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European Journal of Echocardiography Advance Access originally published online on March 11, 2008
European Journal of Echocardiography 2008 9(5):631-640; doi:10.1093/ejechocard/jen034
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Prognostic value of Doppler-derived mitral deceleration time on left ventricular reverse remodelling after undersized mitral annuloplasty

Sandro Gelsomino1,*, Roberto Lorusso2, Carlo Rostagno1, Sabina Caciolli1, Giuseppe Billè1, Giuseppe De Cicco2, Stefano Romagnoli1, Cristina Porciani1, Pierluigi Stefàno1 and Gian Franco Gensini1

1 Experimental Surgery Unit, Cardiac Surgery, Department of Heart and Vessels, Careggi Hospital, Viale Morgagni 85, 50134 Florence, Italy
2 Cardiac Surgery Unit, Civic Hospital, Brescia, Italy

Received 15 October 2007; accepted after revision 6 January 2008; online publish-ahead-of-print 11 March 2008.

* Corresponding author. Tel: +39 055 794 7628; fax: +39 055 794 7467. E-mail address: sandro.gelsomino{at}libero.it


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Conclusions
 References
 
Aims: This study was aimed at exploring the predictive value of Doppler-Derived Mitral Deceleration Time (DT) on left ventricular reverse remodelling (LVRR) in patients with chronic ischaemic mitral regurgitation (CIMR) undergoing combined undersized mitral annuloplasty (UMRA) and coronary artery bypass grafting (CABG).

Methods and results: Two hundred and fifteen patients undergoing combined UMRA and CABG for CIMR between September 2001 and September 2007 in our Institution were divided into four groups on the basis of baseline DT: Group 1, normal (n = 48), Group 2, impaired relaxation (n = 61), Group 3, pseudonormal (n = 50), and Group 4, restrictive (n = 56). Echocardiograms were performed, pre-operatively, at discharge and at follow-up appointments (100% complete, early, median 6 months [interquartile range 4–8 months]) and late, median 38 months (17–61 months). Left ventricular reverse remodelling, defined as a reduction in ESV > 15%, occurred in 95.7, 96.3, 88.3, and 0% in Groups 1, 2, 3, and 4, respectively (P < 0.001). Logistic regression analysis showed that DT ≤ 125 (P < 0.001) was a strong predictor of LVRR after annuloplasty.

Conclusion: Pre-operative assessment of DT adds significant information to commonly used indexes of global and regional function, and represent a very easy and cost-effective tool to accurately identify CIMR patients who can really benefit from annuloplasty.

Keywords: Mitral valve; Mitral regurgitation; Mitral valve repair


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Conclusions
 References
 
The usefulness of Doppler examination of left ventricular (LV) filling based on transmitral flow patterns has been demonstrated in various pathologic conditions.1–3 Indeed LV filling patterns were studied in patients with dilated cardiomiopathy, acute myocardial infarction, and congestive heart failure.4–8 In addition its prognostic value has recently been demonstrated in patients undergoing coronary artery bypass (CABG).9

Combined undersized mitral ring annuloplasty (UMRA) and CABG is a standard surgical approach to relieve chronic ischaemic mitral regurgitation (CIMR),10,11 although the efficacy is still controversial with many studies revealing a significant recurrence of mitral regurgitation (MR)12–15 mainly related to continued LV remodelling and persistent leaflet tethering. Therefore, left ventricular reverse remodelling (LVRR) is considered a significant post-operative target.15 Doppler-Derived Mitral Deceleration Time (DT) has been demonstrated to be a strong predictor of LVRR and survival after myocardial infarction.16 Nevertheless, the relationship between LV diastolic filling and its change over time and remodelling after reductive annuloplasty, as well as the prognostic impact of serial assessment of LV filling on post-operative LVRR, have not been systematically addressed in a large population.

Therefore, the objective of this study was to evaluate the impact of LV filling on reverse remodelling after combined UMRA and CABG for CIMR.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Conclusions
 References
 
Definitions
Chronic ischaemic mitral regurgitation was defined as the combination of mild-to-severe MR with (i) Prior myocardial infarction (MI) >16 days;17 (ii) 75% or greater stenosis of at least one coronary vessel; (iii) a corresponding regional wall motion abnormality; (iv) type IIIb leaflet dysfunction following Carpentier's classification3 with or without annular dilatation.

