Left Atrial Remodeling in Segmental vs. Global Mitral Valve Prolapse　– Three-Dimensional Echocardiography –

Abstract

Background: Segmental and global mitral valve prolapse (MVP) comprise 2 representative phenotypes in this syndrome. While mitral regurgitation (MR) severity is a major factor causing left atrial (LA) remodeling in MVP, prominent mitral valve (MV) annulus dilatation in global MVP may specifically cause inferiorly predominant LA remodeling. We compared MV annulus and LA geometry in patients with segmental and global MVP.

Methods and Results: LA volume as well as inferior, middle, and superior LA cross-sectional areas (CSA) were measured on 3-D echocardiography in 20 controls, in 40 patients with segmental MVP, and in 18 with global MVP. On multivariate analysis, MR severity was primarily associated with LA dilatation in segmental MVP (P<0.001), while MV annular dilatation was primarily associated with LA dilatation in global MVP (P<0.001). Although there was no regional predominance in LA dilatation in segmental MVP, inferior predominance of LA dilatation was significant in global MVP (increase in inferior, middle, and superior LA-CSA relative to mean of the controls: +220±70% vs. +171±55% vs. +137±37%, P<0.001).

Conclusions: LA remodeling in segmental and global MVP is considerably different regarding its association with MR volume or MV annular dilatation and its regional predominance. While MR volume may mainly contribute to LA remodeling in segmental MVP, MV annular dilatation seems to have an important role in LA remodeling in global MVP. (Circ J 2016; 80: 2533–2540)

Mitral valve prolapse (MVP) is a syndrome involving systolic superior displacement of the closed mitral valve (MV) leaflets beyond the annular level.^1,2 One typical phenotype is segmental MVP with modest leaflet enlargement, chordal elongation or rupture, not thick leaflets, only mild annular dilatation, and mild-severe holo-systolic mitral regurgitation (MR).³ This segmental MVP is also called fibroelastic deficiency.² Another phenotype is global MVP with advanced leaflet enlargement, chordal elongation or rupture, thick leaflets, prominent annular dilatation, and mild–severe late-systolic MR.^1,3,4 This global MVP is also called Barlow’s disease. While the degree of MR is a major determinant of left atrial (LA) remodeling in MVP,⁵ the role of MV annular dilatation in LA remodeling is not fully investigated.

Given that the MV annulus is anatomically connected to the inferior LA, prominent MV annular dilatation in global MVP can be associated with adjacent and inferior LA remodeling specifically in this group. In addition, this prominent MV annular dilatation in global MVP is frequently associated with only mild MR.⁶ This suggests that MV annular dilatation may be associated with adjacent and inferior LA remodeling independently from the degree of MR, especially in patients with global MVP (Figure 1).⁷ In addition, such inferiorly predominant LA remodeling may not be proportional to severity of heart failure (HF) due to its potential discrepancy with MR severity. These characteristics of LA remodeling in global MVP, however, have not been fully investigated.

Figure 1.

Potential differences in left atrial (LA) remodeling between segmental and global mitral valve prolapse (MVP). Patients with segmental MVP may have only mild mitral valve (MV) annular dilatation and generalized dilatation of the whole LA, which is proportional to mitral regurgitant (MR) severity. In contrast, patients with global MVP may have prominent MV annular dilatation and inferiorly predominant LA dilatation, which may not be proportional to MR severity. LV, left ventricle.

We, therefore, hypothesized that LA remodeling associated with segmental MVP may show general dilatation without regional predominance, which is proportional to MR and HF severity, while LA remodeling with global MVP can be predominant in its inferior region, which is proportional to MV annular dilatation and may not have a close correlation with MR or HF severity (Figure 1). The purpose of this investigation was to investigate and compare characteristics of LA remodeling in patients with segmental and global MVP on 3-D echocardiography. This is important because LA dilatation is a major prognostic marker of MVP, requiring accurate interpretation for clinical decision making.

Methods

Subjects

We prospectively enrolled 58 consecutive patients with MVP who underwent clinically indicated echocardiography, including 3-D transthoracic echocardiography (TTE). MVP was defined as systolic superior displacement (>2.0 mm) of MV leaflets into the LA beyond the annular level.⁸ Patients with other organic heart disease were excluded. Patients with atrial fibrillation were also excluded due to the difficulty in performing 3D-TTE. Segmental MVP was defined as single segment or multiple segment billowing in a single leaflet, and global MVP was defined as multisegmental MV billowing in both leaflets on multiplane echocardiography.³ Accordingly, 40 patients were classified as having segmental MVP and 18, global MVP. From a pool of subjects undergoing clinically indicated echocardiography, 20 healthy subjects were randomly selected for the controls. The study was approved by an institutional ethical review board and informed consent was obtained from all patients.

