooling. Cold blood cardioplegia has been used with terminal hot shot. The route of cardioplegia delivery (antegrade, retrograde, through a venous graft) was determined by measuring myocardial temperatures according to a technique previously described [7]. Our approach to revascularization has been quite aggressive and includes grafting small vessels (1 mm in size) when necessary to achieve complete revascularization [8]. Information obtained from the operative records include number of grafts, use of left internal thoracic artery (LITA), need for endarterectomy or vein patch angioplasty, pump time, cross clamp time, and completeness of revascularization (Table 3).

Population characteristics
Patient characteristics are shown in Table 1. There were 167 patients in the MR group and 1,772 in the no MR group. Patients with MR were older, more often women, and presented more often with a history of prior diabetes, hypertension, peripheral vascular disease, renal insufficiency, prior CVA, prior MI, symptoms of heart failure or unstable angina, and required surgery more often on an urgent basis or with preoperative IABP support. Patients with MR were also more likely to have a history of atrial fibrillation or ventricular arrhythmias.

Catheterization data are shown in Table 2. Patients with MR had worse LV function and more extensive coronary artery disease. Intraoperative data are given in Table 3. In MR patients with more diseased vessels, the cross clamp and pump times were longer.

	Results

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Short-term results
The operative mortality was 1.8% in the MR group versus 0.7% in the no MR group. This difference was not statistically significant (p = 0.153; Table 4). There were 2 deaths in the 2+ MR group (1.4%) versus 1 death in the 3+ MR group (4%; p = 0.387). The need for IABP and postoperative inotropic agents was higher in the MR group (15% versus 6%, p < 0.000; and 14% versus 4%, p = 0.001). The incidence of perioperative MI and need for reexploration for bleeding was higher in the no MR group (3.2% versus 0.6%, p = 0.033; and 1.9% versus 0%, p = 0.050). Incidence of postoperative VT was higher in the MR group (6.3% versus 2.6%, p = 0.015) but the incidence of postoperative atrial fibrillation was similar (22% versus 19.7%, p = 0.279). Patients in the MR group were more likely to have a perioperative CVA (6% versus 2%, p = 0.004).

Long-term results
Follow-up was 98.2% complete with only 35 patients lost to follow-up. Follow-up extends from 6 months to 13 years with mean follow-up 62 ± 41 months. Survival was significantly less for patients with MR (10 year survival 60% versus 78%, p < 0.000; Fig 1).

View larger version (16K): [in this window] [in a new window]   Fig 1. Actuarial survival for mild (2) to moderate (3+) mitral regurgitation (MR) group (dashed line) and no MR group (solid line). 5-year survival: no MR, 93% ± 0.7%; MR, 82% ± 4%. 10-year survival: no MR, 78% ± 1.7%; MR, 60% ± 7% (p = 0.000).

View larger version (17K): [in this window] [in a new window]   Fig 2. Cumulative freedom from death or repeat hospitalization for mild (2) to moderate (3+) mitral regurgitation (MR) group (dashed line) and no MR group (solid line). 5-year survival: no MR, 86% ± 1%; MR, 65% ± 5%. 10-year survival: no MR, 55% ± 2%; MR, 21% ± 6% (p = 0.000).

View larger version (13K): [in this window] [in a new window]   Fig 3. Actuarial survival for mild (2) to moderate (3+) mitral regurgitation (MR) group (dashed line) and no MR group (solid line). (A) Patients with good left ventricular (LV) function ejection fraction (EF) more than 40%. 5-year survival: no MR, 95% ± 0.7%; MR, 86% ± 7%. 10-year survival: no MR, 80% ± 2%; MR, 78% ± 10% (p = 0.265). (B) Patients with poor LV function EF less than 40%. 5-year survival: no MR, 89% ± 1.7%; MR, 80% ± 5%. 10-year survival: no MR, 75% ± 3%; MR, 53% ± 9% (p = 0.001).

