Background
Because of the lack of reliable echocardiographic parameters to predict recovery after surgery, the optimal timing of surgery for severe mitral regurgitation remains controversial. The aim of this study was to determine whether global longitudinal strain (GLS) recorded preoperatively could help in predicting left ventricular (LV) ejection fraction (LVEF) postoperatively.
Methods
A total of 88 patients (mean age, 63 ± 13 years; 59 men) with severe degenerative mitral regurgitation were included prospectively in this study. Rest echocardiography was performed before and 6 ± 1 months after mitral valve surgery. Patients were divided into two groups: group A (postoperative LVEF ≥ 50%) and group B (postoperative LVEF < 50%).
Results
In group B, patients had larger preoperative LV end-systolic diameters (21.6 ± 2.6 vs 19.2 ± 3.7 mm/m 2 , P = .02) and impaired preoperative GLS (−17 ± 2.8% vs −19.6 ± 3.6%, P = .01), whereas there was no difference in preoperative LVEF. Preoperative LV end-systolic diameter ≥ 22 mm/m 2 and GLS < −18% were independent predictors of postoperative LV dysfunction.
Conclusions
LV end-systolic diameter is a well-recognized prognostic marker. In addition, this study demonstrates the additive and independent predictive value of preoperative GLS for predicting postoperative LV dysfunction.
Physicians who treat degenerative mitral regurgitation (MR) must make decisions regarding the optimal timing of surgery for significant MR. Without surgical treatment, the 10-year morbidity and mortality for patients with severe MR can be as high as 90%. In contrast, with successful surgical correction of MR before the appearance of complications, patients have life expectancies similar to that of the general population.
According to European recommendations, mitral valve repair must be proposed to symptomatic patients and to patients with significant left ventricular (LV) remodeling as a consequence of the severity of MR. A significant decline in LV function is defined, in these recommendations, echocardiographically as an LV ejection fraction (LVEF) < 60% or an LV end-systolic diameter (LVESD) > 45 mm. Preoperative LV systolic function and LVESD are important postoperative prognostic factors. However, it is still difficult to decide when a patient should be referred for surgery. The early detection of LV systolic dysfunction remains a challenge. MR causes low LV afterload, and the ejection fraction thus remains normal or supernormal until the disease reaches an advanced stage. Various ultrasound techniques for evaluating LV function have been tested in the hope of better predicting the capacity of the left ventricle to return to normal function postoperatively. Some authors have suggested the additive value of deformation indices as more sensitive than the ejection fraction to detect subclinical LV systolic dysfunction. The goal of our study was thus to determine ultrasound factors that predict LV dysfunction after surgical treatment for degenerative MR. In particular, we sought to study the value of preoperative LV longitudinal strain. Longitudinal strain is now widely available using a speckle-tracking approach, and it can be used in addition to other conventional echocardiographic measurements such as diameters.
Methods
Patients
Between 2008 and 2010, 88 of 120 patients admitted for surgical treatment of degenerative MR were prospectively enrolled at the University Hospital in Rennes. All patients with degenerative MR (fibroelastic degenerative MR or Barlow’s disease) who were scheduled for mitral valve surgery were eligible for inclusion in the study. Not all patients had flail leaflets; in some, leaflets were highly redundant and “prolapsing” in the atrium. We defined a flail leaflet as a lack of normal mitral leaflet apposition and abnormal pointing of the flail component into the left atrium during systole. The European recommendations of 2007 were used as guidelines for determining the indication for surgery. In patients with severe MR but without complications, surgery was recommended when anatomic conditions were favorable for mitral valve repair. Exclusion criteria were age < 18 years, MR of ischemic or functional origin, hemodynamic instability, the need for urgent surgery, and patient refusal of the study (patients were asked to return for follow-up at 6 months). Each patient gave his or her signed consent after receiving clear information both in writing and orally. The study was the object of an agreement of the ethics committee (Person Protection Committee V; PIME 08/16-675).
