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Ann Thorac Surg 2008;85:1319-1330. doi:10.1016/j.athoracsur.2007.12.074
© 2008 The Society of Thoracic Surgeons
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Original Articles: Adult Cardiac

Left Ventricular Reverse Remodeling After Undersized Mitral Ring Annuloplasty in Patients With Ischemic Regurgitation

Sandro Gelsomino, MDa,*, Roberto Lorusso, PhDb, Irene Capecchi, MDa, Carlo Rostagno, MDa, Stefano Romagnoli, MDa, Giuseppe Billè, MDa, Giuseppe De Cicco, MDb, Cecilia Tetta, MDa, Pierluigi Stefàno, MDa, Gian Franco Gensini, MDa

a Experimental Surgery Unit, Cardiac Surgery Unit, Department of Heart and Vessels, Careggi Hospital, Florence, Italy
b Cardiac Surgery Unit, Civic Hospital, Brescia, Italy

Accepted for publication December 31, 2007.

* Address correspondence to Dr Gelsomino, Experimental Surgery Unit, Careggi Hospital, Viale Morgagni 85, Florence, 50134, Italy (Email: sandro.gelsomino{at}libero.it).


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Background: Long-term durability of combined coronary artery bypass grafting and of undersized mitral ring annuloplasty (UMRA) is uncertain. A considerable number of patients show recurrent regurgitation. This study examines the difference in the benefit of UMRA on clinical end points and recurrence of mitral regurgitation between responders and nonresponders of left ventricular reverse remodeling.

Methods: Study eligibility criteria were fulfilled by 204 patients with chronic ischemic mitral regurgitation (CIMR) who survived combined coronary artery bypass grafting and reductive annuloplasty between September 2001 and September 2006. Patients underwent echocardiography preoperatively, at discharge, and at follow-up appointments (100% complete). Median early follow-up was 6 months (interquartile range [IRQ], 3 to 8 months; late follow-up, 35 months (IRQ, 21 to 50 months). Reverse remodeling was considered a reduction in left ventricular end systolic volume index exceeding 15%.

Results: There were 84 responders (41.2%) of reverse remodeling (age, 68 ± 7.4 years; 51 men) and 120 nonresponders (58.8%; age, 67 ± 7.6 years; 78 men). Nonresponders had a higher recurrence of mitral regurgitation (p < 0.001), higher reoperation rate for failed repair (p < 0.001), and significantly larger left ventricular volumes and dimension at any study point (p < 0.001), with significant late increase of sphericity indexes exceeding preoperative values (p < 0.001). At multivariable analysis, a baseline myocardial performance index of less than 0.90 (p < 0.001), a systolic sphericity index of less than 0.72 (p < 0.001), and wall motion score index of less than 1.59 (p = 0.003) were independent predictors of reverse remodeling.

Conclusions: Our experience suggests that more information on possible echo predictors of an inadequate result may improve preoperative decision making of CIMR patients for UMRA.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Despite better understanding of mechanisms leading to chronic ischemic mitral valve regurgitation (CIMR) and notwithstanding improvement of mitral repair results [1, 2], ongoing dissatisfaction with outcomes has yielded different techniques [3–6]. An established therapeutic approach to relieve CIMR, in association with coronary artery bypass grafting (CABG), is undersized mitral ring annuloplasty (UMRA) [7, 8] which, by reducing the anterior-posterior dimensions (or septal-lateral in anatomic terms) and the valve area, brings both mitral leaflets into apposition. The long-term efficacy of UMRA is still unclear, however, and recurrence of mitral regurgitation (MR) has been predominantly related to progressive left ventricular (LV) remodeling [9–11]. Cardiac remodeling is a well-known important aspect of myocardial disease progression, making LV reverse remodeling (LVRR) a critical postoperative factor [12].

This study examines the difference in the benefit of UMRA on clinical end points and recurrence of MR between responders and nonresponders of LVRR. It also explores potential useful predictors of successful reverse remodeling, including clinical and surgical data, volumetric and geometric indicators, and indexes of LV function assessed by echocardiography.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 Acknowledgments
 References
 
Ethical Issue
The study followed the World Medical Association guidelines concerning ethical principles for medical research involving human subjects [13] and was approved by Institutional Ethics Board. All patients gave their informed consent.