Exclusion criteria were (i) degenerative or other non-ischaemic aetiology; (ii) ischaemic isolated type I or type II dysfunction;18 (iii) additional mitral valve repair procedures; (iv) other valvular or congenital heart diseases; (v) previous cardiac surgery/percutaneous transluminal coronary angioplasty; (vi) atrial fibrillation or sinus rhythm with heart rate at rest >100 bpm.

Patients population
Among 270 subjects with CIMR undergoing combined CABG and UMRA in our Institution (Cardiac Surgery, Careggi Hospital, Florence, Italy) between September 2001 and September 2007 and prospectively enrolled in the study, 55 were excluded: four had intraoperative annuloplasty failure, 12 showed residual MR (insufficiency ≥2+ following valve repair documented at discharge.), 19 died [these were excluded because of unavailable complete data (4 early, 15 late)], and 20 had incomplete data. The study population consisted of 215 patients.

Follow-up
Clinical follow-up information was obtained from all survivors through outpatient visits and was 100% complete. Clinical information regarding New York Heart Association class, recurrence of angina, myocardial infarction, heart failure, re-operation for failed repair were recorded. Median early follow-up was 6 months (interquartile range [IQR] 3–8), median late follow-up was 38 months (IQR 17–53).

Ethical issue
Following the World Medical Association guidelines concerning ethical principles for medical research involving human subjects, the study was approved by Institutional Ethics Board. Furthermore, all patients gave their informed consent. The authors had full access to the data and take responsibility for its integrity. All authors have read and agreed to the manuscript as written.

Echocardiographic study
The echocardiographic evaluation was as follows. Tansthoracic (TTE) and a transoesophageal (TEE) echocardiograms were performed within 5 days before surgery and serial TTE were performed at discharge and at follow-up appointments. Echocardiographic studies were performed on Acuson Sequoia imaging device equipped with a 3.5-MHz ultrasound transducer (Acuson Corporation, Mountain View, CA) Echocardiographic measurements were averaged over three cardiac cycles. Inter-observer (S.C e C.R) and intra-observer variability for measurement of DT end-systolic volume (ESV) and grade of MR were <5% (DT, intraobserver 0.7–3.1%, interobserver 0.6–4.6%; ESV, intraobserver 0.3–2.9%, interobserver 0.4–4.0; MR, intraobserver 0.4–2.6%, interobserver 0.3–3.4%).

Left ventricular volumes and geometry
Left ventricular volume and LV ejection fraction (LVEF) were assessed by the bi-apical Simpson disk method.19 The sphericity index (SI) was obtained at end diastole and end systole (SID and SIS, respectively) 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

Quantitation of mitral regurgitation
The following quantitative measurements were simultaneously employed to grade the severity of MR and final results were averages of measured values:22–23 (i) Quantitative Doppler; (ii) Proximal Isovelocity Surface Area (PISA).

For each measurement, minimum of three cardiac cycles were averaged. The respective thresholds for mild, moderate, and severe MR were <30, 30–59 and ≥60 mL/beat for regurgitant volume (RV), <30, 30–49, and ≥50% for regurgitant fraction (RF), <20, 20–39, and ≥40 mm2 for effective regurgitant orifice (ERO), respectively. In patients with no or trivial MR by color Doppler, RV, and RF were used as calculated and ERO was assumed as null. The tenting area (TA) was measured by the area enclosed between the annular plane and mitral leaflets from the parasternal long-axis view at mid-systole. The distance between leaflet coaptation and the mitral annulus plane at early and end systole measured displacement of mitral coaptation towards the LV apex.

Recurrent MR was the insufficiency ≥2+ at follow-up appointments in patients with no/trivial MR at discharge.

Left ventricular diastolic filling patterns
Diastole was evaluated by measuring transmitral flow. Peak early transmitral flow velocity (E), peak late transmitral flow velocity (A), E/A ratio, and deceleration time of E velocity (DT) were obtained by pulsed Doppler.24 The isovolumic relaxation time (IVRT) was obtained by continuous wave Doppler with the wave beam directed from the apical five-chamber view across the region between the aortic outflow tract and the inflow tract.

