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Background: Recent advances in mitral valve (MV) percutaneous interventions have escalated the need for a more quantitative and comprehensive assessment of the MV, which can be best achieved using three-dimensional echocardiography. Understanding normal valve size, structure, and function is essential for differentiation of healthy from disease states. The aims of this study were to establish normative values for MV apparatus size and morphology and to determine how they vary across age, sex, and race groups using data from the World Alliance Societies of Echocardiography Normal Values Study., Methods: Three-dimensional volumetric data sets obtained on transthoracic echocardiography in 748 normal subjects (51% men) were analyzed using commercial MV analysis software (TomTec Imaging Systems) to determine annular and leaflet dimensions and areas. The subjects were divided into groups by sex (378 men and 370 women) and age (18 to 40 years [n = 266], 41 to 65 years [n = 249], and >65 years [n = 233]) to identify sex- and age-related differences. In addition, differences among black, white, and Asian populations were studied. Inter- and intraobserver variability was assessed in a subset of 30 subjects and expressed as mean absolute difference between pairs of repeated measurements., Results: Compared with women, men had larger annular size measurements, larger tenting size parameters, and larger leaflet length and area. Compared with the black and white populations, the Asian population showed significantly smaller mitral annular size. Although many of the age, sex, and race differences in MV parameters were statistically significant, they were comparable with or smaller than the corresponding measurement variability. Indexing to body surface area and height did not eliminate these differences consistently, suggesting that parameters may need to be indexed according to their dimensionality., Conclusions: This analysis of the World Alliance Societies of Echocardiography data provides normative values of mitral apparatus size and morphology. Although sex- and age-related differences were noted, they need to be interpreted with caution in view of the associated measurement variability., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Topological data analysis (TDA) can generate patient-patient similarity networks by analyzing large, complex data and derive new insights that may not be possible with standard statistics., Objectives: The purpose of this paper was to discover novel phenotypes of chronic primary mitral regurgitation (MR) patients and to analyze their clinical implications using network analysis of echocardiographic data., Methods: Patients with chronic moderate to severe primary MR were prospectively enrolled from 11 Asian tertiary hospitals (n = 850; mean age 56.9 ± 14.2 years, 57.9% men). We performed TDA to generate network models using 14 demographic and echocardiographic variables. The patients were grouped by phenotypes in the network, and the prognosis was compared by groups., Results: The network model by TDA revealed 3 distinct phenogroups. Group A was the youngest with fewer comorbidities but increased left ventricular (LV) end-systolic volume, representing compensatory LV dilation commonly seen in chronic primary MR. Group B was the oldest with high blood pressure and a predominant diastolic dysfunction but relatively preserved LV size, an unnoticed phenotype in chronic primary MR. Group C showed advanced LV remodeling with impaired systolic, diastolic function, and LV dilation, indicating advanced chronic primary MR. During follow-up (median 3.5 years), 60 patients received surgery for symptomatic MR or died of cardiovascular causes. Kaplan-Meier curves demonstrated that although group C had the worst clinical outcome (P < 0.001), group B, characterized by diastolic dysfunction, had an event-free survival comparable to group A despite preserved LV chamber size. The grouping information by the network model was an independent predictor for the composite of MR surgery or cardiovascular death (adjusted HR: 1.918; 95% CI: 1.257-2.927; P = 0.003)., Conclusions: The patient-patient similarity network by TDA visualized diverse remodeling patterns in chronic primary MR and revealed distinct phenotypes not emphasized currently. Importantly, diastolic dysfunction deserves equal attention when understanding the clinical presentation of chronic primary MR., Competing Interests: Funding Support and Author Disclosures This work was supported by grants from the National Research Foundation of Korea; a grant funded by the Korean government (Ministry of Science and ICT) (No. 2019R1A2C2084099); and the Seoul National University Hospital research fund (03-2020-0430). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Clinicians often have a difficulty in determining the presence of mitral regurgitation (MR)-related symptoms because of subjectivity. However, there are few actual measurement data for echocardiographic left ventricular (LV) and left atrial (LA) size related to the severity of MR and the relationship between MR-related symptoms and these echocardiographic parameters. Among patients enrolled in the Asian Valve Registry, we investigated 778 consecutive patients with primary MR showing sinus rhythm. Symptoms were determined by New York Heart Association grade (≤ II or ≥ III). MR severity was mild in 106, moderate in 285, and severe in 387 patients. LA volume index, LV end-diastolic diameter, and LV mass index increased with increasing MR grade [LA volume index: 47.9 (mild), 56.2 (moderate), and 64.9 ml/m 2 (severe) (p < 0.001), LV end-diastolic diameter: 51.2, 54.5, 58.1 mm (p < 0.001), and LV mass index: 101, 109, 123 g/m 2 (p < 0.001)]. Regarding moderate and severe MR, 70 patients (10.4%) were symptomatic. In multivariable analysis, for being symptomatic in moderate and severe MR patients, LV mass index (odds ratio [OR] per 10 g/m 2 increment; 1.09; 95% confidence interval [CI]: 1.005-1.18, p = 0.040), ejection fraction (OR per 1% increment; 0.96, 95%CI: 0.93-0.98, p < 0.001), female gender (OR 2.28; 95% CI: 1.31-3.98, p = 0.004), and heart rate (OR per 1 bpm increment; 1.03; 95%CI: 1.01-1.05, p = 0.007) were independent factors. LV and LA parameters on echocardiography worsened as MR severity progressed. Larger LV mass index and lower ejection fraction were independent determinant factors for MR-related symptoms. We should also pay attention to LV hypertrophy in patients with primary MR.

