Version May 2024
INTRODUCTION — Mitral annular calcification (MAC) is a chronic, progressive process involving the fibrous annulus of the mitral valve. It is most commonly asymptomatic and identified incidentally during cardiac imaging studies. MAC tends to be more prominent with aging, although other underlying processes, such as atherosclerosis, altered mineral metabolism, or increased mechanical stress, promote development of MAC. In advanced cases, MAC may be significant, causing obstruction of left ventricular (LV) inflow and symptomatic mitral stenosis. Cohort studies have demonstrated an association of MAC with atherosclerotic disease and adverse cardiovascular events, including stroke and increased mortality. Additionally, there is an association of MAC with arrhythmia, including atrial fibrillation (AF) and conduction system disease.
The clinical manifestations (including associated conditions) and diagnosis of MAC are discussed here. Management and prognosis in patients with MAC is discussed separately. (See "Management and prognosis of mitral annular calcification".)
ANATOMY AND PATHOLOGY — The mitral valve (MV) annulus has a complex three-dimensional shape analogous to a saddle with the relative nadirs of the annulus located medially and laterally. At the base of the LV, the annulus is composed of a C-shaped segment of fibrous skeleton. The MV leaflets are suspended from the mitral annulus, which provides structural support to the valve apparatus along the medial, posterior, and lateral aspects of the valve. Anteriorly, the midsection of the anterior mitral leaflet is in fibrous continuity with the posterior aortic root via the intervalvular fibrosa, without intervening annular tissue. In systole, normal mitral annular contraction is along the anteroposterior plane, resulting in folding along the mediolateral plane with a reduction in annular cross-sectional area, facilitating leaflet coaptation [1,2]. Three-dimensional echocardiography studies in patients with MAC have shown a relative loss of annular systolic motion, resulting in a larger, flatter annulus in systole [3].
Mitral annular calcification — MAC is characterized by progressive calcium deposition along and beneath the MV annulus [4]. MAC generally follows the C-shaped fibrous skeleton of the posterior mitral annulus, with relative sparing of the base of the anterior mitral leaflet. Sparing of involvement of the mitral leaflet commissures and anterior annulus distinguishes MAC from rheumatic mitral disease. MAC is readily seen by echocardiography, appearing as a bright echodense region adjacent to the posterior atrioventricular (AV) groove (image 1A and image 1B). Echocardiographic features of MAC are described below. (See 'Identification of mitral annular calcification' below.)
MAC is differentiated from other causes of calcific or degenerative MV disease, such as radiation valve disease. Mediastinal radiation therapy is a component of treatment for several malignancies, such as breast cancer and Hodgkin lymphoma. Patients who develop radiation-associated valve disease develop heavy calcification and fibrosis of left-sided cardiac structures, typically presenting after a lengthy latency period (10 to 20 years) following exposure. Severity of valve involvement is associated with radiation dose [5]. In contrast to MAC, which tends to involve the posterior mitral annulus, radiation valve disease is more likely to involve the aortic and MV and surrounding structures such as the aorto-mitral curtain, anterior MV annulus, and subvalvular apparatus. (See "Cardiotoxicity of radiation therapy for breast cancer and other malignancies".)
Caseous calcification — Caseous calcification of the mitral annulus is a rare (less than 1 percent) variant of MAC that appears as a smooth, round periannular mass [6-8]. Echocardiographic features are described below. (See 'Caseous calcification' below.)
PATHOPHYSIOLOGY — Data on the pathophysiology of MAC are limited. Initially thought to be a passive, degenerative process, MAC is now understood to be a more active process, akin to atherosclerosis and calcific aortic valve disease [9]. There is a strong association between atherosclerotic risk factors and valve calcification [10,11]. (See 'Clinical manifestations' below.)
MAC is thought to be initiated by endothelial disruption at foci of increased mechanical stress at the junction between the mitral valve (MV) annulus and ventricular myocardium. Focal accumulation of oxidized lipids serves as a nidus for chronic inflammatory cell infiltrates including T lymphocytes and macrophages, as well as activated mast cells that promote extracellular matrix remodeling [12,13]. Focal calcific deposits in regions of microinjury and lipoprotein accumulation may then coalesce over time into the dense, fibrotic, rigid band macroscopically evident as MAC. Conditions that increase mitral annular stress, such as higher LV systolic pressure (aortic stenosis or systemic hypertension) or higher leaflet tension (MV prolapse), are associated with MAC [14,15].
MAC may reflect systemic disorders of tissue mineralization. Among patients with end-stage renal disease, MAC was associated with an elevated calcium-phosphate product [16,17]. Increased serum phosphate has also been associated with aortic valve calcification, aortic annular calcification, and MAC [18].
