Factors correlating to mitral annulus calcification (MAC) include risk factors predisposing to atherosclerosis. In patients with mitral valve (MV) prolapse (MVP), other anatomic or mechanical factors have been supposed to facilitate MAC. The aims of this study were, in patients with MVP undergoing MV repair, (1) to describe the prevalence and characteristics of MAC, (2) to correlate MAC with clinical risk factors, coronary involvement, and aortic valve disease, and (3) to describe prevalence, site, and extension of MAC in fibroelastic deficiency (FED) versus Barlow’s disease (BD) and correlate MAC to surgical outcomes (repair vs replacement). In 410 consecutive patients with MVP suitable for surgical MV repair, detailed clinical and echocardiographic data were collected to characterize MAC in BD and FED. MAC was found in 99 patients (24%). Age, female gender, coronary artery disease, and cardiovascular risk factors were correlated with MAC. MAC was equally distributed in FED and BD groups despite patients with FED being older with more cardiovascular risk factors. The most common localization of MAC was annular involvement adjacent to P2 (75%), P1 (31%), and P3 (35%). The presence of MAC affected surgical outcomes in both groups (8% patients with MAC underwent replacement after a first attempt of repair vs 3% without MAC). MAC is a common finding in patients undergoing MV repair, and several clinical characteristics correlate with MAC either in FED or BD. In conclusion, despite very high percentage of repairability, MAC influences surgical outcomes and very detailed echo evaluation is advocated.
Mitral annulus calcification (MAC) is one of the more frequent abnormalities of the heart. Factors predisposing to MAC include age, hypertension, diabetes mellitus, hypercholesterolemia, chronic renal insufficiency, prolapsing mitral valve (MV), and other congenital and acquired diseases. The frequent occurrence of factors predisposing to atherosclerosis in patients with MAC supports a common etiologic basis for both MAC and atherosclerosis. In patients with MV prolapse (MVP), several anatomic or mechanical factors have been supposed to facilitate MAC. Specifically, an extensive calcification of the MV annulus is encountered either in elderly subjects with a fibroelastic deficiency (FED) of the MV or in younger adults with Barlow’s disease (BD). MV repair has become preferential to replacement in MVP. However, the operation in patients with MAC remains a challenge for the surgeon, because, both in patients with FED and patients with BD, an annuloplasty ring should be inserted to stabilize the annulus and the suture line with obvious technical implications in MAC cases. The aims of this study are threefold: (1) to describe in detail the prevalence and anatomic characteristics (echocardiography) of MAC in a large consecutive series of patients undergoing MV repair for degenerative MVP, (2) to correlate MAC with clinical risk factors, coronary involvement, and coexisting aortic valve disease, and (3) to describe prevalence, site, and extension of MAC in patients with FED or BD and correlate echocardiographic findings to surgical outcomes (repair vs replacement).
Methods
This is a retrospective analysis including 410 consecutive patients with MVP who underwent MV surgery in our hospital from January 2008 to June 2012. All patients have an established diagnosis of severe mitral regurgitation (MR) due to degenerative MVP evaluated by 2-dimensional transthoracic echocardiography (TTE) and were suitable for surgical MV repair. Exclusion criteria were (1) association of MV stenosis, (2) previous or active endocarditis, and (3) history of coronary artery disease (CAD), previous myocardial ischemia or infarction, bypass graft surgery, or coronary stent implantation. The local ethics committee approved the study. Informed consent was obtained from all patients.
Detailed baseline demographic and clinical data were collected. Current smoking was defined as self-report of ≥1 cigarettes in the past 30 days. Hyperglycemia requiring previous or ongoing pharmacologic therapy was considered as diabetes. High blood pressure was described as either systolic or diastolic elevation of blood pressure (>140/90 mm Hg) or ongoing antihypertensive treatment. Hypercholesterolemia was defined as total cholesterol level of >200 mg/dl or a value <200 mg/dl in association with hypolipidemic therapy. The presence of CAD was evaluated by preoperative coronary angiography. The surgical approach for MV repair varied according to MV morphology and to the surgeon’s choice. However, the procedure was completed with annular ring implantation in all patients. The surgical repair was considered successful in the absence of significant residual MR (more than mild), stenosis (mean diastolic MV gradient >6 mm Hg), and/or systolic anterior motion of the anterior leaflet evaluated by intraoperative transesophageal echocardiography. MV replacement was performed only in case of unsuccessful repair.
