Echocardiographic Indices for Optimal Timing of Mitral Valve Repair in Degenerative Mitral Regurgitation in Japanese Patients

Abstract

Background: Left ventricular (LV) dysfunction after mitral valve (MV) repair for degenerative mitral regurgitation (DMR) is a poor prognostic factor. Preoperative LV end-systolic diameter (LVESD) and LV ejection fraction (LVEF) are used in guidelines as indices for LV dysfunction, with cut-off values of 60% for LVEF and 40 mm for LVESD. However, these factors have received little validation in Japanese patients.

Methods and Results: We evaluated preoperative echocardiographic data in 322 Japanese patients who underwent MV repair for DMR to identify factors associated with postoperative LV dysfunction. Postoperative LV dysfunction was observed in 31 (10%) patients, who had greater LVESD (39±6 mm vs. 33±5 mm; P<0.001) and lower LVEF (62±5% vs. 67±5%; P<0.001) preoperatively, compared with the non-LV dysfunction group. The optimal threshold of preoperative LVESD and LVEF for predicting postoperative LV dysfunction in receiver operating characteristic curve analysis was 36 mm (AUC=0.819; P<0.001) and 61% (AUC=0.706; P<0.001), respectively. Kaplan–Meier analysis showed a significantly lower rate of avoided adverse cardiac events in the LV dysfunction group (P<0.001).

Conclusions: The criteria for LVESD in MV repair in patients with DMR should be lower than the values indicated by the guidelines. Adoption of these revised criteria may improve prognosis after surgery in Japanese patients.

Central Figure

Mitral valve (MV) repair is currently the standard treatment for degenerative mitral regurgitation (DMR).^1,2 While the reported long-term clinical outcomes after MV repair are good,^3,4 postoperative left ventricular (LV) dysfunction after repair is a poor prognostic factor.^5,6 Accordingly, the guidelines recommend MV repair for DMR with already reduced LV function, even in asymptomatic patients.⁷ Preoperative LV dysfunction was defined in the JCS/JSCS/JATS/JSVS 2020 Guidelines on the Management of Valvular Heart Disease as an LV ejection fraction (LVEF) of 60% or less or LV end-systolic diameters (LVESD) of 40 mm or more.⁷ However, these indices were calculated based on surgical outcomes obtained in the 1970s–1990s, including MV replacement, and may not be suitable for use in determining indications for MV repair in recent years. In addition, little validation in Japanese patients has been reported. Because body size and echocardiographic parameters differ between Japanese and Western populations, population-specific data are needed to determine the surgical indications for DMR in Japanese patients.^8,9

Here, we aimed to determine echocardiographic parameters for the optimal timing of MV repair for DMR by investigating preoperative echocardiographic data related to postoperative LV dysfunction and the association between postoperative LV dysfunction and prognosis.

Methods

Study Design

We retrospectively studied 411 consecutive patients who underwent MV repair for DMR at Chiba University Hospital or Kawasaki Saiwai Hospital between April 2014 and December 2023. The indication for MV repair for DMR was determined according to the valvular heart disease guidelines, with cases meeting the criteria of LVEF ≤60%, LVESD ≥40 mm, atrial fibrillation, and pulmonary hypertension judged to be candidates for MV repair. Furthermore, 155 patients who did not fit any of these indications were discussed at the heart team conference on a case-by-case basis and determined to have high repairability, and subsequently underwent MV repair. We excluded patients with low EF due to the complication of tethering of valve leaflets and possible requirement for additional procedures, such as papillary muscle suspension, which differed from standard MV repair for DMR. As the lower limit of the LVEF normal range in the ASE guidelines¹⁰ is 52% for men and 54% for women, the excluded cut-off value for LVEF was set at 55%, which includes abnormal values for both men and women. Patients with intraoperative myocardial infarction and significant residual MR immediately after surgery were also excluded because these are poor prognostic factors regardless of the presence or absence of preoperative myocardial damage. As a result, we excluded 19 patients with an LVEF less than 55% or with asynergy preoperatively, 30 who underwent concomitant aortic valve surgery, 2 with intraoperative myocardial infarction, 36 without follow-up echocardiography evaluation within the defined term, and 2 with residual regurgitation greater than moderate in the immediate postoperative period. Finally, 322 patients were available for analysis.

Preoperative transthoracic echocardiography (TTE) was performed within 1 month before MV repair, postoperative TTE was performed before discharge, and follow-up TTE was performed 6–12 months after MV repair.

