Flow adjusted transmitral pressure gradient as a modified indicator of functional mitral stenosis after repair for degenerative mitral regurgitation.

BACKGROUND AND AIM: After repair of degenerative mitral regurgitation (DMR), the focus is on functional mitral stenosis (FMS) when there is a decline of mitral hemodynamics. Yet, the clinical impacts and a standardized definition are still undecided. Since common mitral hemodynamic parameters are influenced by transmitral flow, the aim of this study is to seek the impact of flow adjusted transmitral pressure gradient (TMPG) by left ventricular stroke volume (LVSV) on the midterm outcomes. METHODS: Three hundred one patients who had undergone isolated mitral valve repair for degenerative lesions with annuloplasty prosthesis between October 2012 and June 2019 were included. Postoperative adverse events occurred in 20 patients (6.6%). Flow adjusted TMPG was defined as TMPG/LVSV. RESULTS: Common mitral hemodynamic parameters were not associated with adverse events. By multivariable analysis, patients' age, left ventricular ejection fraction (LVEF) and mean TMPG/LVSV were isolated as independent predictors (adjusted hazard ratio: 1.05, 0.95, and 1.16; p = .037, .005, and .035). Flow adjusted TMPG was significantly higher in the full ring group compared to the partial band group (0.051 mmHg/ml, [0.038-0.068] vs. 0.041 mmHg/ml, [0.031-0.056]; p < .001) and had a significantly negative correlation with the size of the annuloplasty prosthesis (r = -0.37, p < .001). CONCLUSIONS: Conventional mitral hemodynamic parameters were not associated with adverse cardiac events after repair for DMR. Adjustment by flow has a potential to advance pressure gradient to a more sensitive indicator of FMS associated with clinical outcomes.

Potential mechanism of left ventricular spherical remodeling: association of mitral valve complex-myocardium longitudinal tissue remodeling mismatch.

Since mitral valve (MV) complex (MVC) longitudinally bridges left ventricular (LV) base end and its middle, insufficient MVC longitudinal tissue length (TL) elongation relative to whole LV myocardial longitudinal TL elongation could limit LV-base-longitudinal-TL elongation, leading to predominant LV-base-transverse-TL elongation, constituting LV spherical remodeling. In 30 patients with dilated cardiomyopathy (DCM), 30 with aortic regurgitation (AR), and 30 controls, LV sphericity, LV-apex- or base-transverse- and longitudinal-TL, MVC-longitudinal-TL, and whole-LV-longitudinal-TL were measured by three-dimensional (3D) echocardiography. Ratio of each measure versus mean normal value (i.e., LV-apex-transverse-TL ratio) was considered to express the directional and regional tissue elongation. [LV-base-longitudinal-TL ratio/global-LV-TL ratio] and [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] were obtained as the degree of LV-base-longitudinal-TL or MVC-longitudinal-TL elongation relative to the whole LV elongation. LV-apex-transverse-, LV-apex-longitudinal-, and LV-base-transverse-TL ratios were significantly increased (1.27 to 1.42, P < 0.01) in both DCM and AR, while the LV-base-longitudinal-TL ratio was not increased in DCM [1.04 ± 0.19, not significant (ns)] and only modestly increased in AR (1.12 ± 0.21, P < 0.01). Whole-LV-longitudinal-TL ratio was significantly increased in both DCM and AR (1.22 ± 0.18 and 1.20 ± 0.16, P < 0.01), while MVC-longitudinal-TL ratio was not or only modestly increased in both groups (1.07 ± 0.15, ns, and 1.12 ± 0.17, P = 0.02, respectively). Multivariable analysis revealed that LV sphericity was independently related to a reduced [LV-base-longitudinal-TL ratio/global-LV-TL ratio] (standard ß = -0.42, P < 0.01), which was further related to a reduced [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] (standard ß = 0.72, P < 0.01). These are consistent with the hypothesis that relatively less MVC-longitudinal-TL elongation in the process of primary LV myocardial tissue elongation may limit LV-base-longitudinal-TL elongation, contributing to LV spherical remodeling.NEW & NOTEWORTHY Left ventricular (LV) spherical remodeling is associated with poor prognosis and less-effective cardiac performance, which commonly develops in dilated cardiomyopathy. However, its mechanism remains unclear. We hypothesized and subsequently clarified that less mitral valve complex (MVC) tissue longitudinal elongation relative to whole LV myocardial tissue longitudinal elongation is related to disproportionately less LV base longitudinal versus transverse myocardial tissue elongation, constituting spherical remodeling. This study suggests modification of MVC tissue elongation could be potential therapeutic targets.

