Three-Dimensional Echocardiographic Assessment of Mitral Apparatus and Left Atrial Remodeling to Guide TEER in Eccentric versus Central Ischemic Mitral Regurgitation

Three-Dimensional Echocardiographic Assessment of Mitral Apparatus and Left Atrial Remodeling to Guide TEER in Eccentric versus Central Ischemic Mitral Regurgitation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Three-Dimensional Echocardiographic Assessment of Mitral Apparatus and Left Atrial Remodeling to Guide TEER in Eccentric versus Central Ischemic Mitral Regurgitation xiaona huang, cong liu, kai xu, yang li, tingting zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8927278/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Three-dimensional echocardiography combined with speckle-tracking imaging was employed to compare mitral valve geometry, dynamic deformation, and left atrial (LA) function derived from strain between eccentric-jet and central-jet ischemic mitral regurgitation (IMR). Integrated thresholds were derived to refine IMR phenotyping and inform planning for transcatheter edge-to-edge repair (TEER). Methods In this single-center cross-sectional study, 111 consecutive patients with moderate-to-severe IMR (54 eccentric, 57 central) and 60 frequency-matched controls were prospectively enrolled. Mitral valve geometry was quantified offline using full-volume, three-dimensional transesophageal datasets. LA strain was measured by high-frame-rate two-dimensional speckle-tracking imaging. Determinants of jet eccentricity were identified by multivariable logistic regression adjusted for clinical and echocardiographic covariates. Results Eccentric jets exhibited greater anterior–posterior annular diameter, larger posterior leaflet angle, and lower anterior-to-posterior coaptation-length ratio, whereas central jets displayed increased tenting volume and height (all P < 0.05). Both IMR groups demonstrated significantly reduced LA reservoir strain (eccentric: 9.40% vs. central: 10.35%, P < 0.001) and lower total emptying fractions (LATEF: eccentric 32.7% vs. central 36.8%, P < 0.001) compared to controls (LASr: 28.55%, LATEF: 66.95%). Notably, the eccentric group showed relatively preserved reservoir strain but more severely reduced active emptying fraction (LAAEF: 17.4% vs. 20.8%, P < 0.05) and increased LA stiffness index (all P < 0.05), suggesting differential atrial functional remodeling patterns between IMR phenotypes. Conclusions Eccentric IMR exhibits asymmetric mitral deformation and LA remodeling with relatively preserved but still impaired reservoir function. In contrast, central IMR reflects global left ventricular (LV) sphericalization with comparatively less impaired LA stiffness. Integrated three-dimensional echocardiography provides reproducible metrics for patient-specific TEER planning. ischemic mitral regurgitation eccentric regurgitation transcatheter edge-to-edge repair three-dimensional echocardiography left atrial strain TEER planning mitral apparatus remodeling Figures Figure 1 Figure 2 Introduction Functional mitral regurgitation (FMR) is not merely an echocardiographic finding but a major public health concern. Population-based cohorts report grade ≥2 FMR in 16-24% of patients with heart failure, increasing to more than 35% among those with reduced ejection fraction. Despite guideline-directed medical therapy, five-year mortality remains as high as 43%, exceeding that of many malignancies. Importantly, the prevalence of FMR is projected to double by 2040 as post-infarction survival improves and the population ages. Yet, no medical therapy has been proven to reverse FMR, and up to 40% of patients are considered ineligible for surgery, underscoring the urgent need for refined patient stratification to identify those most likely to benefit from transcatheter options [1, 2] . Unlike primary mitral regurgitation, FMR occurs in the setting of a structurally normal valve. Its mechanism is driven by ventricular dysfunction, papillary muscle displacement, and annular dilatation. Following myocardial infarction, ischemic mitral regurgitation (IMR) emerges as the most common valvular sequela, affecting approximately one-fifth of patients in the acute phase and nearly half of those who subsequently develop heart failure [3-5] . Aging and delayed revascularization further expand its prevalence. Rather than primary leaflet pathology, IMR results from maladaptive LV remodeling that displaces papillary muscles posterolaterally and apically, tethers otherwise normal leaflets, and impairs coaptation (Carpentier type IIIb), while concomitant annular dilatation reduces closing forces [6] . Collectively, papillary muscle displacement, increased chordal tension, apical coaptation, annular expansion, and global LV sphericity distort the subvalvular apparatus, creating a feedback loop in which regurgitation itself accelerates adverse cardiac remodeling [7] . Inferior infarction, by preferentially tethering the posterior leaflet, may direct the jet along the atrial wall, whereas anterior or multivessel disease tends to produce a centrally directed jet; loading conditions may still alter jet orientation [8] . Guideline-directed medical therapy and timely revascularization remain the therapeutic foundation, yet moderate-to-severe IMR often requires restrictive annuloplasty or patient-specific TEER. Based on jet direction, IMR is classified into two phenotypes: central jets, directed toward the mid–LA cavity and causing predominantly symmetric volume overload; and eccentric jets, directed along the atrial wall, producing asymmetric flow and wall stress (wall-hugging jets) [9-11] . In FMR, increased leaflet tethering and annular dilatation impose chronic mechanical stress on the mitral leaflets. This stress activates fibroblasts within the spongiosa layer, leading to extracellular matrix deposition and fibrotic remodeling, initially serving as a compensatory response to limit regurgitation severity. When the hemodynamic burden persists, however, this response becomes maladaptive. Progressive fibrosis increases leaflet stiffness and compromises coaptation, thereby worsening mitral regurgitation. The ensuing rise in mechanical stress further promotes fibrosis, establishing a vicious cycle of valve dysfunction and structural remodeling [12] . TEER has become the standard treatment for patients with severe degenerative mitral regurgitation who are at high or prohibitive surgical risk [13] . Post-procedural reduction in regurgitation depends on the individual anatomy of the mitral apparatus, whereas LA reverse remodeling is influenced by preoperative functional reserve and the extent of interstitial fibrosis [14] . By integrating real-time three-dimensional transesophageal echocardiography (RT-3D-TEE) with two-dimensional speckle-tracking imaging (2D-STI), high-resolution characterization of mitral apparatus remodeling and LA myocardial strain was achieved. By analyzing consecutive patients with eccentric or central IMR, subtype-specific remodeling patterns were compared to identify key pre-procedural echocardiographic parameters relevant to interventional decision-making [15, 16] . Accordingly, a comprehensive single-center observational study was conducted using RT-3D-TEE and 2D-STI to compare mitral valve complex geometry, leaflet tethering asymmetry, and LA fibro-functional properties between eccentric- and central-jet IMR. It was hypothesized that (i) eccentric IMR is characterized by pronounced anterior–posterior asymmetric deformation and increased LA stiffness, whereas central IMR is dominated by global LV sphericity with relatively less impaired LA compliance, and (ii) integrated annular geometric and LA strain metrics can refine pre-TEER phenotyping and guide individualized clip implantation strategies. Methods Study population and design This retrospective, single-center cohort study consecutively identified patients with grade ≥3 IMR according to the ASE 2017 guidelines. Ultimately, 54 patients with eccentric jets, 57 with central jets, and 60 controls were enrolled. The study comprised 111 IMR patients (eccentric IMR: 54 patients, 30 males, 24 females, age 65.2 ± 6.8 years; central IMR: 57 patients, 32 males, 25 females, age 64.8 ± 7.1 years) and 60 controls (28 males, 32 females, age 62.1 ± 5.9 years), with comparable age and sex distributions (P > 0.05 for all). Inclusion criteria were effective regurgitant orifice area >0.30 cm², regurgitant volume >45 mL, or regurgitant fraction >40%, each quantified by 3D transesophageal proximal isovelocity surface area (PISA). Patients with organic valve disease, previous valve surgery, or suboptimal image quality were excluded. All patients had documented coronary artery disease, defined as ≥50% stenosis in at least one major epicardial coronary artery confirmed by invasive angiography. Patients with primary dilated cardiomyopathy (no significant coronary lesions) or organic valvular disease were also excluded. Ischemic etiology was confirmed by concordance between infarct location on electrocardiography or echocardiography and coronary angiography findings. The study was approved by the Chinese People's Liberation Army Ethics Committee (Approval No. 056/2022). Written informed consent was provided by all patients. For retrospective data analysis, a waiver of informed consent was granted. Clinical trial number: not applicable. Echocardiographic image acquisition and analysis All echocardiographic examinations were performed using a Philips EPIQ 7C ultrasound system (Philips Healthcare, Andover, MA, USA) equipped with an X7-2t real-time three-dimensional transesophageal matrix-array transducer (2-7 MHz) for RT-3D-TEE, and an X5-1 broadband transthoracic transducer (1-5 MHz) for two-dimensional speckle-tracking imaging (2D-STI). RT-3D-TEE datasets were acquired from the mid-esophageal position at 0-30° interrogation angles. Full-volume datasets were captured over four consecutive cardiac cycles during an end-expiratory breath-hold, with electrocardiographic gating efficiency ≥80%, and stored in raw volumetric format. 