Background
Mitral annular calcification (MAC) is a chronic inflammatory process with similarities to atherosclerosis. It is common in elderly patients and those with renal dysfunction. Although MAC is associated with cardiovascular morbidity, its relationship to infective endocarditis is unclear. The aim of this study was to test the hypothesis that MAC would be prevalent in patients with mitral valve vegetations and that vegetations would frequently occur on calcific nodules. A secondary aim was to look for possible bacteriological differences between vegetations attached to the calcified annulus versus leaflet vegetations.
Methods
We retrospectively reviewed all echocardiographic studies of patients with native mitral valve vegetations from January 2007 to August 2015 ( N = 56). We searched for (1) presence of MAC, (2) location of MAC, and (3) vegetation location (on calcium deposits or distant). MAC was defined as focal echo brightness in a nodular or band-like pattern. The modified Duke criteria were used to confirm the diagnosis of infective endocarditis. Transthoracic, transesophageal, and three-dimensional echocardiograms (when available) at the time of infection were evaluated by a single reader.
Results
Twenty-eight subjects were infected with Staphylococcus aureus , 17 with a streptococcal species, and five with other organisms; blood cultures were sterile in 6. Thirty-four (61%) subjects had some degree of MAC, while 22 (39%) had none. Among those with MAC, the vegetation was located on the calcium deposits in 22 (65%), versus in 12 (35%) where it was not. Among all 56 subjects, when S. aureus was the infecting organism it was present on MAC in 16/28 (57%) versus 6/28 (21%; P = .01) for other bacterial species. By contrast, streptococcal infections more frequently involved the leaflets (16/17 [94%]) versus nonstreptococcal infections (18/39 [46%]; P = .0008).
Conclusions
MAC may act as a nidus for infection especially with S. aureus . Differences in mechanism of attachment between S. aureus and streptococci may account for the observed difference in frequency of attachment of vegetations to MAC.
Highlights
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Mitral annular calcification is an inflammatory process that can serve as a nidus for infective endocarditis
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Vegetations arising from the calcified annulus are frequently due to S. aureus.
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Infections involving the calcified annulus sometimes produce large, speckled vegetations; these possibly represent destruction of annular tissue resulting in distribution of flecks of calcium throughout the vegetation.
Mitral annular calcification (MAC) is a chronic degenerative process within the cardiac fibrous skeleton that bears similarities to valvular and vascular calcification. It is commonly encountered on echocardiography, particularly in the elderly and those with renal dysfunction. The prevalence of MAC has been reported to be between 8% and 15%.
MAC is associated, through common risk factors, with cardiovascular disease, including coronary disease and stroke. Calcification affects the posterior portion of the mitral annulus more than the anterior portion (interannular fibrosa) and is associated with impaired annular motion. MAC, like cardiac calcification in general, involves inflammation and disruption of the endocardial surface, factors that might predispose to infective endocarditis. Multiple case reports and small case series describe endocarditis in association with MAC. We therefore reviewed our own experience with mitral valve endocarditis to determine the presence of MAC and its association with infective vegetations. Most of our subjects underwent transesophageal echocardiography (TEE), including three-dimensional imaging in many, allowing precise determination of vegetation location and relation to any MAC. Finally, we examined the microbiology involved to see whether particular species were associated with vegetations involving the calcified annulus.
Methods
This was a retrospective cohort study. Hospital records and echocardiogram reports from January 2007 to August 2015 were searched to identify those patients with reported mitral valve vegetations. The resulting 71 records were reviewed by a single reader (G.S.P.). Fifteen subjects were excluded: eight without a definite vegetation (thickened leaflets or chordae, valve strands, mobile calcification), three with annuloplasty rings, two with mechanical valves, one with a healed vegetation, and one with a valve tumor (probable papillary fibroelastoma). This left a set of 56 subjects, all with native mitral valve endocarditis, for analysis. The modified Duke criteria were used to confirm the diagnosis of infective endocarditis in patients with native valve mitral endocarditis, fulfilling either two major, one major and three minor, or five minor criteria. MAC was defined as focal echogenic brightness in a nodular or band-like pattern. In each case the diagnostic echocardiogram and any other echocardiograms (transthoracic or transesophageal) done during the index admission for endocarditis were carefully reviewed. All echocardiograms were interpreted without knowledge of the infecting organism. We noted (1) the location of the vegetation and (2) the presence or absence of MAC and its location. In MAC subjects the location of the vegetation was recorded as either (1) on or overlying calcium deposits or (2) distinct from them. Also recorded was the presence or absence of apparent calcifications in the vegetation and annular complications (abscess, perforation at the base of the leaflet, or fistula formation).
Continuous variables are presented as mean and standard deviation. Comparisons between categorical variables were done using either the χ 2 test or Fisher’s exact test, as appropriate. A two-tailed P value < .05 was considered statistically significant. Statistical analyses were performed using JMP 11.0 (SAS Institute, Cary, NC).