View larger version (13K): [in this window] [in a new window]   Fig 4. Cumulative freedom from death or repeat hospitalization for mild (2) to moderate (3+) mitral regurgitation (MR) group (dashed line) and no MR group (solid line). (A) Patients with good left ventricular (LV) function ejection fraction (EF) more than 40%. 5-year survival: no MR, 88% ± 1%; MR, 79% ± 9%. 10-year survival: no MR, 59% ± 3%; MR, 25% ± 14% (p = 0.041). (B) Patients with poor LV function EF less than 40%. 5-year survival: no MR, 79% ± 2%; MR, 60% ± 6%. 10-year survival: no MR, 46% ± 4%; MR, 21% ± 7% (p = 0.000).

	Comment

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Mitral insufficiency has also recently been reported to affect the outcome of patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) [13]. In this study 203 of 4,421 patients, or 4.8% of those presenting for PCI, had 2 to 4+ MR. The 3-year actuarial survival with no, mild, moderate, and severe MR differed significantly (92.3%, 84.5%, 74.6%, and 68.6% respectively) and MR was an independent negative prognostic factor. The authors concluded that moderate or severe MR should be considered a relative contraindication for PCI [13].

In our study of patients undergoing CABG, mild to moderate MR was found in 8.8%. This incidence is higher than that in the PCI series but lower than that reported after an acute MI. This is not surprising given the fact that we excluded patients with trace or severe MR.

Our series provides long-term follow-up in a large number of patients with mild to moderate MR treated with CABG alone. Patients with 2 to 3+ MR had a different clinical presentation than no MR patients. They had more extensive coronary disease and presented with worse ventricular function. Despite these differences with careful myocardial protection and an aggressive revascularization policy that allowed complete revascularization in all but 29 patients [8] we experienced few operative deaths. The operative mortality was slightly higher in the MR group (1.8% versus 0.7%) but the difference did not reach statistical significance (p = 0.153).

With respect to long-term survival our data show that patients with mild to moderate MR have a significantly lower long-term survival compared with patients with no MR (82% versus 93% at 5 years and 60% versus 78% at 10 years, p < 0.001). When analyzed in a multivariate way however mild to moderate MR was not an independent predictor of poor long-term outcome. Clearly other patient variables have a more important impact on long-term survival. Independent predictors of decreased survival included age, poor LV function, diabetes, peripheral vascular disease, prior CVA, congestive heart failure, and no use of LIMA. Others have reported similar predictors of poor outcome [14–16].

In this series use of a LIMA graft was lower in the MR group (69.5% versus 77.5%, p = 0.014). There are several reasons for this. As reported earlier we use a LIMA less often in those requiring urgent surgery [8]. We have also been reluctant to use a LIMA in elderly women with a fragile sternum.

Many studies have confirmed that poor LV function has a major impact on long-term survival in CABG patients [14–16]. The interaction between mitral insufficiency and poor LV function and their influence on long-term survival is a complex one. It is likely that volume overload secondary to mitral insufficiency amplifies and accelerates the adverse LV remodeling process leading to higher filling pressures [17, 18], heart failure, and premature death [19]. In our series most patients with 2 to 3+ MR (67%) had poor LV function (grade 3 or 4) and 10-year survival was clearly decreased in this group. This agrees with the findings reported by Ellis and associates [13] in patients after PCI. Survival was similar for patients with and without MR provided LV function was relatively preserved, that is ejection fraction more than 40%. However survival was significantly decreased for patients with 2 to 3+ MR and poor LV function, ejection fraction less than 40%. Their 3-year survival in patients with grade 2 MR and an ejection fraction less than 40% of only 60% can be compared with our 5-year survival of 80% in patients with an ejection fraction less than 40% and 2 to 3+ MR. In our series complete revascularization was achieved in 98% whereas in the PCI series complete revascularization was achieved in only 11% to 17% of patients with 2 to 4+ MR [13]. Completeness of revascularization may be one factor related to increased long-term survival in the surgical group.

