Background
Increased left ventricular (LV) dimensions are an indication for surgery in patients with asymptomatic mitral regurgitation, but M-mode or two-dimensional measurements have known limitations. The aim of this study was to determine the value of three-dimensional echocardiography in predicting postoperative outcomes after mitral surgery.
Methods
Sixty-seven patients with severe asymptomatic or minimally symptomatic mitral regurgitation (69% men; mean age, 62 ± 13 years) who underwent mitral valve surgery from January 2010 to December 2011 were studied. In addition to standard echocardiography, baseline three-dimensional echocardiography was performed for accurate quantification of LV size. Patients were followed over a median time of 1 month (interquartile range, 0–8 months) for postoperative development of atrial fibrillation or LV dysfunction. A multivariate regression analysis was performed to identify associations with events.
Results
Postoperative LV dysfunction developed in 15 patients (22%), and 21 patients (31%) had postoperative atrial fibrillation. There was no association between two-dimensional end-systolic volume index and outcomes (hazard ratio, 1.02; P = .18). Postoperative atrial fibrillation or LV dysfunction was associated with baseline three-dimensional LV end-systolic volume index (hazard ratio, 1.06; 95% confidence interval, 1.04–1.16), independent of age and presence of coronary artery disease. LVESVi ≥ 40 mL/m 2 was the best cutoff value to predict postoperative events (sensitivity, 80%; specificity, 85%). After adding LVESVi to a model containing clinical and echocardiographic parameters, net reclassification improvement was 0.27 (95% confidence interval, 0.25–0.29; P = .024).
Conclusions
LVESVi from three-dimensional echocardiography is an independent predictor of postoperative outcomes in patients with severe mitral regurgitation that is incremental to other clinical and echocardiographic variables.
The American College of Cardiology and American Heart Association guidelines indicate that asymptomatic patients with chronic severe mitral regurgitation (MR) with mild to moderate left ventricular (LV) dysfunction and/or LV end-systolic dimension (LVESD) ≥ 40 mm is a class I indication for mitral valve operation. Although the traditional measurement of LVESD by two-dimensional (2D) echocardiography (2DE) is well accepted and has been shown to predict postoperative prognosis, 2D LV quantification has its own limitations, including off-axis cut planes, geometric assumptions, and boundary-tracing errors. Inexact LV assessment may result in a failure to provide timely mitral surgery, which in turn may contribute to postoperative LV dysfunction after patients eventually undergo surgery. Indeed, a number of patients who undergo surgery after the application of current criteria develop postoperative LV dysfunction, and this has led to lower thresholds for recommending surgery.
Three-dimensional (3D) echocardiography (3DE) enables the accurate measurement of LV volumes, avoiding those 2D limitations. Several studies have shown that measurements of LV volumes and LV ejection fraction (LVEF) with 3DE are significantly more accurate and reproducible than with conventional 2DE when compared with cardiac magnetic resonance as the reference technique. We sought to define the value of 3D LV quantification to predict the postoperative outcomes of patients with MR. Specifically, we examined the potential impact of a new cutoff value of 3DE-derived LV end-diastolic volume (LVEDV) to reclassify the candidacy of patients for mitral valve surgery.
Methods
Patients
The study population included patients with severe MR who underwent 3DE before mitral valve surgery between January 2010 and December 2011 at two centers. Patients were excluded if they had any additional hemodynamically significant valvular lesion. We screened 1,064 patients with diagnoses of severe MR of any etiology who underwent echocardiography. Among those, only 99 patients underwent complete 3D echocardiographic studies, mitral valve surgery, and complete follow-up echocardiography. After these exclusions, we enrolled a total of 67 patients (69% men; mean age, 62 ± 13 years). The protocol was approved by the relevant institutional review boards.
Clinical Characteristics and Echocardiography
Patients with asymptomatic or minimally symptomatic severe MR underwent detailed evaluations, including clinical evaluation, standard echocardiography, and 3DE. Standard echocardiography was performed by experienced sonographers using commercially available ultrasound systems. The LV dimensions were obtained from the left parasternal long-axis view using M-mode echocardiography or, if the imaging plane was unsuitable, by 2D measurement. Two-dimensional LVEF was measured using the biplane Simpson’s method. Other parameters for LV quantification were measured according to American Society of Echocardiography recommendations. MR was quantified using a multiparametric approach, including color jet flow area, measurement of the effective regurgitant orifice area, vena contracta, and pulmonary venous flow pulse Doppler. Effective regurgitant orifice area was measured using flow convergence zone (proximal isovelocity surface area) measures. Vena contracta width was measured from parasternal views. The same variables were used regardless of whether the MR jet was bounded or unbounded by adjacent structures. Severe MR was defined as MR with a large central jet or a variably sized wall-impinging jet swirling in the left atrium, when quantitative evaluation identified an effective regurgitant orifice area ≥ 0.40 cm 2 or vena contracta width ≥0.7 cm.
3D Echocardiographic Analysis
LV volume analysis was performed offline (TomTec 4D LV-Analysis; TomTec Imaging Systems, Munich, Germany) by manual tracing of the endocardial border of both the end-diastolic and end-systolic images in the three apical views from the full-volume data set. The endocardial border was traced just outside the apparent blood-tissue interface. The resulting segmentation of myocardium and blood pool was applied by the software to the entire 3D data set. The adequacy of fit to the entire left ventricle was evaluated by visual review in multiple image planes, and the contour detection was adjusted so that the papillary muscles and most endocardial trabeculae were included in the LV cavity. This information was used to fit an LV model, automatically delineating the total LV endocardial border but permitting manual correction. The end-diastolic and end-systolic frames were identified automatically, and LVEDV, LV end-systolic volume (LVESV), and LVEF measurements were derived.