Results
Baseline characteristics of the study group are displayed in Table 1 . Fifty subjects had the diagnosis of endocarditis made on TEE (89.2%), while in six patients transthoracic echocardiography (TTE) alone was performed. In 10 patients TTE was unable to visualize a vegetation that was only seen on TEE.
| Total group | MAC | No MAC | P value | |
|---|---|---|---|---|
| Age | 60 ± 15 | 65 ± 15 | 52 ± 12 | .001 |
| Gender (% male) | 59 | 56 | 64 | .59 |
| Race | ||||
| Black | 32 | 20 | 12 | |
| White | 13 | 7 | 6 | .61 |
| Hispanic | 8 | 6 | 2 | |
| Other | 3 | 1 | 2 | |
| Hypertension (%) | 68 | 79 | 50 | .04 |
| Diabetes (%) | 41 | 56 | 18 | .006 |
| Smoking (%) | 45 | 32 | 64 | .03 |
| Hyperlipidemia (%) | 13 | 15 | 9 | .69 |
| CKD (%) | 41 | 56 | 18 | .006 |
| Coronary artery disease (%) | 25 | 35 | 9 | .03 |
| Heart failure (%) | 25 | 38 | 5 | .005 |
Mitral Annular Calcification
Thirty-four subjects had some degree of MAC, and 22 had none. Three patients had MAC limited to the anterior annulus; in all others MAC involved posterior annular segments or both anterior and posterior segments. Five subjects had flail segment(s) of the mitral valve; otherwise the valves were structurally normal. MAC patients were older than patients without MAC (65 ± 15 years vs 52 ± 12 years; P = .001). They had more hypertension, diabetes, and coronary disease ( Table 1 ). They also had more chronic kidney disease (CKD, [estimated glomerular filtration rate < 60 mL/min/1.73 m 2 ] 56% vs 18%; P = .006), with 18 subjects on chronic hemodialysis (32% of the study sample). Vegetations were located on the posterior mitral leaflet or annulus in 21 subjects, the anterior leaflet or annulus in 16, and both in 19. Of the 34 cases in which MAC was present, vegetations were noted on a calcified segment in 22 (65%); in 12 (35%) the vegetation was not visibly attached to the MAC.
Bacteriology
Bacteriology for the study subjects is displayed in Table 2 and Figures 1 A and 1B. Twenty-eight patients were infected with Staphylococcus aureus , 17 with a streptococcal species (including enterococcus ), and five with other organisms. In six cases blood cultures were sterile (five of the six had previously received antibiotics). In each of these cases, the diagnosis of endocarditis was made based on clinical and echocardiographic characteristics. Among the 56 patients included in this study, 15 (27% of the entire sample) had a central venous catheter as a possible source of endocarditis; six of them had S. aureus (methicillin resistant in two). Of the total cohort, six were active intravenous drug users (11% of the total sample).
| Organism | Number of subjects |
|---|---|
| S. aureus | 28 |
| Streptococcal species ( enterococcus ) | 17 (11) |
| Klebsiella species | 1 |
| Staphylococcus coagulase negative | 1 |
| Hemophilus parainfluenza | 1 |
| Eikinella corrodens | 1 |
| Candida albicans | 1 |
| No growth | 6 |
| Total | 56 |
Comparing those with S. aureus with those infected with other organisms, there was no significant difference in the percentage of cases with MAC. Among all 56 subjects, when S. aureus was the infecting organism it was present on MAC in 16/28 (57%) versus other bacterial species where vegetations were present on MAC in 6/28 (21%; P = .01; Figure 2 and Table 3 ). By contrast, streptococcal infections more frequently involved the leaflets (16/17 [94%]) versus nonstreptococcal infections (18/39 [46%]; P = .0008; Table 3 ). When analyses were limited to subjects with MAC ( n = 34), similar results were obtained. S. aureus infections were more common among MAC vegetations than among leaflet vegetations (16/22 [73%] vs 4/12 [34%]; P = .036). By contrast, streptococcal infections were more often involved in leaflet vegetations than in annular vegetations (6/12 [50%] vs 1/22 [4%]; P < .01). See the photomontage ( Figure 3 ) for various examples of S. aureus and streptococcal infections.
| Organism | On MAC | Not on MAC ∗ | Stippled mass | Complications † |
|---|---|---|---|---|
| S. aureus | 16 ‡ | 12 | 12 ¶ | 10 || |
| Streptococcal species | 1 | 16 § | 3 | 1 |
| Others | 5 | 6 | 5 | 3 |
| Total | 22 | 34 | 18 | 14 |
∗ Vegetation attached to leaflets or to the noncalcified annulus.
† Perforation, abscess, fistula.
‡ P = .01 comparing S. aureus with all other organisms.
§ P = .0008 comparing streptococcal infections with all other organisms.
|| P = .03 comparing S. aureus with streptococcal infections.
¶ P = .055 comparing S. aureus with streptococcal infections.
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