Relations of Augmented Systolic Annular Expansion and Leaflet/Papillary Muscle Dynamics in Late-Systolic Mitral Valve Prolapse Evaluated by Echocardiography with a Speckle Tracking Analysis.

The mechanism of systolic annular expansion in mitral valve prolapse (MVP) is not clarified. Since annular expansion is systolic outward shift of MV leaflet/chorda tissue complex at superior and outer ends, annular expansion could be related to inward (superior) shift of the complex at another inferior and inner end of the papillary muscle (PM) tip and/or systolic lengthening of the tissue complex, especially MV leaflets.MV annulus systolic expansion, PMs' systolic superior shift, and MV leaflets' systolic lengthening were evaluated by echocardiography with a speckle tracking analysis in 25 normal subjects, 25 subjects with holo-systolic MVP and 20 subjects with late-systolic MVP.PMs' superior shift, MV leaflets' lengthening, MV annular area at the onset of systole and subsequent MV annulus expansion were significantly greater in late-systolic MVP than in holo-systolic MVP (4.6 ± 1.6 versus 1.5 ± 0.7 mm/m2, 2.5 ± 1.4 versus 0.6 ± 2.0 mm/m2, 6.8 ± 2.5 versus 5.7 ± 1.0 cm2/m2 and 1.6 ± 0.8 versus 0.1 ± 0.5 cm2/m2, P < 0.001, respectively). Multivariate analysis identified MV leaflets' lengthening and PMs' superior shift as independent factors associated with MV annular expansion.Conclusions: These results suggest that systolic MV annular expansion in MVP is related to abnormal MV leaflets' lengthening and PMs' superior shift.

Prognostic Value of BNP Reduction During Hospitalization in Patients With Acute Heart Failure.

BACKGROUND: Prognostication of patients discharged after acute heart failure (AHF) hospitalization remains challenging. Body weight (BW) reduction is often used as a surrogate marker of decongestion despite the paucity of evidence. We thought to test the hypothesis that B-type natriuretic peptide (BNP) reduction during hospitalization has independent prognostic value in AHF. METHODS AND RESULTS: We studied the prognostic predictability of percentage BNP reduction achieved during hospitalization in patients from the REALITY-AHF study. Percentage BNP reduction was defined as (BNP on admission - BNP at discharge) / BNP on admission × 100. The primary endpoint was 1-year all-cause death. In 1028 patients (age, 77 ± 13 years; 57% male; left ventricular ejection fraction, 47 ± 16%) with AHF, median BNP level at admission was 747 ng/L (interquartile range, 439-1367 ng/L) and median percentage BNP reduction was 62.5% (interquartile range, 36.5-78.5%). The smallest percentage BNP reduction quartile had more than 2-fold higher risk of all-cause death than the greatest quartile (23.0% vs 9.7%, P< .001). After adjusting for covariates including BNP at discharge, the percentage BNP reduction was significantly associated with all-cause death (hazard ratio 0.96, 95% confidence interval 0.93-0.99, P= .032), whereas percentage BW reduction was not. Percentage BNP reduction was more predictive in patients with heart failure with reduced ejection fraction than in those with preserved ejection fraction. CONCLUSIONS: The prognostic value of percentage BNP reduction during hospitalization was superior to that of percentage BW reduction and was independent of other risk markers, including BNP at discharge.

Surgical as Opposed to Transcatheter Aortic Valve Replacement Improves Basal Interventricular Septal Hypertrophy.

BACKGROUND: Basal interventricular septum (IVS) hypertrophy (BSH) with reduced basal IVS contraction and IVS-aorta angle is frequently associated with aortic stenosis (AS). BSH shape suggests compression by the longitudinally elongated ascending aorta, causing basal IVS thickening and contractile dysfunction, further suggesting the possibility of aortic wall shortening to improve the BSH. Surgical aortic valve replacement (SAVR), as opposed to transcatheter AVR (TAVR), includes aortic wall shortening by incision and stitching on the wall and may potentially improve BSH. We hypothesized that BSH configuration and its contraction improves after SAVR in patients with AS. Methods and Results: In 32 patients with SAVR and 36 with TAVR for AS, regional wall thickness and systolic contraction (longitudinal strain) of 18 left ventricular (LV) segments, and IVS-aorta angle were measured on echocardiography. After SAVR, basal IVS/average LV wall thickness ratio, basal IVS strain, and IVS-aorta angle significantly improved (1.11±0.24 to 1.06±0.17; -6.2±5.7 to -9.1±5.2%; 115±22 to 123±14°, P<0.001, respectively). Contractile improvement in basal IVS was correlated with pre-SAVR BSH (basal IVS/average LV wall thickness ratio or IVS-aorta angle: r=0.47 and 0.49, P<0.01, respectively). In contrast, BSH indices did not improve after TAVR. CONCLUSIONS: In patients with AS, SAVR as opposed to TAVR improves associated BSH and its functional impairment.