Patient Population
Chronic ischemic MR was defined as the combination of mild-to-severe MR with (1) prior myocardial infarction (MI) occurring more than 16 days earlier [14], (2) 75% or greater stenosis of at least one coronary vessel, (3) a corresponding regional wall motion abnormality, and (4) type IIIb leaflet dysfunction according to Carpentier’s classification [15], with or without annular dilatation. Exclusion criteria were (1) degenerative or other nonischemic etiology, (2) ischemic isolated type I or type II dysfunction [15], (3) additional mitral valve repair procedures, (4) other valvular or congenital heart diseases, (5) previous cardiac operations/percutaneous transluminal coronary angioplasty, and (6) atrial fibrillation or sinus rhythm with the heart rate at rest exceeding 100 beats/min.

Between September 2001 and September 2006, 239 subjects with CIMR undergoing combined CABG and UMRA at Careggi Hospital (Florence, Italy) were prospectively enrolled in the study. Of these, 35 were excluded because 4 had intraoperative annuloplasty failure, 12 showed residual MR (insufficiency of 2+ or more after valve repair documented at discharge), 4 died within 30 days, and 15 had incomplete data available.

Patient Classification
The criteria of Stellbrink and coworkers [16] were used to classify patients as responders in terms of LVRR if the end-systolic volume index (ESVI) was reduced more than 15% at late follow-up compared with baseline volumes and as nonresponders if ESVI was reduced less than 15% or more. Among the 204 patients, 84 were responders (41.2%) to LVRR and 120 were nonresponders (58.8%).

Follow-Up
Clinical follow-up information was obtained from all survivors through outpatient visits and telephone calls and was 100% complete. Early follow-up was a median of 6 months (interquartile range [IQR], 3 to 8 months), and late follow-up was a median of 35 months (IQR, 21 to 50 months).

Surgical Procedures
All patients underwent associated CABG. For the purpose of this study, complete revascularization was accomplished when at least one graft was placed distal to an approximately 50% diameter narrowing in each of the three major vascular systems in which arterial narrowing of this severity was noted in a vessel with a diameter of 1. 5 mm or more. It was not considered necessary to bypass all obstructed diagonal branches of the anterior descending or marginal branches of the circumflex coronary arteries for a classification of complete revascularization. According to this definition, 100% patients underwent complete revascularization.

The ring size was determined by standard measurements of the intertrigonal distance and anterior leaflet height. A downsizing by two ring sizes was performed in all patients. Two types of ring were used in all patients: Carpentier’s classic ring (Edwards Life Sciences, Irvine, CA) in 112 patients (54.9%) and Physio ring (Edwards Life Sciences) in 92 (45.1%). Median ring size was 28 mm (IQR, 26 to 28 mm). No difference was detected in ring size between the two types of ring used (both, 28 mm; IQR, 26 to 28 mm, p > 0.9).

After cardiopulmonary bypass (CPB), a transesophageal echocardiography (TEE) was performed to assess residual MR. A successful repair was assessed as leaflet coaptation of 0.5 cm or more, MR of 1 or less, and systolic MV area exceeding 2 cm2.

Echocardiographic Measurements and Calculations
The clinical echocardiographic evaluation included transthoracic (TTE) and transesophageal (TEE) echocardiograms within 5 days before operation. Then a TTE was performed at discharge and at follow-up appointments. Echocardiographic studies were done on an Acuson Sequoia imaging device equipped with a 3.5-MHz ultrasound transducer (Acuson Corp, Mountain View, CA) preoperatively, at discharge, and at follow-up appointments The reliability of echocardiographic measurements was assessed by calculating between-observer (I. C. and C. R.) interval of agreements of main direct measures used in this study in a different group of 20 subjects (10 MR) [17].

Global Left Ventricular Remodeling
The LV volumes and ejection fraction (LVEF) were assessed by the by the biapical Simpson disk method [18]. The myocardial performance index (MPI) was measured using the method described by Tei and colleagues [19]. The sphericity index was obtained at end diastole and end systole as the volume of the left ventricle divided by the volume of a sphere with a diameter equal to the longest axis of the left ventricle measured in the apical view [20]. The wall motion score index (WMSI) was calculated according to a 17-segment model [21].