After enrollment in the study but before surgery, patients underwent detailed evaluations, including clinical evaluation and 12-lead resting electrocardiography, resting echocardiography, and exercise echocardiography. Resting echocardiography was performed using a Vivid scanner (GE Vingmed Ultrasound AS, Horten, Norway), with the patient in the left lateral decubitus position. Secondary analysis of the data was performed using EchoPAC software (GE Vingmed Ultrasound AS). Multiple parameters were studied during the resting echocardiography. Ventricular diameters (end-diastolic and end-systolic) were obtained using M-mode analysis with the left parasternal long-axis view. MR was quantified using a multiparametric approach, including measurement of the effective regurgitant orifice and the regurgitated volume using the proximal isovelocity surface area method, analysis of the vena contracta, analysis of the relationship of the aortic and mitral velocity-time integral, and study of the pulmonary venous systolic reflux. LVEF was measured using the biplane Simpson’s method. Tissue Doppler was used to measure the S wave at the mitral annulus (with septal and lateral values averaged). Myocardial deformation was measured using two-dimensional strain, with the assistance of a speckle-tracking technique. Two-dimensional grayscale images were acquired in the standard apical four-chamber, three-chamber, and two-chamber views at a frame rate of about 80 frames/sec (mean, 89 ± 4 frames/sec). The left ventricle was divided into 16 segments, and each segment was analyzed individually. Using a dedicated software package (EchoPAC PC; GE Healthcare, Milwaukee, WI), global longitudinal strain (GLS; averaged longitudinal strains) was calculated automatically by the software. Two-dimensional strain is a non-Doppler-based method for the evaluation of systolic strain using standard two-dimensional acquisitions. After placing three endocardial markers in an end-diastolic frame, the software automatically tracks the contour on subsequent frames. Adequate tracking can be verified in real time and corrected by adjusting the region of interest or by manually correcting the contour to ensure optimal tracking. Two-dimensional longitudinal strain was assessed in apical views. Average longitudinal strains were calculated for the 16 segments.
Deformations analyzed by two-dimensional strain represent a promising technique for the evaluation of LV systolic function. However, this measurement is load and geometry dependent. We evaluated an index combining longitudinal deformations and LV systolic diameters.
Diastolic LV function was measured by analysis of the E and A waves of the transmitral inflow. Pulse tissue Doppler e′ at the mitral annulus (the average value on the basis of septal and lateral values) and left atrial size (end-systolic measurement) were recorded as well. The left atrium was measured using Simpson’s biplane technique. Systolic function of the right ventricle was measured using tricuspid annular plane systolic excursion of the M-mode model. Systolic pulmonary artery pressure (sPAP) during tricuspid regurgitation was estimated according to the Bernoulli equation (pulmonary artery pressure = 4 V 2 + estimated right atrial pressure, where V is the maximal velocity of the flow of tricuspid regurgitation, and right atrial pressure is the pressure in the right atrium estimated according to the size and compliance of the inferior vena cava).
As stipulated at the time of inclusion in the study, patients were asked to return for follow-up echocardiography using the same modalities 6 ± 1 months after surgery. Intraobserver and interobserver reproducibility as well as test-retest variability were reassessed recently in our laboratory, especially for strain analysis.
Patients were divided into two subgroups on the basis of postoperative LVEF. Group A included patients with postoperative LVEFs ≥ 50%, and group B included those with LV dysfunction and postoperative LVEFs < 50%.
Intraobserver and interobserver reproducibility were assessed by calculating the difference between the mean values of 15 randomly selected patients. Intraobserver reproducibility is expressed as the absolute mean difference between the 15 measurements. In parallel, data from 15 randomly selected patients were analyzed by an independent operator to validate the reproducibility of echocardiographic measurements ( Table 1 ).
| Variable | Mean ± SD | Intraobserver variability | Interobserver variability | ||
|---|---|---|---|---|---|
| Absolute difference | Relative difference (%) | Absolute difference | Relative difference (%) | ||
| GLS (%) | −20.9 ± 2.7 | 1.4 ± 1.1 | 0.05 | 1.4 ± 1.5 | 0.04 |
| LVEF (%) | 66 ± 7 | 4.1 ± 3.0 | 0.06 | 3.7 ± 3.3 | 0.06 |
| LVESD (mm) | 35.1 ± 4.7 | 0.4 ± 0.5 | 0.01 | 0.7 ± 0.7 | 0.02 |
Statistical Analysis
Statistical analyses were performed using SAS version 9.1 (SAS Institute Inc., Cary, NC). Quantitative data are expressed as mean ± SD. Qualitative data are expressed in numbers and percentages. Fisher’s exact tests were used to determine if there were nonrandom associations between two categorical variables. Student’s t tests for comparisons of independent samples were used for comparisons of means, and paired Student’s t tests were used for intragroup comparisons. Comparisons of qualitative variables were performed using χ 2 tests. Pearson’s test was used to assess correlation. Receiver operating characteristic curves were constructed to detect the best sensitivity and specificity.