Background: The morbidity and mortality of patients with functional mitral regurgitation (MR) remain high, but no pharmacological therapy has been proven effective. The hypothesis of this study was that sacubitril/valsartan would be superior to valsartan alone in improving functional MR via dual inhibition of the renin-angiotensin system and neprilysin., Methods: In this double-blind trial, we randomly assigned 118 patients with heart failure with chronic functional MR secondary to left ventricular (LV) dysfunction to receive either sacubitril/valsartan or valsartan, in addition to standard medical therapy for heart failure. The primary end point was the change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, LV end-systolic volume, LV end-diastolic volume, and incomplete mitral leaflet closure area., Results: The decrease in effective regurgitant orifice area was significantly greater in the sacubitril/valsartan group than in the valsartan group (-0.058±0.095 versus -0.018±0.105 cm 2 ; P=0.032) in an intention-to-treat analysis including 117 (99%) patients. Regurgitant volume was also significantly decreased in the sacubitril/valsartan group in comparison with the valsartan group (mean difference, -7.3 mL; 95% CI, -12.6 to -1.9; P=0.009). There were no significant between-group differences regarding the changes in incomplete mitral leaflet closure area and LV volumes, with the exception of LV end-diastolic volume index ( P=0.044). We noted no significant difference in the change of blood pressure between the treatment groups, and 7 patients (12%) in the sacubitril/valsartan group and 9 (16%) in the valsartan group had ≥1 serious adverse events ( P=0.54)., Conclusions: Among patients with secondary functional MR, sacubitril/valsartan reduced MR to a greater extent than did valsartan. Our findings suggest that an angiotensin receptor-neprilysin inhibitor might be considered for optimal medical therapy of patients with heart failure and functional MR., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02687932.

Background: Exercise stress echocardiography (ESE) can be used to identify left ventricular (LV) dysfunction in asymptomatic chronic MR. NT-proBNP is the best marker for monitoring LV dysfunction., Objective: The aim of this study was to estimate the complementary prognostic value of ESE and NT-proBNP in asymptomatic degenerative MR with preserved LV ejection fraction (EF)., Methods: Symptom-limited treadmill ESE was performed in 114 asymptomatic with significant degenerative MR (ERO >20mm, RV >30ml), LV end-systolic diameter <40mm and preserved LV function (EF >60%). Post-exercise EF increase of >4% was defined as contractile reserve (CR)+., Results: MV operation was performed in 19 (16.7%) and new-onset LV systolic dysfunction was developed in 23 (20.2%) patients over 3.5±1.5years. Based on ROC curve analysis, a NT-pro BNP of 100 was deemed the most relevant cutoff value to predict primary outcome with Youden's index=131.84. In sequential Cox models, a model based on clinical data and resting echocardiography variables (χ 2 =6.87) was improved by NT-proBNP (χ 2 =13.9) and presence of CR in ESE (χ 2 =20.8; p=0.0002)., Conclusions: In asymptomatic moderate to severe or severe degenerative MR and preserved LVEF, the presence of CR in ESE and NT-proBNP provide important incremental clinical determinants. In particular, the prognosis is markedly poor for those with high NT-proBNP but with absence of CR than low NT-proBNP with presence of CR., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study sought to compare long-term outcomes of early surgery with a conventional treatment strategy in asymptomatic patients with severe mitral regurgitation (MR)., Background: The timing of surgery in asymptomatic severe MR remains controversial., Methods: From 1996 to 2009, 610 consecutive asymptomatic patients (364 men, 50 ± 14 years of age) with severe degenerative MR and preserved left ventricular function were evaluated prospectively. Early surgery was performed on 235 patients, and the conventional treatment strategy was chosen for 375 patients. We compared overall mortality, cardiac mortality, and cardiac