Quantification of Mitral Regurgitation and Definitions
The following quantitative measurements were simultaneously used to grade the severity of MR, and final results were averages of measured values [1, 22, 23]: (1) quantitative Doppler and (2) proximal isovelocity surface area. For each measurement, a minimum of three cardiac cycles was averaged.

The tenting area was measured by the area enclosed between the annular plane and the mitral leaflets from the parasternal long-axis view at mid-systole. Apical displacement of the coaptation was measured as coaptation height, and coaptation length was directly measured [2, 24]. Mitral annular areas were obtained from mitral annular dimensions in apical long-axis, 4-chamber, and 2-chamber views, using an ellipsoid assumption [25].

Recurrent MR was the insufficiency of 2+ or more at follow-up appointments in patients with no or trivial MR at discharge.

Local Left Ventricular Remodeling
Lateral and posterior displacements of anterior papillary muscles (APM) and posterior papillary muscles (PPMs) were measured as distances from well-defined anatomic landmarks at early and end-systole [2]. Separation between PMs was directly measured from body to body of PMs. In the long-axis view, the apical displacement of the PPM was measured as the distance between the papillary muscle head and the fixed intervalvular fibrosa (annular papillary distance). The WMSI of the basal and mid-posterior and inferior segments for the PPM and of basal and mid-lateral and anterior segments for the APM were calculated [1].

Statistical Analysis
The sample size was determined by GraphPad StatMate 2.00 (GraphPad Prism Software, Inc, San Diego, CA) on the basis of preliminary data obtained by echocardiography and was determined on the basis of the following assumptions: type I error of 0.05 (two-sided), power of 80%, and difference in end-systolic volume of 0.78 ± 2.4 between patients with or without recurrent mitral regurgitation.

The calculated study population was 200. However 239 patients were recruited to allow for possible analytic problems while processing them or other eventualities potentially leading to patient attrition. Variables were tested for normal distribution by the Kolmogorov-Smirnov test. Continuous variables are presented as mean and standard deviation (SD), categoric variables as percentage, and nonnormally distributed variables as median and interquartile range (IRQ). Bivariate association between the independent variables and LV reverse remodeling was assessed by the Student t test, Mann Whitney U test, {chi}2 test, and the Fisher exact test, where appropriate.

Echocardiographic variables over time were analyzed by means of repeated measures analysis of variance, followed by the Tukey post hoc test and Friedman test, where appropriate. We investigated 49 demographic, clinical, operative, and echocardiographic indicators for their predictive value of LVRR by univariable and multivariable models. To enhance the accuracy of the model, the clustering method [26] was used to reduce the number of variables [27].

Multivariable logistic regression analysis by means of a backward stepwise algorithm (cutoff for entry, 0.05; for removal, 0.10) was performed to select independent predictors of reverse remodeling. Categoric variables with more than two levels in the regression model were converted to dummy variables.

Model assumptions (linearity and additivity assumptions) were checked by piecewise cubic polynomials (spline functions) and pooled interaction test [28], respectively, and found to be satisfied. The goodness of fit of the final logistic regression models was assessed with the Hosmer-Lemeshow statistic [27, 28], and predictive accuracy was assessed by the concordance index [27, 28]. Internal validation of predictors generated by multivariable logistic regression was performed by means of bootstrapping techniques with 1000 cycles, and generation of odds ratios (OR) and bias-corrected 95% confidence intervals (CI) [28].

Optimal cutoff values were determined as the rounding cutoff that gives the maximum sum of sensitivity and specificity. This value should be the shoulder at the top left of the receiver operating characteristic curve (ROC). Bootstrapping techniques were used to validate the results. A logistic regression analysis was done to evaluate the influence of the severity of preoperative regurgitation on recurrence of moderate/severe MR. Cumulative probability for death and reoperation were estimated by the Kaplan-Meier method. SPSS 12.0 (SPSS, Chicago, IL) and Stats Direct 2.5.7 (StatsDirect, Sale, United Kingdom) were used for these calculations. Significance for hypothesis testing was set at the 0.05 two-tailed level.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 Acknowledgments
 References
 
