The purpose of this study is to determine the site of attachment of the posterior mitral annulus to the left ventricle in patients with mitral annular disjunction (MAD) and mitral valve prolapse (MVP). The posterior annulus normally attaches to the inlet of the left ventricle. Some histological findings suggest that the disjunctive annulus may instead attach anomalously to the left ventricular (LV) crest in patients with MVP. We used cardiac magnetic resonance imaging to determine the site of attachment of the posterior mitral annulus (crest vs inlet) in 25 patients with MVP with MAD (MAD+ group) and 24 patients with MVP without MAD (MAD- group). The site of annular attachment was determined in the 3-chamber view during diastole. Our data demonstrate complete separation in mitral annular attachment site between MAD+ and MAD- groups. All patients in the MAD+ group demonstrated annular attachment to the LV crest, whereas all those in the MAD- group demonstrated annular attachment to the LV inlet (p <0.001). The presence of anomalous annular attachment in MAD+, but not MAD- patients, suggests this anatomic abnormality represents a feature of the MAD phenotype rather than the myxomatous phenotype. Anomalous annular attachment may potentially influence the arrhythmic potential of MAD.
Mitral valves prolapse (MVP) occurs in approximately 2.5% of the population. Complications of this disorder include mitral regurgitation and a phenotype (arrhythmic MVP) characterized by ventricular arrhythmias and sudden cardiac death. Considerable research has been performed in an effort to identify morphologic findings that predict increased arrhythmic risk. In this respect, an international arrhythmogenic MVP registry of 148 survivors of sudden cardiac arrest and ventricular tachycardia or ventricular fibrillation, as well as the 2022 European Heart Rhythm Association Expert Consensus Statement, consider mitral annular disjunction (MAD), found in approximately 7% of patients with MVP, a morphologic marker of increased arrhythmic risk.
The patho-anatomy of MAD continues to be refined. MAD has traditionally been defined as displacement of the posterior mitral leaflet (PML)/left atrial (LA) junction away from the left ventricular (LV) myocardium during systole. Recently, a cardiac magnetic resonance (CMR) and echocardiographic imaging study by Fiore, et al, observed that the PML/LA junction also remains separated from the left ventricle during diastole ( Figure 1 ). In addition, Silbiger, and Bazaz noted that histologic specimens demonstrating MVP and MAD may reveal anomalous attachment of the posterior mitral annulus to the LV crest, instead of to the LV inlet, its normal site of attachment ( Figure 2 ). , The prevalence of this abnormality in patients with MVP however is not known. We therefore undertook a CMR imaging study to determine the anatomic site of annulus attachment in patients with MVP and MAD.
The MAD trench. A. Diastolic MAD. The asterisk indicates the location of the LV inlet, the normal site of annulus attachment. Note that the posterior annulus is anomalously attached to the LV crest and forms the floor of the MAD trench. The double-headed red arrow indicates diastolic MAD length. B. Systolic MAD. Note the increase in MAD length during systole (double-headed arrow). The asterisk indicates the location of the LV inlet. LA = left atrium.
Histology of the posterior mitral annulus (Mason’s trichrome stain). A. Sagittal section of the normal posterior mitral annulus. Note that the annulus is attached to the LV inlet (asterisk). B. Sagittal section demonstrating MAD. Note that the elongated (disjunctive) annulus, indicated by a double-headed arrow, is attached to the LV crest near the epicardial surface of the left ventricle. Reproduced with permission from.
Methods
Patients with MVP were identified by querying our institution’s CMR imaging database for the period between 2018 and 2022 using the search term mitral valve prolapse . Prolapse was defined as ≥2 mm of leaflet protrusion above a line connecting the mitral leaflets’ hinge points. All patients in the study underwent simultaneous CMR imaging and ¹⁸F-fluoro-deoxyglucose positron emission tomography (PET), however we limited our analysis to their CMR images. Imaging was performed with an integrated hybrid positron emission tomography (PET)/CMR system (Biograph mMR, Siemens Healthineers, Erlangen, Germany). Cine images were obtained using balanced steady-state free precession sequences in standard long-axis and short-axis views. To minimize artifacts, images were repeated in 2 orthogonal phase-encoding directions. CMR postprocessing was performed using dedicated software (cvi42, Circle Cardiovascular Imaging, Calgary, Canada).