events (operative mortality, cardiac mortality, repeat surgery, and urgent admission due to heart failure) between the 2 treatment strategies in the propensity score-matched cohort., Results: For the 207 propensity score-matched pairs, early surgery had a lower risk of cardiac mortality (hazard ratio [HR]: 0.109; 95% confidence interval [CI]: 0.014 to 0.836; p = 0.033) and cardiac events (HR: 0.216; 95% CI: 0.083 to 0.558; p = 0.002) than conventional treatment. On Cox proportional hazard model analysis, the risk of cardiac events was significantly lower in the early surgery group than in the conventional treatment group in patients aged 50 years of age and older (HR: 0.221; 95% CI: 0.086 to 0.567; p = 0.002), but not significantly different in those younger than 50 years of age (p = 0.20)., Conclusions: Compared with conservative management, early surgery is associated with significant long-term reductions of cardiac mortality and cardiac events in asymptomatic severe MR. These benefits were evident among patients age 50 years of age and older., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to investigate preoperative clinical and echocardiographic characteristics and N-terminal pro-B type natriuretic peptide (NT-proBNP) levels as prognostic factors for regression of the left ventricular (LV) mass after valvular surgery in patients with chronic severe mitral regurgitation (MR)., Methods: One hundred seventeen patients undergoing surgery for chronic severe MR were included. Plasma NT-proBNP measurements and echocardiography were performed preoperatively, immediately postoperatively, and at six and 12 months after surgery. Any regression of the LV mass was evaluated by echocardiography., Results: During follow-up, 90 patients (77%) were classified as an LV mass regression group (LVMR), defined as having a postoperative reduction in LV mass indexed against body surface area (LVMI). The remaining 27 (23%) patients were classified as NON-LVMR. The LVMR group was younger (p=0.029) and had significantly lower ratios of patients with hypertension (p=0.045) and diuretic use (p=0.005) than the NON-LVMR group. They also had lower levels of NT-proBNP (median: 446.4 pg/ml versus 1394.0 pg/ml, p=0.001). In multivariate analysis, higher preoperative NT-proBNP levels were independent predictors of no significant regression of the LV mass (odds ratio=1.731, 95% confidence intervals 1.052-2.844, p=0.010)., Conclusions: A lower preoperative NT-proBNP level predicted the regression of LV mass after valvular surgery in patients with chronic severe MR. This measure could be used as a biomarker for predicting the postoperative course in such patients., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Noninvasively measured left ventricular stroke work index (LVSWI) may be an ideal indicator that can provide more relevant information about cardiac performance in severe mitral regurgitation (MR). We sought to correlate the noninvasive LVSWI with invasive measure of LVSWI and validate its clinical usefulness by comparing the noninvasive LVSWI with exercise capacity., Methods: Twenty-nine patients with severe MR who underwent cardiac catheterization and 61 patients with severe MR who underwent cardiopulmonary exercise test were evaluated for comparison of noninvasive LVSWI with invasive LVSWI via cardiac catheterization and peak exercise capacity, respectively., Results: Mean noninvasive LVSWI was 33.1 ± 9.7 g·m/m², which was in a good agreement with invasive LVSWI (34.9 ± 15.1 g·m/m², intraclass correlation coefficient = 0.72, P < 0.001). Noninvasive LVSWI (β= 0.35, P = 0.001) was independently related with peak exercise capacity. Indexed left atrial volume (β=-0.27, P = 0.042), mean blood pressure (β=-0.21, P = 0.030), age (β=-0.47, P < 0.001) estimated pulmonary artery systolic pressure (β=-0.21, P = 0.030) and male gender (β= 0.36, P = 0.001) were also independently associated with exercise capacity., Conclusions: Noninvasive LVSWI has a good correlation with invasively measured LVSWI and is a clinically useful parameter for evaluating true cardiac performance in patients with severe MR., (© 2010, Wiley Periodicals, Inc.)