Our results agree with those of other reports available in the literature. In CABG patients Ryden and associates [20] reported a 3-year survival for patients with 2+ ischemic MR of 84% versus 92% for patients without MR. This compares with our 5-year survival of 82% and 93% in the two groups. They performed a case control study (n = 89) of patients with 2+ MR and control patients without MR (matched for age, sex, and ejection fraction). Three-year survival in the two groups was 84% and 88% respectively, a difference that was not statistically significant [20]. In a similar study (n = 58), Duarte and associates [21] matched patients with moderate MR and no MR for age, sex, and ejection fraction. They found after 10 years of follow-up survival was 52% and 55% respectively (p = 0.59). They concluded that MR was not an independent predictor for mortality. These studies support our conclusion that mild to moderate MR is not an independent predictor of mortality in patients treated with CABG alone. However our data would suggest that during long-term follow-up even in those with relatively well preserved LV function, presence of 2 to 3+ MR is associated with increased likelihood of repeat hospitalization.

A major limitation of this study is its retrospective design. Quality of the perioperative echocardiograms did not always allow us to determine exact etiology of MR, which may have an important effect on prognosis. Furthermore it is difficult to compare our results with those of other reported series because the criteria used for grading MR are not always the same and full clinical information describing the patient populations is often not provided. In surgical series reporting use of combined procedure involving CABG plus mitral valvoplasty or valve replacement the etiology of MR is not always reported and some series include patients with nonischemic dilated cardiomyopathy. Operating room mortality and long-term results in these cases may be very different from those with coronary artery disease. Nevertheless to try to put things in perspective some comparisons will be made.

In the past, based on the reported high operative mortality of patients undergoing combined CABG and mitral valve replacement (15% in the series by He and associates [22]) a conservative approach to moderate MR in CABG patients has been recommended. Aklog and colleagues [23] reviewed preoperative and postoperative echocardiograms of 136 CABG patients with moderate ischemic MR and concluded that CABG alone does not correct MR in the majority of patients. They suggested a wider application of mitral annuloplasty to treat this kind of MR. Recently reported operative mortality for mitral valve repair for ischemic MR is still 10% to 12% [24–26], which is much higher than the operative mortality that we observed in our 2 to 3+ MR group with CABG alone (1.8%). Bolling and coworkers [27] have used an undersized annuloplasty ring to treat severe MR in patients with dilated hearts with excellent results. However about half of the patients in their series did not have coronary artery disease. Long-term follow-up of these patients is still pending and results with this approach in other centers have been less consistent [25, 28]. To date a consensus has not been reached with regard to the optimal approach for surgically dealing with 2 to 3+ mitral regurgitation associated with coronary artery disease.

This study reports the long-term follow-up of CABG patients presenting with mild to moderate MR who are treated with revascularization alone. Although the presence of MR predicts increased need for repeated hospitalization (after 5 years) it seems to have little affect on 10-year survival. A multvariate analysis showed that mitral regurgitation was not an independent predictor of mortality. In the subgroup of patients with significant LV dysfunction however we have clearly shown that long-term survival is lower in patients with mild to moderate MR compared with patients with no MR.

The unresolved question remains whether all patients with mild to moderate mitral regurgitation undergoing CABG should have an additional procedure addressing their mitral insufficiency. Can that be accomplished with an acceptable operative mortality and will this approach further improve long-term outcome? A prospective randomized trial is needed to compare CABG versus CABG plus valve procedure to determine whether the increased surgical risk is justified by improved long-term outcomes.

	Acknowledgments

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
We extend out appreciation to Hilary Vincent for the excellent preparation of the manuscript.

	References

Top Abstract Introduction Material 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): Domenico Paparella Lynda L. Mickleborough Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Paparella, D. Articles by Ivanov, J. Search for Related Content PubMed PubMed Citation Articles by Paparella, D. Articles by Ivanov, J. Related Collections Coronary disease