New Evidence Supporting a Novel Conceptual Framework for Distinguishing Proportionate and Disproportionate Functional Mitral Regurgitation

Abstract

ImportanceTraditionally, physicians distinguished between mitral regurgitation (MR) as a determinant of outcomes and MR as a biomarker of left-ventricular (LV) dysfunction by designating the lesions as primary or secondary, respectively. In primary MR, leaflet abnormalities cause the MR, resulting in modest increases in LV end-diastolic volume over time, whereas in patients with classic secondary MR, LV dysfunction and dilatation lead to MR without structural leaflet abnormalities. However, certain patients with global LV disease (eg, those with left bundle branch block or regional wall motion abnormalities) have the features of primary MR and might respond favorably to interventions that aim to restore the proper functioning of the mitral valve apparatus.ObservationsA novel conceptual framework is proposed, which classifies patients with meaningful LV disease based on whether the severity of MR is proportionate or disproportionate to the LV end-diastolic volume. Treatments that reduce LV volumes (eg, neurohormonal antagonists) are effective in proportionate MR but not disproportionate MR. Conversely, procedures that restore mitral valve function (eg, cardiac resynchronization and mitral valve repair) are effective in patients with disproportionate MR but not in those with proportionate MR. The proposed framework explains the discordant findings in the Multicentre Randomized Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation (MITRA-FR) and the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trials; differences in procedural success and medical therapy in the 2 studies cannot explain the different results. In addition, the small group of patients in the COAPT trial who had the features of proportionate MR and were similar to those enrolled in the MITRA-FR trial did not respond favorably to transcatheter mitral valve repair.Conclusions and RelevanceThe characterization of patients with functional MR into proportionate and disproportionate subtypes may explain the diverse range of responses to drug and device interventions that have been observed.

Impact of left ventricular assist device implantation on mitral regurgitation: An analysis from the MOMENTUM 3 trial

“…The notion that MR proportionate to the degree of ventricular dilatation may be best served by a therapy that targets the ventricle rather than the valve has been proposed. 13,14 The 2-year mortality in such patients irrespective of treatment of the MV is 34% and mimics the survival seen in an advanced HF population. 12 Our data suggest that LVAD implantation is associated with a rapid and marked improvement in the severity of MR with a 2-year mortality rate (»20%) that is significantly lower even when compared with interventional studies of percutaneous MR repair.…”

Reply from authors: Discordant trial results lead to disproportionate learnings

“…Patients with proportionate MR tend to have symmetrical mitral leaflet tethering from LV dilation and can reasonably be expected to respond to GDMT directed toward the LV, especially with neurohormonal antagonists. 5 Patients with disproportionate MR have asymmetric mitral leaflet tethering due to anatomic factors such as left bundle branch block, inferobasal LV aneurysm, or severe fibrosis of the posterior leaflet, in which additional treatment needs to be directed toward the mitral valve with resynchronization therapy or valve repair. These are 2 different mechanisms of MR, and one does not lead to the other.…”

“…It is of note that a small subgroup of patients in the COAPT trial with echocardiographic parameters similar to those of patients in the MITRA-FR trial did not benefit from MV intervention. 5 The main takeaway is that we are now better able to discriminate which patients can reasonably be expected to respond to GDMT from those who will need intervention directed toward the mitral valve to correct MR.…”

Transcatheter mitral valve repair with clip for treatment of secondary or functional mitral insufficiency. Literature review

“…Another recent important concept formulated to explain differences between both trials is the occurrence of disproportionate MI (Figure 4). 16 Patients with severe left ventricle dysfunction may be further categorized according to MI severity, and whether it is proportionate or disproportionate to the degree of ventricular dysfunction ( Figure 4). 17 Medical management aimed at decreasing left ventriclar volume overload (such as neurohormonal blockers) are effective in proportionate MI but no so much in disproportionate MI.…”