A complete presurgical TTE was performed in all patients using a Philips iE33 or a GE Vivid 7 ultrasound system equipped with S5 or M4S probes, respectively (Philips Medical Systems, Andover, Massachusetts, or GE Healthcare, Horten, Norway). All images were digitally acquired and stored for off-line analysis and included standard 2-dimensional, color, and pulse- and continuous-wave Doppler acquisitions. MR was defined as severe when the effective regurgitant orifice area was ≥0.4 cm 2 estimated by proximal isovelocity surface area and/or in presence of vena contracta width >7 mm or of chordal rupture associated with flail leaflets. MVP diagnosis was based on 2- and 3-dimensional TTE. To assess MV anatomy, we used Carpentier’s widely recognized nomenclature that divides the posterior leaflet into 3 scallops: lateral (P1), middle (P2), and medial (P3), and the anterior leaflet into 3 segments: lateral (A1), middle (A2), and medial (A3). The anterolateral and posteromedial commissures were also evaluated. All segments were classified as normal, prolapsing (3 mm beyond the annulus plane), or flail. The presence of ruptured chordae was annotated. MAC was defined as an intense echo-producing structure with stone shadow, usually localized at the posterior mitral annulus, sometimes involving the whole annulus, the base of ≥1 MV scallops, chordae, and ventricular endocardium ( Figure 1 ). To assign the localization of each calcification involving the annulus, the leaflets, or the commissures, we used the conventional Carpentier’s nomenclature as described previously.
Patients were divided into 2 subgroups based on the 2 main phenotypes of degenerative MVP, which are BD and FED. BD is characterized by severe myxomatous degeneration of the leaflets with excess thickened tissue, billowing and/or prolapse of multiple segments of the valve, elongated and thickened, fused, or calcified chordae, and highly dilated annulus. Conversely, the diagnosis of FED is established in case of normal or even thinner leaflets because of impaired production of connective tissue that affects also the chordae tendineae, no billowing, a single prolapsing segment (usually P2) frequently associated with chordal rupture, and slight annular dilation. In the intermediate forms in which the sole prolapsed area presented some degree of myxomatous involvement, the size of the mitral annulus was also taken into consideration. All images were independently evaluated by 2 experienced cardiologists blinded to clinical data. Conflict was resolved by involving a third expert in the decision.
Continuous variables are presented as mean ± SD and categorical variables as frequency and relevant percentage. The data distribution normality of continuous variables was assessed using the Kolmogorov-Smirnov test. Continuous variables were compared using the unpaired Student t test or Mann-Whitney U test, and for categorical variables, the chi-square test or Fisher’s exact test was used, as appropriate, both for comparison between patients with and without MAC and between BD and FED groups. Differences were considered statistically significant at p <0.05. Significant variables in univariate analysis were included in a multivariate logistic regression analysis with stepwise method for the identification of independent variables predicting MAC. Goodness of fit was assessed using the Hosmer and Lemeshow test, in which a p value of <0.05 indicated a lack of fit of the model. Statistical analyses were conducted using SPSS, version 20.0 (SPSS Inc., Chicago, Illinois).
Results
This study included 410 patients with severe MR due to MVP undergoing MV repair in our institution from January 2008 to June 2012. The mean age of this cohort was 62 ± 13 year and 274 patients (67%) were male ( Table 1 ). Female patients were significantly older than male patients (64 ± 12 vs 61 ± 12 years, p = 0.020). Prevalence of MAC was 24% and was higher in female patients (35% in women vs 19% in men, p <0.001). The most common site of MAC was annular involvement adjacent to P2 (75.8%), P1 (31.3%), and P3 (35.4%; Figure 2 ). Involvement of anterior annulus or leaflets was very uncommon. In 17 of 99 patients (17%) the calcium involved the chordae tendineae and in 18 (18%) the posterior-basal left ventricular endocardium. Surgical inspection confirmed echocardiographic findings in all patients with MAC. Hypertension, dyslipidemia, and positive smoking history were significantly more frequent in patients with MAC. Slightly greater prevalence of CAD was found in patients with MAC compared with patients without MAC, with higher rates of severe CAD. Percentage of aortic valve calcification was higher in patients with MAC. Concomitant coronary bypass grafting was performed in 19 patients (19%) with MAC and 42 (14%) without MAC (p = 0.166). The logistic regression analysis revealed that independent predictors of MAC were age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.05 to 1.10, p <0.001), smoking (OR 3.06, 95% CI 1.44 to 6.52, p = 0.004), female gender (OR 2.17, 95% CI 1.32 to 3.57, p = 0.002), and dyslipidemia (OR 1.86, 95% CI 1.06 to 3.26, p = 0.029). The model displayed satisfactory goodness of fit (p = 0.27).
