Background
Annulo-leaflet mitral ring (ALMR) is a rare congenital cardiac anomaly caused by fibrous tissue on the atrial surface of the mitral valve, which can progress to cause severe stenosis. Because little information is available on the detailed echocardiographic features of the anomaly and their associations with surgical resection, this study was undertaken to address these questions.
Methods
A retrospective single-center study of clinical and echocardiographic data from patients with ALMR from 2004 through 2012 was conducted. Data were analyzed for associations with surgical resection.
Results
The median age at diagnosis of the 57 study patients was 1.8 years, and 63% were male. Isolated ALMR was found in six patients (11%). The remaining 51 patients (89%) had associated lesions: additional mitral valve abnormalities in 35 (61%), coarctation in 11 (19%), and subaortic stenosis in 15 (26%). ALMR was best visualized in the apical four-chamber view, and the lesion was indistinct from the parasternal long-axis view in 25% of patients. Seven patterns of ALMR were identified, differentiated by leaflet involvement (anterior, posterior, or both) and location (annular vs intraleaflet). Compared with other patterns, intraleaflet morphology had a higher mean mitral stenosis gradient than in patients without (8.4 vs 5.8 mm Hg, P = .01). Among the 57 patients, 32 (56%) underwent ALMR resection, at a median age of 1.5 years. Younger age at echocardiographic diagnosis ( P = .02) and short chordae ( P = .03) were associated with resection.
Conclusions
The morphology of ALMR as evaluated by echocardiography is heterogeneous and can be classified on the basis of lesion location and leaflet involvement. Intraleaflet morphology is associated with significant mitral stenosis; younger age at diagnosis and short chordae are associated with ALMR resection.
Annulo-leaflet mitral ring (ALMR) is a rare form of mitral stenosis and often presents a diagnostic challenge. This lesion has multiple pseudonyms, including “supramitral” ring, despite several investigations suggesting that the lesion is not truly supra-annular. ALMR has been defined as a ridge of connective tissue adherent to the atrial surface of the mitral valve or slightly superior to the annulus and distal to the left atrial (LA) appendage. First recognized in 1902, ALMR is often associated with additional left-sided obstructive lesions, including mitral valve, aortic valve, and aortic arch abnormalities. Shone et al . described ALMR in 1963 as part of a complex association of left heart obstructive lesions, which included parachute mitral valve, discrete subaortic stenosis, and coarctation of the aorta. The ALMR, called “supravalvar ring of left atrium” in their study, was noted to be “present but not functionally significant” in five of the eight studied patients, an observation that highlights the substantial heterogeneity of this lesion. In addition to its association with left heart obstructive lesions, ALMR has also been described in the setting of a variety of other congenital cardiac anomalies, including tetralogy of Fallot.
ALMR was first demonstrated by M-mode echocardiography in 1972 and later by two-dimensional echocardiography in 1980. These early studies demonstrated that ALMR presented a diagnostic challenge. Since these initial descriptions of ALMR, several studies have described pathologic, histologic, and surgical aspects of the anomaly. Surgical reports note that when isolated, the lesion is amenable to resection with good outcomes, but results are often less satisfactory when ALMR is associated with other lesions. Balloon valvuloplasty is recognized as having limited utility in the setting of ALMR.
A paucity of information is available regarding echocardiographic characteristics of ALMR. Toscano et al ., in the largest study to date ( n = 25), importantly recognized two different variants of this anomaly, namely “supramitral” and “intramitral.” They noted that supramitral lesions were less likely to have associated abnormalities and had a better prognosis compared with intramitral lesions. However, detailed characterization of the lesion by echocardiography is lacking. Therefore, we undertook this study to (1) characterize the echocardiographic features of ALMR in a relatively large cohort, (2) create a classification system on the basis of lesion location, and (3) identify echocardiographic characteristics associated with resection.
Methods
Patients
The database of the Boston Children’s Heart Center was searched for patients with the diagnostic code of supravalvar mitral stenosis. Included patients underwent echocardiography from March 2004 through December 2012. This period was selected to coincide with the use of digital image archiving. Exclusion criteria were (1) prior surgical or catheter-based intervention on the mitral valve, (2) diagnosis of atrioventricular canal defect, and (3) functional single ventricle. Medical records were reviewed for demographic and clinical data. Demographic data, presence of genetic syndromes, and a history of surgical or catheter-based interventions were recorded. Additional clinical data included outpatient notes, catheterization reports, and surgical reports. Primary echocardiographic data were reviewed as described below. The Boston Children’s Hospital Committee on Clinical Investigations approved the study protocol and waived the requirement for informed consent.