Multivariate analysis was performed using a multiple linear regression model and by logistic regression to define parameters predictive of LV dysfunction at 6 months after surgical intervention. The threshold for significance was defined as P < .05.
Results
Description of the Patient Population
Eighty-eight patients were enrolled in this study (mean age, 63.1 ± 13 years; 59 men). Table 2 summarizes the clinical characteristics of the patients at the time of inclusion in the study. Most of the patients ( n = 83) had degenerative MR with flail leaflets or excessive prolapse. One patient had congenital mitral insufficiency, and four patients had restrictive mitral insufficiency. All patients underwent mitral valve surgery; mitral valve repair was the most commonly performed procedure ( n = 72). The most frequent intervention was a quadrangular or triangular resection of P2 with or without annuloplasty, with placement of a new Gore-Tex (W. L. Gore & Associates, Newark, DE) sling. Sixteen patients underwent mitral valve replacement; eight had mechanical valve replacement, and eight received biologic valves. The subvalvular apparatus was conserved whenever possible, but it was not conserved in four patients. Six patients also underwent associated tricuspid annuloplasty. The specifics of these few patients in the study did not influence further results.
| Variable | Total population ( n = 88) | Group A ( n = 73) | Group B ( n = 15) | P |
|---|---|---|---|---|
| Clinical | ||||
| Age (y) | 63.1 ± 13 | 63.5 ± 13.3 | 61.3 ± 16.6 | .57 |
| Men | 59 (67%) | 45 (61.6%) | 14 (93.3%) | .01 |
| AF | 15 (17%) | 11 (15%) | 4 (26.6%) | .27 |
| Hypertension | 38 (44%) | 32 (46.3%) | 6 (40%) | .65 |
| Diabetes | 3 (3.5%) | 2 (2.8%) | 1 (6.6%) | .46 |
| BMI (kg/m 2 ) | 25.3 ± 432 | 25 ± 4.1 | 25.5 ± 4.8 | .9 |
| NYHA class (I/II/III/IV) | 28/53/6/1 | 25/43/4/1 | 3/10/2/0 | .5 |
| Coronary heart disease | 13 (15%) | 10 (13.7%) | 3 (20%) | .53 |
| Treatment | ||||
| β-blockers/calcium channel blockers | 37 (42%) | 31 (42.5%) | 6 (40%) | .86 |
| ACE inhibitors/angiotensin II receptor antagonists | 42 (48%) | 34 (46.5%) | 8 (53%) | .63 |
| AVK/AAP agents | 30 (35%) | 25 (35.2%) | 5 (33.3%) | .89 |
| Surgery | ||||
| MVR | 16 (18%) | 15 (20.5%) | 1 (6.6%) | .3 |
| ECC duration (min) | 109 ± 40 | 109.7 ± 42.2 | 104.1 ± 27.3 | .66 |
| Clamping duration (min) | 80 ± 29 | 80.2 ± 30.5 | 79.5 ± 22.4 | .93 |
Extracorporeal circulation lasted 109 ± 40 min on average, and the average duration of clamping was 80 ± 29 min. The duration of extracorporeal circulation and clamping did not differ between group A and group B. The postoperative period and the duration of the hospital stay were identical in group A and B. There was also no difference between the two groups of patients in the type of surgery (repair vs replacement) performed. Repeat surgery with revision of the mitral valve repair was required in two patients (at 2 weeks and 6 months) because of recurrent severe mitral insufficiency. None of these clinical and surgical characteristics of our population were correlated with LVEF at 6-month follow-up. No patient required any coronary artery revascularization.
On 6-month follow-up echocardiography, no patient had any dysfunction of the valve repair or of the prosthetic valve. We did not find any MR with an effective regurgitant orifice reaching 10 mm 2 .
Echocardiographic Data
Main preoperative echocardiographic data at rest and during exercise are reported in Table 3 . On the basis of the multiparametric evaluation described above, all patients in this study had severe (grade 4/4) mitral insufficiency. Eleven patients had LV dysfunction (LVEF < 60%) at inclusion, with only one patient having an LVEF < 50% (49%). Eighteen patients had LVESDs ≥ 22 mm/m 2 , and two of these patients had LVESDs ≥ 26 mm/m 2 . Twenty-six patients had LVESDs ≥ 40 mm, and eight of these patients had LVESDs ≥ 45 mm. Twenty-four patients had alterations in LV GLS, defined as a shortening of the longitudinal myocardial fibers of <18%. Five patients had right ventricular dysfunction on the basis of visual and tricuspid annular plane systolic excursion assessments (measured value < 18 mm) and the S wave at the tricuspid annulus on tissue Doppler (<11 cm/sec). Eight patients had sPAP > 50 mm Hg at rest.