3D-TTE Protocol

In addition to standard 2-D Doppler echocardiography, 3D-TTE was performed using an iE33 ultrasound system (Philips Healthcare, Andover, MA, USA) equipped with a 2.5-MHz transducer, with the patient in the left lateral decubitus position. Management and maintenance of echocardiography equipment was carried out according to guidelines.⁹ Full-volume datasets via the apical approach were acquired from 4 to 6 consecutive cardiac cycles. Care was taken to include the entire left ventricle (LV) and LA within the imaging volume, using automatically generated simultaneous 2-D reference planes.

LV Volume Measurements Image analysis was performed using commercially available software (QLAB 3DQ-Adv, Philips). From the full volume datasets, 2 orthogonal LV long-axis views and 1 short-axis view were selected. In the end-diastolic image, 5 endocardial reference points were placed manually on septal and lateral MV annuli in the 4-chamber cut plane, on anterior and inferior MV annuli in the 2-chamber cut plane, and on the LV apex. The semi-automatically derived endocardial contour was manually adjusted. The process was repeated at end-systole. From the voxel count inside the endocardial contours, LV end-diastolic and end-systolic volumes (EDV and ESV, respectively) and LV ejection fraction (LVEF) were derived.

LA Volume, LA Cross-Sectional Areas and MV Annular and Leaflet Structure End-systolic maximum LA volume (LA_max) was measured using the same method as that for the LV volume just before the MV opening. Manual adjustment was done to ensure that the LA long axis was delineated accurately. Five reference points were placed on the septal, lateral, anterior, and inferior MV annuli, and on the LA roof. After semi-automatic endocardial contour visualization, manual adjustment was performed if needed. Minimum LA volume in end-diastole (LA_min) and mid diastolic LA volume prior to atrial contraction (LA_pre-A) were also measured. Total LA emptying index [(LA_max–LA_min)/LA_max], passive LA emptying index [(LA_max–LA_pre-A)/LA_max], and active LA emptying index [(LA_pre-A–LA_min)/LA_pre-A] were calculated as LA functional indices. The LA long axis was trisected to determine the inferior, middle, and superior LA (Figure 2A). LA cross-sectional area (CSA) in the inferior, middle, and superior levels at end-systole was measured in cross-sectional image planes, perpendicular to the LA long axis and parallel to the MV annulus. Figure 2B–D shows measurement of CSA of the inferior LA. CSA of the middle and superior LA were similarly measured.

Figure 2.

Measurement of inferior, middle, and superior left atrial (LA) cross-sectional areas (CSA). (A) Inferior, middle, and superior LA according to trisection of the LA long axis. (B,C) Level of cross-section of the inferior LA in the apical 4- and 2-chamber views. (D) Cross-sectional plane of the inferior LA and measurement of area. CSA of the middle and superior LA was measured in the same way. LV, left ventricle.

The MV annular dimensions in the apical 4- and 2-chamber views were measured to obtain MV annular area assuming an elliptical shape.¹⁰ From the 3D-TTE dataset, total leaflet billow volume as well as annular height to commissural width ratio (AHCWR) were measured using custom software (Real view^®, YD, Nara, Japan) as previously described.¹¹

Chordal rupture was defined as fluctuating chordal tendineae or flail mitral leaflets in the LA cavity during systole.¹² In contrast, chordal elongation was defined as MVP without chordal rupture. In diastole, the thickness of the anterior and posterior MV leaflets were measured in parasternal long axis view at the mid-portion of the leaflets between the annulus and tip.¹³

MR Severity, Direction and HF Severity MR volume was quantified on Doppler echocardiogram, using a continuity equation (CE). The mitral filling volume was calculated as LVEDV-LVESV. The aortic ejection stroke volume was calculated as the product of the LV outflow tract area and the velocity-time integral of ejection flow. The MR volume was then calculated as the difference between the mitral filling volume and the aortic ejection volume. In 38 patients with continuous wave Doppler recording of MR jet, MR was also quantified using the proximal isovelocity surface area (PISA) method.¹⁴ Moderate or greater MR was defined as MR volume ≥30 ml/beat. On color Doppler echocardiography, MR jet direction was determined as central or wall jet.¹⁴ Tricuspid regurgitant (TR) pressure gradient, mitral flow early diastolic (E) velocity, as well as mitral flow to annular tissue velocity ratio (E/E’) were used to describe HF severity.¹⁵