2D-STI data were recorded from standard apical four-chamber, two-chamber, and long-axis views at frame rates ≥60 frames/s. Three consecutive beats in sinus rhythm were averaged to minimize variability. Mitral regurgitation severity was quantified online using the 3D PISA method to derive effective regurgitant orifice area (EROA), regurgitant volume (RVol), and regurgitant fraction (RF). Jet direction was evaluated at mid-systole and classified as central if the high-velocity core was directed toward the mid-atrial cavity, or eccentric if the jet hugged the atrial wall for ≥50% of systole. Classifications were performed by two level-III echocardiographers blinded to clinical data, and discrepancies were resolved by consensus. All datasets were anonymized, exported to a dedicated offline analysis workstation, and archived for post-processing. Statistical analysis Continuous variables are expressed as mean ± standard deviation or median (25th-75th percentile), and categorical variables as counts (%). Intergroup comparisons were conducted using one-way ANOVA or Kruskal-Wallis tests as appropriate. Categorical variables were compared using χ² or Fisher’s exact tests. Multivariable logistic regression was performed to identify independent determinants of jet eccentricity. Intra- and inter-observer reproducibility were assessed using intraclass correlation coefficients (ICC). Two-sided P-values <0.05 were considered statistically significant. Statistical analyses were performed with SPSS 27.0 . Results Mitral annular geometry Table 1 summarizes annular dimensions. Compared with controls, both IMR groups exhibited greater anterolateral-posteromedial (AL-PM) diameter, anterior-posterior (AP) diameter, 3D circumference, and 2D projected area (all P < 0.05). Eccentric IMR showed relatively preserved annular height (AH) and saddle shape (higher AH/AP ratio). In contrast, central IMR had significant saddle flattening (lower AH and AH/AP ratio, both P < 0.05 vs. eccentric). Non-planarity angles did not differ among groups. Mitral leaflet morphology Table 2 presents leaflet measurements. Eccentric IMR exhibited larger anterior leaflet surface area, smaller posterior leaflet area, greater anterior-to-posterior coaptation-area ratio, smaller anterior leaflet angle, larger posterior leaflet angle and mean tethering-angle difference, shorter coaptation length, smaller tenting volume and height, and greater papillary-muscle-to-leaflet distances (all P < 0.05 vs. central). Central IMR demonstrated the opposite pattern, including larger posterior leaflet area, greater tenting volume and height, larger anterior leaflet angle, shorter papillary-muscle distances, and a relatively preserved central coaptation line (all P < 0.05 vs. eccentric). LV remodeling Table 3 summarizes LV findings. Both IMR groups presented markedly increased indexed LV end-diastolic and end-systolic volumes, as well as significantly reduced LV ejection fraction and global longitudinal strain compared with controls (all P < 0.001). Central IMR had a lower LV ejection fraction than eccentric IMR (median 40.2% vs. 45.3%, P < 0.05). LA remodeling and function Table 4 presents LA findings. Eccentric IMR showed larger maximal and minimal LA volumes, higher expansion index, pre-contractile volume, reservoir and contractile strain, yet lower total, passive, and active emptying fractions, peak atrial longitudinal strain, and stiffness index (all P < 0.05 vs. central). Central IMR demonstrated smaller LA volumes, relatively preserved strain values, and lower stiffness index (P < 0.05). Conduit strain did not differ significantly between IMR groups. Multivariable determinants of eccentric jet Annular height-to-diameter ratio remained an independent inverse predictor (β = -0.682, P < 0.001). Meanwhile, global tenting volume (β = 0.772, P < 0.001), more negative mean tethering-angle difference (β = -0.487, P < 0.001), reduced anterior-to-posterior coaptation-area ratio (β = -0.547, P < 0.001), and increased posterior papillary-muscle-to-leaflet distance (β = 0.708, P < 0.001) independently predicted central jets. LA stiffness index correlated inversely with all LA emptying fractions (r = -0.620 to -0.682, all P < 0.001). Reproducibility Intraclass correlation coefficients for all key parameters exceeded 0.77 (good to excellent). Discussion 1. Mitral apparatus deformation patterns Within the mitral valve complex, the annulus maintains a natural saddle shape, whose curvature and cyclic motion reduce leaflet stress [17] . Patients with eccentric IMR exhibited significantly increased MTAD compared with controls (22.70° vs. 7.60°, P < 0.001). This finding indicates pronounced posterior leaflet tethering, correlating with asymmetric leaflet stress due to localized papillary muscle displacement. Eccentric IMR features localized and asymmetric remodeling. The anteroposterior diameter widens, annular height remains relatively preserved or even increased, and the saddle shape becomes more pronounced [18] . Concurrently, the mean tethering-angle difference becomes more negative, the posterior leaflet angle frequently exceeds 45°, and the coaptation line shifts posteriorly, findings associated with poor prognosis [12] . Outward displacement of papillary muscles increases their distance from the leaflets, generating eccentric tensile vectors involving the papillary muscle, annulus, and leaflet as a functional triad. The high-velocity eccentric jet skims the atrial wall, rebounds toward the annulus, progressively reduces ring elasticity, and increases leaflet strain. This sequence establishes a self-amplifying cycle in which mechanical impact causes loss of elasticity and greater strain. A posterior leaflet angle exceeding 45° predicts inferior repair durability, mandating alternative surgical approaches. Thus, although the saddle remains deep in eccentric IMR, focal geometric distortion predominates, imposing greater demands on clip positioning and orientation. Conversely, central IMR displays global and symmetric remodeling. Anteroposterior diameter and annular height both decrease, saddle shape flattens, posterior leaflet area and tenting volume increase, leaflet angle changes are minimal, papillary muscle displacement is slight, and the coaptation line remains central. The central jet strikes the atrial cavity directly, distributing force uniformly and causing only modest increases in annular and leaflet stress [19] , thus reducing complexity in repair (Figure 1). 2. Phasic LA strain-derived reservoir, conduit, and contractile function In central IMR, the centrally directed jet impinges upon the mid-atrial cavity, dispersing radially throughout the cardiac cycle and creating relatively uniform intra-atrial pressure with minimal regional gradients. Despite evident LA enlargement, longitudinal strain is only slightly reduced, active emptying fraction decreases modestly, and conduit function remains relatively preserved (Figure 2). Consequently, the LA stiffness index (LASI) remains lower compared to eccentric IMR, indicating limited fibrosis and relatively preserved compliance. Emerging evidence suggests that LASI strongly correlates with histological fibrosis burden, serving as a non-invasive surrogate marker. Although a universal threshold remains unestablished, provisional application in research and early clinical evaluation is justified [20] . In this study, the mean LASI in eccentric IMR patients (4.90) significantly exceeded that in the central IMR group (4.12, P < 0.05), reflecting more severe LA fibrosis associated with eccentric regurgitation [21] . In contrast, eccentric jets adhering to the atrial wall generate a high-intensity vortex and a focal high-pressure zone opposite the regurgitant orifice. Chronic impingement drives progressive atrial enlargement and reduced peak atrial longitudinal strain. Peak longitudinal strain decreases significantly, active emptying fraction declines, whereas conduit function remains unchanged during follow-up. In IMR, an eccentric jet accelerates through the orifice and strikes the LA wall at high velocity, amplifying local wall shear stress, the frictional force exerted by blood on the endocardium. Chronic exposure to elevated shear stress promotes endothelial activation, extracellular matrix remodeling, and progressive atrial fibrosis [22] . Importantly, LASI in eccentric IMR surpasses central IMR, reflecting increased collagen deposition, reduced myocardial elasticity, and impaired compliance. Sustained elevation of LASI further impairs atrial contractility, initiating a sequential cascade in which eccentric jets produce local high pressure, decrease strain progressively, stimulate collagen accumulation, and ultimately lead to pump failure. Thus, LASI serves as a surrogate for atrial fibrosis in eccentric IMR, identifying patients who might benefit from more aggressive interventions. During pre-procedural planning for TEER, integrating annular geometry with LA functional indices facilitates accurate phenotypic classification. Eccentric cases require posterior clip positioning and frequent follow-up at three-month intervals. Elevated LASI identifies patients who may benefit from concomitant