Left Ventricular Reverse Remodeling
Table 1 reports perioperative data. No difference was detected between groups. In responders (Fig 1A), the mean ESVI decreased significantly at discharge (p < 0.001), early (p < 0.001), and late controls (p < 0.001). In contrast in nonresponders (Fig 1B), ESVI reduced significantly at discharge (p = 0.01), was stable at early follow-up (p = 0.61), but increased again at the late control (p < 0.001). When the degree of LV reverse remodeling was compared further in the two groups, ESVI in nonresponders was reduced 10% or more in 10 (8.3%), less than 10% in 83 (69.2%), was relatively stable (±1%) in 15 (12.5%), and enlarged in 12 (10.0%). Among responders, 79 (94.0%) had a reduction in ESVI of 15% to 20% and 5 (6.0%) a reduction of more than 20%. The type of ring used did not influence LVRR (Fig 2).


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  		Table 1 Perioperative Data (n = 204)
 

Figure 1
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  		Fig 1. (A) Reduction in end-systolic volume index (EDVI) in responders and (B) nonresponders of left ventricular reverse remodeling. See text.

 

Figure 2
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  		Fig 2. Left ventricular reverse remodeling (LVRR) by ring type (Physio, black bars; Classic, clear bars) and size. The extent of remodeling was not significantly different between rings at different sizes.

 
Clinical End Points and Mitral Regurgitation
Early clinical outcome did not differ between the groups (Table 2). At late follow-up, New York Heart Association (NYHA) functional class was greater in nonresponders (p < 0.001).


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  		Table 2 Clinical Outcome (n = 204)
 
During the follow-up, 15 patients died: 2 nonresponders and 13 responders. The cause of death in responders was malignancy at 55 months and sudden, unexplained death at 22 months. Cause of death in responders was heart failure in 3 at 36, 45, and 54 months; infection at 3 and 8 months in 2 patients each, stroke at 12 and 43 months, or MI at 31 and 42 months; and in 1 patient each, arrhythmia at 59 months, multiorgan failure at 6 months, respiratory failure at 14 months, and malignancy at 59 months. The 5-year actuarial survival was 83.2 ± 4.4 overall, but was significantly lower in nonresponders (Fig 3).


Figure 3
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  		Fig 3. Five-year actuarial survival by groups (responders, thin line; nonresponders, dashed line; all subjects, thick line). See text.

 
The MR data are summarized in Table 3. Jet direction was posterior in most responders but was central or anterior in most nonresponders. In addition, tenting area (p < 0.001) and coaptation height (p = 0.02) were preoperatively higher, and coaptation length (p = 0.04) was shorter in nonresponders. No further significant difference between the two groups was found for qualitative and quantitative MR data. At early control, the incidence of recurrent MR was 2.4% in responders and 43.9% in nonresponders (p < 0.001). At late control, recurrent MR was unchanged in responders but showed a further increment in nonresponders of 67.3% (p < 0.001 vs responders). Although none of nonresponders showed a late recurrent MR of 4 or more, 18 nonresponders (15%) experienced moderate/severe recurrent MR. Of interest in the latter group, among 28 patients with severe (4+) preoperative MR, severe MR developed in 7 (25%), and moderate recurrent MR developed in 11 (39.2%). At logistic regression analysis, MR grade 3 or higher was a predictive factor of recurrent moderate/severe MR (OR, 5.2; 95% bias-corrected CI, 24 to 6.3; p < 0.001). Among responders, none underwent reoperation for a failed repair. In contrasting, 4 nonresponders (3.7%) had a repeat MV repair, and 13 (12.1%) underwent MV replacement. The 5-year rates of freedom from reoperation for failed repair were 100% in responders and 44% ± 7% in nonresponders, respectively (p < 0.001).


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  		Table 3 Mitral Regurgitation
 
Finally, 3 nonresponders (3.7%) experienced cardiac-related events during the follow-up period (p < 0.001) vs none in responders.