Patients were divided into 2 groups: an LV dysfunction group, defined by postoperative LV dysfunction with an LVEF less than 50% based on follow-up TTE performed 6–12 months postoperatively; and a non-LV dysfunction group. Predictors of postoperative LV dysfunction were identified by comparison of the 2 groups for various factors, including preoperative TTE findings. Major adverse cardiac events were classified as cardiovascular death and heart failure hospitalization, and their rates of avoidance between the 2 groups were compared. Furthermore, the 2 groups were divided into 4 groups based on postoperative LVEF trend to investigate the relationship between postoperative LVEF trend and prognosis.

TTE

TTE was performed preoperatively, postoperatively, and during the follow-up period as routine clinical practice using the EPIQ system and X5-1 transducers (Philips Medical Systems, Andover, MA, USA) or Vivid E9 and M5S transducers (GE Vingmed, Horten, Norway) using standard methods according to the guidelines of the American Society of Echocardiography and European Association of Cardiovascular Imaging.¹⁰ Left atrial diameter, LV end-diastolic diameter (LVEDD), and LVESD were measured in the parasternal long-axis view. LVEDD index and LVESD index were calculated by dividing the EDD and ESD by body surface area (BSA), respectively. LVEF was measured using the modified Simpson method in the apical view. E wave of trans mitral flow was measured in the apical view. The value of e′ was the average of the septal and lateral sides of the MV annulus. Right ventricular systolic pressure was determined from peak tricuspid regurgitant jet velocity using the simplified Bernoulli equation; this value was combined with an estimate of right atrial pressure based on the size and respiratory collapsibility of the inferior vena cava.

Operative Procedure

MV repair in this study was performed via a median sternotomy approach (n=284; 88%) or a minimally invasive cardiac surgery approach (n=38; 12%). Posterior leaflet lesion and commissure leaflet prolapse were repaired by leaflet resection, neo-chordal placement, or both. Anterior leaflet prolapse was repaired by neo-chordal placement. Edge-to-edge repair was added when needed. The surgeon in charge of each patient determined the range and shape of the resection. Ring annuloplasty was performed in all cases. The type and size of the ring were chosen based on the surgeon’s preference according to MV morphology.

Statistical Analysis

Continuous variables are expressed as mean±standard deviation and categorical variables are summarized as percentages and counts. Continuous variables between patient groups were compared using the Student’s t-test. Differences in proportions were examined using the χ² test or Fisher’s exact test when the number of observations was small. A P value <0.05 was considered significant. Associated variables in univariable analyses (P<1.00) were considered for inclusion in the multivariable logistic regression analysis model to identify predictors of postoperative LV dysfunction after MV repair. Multicollinearity among parameters was confirmed using a variance inflation factor greater than 3 as the cut-off value. Optimal cut-off values for the prediction of TTE parameters were obtained from receiver operating characteristic (ROC) curve analysis, and areas under the curve (AUC) were calculated. Delong’s test was used to compare AUCs between parameters. Kaplan-Meier analysis was used to determine the event-free survival rate, and the difference between groups was analyzed using the log-rank test. Major adverse cardiovascular events were defined as cardiac death or hospital admission for heart failure. All statistical analyses were performed using the JMP software program, version 18.0.0 (SAS Institute Inc., Cary, NC, USA). This study was approved by Chiba University Hospital and Kawasaki Saiwai Hospital Ethics Committee (reference no. HK202411-14).

Results

A total of 31 (10%) patients presented with postoperative LV dysfunction on TTE performed during the defined period. Clinical characteristics in patients with and without postoperative LV dysfunction are compared in Table 1. There were 199 (62%) men and 123 (38%) women with a mean age of 61±14 years. The LV dysfunction group tended to be younger than the non-LV dysfunction group. In contrast, the groups did not differ with regard to the degree of heart failure symptoms, B-type natriuretic peptide levels, or percentage of comorbidities.

Table 1.

