A central component of the current American College of Cardiology (ACC) and American Heart Association (AHA) guidelines for the management of mitral regurgitation (MR) is the importance of accurately diagnosing severe MR.¹ The current guidelines rely primarily on echocardiography to discern severe from non-severe MR. However, studies have questioned the accuracy of echocardiography for differentiating severe from non-severe MR, showing high interobserver and intraobserver variability.^2,3 For example, Biner et al. found a low intraclass correlation (high interobserver variability) for vena contracta, proximal isovelocity surface area (PISA), and color Doppler jet size for differentiating severe and non-severe MR.² An accompanying editorial raised concerns regarding the capability of accurately diagnosing severe MR with echocardiography and appropriately recommend patients for mitral valve surgery.⁴ These findings highlight the lack of a single, reliable, reproducible quantitative echocardiographic parameter. In fact, the current American Society of Echocardiography guidelines recommend integrating multiple qualitative, semi-quantitative, and quantitative echocardiographic parameters that have been primarily validated in small studies against either ventriculography or other echocardiographic parameters, but never against an objective quantitative method.⁵ These findings have contributed to the interest in studying other noninvasive imaging modalities, such as magnetic resonance imaging (MRI), as tools to quantify MR.

Quantification of mitral regurgitant volume using MRI does not rely on direct assessment of the mitral regurgitant jet, which is in contrast to the most commonly used echocardiographic parameters. Regurgitant volume by MRI is most commonly calculated as the difference between the left ventricular stroke volume (LVSV) and forward flow.^6-10 Left ventricular (LV) and right ventricular (RV) end-diastolic volume (EDV) and end-systolic volume (ESV) are calculated by segmenting a contiguous short axis stack of the ventricle using steady-state free-precession images (Figure 1). These images have the advantages of a high contrast between the bright blood and the myocardium and the lack of geometric assumptions. Although not all patients with severe MR will have severe LV dilatation (e.g., patients with severe diastolic disease, hypertrophic cardiomyopathy, or infiltrative cardiomyopathies) and those with secondary MR may have dilatation out of proportion to MR severity, it is important to corroborate the presence of LV dilatation in patients with primary severe MR. Phase contrast images are used to measure flow in the proximal aorta and pulmonary artery and have been shown to be accurate and reproducible. Mitral regurgitant volume calculated by subtracting the LVSV from the forward flow has been shown to be a highly reproducible approach.^6,9,10 Furthermore, because MRI can directly measure aortic insufficiency using phase contrast imaging of the proximal aorta,¹⁰ MRI can accurately measure regurgitant volumes in patients with both MR and aortic regurgitation.

Figure 1: Patient With MR

Multiple studies have shown discordance between echocardiography and MRI in the assessment of MR; a few of the most important studies are listed in Table 1. It is important to note that although the methods for determining severity of MR by echocardiography differ among the studies listed, the method for MRI has been largely consistent in using LVSV – forward flow, highlighting the consensus of a single reproducible method for quantifying MR by MRI. There is no gold standard to validate noninvasive imaging parameters for MR, but there is a reference standard that can be used. In chronic MR, the LV will compensate by dilating, leading to an increased EDV. Our group has shown a tight correlation between LVEDV and mitral regurgitant volume by MRI, with LVEDV increasing with worsening severity of MR.¹⁰ In addition, studies have shown that with removal of the volume overload of MR using mitral valve surgery, there is a reverse remodeling of the LV in which the EDV will decrease.^11,12 In a prospective multicenter study, we found significant discordance between echocardiography and MRI in the quantification of MR, using both the American Society of Echocardiography-integrated method and PISA-based regurgitant volume for echocardiography and regurgitant volume by MRI.⁹ This discordance was particularly profound in patients who were referred for mitral valve surgery, all of whom were referred based on the severity of MR by echocardiography and the current ACC/AHA recommendations. Among the patients referred for mitral valve surgery, approximately two-thirds did not have severe MR by MRI. There was a tight correlation between the regurgitant volume calculated using MRI and the degree of LV negative remodeling post mitral valve surgery. There was no relationship between the PISA-derived mitral regurgitant volume using echocardiography and the degree of LV negative remodeling post-surgery. These data suggest that regurgitant volume by MRI is more accurate than PISA-based regurgitant volume by echocardiography.

Table 1: Studies That Have Compared the Assessment of MR by Echocardiography and MRI

A recent retrospective analysis of asymptomatic patients with moderate or severe MR by echocardiography followed patients for a mean duration of 2.5 ± 1.9 years for progression to an indication for mitral valve surgery.¹³ Each patient had a baseline MRI and echocardiogram. Patients who did not progress to an indication for surgery and those who did both had mean regurgitant volumes by echocardiography in the severe range (74 ± 74 ml vs. 89 ± 36 ml). By MRI, those who did not progress to an indication for mitral valve surgery had lower mean regurgitant volumes than those who did progress (39 ± 20 ml vs. 66 ± 24 ml). Using receiver operating characteristic analysis, the authors found that regurgitant volume by MRI had an area under the curve of 0.80 for determining which patients would develop an indication for mitral valve surgery. The authors found that using a cutoff of MRI-derived mitral regurgitant volume of 55 ml differentiated those who would progress to an indication for surgery from those who would not. However, a cutoff of an effective regurgitant orifice area of 0.40 cm² could not differentiate those who would progress to an indication for mitral valve surgery from those who would not. These data highlight the predictive value of quantification using MRI in patients with mitral valve disease.