Global and Local Left Ventricular Remodeling
Changes in EDVI and WMSI mirrored those of ESVI (Table 4). Left ventricular dimensions decreased in responders at any study point (p < 0.001). In contrast for nonresponders, LV dimensions were initially reduced at discharge (p = 0.01) and early control (p = 0.02 and p = 0.04 for ESD and EDD, respectively), followed by a significant increase at the late postoperative stage (p < 0.001). Ejection fraction (p = 0.001) and MPI (p = 0.01) significantly improved at late follow-up only in responders, but remained unchanged in nonresponders at any study point. Systolic and diastolic sphericity indexes improved in responders at discharge (p < 0.001), early (systolic sphericity index, p = 0.02 and diastolic sphericity index, p = 0.03, respectively) and late controls (p < 0.001). In nonresponders, there was an initial but not significant reduction in both systolic and diastolic sphericity indexes, with a late increase exceeding the preoperative value (p < 0.001).


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  		Table 4 Global and Local Left Ventricular Remodeling
 
Nonresponders had greater preoperative APM lateral and APM posterior, wider PMs separation, and larger APM WMSI. In contrast, PPM WMSI was higher in responders, whereas PPM posterior, PPM lateral, and PPM fibrosa were comparable in the two groups.

At discharge in responders, indexes of posterior and lateral displacement of PMs, PMs separation, PPM fibrosa, and WMSIs were reduced significantly. None of these indexes showed any significant change afterwards. In nonresponders, all the above indexes except for APM WMSI, which remained constant over time, showed a reduction, even though not significant, at discharge, and remained constant at early control showing a significant late increase.

Predictors of Left Ventricular Reverse Remodeling
At univariable analysis (Table 5), LV diameters, sphericity indexes, LVEF, WMSI, MPI, APM posterior and lateral, PM separation, and APM WMSI were predictors of LVRR. By multiple regression analysis (Table 6), baseline MPI, sphericity indexes, and WMSI were independent predictors of LVRR.


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  		Table 5 Univariable Predictors of Left Ventricular Reverse Remodeling
 

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  		Table 6 Logistic Regression for Left Ventricular Reverse Remodeling
 
Internal validation of such multivariable analysis by means of bootstrapping, including the same variables of standard logistic regression model, further confirmed the significant predictive ability for recurrent MR (bootstrap OR, 2.4; bias-corrected 95% CI, 1.1 to 5.3). Finally, the logistic regression model was reliable (Hosmer-Lemeshow test, p = 0.6) and accurate (concordance index = 0.8). The ROC curve analysis to determine optimal cutoff values to predict LVRR (Fig 4, 5, and 6) Go Go showed that the systolic sphericity index had 90% sensitivity and specificity with an optimal cutoff of less than 0.7 (95% CI by bootstrapping, 0.58 to 0.81). The MPI with a cutoff of less than 0.9 (95% CI by bootstrapping, 0.75 to 0.96) had 100% sensitivity and specificity. Finally, WMSI of less than 1.5 (95% CI by bootstrapping, 1.35 to 1.62) had 80% sensitivity and 82% specificity.


Figure 4
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  		Fig 4. (A, B) Receiver operating characteristic (ROC) for systolic sphericity index to predict left ventricular remodeling. (CI = confidence interval; SE = standard error).

 

Figure 5
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  		Fig 5. (A, B) Receiver operating characteristic (ROC) for myocardial performance index to predict left ventricular remodeling. (CI = confidence interval).

 

Figure 6
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  		Fig 6. (A, B) Receiver operating characteristic (ROC) for wall motion score index to predict left ventricular remodeling. (CI = confidence interval; SE = standard error).

 

   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
Acknowledgments
 References
 
The most common surgical technique for CIMR is UMRA [7]. Although this procedure does not fully address the ventricular causes of CIMR, it is simple to perform and reproducible, and therefore has been widely adopted worldwide by cardiac surgeons. Nonetheless, after encouraging initial results [8], different studies have revealed that recurrent MR develops in a significant proportion of patients during follow-up [6, 10], which has been mainly related to continued LV remodeling and persistent leaflet tethering [9, 29, 30]. Thus, LVRR is an important aim in the surgical treatment of CIMR.

Using the same criterion as Stellbrink and colleagues [15], our study observed 58.8% of the study population were nonresponders, which included 10% with a further increase in ESVI. Braun and coworkers [31] demonstrated 39.5% of nonresponders among 87 consecutive patients with CIMR undergoing restrictive mitral annuloplasty, considering a 10% reduction in LVED dimension as significant LVRR. However, measurements of LV volumes have been demonstrated to be more reliable than LV diameters in assessing LV remodeling, especially in enlarged ventricles [32].