Comparison of Preoperative Data, Operative Data and Follow-up TTE Data Between Patients With and Without Postoperative LV Dysfunction

	Postoperative LV dysfunction (n=31)	Non-postoperative LV dysfunction (n=291)	P value
Patient characteristic
Age (years)	56±14	61±14	0.048*
Men	24 (77)	175 (60)	0.091
Body surface area (m2)	1.7±0.2	1.6±0.2	0.120
Preoperative NYHA
I	11 (36)	125 (43)
II	15 (48)	118 (41)	0.716
III	5 (16)	43 (14)
IV	0 (0)	4 (2)
BNP (pg/mL)	121±151	121±198	0.998
Comorbidity
Hypertension	13 (42)	154 (53)	0.244
Diabetes	5 (16)	23 (8)	0.226
Chronic kidney disease	8 (26)	44 (15)	0.122
Atrial fibrillation	10 (32)	60 (21)	0.200
Coronary artery disease	6 (19)	28 (10)	0.171
Medication
Calcium channel blocker	8 (26)	81 (28)	0.810
ACEI/ARB	9 (29)	113 (39)	0.219
MRA	9 (29)	57 (20)	0.315
Diuretics	8 (26)	97 (33)	0.517
Statin	5 (16)	64 (22)	0.599
β-blocker	11 (36)	68 (23)	0.136
Antiplatelet drugs	2 (6)	12 (4)	0.888
Preoperative TTE parameters
LAD (mm)	48±8	47±10	0.403
LVEDD (mm)	58±7	53±8	<0.001*
LVEDD index (mm/m2)	35±4	33±5	0.051
LVESD (mm)	39±6	33±5	<0.001*
LVESD index (mm/m2)	23±3	21±3	<0.001*
LVEF (%)	62±5	67±6	<0.001*
RVSP (mmHg)	36±19	33±14	0.319
E value (cm/s)	114±32	116±31	0.664
E/e′	10±5	12±6	0.247
Prolapse site
Anterior mitral leaflet	2 (6)	52 (18)
Posterior mitral leaflet	23 (74)	190 (65)	0.565
Bileaflet prolapse	3 (10)	16 (5)
Commissure leaflet	3 (10)	33 (12)
Effective regurgitant orifice (cm2)	0.49±0.15	0.48±0.16	0.992
Regurgitant volume (mL)	69±16	68±19	0.726
Regurgitant fraction (%)	58±10	54±9	0.145
Operative data
Minimally invasive cardiac surgery approach	4 (13)	34 (12)	0.926
Extracorporeal circulation time (min)	199±41	173±60	0.137
Aorta cross-clamp time (min)	132±36	123±46	0.298
Procedures
Resection and suture	22 (71)	205 (70)	0.883
Chordal replacement	22 (71)	206 (71)	0.852
Prosthetic valve ring
Full ring	10 (32)	121 (42)	0.315
Semi-rigid type	26 (84)	219 (75)	0.397
Concomitant procedure
CABG	6 (19)	28 (10)	0.171
PVI	3 (10)	15 (5)	0.528
Maze	4 (13)	22 (8)	0.489
TAP	8 (26)	53 (18)	0.433
Follow-up TTE parameters
Mean follow-up duration (months)	10±3	10±3	0.751
LVEDD (mm)	50±5	47±6	0.002
LVEDD index (mm/m2)	30±3	29±4	0.002
LVESD (mm)	37±4	31±6	<0.001
LVESD index (mm/m2)	22±3	19±4	<0.001
LVEF (%)	44±7	62±4	<0.001
Residual mitral regurgitation
None	26 (84)	219 (75)
Mild	5 (16)	64 (22)	0.781
Moderate	0 (0)	8 (3)

Data are presented as mean±SD, or n (%). *Significance (P value <0.05). ACEI, angiotensin converting enzyme inhibitors; ARB, angiotensin receptor blockers; BNP, B-type natriuretic peptide; CABG, coronary artery bypass graft; LAD, left atrial diameter; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic diameter; MRA, mineralocorticoid receptor antagonist; NYHA, New York Heart Association; PVI, pulmonary vein isolation; RVSP, right ventricular systolic pressure; TAP, tricuspid annuloplasty; TTE, transthoracic echocardiography.

Preoperative Echocardiographic Parameters

Preoperative TTE parameters of the 2 groups are compared in Table 1. LVEDD and LVESD were greater in the LV dysfunction group than in the non-LV dysfunction group. Although all patients in the study had a preoperative LVEF of 55% or more, postoperative LV dysfunction group patients had lower preoperative EFs than the non-LV dysfunction group. No differences in LV diastolic function or pulmonary hypertension parameters were found. MV prolapse locations were also similar in the 2 groups.

Operative Procedures

Operative procedures in the 2 groups are compared in Table 1. Extracorporeal circulation time and aorta cross-clamp time were similar between the groups. Furthermore, the 2 groups did not differ with regard to the selection of prosthetic valve rings or procedure techniques, and the frequencies of concomitant procedures were also similar.