Outcomes
In this observational study, the composite end point was postoperative LV dysfunction (reduction of LVEF by 10 units, resulting in LVEF < 50%) or postoperative atrial fibrillation (POAF) after a median follow-up time of 1 month (interquartile range, 0–8 months). End points were adjudicated blindly, after the baseline measurements were complete. POAF was defined as any evidence of new atrial fibrillation (by electrocardiography when patients reported symptoms or continuous monitoring during the postoperative stay) that lasted ≥30 min.
Statistical Analysis
Statistical analysis was performed using standard software (SPSS version 16; SPSS, Inc, Chicago, IL). Data are expressed as mean ± SD. Group comparisons were performed using χ 2 tests for categorical data and one-way analysis of variance for continuous variables. Paired t tests were used for comparisons of preoperative and postoperative echocardiographic parameters. The association between 3D LV dimension and clinical outcomes was analyzed using univariate logistic regression. A series of exploratory models was created using multivariate logistic regression to find the strongest predictors of outcomes, on the basis of the greatest pseudo- R 2 value. Variables were entered allowing one variable per 10 events. The discrimination of the model was evaluated using concordance (C) statistics (representing the area under the receiver operating characteristic [ROC] curve) and 95% confidence intervals. ROC curves were generated and compared using MedCalc version 12.3.0.0 (MedCalc Software, Mariakerke, Belgium). Bootstrap estimation with resampling from 1,000 simulations was used to generate valid estimates of association accuracy. A reclassification table was constructed, and net reclassification improvement was used to determine whether the replacement of LVESD with 3D LVESV index (LVESVi) would improve the ability to predict the postoperative outcome. Statistical significance was defined as P < .05.
Results
Clinical and Echocardiographic Characteristics
The clinical characteristics of the patients are listed in Table 1 . Most patients ( n = 58 [86.5%]) had degenerative MR; the others had rheumatic MR ( n = 3 [4.5%]), infective endocarditis ( n = 1 [1.5%]), ischemic MR ( n = 2 [3.0%]), functional MR including annular dilatation ( n = 1 [1.5%]), and MR due to other causes ( n = 2 [3.0%]). Multiparametric assessment of MR demonstrated severe MR in all patients. Table 1 lists the baseline characteristics and compares patients with and without events. Two-dimensional LVEFs were <50% at inclusion in eight patients (12%). Three-dimensional echocardiographic parameters were available in all patients.
| Variable | Total ( n = 67) | Events ( n = 30) | No events ( n = 37) | P |
|---|---|---|---|---|
| Age (y) | 62 ± 13 | 66.5 ± 10.1 | 58.7 ± 13.3 | .009 |
| Men | 46 (69%) | 22 (73%) | 24 (65%) | .457 |
| BMI (kg/m 2 ) | 27 ± 5 | 25.7 ± 3.5 | 27.2 ± 5.3 | .139 |
| Hypertension | 29 (43%) | 15 (50%) | 14 (38%) | .318 |
| Diabetes | 4 (6%) | 2 (7%) | 2 (6%) | .828 |
| Hypercholesterolemia | 31 (46%) | 14 (47%) | 17 (46%) | .953 |
| History of paroxysmal AF | 24 (36%) | 13 (43%) | 11 (30%) | .248 |
| Coronary artery disease | 14 (21%) | 10 (33%) | 4 (11%) | .024 |
| ACE inhibitors/ARBs | 13 (19%) | 7 (23%) | 6 (16%) | .464 |
| β-blockers | 28 (42%) | 14 (47%) | 14 (38%) | .466 |
| MV replacement | 17 (25%) | 9 (30%) | 8 (22%) | .433 |
| LVEF | 59 ± 10.8 | 57.0 ± 12.8 | 62.4 ± 6.1 | .039 |
| LVEDD (cm) | 5.6 ± 0.9 | 5.9 ± 0.9 | 5.3 ± 0.9 | .011 |
| LVESD (cm) | 3.7 ± 0.9 | 4.0 ± 0.9 | 3.4 ± 0.8 | .002 |
| LAVI (mL/m 2 ) | 37.82 ± 8.76 | 39.0 ± 8.4 | 36.9 ± 9.0 | .351 |
| LVEDVi (mL/m 2 ) | 71.1 ± 31.5 | 91.3 ± 37.8 | 65.6 ± 19.1 | .002 |
| LVESVi (mL/m 2 ) | 36.9 ± 24.4 | 41.7 ± 20.2 | 33.0 ± 27.0 | .137 |
| 3D LVEDVi (mL/m 2 ) | 85.3 ± 31.9 | 100.2 ± 36.1 | 75.2 ± 24.0 | .002 |
| 3D LVESVi (mL/m 2 ) | 42.7 ± 24.1 | 58.9 ± 28.5 | 31.9 ± 8.6 | <.001 |
| 3D LVEF | 63.4 ± 11.9 | 59.9 ± 15.8 | 66.3 ± 6.3 | .045 |
| EROA | 0.70 ± 0.39 | 0.72 ± 0.38 | 0.69 ± 0.41 | .744 |
| VC | 0.82 ± 0.17 | 0.81 ± 0.14 | 0.82 ± 0.19 | .780 |
| RVSP | 40 ± 13 | 43.9 ± 12.8 | 39.2 ± 14.8 | .186 |
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