The site of posterior annulus attachment (crest vs inlet) was evaluated in the 3-chamber view during diastole. Among patients with MAD, systolic and diastolic MAD lengths, measured from the LV to the PML/LA junction ( Figure 1 ), were assessed in the 3-chamber view. In patients with pseudo-MAD the pseudo-MAD length, measured from the LV to the pseudo-PML/LA junction ( Figure 3 ), was determined, as was the presence or absence of curling (systolic posterior/outward motion of the posterior annulus and adjacent LV crest). Prolapse area, defined as the planimetered area between a line connecting the mitral leaflet hinge points and the superior extent of leaflet systolic excursion, and prolapse height, defined as the vertical distance from a line connecting mitral leaflet hinge points to the most superior point of mitral leaflet excursion, were both measured in the 3-chamber view at end-systole ( Figure 4 ). End-systolic and end-diastolic antero-posterior (AP) and intercommissural (IC) annular diameters were measured and used to calculate mitral annular area assuming an elliptical shape. The percent change of linear (AP and IC) diameters and area was obtained using the formula: (end-systolic parameter)—(end-diastolic parameter)/(end-diastolic parameter) X 100. Quantitative LV analysis including end-diastolic and end-systolic volumes and ejection fraction were measured using Simpson’s disk summation method. LA volumes were quantified using the bi-plane area-length method and indexed to body-surface area. Mitral regurgitation data was evaluated echocardiographically and graded on a scale of 1 to 4+ according to the guidelines of the American Society of Echocardiography.
The pseudo-MAD trench. A. During diastole, the posterior mitral annulus and PML, at its base, rest on the LV inlet. B. During systole, curling, indicated by the curved black arrows, moves the PML onto the endocardial surface of the left atrium thereby forming the floor of the pseudo-MAD trench. LA = left atrium.
Prolapse area and height. The yellow line connects the hinge points of the mitral leaflets. Prolapse area is enclosed by the blue tracing. Prolapse height is indicated by the vertical red line.
Statistics
Intergroup comparisons were performed using Welch’s 2-sample t-test for continuous variables and Fisher’s exact test for categorical variables. The relative risk of MAD among patients with bi-leaflet versus isolated PML prolapse was calculated with exact Koopman confidence intervals (95% CI). Intragroup comparisons of annular dimensions (AP and IC) and area during systole and diastole were made using paired t-tests. p-values <0.05 were considered statistically significant. This study was approved by the Institutional Review Board of the Icahn School of Medicine at Mount Sinai.
Results
Of the 50 patients with MVP identified in our database, 1 with prolapse confined to anterior mitral leaflet was excluded from the study. The remaining patients were divided into 2 groups according to MAD presence, n = 25 (MAD+ group), or MAD absence, n = 24 (MAD- group). Fifteen patients in the MAD- group demonstrated pseudo-MAD, of which 14 (93%) revealed curling. Of the remaining 9 patients in this group, 7 (78%) demonstrated curling. When the entire study cohort is considered, 35 patients had bi-leaflet prolapse and 14 had isolated prolapse of the posterior leaflet. MAD was 4.6X more common among patients with bi-leaflet prolapse compared to those with posterior leaflet prolapse (65.7 vs 14.3%; RR 4.6, 95% CI 1.6 to 16.7; Fisher’s exact p = 0.002).
Demographic and CMR data stratified by group are displayed in Table 1 . There was no significant difference in age, sex, body-surface area, LV diastolic and systolic volumes and ejection fraction, LA volume index, or mitral regurgitation grade between groups. Notably, there was complete separation in the site of mitral annular attachment between groups, i.e., all MAD+ patients demonstrated annular attachment to the LV crest, whereas all MAD- patients demonstrated annular attachment to the LV inlet (p <0.001).