Statistical Analysis

Categorical variables are presented as frequencies and continuous variables as mean±SD. Continuous variables were compared using the unpaired t-test or Mann-Whitney U-test according to the data distribution. Differences between proportions were assessed on chi-squared analysis. One-way analysis of variance followed by post-hoc analysis with Bonferroni test was used to compare 3 groups. CE-derived and PISA-derived MR volumes were compared on linear regression with Pearson correlation coefficients, and agreement between CE and PISA was evaluated using Bland-Altman analysis by calculating mean difference (bias) and 95% limits of agreement (defined as 2 SD around the mean). Correlations between LA volume vs. MV annular area, MR volume and other indices, and correlations between indices of HF severity vs. LA volume and MR volume were explored on Pearson analysis. To evaluate the contribution of the different variables to LA enlargement, the key clinical and echocardiographic variables, including age, LVEDV, LVEF, MV annular area, MV billow volume, AHCWR and MR volume were entered into multivariate linear regression analysis. P<0.05 was considered statistically significant. Analysis was performed with JMP version 10.0 (SAS Institute, Cary, NC, USA).

Results

Patient Characteristics

Clinical subject characteristics were generally similar between groups, except for the difference in systolic and diastolic blood pressure with regard to segmental vs. global MVP (Table 1). EF was similar between the 3 groups, but LV volume was larger in the MVP groups. Compared with controls, MR volume was significantly greater for both segmental and global MVP (P<0.01). Compared with segmental MVP, MR volume tended to be smaller and the incidence of moderate or severe MR significantly smaller for global MVP. In 38 patients with both CE and PISA volumes, CE-derived MR volume correlated well with the PISA-derived volumes (r=0.96), and on Bland–Altman analysis there was no significant differences between CE- and PISA-derived MR volume, as reflected by the minimal bias of 1.7 ml and 95% limits of agreement at ±7.1 ml.

Table 1. Subject Clinical and Echocardiographic Characteristics

Variable	Control (n=20)	MVP
		Segmental (n=40)	Global (n=18)
Clinical
Age (years)	58±13	62±17	55±13
Male	9 (45)	21 (53)	10 (56)
SBP (mmHg)	126±11	135±19	124±17†
DBP (mmHg)	74±9	78±14	68±9†
Heart rate (beats/min)	60±8	67±11*	65±12
Hypertension	0 (0)	16 (41)	5 (28)
Hyperlipidemia	0 (0)	10 (26)	2 (11)
Diabetes mellitus	0 (0)	2 (5)	0 (0)
Echocardiographic measurements
End-diastolic LV volume (ml/m2)	50±7	76±20*	81±17*
End-systolic LV volume (ml/m2)	18±5	28±10*	31±9*
LVEF (%)	65±7	63±7	62±6
LA volume (ml/m2)
Maximum (end-systole)	25±6	48±17*	51±21*
Pre-A (mid diastole)	16±6	34±15*	36±20*
Minimum (end-diastole)	11±4	28±14*	30±16*
LA function
Total emptying index	55±9	45±11*	43±11*
Passive emptying index	35±9	31±9	25±8*
Active emptying index	31±9	21±11*	24±11
MR volume (ml)	1±4	36±18*	27±22*
Moderate-severe MR	0 (0)	26 (65)	6 (33)†
LA volume/MR volume	–	2.3±1.0	4.3±2.5†
MV and LA structure
Prolapse site
P2	–	15 (38)	0 (0)
P3	–	10 (25)	0 (0)
P1+P2	–	2 (5)	0 (0)
P2+P3	–	1 (3)	0 (0)
A2	–	5 (13)	0 (0)
A3	–	5 (13)	0 (0)
Other segments	–	3 (8)	0 (0)
Both leaflets	–	0 (0)	18 (100)
Jet direction (central)	–	0 (0)	10 (56)†
Chordal rupture	0 (0)	20 (59)	3 (17)†
AL thickness (mm/m2)	0.8±0.1	1.1±0.3*	1.4±0.4*,†
PL thickness (mm/m2)	0.7±0.1	1.2±0.4*	1.3±0.5*
MV annular area (cm2/m2)	4.7±0.8	6.1±1.4*	9.2±3.0*,†
Increase vs. mean of controls (%)		131±31	197±64†
AHCWR	13.1±4.0	10.9±4.2	9.2±5.0*
MV billow volume (ml/m2)	−0.1±0.1	0.6±0.5*	3.5±2.5*,†
Inferior LA CSA (cm2/m2)	5.2±1.4	8.7±2.5*	11.4±3.6*,†
Increase vs. mean of controls (%)		159±39	220±70†,‡,§
Middle LA CSA (cm2/m2)	6.3±1.8	11.1±3.3*	10.5±3.3*
Increase vs. mean of controls (%)		172±46	171±55
Superior LA CSA (cm2/m2)	6.1±2.0	10.0±3.0*	8.2±2.2*,†
Increase vs. mean of controls (%)		160±44	137±37†
LA longitudinal length (cm/m2)	3.4±0.5	4.0±0.7*	4.0±0.7*