Finally, systolic and diastolic pulmonary venous flow and their ratio (S/D) were routinely assessed.24

Surgery
Indication for CABG surgery was given following AHA/ACC guidelines.25 Patients with CIMR showing an ERO > 20 mm2 and RV > 30 ml were scheduled for operation.26 When MR was 2/4, surgery was indicated: (1) in the presence of a dilated LV (end-diastolic volume >110 mL/m2) or low EF (<0.35), as in the case of dilated cardiomyopathy;27 (2) in patients with an increase of ERO > 13 mm2 at TTE echocardiographic exercise test;28 (3) in ischaemic patients with fluctuating MR showing an MR ≥ 3 after intra-operative loading test.29

All patients underwent associated coronary artery bypass grafting. For the purpose of this study, complete revascularization was accomplished when, at least one graft was placed distal to an ~50% diameter narrowing in each of the three major vascular system in which arterial narrowing of this severity was noted in a vessel ≥1.5 mm of diameter. 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. Following this definition 100% patients underwent complete revascularization.

The ring size was determined by standard measurements of the inter-trigonal distance and anterior leaflet height. A downsizing by two ring sizes was performed in all patients. After cardiopulmonary bypass (CPB), a transoesophageal echocardiography (TEE) was performed to assess residual MR: leaflet coaptation ≥0.5 cm, MR ≤ 1, and systolic MV area >2 cm2 was assessed as successful repair.

Patient classification
According to baseline S/D and DT, irrespective of filling profile, patients were assigned to one of four groups:24 Group 1 (n = 48), Normal pattern (S/D ≥ 1; DT < 220 ms); Group 2 (n = 61), impaired relaxation LV filling pattern (S/D ≥ 1; DT > 220 ms); Group 3 (n = 50), pseudonormal LV filling pattern (S/D < 1; DT 140–200 ms); Group 4 (n = 56), restrictive LV filling pattern (S/D < 1;DT < 140 ms). The 140 value was chosen because it unequivocally identifies patients with restrictive filling and worse prognosis after myocardial infarction.30 In no-restrictive patients presenting E/A between 1 and 2, the Valsalva manoeuvre was performed to unmask the presence of impaired relaxation: the diagnosis of normal diastolic function was confirmed in the absence of reversal of the E/A below 1, during the strain phase of the manoeuvre.31

Primary end-point
Based on the same criterion used by Stellbrink et al.32 patients were classified as responders of LVRR if the ESV was reduced >15% compared with baseline volumes, and as non-responders if ESV was reduced ≤15% at late control following UMRA.

Statistical analysis
The sample size was determined by GraphPad StatMate release 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%, difference in end systolic volume between patients with or without recurrent mitral regurgitation of 0.78, standard deviation of 2.4. The calculated study population was 200. However 270 patients were recruited to allow for possible analytic problems while processing the or other eventualities potentially leading to patient attrition. All data were analyzed with the SPSS for Windows, release 15.0 (SPSS, Inc, Chicago, IL) statistical package and with Graph-Pad Prism for Windows, release 4.0 (Graph-Pad Prism Software, Inc., San Diego, CA). Variables were tested for normal distribution by the Kolmogorov–Smirnov test. Continuous data were expressed as mean±SD and compared using repeated ANOVA with the Tukey post-hoc test for multiple groups comparison. Comparison of proportions was performed using contingency {chi}2 analysis or Fisher's test, where appropriate. Non-normally distributed variables were presented as median and interquartile range The Mann–Whitney and Kruskal–Wallis tests were used to compare non-parametric variables with Dunn's test for multiple comparisons.