Prolapse Volume to Prolapse Height Ratio for Differentiating Barlow's Disease From Fibroelastic Deficiency.

BACKGROUND: As mitral valve (MV) repair for Barlow's disease remains surgically challenging, it is important to distinguish Barlow's disease from fibroelastic deficiency (FED) preoperatively. We hypothesized that the prolapse volume to prolapse height ratio (PV-PH ratio) may be useful to differentiate Barlow's disease and FED.Methods and Results:In 76 patients with MV prolapse who underwent presurgical transesophageal echocardiography, the 3D MV morphology was quantified: 19 patients were diagnosed with Barlow's disease and 57 with FED. The patients with Barlow's disease had greater prolapse volume and height than the patients with FED, as well as greater PV-PH ratio (0.61±0.35 vs. 0.17±0.10, P<0.001). Receiver-operating characteristic analysis revealed that with a cutoff value of 0.27, the PV-PH ratio differentiated Barlow's disease from FED with 84.2% sensitivity and 84.2% specificity. Net reclassification improvement showed that the differentiating ability of the PV-PH ratio was significantly superior to prolapse volume (1.30, P<0.001). After being adjusted by each of prolapse volume and height, annular area and shape, and the number of prolapsed segments, the PV-PH ratio had an independent association with Barlow's disease. CONCLUSIONS: The PV-PH ratio was able to differentiate Barlow's disease from FED with high accuracy. 3D quantification including this value should be performed before MV repair.

Efficacy and Accuracy of Novel Automated Mitral Valve Quantification: Three-Dimensional Transesophageal Echocardiographic Study.

BACKGROUND: Previous studies indicated that the three-dimensional features of the mitral valve (MV) have a significant impact on MV disease. However, quantification of MV with manual tracing software was too time-consuming for routine clinical practice. This study was performed to investigate the efficacy and accuracy of MV quantification with a novel highly automated commercially available software package developed for this purpose. METHODS: Using the manual tracing and automated package, two expert sonographers and one cardiologist individually analyzed three-dimensional datasets acquired with transesophageal echocardiography from 74 patients (15 with functional mitral regurgitation, 32 with MV prolapse, and 27 normal subjects) retrospectively. Time for analysis and inter-observer agreement were compared between the two methods, and agreement of measurements was analyzed using Cronbach's α. RESULTS: Time for analysis using the automated package was significantly shorter than manual tracing (whole cohort, 260 ± 65 vs. 381 ± 68 seconds, P < 0.001; functional mitral regurgitation, 234 ± 42 vs. 378 ± 64 seconds, P < 0.001; MV prolapse, 293 ± 69 vs. 407 ± 67 seconds, P < 0.001; normal controls, 235 ± 52 vs. 351 ± 60 seconds, P < 0.001). There was good agreement among all three observers using both methods, and measurements with the automated package agreed well with the manual tracing values. CONCLUSIONS: The novel automated software package reduced time for quantification of MV with similar accuracy compared to the manual method. Automated quantification is useful and may be a key to widespread adoption of three-dimensional quantification in clinical practice.

Dynamic changes in echocardiographic parameters in acute decompensated heart failure: REALITY-ECHO.

BACKGROUND: Appropriate evaluation of hemodynamic status is vital in the management of acute heart failure (AHF). We aimed to investigate the changes in echocardiographic parameters during very acute phases of AHF and their association with clinical outcomes. METHODS: Patients who were admitted to four Japanese hospitals with AHF were prospectively enrolled. Comprehensive echocardiography and B-type natriuretic peptide (BNP) were assessed both on admission and the second day. RESULTS: A total of 271 patients (80 ±â€¯12 years old, 52 % male) was included. Overall, transmitral E velocity, E/A, tricuspid regurgitation pressure gradient (TRPG), and inferior vena cava diameter significantly decreased, and stroke volume and left ventricular ejection fraction showed a significant increase by the second day, whereas E/e' did not change. On the second day, BNP increased in 50 patients (18 %). Despite similar baseline characteristics, patients with increased BNP showed a significantly smaller improvement in transmitral flow parameters (E and A velocity, E/A, and flow patterns) and a smaller decrease in TRPG compared with patients with decreased BNP. Other echocardiographic parameter changes were not different between the groups. A combination of improvement in transmitral flow and TRPG was significantly associated with 90-day and 1-year composite events of all-cause death and heart failure hospitalization after adjustment by the Get With the Guidelines-Heart Failure risk score. CONCLUSIONS: Echocardiographic parameters show a dynamic change in the very acute phase of AHF. Several parameters, such as the transmitral flow and TRPG might be useful in monitoring favorable hemodynamic change.