Outcome
The primary clinical outcome was surgical resection of ALMR.
Echocardiography
Echocardiography was performed using either a Hewlett-Packard 7500 (Hewlett-Packard, Palo Alto, CA) or a Philips iE33 (Philips Medical Systems, Andover, MA) scanner. Digitally archived studies were reviewed using HeartSuite VERICIS workstations (Emageon, Hartland, WI). Studies were analyzed for LA, left ventricular, mitral valve, aortic valve, and aortic arch dimensions and morphology. A single reviewer (D.N.S.), who was blinded to patient outcomes, performed all of the measurements listed below. Categorization of ALMRs was made by consensus of two investigators (D.N.S .and T.G.), who were blinded to patient outcomes on the basis of predefined criteria.
For patients with serial echocardiographic examinations, the preoperative study was used for data collection. For patients who did not undergo surgery, the highest quality study at diagnosis was used. Patients who underwent serial echocardiographic examinations had the mitral valve gradient recorded at each study.
The following data were collected: (1) mitral valve diameters (anteroposterior and lateral) and Z scores, (2) left ventricular end-diastolic volume and Z score, (3) left ventricular mass and Z score, (4) ejection fraction, (5) LA area adjusted to body surface area, and (6) mean mitral valve gradient. Body surface area was calculated from the patient’s height and weight using the Haycock formula. Z scores were calculated using our laboratory’s published normative data.
Echocardiograms were reviewed for the following associated abnormalities: (1) short chordae, (2) closely spaced papillary muscles, (3) parachute mitral valve, (4) subaortic stenosis, (5) aortic valve morphology (categorized as tricommissural, bicommissural, or unicommissural), and (6) additional congenital cardiac anomalies. Shortened chordae and closely spaced papillary muscles were determined on the basis of qualitative assessment. The designation of shortened chordae was assigned when there was markedly diminished chordal length and a short distance from the edge of the mitral leaflets to the papillary muscles on the apical four-chamber view. The designation of closely spaced papillary muscles was assigned when the normal interpapillary distance was markedly reduced when assessed by the parasternal or subcostal short-axis views in diastole. For patients with serial echocardiograms, the initial mean mitral valve gradient at the time of diagnosis was recorded. The following measurements of the ALMR were performed from the apical four-chamber view in diastole: (1) membrane length, (2) mitral valve leaflet lengths, and (3) location of obstructive ridge (categorized as annular or intraleaflet). Annular lesion was defined as a tissue ridge extending from the atrioventricular junction toward the lumen without significant adherence to the atrial surface of the leaflet tissue. An intraleaflet lesion was defined as a tissue ridge extending from the atrioventricular junction along the atrial surface of one or both mitral leaflets with the leading edge protruding into the lumen some distance from the annulus.
To allow analysis of the degree of lesion extension onto the mitral leaflets as a continuous variable, we measured the length of the obstructive membrane from the atrioventricular junction to its edge as well as the length of the respective leaflet. These measurements were then used to calculate the extent of the lesion, termed the membrane extent index, using the following formula: [(anterior membrane length/anterior leaflet length) + (posterior membrane length/posterior leaflet length)]/2 ( Figure 1 ). Measurements were performed exclusively in the apical four-chamber view during diastole. Care was taken to exclude the chordae tendineae from measurements of the mitral leaflet length on the basis of review of cine loops. As indicated by the formula, anterior and posterior indices were averaged to yield the membrane extent index.
Statistical Analysis
Continuous variables were summarized using the median and range, unless otherwise noted. Categorical variables were summarized as frequencies and percentages and were compared using the Fisher exact test. Comparison was made between patients who underwent ALMR resection and those who did not using the Wilcoxon rank sum test or the unpaired t test for continuous variables, as appropriate. Logistic regression was used to estimate odds ratios and 95% confidence intervals of ALMR resection. P values < .05 were considered to indicate statistical significance. Statistical analysis was performed using commercially available statistical analysis software (Stata version 12; StataCorp LP, College Station, TX).