Follow-up Echocardiographic Parameters

Follow-up TTE was performed on average 10±3 months after surgery. The parameters of the 2 groups are compared in Table 1. The mean values of LVEF were 44±7% in the LV dysfunction group and 62±4% in the non-LV dysfunction group (P<0.0001). LVEDD and LVESD were greater and the degree of residual MR was similar between the groups.

Preoperative and Intraoperative Parameters for the Prediction of Postoperative LV Dysfunction

Univariate and multivariate logistic regression analyses are shown in Table 2. On univariate logistic analysis, age, LVEDD, LVEDD index, LVESD, LVESD index and LVEF were associated with postoperative LV dysfunction. Multicollinearity was identified between LVEDD, LVESD, and the LVEDD and LVESD indexes. Of these, LVESD, having the highest AUC on ROC analysis, was selected for multivariate analysis. The multivariable logistic regression model, which included age, LVESD and LVEF, showed that only LVESD was an independent predictor of postoperative LV dysfunction (LVESD increase: odds ratio 1.183; 95% confidence interval 1.083–1.303; P<0.001). As shown in Table 3 and Figure 1, on ROC curve analysis, LVESD had the highest AUC in predicting postoperative LV dysfunction with an AUC of 0.819, vs. LVEF (AUC 0.706), LVESD index (AUC 0.722), LVEDD (AUC 0.722), and LVEDD index (AUC 0.609). This analysis also revealed that an LVESD of 36 mm or more had 81% sensitivity and 76% specificity for predicting postoperative LV dysfunction. Delong’s test revealed that the AUC of LVESD was significantly superior to that of the other parameters.

Table 2.

Univariate and Multivariate Logistic Regression Analysis for Prediction of Postoperative LV Dysfunction

Variable	Univariable		Multivariable
	OR (95% CI)	P value	OR (95% CI)	P value
Age	0.974 (0.949–0.999)*	0.048*	0.989 (0.988–1.018)	0.448
Body surface area	1.013 (0.996–1.029)	0.133
Atrial fibrillation	1.872 (0.806–4.104)	0.139
BNP	0.999 (0.998–1.000)	0.998
LAD	1.013 (0.978–1.045)	0.426
LVEDD	1.085 (1.033–1.149)*	<0.001*
LVEDD index	1.079 (0.999–1.163)*	0.048*
LVESD	1.236 (1.147–1.345)*	<0.001*	1.183 (1.083–1.303)*	<0.001*
LVESD index	1.252 (1.126–1.400)*	<0.001*
LVEF	0.832 (0.769–0.895)*	<0.001*	0.917 (0.826–1.018)	0.104
RVSP	1.012 (0.986–1.035)	0.321
Extracorporeal circulation time	1.005 (0.998–1.011)	0.139
Aorta cross-clamp time	1.004 (0.996–1.012)	0.314
Concomitant CABG	2.254 (0.785–5.666)	0.123

*Statistical significance (P value <0.05). CI, confidence interval; OR, odds ratio. Other abbreviations as in Table 1.

Table 3.

Results of Receiver Operating Characteristic Curve Analysis and Delong’s Test

TTE parameter	AUC (95% CI)	Optimal cut-off	Sensitivity (%)	Specificity (%)	P value compared with LVESD using Delong’s test
LVESD	0.819 (0.741–0.877)	36 mm	81	76
LVEF	0.706 (0.597–0.796)	61%	68	87	0.016
LVESD index	0.722 (0.632–0.797)	20.5 mm/m2	81	53	0.013
LVEDD	0.722 (0.616–0.807)	56 mm	68	68	<0.001
LVEDD index	0.609 (0.508–0.703)	31.4 mm/m2	84	36	<0.001

AUC, area under the curve; CI, confidence interval. Other abbreviations as in Table 1.

Figure 1.

Receiver operating characteristic curve analyses of preoperative transthoracic echocardiographic parameters to predict postoperative left ventricular dysfunction. The receiver operating characteristic curve demonstrates good discriminatory ability of preoperative left ventricular end-systolic diameter (LVESD) in predicting postoperative left ventricular dysfunction (area under the curve=0.819; P<0.001). LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction.

