Introduction
Both left atrial enlargement and remodeling are compensatory mechanisms in patients with chronic severe mitral regurgitation (MR). These changes allow the left atrium to accommodate the regurgitant volume without increased pressure [
1‐
3]. It is recognized that left atrial enlargement is a marker of major cardiovascular events such as atrial fibrillation, stroke, and death in patients with cardiac disease [
4‐
8]. In patients with chronic severe MR, left atrial size seems to be an important predictor of outcome, either during conservative treatment or after mitral valve surgery [
3,
9‐
11]. A decrease in left atrial size, or reverse remodeling, has been observed after mitral valve surgery [
12‐
17]. These prior studies included patients with different causes of MR, analyzed left atrial size using different techniques, and found different pre- and postoperative factors related to postoperative left atrial reverse remodeling (LARR). Different definitions of LARR after MR surgery have also been used; some considered any reduction value and others no more than 15% [
12‐
17]. Low values may be very sensitive and may not have great hemodynamic meaning. We hypothesized that larger postoperative LARR would represent a stronger hemodynamic impact by surgery and have different predictor factors. The objectives of our study were to assess the changes in left atrial size after surgery for MR and to verify the preoperative parameters that may be associated with or predictive of a reduction in left atrial volume index (LAVI) of at least 25%.
Results
The baseline characteristics of the patients are presented in Table
1. Thirty-four patients (54.8%) underwent mitral valve repair and 28 (45.2%) underwent valve replacement, using 19 biological and 9 mechanical prostheses. Surgical atrial reduction was not performed in any patients included in the study. In the postoperative evaluation, 52 patients were in sinus rhythm, and 10 in atrial fibrillation. Sixty (98.8%) patients had a preoperative LAVI ≥40 mL/m
2. The LAVI decreased from a preoperative mean of 85.5 mL/m
2 to a postoperative mean of 49.6 mL/m
2 (
p <0.001); the mean reduction was 39%. LARR was observed in 46 (74.2%) patients.
Table 1
Baseline patient characteristics
Male sex | 37 (59.7) |
Body surface area (m2); mean ± SD | 1.73 ± 0.19 |
Stage 1 systemic hypertension | 37 (59.7) |
Rhythm: | |
Sinus | 50 (80.6) |
Atrial fibrillation | 12 (19.4) |
Functional class: | |
II | 43 (69.4) |
III / IV | 19 (30,6) |
Medications: | |
Diuretic | 54 (84.4) |
ACE inhibitor | 38 (59.4) |
Beta blocker | 25 (39.1) |
Calcium channel blocker | 9 (14.1) |
Digoxin | 9 (14.1) |
Amiodarone | 1 (1.6) |
Aspirin | 13 (20.3) |
Oral anticoagulant | 3 (4.7) |
Categorical variables such as sex, age ≥ or <50 years old, the presence or absence of systemic hypertension, functional class of I/II or III/IV, type of surgery performed (repair or replacement), postoperative mean diastolic gradient and preoperative cardiac rhythm (sinus or atrial fibrillation) were not significantly associated with LARR, with
p-values ranging from 0.14 to 1.0. All echocardiographic variables, including LVEF, decreased significantly after surgery, but the difference in left ventricular systolic volume was not statistically significant (Table
2). Patients with LARR had smaller preoperative left ventricular systolic volume values and higher LVEF values (
p =0.022, 0.034, respectively); other preoperative variables were not significantly different between patients with or without LARR (Table
3). Stepwise multiple regression analysis revealed that LVEF was the only preoperative variable significantly associated with LARR (odds ratio, 1.086; 95% confidence interval, 1.002–1.178). A cutoff value of 63.5% for preoperative LVEF identified patients with LARR ≥25% after surgery, with a sensitivity of 72% and a specificity of 56%.
Table 2
Echocardiographic variables
LAVI (mL/m2) | 85.5 ± 36.8 | 49.7 ± 25.1 | < 0.001 |
LVdD (mm) | 61.0 ± 5.3 | 52.4 ± 5.5 | < 0.001 |
LVsD (mm) | 38.3 ± 5.2 | 35.3 ± 6.0 | < 0.001 |
LVdV (mL) | 133.8 ± 40.1 | 98.2 ± 32.1 | < 0.001 |
LVsV (mL) | 46.5 ± 23.3 | 41.6 ± 19.8 | 0.23 |
LVEF (%) | 66.1 ± 7.5 | 59.1 ± 9.1 | < 0.001 |
Table 3
Comparison of age and preoperative echocardiographic variables of patients with or without postoperative left atrium reverse remodeling
Age (years) | 50.3 ± 17.3 | 53.3 ± 14.3 | 0.42 |
LAVI (mL/m2) | 77.3 ± 39 | 88.4 ± 36 | 0.15 |
LVdD (mm) | 61,6 ± 5.4 | 60.8 ± 5.3 | 0.75 |
LVsD (mm) | 39.8 ± 5.0 | 37.8 ± 5.1 | 0.25 |
LVdV (mL) | 151 ± 46 | 128 ± 37 | 0.050 |
LVsV (mL) | 60 ± 28 | 42 ± 20 | 0.022 |
LVEF (%) | 63 ± 9.0 | 67 ± 6.7 | 0.034 |
RV (mL) | 88 ± 27 | 96 ± 45 | 0.88 |
EROA (cm2) | 0.56 ± 0.18 | 0.60 ± 0.24 | 0.83 |
Analysis of intra- and interobserver variability showed a high and significant correlation in LAVI measures (r =0.97; p <0.0001) with a mean difference of 8.7% (p =0.10). The mean difference between the 2 LAVI measurements by the same observer was 9.3% (p =0.10) and the measurements were highly correlated (r =0.98; p <0.0001).