| Variable | Overall (n = 410) | Mitral Annular Calcium | p Value | |
|---|---|---|---|---|
| Yes (n = 99) | No (n = 311) | |||
| Age (yrs) | 62 ± 13 | 68 ± 10 | 60 ± 13 | <0.001 |
| Men | 274 (67) | 51 (51) | 223 (72) | <0.001 |
| Body surface area (m 2 ) | 1.81 ± 0.19 | 1.75 ± 0.18 | 1.82 ± 0.18 | <0.001 |
| Hypertension | 224 (55) | 67 (68) | 157 (51) | 0.003 |
| Diabetes mellitus | 22 (5) | 8 (8) | 14 (4) | 0.169 |
| Dyslipidemia | 265 (65) | 75 (76) | 190 (61) | 0.008 |
| Smoker | 43 (11) | 16 (16) | 27 (9) | 0.031 |
| Coronary artery disease | 87 (21) | 32 (32) | 55 (18) | 0.002 |
| No. of coronary arteries involved | 0.011 | |||
| 0 | 323 (79) | 67 (68) | 256 (82) | |
| 1 | 50 (12) | 18 (18) | 32 (10) | |
| 2 | 20 (5) | 6 (6) | 14 (5) | |
| 3 | 17 (4) | 8 (8) | 9 (3) | |
| End-diastolic volume index (ml/m 2 ) | 76 ± 19 | 73 ± 16 | 77 ± 20 | 0.025 |
| End-systolic volume index (ml/m 2 ) | 27 ± 9 | 27 ± 9 | 27 ± 10 | 0.421 |
| Ejection fraction (%) | 65 ± 7 | 64 ± 8 | 65 ± 7 | 0.386 |
| Aortic valve calcification | 18 (4) | 13 (13) | 5 (2) | <0.001 |
| Pulmonary artery systolic pressure (mm Hg) | 38 ± 12 | 40 ± 12 | 37 ± 12 | 0.013 |
| Annulus anteroposterior diameter (mm) | 36 ± 5 | 35 ± 5 | 36 ± 5 | 0.023 |
| Annulus mediolateral diameter (mm) | 40 ± 5 | 39 ± 5 | 41 ± 5 | 0.041 |
| Eccentricity | 0.10 ± 0.07 | 0.11 ± 0.07 | 0.10 ± 0.07 | 0.306 |
The presence and extent of calcium on MV apparatus influences repair feasibility. Indeed, MV replacement was achieved in 8 patients (8%) with MAC and 9 (3%) without MAC (p = 0.038). No intra- and/or peri-operative death was observed. The presence of MAC was always confirmed by surgical inspection. Concerning morphologic classification, 317 patients (77%) had BD and 93 (23%) had FED. Slightly, but not significantly, higher percentage of MAC was present in the FED group. Patients with FED were older, with greater prevalence of hypertension, diabetes mellitus, and CAD. Patients with BD were characterized by greater anteroposterior and mediolateral diameters. The prevalence of MV and aortic valve calcification was similar in BD and in FED groups ( Table 2 ). Figure 3 describes the localization of the calcifications adjacent to MV scallops in BD and FED. MV replacement was performed in 10 patients (4%) with BD and 7 (8%) with FED (p = 0.076). Patients with and without MAC grouped by BD and FED are compared in Table 3 for clinical characteristics and echocardiographic findings. The localization of MVP involved the posterior leaflet in 279 patients (68%), the anterior leaflet in 50 (12%), and both MV leaflets in 81 (20%). Ruptured chordae was diagnosed in 268 patients (65%). Figure 4 is a flowchart showing surgical outcomes (repair vs replacement) according to BD and FED classification and presence or absence of MAC.
