Novel 3-dimensional Echocardiographic Quantification of Mitral Regurgitant Volume

A complete understanding of the etiology of mitral regurgitation (MR) is crucial for a correct diagnosis of valvular dysfunction, and consequently to define and plan the most appropriate therapeutic approach, either surgical or percutaneous. Two main mechanisms have been identified underlying MR: Primary or organic MR due to intrinsic involvement of mitral valve (MV) leaflets and chordae tendinae and secondary or functional MR caused by LV pathology. Another classification of mitral valve dysfunction based on leaflet motion was proposed by Carpentier et al in 1983 which is still widely used. According to this classification, type I MR is defined as normal leaflet motion, with annular dilatation (by LV or LA dilatation) or leaflet perforation (by endocarditis). Type II MR is characterized by excessive leaflet motion due to degenerative MV disease with chordal elongation or rupture and redundant leaflets, or to papillary muscle rupture (mainly ischemic origin). Finally, type III MR can be distinguished in 2 subtypes: type IIIa, with restricted leaflet motion both in systole and diastole related to leaflet and chordal thickening and retraction secondary to rheumatic valve disease and type IIIb, with restricted leaflet motion only in systole due to LV remodeling (either global or localized) with papillary muscles displacement and chordal tethering. This functional classification can be further refined by segmental MV analysis, including scallops and commissures assessment which permits precise localization of valve dysfunction. Particularly among the degenerative MV diseases (type II MR), this analysis allows the distinction between the 2 most common forms: 1. Barlow disease, where the MV shows multi-segment redundancy, billowing and thickened tissue, and 2. fibroelastic deficiency, where the typical lesion is a chordal rupture with involvement of one single scallop. Characterization of MR etiology and MV dysfunction is performed mainly by echocardiography and is crucial to guide surgery or transcatheter intervention. Standard 2-dimensional (2D) transthoracic and transesophageal echocardiography both permit good morphological analysis of MV and subvalvular apparatus with >85% accuracy as compared to surgical inspection. However, 2D echocardiography showed suboptimal accuracy in the case of complex mitral lesions, such as commissural prolapse, bileaflet prolapse or cleft. Furthermore, 2D echocardiography is dependent on operator experience and uses geometric assumptions when providing quantitative measures for MR severity (vena contracta width and PISA) or mitral valve dimensions (annular diameters, leaflet height, etc). The introduction of real-time 3D (transesophageal) echocardiography, has significantly improved the diagnostic accuracy, showing a >95% agreement with surgical findings and providing detailed description of MV dysfunction even in complex lesions, allowing a better communication with the surgeon or interventionist. Furthermore, when using 3D echocardiography, acquisition and interpretation of the images are faster and less operator-dependent. Finally, 3D echocardiography enables unlimited image plane orientation for better understanding of the complex geometry and spatial relationship between cardiac structures and an optimal alignment for geometric assumption-free measurements.

Transthoracic echocardiography is recommended as the first-line imaging modality for MR assessment and provides useful information including valve anatomy, valve hemodynamics and hemodynamic consequences. When transthoracic echocardiography is of non-diagnostic value or when further diagnostic refinement is required, transesophageal echocardiography is advocated. Additionally, recent studies have shown the additional value of magnetic resonance imaging (MRI) in assessing the MR severity.

Qualitatively, colour flow imaging is mostly used to assess MR severity. With increasing MR, the size and extent of the regurgitant jet into the LA increases. The presence of a large eccentric jet adhering, swirling and reaching the posterior LA wall supports significant MR. The jet density of the continuous wave (CW) Doppler envelope of the MR jet can be a guide to MR severity. A dense MR signal with a full envelope indicates more severe MR than a faint signal. In severe MR, the CW envelope may be truncated with a triangular contour and an early peak velocity. The presence of flow convergence at a Nyquist limit of 50-60 cm/s should alert to the presence of significant MR. A vena contracta width <3 mm indicates mild MR, whereas a width ≥7 mm defines severe MR. Intermediate values are not accurate for distinguishing moderate from mild or severe MR and require the use of another method for verification. Pulsed wave Doppler evaluation of the pulmonary venous flow pattern helps grading MR severity. A peak E wave velocity >1.5 m/s suggests severe MR in the absence of mitral stenosis. Conversely, a dominant A wave virtually excludes severe MR. The pulsed wave Doppler mitral to aortic time velocity integral (TVI) ratio is also used as an easily measured index in organic MR. A TVI ratio >1.4 strongly suggests severe MR whereas a TVI ratio <1 favours mild MR.

