The following are key points to remember from a state-of-the-art review on the evolving concept of secondary mitral regurgitation (MR) phenotypes and lessons from the mitral transcatheter edge-to-edge repair (M-TEER) trials:

1. Secondary mitral regurgitation (SMR) heterogeneity. SMR typically occurs in patients with a structurally normal mitral valve. SMR with a ventricular cause (vSMR) typically is associated with heart failure (HF) with reduced left ventricular ejection fraction (LVEF), and is distinguished from SMR with a predominantly atrial cause (aSMR) that usually is associated with HF with preserved LVEF.
2. Proportionate and disproportionate vSMR. vSMR can be thought of as “proportionate” if the severity of MR is proportionate to the degree of LV enlargement, typically seen with global and homogeneous LV dilation and dysfunction, and probably is more amenable to treatment with guideline-directed medical therapy (GDMT). In contrast, with “disproportionate” vSMR, the severity of MR is out of proportion to the degree of LV dilation, typically seen in the setting of asymmetric tethering or LV dyssynchrony, and probably is less likely to respond to GDMT but more likely to respond to M-TEER.
3. The MITRA-FR and COAPT trials. Differences between patient cohorts in the ratio of MR regurgitant volume (RVol) to LV end-diastolic volume (LVEDV) in the two clinical trials could explain why M-TEER was associated with clinical benefit in the COAPT trial (mean RVol/LVEDV 0.31) but not in the MITRA-FR trial (mean RVol/LVEDV 0.18). Other differences between the two trials include a lower threshold to define severe MR in MITRA-FR; and inclusion in MITRA-FR of patients with more severe LV dilation, more severe LV systolic dysfunction, and severe right ventricular (RV) systolic dysfunction.
4. SMR quantitation. Accurate and reliable quantitation of SMR is challenging. The proximal isovelocity surface area (PISA) method used to calculate effective regurgitant orifice area and RVol can underestimate or overestimate SMR severity, and Doppler volumetric quantitation has high variability.
5. SMR response to GDMT. GDMT is associated with improvement in MR severity in 40-60% of patients with vSMR and should be a cornerstone of treatment both before and after M-TEER. Existing trials that assessed MR severity and patient prognosis with GDMT for vSMR did not include the use of sacubitril/valsartan or sodium-glucose cotransporter-2 (SGLT2) inhibitors.
6. LV fibrosis/scar, RV dysfunction. LV fibrosis/scar detected on magnetic resonance imaging and RV dysfunction both are associated with worse prognosis among patients with SMR.
7. Predicting outcomes for M-TEER. There is not a good model to reliably predict the clinical benefit of M-TEER among individual patients with vSMR, in part owing to the heterogeneity of vSMR patients.
8. aSMR phenotypes. The mechanism of aSMR is left atrial enlargement leading to isolated mitral annular dilation. The more common aSMR phenotype is with leaflet malcoaptation leading to a central jet in the middle of the mitral leaflets, whereas a less common aSMR phenotype is caused by “hamstringing” of the posterior leaflet leading to an eccentric posteriorly located jet.
9. aSMR treatment and prognosis. Restoration of sinus rhythm can reduce the severity of MR among patients with aSMR and atrial fibrillation. Data on the use of SGLT2 inhibitors specifically among patients with aSMR are lacking. Single-center observational studies suggest good results with surgical annuloplasty for aSMR. Retrospective data suggest that M-TEER among patients with aSMR is associated with good procedural success and improvement in HF symptoms. However, prospective randomized data are lacking for the use of M-TEER in aSMR.
10. Ongoing investigation. The ongoing MATTERHORN (A multicenter, randomized, controlled study to assess mitral valve reconstruction for advanced insufficiency of functional or ischemic origin) trial is a randomized comparison of transcatheter and surgical treatment of SMR that might help inform future therapies for SMR.

Clinical Topics: Heart Failure and Cardiomyopathies, Valvular Heart Disease, Mitral Regurgitation

Keywords: Mitral Valve Insufficiency, Ventricular Dysfunction, Right

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