Data given as mean±SD or n (%). P<0.05 *vs. control, ^†vs. segmental MVP, ^‡vs. middle LA, ^§vs. superior LA. AHCWR, annular height to commissural width ratio; AL, anterior leaflet; CSA, cross-sectional area; DBP, diastolic blood pressure; EF, ejection fraction; LA, left atrium; LV, left ventricle; MR, mitral regurgitation; MV, mitral valve; MVP, mitral valve prolapse; PL, posterior leaflet; pre-A, pre-atrial contraction; SBP, systolic blood pressure.

MV and LA Structure/Function Characteristics in Segmental vs. Global MVP

Prolapse site differed for segmental vs. global MVP by definition (Table 1). Incidence of wall jet was also more frequent for segmental MVP compared with global MVP (P<0.01). Chordal rupture was more frequent for segmental MVP (P<0.01). Leaflet thickness tended to increase in patients with global MVP.

Compared with the controls, both of the MVP groups had a significantly larger MV annulus (P<0.01). In addition, compared with segmental MVP, MV annular area was further significantly greater for global MVP (P<0.0001). Similarly, AHCWR tended to be reduced for segmental MVP (vs. control, P=0.07), and further reduced for global MVP (P<0.01). MV billow volume was increased in patients with segmental MVP (vs. control, P<0.05), and further increased for global MVP (P<0.0001). Compared with controls, LA volume was significantly greater in both MVP groups (P<0.0001). In contrast to MV annular dilatation, LA volume was similarly increased for both segmental and global MVP (P=0.6). Consequently, compared with segmental MVP, LA volume to MR volume ratio was significantly greater for global MVP. LA functional indices were significantly or tended to be reduced for both segmental and global MVP compared with controls. Increases in inferior, middle, and superior LA CSA relative to the mean of the control group were not significantly different at all levels for segmental MVP, demonstrating the absence of regional predominance in LA remodeling in this group. In contrast, increase in inferior LA CSA was significantly greater than for middle and superior LA in patients with global MVP (P<0.01 and P<0.001, respectively), demonstrating the inferior region predominance of LA remodeling in global MVP. Compared with controls, LA remodeling in the long axis direction in both groups was significant (P<0.01) and similar.

Factors Associated With LA Remodeling in Segmental and Global MVP

The association between LA volume and MV leaflet prolapse site was evaluated in patients with segmental MVP. LA volume was not significantly different between those with and without P2 prolapse (51±16 ml/m² vs. 46±18 ml/m², P=0.3), with and without P3 prolapse (50±18 ml/m² vs. 48±17 ml/m², P=0.8), and between those with and without anterior leaflet prolapse (44±19 ml/m² vs. 50±16 ml/m², P=0.3). In addition, LA volume was not significantly different between patients with central jet and those with wall jet (49±21 ml/m² vs. 49±18 ml/m², P=1.0).

In segmental MVP, there was a good and significant correlation between LA volume and MR volume, while the correlation between LA volume and MV annular area was significant but relatively weak (Figure 3, left 2 panels). In global MVP, however, the correlation between LA volume and MR volume was significant but relatively weak, while the correlation between LA volume and MV annular area was good and significant (Figure 3, right 2 panels). On multivariate analysis of LA volume in segmental MVP, a significant association with MR volume along with MV annular dilatation and aging was identified (Table 2). In contrast, on multivariate analysis of LA volume in global MVP, significant associations with MV annular dilatation and with MR volume were identified (Table 2). This suggests that MR severity is a significant indicator of LA remodeling in segmental MVP, while in global MVP, MV annular dilatation is a significant indicator of LA remodeling.

