Three-Dimensional Transthoracic Static and Dynamic Normative Values of the Mitral Valve Apparatus: Results from the Multicenter World Alliance Societies of Echocardiography Study

doi:10.1016/j.echo.2022.02.010

Journal of the American Society of Echocardiography

Volume 35, Issue 7, July 2022, Pages 738-751.e1

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https://doi.org/10.1016/j.echo.2022.02.010 Get rights and content

Highlights

•
A total of 748 healthy adult subjects were studied.
•
Normal values of 3D static and dynamic MV parameters were established.
•
Age, sex, and race affect 3D MV measurements.

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.

Section snippets

Methods

The rationale and design of the WASE Normal Values Study have been previously described.¹⁷ Briefly, this was a multicenter international, observational, prospective, cross-sectional study of healthy adult individuals. The American Society of Echocardiography invited representatives of member societies of the American Society of Echocardiography International Alliance Partners (as of March 2016) to participate in this study by enrolling 100 “normal” local healthy adult volunteers at each of the

Comparison between Sex Groups

The results of the MV analysis according to sex are shown in Table 2, Table 3, Table 4. As expected, the male population had larger BSA and was taller than the female population. MA size, shape, and leaflet measurements were all larger in men than in women (Table 2). The only parameters not significantly different between sexes were NPA, sphericity index, and annular height. Interestingly, the statistical significance of the differences between sexes in length measurements were mostly

Discussion

Previous studies reported echocardiographic normal values in specific countries or regions or performed meta-analyses to establish global normal reference ranges. Although reference values from MV quantitative analysis using data from 3D TTE and TEE have been reported,¹⁶^,22, 23, 24 to the best of our knowledge, this is the first report of normative values from a large group of multiethnic healthy individuals, derived from images obtained using a uniform acquisition protocol and analyzed in a

Conclusion

The heterogeneity of imaging acquisition protocols and populations limiting previous studies may restrict the applicability of normal values of MV parameters reported in the literature. As a part of the WASE Normal Values Study, this report provides important information with a potential to overcome these obstacles and helps in reassessing normative values of static and dynamic parameters of the MV across sex, age, and racial groups. This information may contribute to building the foundation

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Intervention for repair of secondary mitral valve disease is frequently associated with recurrent regurgitation. We sought to determine if there was sufficient evidence to support inclusion of anatomic indices of leaflet dysfunction in the management of secondary mitral valve disease.
We performed a systematic review and meta-analysis of published reports comparing anatomic indices of leaflet dysfunction with the complexity of valve repair and the outcome from intervention. Patients were stratified by the severity of leaflet dysfunction. A secondary analysis was performed comparing outcomes when procedural complexity was optimally matched to severity of leaflet dysfunction and when intervention was not matched to dysfunction.
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The classification of secondary mitral regurgitation (MR) is based on atrial functional MR (AFMR) or ventricular functional MR (VFMR) and volume changes, but the mitral leaflet coaptation angle also contributes to the MR mechanism. The clinical implications of the coaptation angle on cardiovascular (CV) outcomes have not been well evaluated. A total of 469 consecutive patients (265 AFMR vs 204 VFMR) with more than moderate MR were evaluated for the occurrence of heart failure, mitral valve operations, and CV death. The coaptation angle was assessed by measuring the internal angle between both leaflets at mid-systole using the apical 3-chamber view. A coaptation angle ≥130° was classified as leaflet flattening, and an angle <130° was classified as leaflet tethering. AFMR and VFMR were associated with higher frequencies of leaflet flattening and tethering, respectively. AFMR was more likely to be associated with older age, atrial fibrillation, and preserved ejection fraction, all of which were related to leaflet flattening. During a follow-up of 2.3 years, 83 patients had heart failure (17.7%), 21 patients underwent mitral valve operations (4.5%), and 34 patients died (7%). Compared with leaflet tethering, leaflet flattening was more significantly related to CV events, whereas CV event rates were less markedly different in A/VFMR. Irrespective of A/VFMR, leaflet flattening and atrial fibrillation were associated with a higher frequency of CV events. Adjusted analysis showed that leaflet flattening remained an independent predictor of CV events (hazard ratio 3.5, 95% confidence interval 1.11 to 4.88, p = 0.003), whereas A/VFMR did not. In conclusion, the leaflet coaptation angle in patients with functional MR could provide risk stratification superior to that of A/VFMR. Leaflet flattening appears to be associated with unfavorable clinical outcomes.
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Mitral regurgitation is the most common valvular disease, particularly in older adults. Recent literature has consistently supported that there are significant differences in mitral regurgitation outcomes between male and female patients and that this is likely multifactorial. Numerous sex differences in anatomy and pathophysiology may play a role in delayed diagnoses, referrals, and treatments for female patients. Despite the recognition of these discrepancies in the literature, many guidelines that steer clinical care do not incorporate these factors into society recommendations. Identifying and validating sex-specific diagnostic parameters and increasing the representation of female patients in trials of new mitral regurgitation treatment modalities are key factors in improving outcomes for female patients.
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Functional or secondary mitral regurgitation (MR) is associated with increased cardiovascular morbidity and mortality. Mechanistically, secondary MR is attributable to an imbalance between mitral leaflet tethering and closure forces, leading to poor coaptation. The pathophysiology of functional MR is most often the result of abnormalities in left ventricular function and remodeling, seen in ischemic or nonischemic conditions. Less commonly and more recently recognized is the scenario in which left ventricular geometry and function are preserved, the culprit being mitral annular enlargement associated with left atrial dilatation, termed atrial functional mitral regurgitation (AFMR). This most commonly occurs in the setting of chronic atrial fibrillation or heart failure with preserved ejection fraction. There is variability in the published reports and in current investigations as to the definition of AFMR. This paper reviews the pathophysiology of AFMR and focus on the need for a collective definition of AFMR to facilitate consistency in reported data and enhance much-needed research into outcomes and treatment strategies in AFMR.

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: Drs. Henry and Cotella contributed equally to this study.

: Drs. Lang and Asch contributed equally to this study.

: Dr. Henry was funded by a T32 Cardiovascular Sciences Training Grant (5T32HL7381). Mr. Schreckenberg, Mr. Blankenhagen, and Mr. Hitschrich are employees of TomTec Imaging Systems. All authors were involved in the design of the WASE study, patient enrollment, and/or data analysis, and all critically reviewed and approved the final manuscript before submission. A full list of WASE investigators is provided in the Appendix.

: Linda D. Gillam, MD, MPH, FASE, served as guest editor for this report.

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2022 by the American Society of Echocardiography.

Clinical InvestigationsThree-dimensional Echocardiography: Normal ValuesThree-Dimensional Transthoracic Static and Dynamic Normative Values of the Mitral Valve Apparatus: Results from the Multicenter World Alliance Societies of Echocardiography Study

Highlights

Background

Methods

Results

Conclusions

Section snippets

Methods

Comparison between Sex Groups

Discussion

Conclusion

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Clinical Investigations
Three-dimensional Echocardiography: Normal Values
Three-Dimensional Transthoracic Static and Dynamic Normative Values of the Mitral Valve Apparatus: Results from the Multicenter World Alliance Societies of Echocardiography Study