In our experience, nonresponders had a higher postoperative NYHA class (p < 0.001), higher recurrence of MR (p < 0.001), and higher reoperation rate for failed repair (p < 0.001). In addition, 5-year survival was significantly lower in nonresponders.

By comparing the two groups in our study, it appears evident that nonresponders were preoperatively much more globally remodeled and that at the late control they still showed more a spherical, enlarged, and dysfunctional left ventricle. Furthermore, the late increase in sphericity indexes in nonresponders, exceeding the preoperative value, was consistent with further remodeling after UMRA and reflects increased tethering on the mitral valve and greater displacement of PMs. Furthermore, in our experience, nonresponders had preoperatively a greater lateral and posterior displacement of the APM and a wider PM separation. Previous studies [11, 33] demonstrated that the local remodeling of the LV segments supporting the PPM is a necessary condition for the development of MR and, accordingly, we found that PPM displacement occurred preoperatively in both groups; even in nonresponders, the lateral and posterior displacement of APMs was predominant.

In addition, this group had larger WMSI of the segments underlying the APM, whereas PPM WMSI was higher in responders. These results support previous clinical findings reported by Agricola and colleagues [34], who described two groups of patients with CIMR according to tethering pattern. Likewise as in nonresponders in our study, their symmetric group had prevalent posterior and lateral displacement of APMs (both p < 0.04), PMs separation, and APM WMSI (both p < 0.0001).

Of interest was that this different distribution of local wall abnormalities did not reflect, in our experience, a different infarct localization. We cannot exclude that this different pattern of regional functional abnormalities is caused by progressive deterioration in contractile function with progressive recruitment of border zone myocardium into scar in patients with more dysfunctional left ventricles. Thus, the predominant displacement of APM and the larger APM WMSI might represent a sign of disease progression. Nonetheless in our study, this pattern clearly identified subjects who are expected not to reverse-remodel after annuloplasty. It would have been helpful to assess the regional viability of the regions associated with the anterior and posterior papillary muscles to confirm these findings.

After the surgical procdures, we showed that continued LV local remodeling occurs and predominantly involves the region of the left ventricle supporting the PPM, whereas APM WMSI remained constant over time in both groups.

Continued LV remodeling increases leaflets tethering, leading to progressive lack of coaptation. In this setting, the coaptation length gained at the end of procedure could play a significant role in preventing MR recurrence. The coaptation length should be sufficient to balance tethering forces secondary to postoperative remodeling, thus another reason for these results might be the acceptance of a leaflet coaptation of only 5 mm at the end of the procedure, which might not be adequate for all patients. Indeed, nonresponders showed a coaptation length of less than 5 mm at any postoperative control, and this value was significantly lower than responders (p < 0.001) even with comparable ring size between groups (p = 0.53).

Thus, we actually believe that in subjects who are expected not to reverse remodel, a minimum coaptation length of 8 mm should be achieved [31]. In contrast, in patients with a strongly tethered AML or with an anterior leaflet that is less tethered but which is not sufficiently long to ensure a proper postoperative coaptation length, regurgitation cannot be eliminated by ring annuloplasty. In these patients a chordal-sparing MV replacement technique should be considered.

A key point for achieving an appropriate leaflet coaptation and to ensure durable results is a true undersizing, and in this setting, a pivotal role can be played by the type of ring chosen. In the present experience, we used only two rings: Carpentier’s rigid or Physio semi-flexible rings. These two rings are not at all identical; thus, even we have undersized by two sizes both rings, although we might have been less restrictive with the Physio ring than with the Classic ring. In our experience, however, the extent of LVRR was comparable between rings at any size. Furthermore, neither ring type nor ring size was predictive of LVRR at logistic regression analysis.

In addition, 15% of nonresponders experienced moderate/severe recurrent MR. Of interest, 64.2% of nonresponders with preoperative severe (4+) MR presented with a late recurrent MR of 3+ or higher, and preoperative MR grade exceeding 3 was a predictive factor of recurrent moderate/severe MR (p < 0.001). This finding deserves further investigation, because these subjects might be not ideal candidates for UMRA and could benefit more from a chordal-sparing MV replacement.