Figure 3.

Left atrial (LA) volume vs. mitral regurgitant (MR) volume or mitral valve (MV) annular area in segmental vs. global mitral valve prolapse (MVP). LA volume correlated well with MR volume, but not as well with MV annular area in segmental MVP (left 2 panels). In contrast, LA volume had a weak correlation with MR volume, while it correlated well with MV annular area in global MVP (right 2 panels).

Table 2. Factors Associated With LA Volume

Variables	Univariate		Multivariate
	β	P-value	β	P-value
Segmental MVP
Age	0.57	0.002	0.28	0.0003
LVEDV	0.68	<0.0001
LVEF	−0.04	0.8
MV annular area	0.43	0.006	0.38	<0.0001
MV billow volume	0.35	0.04
AHCWR	−0.09	0.6
MR volume	0.77	<0.0001	0.70	<0.0001
Global MVP
Age	0.25	0.3	0.20	0.06
LVEDV	0.62	0.006
LVEF	−0.24	0.3
MV annular area	0.81	<0.0001	0.74	<0.0001
MV billow volume	0.67	0.002
AHCWR	0.16	0.5
MR volume	0.56	0.02	0.38	0.002

LVEDV, left ventricular end-diastolic volume. Other abbreviations as in Table 1.

LA Volume vs. MR Severity, HF Parameters and LA Function

Mitral E velocity, E/E’, and TR pressure gradient were all significantly correlated with LA volume in segmental MVP (P<0.05), suggesting that LA dilatation reflects the severity of HF in this group. Increase in LA volume, however, was associated with none of these HF parameters in global MVP, suggesting that LA dilatation may not necessarily reflect HF severity in this group. In addition, MR volume was significantly associated with TR pressure gradient in segmental MVP (r=0.46, P<0.01), but not in global MVP.

Increase in LA volume was correlated with reduced LA function (total LA emptying index, r=–0.59, P<0.001; passive LA emptying index, r=–0.56, P<0.001; and active LA emptying index, r=–0.53, P<0.01) in segmental MVP. Similarly, increase in LA volume was significantly or tended to be, correlated with reduced LA function (total LA emptying index, r=–0.50, P<0.05; passive LA emptying index, r=–0.23, P=0.4; and active LA emptying index, r=–0.64, P<0.05) in global MVP.

Representative Patients

Figure 4 shows 2 representative patients: 1 with segmental MVP, mild MV annular dilatation, severe MR, HF symptoms and general LA remodeling without regional predominance (Figure 4A); and 1 with global MVP, prominent MV annular dilatation, only mild MR without HF, and LA remodeling with inferior predominance (Figure 4B). Differences in the LA remodeling between the 2 patients with segmental and global MVP are clear.

Figure 4.

Representative patients with (A) segmental and (B) global mitral valve prolapse (MVP). (A) This patient has segmental MVP (arrowheads), only mild mitral valve (MV) annular dilatation (small yellow arrows), severe mitral regurgitation (MR; not shown), and generalized left atrial (LA) remodeling (large green arrows). (B) This patient has global MVP (arrowheads), prominent MV annular dilatation (small yellow arrows), only mild MR (not shown), and inferiorly predominant LA remodeling (large green arrows). RV, right ventricle.

Discussion

In the present study, associations of LA dilatation with other factors were considerably different in segmental vs. global MVP. In patients with segmental MVP, association of LA dilatation with MR volume was strong and significant, while the association with MV annular dilatation was significant but not as strong. In global MVP, however, association of LA dilatation with MR volume was only fair, while the association with MV annular dilatation was significant. In addition, compared with segmental MVP, LA volume to MR volume ratio was significantly greater in global MVP. Significant LA dilatation with only mild MR was observed frequently in global MVP. Further, there was no clear regional predominance of LA dilatation in segmental MVP, while inferior predominance of LA remodeling was significant in global MVP. Finally, LA dilatation in segmental MVP was proportional to HF severity, while LA dilatation in global MVP was not necessarily proportional to HF severity. These results support the present hypothesis. Therefore, characteristics of LA remodeling differ considerably for segmental vs. global MVP, suggesting different mechanisms and clinical implications of LA remodeling between the 2 groups.