atrial ablation or experimental anti-fibrotic therapies. Limitations This series included only 111 participants and lacked systematic postoperative imaging follow-up, underscoring the need for larger prospective studies. Simultaneous electrophysiological mapping was not conducted, and LA strain indices were not validated against myocardial collagen quantification. Restricted recruitment channels and echocardiography throughput prevented assignment of IMR to specific coronary territories. Conclusions Eccentric IMR is characterized by asymmetric mitral apparatus deformation and pronounced LA fibro-functional decline, whereas central IMR predominantly involves global LV remodeling with relatively preserved LA mechanics. Real-time 3D transesophageal echocardiography combined with 2D speckle-tracking imaging provides robust quantitative and qualitative parameters to refine pre-TEER phenotyping and inform patient-specific procedural planning. Abbreviations IMR: Ischemic mitral regurgitation; TEER: Transcatheter edge-to-edge repair; RT-3D-TEE: Real-time three-dimensional transesophageal echocardiography; 2D-STI: Two-dimensional speckle-tracking imaging; LA: Left atrial; LV: Left ventricular; AL-PM: Anterolateral-to-posteromedial; AP: Anterior-posterior; AH: Annular height; 3DC: Three-dimensional circumference; 2DA: Two-dimensional projected area; NPA: Non-planarity angle; MVALA: Mitral valve anterior leaflet area; MVPLA: Mitral valve posterior leaflet area; ALA/PLA CR: Anterior-to-posterior leaflet coaptation-area ratio; Vtent: Tenting volume; ALA: Anterior leaflet angle; PLA: Posterior leaflet angle; MTAD: Mean tethering-angle difference; Htent: Tenting height; AMA: Aorto-mitral angle; ALPM: Distance from anterior papillary-muscle tip to anterior leaflet; PLPM: Distance from posterior papillary-muscle tip to posterior leaflet; LVEDVi: Left ventricular end-diastolic volume index; LVEF: Left ventricular ejection fraction; LVGLS: Left ventricular global longitudinal strain; E/e': Ratio of early transmitral velocity to tissue Doppler velocity; LAD: Left atrial anteroposterior diameter; LAVmax: Maximal left atrial volume; LAVmin: Minimal left atrial volume; LAEI: Left atrial expansion index; LATEF: Left atrial total emptying fraction; LAVpre: Left atrial pre-contractile volume; LAPEF: Left atrial passive emptying fraction; LAAEF: Left atrial active emptying fraction; LAVmaxi/LAVmini: Indexed left atrial volumes; PALS: Peak atrial longitudinal strain; LASr: Left atrial reservoir strain; LAScd: Left atrial conduit strain; LASct: Left atrial contractile strain; LASI: Left atrial stiffness index; EROA: Effective regurgitant orifice area; RVol: Regurgitant volume; RF: Regurgitant fraction; PISA: Proximal isovelocity surface area; ICC: Intraclass correlation coefficient; ASE: American Society of Echocardiography. Declarations Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki. The study was approved by the Ethics Committee of General Hospital of Northern Theater Command (Approval No. 056/2022). All participants provided written informed consent. For retrospective data analysis, a waiver of informed consent was granted. Consent for publication All authors have read and approved the final manuscript for publication. Availability of data and materials The datasets generated and/or analyzed during the current study are not publicly available due to patient privacy and ethical restrictions but are available from the corresponding author on reasonable request. Competing Interests The authors declare that they have no competing interests. Funding This work was supported by the National Key R&D Program of China (Grant No. 2022YFC2503403). Authors' contributions Conceptualization: Cong Liu; Data curation: Xiaona Huang, Yang Li, Tingting Zhang; Formal analysis: Xiaona Huang; Funding acquisition: Kai Xu; Investigation: Xiaona Huang, Yang Li, Tingting Zhang; Methodology: Cong Liu, Xiaona Huang; Project administration: Cong Liu; Resources: Cong Liu; Supervision: Cong Liu; Writing – original draft: Xiaona Huang; Writing – review & editing: Cong Liu. All authors read and approved the final manuscript. Acknowledgements Not applicable. References FIGLIOLI G, STICCHI A, CHRISTODOULOU M N, et al. Global Prevalence of Mitral Regurgitation: A Systematic Review and Meta-Analysis of Population-Based Studies [J]. J Clin Med, 2025, 14(8). SCIATTELLA P, MARTí-SáNCHEZ B, VERNIA M, et al. A Retrospective Analysis of the Clinical and Economic Burden of Mitral Regurgitation in Italy Using Real-World Data [J]. Clin Drug Investig, 2025, 45(11): 865-75. VAJAPEY R, KWON D. Guide to functional mitral regurgitation: a contemporary review [J]. 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Comparison of mitral annular geometry among control, eccentric IMR and central IMR groups Parameter Control (n = 60) Central IMR (n = 57) Eccentric IMR (n = 54) P value AL-PM/cm 3.68（3.54-3.95） 3.87（3.71-4.18） ① 3.89（3.70-4.00） ① 0.009 APD/cm 2.88（2.56-3.09） 3.34（3.16-3.49） ① 3.42（3.20-3.81） ①② ＜0.001 AH/cm 0.52（0.47-0.63） 0.42（0.39-0.44） ① 0.52（0.42-0.58） ② ＜0.001 AH/APD 0.19（0.15-0.21） 0.12（0.11-0.13） ① 0.14（0.13-0.15） ①② ＜0.001 3DC/cm 11.76（11.49-12.01） 13.79（13.05-14.01） ① 13.02（11.88-14.89） ① ＜0.001 2DA/cm² 9.36（8.56-9.87） 10.29（9.95-11.40） ① 11.34（10.67-12.66） ① ＜0.001 NPA/° 117.80（109.40-123.40） 117.60（112.75-118.98） 117.75（117.13-128.15） 0.362 Data are median (interquartile range). AL-PM, anterolateral-to-posteromedial diameter; AP, anterior–posterior diameter; AH, annular height; 3DC, three-dimensional circumference; 2DA, two-dimensional projected area; NPA, non-planarity angle. ① P < 0.05 vs control; ② P < 0.05 vs central IMR. Table 2. Comparison of mitral leaflet parameters among groups Parameter Control (n = 60) Central IMR (n = 57) Eccentric IMR (n = 54) P value MVALA/cm² 6.28（5.55-6.85） 6.89（6.65-7.69） ① 8.54（7.20-9.99） ①② ＜0.001 MVPLA/cm² 4.10（3.29-4.39） 5.52（5.00-6.12） ① 4.67（3.71-5.23） ①② ＜0.001 ALA/PLA CR 1.48（1.29-1.82） 1.22（1.18-1.28） ① 1.91（1.82-1.98） ①② ＜0.001 Vtent/ml 1.60（1.10-1.90） 4.90（4.10-5.40） ① 3.20（2.75-3.75） ①② ＜0.001 ALA/° 26.70（21.90-29.40） 24.80（23.20-26.90） 15.20（13.35-17.65） ①② ＜0.001 PLA/° 32.40（31.50-38.40） 28.40（27.10-32.60） ① 37.80（34.75-42.60） ①② ＜0.001 MTAD/° 7.60（6.40-9.90） 3.30（2.60-7.00） ① 22.70（21.40-24.90） ①② ＜0.001 Htent/mm 5.10（3.70-6.00） 9.70（8.90-9.90） ① 7.70（6.25-8.50） ①② ＜0.001 AMA/° 125.20（122.00-128.90） 137.90（123.00-140.20） ① 132.80（129.45-140.25） ① 0.001 ALPM/mm 19.50（17.60-20.70） 20.50（19.20-22.50） 26.00（24.70-26.95） ①② ＜0.001 PLPM/mm 18.00（17.50-18.90） 21.40（20.50-23.00） ① 26.20（25.15-27.35） ①② ＜0.001 Data are median (interquartile range). MVALA, anterior-leaflet area; MVPLA, posterior-leaflet area; ALA/PLA CR, coaptation-area ratio; Vtent, tenting volume; ALA, anterior-leaflet angle; PLA, posterior-leaflet angle; MTAD, mean tethering-angle difference; Htent, tenting height; AMA, aorto-mitral angle; ALPM, distance from anterior papillary-muscle tip to anterior leaflet; PLPM, distance from posterior papillary-muscle tip to posterior leaflet. ① P < 0.05 vs control; ② P < 0.05 vs central IMR. Table 3. Comparison of left-ventricular parameters Parameter Control (n = 60) Central IMR (n = 57) Eccentric IMR (n = 54) P value LVEDVi 36.16（28.27，44.04） 94.20（85.91，102.48） ① 92.44（83.75，101.08） ① ＜0.001 LVEF/% 64.40（60.83，67.96） 40.20（30.05，50.35） ① 45.25（42.32，48.17） ①② ＜0.001 LVGLS/% -21.85（-24.56，-19.13） -12.3（-13.82，-10.77） ① -12.9（-15.15，-10.65） ① ＜0.001 E/e' 7.0（6.2-7.9） 15.8（13.2-18.5） ① 13.8（11.5-16.2） ① ＜0.001 Data are median (interquartile range). LVESVi, indexed end-systolic volume; LVEDVi, indexed end-diastolic volume; LVEF, left-ventricular ejection fraction; LVGLS, global longitudinal strain; E/e′, ratio of early transmitral velocity to tissue Doppler velocity. ① P < 0.05 vs control; ② P < 0.05 vs central IMR. Table 4. Comparison of left-atrial function Parameter Control (n = 60) Central IMR (n = 57) Eccentric IMR (n = 54) P value LAD/mm 34.00（33.50，34.50） 45.00（42.50，47.50） ① 49.85（36.75，62.75） ①② ＜0.001 LAVmax/mL 36.55（35.28，37.81） 90.30（80.42，100.17） ① 106.40（90.83，121.96） ①② ＜0.001 LAVmin/mL 14.45（13.12，15.77） 62.13（53.32，70.93） ① 67.48（60.27，74.69） ① ＜0.001 LAEI 1.53（1.37，1.70） 0.48（0.38，0.57） ① 0.58（0.48，0.68） ①② ＜0.001 LATEF/% 66.95（61.89，72.01） 36.75（31.75，41.75） ① 32.70（29.07，36.32） ① ＜0.001 LAVpre/mL 25.60（24.08，27.11） 75.60（66.70，84.70） ① 82.90（70.65，95.15） ①② ＜0.001 LAPEF/% 30.37（23.41，36.01） 20.34（17.23，23.65） ① 18.02（14.23，22.45） ① ＜0.001 LAAEF/% 44.28（36.64，52.07） 20.76（16.15，24.44） ① 17.43（11.48，23.60） ①② ＜0.001 LAVmaxi 21.70（21.01，22.39） 51.28（45.18，57.38） ① 61.25（52.46，70.04） ①② ＜0.001 LAVmini 8.36（7.73，8.99） 34.90（29.00，40.80） ① 39.21（34.71，43.71） ① ＜0.001 PALS/% 30.70（20.56，40.83） 10.65（8.75，12.25） ① 9.20（7.97，10.42） ①② ＜0.001 LASr/% 28.55（24.76，32.35） 10.35（9.58，11.11） ① 9.40（6.10，12.70） ①② ＜0.001 LAScd/% -10.20（-12.50，-8.10） -6.20（-9.30，-4.10） ① -5.50（-8.02，-3.37） ①② ＜0.001 LASct/% -11.80（-13.60，-9.20） -4.75（-7.25，-2.24） ① -3.80（-5.07，-2.52） ①② ＜0.001 LASI 0.63（0.52，0.73） 4.12（3.31，4.93） ① 4.90（4.31，5.48） ①② ＜0.001 Data are median (interquartile range). LAD, left-atrial anteroposterior diameter; LAVmax, maximal volume; LAVmin, minimal volume; LAEI, expansion index; LATEF, total emptying fraction; LAVpre, pre-contractile volume; LAPEF, passive emptying fraction; LAAEF, active emptying fraction; LAVmaxi/LAVmini, indexed volumes; PALS, peak atrial longitudinal strain; LASr, reservoir strain; LAScd, conduit strain; LASct, contractile strain; LASI, LA stiffness index. ① P < 0.05 vs control; ② P < 0.05 vs central IMR. