Echocardiographic Predictors of Successful Versus Unsuccessful Mitral Valve Repair in Ischemic Mitral Regurgitation

Echocardiographic Predictors of Successful Versus Unsuccessful Mitral Valve Repair in Ischemic Mitral Regurgitation Vorachai Kongsaerepong, MDa, Maiko Shiota, BSa, A. Marc Gillinov, MDb,†, Jong-Min Song, MDa, Shota Fukuda, MDa, Patrick M. McCarthy, MDd,‡, Timothy Williams, MDa, Robert Savage, MDc, Masao Daimon, MDa, James D. Thomas, MDa, and Takahiro Shiota, MDa,* Mitral valve (MV) annuloplasty is the standard surgical technique for the management of ischemic mitral regurgitation (MR). However, <1/3 of patients develop recurrent MR after annuloplasty. Therefore, we sought to identify the preoperative echocardiographic parameters that predict annuloplasty failure in patients with ischemic MR. Intraoperative transesophageal echocardiograms from 365 patients who underwent MV repair for ischemic MR were reviewed. Of the 365 patients, 297 (81%) had satisfactory outcomes with <2ⴙ MR, and 68 (19%) had recurrent MR (>2ⴙ) during a mean follow-up of 269 days. The mitral annular parameters, including mitral annular diameter, tethering height, and tethering area of the mitral leaflets, were determined in 3 different echocardiographic views. On multiple logistic stepwise regression analysis, a higher mitral annular diameter, higher tethering area, and higher MR severity were identified as independent predictors for failure of MV repair (p <0.0001). In conclusion, these results demonstrated that preoperative echocardiographic findings can be used to identify patients with ischemic MR at increased risk of repair failure. These echocardiographic measurements should be used to guide the cardiologist and cardiac surgeon in the choice of MV repair versus replacement in patients with ischemic MR. © 2006 Elsevier Inc. All rights reserved. (Am J Cardiol 2006;98: 504 –508) Ischemic mitral regurgitation (MR) develops in ⱕ15% of patients after myocardial infarction1 and is associated with excess cardiac morbidity and mortality.2– 4 When ischemic MR is severe, patients frequently develop intractable heart failure and are often referred for surgical treatment of the mitral valve (MV). The standard surgical repair entails an undersized annuloplasty, which seeks to increase mitral leaflet coaptation by reducing mitral annular diameter.5,6 Recent data have demonstrated, however, that recurrent MR is common with this approach, developing in ⱕ1/3 of patients after surgical annuloplasty.7,8 This suggests that some patients with ischemic MR might be better served by MV replacement rather than repair. Currently, few data are available to guide this decision. The aim of this study was Departments of aCardiovascular Medicine, bThoracic and Cardiovascular Surgery, and cCardiothoracic Anesthesia, Cleveland Clinic Foundation, Cleveland, Ohio; and dBluhm Cardiovascular Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. Manuscript received October 20, 2005; revised manuscript received February 13, 2006 and accepted February 16, 2006. This study was supported in part by Bangkok Metropolitan Administration, Bangkok, Thailand. * Corresponding author: Tel: 216-445-7287; fax: 216-445-7306. E-mail address: [email protected] (T. Shiota). † Dr. Gillinov is a consultant to Edwards Lifesciences, LLC and has an equity interest in Viacor, Inc., Wilmington, Massachusetts. ‡ Dr. McCarthy is a consultant to Edwards Lifesciences, LLC and an inventor, for which he receives royalties from Edwards Lifesciences, LLC, Irvine, California. 0002-9149/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2006.02.056

to identify preoperative echocardiographic parameters associated with repair failure in patients with ischemic MR. Methods Study patients: Examination of the Cardiovascular Information Registry and Echocardiography Databases at the Cleveland Clinic identified 365 patients who had undergone annuloplasty for ischemic MR and who had complete preoperative transesophageal echocardiographic (TEE) studies from April 1990 to November, 2002. The institutional review board approved the use of the database for clinical research. All patients had functional ischemic MR according to established definitions,5 and none had organic MV disease. All patients left the operating room with MR that was graded as equal to or less than mild. Echocardiographic studies: The digitized intraoperative echocardiographic data were retrieved for off-line frame-by-frame analysis. During these intraoperative TEE studies, volume and vasopressors were used routinely to raise the systemic blood pressure to the patient’s preoperative blood pressure at rest. We recognized, however, that intraoperative transesophageal echocardiography under general anesthesia frequently results in downgrading of MR. All 4-chamber, 2-chamber, and long-axis views were studied during systole (Figure 1). The parameters measured included mitral annular diameter, defined as the distance between the hinge points of the anterior and posterior mitral leaflets; tethering height, defined as the shortest distance www.AJConline.org