Frequency of Detection of Preoperative and Postoperative LV Dysfunction According to LVESD and LVEF

Preoperative LV dysfunction detected from the conventional cut-off values of preoperative LVESD >40 mm and/or LVEF <60% was identified in 58 (18%) cases, while postoperative LV dysfunction was undetected in 16 (52%) cases (Figure 2A). In contrast, when classified using the novel index LVESD >36 mm and/or LVEF <61%, detection of preoperative myocardial damage increased to 113 (35%) cases, and the number of undetected postoperative LV dysfunction cases decreased to 4 (13%; Figure 2B). The diagnostic performance of the conventional indices, a combination of LVEF 60% and LVESD 40 mm, showed a sensitivity of 48% and specificity of 85%. In contrast, the combination of LVEF 61% and LVESD 36 mm based on the results of this study showed a sensitivity of 87% and specificity of 70%. Application of these novel indices significantly improved sensitivity (P=0.003) but resulted in a significant decrease in specificity (P<0.001).

Figure 2.

Frequency of detection of preoperative and postoperative left ventricular (LV) dysfunction according to LV end-systolic diameter (LVESD) and LV ejection fraction (LVEF). Frequency of preoperative and postoperative LV dysfunction detected from conventional cut-off values (A) and novel cut-off values (B).

Comparison of Major Events After MV Repair Between Patients With and Without LV Dysfunction

During the mean follow-up period of 43±29 months, 3 cardiac deaths and 6 hospitalizations due to heart failure occurred. The Kaplan-Meier curve demonstrated that the rate of avoidance of cardiac events was significantly diminished in patients with postoperative LV dysfunction (P<0.001; Figure 3).

Figure 3.

Comparison of cardiac events after mitral valve repair between patients with and without left ventricular (LV) dysfunction. Kaplan-Meier curves for freedom from cardiac death and hospital admission for heart failure. The rate of freedom from cardiac events was significantly decreased in patients with postoperative LV dysfunction.

Characteristics of Patients With Adverse Cardiac Events

Patients were stratified into 2 groups based on the occurrence of adverse cardiac events, and their clinical characteristics and the distribution of patients above or below the novel cut-off values (LVESD 36 mm, LVEF 61%) were compared (Table 4). A total of 9 adverse cardiac events were observed, comprising 3 cardiovascular deaths and 6 hospitalizations due to heart failure. Patients in the adverse cardiac event group were significantly older, and had a larger preoperative LVESD and lower preoperative LVEF. Although the proportion of patients meeting either or both of the novel cut-off criteria (LVESD ≥36 mm and/or LVEF ≤61%) did not differ significantly between the groups, the proportion of patients meeting both criteria (LVESD ≥36 mm and LVEF ≤61%) was significantly higher in the adverse event group.

Table 4.

Characteristics of Patients With Adverse Cardiac Events

	Cardiac event (+; n=9)	Cardiac event (−; n =313)	P value
Age at MV repair (years)	71±15	61±14	0.021
LVEDD (mm)	56±6	54±7	0.431
LVEDD index (mm/m2)	35±3	34±5	0.403
LVESD (mm)	37±4	34±0.3	0.039
LVESD index (mm/m2)	23±2	21±3	0.029
LVEF (%)	61±4	66±5	0.003
LVESD ≥36 mm and/or LVEF ≤61%	5 (56)	108 (35)	0.287
LVESD ≥36 mm and LVEF ≤61%	3 (33)	23 (7)	0.028

MV, mitral valve. Other abbreviations as in Table 1.

Changes in LVEF Over Time Postoperatively

Of a total of 322 patients, 33 patients had LVEF <50% and 289 patients had LVEF >50% in the immediate postoperative TTE, performed on a mean of 6.3±2.8 postoperative days. Of the 33 patients with LVEF <50% in the immediate postoperative TTE, 21 improved to LVEF >50% in the follow-up TTE (Group 2). In contrast, of the patients with LVEF >50% in the immediate postoperative period, 19 decreased to LVEF <50% at follow-up TTE (Group 3). We divided the patients into 4 groups based on the postoperative course of LVEF, as shown in Figure 4, and compared cardiac events after MV repair among them. Group 4 had the poorest prognosis, followed by Group 3 (P<0.0001).

Figure 4.

Changes in left ventricular (LV) ejection fraction (LVEF) over postoperative time and comparison of cardiac events after mitral valve (MV) repair among the 4 groups. All patients were divided into 4 groups based on the postoperative course of LVEF. Kaplan-Meier curves for freedom from cardiac death and hospital admission for heart failure in the 4 groups. The rate of freedom from cardiac event patients was significantly diminished in Group 4, followed by Group 3. MVP, mitral valve prolapse.