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8927278","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":600230913,"identity":"4bd32fa8-0056-4c7b-8b7f-21c07e854893","order_by":0,"name":"xiaona huang","email":"","orcid":"","institution":"General Hospital of Northern Theater Command","correspondingAuthor":false,"prefix":"","firstName":"xiaona","middleName":"","lastName":"huang","suffix":""},{"id":600230914,"identity":"6a55c493-7297-46bc-909e-19c67b876649","order_by":1,"name":"cong liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9ElEQVRIiWNgGAWjYBACPmYIzcPP3thwIKHChoGNkBY2qBYZyZ7DBw88OJNGhBYobWNwIy354MO2w4QdxsbOY/jh445aHoMzZwwOJLadt+eTbn7A8KNiGx6H8RhLzjxznEfyeI/BgYRztxPbZI4ZMPacuY1Pixkzb9sxHj6QLQlltxPYJBIMmBnbiNDCcCMHqIXtnD2bRPoHYrTU8AjcSEs4kNB2gLFNIoeQLWzFkjPbDvAAA/nAgYQzyYlALQUH8fmFn//wxg8f2+rsgVHZ/PFHhZ29/Iz0jQ9+VODWAgVo0XGAkHogqCNCzSgYBaNgFIxYAAASOVhcGb9YAwAAAABJRU5ErkJggg==","orcid":"","institution":"General Hospital of Northern Theater Command","correspondingAuthor":true,"prefix":"","firstName":"cong","middleName":"","lastName":"liu","suffix":""},{"id":600230915,"identity":"bba6c143-8265-4337-8149-644fbb4dab36","order_by":2,"name":"kai xu","email":"","orcid":"","institution":"General Hospital of Northern Theater Command","correspondingAuthor":false,"prefix":"","firstName":"kai","middleName":"","lastName":"xu","suffix":""},{"id":600230916,"identity":"90141699-5be1-42ec-9016-c7ccc3296393","order_by":3,"name":"yang li","email":"","orcid":"","institution":"General Hospital of Northern Theater Command","correspondingAuthor":false,"prefix":"","firstName":"yang","middleName":"","lastName":"li","suffix":""},{"id":600230917,"identity":"661c7216-a6c9-4aab-a850-c367b03e0808","order_by":4,"name":"tingting zhang","email":"","orcid":"","institution":"General Hospital of Northern Theater Command","correspondingAuthor":false,"prefix":"","firstName":"tingting","middleName":"","lastName":"zhang","suffix":""}],"badges":[],"createdAt":"2026-02-20 15:23:43","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8927278/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8927278/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104404005,"identity":"b11cdf6d-b23d-4e5b-9cb2-903d9b855abf","added_by":"auto","created_at":"2026-03-11 12:19:34","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":111032,"visible":true,"origin":"","legend":"\u003cp\u003eMorphologic comparison of the mitral annulus among control (A), eccentric IMR (B) and central IMR (C) groups. AL, anterolateral; PM, posteromedial; A, anterior; P, posterior; Ao, aorta.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8927278/v1/562bbe819012d9d3d652a221.jpeg"},{"id":104172016,"identity":"3b918ede-0aa5-45d4-af78-55bea02303e0","added_by":"auto","created_at":"2026-03-08 14:58:25","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":199529,"visible":true,"origin":"","legend":"\u003cp\u003eLeft-atrial strain curves in control (A), central IMR (B) and eccentric IMR (C) groups.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8927278/v1/267d76ee552acc641eed6b00.jpeg"},{"id":105556085,"identity":"3b0d7628-9e2c-49ce-a260-2df4db51a07b","added_by":"auto","created_at":"2026-03-27 10:57:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1104984,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8927278/v1/db103286-c965-41c9-a4b5-e047c5b19873.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Three-Dimensional Echocardiographic Assessment of Mitral Apparatus and Left Atrial Remodeling to Guide TEER in Eccentric versus Central Ischemic Mitral Regurgitation","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFunctional mitral regurgitation (FMR) is not merely an echocardiographic finding but a major public health concern. Population-based cohorts report grade \u0026ge;2 FMR in 16-24% of patients with heart failure, increasing to more than 35% among those with reduced ejection fraction. Despite guideline-directed medical therapy, five-year mortality remains as high as 43%, exceeding that of many malignancies. Importantly, the prevalence of FMR is projected to double by 2040 as post-infarction survival improves and the population ages. Yet, no medical therapy has been proven to reverse FMR, and up to 40% of patients are considered ineligible for surgery, underscoring the urgent need for refined patient stratification to identify those most likely to benefit from transcatheter options\u003csup\u003e[1, 2]\u003c/sup\u003e .\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUnlike primary mitral regurgitation, FMR occurs in the setting of a structurally normal valve. Its mechanism is driven by ventricular dysfunction, papillary muscle displacement, and annular dilatation. Following myocardial infarction, ischemic mitral regurgitation (IMR) emerges as the most common valvular sequela, affecting approximately one-fifth of patients in the acute phase and nearly half of those who subsequently develop heart failure\u003csup\u003e[3-5]\u003c/sup\u003e. Aging and delayed revascularization further expand its prevalence. Rather than primary leaflet pathology, IMR results from maladaptive LV remodeling that displaces papillary muscles posterolaterally and apically, tethers otherwise normal leaflets, and impairs coaptation (Carpentier type IIIb), while concomitant annular dilatation reduces closing forces\u003csup\u003e[6]\u003c/sup\u003e. Collectively, papillary muscle displacement, increased chordal tension, apical coaptation, annular expansion, and global LV sphericity distort the subvalvular apparatus, creating a feedback loop in which regurgitation itself accelerates adverse cardiac remodeling\u003csup\u003e[7]\u003c/sup\u003e. Inferior infarction, by preferentially tethering the posterior leaflet, may direct the jet along the atrial wall, whereas anterior or multivessel disease tends to produce a centrally directed jet; loading conditions may still alter jet orientation\u003csup\u003e[8]\u003c/sup\u003e. Guideline-directed medical therapy and timely revascularization remain the therapeutic foundation, yet moderate-to-severe IMR often requires restrictive annuloplasty or patient-specific TEER. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBased on jet direction, IMR is classified into two phenotypes: central jets, directed toward the mid\u0026ndash;LA cavity and causing predominantly symmetric volume overload; and eccentric jets, directed along the atrial wall, producing asymmetric flow and wall stress (wall-hugging jets)\u003csup\u003e[9-11]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIn FMR, increased leaflet tethering and annular dilatation impose chronic mechanical stress on the mitral leaflets. This stress activates fibroblasts within the spongiosa layer, leading to extracellular matrix deposition and fibrotic remodeling, initially serving as a compensatory response to limit regurgitation severity. When the hemodynamic burden persists, however, this response becomes maladaptive. Progressive fibrosis increases leaflet stiffness and compromises coaptation, thereby worsening mitral regurgitation. The ensuing rise in mechanical stress further promotes fibrosis, establishing a vicious cycle of valve dysfunction and structural remodeling\u003csup\u003e[12]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eTEER has become the standard treatment for patients with severe degenerative mitral regurgitation who are at high or prohibitive surgical risk\u003csup\u003e[13]\u003c/sup\u003e. Post-procedural reduction in regurgitation depends on the individual anatomy of the mitral apparatus, whereas LA reverse remodeling is influenced by preoperative functional reserve and the extent of interstitial fibrosis\u003csup\u003e[14]\u003c/sup\u003e. By integrating real-time three-dimensional transesophageal echocardiography (RT-3D-TEE) with two-dimensional speckle-tracking imaging (2D-STI), high-resolution characterization of mitral apparatus remodeling and LA myocardial strain was achieved. By analyzing consecutive patients with eccentric or central IMR, subtype-specific remodeling patterns were compared to identify key pre-procedural echocardiographic parameters relevant to interventional decision-making\u003csup\u003e[15, 16]\u003c/sup\u003e. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAccordingly, a comprehensive single-center observational study was conducted using RT-3D-TEE and 2D-STI to compare mitral valve complex geometry, leaflet tethering asymmetry, and LA fibro-functional properties between eccentric- and central-jet IMR. It was hypothesized that (i) eccentric IMR is characterized by pronounced anterior\u0026ndash;posterior asymmetric deformation and increased LA stiffness, whereas central IMR is dominated by global LV sphericity with relatively less impaired LA compliance, and (ii) integrated annular geometric and LA strain metrics can refine pre-TEER phenotyping and guide individualized clip implantation strategies. \u0026nbsp;\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy population and design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective, single-center cohort study consecutively identified patients with grade \u0026ge;3 IMR according to the ASE 2017 guidelines. Ultimately, 54 patients with eccentric jets, 57 with central jets, and 60 controls were enrolled. The study comprised 111 IMR patients (eccentric IMR: 54 patients, 30 males, 24 females, age 65.2 \u0026plusmn; 6.8 years; central IMR: 57 patients, 32 males, 25 females, age 64.8 \u0026plusmn; 7.1 years) and 60 controls (28 males, 32 females, age 62.1 \u0026plusmn; 5.9 years), with comparable age and sex distributions (P \u0026gt; 0.05 for all). Inclusion criteria were effective regurgitant orifice