Mitral valve early systolic billowing induces following annular expansion and leaflet augmentation in Barlow's disease: sequential analysis using 3D echocardiography.

AIMS: Although systolic expansion of the annulus has been recognized in Barlow's disease, the mechanisms of the unique pathological movement of the annulus and its relation to the leaflet augmentation have not yet been clarified. We aimed to investigate the detailed mechanisms of the characteristic mitral apparatus dynamics in Barlow's disease by frame-by-frame sequential geometric analysis using real-time 3D transoesophageal echocardiography. METHODS AND RESULTS: Fifty-three patients with Barlow's disease and severe mitral regurgitation without torn chordae, as well as 10 controls, were included. We evaluated geometric changes in the mitral complex using 3D transoesophageal echocardiography at five points during systole. To identify early systolic billowing of leaflets, the annulo-leaflet angle was measured. We also performed a more detailed analysis in four consecutive frames just before and after leaflet free-edge prolapse above the annulus plane. The median annulo-leaflet angle of both leaflets in early systole was >0° (above annulus plane) in patients with Barlow's disease, and billowing of the leaflet body was observed from early systole. The prolapse volume of both leaflets increased markedly from early to mid-systole [1.60 (0.85-2.80) to 4.00 (2.10-6.45) mL; analysis of variance (ANOVA), P < 0.001; post hoc, P < 0.05]. With frame-by-frame analysis, dynamic augmentation of the annulus and leaflets developed between frames just before and just after leaflet free-edge prolapse (ANOVA, P < 0.01; post hoc, P < 0.05). CONCLUSION: In Barlow's disease, early systolic billowing of the mitral leaflet induces systolic annulus expansion followed by leaflet augmentation and leaflet free-edge prolapse.

Bendopnea prevalence and prognostic value in older patients with heart failure: FRAGILE-HF-SONIC-HF post hoc analysis.

AIMS: This study aimed to investigate the prevalence, clinical characteristics, and prognostic value of bendopnea in older patients hospitalized for heart failure. METHODS: This post hoc analysis was performed using two prospective, multicenter, observational studies: the FRAGILE-HF (main cohort) and SONIC-HF (validation cohort) cohorts. Patients were categorized based on the presence of bendopnea, which was evaluated before discharge. The primary endpoint was 2-year all-cause mortality after discharge. RESULTS: Among the 1,243 patients (median age, 81 years; 57.2% male) in the FRAGILE-HF cohort and 225 (median age, 79 years; 58.2% men) in the SONIC-HF cohort, bendopnea was observed in 31 (2.5%) and 10 (4.4%) patients, respectively. Over a 2-year follow-up period, all-cause death occurred in 20.8% and 21.9% of the patients in the FRAGILE-HF and SONIC-HF cohorts, respectively. Kaplan-Meier survival curves demonstrated significantly higher mortality rates in patients with bendopnea than in those without bendopnea in the FRAGILE-HF (log-rank P = 0.006) and SONIC-HF cohorts (log-rank P = 0.014). Cox proportional hazard analysis identified bendopnea as an independent prognostic factor for all-cause mortality in both the FRAGILE-HF (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.18-3.78, P = 0.012) and SONIC-HF cohorts (HR 4.20, 95% CI 1.63-10.79, P = 0.003), even after adjusting for conventional risk factors. CONCLUSIONS: Bendopnea was observed in a relatively small proportion of older patients hospitalized for heart failure before discharge. However, its presence was significantly associated with an increased risk of all-cause mortality.

This study investigated how common it is for older patients with heart failure to have trouble breathing when they bend forward, and whether this affects their chances of survival. The study found that although this problem is not very common, it is linked to a higher risk of death. Key findings: Only a small number of older patients with heart failure have trouble breathing when they bend forward.However, those who do have this problem are more likely to die.