Discussion

In this study, 31 (10%) of 322 patients who underwent MV repair for DMR showed postoperative LV dysfunction. This was a lower proportion than those in previous reports.⁶ A larger preoperative LVESD and lower preoperative LVEF were predictors of postoperative LV dysfunction, with cut-off values of 36 mm and 61%, respectively.

Myocardial Impairment in Mitral Regurgitation

Mitral regurgitation is a condition that causes a volume load on the LV, which results in LV enlargement and LV dysfunction during the uncompensated phase of the disease. A previous study reported that myocardial biopsy of patients with MR and normal LVEF showed significant myocardial fibrosis compared with control patients.¹¹ However, myocardial strain analysis in that study based on cardiac magnetic resonance imaging (MRI) showed no significant difference in preoperative strain values compared with control patients, which indicated the presence of a level of myocardial damage that cannot be detected by imaging. In recent years, advances in CT and MRI technology have demonstrated their utility in detecting preoperative myocardial damage in the management of valvular heart disease.^12–14 Particularly in patients with DMR, the presence of late gadolinium enhancement on MRI has been reported as a prognostic predictive factor.¹⁵ Currently, the relatively long examination time and high cost of MRI make it difficult for all DMR patients to undergo MRI for the purpose of detecting preoperative myocardial damage. However, if these problems can be overcome, then MRI might be expected to become a powerful diagnostic tool that is routinely performed for all patients with DMR.

Preoperative Predictive Factors of Postoperative LV Dysfunction

While previous studies have reported that the severity of MR regurgitant volume is associated with postoperative LV dysfunction, the present study demonstrated no significant difference in regurgitant volume.¹⁶ In this cohort, approximately half of the patients underwent surgery at an earlier stage, namely prior to the onset of LV dysfunction, pulmonary hypertension, or atrial fibrillation. This earlier surgical intervention in patients with lower regurgitant volumes compared with those in previous studies may have contributed to the lack of a significant difference in regurgitant volume.

Studies of echocardiographic strain analysis have reported the usefulness of preoperative GLS in detecting post-MV repair cardiac dysfunction.¹⁷ However, echocardiographic strain analysis is heavily influenced by image quality, as well as by differences between vendors, and results have differed from report to report. Accordingly, no conclusive cut-off values have been established.¹⁸ Presently, the most appropriate method of determining the optimal time for mitral valvuloplasty appears to be based on LVEF and LVEDD. A previous report on Japanese patients suggested a preoperative LVEF <55% and LVESD ≥40 mm as predictive factors, but these are unsuitable for determining the timing of surgery in patients with DMR because the study included functional mitral regurgitation cases.¹⁹ Overseas reports limited to cases of DMR showed a preoperative LVEF of less than 64% and an LVESD of 36 mm or more as predictive factors, with results similar to those reported here.

Because of the smaller body size of Japanese people compared with Westerners, the Japanese Circulation Society guidelines use LV diameter standardized by BSA as an indicator for MV repair.

In the present study, the LVESD index had a poorer ability to detect postoperative LV dysfunction than LVESD. Indexed LV diameter is reported to overcorrect, particularly for smaller patients,²⁰ possibly reflecting the difficulty in accurately correcting for differences in body size using this index. The newly determined cut-off values in the present study enhanced sensitivity for detecting postoperative LV dysfunction, albeit at the expense of reduced specificity. Although improved sensitivity is advantageous for identifying subclinical preoperative LV myocardial damage, the concomitant decline in specificity indicates the need for continued efforts to achieve durable valve repair.

Utility of MV Repair Before LV Enlargement Occurs

MV repair has become an established treatment and guidelines now recommend MV repair at an earlier stage than previously. Better outcomes with earlier MV repair than in current guidelines have also been reported.²¹ In contrast, an early decision to MV repair is predicated on the completion of a durable valve repair. LV enlargement is not only an indicator of postoperative LV dysfunction, but tethering due to LV enlargement also affects MV repair. The tethering of the MV leaflets caused by LV enlargement has been found to affect postoperative MV morphology and increase the risk of residual eccentric regurgitation, resulting in poor postoperative outcomes.²² MV repair before the development of LV enlargement is desirable in terms of postoperative MV durability.