area \u0026gt;0.30 cm\u0026sup2;, regurgitant volume \u0026gt;45 mL, or regurgitant fraction \u0026gt;40%, each quantified by 3D transesophageal proximal isovelocity surface area (PISA). Patients with organic valve disease, previous valve surgery, or suboptimal image quality were excluded. All patients had documented coronary artery disease, defined as \u0026ge;50% stenosis in at least one major epicardial coronary artery confirmed by invasive angiography. Patients with primary dilated cardiomyopathy (no significant coronary lesions) or organic valvular disease were also excluded. Ischemic etiology was confirmed by concordance between infarct location on electrocardiography or echocardiography and coronary angiography findings. The study was approved by the Chinese People\u0026apos;s Liberation Army Ethics Committee (Approval No. 056/2022). Written informed consent was provided by all patients. For retrospective data analysis, a waiver of informed consent was granted. Clinical trial number: not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEchocardiographic image acquisition and analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll echocardiographic examinations were performed using a Philips EPIQ 7C ultrasound system (Philips Healthcare, Andover, MA, USA) equipped with an X7-2t real-time three-dimensional transesophageal matrix-array transducer (2-7 MHz) for RT-3D-TEE, and an X5-1 broadband transthoracic transducer (1-5 MHz) for two-dimensional speckle-tracking imaging (2D-STI). RT-3D-TEE datasets were acquired from the mid-esophageal position at 0-30\u0026deg; interrogation angles. Full-volume datasets were captured over four consecutive cardiac cycles during an end-expiratory breath-hold, with electrocardiographic gating efficiency \u0026ge;80%, and stored in raw volumetric format. 2D-STI data were recorded from standard apical four-chamber, two-chamber, and long-axis views at frame rates \u0026ge;60 frames/s. Three consecutive beats in sinus rhythm were averaged to minimize variability. Mitral regurgitation severity was quantified online using the 3D PISA method to derive effective regurgitant orifice area (EROA), regurgitant volume (RVol), and regurgitant fraction (RF). Jet direction was evaluated at mid-systole and classified as central if the high-velocity core was directed toward the mid-atrial cavity, or eccentric if the jet hugged the atrial wall for \u0026ge;50% of systole. Classifications were performed by two level-III echocardiographers blinded to clinical data, and discrepancies were resolved by consensus. All datasets were anonymized, exported to a dedicated offline analysis workstation, and archived for post-processing. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContinuous variables are expressed as mean \u0026plusmn; standard deviation or median (25th-75th percentile), and categorical variables as counts (%). Intergroup comparisons were conducted using one-way ANOVA or Kruskal-Wallis tests as appropriate. Categorical variables were compared using \u0026chi;\u0026sup2; or Fisher\u0026rsquo;s exact tests. Multivariable logistic regression was performed to identify independent determinants of jet eccentricity. Intra- and inter-observer reproducibility were assessed using intraclass correlation coefficients (ICC). Two-sided P-values \u0026lt;0.05 were considered statistically significant. Statistical analyses were performed with SPSS 27.0 .\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eMitral annular geometry\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 1 summarizes annular dimensions. Compared with controls, both IMR groups exhibited greater anterolateral-posteromedial (AL-PM) diameter, anterior-posterior (AP) diameter, 3D circumference, and 2D projected area (all P \u0026lt; 0.05). Eccentric IMR showed relatively preserved annular height (AH) and saddle shape (higher AH/AP ratio). In contrast, central IMR had significant saddle flattening (lower AH and AH/AP ratio, both P \u0026lt; 0.05 vs. eccentric). Non-planarity angles did not differ among groups. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMitral leaflet morphology\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 presents leaflet measurements. Eccentric IMR exhibited larger anterior leaflet surface area, smaller posterior leaflet area, greater anterior-to-posterior coaptation-area ratio, smaller anterior leaflet angle, larger posterior leaflet angle and mean tethering-angle difference, shorter coaptation length, smaller tenting volume and height, and greater papillary-muscle-to-leaflet distances (all P \u0026lt; 0.05 vs. central). Central IMR demonstrated the opposite pattern, including larger posterior leaflet area, greater tenting volume and height, larger anterior leaflet angle, shorter papillary-muscle distances, and a relatively preserved central coaptation line (all P \u0026lt; 0.05 vs. eccentric). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLV remodeling\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 3 summarizes LV findings. Both IMR groups presented markedly increased indexed LV end-diastolic and end-systolic volumes, as well as significantly reduced LV ejection fraction and global longitudinal strain compared with controls (all P \u0026lt; 0.001). Central IMR had a lower LV ejection fraction than eccentric IMR (median 40.2% vs. 45.3%, P \u0026lt; 0.05). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLA remodeling and function\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 4 presents LA findings. Eccentric IMR showed larger maximal and minimal LA volumes, higher expansion index, pre-contractile volume, reservoir and contractile strain, yet lower total, passive, and active emptying fractions, peak atrial longitudinal strain, and stiffness index (all P \u0026lt; 0.05 vs. central). Central IMR demonstrated smaller LA volumes, relatively preserved strain values, and lower stiffness index (P \u0026lt; 0.05). Conduit strain did not differ significantly between IMR groups. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMultivariable determinants of eccentric jet\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnnular height-to-diameter ratio remained an independent inverse predictor (\u0026beta; = -0.682, P \u0026lt; 0.001). Meanwhile, global tenting volume (\u0026beta; = 0.772, P \u0026lt; 0.001), more negative mean tethering-angle difference (\u0026beta; = -0.487, P \u0026lt; 0.001), reduced anterior-to-posterior coaptation-area ratio (\u0026beta; = -0.547, P \u0026lt; 0.001), and increased posterior papillary-muscle-to-leaflet distance (\u0026beta; = 0.708, P \u0026lt; 0.001) independently predicted central jets. LA stiffness index correlated inversely with all LA emptying fractions (r = -0.620 to -0.682, all P \u0026lt; 0.001). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eReproducibility\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIntraclass correlation coefficients for all key parameters exceeded 0.77 (good to excellent). \u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e1. Mitral apparatus deformation patterns\u003c/p\u003e\n\u003cp\u003eWithin the mitral valve complex, the annulus maintains a natural saddle shape, whose curvature and cyclic motion reduce leaflet stress\u003csup\u003e[17]\u003c/sup\u003e. Patients with eccentric IMR exhibited significantly increased MTAD compared with controls (22.70\u0026deg; vs. 7.60\u0026deg;, P \u0026lt; 0.001). This finding indicates pronounced posterior leaflet tethering, correlating with asymmetric leaflet stress due to localized papillary muscle displacement. Eccentric IMR features localized and asymmetric remodeling. The anteroposterior diameter widens, annular height remains relatively preserved or even increased, and the saddle shape becomes more pronounced\u003csup\u003e[18]\u003c/sup\u003e. Concurrently, the mean tethering-angle difference becomes more negative, the posterior leaflet angle frequently exceeds 45\u0026deg;, and the coaptation line shifts posteriorly, findings associated with poor prognosis\u003csup\u003e[12]\u003c/sup\u003e. Outward displacement of papillary muscles increases their distance from the leaflets, generating eccentric tensile vectors involving the papillary muscle, annulus, and leaflet as a functional triad. The high-velocity eccentric jet skims the atrial wall, rebounds toward the annulus, progressively reduces ring elasticity, and increases leaflet strain. This sequence establishes a self-amplifying cycle in which mechanical impact causes loss of elasticity and greater strain. A posterior leaflet angle exceeding 45\u0026deg; predicts inferior repair durability, mandating alternative surgical approaches. Thus, although the saddle remains deep in eccentric IMR, focal geometric distortion predominates, imposing greater demands on clip positioning and orientation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConversely, central IMR displays global and symmetric remodeling. Anteroposterior diameter and annular height both decrease, saddle shape flattens, posterior leaflet area and tenting volume increase, leaflet angle changes are minimal, papillary muscle displacement is slight, and the coaptation line remains central. The central jet strikes the atrial cavity directly, distributing force uniformly and causing only modest increases in annular and leaflet stress\u003csup\u003e[19]\u003c/sup\u003e, thus reducing complexity in repair (Figure 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2. Phasic LA strain-derived reservoir, conduit, and contractile function\u003c/p\u003e\n\u003cp\u003eIn central IMR, the centrally directed jet impinges