Table 1
Demographic and CMR imaging variables
| Variables |
Overall
n = 49 |
MAD−
n = 24 |
MAD+
n = 25 |
p-value |
|---|---|---|---|---|
| Age (years) | 57±11 | 56±13 | 58±9 | 0.592 |
| Body surface area (m²) | 1.79±.18 | 1.80±.2 | 1.77±.16 | 0.536 |
| Sex | 0.567 | |||
| Female | 28 (57%) | 15 (63%) | 13 (52%) | |
| Male | 21 (43%) | 9 (38%) | 12 (48%) | |
| Mitral annulus attachment | <0.001 | |||
| LV Inlet | 24 (49%) | 24 (100%) | 0 (0%) | |
| LV Crest | 25 (51%) | 0 (0%) | 25 (100%) | |
| Mitral annular dimensions and area | ||||
| AP systolic dimension (cm) | 4.27±.65 | 4.18±.71 | 4.36±.59 | 0.346 |
| AP diastolic dimension (cm) | 3.84±.56 | 3.77±.49 | 3.92±.62 | 0.369 |
| AP dimension change (%) | 11±11 | 11±14 | 12±9 | 0.792 |
| IC systolic dimension (cm) | 5±.68 | 4.80±.65 | 5.19±.66 | 0.04 |
| IC diastolic dimension (cm) | 4.39±.61 | 4.34±.48 | 4.44±.72 | 0.575 |
| IC dimension change (%) | 14±12 | 11±10 | 18±13 | 0.025 |
| Systolic annular area (cm 2) | 17±4.6 | 16±4.7 | 18±4.4 | 0.137 |
| Diastolic annular area (cm 2) | 13.4±3.6 | 13±2.9 | 13.9±4.1 | 0.368 |
| Annular area change (%) | 28±21 | 23±22 | 33±20 | 0.14 |
| Systolic MAD length (cm) | .8 ±.22 | |||
| Diastolic MAD length (cm) | .29 ±.11 | |||
| Pseudo-MAD length (cm) | .59 ±.3 | |||
| Mitral regurgitation grade (1-4+) | 0.733 | |||
| 1+ | 8 (17%) | 3 (13%) | 5 (21%) | |
| 2+ | 6 (13%) | 2 (8.3%) | 4 (17%) | |
| 3+ | 2 (4.2%) | 1 (4.2%) | 1 (4.2%) | |
| 4+ | 32 (67%) | 18 (75%) | 14 (58%) | |
| Leaflet prolapse | 0.002 | |||
| PML prolapse | 14 (29%) | 12 (50%) | 2 (8%) | |
| Bi-leaflet prolapse | 35 (71%) | 12 (50%) | 23 (92%) | |
| Prolapse area and height | ||||
| Posterior prolapse area (cm 2) | 1.62±.81 | 1.29±.61 | 1.85±.87 | 0.018 |
| Anterior prolapse area (cm 2) | .96±.49 | 1.02±.48 | .92±.5 | 0.585 |
| Combined prolapse area (cm 2) | 2.71±1.05 | 2.58±.88 | 2.77±1.13 | 0.591 |
| Posterior prolapse height (cm) | .91±.33 | .79 ±.28 | .99±.34 | 0.042 |
| Anterior prolapse height (cm) | .61±.26 | .58 ±.24 | .63±.28 | 0.648 |
| Cardiac chambers | ||||
| LA volume index (mL/m²) | 46±19 | 47±19 | 44±20 | 0.562 |
| LV end diastolic volume (mL) | 173±50 | 182±50 | 164±50 | 0.21 |
| LV end systolic volume (mL) | 66±20 | 67±20 | 65±20 | 0.689 |
| Ejection fraction (%) | 63±7 | 63±7 | 62±7 | 0.637 |
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