Results
Patients
Demographic, clinical, and prior surgical characteristics of the 57 patients meeting inclusion criteria are summarized in Table 1 . The majority of patients were diagnosed before 2 years of age, but the age at diagnosis ranged from 0 to 76.9 years. Of the 57 patients, 32 (56%) had prior non–mitral valve surgery. This most commonly included coarctation repair in 23 patients (40%), followed by ventricular septal defect closure in five (9%). Genetic abnormalities were present in 11 patients (19%), but there was no predominant syndrome among this group. Diagnostic or interventional catheterization was performed in 22 patients (39%). Of the 32 patients who underwent ALMR resection, 17 (53%) underwent preoperative catheterization (16 diagnostic and one balloon mitral valvuloplasty). In contrast, among the 25 patients who did not undergo ALMR resection, five (20%) underwent catheterization (four diagnostic and one balloon mitral valvuloplasty).
| Variable | All patients ( n = 57) | ALMR resection ( n = 32) | No ALMR resection ( n = 25) | P |
|---|---|---|---|---|
| Age at diagnosis (y) | 1.8 (0–76.9) | 1.6 (0–16.8) | 3.7 (0.1–76.9) | .24 |
| Age at echocardiography (y) | 2.1 (0–76.9) | 1.7 (0–16.8) | 4.2 (0.1–76.9) | .08 |
| BSA (m 2 ) | 0.49 (0.21–2.27) | 0.42 (0.21–1.48) | 0.80 (0.23–2.27) | .01 |
| Male gender | 35 (61%) | 19 (59%) | 16 (64%) | .79 |
| Genetic syndrome ∗ | 11 (19%) | 6 (19%) | 5 (20%) | 1.00 |
| Associated anomalies | 51 (89%) | 30 (52%) | 21 (37%) | .89 |
| Subaortic stenosis | 15 (26%) | 11 (34%) | 4 (16%) | .14 |
| Aortic valve stenosis | 14 (25%) | 8 (25%) | 6 (24%) | 1.00 |
| BAV | 22 (39%) | 15 (47%) | 7 (28%) | .18 |
| UAV | 7 (12%) | 3 (9%) | 4 (16%) | .69 |
| Coarctation | 11 (19%) | 7 (22%) | 4 (16%) | .74 |
| Shone association † | 5 (9%) | 3 (5%) | 2 (4%) | .64 |
| Prior surgery | 32 (56%) | 21 (66%) | 11 (44%) | .12 |
| CoA repair | 23 (40%) | 16 (50%) | 7 (28%) | .11 |
| VSD repair | 5 (9%) | 4 (13%) | 1 (4%) | .37 |
| Other surgery | 14 (25%) | 9 (28%) | 5 (20%) | .55 |
∗ Adams-Oliver syndrome ( n = 1), Apert syndrome ( n = 1), DiGeorge syndrome ( n = 1), Down syndrome ( n = 1), hemochromatosis ( n = 1), heterotaxy ( n = 1), mosaic trisomy 20 ( n = 1), unspecified syndrome ( n = 2), Turner syndrome ( n = 1), Williams syndrome ( n = 1).
† Shone association defined as ALMR and two or more of the following: (1) parachute mitral valve, (2) subaortic stenosis, and (3) coarctation.
Echocardiographic Data
Annulo-Leaflet Mitral Ring and Associated Anomalies
Echoardiographic data pertaining to the mitral valve, left ventricle, aortic valve, and aortic arch are summarized in Table 2 . ALMR was not associated with other cardiovascular anomalies (i.e., “isolated”) in only six of the 57 patients (11%). Associated mitral valve abnormalities were common and included short chordae in 23 patients (40%), closely spaced papillary muscles in 19 (33%), and parachute deformity in eight (14%). Mitral regurgitation was present in 14 patients (25%) and was mild in 12. Subvalvar and valvar aortic stenoses were noted in 25% and 26% of patients, respectively. The aortic valve was frequently abnormal with bicommissural or unicommissural valve in 29 patients (51%), whereas coarctation of the aorta was diagnosed in 11 (19%). ALMR was part of a Shone association in five patients (9%).