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Figure 1. Measurement of mitral annular diameter (MAD), tethering height (TH), and tethering area in 3 major intraoperative TEE views: (A) 4-chamber view, (B) 2-chamber view, and (C) long-axis view.

Figure 2. Transthoracic echocardiograms showing examples of recurrent ischemic MR during follow-up at (A) 5 days and (B) 9 months after MV repair with annuloplasty. Note, MR became worse during follow-up (flow convergence noted in B).

during systole from the coaptation point of the anterior and posterior mitral leaflets to the mitral annular plane; and the tethering area, defined as the smallest area during systole bounded by the leaflets and the mitral annular plane. Left ventricular volumes were calculated by the area–length method at end-diastole and end-systole from the TEE 4-chamber views, and the ejection fraction was calculated in standard fashion. MR severity was semi-quantitatively assessed by the color Doppler jet area method with the flow convergence or proximal isovelocity surface area method from intraoperative transesophageal echocardiography and scaled from 0 to 4⫹.9,10 The MR jet direction was assessed by color flow mapping in all 3 TEE views and assigned as anterior, central, or posterior. Criterion for failure of MV repair: The criterion for failure of MV repair was “MR 2⫹ or higher,” demonstrated during follow-up either by standard transthoracic echocar-

diography or transesophageal echocardiography.9,11 The mean follow-up time for the echocardiographic studies was 269 days. Intra- and interobserver variabilities: Intra- and interobserver variabilities were investigated for the reliability of echocardiographic measurements. Two independent observers studied 10 randomly selected patients for interobserver variation, and 1 observer repeated the observations in the same cohort of 10 patients on different days to assess the intraobserver variation. Statistical analysis: All continuous variables are expressed as means ⫾ SDs. Descriptive variables were assigned noncontinuous figures. The unpaired Student’s t test and the chi-square test were used for the comparisons of characteristics between patient groups. Logistic regression analysis was used for the analysis of the correlation among variables. Multivariate stepwise regression analysis was

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Table 1 Baseline characteristics of patients with successful versus unsuccessful mitral valve (MV) repair in ischemic mitral regurgitation (MR) Variable

MV Repair

Follow-up (d) Age (yrs) Men/women Coronary artery bypass grafting ⫹ MV repair MV repair Mitral annuloplasty Partial ring Complete ring

Successful (n ⫽ 297)

Unsuccessful (n ⫽ 68)

262 ⫾ 546 65 ⫾ 9 192/105 281

269 ⫾ 595 67 ⫾ 8 42/26 62

16

6

280 17

64 4

Data are presented means ⫾ SDs.

Table 2 Preoperative transesophageal echocardiographic (TEE) measurements in patients with successful and unsuccessful mitral valve (MV) repair Variable

Ejection fraction (%) Left ventricular diastolic volume (cm3) Left ventricular systolic volume (cm3) MR jet direction Anterior Central Posterior MR severity Mitral annular diameter (cm) 4-chamber view 2-chamber view Mitral annular diameter, long-axis view (cm) Tethering height (cm) 4-chamber view 2-chamber view, Long-axis view Tethering area (cm2) 4-chamber view 2-chamber view Long-axis view

MV Repair Successful (n ⫽ 297)