Physiological and prognostic differences between types of exercise stress echocardiography for functional mitral regurgitation.

OBJECTIVE: Secondary mitral regurgitation (MR) demonstrates dynamic change during exercise. This prospective observational study aimed to compare exercise stress echocardiography (ESE) where handgrip exercise (handgrip-ESE) or semisupine ergometer exercise was performed (ergometer-ESE) for patients with secondary MR. METHODS: Handgrip-ESE and symptom-limited ergometer-ESE were performed for 53 patients (median age (IQR): 68 (58-78) years; 70% male) on the same day. Baseline global longitudinal strain (GLS) was 9.2% (6.0%-14.0%) and MR volume was 20 (14-26) mL. All-cause death and cardiac hospitalisation were tracked for median 439 (101-507) days. RESULTS: Handgrip-ESE induced slightly but significantly greater degrees of MR increase (median one grade increase; p<0.001) than ergometer-ESE, although the changes in other parameters, including GLS (+1.1% vs -0.6%, p<0.001), were significantly smaller. Correlations between the two examinations with respect to the changes in the echocardiographic parameters were weak. Kaplan-Meier analyses revealed poor improvement in GLS during ergometer-ESE, but not the change in MR, was associated with adverse events (p=0.0065). No echocardiographic change observed during handgrip-ESE was prognostic. After adjusting for a clinical risk score, GLS changes during ergometer-ESE remained significant in predicting the adverse events (HR 0.39, p=0.03) A subgroup analysis in patients with moderate or greater MR at baseline (n=27) showed the same results as in the entire cohort. CONCLUSIONS: The physiological and prognostic implications of handgrip-ESE and ergometer-ESE findings significantly differ in patients with left ventricular dysfunction and secondary MR. The type of exercise to be performed in ESE should be carefully selected.

Impact of type and size of annuloplasty prosthesis on hemodynamic status after mitral valve repair for degenerative disease.

OBJECTIVE: The aim of this study is to evaluate mitral valve hemodynamics after mitral valve repair for degenerative disease, and seek the impact of type/size of annuloplasty prosthesis on resting cardiac hemodynamics. METHODS: Between October 2012 and June 2019, 301 patients underwent isolated mitral valve repair for degenerative disease were enrolled. Correlation between postoperative mitral hemodynamics and type/size of annuloplasty prosthesis was evaluated. RESULTS: There were significant correlations between annuloplasty size and peak velocity (r = -0.41, p < 0.001), peak transmitral pressure gradient (TMPG) (r = -0.40, p < 0.001), mean TMPG (r = -0.41, p < 0.001), effective orifice area (EOA) (r = 0.26, p < 0.001), and pulmonary artery systolic pressure (r = -0.15, p = 0.010). In patients with larger annuloplasty prostheses (≥30 mm), the type of annuloplasty prosthesis (band or ring) did not influence the mitral hemodynamics, however, mean TMPG was significantly greater in patients with a full ring (2.9 mmHg [2.1-3.7] vs. 4.0 mmHg [2.8-5.0], p < 0.001) in patients with smaller annuloplasty (<30 mm). Left ventricular ejection fraction and stroke volume were significantly associated with an increase of TMPG (r = 0.14, p = 0.016 and r = 0.24, p < 0.001). CONCLUSIONS: A larger partial band had the potential to improve mitral hemodynamics after mitral repair for degenerative disease. However, echocardiographic mitral hemodynamics was influenced by LV function. Therefore, a more accurate method is required to elucidate the true impact of mitral repair on hemodynamics.

Exercise stress echocardiogram for the evaluation of change in the ventricular-arterial interaction after thoracic endovascular aortic repair.