| Variable | All patients ( n = 57) | ALMR resection ( n = 32) | No ALMR resection ( n = 25) | P |
|---|---|---|---|---|
| Isolated ALMR | 6 (11%) | 1 (3%) | 5 (20%) | .08 |
| Initial MV gradient ∗ (mm Hg) | 6 (1 to 25) | 7.5 (1 to 20.0) | 5 (1 to 25.0) | .06 |
| Highest MV gradient ∗ (mm Hg) | 8 (1 to 16) | 9 (1 to 15) | 5 (1 to 16) | <.001 |
| Lateral MV annular Z score | −0.30 (−4.00 to 2.79) | −0.5 (−4.0 to 2.5) | −0.1 (−2.6 to 2.8) | .34 |
| AP MV annular Z score | −0.09 (−3.00 to 4.60) | 0.1 (−2.5 to 3.8) | −0.1 (−3.0 to 4.6) | .87 |
| Mitral valve morphology | ||||
| Closely spaced PMs | 19 (33%) | 12 (38%) | 7 (28%) | .57 |
| Short chordae | 23 (40%) | 17 (53%) | 6 (24%) | .03 |
| Parachute MV | 8 (14%) | 4 (13%) | 4 (16%) | .72 |
| LA area index (cm 2 /m 2 ) | 14.7 (4.1 to 46.1) | 17.5 (6.8 to 28.6) | 9.4 (4.1 to 46.1) | .005 |
| LV EDV Z score | 0.60 (−2.03 to 8.25) | 0.3 (−2.0 to 7.2) | 0.6 (−1.1 to 8.3) | .77 |
| LV mass Z score | 0.97 (−6.18 to 10.55) | 0.9 (−2.1 to 4.3) | 1.5 (−6.2 to 10.6) | .45 |
| LV ejection fraction | 65 (11 to 78) | 66 (50 to 77) | 65 (11 to 78) | .70 |
Imaging Considerations
ALMR was best visualized in the apical four-chamber plane. Prominent lesions ware also seen in the parasternal long-axis views but were often less distinct. Importantly, in 25% of patients, the lesions were indistinct when imaged from the parasternal long-axis view, and the diagnosis was made exclusively from the apical window. Side-by-side display of two-dimensional and color-coded Doppler images was particularly helpful, with the latter showing the location of flow acceleration and the former depicting the anatomic details. Three-dimensional imaging was available only in a small number of cases, and its contribution to the diagnostic evaluation could not be assessed in this study.
Classification of ALMR Morphology
Types of ALMR were categorized on the basis of leaflet involvement (anterior, posterior, or both) and whether the lesion was protruding from the basal portion of the leaflets into the lumen (annular ALMR) or adherent and extending onto the atrial surface of the leaflet (intraleaflet ALMR). On the basis of these criteria, we identified seven distinct types of ALMR, which are shown diagrammatically in Figure 2 and by echocardiography in Figure 3 . As expected, the membrane extent index was significantly higher in patients with intraleaflet involvement compared with those with annular lesions (0.5 ± 0.21 vs 0.27 ± 0.27, P < .001). Moreover, compared with the annular type, the mean mitral valve gradient was significantly higher in the intraleaflet type (8.4 ± 3.7 vs 5.8 ± 3 mm Hg, P = .01).
Factors Associated with ALMR Resection
Of the 57 patients, 32 (56%) underwent ALMR resection at a median age of 1.5 years (range, 0–16.8 years). Compared with patients who did not undergo ALMR resection, those who did tended to be younger at the time of diagnosis (median age, 1.6 vs 3.7 years; P = .24), had significantly lower body surface areas (median, 0.42 vs 0.8 m 2 ; P = .01), had larger indexed LA areas (17.5 vs 9.4 cm 2 /m 2 ; P = .005), and more frequently had short chordae (53% vs 24%, P = .03). In addition, the mean mitral inflow Doppler gradient at the first echocardiographic examination was higher in those who underwent resection (median, 7.5 vs 5 mm Hg; P = .06), with a subsequent increase in the gradient in the resection group as opposed to nonprogression in those who did not (latest mean gradient, 9 vs 5 mm Hg; P < .001). Logistic regression analysis identified younger age at diagnosis and short chordae as factors associated with resection ( Table 3 ). A larger LA area index tended to be related to ALMR resection ( P = .06), but this did not reach statistical significance. The morphologic type of ALMR was not significantly different between those who did and those who did not undergo resection.