Background: Chronic severe mitral regurgitation is associated with poor clinical outcome because chronic volume overload leads to hemodynamic changes and left ventricular and left atrial remodeling. Few data are available regarding left atrial volume index regression (LAVIR) and left ventricular mass index regression (LVMIR) after valve surgery for mitral regurgitation. We aimed to identify predictive correlates of LAVIR and LVMIR and to assess the relationship between these regressions., Hypothesis: Volume overload in chronic severe mitral regurgitation may influence left atrial and ventricular remodeling and reverse remodeling., Methods: Eighty-five patients who underwent valve repair for severe chronic mitral regurgitation were consecutively enrolled. Plasma N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) and echocardiographic measurements were performed before surgery, before discharge, and at 12 months after surgery. LAVIR and LVMIR were assessed using serial echocardiography., Results: There were significant decreases in left ventricular mass index (LVMI; from 125.9 ± 31.3 g/m² to 94.8 ± 28.6 g/m², P = 0.001) and left atrial volume index (LAVI; from 75.3 ± 33.5 mL/m² to 41.7 ± 16.0 mL/m², P = 0.001) after surgery. Preoperative LAVI positively correlated with preoperative LVMI (r = 0.437, P = 0.001) and LAVIR positively correlated with LVMIR (r = 0.347, P = 0.001). In multivariate stepwise linear regression analysis, preoperative LAVI, age, hypertension, and atrial fibrillation were independently predictive of LAVIR, and preoperative LVMI, hypertension, and NT-proBNP were independently predictive of LVMIR., Conclusions: Volume overload in chronic severe mitral regurgitation may influence left ventricular remodeling and reverse remodeling, as well as left atrial remodeling and reverse remodeling. Preoperative lower LAVI, younger age, absence of hypertension, and absence of atrial fibrillation may predict LAVIR, and preoperative lower LVMI, lower NT-proBNP levels, and absence of hypertension may predict LVMIR after surgery for chronic severe mitral regurgitation., (© 2010 Wiley Periodicals, Inc.)

Background: Functional mitral regurgitation (MR) is commonly seen in dilated cardiomyopathy (DCM), which may result from left ventricular (LV) dilatation and alteration in the geometric relationship of mitral valve apparatus. However, not all patients with DCM show significant MR and left atrial (LA) enlargement. The aim of this study was to assess responsible factors for developing mitral valve regurgitation., Methods: Of 300 patients enrolled in the Acorn trial, baseline echocardiography studies were available in 288, of whom 144 were excluded because of a variety of reasons. Echocardiographic data were examined for the remaining 144 patients in sinus rhythm with DCM, but without organic mitral valve disease and ischemic heart disease. Mitral regurgitation was assessed by color-flow imaging. All echocardiographic parameters were indexed to body surface area., Results: Of 144 patients, 87 had MR grade > or =2 (group 1) and 57 had MR grade 0 or +1 (group 2). Group 1 had larger tenting area, tenting height, tethering distance, LA volume index, and mitral annular area than group 2 (all P < .001); LV volume index and ejection fraction were similar between groups. The major determinant of MR severity was tenting area (r = 0.49, P < .001), and this was best related to mitral annular area (r = 0.85, P < .001). Mitral annular area was most strongly associated with LA volume (r = 0.56, P < .001). In addition, LA volume index was highly correlated with LV diastolic dysfunction (r = 0.58, P < .001), both in total and in group 2 only., Conclusions: For patients with DCM in the Acorn trial, MR severity was associated with LA volume and mitral annular area but not with LV volume. Mitral annular area and LA volume were closely related, even in patients without significant MR. These findings suggest that LA enlargement caused by advanced diastolic dysfunction may contribute to causing significant MR by augmenting mitral annular dilatation in DCM.

Objective: Chronic mitral regurgitation (MR) results in volume overload followed by left ventricular (LV) and left atrial remodeling. The aim of this study was to investigate the relation of clinical, echocardiographic findings and N-terminal B-type natriuretic peptide (NT-proBNP) to LV reverse remodeling (LVRR) early after valve repair for severe chronic MR concomitant with modified maze procedure for atrial fibrillation (AF)., Methods: We retrospectively evaluated 60 patients who were surgically treated for severe chronic MR and AF. Plasma NT-proBNP and echocardiographic measurements were performed before surgery, before discharge and 12 months after surgery. Echocardiogram was additionally performed at 6 months. LVRR was assessed by looking at regression of LV mass index (LVMI) using echocardiography., Results: Fifty-two patients (87%) were classified in the LVRR group, defined as having a postoperative reduction in LVMI. The remaining patients were classified in the non-LVRR group. The non-LVRR group was older (p = 0.004), had a significantly higher ratio of patients with hypertension (p = 0.022), higher NT-proBNP levels (p = 0.007) and lower ejection fraction (p = 0.034) compared to the LVRR group. In multivariate analysis, age (odds ratio 0.874, p = 0.013) and NT-proBNP levels (odds ratio 0.185, p = 0.040) were independent predictors of LVRR., Conclusions: Preoperative lower NT-proBNP levels and younger age may predict LVRR early after surgical correction of chronic MR with AF., (Copyright 2009 S. Karger AG, Basel.)