Quantitatively, the flow convergence method is the most recommended quantitative approach. The radius of the proximal isovelocity surface area (PISA) is measured at mid-systole using the first aliasing velocity. Regurgitant volume and effective regurgitant orifice area (EROA) are obtained using the standard formula. The PISA method is based on the assumption of hemispheric symmetry of the velocity distribution proximal to the regurgitant lesion, which may not hold for eccentric jets, multiple jets, or complex or elliptical regurgitant orifices. In the EACVI recommendations, primary MR is considered severe if EROA is ≥40 mm2 and regurgitant volume ≥60 mL. In secondary MR, the thresholds of severity, which are of prognostic value, are 20 mm2 and 30 mL, respectively. In the 2017, the American Society of Echocardiography focused update on the assessment of MR, both primary and secondary MR are considered severe if EROA is ≥40 mm2, regurgitant volume ≥60 mL and regurgitant fraction ≥50%. Assessment of MR using MRI is reasonable to provide additional information on aetiology and severity, especially for measurements of regurgitant volume and fraction, whereas the feasibility of MRI for assessing the mechanism of MR and valve repairability are not defined yet. Of note, although MRI is more reproducible, each modality has its potential errors and limitations and is technically demanding. Finally, the presence of severe MR has significant hemodynamic effects, primarily on the LV and LA. When MR is more than mild, it is mandatory to provide the LV diameters, volumes and ejection fraction as well as the LA volume and the pulmonary arterial systolic pressure in the final echocardiographic report.

These highlight the unmet clinical need that we still face in clinical practice: low agreement across methodologies and observers to grade MR, reliance on 2D echocardiographic data with numerous limitations, evaluation of a single frame to extrapolate the quantification of regurgitant volume and limited data to compare 3D imaging techniques (echocardiography and MRI) to establish the true gold standard for the measurement of the regurgitant volume.

Current technical developments have allowed the 3D reconstruction of the convergence zone of the mitral regurgitant jet along the entire systole. This methodology is semiautomated, limiting the manipulation of the observer at minimum and therefore improving reproducibility of the measurement of regurgitant volume. The 3D-CFQ software (proprietary of Philips Ultrasound) has been used in limited cohort of patients and the comparison with 3-dimensional vena contracta area of the regurgitant jet as well as with cardiac magnetic resonance-derived regurgitant volume has not been extensively evaluated.

The present study has two hypotheses:

1. -The 3D-CFQ software provides better agreement with cardiac magnetic resonance to quantify mitral regurgitant volume from 3-dimensional transesophageal echocardiography as compared to 2-dimensional echocardiographic quantification of mitral regurgitant volume.
2. -In addition, the correlation between 3-dimensional vena contracta area measured on 3-dimensional echocardiographic data of the regurgitant jet and the regurgitant volume quantified with the novel 3D-CFQ software is better than the correlation with 2-dimensional effective regurgitant orifice area quantified with the proximal isovelocity surface area method.

The primary objective is to demonstrate that 3D-CFQ software for the quantification of the mitral regurgitation is more reproducible and accurate than the conventional assessment of mitral regurgitation performed with 2-dimensional echocardiography.

The secondary objective is to demonstrate the agreement between 3D-CFQ measurement of the mitral regurgitant volume and the cardiac magnetic resonance measurement of the regurgitant volume is better than the agreement between 2-dimensional echocardiography and cardiac magnetic resonance.

This is a prospective, multicenter observational study. Patients with at least moderate mitral regurgitation of any etiology who are referred for transesophageal echocardiographic evaluation will be included. Patients without contraindications for cardiac magnetic resonance will undergo this exam to compare the echocardiographic data with the cardiac magnetic resonance data as indicated in the study.

Patients with at least moderate mitral regurgitation of any etiology who are referred for transesophageal echocardiographic evaluation will be included. Patients without contraindications for cardiac magnetic resonance will undergo this exam to compare the echocardiographic data with the cardiac magnetic resonance data as indicated in the study.