OBJECTIVES: The aim of this study was to explore, with exercise echocardiography, the potential impact of thoracic endovascular aortic repair (TEVAR) on the ventricle-aorta coupling, based on the hypothesis that the interaction between the ventricle and aorta may be influenced by an increase in aortic stiffness due to the stent graft. METHODS: Of the patients who underwent isolated TEVAR for thoracic aortic diseases between April 2016 and December 2016, changes found in haemodynamic and echocardiographic parameters between the control (n = 17) and TEVAR (n = 30) groups were analysed by a stress echocardiogram. RESULTS: The end-systolic elastance significantly increased with stress in both groups [from 3.0 (2.5-4.5) mmHg/ml to 4.8 (3.7-6.5) mmHg/ml, P < 0.001, in the control group and from 2.9 (2.0-3.5) mmHg/ml to 3.4 (2.6-4.2) mmHg/ml, P < 0.001, in the TEVAR group]. The arterial elastance significantly elevated only in the TEVAR group [from 1.6 (1.3-1.8) mmHg/ml to 1.7 (1.5-2.0) mmHg/ml, P = 0.007] and arterial elastance/end-systolic elastance (ventricular-arterial coupling) significantly decreased only in the control group [from 0.5 (0.4-0.7) to 0.4 (0.3-0.5), P = 0.002, in the control group and from 0.6 (0.4-0.8) to 0.5 (0.4-0.6), P = 0.10, in the TEVAR group]. In the control group, the change in end-systolic elastance and ventricular-arterial coupling tended to be greater (P = 0.002 and 0.07). CONCLUSIONS: An exercise echocardiogram showed the underlying influences of TEVAR on the interaction between the heart and aorta. TEVAR may have the potential to suppress left ventricular contractile capacity and increase cardiac afterload during exercise. CLINICAL TRIAL REGISTRATION NUMBER: A201770-01.

Residual Mitral Regurgitation After Repair for Posterior Leaflet Prolapse-Importance of Preoperative Anterior Leaflet Tethering.

BACKGROUND: Carpentier's techniques for degenerative posterior mitral leaflet prolapse have been established with excellent long-term results reported. However, residual mitral regurgitation (MR) occasionally occurs even after a straightforward repair, though the involved mechanisms are not fully understood. We sought to identify specific preoperative echocardiographic findings associated with residual MR after a posterior mitral leaflet repair. METHODS AND RESULTS: We retrospectively studied 117 consecutive patients who underwent a primary mitral valve repair for isolated posterior mitral leaflet prolapse including a preoperative 3-dimensional transesophageal echocardiography examination. Twelve had residual MR after the initial repair, of whom 7 required a corrective second pump run, 4 underwent conversion to mitral valve replacement, and 1 developed moderate MR within 1 month. Their preoperative parameters were compared with those of 105 patients who had an uneventful mitral valve repair. There were no hospital deaths. Multivariate analysis identified preoperative anterior mitral leaflet tethering angle as a significant predictor for residual MR (odds ratio, 6.82; 95% confidence interval, 1.8-33.8; P=0.0049). Receiver operator characteristics curve analysis revealed a cut-off value of 24.3° (area under the curve, 0.77), indicating that anterior mitral leaflet angle predicts residual MR. In multivariate regression analysis, smaller anteroposterior mitral annular diameter (P<0.001) and lower left ventricular ejection fraction (P=0.002) were significantly associated with higher anterior mitral leaflet angle, whereas left ventricular and left atrial dimension had no significant correlation. CONCLUSIONS: Anterior mitral leaflet tethering in cases of posterior mitral leaflet prolapse has an adverse impact on early results following mitral valve repair. The findings of preoperative 3-dimensional transesophageal echocardiography are important for consideration of a careful surgical strategy.

Insufficient Leaflet Remodeling in Patients With Atrial Fibrillation: Association With the Severity of Mitral Regurgitation.

BACKGROUND: The relationship between annular dilatation caused by atrial fibrillation (AF) and mitral regurgitation (MR) remains controversial. We hypothesized that the small ratio of total leaflet area/annulus area (TLA/AA), reflecting insufficient leaflet remodeling to annular dilatation, is a main component of MR in patients with AF. METHODS AND RESULTS: Three-dimensional transesophageal echocardiographic data of the mitral valve were analyzed in 28 AF patients with moderate or severe MR (MR group), age- and sex-matched 56 AF patients with mild or less MR (non-MR group), and 16 control subjects. AA was significantly greater in both the MR (645±126 mm2/m2, P<0.001) and non-MR groups (568±121 mm2/m2, P=0.001) compared with control subjects (444±108 mm2/m2). However, TLA/AA was significantly smaller in the MR (1.29±0.10, P<0.001), but not in the non-MR group (1.65±0.24, P>0.99), compared with control subjects (1.70±0.29). In linear regression analysis, TLA/AA was inversely associated with the effective regurgitant orifice (r=-0.73, P<0.001). The area under the receiver-operating-characteristics curve of TLA/AA was significantly greater than that of AA (0.95 versus 0.72, P<0.001). Multivariable analysis revealed that small TLA/AA (P<0.001) was independently associated with significant MR, while AA was not (P=0.26). CONCLUSIONS: In patients with AF, insufficient leaflet remodeling to annular dilatation, rather than crude annular dilatation, was strongly associated with the severity of MR.