Unsuccessful (n ⫽ 68)

p Value

32.2 ⫾ 11.6 176 ⫾ 55.55

33.15 ⫾ 10.97 203 ⫾ 56.87

NS ⬍0.05

122 ⫾ 50.5

139 ⫾ 52.1

⬍0.05

49 147 101 3.0 ⫾ 0.63

14 27 27 3.3 ⫾ 0.66

⬍0.0001

3.5 ⫾ 0.31 3.5 ⫾ 0.33 3.4 ⫾ 0.38

4 ⫾ 0.34 3.9 ⫾ 0.4 3.7 ⫾ 0.33

⬍0.0001 ⬍0.0001 ⬍0.0001

0.8 ⫾ 0.22 0.7 ⫾ 0.21 0.9 ⫾ 0.25

1 ⫾ 0.29 0.8 ⫾ 0.29 1 ⫾ 0.29

⬍0.0001 ⬍0.0001 ⬍0.0001

1.5 ⫾ 0.44 1.3 ⫾ 0.45 1.6 ⫾ 0.52

2 ⫾ 0.64 1.7 ⫾ 0.67 2.1 ⫾ 0.62

⬍0.0001 ⬍0.05 ⬍0.0001

NS

Data are presented as means ⫾ SDs.

used to identify independent predictors of failure of mitral repair. The best cut-off point was determined by a receiveroperating characteristics curve. A p value of ⬍0.05 was considered statistically significant. Results Baseline characteristics: The mean patient age was 66 ⫾ 9 years (range 41 to 83). A total of 344 patients (94%) underwent coronary artery bypass grafting in addition to MV repair, and 21 patients (6%) underwent isolated MV

Figure 3. Receiver-operating characteristics (ROC) curve demonstrated that mitral annular diameter in the 4-chamber view (dashed line), tethering area in the long-axis view (solid line), and MR severity (dashed/dotted line) were 3 independent predictors of repair failure. Mitral annular diameter ⱖ3.7 cm provided sensitivity of 84% and specificity of 76% (p ⬍0.0001) for failure. The best cut-off value for tethering area (long axis) was 1.6 cm2 (sensitivity 80%, specificity 54%) and for preoperative MR grade, this value was 3.5 (sensitivity 42%, specificity 81%).

repair. Also, 21 patients (6%) underwent tricuspid valve annuloplasty for severe tricuspid regurgitation. Success and failure of MV repair: According to the follow-up echocardiographic criteria, 297 patients (81%) had successful mitral repair and 68 (19%) had failed repair (Figure 2). The patients with successful and unsuccessful MV repairs had similar preoperative characteristics and operative procedures (Table 1). The most common annuloplasty technique in the 2 groups was a flexible posterior annuloplasty band. Preoperative transesophageal echocardiography revealed similar left ventricular function and MR jet direction between the 2 groups (Table 2). The left ventricular dimensions were higher in those with failed repair. Patients with failed repair tended to have a more severe preoperative MR grade (3.31 ⫾ 0.66 vs 3.0 ⫾ 0.63, p ⬍0.0001). The preoperative mitral annular diameter and leaflet tethering heights and areas were greater in the failure group on all echocardiographic views (Table 2). By multiple stepwise regression analysis, 3 independent predictors of failure of mitral annuloplasty were identified: (1) mitral annular diameter in the 4-chamber view, (2) tethering area in the long-axis view, and (3) MR severity. The mitral annular diameter in the 4-chamber view was 1 of the strongest predictors of repair failure according to the receiver-operating characteristics curve (Figure 3). The cut-off point of mitral annular diameter ⱖ3.7 cm showed a sensitivity of 84% and specificity of 76% in predicting the failure of mitral annuloplasty. The best cutoff value of the tethering area in the long-axis view was 1.6