Multivariable logistic regression analysis, by means of a backward stepwise algorithm (cut-off for entry 0.05, for removal 0.10) was performed to identify predictors of LVRR. Forty-nine demographic, clinical, and Doppler echocardiographic variables were investigated for their predictive value of LVRR. To enhance the accuracy of the model, the number of variables were reduced using variable clustering33 until the number of variables to use as candidate in the regression analysis was ≤m/10, where for binary outcomes, m is the number of patients in the less frequent outcome category.34

Model assumptions (linearity and additivity assumptions) were checked by piecewise cubic polynomials (spiline functions) and pooled interaction test,35 respectively, and found to be satisfied. Goodness-of-fit of the final logistic regression models was assessed with the Hosmer–Lemeshow statistic36 and predictive accuracy was assessed by the concordance (c) index.31 Internal validation of predictors generated by multivariable logistic regression was performed by means of bootstrapping techniques, with 1000 cycles and generation of OR and bias corrected 95% CI.35

Optimal cutoff values were determined as the rounding cut-off that gives the maximum sum of sensitivity and specificity. This value should be the shoulder at the top left of the ROC (receiver operating characteristic curve). Bootstrapping techniques were employed to validate the results.

Cumulative probability for death and re-operation were estimated by use of the Kaplan–Meier method.

SPSS 12.0 (SPSS, Chicago, IL, USA) and Stats Direct 2.5.7 (Stats Direct, Sale, UK) were used for these calculations. Significance for hypothesis testing was set at the 0.05 two-tailed level.


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 Conclusions
 References
 
Patient baseline profiles
As reported in Table 1, pre-operative demographic, clinical, and intraoperative data were comparable in the four groups. Baseline echocardiographic characteristics of the study population according to pre-operative LV diastolic pattern are reported in Table 2. There was no significant difference between the four groups with respect to quantitative and qualitative MR data. In contrast, patients with restrictive pattern, when compared with those in the other groups, had larger coaptation height (P = 0.001), LV diameters (P = 0.03), and volumes (ESV, P < 0.001; EDV, P = 0.04), a more spherical (P < 0.001), and dysfunctioning LV (WMSI, P < 0.001; LVEF, P = 0.04). Furthermore, they had lower DT and S/D, by definition (P < 0.001) with higher E/A ratio (P = 0.04) and shorther IVRT (P = 0.02).


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  		Table 1 Patients profile (n = 215)

 


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  		Table 2 Baseline echocardiographic findings

 
Changes in echocardiographic variables
Echocardiographic results are shown in Table 3. Mitral regurgitation was significantly reduced at discharge in all groups (p < .001) and it did not change at following controls in Groups 1, 2, and 3. In contrast, in patients with restrictive filling pattern, it remained stable at early control, whereas increased significantly at late control (P < 0.001). Indeed, at late follow-up, among patients in group 4, 59.1% (n = 26) had an MR grade ≥2 vs. 8.3% (n = 4), 9.8% (n = 6), and 10% (n = 5) in Groups 1, 2, and 3, respectively (P < .001).


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  		Table 3 Post-operative echocardiographic results

 
In normal, impaired relaxation and pseudonormal groups, ESV decreased significantly at discharge (P < 0.001), early (P < 0.001), and late controls (P < .001). In contrast, in the restrictive group, ESV was significantly reduced at discharge (P = 0.01) and early follow-up (P = 0.02) but increased again (P < .001) at late control. A 15% reduction in ESV (considered indicative of LVRR) occurred in 95.7, 96.3, 88.3, and 0% in Groups 1, 2, 3, and 4, respectively (P < 0.001). A further comparison of the degree of LVRR in the three groups showed that ESV was reduced 20% or more in 18 patients (40.0%) and <20% in 27 patients (60.0%) in Group 1. In Group 2, 33 patients (62.3%) had a reduction in ESV < 20% and 20 patients (37.3%) had a reduction≥20%. In addition, ESV was reduced 20% or more in 13 patients (34.2%) and <20% or less in 25 patients (65.8%) in Group 3 (between groups P = 0.71,). Finally, among patients with a restrictive pattern ESV was reduced 10% or more in one patient (2.2%), <10% in 27 patients (61.4%), relatively stable (±1%) in four patients (9.1percnt;), and enlarged in 12 patients (27.3%; mean increment 3.9 ± 1.7%). Changes in EDV, ESD, EDD, and WMSI mirrored those of ESV.