Finally, at the multivariable model, systolic sphericity index of less than 0.72, MPI of less than 0.90, and WMSI of less than 1.59 resulted in independent predictors of LVRR. These results emphasize the importance of the extent of preoperative LV global remodeling as having a central role in predicting inadequate results after UMRA. These findings confirm that the increase of the sphericity index at end of systole predicts recurrence of MR after restrictive annuloplasty [9].

This study found that myocardial performance index predicts the likelihood of reverse remodeling, whereas LVEF was not significant. The myocardial performance index is a simply measurable Doppler-derived index of combined systolic and diastolic performance, which differently from LVEF, is independent of LV loading conditions and heart rate [19]. It is the summation of isovolumetric contraction and relaxation time divided by the ejection time. The myocardial performance index has a narrow range of values in subjects with normal LV function (0.37 ± 0.05). Ventricular dysfunction prolongs isovolumetric relaxation and shortens ejection times, resulting in an increase of the index compared with healthy subjects.

Study Limitations
Our study findings should be viewed in light of some inherent limitations:

• Evaluation of LVRR was based on volumes obtained by echocardiography. Volumetry by two-dimensional echocardiography depends on geometric assumptions and is subject to image-plane positioning errors. Hence, it is not accurate in shape-distorted postinfarction left ventricles; however, this limitation belongs to most published articles on this pathology.
• Viability testing was not performed in these patients; therefore, lack of LVRR in nonresponders might be also due to irreversible ischemic myocardial damage (nonviable myocardium). Furthermore, in relation to the papillary muscle displacement data presented, the revascularization of viable regions related to papillary muscle function might be the most important predictor of success with this operation. This issue deserves further investigation.
• Postoperative evaluation of the coronary status was not assessed. It would have been helpful to distinguish surgical failure from coronary disease progression.
• The issue of annulus reshaping during annuloplasty has not been addressed. We used only rigid or semi-flexible plane annuloplasty rings, which may flatten the natural saddle shape and cause greater tension on chordae and leaflets. Innovative annular rings mimicking the shape of healthy mitral annulus have been recently introduced in the market [35–37].
• Estimated cutoffs are known to be very susceptible to changes in the study population. We used bootstrapping techniques to validate the results; nonetheless, it has also been documented that the sensitivity and specificity associated with these cutoffs are overly optimistic.

Strength of the Study
This report comprises a large cohort of CIMR patients with UMRA, with detailed, 100% complete, echocardiographic follow-up. Our patient cohort was also more homogeneous than in the other study [38]: all patients underwent associated CABG, they had no concomitant MV procedures, and the entire cohort was uniform regarding the MV ischemic leaflet dysfunction. Moreover, to assess results for MV repair, we studied true, recurrent MR, excluding those patients with residual MR in whom the insufficiency was presumably never eliminated at operation. In addition, we undertook valve sizing in a standardized fashion, and the degree of undersizing was homogeneous during the 5-year study period.

Clinical Implications
In our experience, combined CABG and UMRA do not ensure successful and durable elimination of MR and significant LVRR in all patients. Those who can benefit from this approach could be preoperatively identified using echo predictors. However, restrictive annuloplasty was ineffective in a large percentage of patients, and the results of this study suggest the need, in most CIMR patients, for different approaches directly addressing ventricular tethering, such as second-order chordal cutting [3], infarct placation [4], papillary muscle sling [5], papillary muscle imbrication [39], and PPM surgical relocation [40]. Nonetheless, although these techniques appear promising, more data are required before they can be recommended for CIMR patients.

In addition, the use of support devices [41, 42] was introduced in recent years in clinical practice, thus experiences with these techniques are actually in their preliminary phase.

Finally, although MV replacement, which was largely used in the past in ischemic regurgitation, eliminates the short-term risk of recurrent MR, it is associated with poor long-term survival [43]. Thus, in our actual policy, we do not consider MV replacement as a reasonable alternative to repair in all patients.

Conclusions
Our experience suggests that more information on possible echo predictors of an inadequate result may improve preoperative decision-making of CIMR patients for UMRA.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
References
 
We gratefully acknowledge Dr Judith Wilson for the English revision of the paper. We thank Dr Orlando Parise for statistical analysis.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 

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