Functional Mitral Valve Regurgitation, Pathophysiology, Leaflet ReModeling, and the Role of Imaging

Abstract

Functional mitral regurgitation (FMR) is a complex left ventricle (LV) and left atrium (LA) disorder in which mitral valve regurgitation is just the "tip of the iceberg." Unlike primary mitral cvalve regurgitation, in which regurgitation occurs due to anatomic abnormalities of the valve itself, the etiology of FMR is multifactorial. Regional and global LV dysfunction, extent and location of fibrotic myocardium (subendocardial/transmural scar), and annulus enlargement are the leading causes of valve regurgitation. A comprehensive understanding of the causes, mechanisms, severity, and clinical consequences of FMVR relies primarily on noninvasive imaging techniques. Echocardiography is the first-line and most commonly used imaging technique. Cardiac magnetic resonance (CMR) has gained growing consensus mainly because it can precisely identify the extent and location of fibrotic myocardium. This review aims to: (a) describe the pathophysiology of the most common phenotypes of FMR, (b) challenge the paradigm that mitral leaflets are structurally normal in FMR, and (c) illustrate the critical role of both echocardiography and CMR in the comprehensive assessment of FMR.

Keywords: functional mitral regurgitation; mitral valve; valve disease.

FIGURE 1

(A) 2D TEE images in long‐axis view showing a patient with asymmetric tethering. The anterior mitral leaflet slides toward the posterior leaflet (curved arrow). The straight arrows point at the akinesia of the posterior wall. (B) The same image as panel A with color Doppler. The regurgitant jet is directed posteriorly (black curved arrow). (C, D) The same patient in a four‐chamber view. The straight arrows point at the akinesia of the lateral wall. AO = aorta; LA = left atrium; LV = left ventricle.

FIGURE 2

3D TEE from (A) atrial and (B) ventricular perspectives. The images clearly show that the medial half of both the anterior mitral leaflet (AML) and posterior mitral leaflet (PML) are tethered outwards (arrows), leaving an orifice in the medial half of the valve (asterisk).

FIGURE 3

(A) An example of symmetric tethering in a four‐chamber view. The arrow points at a visible gap between the leaflets. (B) The same image with color Doppler shows the massive regurgitant jet. (C) 3D TEE of the same patient showing the mitral valve from an atrial perspective. The asterisk indicates the regurgitant orifice, which is more accentuated in the central area. (D) The same images are shown with color Doppler, confirming that the regurgitant jet arises from the central part of the coaptation line.

FIGURE 4

(A) In early systole, the closing forces are weak and the strong tethering forces lengthen the time needed for the leaflets to reach their opposition, leading to a significant rise in early systolic regurgitation. (B) In mid‐systole, leaflets reach their maximum possible apposition at the peak of intraventricular pressure and regurgitation decreases. (C) The interventricular pressures are reduced again at the end of systole and regurgitant flow increases.

FIGURE 5

3D TEE image of the mitral valve in early diastole from the ventricular perspective in (A) an normal individual and (B) a patient with secondary MR and a symmetric tethering pattern. The image in panel B shows an evident restricted diastolic opening (see text). The arrows show that the tethering forces affect mainly the septal‐posterior diameter (double‐headed dotted arrows).

FIGURE 6

TTE images (A) without and (B) with color Doppler showing an example of functional atrial MR. (C, D) 2D TEE image of the same patient (C) without and (D) with color Doppler. Color Doppler shows significant mitral regurgitation. LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.

FIGURE 7

(A) Four‐chamber view in a patient with atrial FMVR. (B) Magnified image of the structure inside the red square of panel A. The image shows the supposed mechanism. The hinge line of the posterior leaflet (yellow circle) slides on the crest of the ventricular myocardium (dotted arrow), increasing the annular‐papillary distance and tethering the posterior leaflet laterally.

FIGURE 8

3D TEE images from an atrial perspective showing a suboptimal outcome after TEER (2 clips) in (A) systole and (B) diastole. The dotted line in panel A indicates the location of the clips. The asterisk in panel B indicates the three residual orifices. Summation of the areas resulted in a total area of 1.15 mm² and a residual gradient of 8 mmHg. This suboptimal result was likely due to an unrecognized “maladaptive” remodeling of the mitral leaflets.

FIGURE 9

(A) In healthy subjects, the stress is concentrated around the trigone. (B) In dilated cardiomyopathy, the stress is diffused over the entire surface of the leaflets.

FIGURE 10

Adaptive analytics algorithm for left‐heart chamber quantification. (A) Diastole and (B) systole (see text).

FIGURE 11

The algorithm, driven by AI, generates a model of the convergence zone displayed as a purple mesh, which perfectly matches the actual 3D color Doppler. The method allows the quantification of all types of MVR throughout the system, including complex cases with multiple jets.

FIGURE 12

Left ventricular chamber quantification. CMR four‐chamber view in (A) diastole and (B) systole. The blue lines correspond to a stack of short‐axis slices covering the left and right ventricles. (C, D) One example of a short‐axis view showing the area of the left (red) and exemplary right (yellow) ventricles. Please note that this approach, which is routinely used, includes the PMs and trabeculations as part of the LV volume (asterisks). LV = left ventricle; RV = right ventricle.

FIGURE 13

(A) SSFP sequence in long‐axis view. The arrows point at the posterior akinetic wall. (B) LGE sequence showing the exact location of the fibrous tissue. (C) SSFP sequence in bi‐commissural view. The arrows point at the inferior akinetic wall. (D) LGE sequence showing the exact location of the fibrous tissue.

FIGURE 14

(A) Steady‐state free‐precession cine images in three‐chamber views. The arrow points at the flow turbulence of the mitral regurgitation jet due to spin‐spin dephasing, which can be visualized as a hypointense area. (B) the corresponding 2D TEE image with color Doppler.