Potential Mechanism

The characteristics of LA remodeling in segmental MVP are not surprising. Although a causal relationship has not been established, it is possible that MR causes global LA dilatation without regional predominance. The characteristics of LA remodeling in global MVP are considerably different and suggest the possibility of primary dilatation of the MV annulus, as opposed to its secondary dilatation due to MR, leading to inferiorly predominant LA dilatation. MV annular dilatation and flattening with no or only mild MR, suggesting its primary nature, has recently been reported.^16,17 The present study is consistent with these, and further, suggests that primary MV annular dilatation/flattening may promote inferior LA remodeling. Further studies are required to establish the suggested mechanism.

Clinical Implications

When MR can be eliminated by surgical leaflet repair, it is controversial as to whether ring annuloplasty is still required.¹⁸ Potential problems with MV annular dilatation have been reported. Morrel et al have reported that MV annular dilatation augments stresses on posterior LV base as well as on MV leaflets.¹⁹ The present study suggests that MV annular dilatation may promote adjacent and inferior LA dilatation with a potential to cause unfavorable events. These suggest that reduction of dilated MV annulus may be beneficial even when MR is repaired by other procedures. These can also be considerations for early surgery with ring annuloplasty to preserve LA integrity and prevent complications. The potential benefits of MV annular size reduction per se, as opposed to those of eliminating MR, require further study and would be especially important in deciding between surgical MV plasty with annulus reduction or a catheter-based approach without annular intervention.^20,21

The LA volume is usually proportional to severity of HF.²² In the present study, this was confirmed in segmental MVP. In global MVP, however, LA volume was not necessarily proportional to HF severity. Given that prominent MV annular dilatation without significant MR is frequent in global MVP, inferiorly predominant LA dilatation without HF is possible in this group. Careful phenotype-specific interpretation is required in evaluating HF severity using LA volume. Increased MR volume is usually proportional to severity of HF.²³ This was also confirmed in patients with segmental MVP in this study. In global MVP, however, increased MR volume was not necessarily proportional to HF severity. This suggests that LA dilatation in global MVP may modify LA compliance and reduce the increase in LA pressure by MR. This potential influence of LA dilatation may be beneficial in the reduction of HF symptoms, but it may also be problematic by masking HF and delaying valve intervention. Careful evaluation of the potential influences of LA dilatation on HF is required for both segmental and global MVP.

Study Limitations

Although the present study has shown that LA remodeling differs considerably between segmental and global MVP, the significance of this is not yet established. A close relationship between LA remodeling and unfavorable outcomes has been established in MVP.^24,25 The question of whether the clinical significance of generalized LA dilatation in segmental MVP, and that of inferiorly predominant LA dilatation in global MVP, differ, remains to be answered. The risks of atrial fibrillation due to LA dilatation in both segmental and global MVP, are extremely important. Given that LA tissue elongation is mainly involved in the genesis of atrial fibrillation,²⁶ atrial fibrillation in segmental MVP may develop with LA dilatation and associated HF, but the fibrillation in global MVP may develop with LA dilatation even in the absence of HF. This was not clarified in the present study. The influences of regional MVP on total LA remodeling, such as LA dilatation by P2 prolapse vs. that by non-P2 prolapse, were not significantly different. The influences of regional MVP or MR wall jet on regional LA remodeling, however, was not clarified. For instance, MR wall jet running on lateral LA by P3 prolapse may specifically dilate lateral LA, but these were not evaluated due to technical difficulties with the current methods.

The aim of this study, however, was fulfilled by demonstrating considerable differences in LA remodeling between patients with segmental and with global MVP. LA remodeling in segmental MVP is primarily associated with MR volume, is proportional to HF severity, and has no regional predominance. In contrast, LA remodeling in global MVP is primarily associated with MV annular dilatation, is not necessarily proportional to HF severity, and has inferior predominance. This suggests differing mechanisms and significance of LA remodeling in segmental and global MVP, requiring phenotype-specific evaluation and further studies.

Funding Sources

S.F., K.M., M.E., Y. Nishimura, S.T. and Y. Otsuji were supported by Grants-in-aid for Scientific Research from the Japan Society of the Promotion of Science (15K10226 for S.F., K.M., M.E., Y. Nishimura, S.T. and Y. Otsuji, and 15K01346 for Y. Otsuji).

Disclosures

None.

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