Mitral regurgitation (MR) is a common finding on echocardiography but can be difficult to quantify due to multiple dynamic factors that affect severity of MR and the three-dimensional (3D) nature of the jet.

Identification of Mechanism of MR

MR should first be identified as primary or secondary. Primary MR is most commonly caused by myxomatous degeneration due to fibroelastic deficiency or Barlow's disease. The abnormality can be focal or diffuse, causing mitral valve (MV) prolapse.¹ In secondary MR, the leaflets themselves are normal, or the degree of leaflet abnormality is not sufficient to cause the degree of MR visualized. Instead, abnormal posterior, lateral, and apical displacement of the papillary muscles causes incomplete closure of the mitral leaflets.² There is often visualized tethering or decreased mobility of the mitral leaflets.³ Apical displacement, informally called tethering, is indicative of a more apical leaflet coaptation point instead of at the annular plane (Figure 1). Apical displacement or tethering is best viewed in apical four-chamber views.

Figure 1

Hemodynamic Considerations

MR is dynamic in nature; therefore, severity varies based on loading conditions such volume status or systemic blood pressure of the patient. The degree of MR on transthoracic echocardiography (TTE) in an awake patient is commonly more severe than that on transesophageal assessment under conscious sedation or in the operating room in context of multiple vasoactive agents. In the context of MR caused by systolic anterior MV motion, it is most commonly associated with hypertrophic obstructive cardiomyopathy or following MV repair with an annuloplasty ring; in these situations, left ventricular (LV) volume significantly affects development of MR. Changes in heart rhythm including right ventricular pacing, prolonged PR interval, premature ventricular complexes, and heart block can influence assessment of severity of MR.⁴

In acute MR due to ruptured chordae tendineae, ruptured papillary muscle, or leaflet perforation, the proximal and distal color MR jet are often eccentrically oriented and, therefore, may be underestimated.⁵ It is important to scan across the coaptation line of the leaflet to fully capture the MR jet. In these situations, assessment of etiology of MR, the presence of hyperdynamic LV function, systolic flow reversal in the pulmonary veins, and clinical findings should be adequate to substantiate the diagnosis of severe MR.

Quantitative Assessment of MR Severity

Color flow Doppler provides three methods of assessing MR degree. Distal jet area relative to left atrial area is the most intuitive but often the least reliable method because the color flow area is dependent on loading factors such as the driving pressure (systemic blood pressure), volume status of patient, shape of the regurgitant orifice, and momentum of blood cells, which can be lost in very eccentric jets. If the regurgitant orifice is thin and narrow, the color flow area will change depending on probe angulation. Machine settings such as Doppler gain and transducer frequency can also impact jet area.⁴ Jet area is typically assessed in apical views (Figure 1), although all views where distal jet area is best imaged can be used. Distal jet areas are best used with central jets because eccentric jets are often underestimated by distal jet area.

Vena contracta (VC) width, the narrowest portion of the MR jet best assessed in the parasternal long-axis view (Figure 2), is a relatively load-independent measure of MR severity. It assumes a circular orifice, and because of this, VC width tends to underestimate secondary MR or MR with a non-circular orifice. The frame with the largest VC width should be used for measurement, and the time point in the cardiac cycle that is used for measurement may vary depending on etiology. The Nyquist limit should be ≥50 cm/s, and gain should be increased so that it is just under the threshold at which color noise occurs,⁶ with the goal of optimizing color Doppler resolution to more accurately measure the VC width. The scale itself should not be decreased (Figure 2). Use of 3D-guided VC width has been shown to improve reproducibility of the measurement and more closely correlates with effective regurgitant orifice area (EROA).⁷ 3D VC area measurement has also been found to correlate more closely to EROA than estimation by two-dimensional (2D) proximal isovelocity surface area (PISA) method.⁸

Figure 2

Flow convergence, or the PISA, is used to calculate an EROA using the formula in Table 1. To perform this measurement, the following steps should be performed:

1. The PISA region should be magnified to optimize PISA measurement.
2. Baseline should be adjusted in the direction of the regurgitant jet. This serves to increase the PISA zone for measurement of the radius. For transthoracic apical views, the baseline is shifted downward. The optimal baseline shift level is the point where the PISA radius can be measured accurately without including random blood flow present in LV cavity. This typically is in the range of 30-40 cm/sec. If the PISA region is particularly large, such as in very large MR jets, the extent of baseline shifting may be less.
3. The radius should be measured from the point of color aliasing (red/yellow border) to the ventricular aspect of the mitral leaflets or the level of VC measurement (Figure 3). Angle correction can be used if the PISA impinges on leaflets or LV wall.⁴

Table 1: Doppler Methods of Assessing MR Severity

Figure 3

Again, the assumption in use of PISA for MR estimation is a single circular regurgitant orifice. Thus, in secondary MR, the 2D PISA can result in underestimation of severity. An EROA of ≥0.4 cm² has been shown to be predictive of a decreased 5-year survival.⁹

VC and PISA measurements are only modestly reliable for distinction between severe and non-severe MR, with a large variation in interobserver agreement.¹⁰ All measurements should be made in a zoomed view to minimize error. It must be noted that all measurements done in a single frame will overestimate MR that is not holosystolic, for example in MV prolapse when MR is late systolic. The application of color Doppler methods for assessing severe MR should be performed in holosystolic MR jets. Parameters used to determine severe MR are found in Table 2.