Discussion
We found that LARR occurs frequently after surgery for chronic severe MR and that preoperative LVEF is the only variable significantly associated with a postoperative LAVI reduction of at least 25%.
The percentage of patients in our study with LARR after mitral valve repair or replacement is similar to other study populations previously described [
12‐
17]. Many factors have been reported as determinants of LARR after mitral regurgitation surgery. These include MR etiology, patient age, preoperative LAVI, cardiac rhythm, mitral valve double dysfunction with predominant MR, systemic arterial pressure, diastolic mitral pressure gradient, postoperative reduction in left ventricle diastolic volume, and residual mitral regurgitation after surgery [
13‐
17]. Prior studies differed from ours regarding the etiology of MR, the criteria used to define LARR, the techniques used to analyze left atrial size, and the statistical methods employed. In our study, a preoperative LVEF of 63.5% or higher identified those patients with at least 25% LARR. This is interesting, since LVEF in MR is an important prognostic factor for postoperative LVEF and functional class, and a determinant for surgical correction in asymptomatic patients. A LVEF of 63.5% is close to the 60% recommended as the threshold for surgery in most guidelines and similar to the finding of a recently published study [
18,
19,
23,
24].
Left atrial size in patients with chronic mitral regurgitation increases with the severity of the regurgitant volume and with the duration and progression of the disease [
1‐
3]. Also influencing left atrial dilation, LVEF is known to deteriorate in patients with advanced MR, and diastolic dysfunction may occur [
2,
3]. As long as left atrial dilation persists or progresses, interstitial wall fibrosis and hypertrophy may develop and make reversal remodeling after surgery less likely [
25‐
27] This may be a reason for the observed association of better preoperative LVEF with postoperative LARR in our study. After successful mitral-valve surgery with reduction in left ventricular volume, a decline in left ventricular filling pressure may have occurred, facilitating left atrium emptying and reverse remodeling.
As suggested by recent study, reducing mitral-regurgitation volume may be an important determinant of LARR after mitral-valve intervention [
23]. This may have been an important reason for the observed LAVI reduction in the present study, since all patients had severe preoperative regurgitant volume and no more than mild postoperative mitral regurgitation. These were predefined conditions to select patients for the study and may explain why both were not associated to LARR.
Some studies define LARR as a reduction of at least 15% in LAVI, but others do not define a cutoff value [
12‐
17]. Failing to use a criterion, or using an inadequate cutoff value, may mean that the observed reduction fell within the range of inter- and intraobserver variability, or that the reduction had a small degree of clinical significance and consequently influenced both the quantitative identification of LARR and the determination of predictor factors. Our use of a reduction in LARR of at least 25% may have been important in the search for preoperative predictors. This value, higher than that used in other studies, was able to overcome the intra- and interobserver variability in left atrium volume measures and may therefore be more clinically relevant.
Considering the known association between increased left atrial size and cardiac events in patients with MR [
10,
11] and the fact that early surgery may avoid excess left atrial dilation, it seems reasonable to point out that LARR after MR surgery may be beneficial. A recent large multicenter study using propensity-score matching found that early surgery in patients with MR due to flail leaflets was associated with less heart failure and lower mortality than medical management. However, there was no difference in atrial fibrilation, which is usually associated with a large left atrium [
28]. In our study, preoperative atrial fibrillation was not associated with postoperative LARR; of 12 patients with preoperative atrial fibrillation, 2 recovered sinus rhythm after surgery. Another retrospective study did not find association between LARR and reduction of cardiovascular events, mortality and atrial fibrillation [
29]. Further studies are needed to verify the prognostic benefits of LARR after mitral-valve surgery in patients with MR.
Study limitations
The time between postoperative echocardiography and surgery was relatively short in our study. Because of our method of patient selection, the results of this study may not be applicable to patients with MR from other causes, to patients with acute mitral insufficiency or to those with more than mild residual MR. Despite in our study the type of surgery was not related to LARR, a finding similar to other study [
16], due to relative small number of patients and variations in type and size of prosthetic valves, we were not able to analyze separately patients who underwent mitral valve repair or replacement. Finally, 3-dimensional echocardiography was not used in our study, although it seems to be slightly more precise for determining LA volume compared with 2-dimensional echocardiography, and facilitates functional analysis.
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Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
LMR: study conception and designing, carried out patient selection and clinical assistance, data acquisition and analyzes and participated in the draft of the manuscript. ZMM: carried out patient selection and clinical assistance, and participated in the draft of the manuscript. DCSLB: Performance of echocardiographic studies with data acquisition, and interobserver variability. RBMB: Performance of echocardiographic studies with data acquisition, and intra and interobserver variability. ACC: study conception and designing, and critical review for important intellectual content. VAM: study conception and designing, data analyzes, participated in the draft of the manuscript, responsible for final changes and corrections, and submission to the journal. All authors read and approved the final manuscript.