| Variable | Overall (n = 410) | BD (n = 317) | FED (n = 93) | p Value |
|---|---|---|---|---|
| Age (yrs) | 62 ± 13 | 60 ± 13 | 68 ± 9 | <0.001 |
| Men | 274 (67) | 205 (65) | 69 (74) | 0.086 |
| Body surface area (m 2 ) | 1.81 ± 0.19 | 1.80 ± 0.18 | 1.83 ± 0.19 | 0.143 |
| Hypertension | 224 (55) | 161 (51) | 63 (68) | 0.004 |
| Diabetes mellitus | 22 (5) | 13 (4) | 9 (10) | 0.036 |
| Dyslipidemia | 265 (65) | 206 (65) | 59 (63) | 0.784 |
| Smoker | 43 (11) | 36 (11) | 7 (7) | 0.289 |
| Coronary artery disease | 87 (21) | 55 (17) | 32 (34) | <0.001 |
| No. of coronary arteries involved | 0.002 | |||
| 0 | 323 (79) | 262 (83) | 61 (66) | |
| 1 | 50 (12) | 33 (10) | 17 (18) | |
| 2 | 20 (5) | 10 (3) | 10 (31) | |
| 3 | 17 (4) | 12 (4) | 5 (16) | |
| End-diastolic volume index (ml/m 2 ) | 76 ± 19 | 79 ± 19 | 68 ± 15 | <0.001 |
| End-systolic volume index (ml/m 2 ) | 27 ± 9 | 28 ± 10 | 25 ± 8 | 0.016 |
| Ejection fraction (%) | 65 ± 7 | 65 ± 7 | 63 ± 8 | 0.034 |
| Aortic valve calcification | 18 (4) | 12 (4) | 6 (6) | 0.260 |
| Mitral annular calcium | 99 (24) | 72 (23) | 27 (29) | 0.211 |
| Pulmonary artery systolic pressure (mm Hg) | 38 ± 12 | 37 ± 12 | 38 ± 11 | 0.283 |
| Annulus anteroposterior diameter (mm) | 36 ± 5 | 37 ± 5 | 34 ± 5 | <0.001 |
| Annulus mediolateral diameter (mm) | 40 ± 5 | 41 ± 5 | 38 ± 5 | <0.001 |
| Eccentricity | 0.10 ± 0.07 | 0.10 ± 0.07 | 0.11 ± 0.06 | 0.513 |
| Variable | BD (n = 317) | p Value | FED (n = 93) | p Value | ||
|---|---|---|---|---|---|---|
| MAC (n = 72) | No MAC (n = 245) | MAC (n = 27) | No MAC (n = 66) | |||
| Age (yrs) | 67 ± 10 | 58 ± 13 | <0.001 | 72 ± 9 | 67 ± 9 | 0.010 |
| Men | 34 (47) | 171 (70) | 0.001 | 17 (63) | 52 (79) | 0.113 |
| Body surface area (m 2 ) | 1.74 ± 0.18 | 1.81 ± 0.18 | 0.001 | 1.78 ± 0.18 | 1.86 ± 0.19 | 0.072 |
| Hypertension | 45 (63) | 116 (47) | 0.024 | 22 (81) | 41 (62) | 0.070 |
| Diabetes mellitus | 4 (6) | 9 (4) | 0.479 | 4 (15) | 5 (8) | 0.284 |
| Dyslipidemia | 53 (74) | 153 (63) | 0.081 | 22 (81) | 37 (56) | 0.021 |
| Smoker | 13 (18) | 23 (9) | 0.042 | 3 (11) | 4 (6) | 0.410 |
| Coronary artery disease | 19 (26) | 36 (15) | 0.021 | 13 (48) | 19 (29) | 0.074 |
| No. of coronary arteries involved | 0.023 | 0.135 | ||||
| 0 | 53 (74) | 209 (85) | 14 (52) | 47 (71) | ||
| 1 | 13 (18) | 20 (8) | 5 (18.5) | 12 (18) | ||
| 2 | 1 (1) | 9 (4) | 5 (18.5) | 5 (8) | ||
| 3 | 5 (7) | 7 (3) | 3 (11) | 2 (3) | ||
| End-diastolic volume index (ml/m 2 ) | 75 ± 16 | 80 ± 20 | 0.017 | 68 ± 14 | 68 ± 15 | 0.790 |
| End-systolic volume index (ml/m 2 ) | 27 ± 9 | 28 ± 10 | 0.508 | 25 ± 9 | 25 ± 8 | 0.738 |
| Ejection fraction (%) | 64 ± 7 | 65 ± 7 | 0.242 | 63 ± 9 | 63 ± 8 | 0.995 |
| Aortic valve calcification | 9 (12) | 3 (1) | <0.001 | 4 (15) | 2 (3) | 0.057 |
| Pulmonary artery systolic pressure (mm Hg) | 39 ± 12 | 37 ± 12 | 0.040 | 40 ± 13 | 37 ± 9 | 0.181 |
| Annulus anteroposterior diameter (mm) | 35 ± 5 | 37 ± 5 | 0.010 | 35 ± 5 | 34 ± 5 | 0.708 |
| Annulus mediolateral diameter (mm) | 40 ± 5 | 41 ± 5 | 0.042 | 38 ± 5 | 38 ± 5 | 0.802 |
| Eccentricity | 0.11 ± 0.07 | 0.10 ± 0.07 | 0.142 | 0.10 ± 0.06 | 0.10 ± 0.06 | 0.584 |
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