upon the mid-atrial cavity, dispersing radially throughout the cardiac cycle and creating relatively uniform intra-atrial pressure with minimal regional gradients. Despite evident LA enlargement, longitudinal strain is only slightly reduced, active emptying fraction decreases modestly, and conduit function remains relatively preserved (Figure 2). Consequently, the LA stiffness index (LASI) remains lower compared to eccentric IMR, indicating limited fibrosis and relatively preserved compliance. Emerging evidence suggests that LASI strongly correlates with histological fibrosis burden, serving as a non-invasive surrogate marker. Although a universal threshold remains unestablished, provisional application in research and early clinical evaluation is justified\u003csup\u003e[20]\u003c/sup\u003e. In this study, the mean LASI in eccentric IMR patients (4.90) significantly exceeded that in the central IMR group (4.12, P \u0026lt; 0.05), reflecting more severe LA fibrosis associated with eccentric regurgitation\u003csup\u003e[21]\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn contrast, eccentric jets adhering to the atrial wall generate a high-intensity vortex and a focal high-pressure zone opposite the regurgitant orifice. Chronic impingement drives progressive atrial enlargement and reduced peak atrial longitudinal strain. Peak longitudinal strain decreases significantly, active emptying fraction declines, whereas conduit function remains unchanged during follow-up. In IMR, an eccentric jet accelerates through the orifice and strikes the LA wall at high velocity, amplifying local wall shear stress, the frictional force exerted by blood on the endocardium. Chronic exposure to elevated shear stress promotes endothelial activation, extracellular matrix remodeling, and progressive atrial fibrosis\u003csup\u003e[22]\u003c/sup\u003e. Importantly, LASI in eccentric IMR surpasses central IMR, reflecting increased collagen deposition, reduced myocardial elasticity, and impaired compliance. Sustained elevation of LASI further impairs atrial contractility, initiating a sequential cascade in which eccentric jets produce local high pressure, decrease strain progressively, stimulate collagen accumulation, and ultimately lead to pump failure. Thus, LASI serves as a surrogate for atrial fibrosis in eccentric IMR, identifying patients who might benefit from more aggressive interventions. During pre-procedural planning for TEER, integrating annular geometry with LA functional indices facilitates accurate phenotypic classification. Eccentric cases require posterior clip positioning and frequent follow-up at three-month intervals. Elevated LASI identifies patients who may benefit from concomitant atrial ablation or experimental anti-fibrotic therapies. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis series included only 111 participants and lacked systematic postoperative imaging follow-up, underscoring the need for larger prospective studies. Simultaneous electrophysiological mapping was not conducted, and LA strain indices were not validated against myocardial collagen quantification. Restricted recruitment channels and echocardiography throughput prevented assignment of IMR to specific coronary territories. \u0026nbsp;\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eEccentric IMR is characterized by asymmetric mitral apparatus deformation and pronounced LA fibro-functional decline, whereas central IMR predominantly involves global LV remodeling with relatively preserved LA mechanics. Real-time 3D transesophageal echocardiography combined with 2D speckle-tracking imaging provides robust quantitative and qualitative parameters to refine pre-TEER phenotyping and inform patient-specific procedural planning.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eIMR: Ischemic mitral regurgitation; TEER: Transcatheter edge-to-edge repair; RT-3D-TEE: Real-time three-dimensional transesophageal echocardiography; 2D-STI: Two-dimensional speckle-tracking imaging; LA: Left atrial; LV: Left ventricular; AL-PM: Anterolateral-to-posteromedial; AP: Anterior-posterior; AH: Annular height; 3DC: Three-dimensional circumference; 2DA: Two-dimensional projected area; NPA: Non-planarity angle; MVALA: Mitral valve anterior leaflet area; MVPLA: Mitral valve posterior leaflet area; ALA/PLA CR: Anterior-to-posterior leaflet coaptation-area ratio; Vtent: Tenting volume; ALA: Anterior leaflet angle; PLA: Posterior leaflet angle; MTAD: Mean tethering-angle difference; Htent: Tenting height; AMA: Aorto-mitral angle; ALPM: Distance from anterior papillary-muscle tip to anterior leaflet; PLPM: Distance from posterior papillary-muscle tip to posterior leaflet; LVEDVi: Left ventricular end-diastolic volume index; LVEF: Left ventricular ejection fraction; LVGLS: Left ventricular global longitudinal strain; E/e\u0026apos;: Ratio of early transmitral velocity to tissue Doppler velocity; LAD: Left atrial anteroposterior diameter; LAVmax: Maximal left atrial volume; LAVmin: Minimal left atrial volume; LAEI: Left atrial expansion index; LATEF: Left atrial total emptying fraction; LAVpre: Left atrial pre-contractile volume; LAPEF: Left atrial passive emptying fraction; LAAEF: Left atrial active emptying fraction; LAVmaxi/LAVmini: Indexed left atrial volumes; PALS: Peak atrial longitudinal strain; LASr: Left atrial reservoir strain; LAScd: Left atrial conduit strain; LASct: Left atrial contractile strain; LASI: Left atrial stiffness index; EROA: Effective regurgitant orifice area; RVol: Regurgitant volume; RF: Regurgitant fraction; PISA: Proximal isovelocity surface area; ICC: Intraclass correlation coefficient; ASE: American Society of Echocardiography.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki. The study was approved by the Ethics Committee of General Hospital of Northern Theater Command (Approval No. 056/2022). All participants provided written informed consent. For retrospective data analysis, a waiver of informed consent was granted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have read and approved the final manuscript for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to patient privacy and ethical restrictions but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Key R\u0026amp;D Program of China (Grant No. 2022YFC2503403).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: Cong Liu; Data curation: Xiaona Huang, Yang Li, Tingting Zhang; Formal analysis: Xiaona Huang; Funding acquisition: Kai Xu; Investigation: Xiaona Huang, Yang Li, Tingting Zhang; Methodology: Cong Liu, Xiaona Huang; Project administration: Cong Liu; Resources: Cong Liu; Supervision: Cong Liu; Writing \u0026ndash; original draft: Xiaona Huang; Writing \u0026ndash; review \u0026amp; editing: Cong Liu. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFIGLIOLI G, STICCHI A, CHRISTODOULOU M N, et al. Global Prevalence of Mitral Regurgitation: A Systematic Review and Meta-Analysis of Population-Based Studies [J]. J Clin Med, 2025, 14(8).\u003c/li\u003e\n\u003cli\u003eSCIATTELLA P, MART\u0026iacute;-S\u0026aacute;NCHEZ B, VERNIA M, et al. A Retrospective Analysis of the Clinical and Economic Burden of Mitral Regurgitation in Italy Using Real-World Data [J]. Clin Drug Investig, 2025, 45(11): 865-75.\u003c/li\u003e\n\u003cli\u003eVAJAPEY R, KWON D. Guide to functional mitral regurgitation: a contemporary review [J]. Cardiovasc Diagn Ther, 2021, 11(3): 781-92.\u003c/li\u003e\n\u003cli\u003eRAHMOUNI K, SHAHINIAN J H, DENG M, et al. Ischemic mitral regurgitation: when should one intervene? [J]. Curr Opin Cardiol, 2021, 36(6): 755-63.\u003c/li\u003e\n\u003cli\u003eSAIDOVA M A, ANDRIANOVA A M. [Ischemic Mitral Regurgitation: Echocardiographic Algorithm, the Place of Three-Dimensional Transesophageal Echocardiography] [J]. Kardiologiia, 2020, 60(2): 54-60.\u003c/li\u003e\n\u003cli\u003eG\u0026uuml;LER A, D\u0026uuml;NDAR C, TIGEN K. Functional mitral regurgitation and papillary muscle dyssynchrony in patients with left ventricular systolic dysfunction [J]. Anadolu Kardiyol Derg, 2011, 11(5): 450-5.\u003c/li\u003e\n\u003cli\u003eHUNG J W. Ischemic (functional) mitral regurgitation [J]. Cardiol Clin, 2013, 31(2): 231-6.\u003c/li\u003e\n\u003cli\u003eUNGER P, MAGNE J, DEDOBBELEER C, et al. Ischemic mitral regurgitation: not only a bystander [J]. Curr Cardiol Rep, 2012, 14(2): 180-9.\u003c/li\u003e\n\u003cli\u003eHASEGAWA H, KUWAJIMA K, KAGAWA S, et al. Impact of eccentric jet on outcomes in patients with atrial functional mitral regurgitation: An echocardiographic study [J]. Int J Cardiol, 2023, 391: 131342.\u003c/li\u003e\n\u003cli\u003eYAMAZAKI S, NUMATA S, YAKU H. Surgical intervention for ischemic mitral regurgitation: how can we achieve better outcomes? [J]. Surg Today, 2020, 50(6): 540-50.\u003c/li\u003e\n\u003cli\u003eOSTAD KARAMPOUR S, CHURCH M, CHOY J. Contrast Echocardiography: Unveiling Eccentric Mitral Regurgitation [J]. CASE (Phila), 2024, 8(2): 50-3.\u003c/li\u003e\n\u003cli\u003eNOGARA A, MINACAPELLI A, ZAMBELLI G, et al. Functional anatomy and echocardiographic assessment in secondary mitral regurgitation [J]. J Card Surg, 2022, 37(12): 4103-11.\u003c/li\u003e\n\u003cli\u003eZHU D, WANG S, LIU J, et al. Initial Experience in GeminiOne\u0026trade; Transcatheter Mitral Valve Edge-to-edge Repair Device [J]. Cardiology Discovery, 2024, 4(3): 250-2.\u003c/li\u003e\n\u003cli\u003eMARSAN N A, MAFFESSANTI F, TAMBORINI G, et al. Left atrial reverse remodeling and functional improvement after mitral valve repair in degenerative mitral regurgitation: a real-time 3-dimensional echocardiography study [J]. Am Heart J, 2011, 161(2): 314-21.