Table 2: Criteria for Severe MR⁴

Quantitative Measures	Specific Criteria*
EROA ≥0.4 cm2 Regurgitant volume ≥60 ml Regurgitant fraction ≥50%	Flail leaflet VC width ≥0.7 cm PISA radius ≥1.0 cm at Nyquist of 30-40 cm/s Central large jet >50% of left atrial area Pulmonary vein systolic flow reversal Enlarged LV with normal function
*Definitely severe if ≥4 specific criteria

Other Echocardiographic Modalities

Exercise stress testing can be useful to assess functional capacity and symptoms associated with MR, particularly if there is an increase in pulmonary artery pressures (≥60 mmHg). Quantification of the MR itself can be challenging due to turbulent flow at high heart rates.

TEE is indicated to identify mechanism of MR, particularly when TTE is inconclusive or for planning of surgical or percutaneous procedures. The additional capability of high-resolution 3D imaging as well as Doppler interrogation of pulmonary vein flow in TEE is valuable in differentiating moderate and severe MR and assessing eccentric jets. However, caution must be used in interpreting transesophageal imaging because the systemic blood pressure is often lower in context of procedural sedation, angulation of Doppler angles differs between TTE and TEE, and jet size may differ due to technical factors.⁴

Cardiac magnetic resonance imaging can be used to provide additional measures of MR severity, particularly when echocardiographic imaging is technically difficult or there are discrepant findings between 2D and Doppler measurements or clinical and echocardiographic findings. Cardiac magnetic resonance imaging can be helpful in determining mechanism of whether MR is primary or secondary and provides ancillary information for decision-making such as myocardial viability in functional MR.

Conclusion

MR should be assessed in an integrative manner because no single parameter is adequate to quantify severity of MR. Rather, the integration of all clinical information and other echocardiographic data including chamber size and pulmonary pressures is necessary to provide an optimal assessment of MR severity.

References

1. Enriquez-Sarano M, Akins CW, Vahanian A. Mitral regurgitation. Lancet 2009;373:1382-94.
2. Dal-Bianco JP, Beaudoin J, Handschumacher MD, Levine RA. Basic mechanisms of mitral regurgitation. Can J Cardiol 2014;30:971-81.
3. Otto CM, Bonow RO. "Valvular Heart Disease." In: Bonow RO, Mann DL, Zipes EP, Libby P, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. St. Louis, MO: Saunders; 2012.
4. Zoghbi WA, Adams D, Bonow RO, et al. Recommendations for Noninvasive Evaluation of Native Valvular Regurgitation: A Report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr 2017;30:303-71.
5. Stout KK, Verrier ED. Acute valvular regurgitation. Circulation 2009;119:3232-41.
6. Thavendiranathan P, Phelan D, Collier P, Thomas JD, Flamm SD, Marwick TH. Quantitative assessment of mitral regurgitation: how best to do it. JACC Cardiovasc Imaging 2012;5:1161-75.
7. Yosefy C, Hung J, Chua S, et al. Direct measurement of vena contracta area by real-time 3-dimensional echocardiography for assessing severity of mitral regurgitation. Am J Cardiol 2009;104:978-83.
8. Zeng X, Levine RA, Hua L, et al. Diagnostic value of vena contracta area in the quantification of mitral regurgitation severity by color Doppler 3D echocardiography. Circ Cardiovasc Imaging 2011;4:506-13.
9. Enriquez-Sarano M, Avierinos JF, Messika-Zeitoun D, et al. Quantitative determinants of the outcome of asymptomatic mitral regurgitation. N Engl J Med 2005;352:875-83.
10. Biner S, Rafique A, Rafii F, et al. Reproducibility of proximal isovelocity surface area, vena contracta, and regurgitant jet area for assessment of mitral regurgitation severity. JACC Cardiovasc Imaging 2010;3:235-43.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Valvular Heart Disease, Implantable Devices, Atrial Fibrillation/Supraventricular Arrhythmias, Echocardiography/Ultrasound, Magnetic Resonance Imaging, Mitral Regurgitation

Keywords: Diagnostic Imaging, Atrial Fibrillation, Blood Cells, Blood Pressure, Cardiomyopathy, Hypertrophic, Chordae Tendineae, Conscious Sedation, Decision Making, Echocardiography, Echocardiography, Doppler, Echocardiography, Transesophageal, Heart Block, Heart Rate, Heart Ventricles, Imaging, Three-Dimensional, Magnetic Resonance Imaging, Mitral Valve, Mitral Valve Prolapse, Mitral Valve Insufficiency, Observer Variation, Operating Rooms, Papillary Muscles, Prolapse, Pulmonary Artery, Pulmonary Veins, Radius, Reproducibility of Results

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