| Variable | Total | Group A ( n = 73) | Group B ( n = 15) | P |
|---|---|---|---|---|
| Left atrium | ||||
| Volume (biplane area-length method) (mL/m 2 ) | 52.3 ± 24.1 | 48.9 ± 20.5 | 68.8 ± 33.3 | .003 |
| Area (apical four-chamber view) (cm 2 ) | 26.2 ± 9 | 24.8 ± 7.9 | 33.1 ± 10.0 | .001 |
| Diameter (parasternal view) (mm) | 44.7 ± 8 | 43.5 ± 7.3 | 50.6 ± 8.6 | <.001 |
| Left ventricle | ||||
| LVESD (mm) | 36 ± 6.1 | 35.0 ± 5.8 | 40.6 ± 5.3 | .001 |
| LVESD index (mm/m 2 ) | 19.7 ± 3.6 | 19.2 ± 3.7 | 21.6 ± 2.6 | .02 |
| LVEDD (mm) | 52.3 ± 23.3 | 54.7 ± 7.8 | 61.5 ± 6.6 | .002 |
| LVESV (mL) | 55.9 ± 8 | 49.8 ± 23.0 | 64.5 ± 21.3 | .02 |
| LVEDV (mL) | 149.8 ± 52.2 | 143.9 ± 50.0 | 178.2 ± 33.4 | .01 |
| E (transmitral pulsed Doppler) (cm/sec) | 129.9 | 128 ± 32 | 127 ± 30 | .48 |
| LV S′ (tissue Doppler) (cm/sec) | 9.3 ± 2.5 | 8.4 ± 3.7 | 9.5 ± 2.0 | .25 |
| LVEF (%) | 66 ± 7 | 66.2 ± 6.4 | 64.6 ± 10.1 | .43 |
| LV GLS (%) | −19.1 ± 3.6 | −19.6 ± 3.6 | −17.0 ± 2.8 | .01 |
| LV GLS/LVESD (%/mm) | −5.4 ± 1.4 | −5.7 ± 1.3 | −4.3 ± 1.1 | .001 |
| Right ventricle | ||||
| sPAP (mm Hg) | 37.1 ± 13 | 35.2 ± 11.6 | 46.0 ± 18.6 | .009 |
| TAPSE (mm) | 22.7 ± .9 | 22.5 ± 4.7 | 23.4 ± 5.4 | .46 |
| S tric (cm/sec) | 14 ± 3.6 | 13.9 ± 3.7 | 15.9 ± 3.4 | .05 |
Comparison of Echocardiographic Parameters according to Postoperative LVEF
Postoperatively, a reduction in LVEF was observed. The average preoperative LVEF was 66 ± 7%, and the average postoperative LVEF was 54.6 ± 7.3% ( P < .001). Fifteen patients had postoperative LVEFs < 50% (group B). Among these, six had class I indications for surgery according to the European Society of Cardiology criteria (one patient had New York Heart Association class III heart failure, and five patients had LVEFs ≤ 60%). None had LVESDs ≥ 26 mm/m 2 . Patients with postoperative LV dysfunction had more dilated left atria compared with patients with normal LVEFs (48.9 ± 20.5 vs 68.8 ± 33.3 mm, P = .003). The left ventricles of these patients were also more dilated at end-systole (LVESD index, 19.2 ± 3.7 vs 21.6 ± 2.6 mm, P = .02) and at end-diastole. Preoperative sPAP at rest was higher in group B. Preoperative LVEF did not differ between the two subgroups at the time of inclusion (66.2 ± 6.4% vs 64.6 ± 10.1%, P = .43). However, LV GLS was more altered in patients with postoperative LV dysfunction (–19.6 ± 3.6% vs −17 ± 2.8%, P = .01).
Correlations of Preoperative Ultrasound Parameters with Postoperative LVEF
Postoperative LVEF was correlated with preoperative LVESD ( r = −0.46, P < .001) and preoperative left atrial dimensions (diameter, surface area, and volume), as shown in Table 4 . A correlation between postoperative LVEF and preoperative resting LVEF was also observed ( r = 0.29, P = .03). Postoperative LVEF was also correlated with preoperative resting GLS; this correlation was stronger when LV GLS was normalized to LVESD ( r = −0.45, P < .001). There was no correlation between postoperative LVEF and preoperative sPAP in our population.