\u003c/li\u003e\n\u003cli\u003eZHU H, YANG C, LI Y, et al. Two-Dimensional Speckle Tracking Echocardiography Identifies Coronary Artery Disease in 690 Patients: A Retrospective Study from a Single Center [J]. Med Sci Monit, 2021, 27: e929476.\u003c/li\u003e\n\u003cli\u003eREID A, BEN ZEKRY S, NAOUM C, et al. Geometric differences of the mitral valve apparatus in atrial and ventricular functional mitral regurgitation [J]. J Cardiovasc Comput Tomogr, 2022, 16(5): 431-41.\u003c/li\u003e\n\u003cli\u003eDAL-BIANCO J P, LEVINE R A. Anatomy of the mitral valve apparatus: role of 2D and 3D echocardiography [J]. Cardiol Clin, 2013, 31(2): 151-64.\u003c/li\u003e\n\u003cli\u003eZENG X, NUNES M C, DENT J, et al. Asymmetric versus symmetric tethering patterns in ischemic mitral regurgitation: geometric differences from three-dimensional transesophageal echocardiography [J]. J Am Soc Echocardiogr, 2014, 27(4): 367-75.\u003c/li\u003e\n\u003cli\u003eMIHĂILĂ S, MURARU D, PIASENTINI E, et al. Quantitative analysis of mitral annular geometry and function in healthy volunteers using transthoracic three-dimensional echocardiography [J]. J Am Soc Echocardiogr, 2014, 27(8): 846-57.\u003c/li\u003e\n\u003cli\u003eXU T, HU H, ZHU R, et al. Ultrasound assessment of the association between left atrial remodeling and fibrosis in patients with valvular atrial fibrillation: a clinical investigation [J]. BMC Cardiovasc Disord, 2025, 25(1): 149.\u003c/li\u003e\n\u003cli\u003eMĂLĂESCU G G, MIREA O, CAPOTĂ R, et al. Left Atrial Strain Determinants During the Cardiac Phases [J]. JACC Cardiovasc Imaging, 2022, 15(3): 381-91.\u003c/li\u003e\n\u003cli\u003eKAMPHUIS V P, WESTENBERG J J M, VAN DER PALEN R L F, et al. Unravelling cardiovascular disease using four dimensional flow cardiovascular magnetic resonance [J]. Int J Cardiovasc Imaging, 2017, 33(7): 1069-81.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Comparison of mitral annular geometry among control, eccentric IMR and central IMR groups\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl (n = 60)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCentral IMR (n = 57)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEccentric IMR (n = 54)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003eAL-PM/cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e3.68（3.54-3.95）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e3.87（3.71-4.18）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e3.89（3.70-4.00）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003eAPD/cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e2.88（2.56-3.09）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e3.34（3.16-3.49）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e3.42（3.20-3.81）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003eAH/cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e0.52（0.47-0.63）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e0.42（0.39-0.44）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e0.52（0.42-0.58）\u003csup\u003e②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003eAH/APD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e0.19（0.15-0.21）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e0.12（0.11-0.13）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e0.14（0.13-0.15）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e3DC/cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e11.76（11.49-12.01）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e13.79（13.05-14.01）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e13.02（11.88-14.89）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e2DA/cm\u0026sup2;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e9.36（8.56-9.87）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e10.29（9.95-11.40）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e11.34（10.67-12.66）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003eNPA/\u0026deg;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e117.80（109.40-123.40）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e117.60（112.75-118.98）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e117.75（117.13-128.15）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.362\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eData are median (interquartile range). AL-PM, anterolateral-to-posteromedial diameter; AP, anterior\u0026ndash;posterior diameter; AH, annular height; 3DC, three-dimensional circumference; 2DA, two-dimensional projected area; NPA, non-planarity angle.\u0026nbsp;\u003csup\u003e①\u003c/sup\u003e P \u0026lt; 0.05 vs control;\u0026nbsp;\u003csup\u003e②\u003c/sup\u003eP \u0026lt; 0.05 vs central IMR. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2. Comparison of mitral leaflet parameters among groups\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl (n = 60)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCentral IMR (n = 57)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEccentric IMR (n = 54)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eMVALA/cm\u0026sup2;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e6.28（5.55-6.85）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e6.89（6.65-7.69）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e8.54（7.20-9.99）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eMVPLA/cm\u0026sup2;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e4.10（3.29-4.39）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e5.52（5.00-6.12）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e4.67（3.71-5.23）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eALA/PLA CR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e1.48（1.29-1.82）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e1.22（1.18-1.28）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e1.91（1.82-1.98）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eVtent/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e1.60（1.10-1.90）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e4.90（4.10-5.40）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e3.20（2.75-3.75）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eALA/\u0026deg;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e26.70（21.90-29.40）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e24.80（23.20-26.90）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e15.20（13.35-17.65）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003ePLA/\u0026deg;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e32.40（31.50-38.40）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e28.40（27.10-32.60）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e37.80（34.75-42.60）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eMTAD/\u0026deg;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e7.60（6.40-9.90）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e3.30（2.60-7.00）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e22.70（21.40-24.90）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eHtent/mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e5.10（3.70-6.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e9.70（8.90-9.90）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e7.70（6.25-8.50）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eAMA/\u0026deg;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e125.20（122.00-128.90）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e137.90（123.00-140.20）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e132.80（129.45-140.25）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eALPM/mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e19.50（17.60-20.70）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e20.50（19.20-22.50）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e26.00（24.70-26.95）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003ePLPM/mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e18.00（17.50-18.90）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e21.40（20.50-23.00）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e26.20（25.15-27.35）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eData are median (interquartile range). MVALA, anterior-leaflet area; MVPLA, posterior-leaflet area; ALA/PLA CR, coaptation-area ratio; Vtent, tenting volume; ALA, anterior-leaflet angle; PLA, posterior-leaflet angle; MTAD, mean tethering-angle difference; Htent, tenting height; AMA, aorto-mitral angle; ALPM, distance from anterior papillary-muscle tip to anterior leaflet; PLPM, distance from posterior papillary-muscle tip to posterior leaflet.\u0026nbsp;\u003csup\u003e①\u003c/sup\u003e P \u0026lt; 0.05 vs control;\u0026nbsp;\u003csup\u003e②\u003c/sup\u003eP \u0026lt; 0.05 vs central IMR. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3. Comparison of left-ventricular parameters\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl (n = 60)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCentral IMR (n = 57)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEccentric IMR (n = 54)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003eLVEDVi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e36.16（28.27，44.04）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e94.20（85.91，102.48）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003e92.44（83.75，101.08）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003eLVEF/%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e64.40（60.83，67.96）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e40.20（30.05，50.35）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003e45.25（42.32，48.17）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003eLVGLS/%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e-21.85（-24.56，-19.13）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e-12.3（-13.82，-10.77）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003e-12.9（-15.15，-10.65）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003eE/e\u0026apos;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e7.0（6.2-7.