Timing to Define Postoperative LV Dysfunction

As previously reported, LVEF decreases after MV repair for DMR but then improves over time.^23,24 Although some of these reports included recoveries over time for up to 5 years, most studies on LV dysfunction after MV repair have been compared with LVEF within the first postoperative year.^5,6 In line with this, our study assessed postoperative LV function at 6–12 months after MV repair. The present study showed that prognosis was poorest in the group with reduced EF both immediately after surgery and at follow up, followed by the group with reduced LVEF at follow up even if LVEF was not reduced immediately after surgery. These results indicate that long-term postoperative follow up is desirable even in patients without problems in the immediate postoperative period. Although 8.8% of patients in this study did not undergo the required follow-up TTEs, these results suggest that no postoperative patient should be lost to routine follow up. In particular, careful follow up of patients at risk of postoperative LV dysfunction is advisable after strict pharmacological treatment.

Preoperative Factors Predicting Postoperative Cardiac Events

In this study, adverse cardiac events occurred in 9 (0.3%) patients during the follow-up period. A greater proportion of patients in the event group met both cut-off values: LVESD ≥36 mm and LVEF ≤61%. In contrast, in addition to larger LVESD and reduced LVEF, patients in the event group were significantly older at the time of MV repair. Due to the limited number of adverse events, definitive conclusions regarding predictive factors could not be drawn. Further studies with larger cohorts are warranted to more accurately identify preoperative determinants of postoperative cardiac events.

Study Limitations

There are several limitations in this study. First, the study was conducted under a retrospective design with a relatively small number of patients, and the power of all statistical analyses was insufficient. Second, the use of several mixed methods of quantitative assessment of preoperative MR meant that MR severity indices could not be used in the analysis.

Conclusions

The criteria for LVESD in MV repair in cases with DMR should be lower than the values indicated by the guidelines. Adoption of these revised criteria may improve prognosis after surgery.

Acknowledgments

This work was supported by JSPS KAKENHI grant number 22K20498.

Disclosures

Y.K., G.M. are members of Circulation Reports’ Editorial Team.

IRB Information

This study was approved by Chiba University Hospital and Kawasaki Saiwai Hospital Ethics Committee (reference no. HK202411-14).