Another advantage of MRI in the assessment of patients with MR is the ability to detect and quantify myocardial fibrosis. This notion has gained interest recently, and small exploratory studies have been performed. Theoretically, fibrosis may be a marker that could alert the clinician to irreversible myocardial damage and could be used as an early marker prior to overt systolic dysfunction. This may be helpful in guiding when to adopt a "surgery now" approach as opposed to a "watchful waiting" approach. At this time, myocardial fibrosis, either as the more traditional late gadolinium enhancement (LGE) or the more recent T1 mapping, has not been adequately assessed. Han et al. found LGE patterns in the papillary muscles in patients with mitral valve prolapse.¹⁴ Van De Heyning et al. studied 39 patients and found that 31% of patients had LGE.¹⁵ Edwards et al. studied 35 patients with degenerative MR using both LGE and T1 mapping.¹⁶ The authors report the finding of LGE and increased T1 mapping-based extracellular volume in patients with MR. Although these studies are small and do not relate clinical outcomes with myocardial fibrosis detected by MRI, these studies can be seen as hypothesis generating.

Based on the data presented, it appears that MRI is an accurate method to determine which patients have severe MR and who might benefit from surgery. It should be noted that the data presented above are observational and that there is no prospective multicenter randomized study on whether echocardiography or MRI is better at identifying patients who would benefit from mitral valve surgery. In the absence of such a study, and on the basis of existing data, clinicians should consider an MRI evaluation of their patients prior to referral for mitral valve surgery.

References

1. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:e57-185.
2. 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.
3. Thomas N, Unsworth B, Ferenczi EA, Davies JE, Mayet J, Francis DP. Intraobserver variability in grading severity of repeated identical cases of mitral regurgitation. Am Heart J 2008;156:1089-94.
4. Grayburn PA, Bhella P. Grading severity of mitral regurgitation by echocardiography: science or art? JACC Cardiovasc Imaging 2010;3:244-6.
5. Zoghbi WA, Enriquez-Sarano M, Foster E, et al. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 2003;16:777-802.
6. Cawley PJ, Hamilton-Craig C, Owens DS, et al. Prospective comparison of valve regurgitation quantitation by cardiac magnetic resonance imaging and transthoracic echocardiography. Circ Cardiovasc Imaging 2013;6:48-57.
7. Gelfand EV, Hughes S, Hauser TH, et al. Severity of mitral and aortic regurgitation as assessed by cardiovascular magnetic resonance: optimizing correlation with Doppler echocardiography. J Cardiovasc Magn Reson 2006;8:503-7.
8. Lopez-Mattei JC, Ibrahim H, Shaikh KA, et al. Comparative Assessment of Mitral Regurgitation Severity by Transthoracic Echocardiography and Cardiac Magnetic Resonance Using an Integrative and Quantitative Approach. Am J Cardiol 2016;117:264-70.
9. Uretsky S, Gillam L, Lang R, et al. Discordance between echocardiography and MRI in the assessment of mitral regurgitation severity: a prospective multicenter trial. J Am Coll Cardiol 2015;65:1078-88.
10. Uretsky S, Supariwala A, Nidadovolu P, et al. Quantification of left ventricular remodeling in response to isolated aortic or mitral regurgitation. J Cardiovasc Magn Reson 2010;12:32.
11. Crawford MH, Souchek J, Oprian CA, et al. Determinants of survival and left ventricular performance after mitral valve replacement. Department of Veterans Affairs Cooperative Study on Valvular Heart Disease. Circulation 1990;81:1173-81.
12. Feldman T, Foster E, Glower DD, et al. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med 2011;364:1395-406.
13. Myerson SG, d'Arcy J, Christiansen JP, et al. Determination of Clinical Outcome in Mitral Regurgitation With Cardiovascular Magnetic Resonance Quantitation. Circulation 2016;133:2287-96.
14. Han Y, Peters DC, Salton CJ, et al. Cardiovascular magnetic resonance characterization of mitral valve prolapse. JACC Cardiovasc Imaging 2008;1:294-303.
15. Van De Heyning CM, Magne J, Piérard LA, et al. Late gadolinium enhancement CMR in primary mitral regurgitation. Eur J Clin Invest 2014;44:840-7.
16. Edwards NC, Moody WE, Yuan M, et al. Quantification of left ventricular interstitial fibrosis in asymptomatic chronic primary degenerative mitral regurgitation. Circ Cardiovasc Imaging 2014;7:946-53.

Clinical Topics: Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Valvular Heart Disease, Echocardiography/Ultrasound, Magnetic Resonance Imaging, Mitral Regurgitation

Keywords: Aorta, Aortic Valve Insufficiency, Cardiomyopathies, Cardiomyopathy, Hypertrophic, Diastole, Dilatation, Echocardiography, Heart Ventricles, Magnetic Resonance Imaging, Mitral Valve, Mitral Valve Insufficiency, Mitral Valve Prolapse, Papillary Muscles, Pulmonary Artery, ROC Curve, Stroke Volume, Systole

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