Valvular Heart Disease/MV Repair in Ischemic Mitral Regurgitation

cm2 (sensitivity 80%, specificity 54%) and that for preoperative grade of MR was 3.5 (sensitivity 42%, specificity 81%). The positive predictive value of all 3 factors together in predicting the failure of mitral annuloplasty was 55%. Intra- and interobserver variabilities: For intraobserver variation, the average difference in the measurements from the 4-chamber, 2-chamber, and the long-axis views was 0.07, 0.12, and 0.09 cm (r ⫽ 0.97, r ⫽ 0.96, and r ⫽ 0.98), respectively, for the mitral annular dimension. The corresponding differences were 0.08, 0.06, and 0.1 cm (r ⫽ 0.95, r ⫽ 0.97, and r ⫽ 0.82) for tethering height and were 0.14, 0.1, and 0.18 cm2 (r ⫽ 0.96, r ⫽ 0.98, and r ⫽ 0.9) for tethering area. The average differences in interobserver measurement, respectively, from the 3 echocardiographic views were 0.1, 0.07, and 0.1 cm (r ⫽ 0.97, r ⫽ 0.97, and r ⫽ 0.98) for mitral annular diameter, 0.1, 0.04, and 0.05 cm (r ⫽ 0.92, r ⫽ 0.96, and 0.94) for tethering height, and 0.15, 0.07, and 0.12 cm2 (r ⫽ 0.9R, r ⫽ 0.97, and r ⫽ 0.95) for tethering area, respectively. Discussion The results of this study demonstrated that routine measurements on preoperative transesophageal echocardiography can be used to identify patients with ischemic MR who are likely to have recurrent MR after surgical annuloplasty. Specifically, increased mitral annular diameter, tethering area, and MR grade were associated with repair failure. Several echocardiographic studies have detailed the mechanisms of ischemic MR and the results of surgical annuloplasty.12–14 The recognition that the pathogenesis of ischemic MR relates largely to alterations in ventricular geometry and function has led some to question the validity of a surgical approach that addresses only the annulus.6,15 Annuloplasty alone fails in 20% to 30% of patients with ischemic MR.7,8 The preoperative factors associated with recurrent MR after annuloplasty include a complex jet of MR, a lateral wall motion abnormality, and an increased MV coaptation depth.8 Other studies have suggested that annuloplasty failure might result from progressive postoperative left ventricular remodeling, including severe dislocation of the papillary muscles.7,16,17 It is likely that increased papillary muscle dislocation results in greater MV tethering, suggesting a close association between the echocardiographic measurements of tethering height and area and changes in papillary muscle geometry. However, with available TEE technology, the leaflet tethering height and area are far simpler to measure than alterations in papillary muscle position. In 1 of the few studies examining preoperative echocardiographic predictors of annuloplasty failure, Calafiore and colleagues18 found that a MV coaptation depth of ⱖ11 mm was associated with a return of substantial MR after annuloplasty. In contrast, when the MV coaptation depth was ⱕ10 mm, residual MR was generally mild to moderate.18

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Our results concerning tethering height were similar, but we augmented the predictive power of echocardiography by highlighting the additional importance of the mitral annular diameter and tethering area and specified the echocardiographic views in which these measurements are most important. Our analysis demonstrated that when the mitral annular dimension was ⱖ3.7 cm in the intraoperative 4-chamber TEE view with a tenting area of ⱖ1.6 cm2 in the long-axis view and a MR grade of ⬎3.5, mitral annuloplasty will fail in ⬎1/2 of patients during follow-up. Key differences between this study of ischemic MR and previous studies are evident in 4 areas.19 –21 First, we ensured that all patients in this study had functional ischemic MR, producing a uniform cohort for analysis. Second, the major geometric parameters of the mitral apparatus were analyzed in 3 standard TEE views, providing detailed data for analysis. Third, multiple stepwise regression analysis and the receiver-operating characteristics curve were used to identify independent echocardiographic predictors of recurrent MR. Finally, we enrolled ⬎300 patients with ischemic MR who had echocardiographic follow-up data after MV repair. As far as we know, this is the largest detailed echocardiographic study of surgically treated patients with ischemic MR. As in any retrospective clinical study, this study had certain limitations. All 3 fundamental TEE views were not completely recorded in some patients; however, all patients had ⱖ2 views for complete analysis, including the 4-chamber view. During the study, we did not routinely perform quantitative echocardiography. Although quantification of MR by a variety of methods (Doppler flow conversion, proximal isovelocity surface area, vena contracta) is now routine, this was not the standard care a decade ago. The color Doppler jet method was the only consistent method available during the study for providing a semi-quantitative assessment of MR. Therefore, the severity of MR may have been over- or underestimated in some echocardiograms, considering the limitations of the color Doppler jet method. However, we usually had multiple postoperative echocardiograms during follow-up for each patient and checked the consistency of grading of MR severity among these studies. Our study did not investigate left ventricular or subvalvular remodeling after surgery, which could be major factors contributing to repair failure. The aim of this study was to predict failure using preoperative information, providing the clinician with guidance regarding the choice of therapy. Associations between the preoperative measurements and postoperative changes in valvular and ventricular geometry remain to be investigated. In conclusion, this study has highlighted the importance of detailed preoperative TEE examination in patients undergoing surgery for ischemic MR. In patients with greater mitral annular diameter, tethering area, and MR severity, additional repair techniques or MV replacement should be considered.

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