References

• 1.   Enriquez-Sarano M, Schaff HV, Orszulak TA, Tajik AJ, Bailey KR, Frye RL. Valve repair improves the outcome of surgery for mitral regurgitation: A multivariate analysis. Circulation 1995; 91: 1022–1028.
• 2.   Suri RM, Schaff HV, Dearani JA, Sundt TM 3rd, Daly RC, Mullany CJ, et al. Survival advantage and improved durability of mitral repair for leaflet prolapse subsets in the current era. Ann Thorac Surg 2006; 82: 819–826.
• 3.   Tanaka S, Shimada S, Lee Y, Komae H, Ando M, Yamauchi H, et al. Mitral valve repair for mitral regurgitation in patients with Marfan syndrome. Circ J 2024; 88: 1980–1985.
• 4.   Lee HA, Chang FC, Yeh JK, Tung YC, Wu VC, Hsieh MJ, et al. Mitral valve repair vs. replacement by different etiologies: A nationwide population-based cohort study. Circ J 2024; 88: 568–578.
• 5.   Enriquez-Sarano M, Tajik AJ, Schaff HV, Orszulak TA, McGoon MD, Bailey KR, et al. Echocardiographic prediction of left ventricular function after correction of mitral regurgitation: Results and clinical implications. J Am Coll Cardiol 1994; 24: 1536–1543.
• 6.   Tribouilloy C, Rusinaru D, Szymanski C, Mezghani S, Fournier A, Lévy F, et al. Predicting left ventricular dysfunction after valve repair for mitral regurgitation due to leaflet prolapse: Additive value of left ventricular end-systolic dimension to ejection fraction. Eur J Echocardiogr 2011; 12: 702–710.
• 7.   Izumi C, Eishi K, Ashihara K, Arita T, Otsuji Y, Kunihara T, et al. JCS/JSCS/JATS/JSVS 2020 Guidelines on the management of valvular heart disease. Circ J 2020; 84: 2037–2119.
• 8.   Asch FM, Miyoshi T, Addetia K, Citro R, Daimon M, Desale S, et al. Similarities and differences in left ventricular size and function among races and nationalities: Results of the World Alliance Societies of Echocardiography Normal Values Study. J Am Soc Echocardiogr 2019; 32: 1396–1406.
• 9.   Nakao T, Nakanishi K, Sawada N, Kawahara T, Miyoshi T, Takeuchi M, et al. Racial differences in age-related changes in left ventricular structural and functional echocardiographic measurements among healthy Japanese and American participants: A subanalysis of the World Alliance Society of Echocardiography Normal Values Study. Circ J 2024; 88: 1461–1471.
• 10.   Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015; 28: 1–39.
• 11.   Ahmed MI, Gladden JD, Litovsky SH, Lloyd SG, Gupta H, Inusah S, et al. Increased oxidative stress and cardiomyocyte myofibrillar degeneration in patients with chronic isolated mitral regurgitation and ejection fraction >60%. J Am Coll Cardiol 2010; 55: 671–679.
• 12.   Kitai T, Kohsaka S, Kato T, Kato E, Sato K, Teramoto K, et al. JCS/JHFS 2025 Guideline on diagnosis and treatment of heart failure. Circ J 2025; 89: 1278–1444.
• 13.   Matsumoto M, Takaoka H, Takahashi M, Ota J, Noguchi Y, Okita S, et al. Preoperative longitudinal strain on computed tomography is a sensitive marker of patient prognosis after transcatheter aortic valve replacement. Circ J 2025; 89: 1488–1498, doi:10.1253/circj.CJ-24-0863.
• 14.   Tsunamoto H, Yamamoto H, Masumoto A, Taniguchi Y, Takahashi N, Onishi T, et al. Efficacy of native T1 mapping for patients with non-ischemic cardiomyopathy and ventricular functional mitral regurgitation undergoing transcatheter edge-to-edge repair. Circ J 2024; 88: 519–527.
• 15.   Figliozzi S, Georgiopoulos G, Lopes PM, Bauer KB, Moura-Ferreira S, Tondi L, et al. Myocardial fibrosis at cardiac MRI helps predict adverse clinical outcome in patients with mitral valve prolapse. Radiology 2023; 306: 112–121.
• 16.   Yamano T, Gillinov AM, Wada N, Matsumura Y, Toyono M, Thomas JD, et al. Doppler-derived preoperative mitral regurgitation volume predicts postoperative left ventricular dysfunction after mitral valve repair. Am Heart J 2009; 157: 875–882.
• 17.   Mascle S, Schnell F, Thebault C, Corbineau H, Laurent M, Hamonic S, et al. Predictive value of global longitudinal strain in a surgical population of organic mitral regurgitation. J Am Soc Echocardiogr 2012; 25: 766–772.
• 18.   Modaragamage Dona AC, Afoke J, Punjabi PP, Kanaganayagam GS. Global longitudinal strain to determine optimal timing for surgery in primary mitral regurgitation: A systematic review. J Card Surg 2021; 36: 2458–2466.
• 19.   Matsumura T, Ohtaki E, Tanaka K, Misu K, Tobaru T, Asano R, et al. Echocardiographic prediction of left ventricular dysfunction after mitral valve repair for mitral regurgitation as an indicator to decide the optimal timing of repair. J Am Coll Cardiol 2003; 42: 458–463.
• 20.   Daimon M, Watanabe H, Nakanishi K, Abe Y, Hirata K, Ishii K, et al. Is left ventricular diameter indexed for body surface area appropriate for assessing left ventricular dilation? J Cardiol 2024; 84: 67–69.
• 21.   Kitai T, Okada Y, Shomura Y, Tanabe K, Tani T, Kita T, et al. Early surgery for asymptomatic mitral regurgitation: Importance of atrial fibrillation. J Heart Valve Dis 2012; 21: 61–70.
• 22.   Sakaguchi T, Kagiyama N, Toki M, Hiraoka A, Hayashida A, Totsugawa T, et al. Residual mitral regurgitation after repair for posterior leaflet prolapse importance of preoperative anterior leaflet tethering. J Am Heart Assoc 2018; 7: e008495.
• 23.   Suri RM, Schaff HV, Dearani JA, Sundt TM, Daly RC, Mullany CJ, et al. Recovery of left ventricular function after surgical correction of mitral regurgitation caused by leaflet prolapse. J Thorac Cardiovasc Surg 2009; 137: 1071–1076.
• 24.   Kislitsina ON, Thomas JD, Crawford E, Michel E, Kruse J, Liu M, et al. Predictors of left ventricular dysfunction after surgery for degenerative mitral regurgitation. Ann Thorac Surg 2020; 109: 669–677.