Systolic and diastolic sphericity indexes improved in Groups 1, 2, and 3 at discharge (P < 0.001), early (Group 1, P = 0.01 for both SIS and SID; Group 2, P < 0.001 for SIS and P = 0.02 for SID; Group 3, P = 0.04 for both SIS and SID) as well as at late control (Group 1, P = 0.03 for SIS and P = 0.01 for SID; Group 2, P = 0.02 for SIS and P = 0.01 for SID; Group 3, P < 0.001 for both SIS and SID). In Group 4, there was an initial, but not significant, reduction in both the systolic and diastolic sphericity indexes, which remained stable at early follow-up with a late increase exceeding the pre-operative value (P < 0.001). In normal, impaired relaxation, and pseudonormal groups, LVEF significantly improved at discharge and at late follow-up, remaining unchanged at early control. In contrast, in the restrictive group it did not significantly change at any study point.

Indices of diastolic function remained stable over time in patients with baseline restrictive filling. In patients with pseudormal filling E/A increased (P = 0.03), whereas DT (P < 0.001), IVRT (P = 0.006) and S/D (P = 0.04) reduced at discharge. All these values remained constant afterwards. In patients with impaired relaxation, E/A reduced (P = 0.02), whereas DT (P = 0.001) and IVRT (P = 0.03) raised at discharge without further changes at subsequent controls. S/D did not show significant changes in this Group. Index of diastolic function did not modify over time in patients with normal LV filling pattern.

Predictive value of DT on LVRR
By multiple regression analysis baseline DT, SIs and WMSI resulted as independent predictors of LVRR. Internal validation of such multivariable analysis by means of bootsrapping, including the same variables of standard logistic regression model, further confirmed the significant predictive of LVRR (bootstrap OR = 2.2, 95% bias-corrected 95% CI = 1.0–4.9). Finally, logistic regression model was reliable (Hosmer–Lemeshow test, P = 0.58) and accurate(c index = 0.77) (Table 4).


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  		Table 4 Independent predictors of left ventricular reverse remodelling

 
Receiver operating characteristic curve analysis to determine optimal cutoff values (Figure 1–3) to predict reverse remodelling showed the following values: DT ≤ 125 ms (95% CI by bootstrapping 108–171 ms), SIS had 90% of sensitivity and specificity with an optimal cutoff ≤0.7 (95% CI by bootstrapping 0.58–0.81), WMSI < 1.5 (95% CI by bootstrapping 1.35–1.62).


Figure 1
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  		Figure 1 Receiver operating characteristic curve for Doppler-derived mitral deceleration time to predict left-ventricular remodelling.

 


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  		Figure 2 Receiver operating characteristic for systolic sphericity index (SIS) to predict left-ventricular remodelling.

 


Figure 3
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  		Figure 3 Receiver operating characteristic for Wall Motion Score Index to predict left-ventricular remodelling.

 
Clinical follow-up
At late control, mean NYHA class was 2.1 ± 0.3, 2.3 ± 0.4, 2.2 ± 0.4, and 3 ± 0.6 in Groups 1, 2, 3, and 4, respectively (P < 0.001). In Group 4, 70.5% patients had NYHA ≥ 3 vs. 33.3% in the pseudonormal group (P < 0.001), 18.1% in the impaired relaxation group (P < 0.001), and 4.6% in the normal Group (P < 0.001).

Seventeen patients underwent re-operation for failed repair (four had a re-repair and 13 underwent mitral valve replacement): none in Group 1, two in Group 2, six in Group 3, and 9 in Group 4. Five-year freedom from re-operation for failed repair were 100, 94 ± 5, 67 ± 9, and 43 ± 7% in Groups 1–4, respectively (P < 0.001). None of the patients developed clinical signs of angina. Furthermore, no myocardial infarction occurred in the post-operative period.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Conclusions
 References
 