For the evaluation of efficacy of cardiopulmonary exercise testing, we compared New York Heart Association functional class with peak oxygen consumption rate (VO(2)peak) in 31 patients with severe mitral regurgitation who underwent mitral valve repair surgery. One year later, the VO(2)peak values did not show significant improvement; however, the patients who had more than a mild degree of residual mitral regurgitation (n = 14) after 1 year of surgery had a VO(2)peak value that was significantly decreased (from 22.7 +/- 6.4 to 21.0 +/- 6.3 ml/kg/min, p = 0.04). Patients with a higher preoperative VO(2)peak value (>/=18.5 ml/kg/min) had a significantly better New York Heart Association functional class 1 year after surgery than patients with a lower VO(2)peak value (<18.5 ml/kg/min, p = 0.03).

Background: We evaluated the efficacy of the cardiopulmonary exercise test as an objective indicator of functional status and as a pre-operative prognostic indicator in patients with mitral regurgitation (MR) and aortic regurgitation (AR)., Methods: Cardiopulmonary exercise tests and echocardiography were performed in 47 patients (MR: 30, AR: 15, MR + AR: 2) before surgery and repeated one year after surgery. We compared the New York Heart Association (NYHA) functional class, peak oxygen consumption rate (VO2peak), exercise duration, left ventricular dimension and ejection fraction, before and after surgery., Results: Initial VO2peak and exercise duration were significantly different according to NYHA class. A year later, NYHA functional class improved from 2.1 +/- 0.1 to 1.4 +/- 0.1 (p < 0.001). The VO2peak was significantly increased (21.7 +/- 1.0 to 23.7 +/- 1.0 mL/kg per min, p = 0.008) and exercise duration also increased (521.7 +/- 35.9 to 623.3 +/- 35.7 seconds, p < 0.001). When patients were analysed according to their post-operative NYHA functional class, those with class I showed significantly different pre-operative VO2peak (class I: 23.7 +/- 1.1, II: 18.3 +/- 1.5 mL/kg per min, p = 0.005) and exercise durations (class I: 587.5 +/- 43.2, II: 415.6 +/- 55.7 seconds, p = 0.02). Patients with higher pre-operative VO2peak (19.0 mL/kg per min) more frequently became NYHA functional class I than those with a lower pre-operative VO2peak (76.7% vs. 35.3%, p = 0.02). But baseline left ventricular dimension and ejection fraction by echocardiography were not different between post-operative class I and II group., Conclusion: VO2peak and exercise duration are excellent parameters to evaluate the subjective functional class and to predict the post-operative functional class of patients with MR and/or AR. Patients with a pre-operative VO2peak of 19.0 mL/kg per min or more will have a better functional status one year after surgery.

Abstract: Purpose: Although takotsubo cardiomyopathy (TTC) has been reported to have an excellent clinical recovery, there are few data regarding clinical, laboratory, and echocardiographic findings in TTC presenting as cardiogenic shock. We aimed to assess the differences in these parameters between TTC presenting with and without cardiogenic shock. Methods: Fifty patients were enrolled from the TTC registry database and divided according to the presence of cardiogenic shock. Sixteen patients presented with cardiogenic shock as initial presentation (S group), and 34 did not (NS group). Results: The S group had a higher prevalence of dyspnea (81% vs 38%, P = .005), pulmonary edema (69% vs 29%, P = .009), and significant reversible mitral regurgitation (44% vs 15%, P = .025) than the NS group. In addition, the S group had significantly higher troponin-I (median, 8.2 vs 1.4 pg/mL; P = .043) and N-terminal prohormone brain natriuretic peptide levels (median, 8831 vs 2348 pg/mL; P = .046). During follow-up (median, 3.1 years), cardiac deaths associated with TTC itself and recurrences of TTC were not noted in both groups. Conclusions: The S group has a higher prevalence of heart failure symptoms, significant reversible mitral regurgitation, and troponin-I and N-terminal prohormone brain natriuretic peptide levels. However, with meticulous therapeutic strategies, prognosis of this syndrome may be excellent irrespective of hemodynamic instability. [Copyright &y& Elsevier]