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e15.8（13.2-18.5）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003e13.8（11.5-16.2）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eData are median (interquartile range). LVESVi, indexed end-systolic volume; LVEDVi, indexed end-diastolic volume; LVEF, left-ventricular ejection fraction; LVGLS, global longitudinal strain; E/e\u0026prime;, ratio of early transmitral velocity to tissue Doppler velocity.\u0026nbsp;\u003csup\u003e①\u003c/sup\u003e P \u0026lt; 0.05 vs control;\u0026nbsp;\u003csup\u003e②\u003c/sup\u003eP \u0026lt; 0.05 vs central IMR. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4. Comparison of left-atrial function\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl (n = 60)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCentral IMR (n = 57)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEccentric IMR (n = 54)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003eLAD/mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e34.00（33.50，34.50）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e45.00（42.50，47.50）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e49.85（36.75，62.75）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003eLAVmax/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e36.55（35.28，37.81）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e90.30（80.42，100.17）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e106.40（90.83，121.96）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003eLAVmin/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e14.45（13.12，15.77）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e62.13（53.32，70.93）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e67.48（60.27，74.69）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003eLAEI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e1.53（1.37，1.70）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e0.48（0.38，0.57）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e0.58（0.48，0.68）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003eLATEF/%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e66.95（61.89，72.01）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e36.75（31.75，41.75）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e32.70（29.07，36.32）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003eLAVpre/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e25.60（24.08，27.11）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e75.60（66.70，84.70）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e82.90（70.65，95.15）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003eLAPEF/%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e30.37（23.41，36.01）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e20.34（17.23，23.65）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e18.02（14.23，22.45）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003eLAAEF/%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e44.28（36.64，52.07）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e20.76（16.15，24.44）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e17.43（11.48，23.60）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003eLAVmaxi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e21.70（21.01，22.39）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e51.28（45.18，57.38）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e61.25（52.46，70.04）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003eLAVmini\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e8.36（7.73，8.99）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e34.90（29.00，40.80）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e39.21（34.71，43.71）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003ePALS/%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e30.70（20.56，40.83）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e10.65（8.75，12.25）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e9.20（7.97，10.42）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003eLASr/%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e28.55（24.76，32.35）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e10.35（9.58，11.11）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e9.40（6.10，12.70）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003eLAScd/%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e-10.20（-12.50，-8.10）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e-6.20（-9.30，-4.10）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e-5.50（-8.02，-3.37）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003eLASct/%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e-11.80（-13.60，-9.20）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e-4.75（-7.25，-2.24）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e-3.80（-5.07，-2.52）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003eLASI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.63（0.52，0.73）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e4.12（3.31，4.93）\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e4.90（4.31，5.48）\u003csup\u003e①②\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eData are median (interquartile range). LAD, left-atrial anteroposterior diameter; LAVmax, maximal volume; LAVmin, minimal volume; LAEI, expansion index; LATEF, total emptying fraction; LAVpre, pre-contractile volume; LAPEF, passive emptying fraction; LAAEF, active emptying fraction; LAVmaxi/LAVmini, indexed volumes; PALS, peak atrial longitudinal strain; LASr, reservoir strain; LAScd, conduit strain; LASct, contractile strain; LASI, LA stiffness index.\u0026nbsp;\u003csup\u003e①\u003c/sup\u003e P \u0026lt; 0.05 vs control;\u0026nbsp;\u003csup\u003e②\u003c/sup\u003eP \u0026lt; 0.05 vs central IMR. \u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"ischemic mitral regurgitation, eccentric regurgitation, transcatheter edge-to-edge repair, three-dimensional echocardiography, left atrial strain, TEER planning, mitral apparatus remodeling","lastPublishedDoi":"10.21203/rs.3.rs-8927278/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8927278/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThree-dimensional echocardiography combined with speckle-tracking imaging was employed to compare mitral valve geometry, dynamic deformation, and left atrial (LA) function derived from strain between eccentric-jet and central-jet ischemic mitral regurgitation (IMR). Integrated thresholds were derived to refine IMR phenotyping and inform planning for transcatheter edge-to-edge repair (TEER).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this single-center cross-sectional study, 111 consecutive patients with moderate-to-severe IMR (54 eccentric, 57 central) and 60 frequency-matched controls were prospectively enrolled. Mitral valve geometry was quantified offline using full-volume, three-dimensional transesophageal datasets. LA strain was measured by high-frame-rate two-dimensional speckle-tracking imaging. Determinants of jet eccentricity were identified by multivariable logistic regression adjusted for clinical and echocardiographic covariates.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eEccentric jets exhibited greater anterior\u0026ndash;posterior annular diameter, larger posterior leaflet angle, and lower anterior-to-posterior coaptation-length ratio, whereas central jets displayed increased tenting volume and height (all P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Both IMR groups demonstrated significantly reduced LA reservoir strain (eccentric: 9.40% vs. central: 10.35%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and lower total emptying fractions (LATEF: eccentric 32.7% vs. central 36.8%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to controls (LASr: 28.55%, LATEF: 66.95%). Notably, the eccentric group showed relatively preserved reservoir strain but more severely reduced active emptying fraction (LAAEF: 17.4% vs. 20.8%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and increased LA stiffness index (all P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), suggesting differential atrial functional remodeling patterns between IMR phenotypes.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eEccentric IMR exhibits asymmetric mitral deformation and LA remodeling with relatively preserved but still impaired reservoir function. In contrast, central IMR reflects global left ventricular (LV) sphericalization with comparatively less impaired LA stiffness. Integrated three-dimensional echocardiography provides reproducible metrics for patient-specific TEER planning.\u003c/p\u003e","manuscriptTitle":"Three-Dimensional Echocardiographic Assessment of Mitral Apparatus and Left Atrial Remodeling to Guide TEER in Eccentric versus Central Ischemic Mitral Regurgitation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-08 14:58:21","doi":"10.21203/rs.3.rs-8927278/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"21563619-b48e-4d97-a23e-bbf4b3440325","owner":[],"postedDate":"March 8th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-27T10:57:20+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-08 14:58:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8927278","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8927278","identity":"rs-8927278","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}