The present study established that a baseline restrictive filling pattern, as expressed by a short DT, identifies patients who are ultimately candidates to continued LV remodelling after UMRA, mitral repair failure and recurrence of mitral regurgitation. Ereminiene et al37 demonstrated, in 55 patients, that diastolic restrictive filling pattern and DT were independent predictors of death and residual moderate MR late (12 months) after ischaemic mitral valve repair. Nonetheless these authors defined the restrictive filling pattern as an E/A ratio >2 or an E/A ratio 1–2 with DT < 150 ms and IVRT < 60 ms. E and E/A ratio are partially dependent on age, heart rate, loading conditions, and degree of MR. In particular, MR may increase the E-wave velocity of transmitral flow, which resembles pseudonormal or restrictive patterns. Several studies have shown that a short DT, even not load independent, irrespective of the ratio of early and late filling velocity (E/A) ratio, is strongly related to pulmonary capillary wedge pressure38,39 and end-diastolic pressure40 and it is an useful parameter for the serial assessment of LV diastolic function in post-infarct patients also in those with MR.41 For this reason, we used DT as a means of assessing LV filling, irrespective of filling pattern. Nonetheless, in an attempt to overcome the limitations of transmitral flow Doppler indices, we used routinely the assessment of pulmonary venous flow. On the basis of these two indices, we classified patients in four Groups: Normal, impaired relaxation, pseudonormal, and restrictive.

Furthermore, we employed the Valsalva manoeuvre in no-restrictive patients presenting E/A between 1 and 2, to unmask the presence of impaired relaxation.

Patients belonging to restrictive Group had larger distance between the coaptation point and the mitral annulus (coaptation height, p = 0.001), which represents a quantitative estimate of incomplete mitral closure. In a recent study, Karagiannis et al.42 showed a linear correlation between coaptation height and both measurements of left ventricular size and indices of systolic performance of the left ventricle. In our experience, subjects with restrictive diastolic pattern had larger diameters (P = 0.03) and volumes (ESV, P < 0.001; EDV, P = 0.04), and a more dysfunctioning LV (LVEF, P = 0.04), and this might explain the larger coaptation height found in this Group.

Cardiac remodelling is a well-known important aspect of CIMR and myocardial disease progression responsible for recurrence of MR after annuloplasty.13,14 Thus LVRR is considered a primary post-operative target. Following the same criterion used by Stellbrink et al.31 a reduction >15% in ESV compared with baseline volumes was considered as LVRR. Other Groups41 considered LV end diastolic dimension as significant index of LVRR. Nonetheless, measurements of LV volumes have been demonstrated to be more reliable than LV diameters in assessing LV remodelling, especially in enlarged ventricles.43 On this basis, LVRR occurred in 95.7, 96.3, 88.3, and 0% in Groups 1, 2, 3, and 4, respectively (P < .001). In addition, among restrictive patients, 12 (27.3%) showed continuous remodelling with a mean increment in ESV of 3.9 ± 1.7% at late examination.

Nonetheless, EDV and ESV decreased at early follow-up also in the restrictive group. Thus, an increase in EDV and ESV at late follow-up could be related to the increasing or recurrence of a significant MR and all this might be inducing the restrictive pattern and not vice versa, since from the beginning, the restrictive group has larger volumes and lower LVEF. A DT value >125 ms was the most powerfull independent predictor of LVRR, whereas, interestingly, LVEF did not provide any prognostic value thus indicating that LV diastolic dysfunction may be more sensitive than LV systolic dysfunction in predicting LVRR after CABG and restrictive annuloplasty. Nonetheless, the lack of improvement in LVEF in the restrictive group could be related to the changes in EDV and ESV in presence of a recurrence of MR. In other words, the fact that LVEF did not show any prognostic value might be due to the presence of MR in this population.

Other predictors of LVRR were SIS (P < 0.001) and WMSI (P < 0.008). By comparing the four groups in our study, it appears evident that patients with pre-operative restrictive filling pattern were much more globally remodelled at every study point; at late control they still showed a more spherical and enlarged LV. Particularly, the late increase in sphericity indexes in this group, which exceeded the pre-operative value, was consistent with further remodelling after UMRA and reflects increased tethering on the mitral valve, thus translating into a significantly higher number of patients with late significant MR in this group (P < 0.001).

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

Similar to other studies,37 we employed conventional indices of LV diastolic function.

Tissue Doppler imaging (TDI) would have been more useful in estimating LV diastolic filling pattern. Nonetheless, DT, even not load independent is strongly related to pulmonary capillary wedge pressure and end-diastolic pressure and it is an useful parameter for the serial assessment of LV diastolic function in post-infarct patients also in those with MR. Furthermore, in an attempt to overcome the limitations of transmitral flow Doppler indices, we used routinely the assessment of pulmonary venous flow.

An evaluation of diastolic function after UMRA and CABG, employing TDI will be ongoing to confirm these findings.

Evaluation of LVRR was based on volumes obtained by echocardiography; volumetry by 2D echocardiography depends on geometric assumptions and is subject to image-plane positioning errors. Hence it is not accurate in left ventricles that are distorted in shape such as after myocardial infarction. However, this limitation belongs to most of published paper regarding this pathology.

Viability testing was not performed in these patients. Therefore lack of LVRR in non-responders might be also due to irreversible ischaemic myocardial damage (not-viable myocardium). This issue deserves further investigation.
Post-operative evaluation of the coronary status was not assessed. It would have been helpful to differentiate between surgical failure (valve repair and CABG) and the progress of the coronary disease.
Fifteen patients with late deaths were not included in the study. They could have benefited from serial echocardiograms possibly with different results.
Estimated cutoffs are known to be very susceptible to changes in the study population.
We employed bootstrapping techniques to validate the results, nonetheless, it has also been documented that the sensitivity/specificity associated with these cutoffs are overly optimistic.

Strength of the study
This is a large cohort reported with UMRA in CIMR patients with detailed (100% complete) echocardiographic follow-up. Furthermore our patient cohort was more homogeneous than in other study and does not display common clinical and methodological pitfalls that limit results from many studies of mitral valve repair:44 all patients underwent associated CABG, they had no concomitant MV procedures, and the entire cohort was uniform regarding the MV ischaemic 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 surgery. Additionally, we undertook valve sizing in a standardized fashion and the degree of undersizing was homogeneous over the 5-year-period of the study. Finally, we used only two rings (Carpentier's rigid or semi-flexible rings).

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 pre-operatively identified utilizing echo predictors. However, restrictive annuloplasty resulted to be ineffective in a large percentage of patients and results of this study suggest the need for different approaches directly addressing ventricular tethering in most of CIMR patients45 These procedures were introduced in the recent years in clinical practice, thus our experience with these techniques is actually in the preliminary phase Furthermore, mitral valve replacement, largely employed in the past in ischaemic regurgitation, although eliminates the short-term risk of recurrent MR, it is associated with poor long-term survival.46 Thus, in our actual policy, we do not consider MV replacement as a reasonable alternative to repair.

Another interesting finding of our study, apart from the predictive value of DT on LVRR, was that in patients with more advanced diastolic dysfunction, evidenced by an LV restrictive filling, UMRA associated to CABG did not cause improvement of diastolic function. In contrast, an improvement of diastolic function occurred in no-restrictive patients. This suggests that an early surgical indication is advisable in patients with CIMR in less severe stages of disease. In the presence of advanced diastolic dysfunction, patients should be considered poor candidates for this procedure and concomitant or alternative procedure should be contemplated.


   Conclusions
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusions
References
 
Pre-operative assessment of DT adds significant information to commonly used indexes of global and regional function, and represent a very easy and cost-effective tool to accurately identify CIMR patients who can really benefit from annuloplasty. Long-term prospective studies on this controversial issue are encouraged.


   Acknowledgements
 
We gratefully acknowledge Dr Orlando Parise for statistical analysis. We thank Dr Judith Wilson for the English revision of the paper.

Conflict of interest: none declared.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusions
 References
 

  1. De Simone G, Greco R, Mureddu G, et al. Relation of left ventricular diastolic properties to systolic function in arterial hypertension. Circulation (2000) 101:152–7.[Abstract/Free Full Text]
  2. Shingu Y, Shiiya N, Mikami T, Matsuzaki K, Kunihara T, Matsui Y. Left ventricular diastolic dysfunction in chronic aortic dissection. Ann Thorac Surg (2007) 83:1356–60.[Abstract/Free Full Text]
  3. Werner GS, Schaefer C, Dirks R, Figulla HR, Kreuzer H. Prognostic value of Doppler echocardiographic assessment of left ventricular filling in idiopathic dilated cardiomyopathy. Am J Cardiol (1994) 73:792–8.[CrossRef][Web of Science][Medline]
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