MAC has been associated with systemic markers of inflammation [19]. In a report from the Cardiovascular Health Study, of 5888 participants, 3585 participants had inflammatory, lipid, and mineral biomarker data available, measured within five years of echocardiography. Fibroblast growth factor (FGF-23) was positively associated with MAC with a relative risk (RR) of 1.040 (95% CI 1.004-1.078), and fetuin A, a multifunctional glycoprotein that inhibits dystrophic calcification, was negatively associated with an RR of 0.989 (95% CI 0.911-0.989) [20]. While other studies have similarly demonstrated the inverse association of MAC with serum fetuin A [21,22], the association between MAC and systemic inflammatory markers may reflect shared risk factors. In a report from the Framingham Heart Study, while valvular calcification was associated with elevated levels of inflammatory markers, the association was no longer significant after adjusting for other cardiovascular disease risk factors [19].
Other contributing factors for earlier development of MAC (in adolescence or young adulthood) include connective tissue abnormalities and genetic abnormalities of the fibrous skeleton, such as Marfan syndrome [23,24], and systemic disease associated with chronic inflammation, such as systemic lupus erythematosus [25]. In an investigation of the potential genetic contribution to valve calcification, genomewide associations with MAC (detected by computed tomography scanning) were identified among 3795 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium. Two single nucleotide polymorphisms, rs17659543 and rs13415097, near IL1F9, a proinflammatory gene, reached significance (p<1.5x10-8) for MAC, but the findings could not be reliably replicated in independent cohorts. Genomewide associations with aortic valve calcification in this study were stronger, with results replicated in independent cohorts [26].
PREVALENCE
General — Given that calcification of the mitral annulus without significant mitral inflow obstruction is asymptomatic, overall prevalence of MAC in the general population is underestimated. Published studies of MAC demonstrate that prevalence and severity of MAC increases with age [27-31]. In cohorts with mean age in the range of 50 to 60 years, reported prevalence of MAC was 3 to 9 percent [14,27,28,32,33]. In the multiethnic Northern Manhattan study cohort of 1955 subjects (older mean age 68 years) without prior myocardial infarction or ischemic stroke, MAC was identified in 27 percent [34]. In two population-based studies of older patients, mean ages of 70 and 76 years, respectively, the prevalence of MAC was 14 percent (by M-mode echocardiography) and 42 percent (by two-dimensional echocardiography) [30,31]. The EuroHeart Survey was a prospective study of 5000 patients with moderate to severe valvular heart disease that showed that among age groups 60 to 70 years, 70 to 80 years, and over 80 years, MAC accounted for 10, 30, and 60 percent of mitral stenosis (MS) cases, respectively [35].
There are conflicting data on whether the prevalence of MAC is higher in females than males, as observed in some populations such as the Framingham Heart Study and the Multi-Ethnic Study of Atherosclerosis (MESA) population [29,31,33,34], or is similar in females and males, as noted in the Atherosclerosis Risk in Communities study and the Cardiovascular Health Study [14,28,30].
A single center study of 1004 patients with severe MAC and mean diastolic gradient over 2 mmHg reported baseline characteristics of older age (mean 73 years) with female preponderance (73 percent) [36]. In a retrospective study on the natural history of severe calcific MS (mitral valve area <1.5 cm2) which included 200 patients, patients with severe MS were older (mean age 78 years) with higher likelihood of female sex (82 percent). With regards to symptom status, only 120 (60 percent) were symptomatic at baseline, with 20 patients (10 percent) developing symptoms during the 2.8-year follow-up period [37].
Kidney disease — In patients with altered mineral metabolism, MAC is more prominent with accelerated progression. In patients with end-stage kidney disease, prevalence of aortic valve and mitral annular calcification is reported in the range of 35 to 50 percent despite a relatively younger age range (mean age of 50 to 60 years old) [16,17,38]. MAC is more common among those dialyzed for a longer period of time [16] and is associated with coronary artery disease, atherosclerotic vascular disease, and mortality [17,38].
Among 3929 subjects (mean age 74±5 years, 60 percent women) in the Cardiovascular Health Study, moderate kidney disease (estimated glomerular filtration rate [eGFR] <45 mL/min/1.73 m2) was significantly associated with MAC (odds ratio [OR] 1.54) but not with aortic annular calcification or aortic valve sclerosis. Cystatin C levels (another marker of renal insufficiency) were also associated with MAC (OR 1.12) [39].
In an analysis from the MESA study, of 6785 participants, MAC was present in 8 percent of participants with eGFR ≥60 mL/min/1.73 m2 (mean age 62 years) but increased to 20 percent of participants with a lower eGFR <60 mL/min/1.73 m2 (mean age 70 years). In adjusted analyses, eGFR <60 mL/min/1.73 m2 was associated with MAC among subjects with diabetes but not among those without diabetes [40]. From the Framingham Heart Study, of 3047 participants, 284 participants (9.3 percent) had valve/annular calcification. Of these, 20 percent had chronic renal insufficiency compared with just 7 percent in those without valve calcification. After adjustment for atherosclerotic risk factors, those with chronic renal insufficiency had a 60 percent increased likelihood of MAC (OR 1.6, 95% CI 1.03-2.5) [41].
CLINICAL MANIFESTATIONS — MAC is typically asymptomatic, identified as an incidental finding in patients undergoing diagnostic imaging such as chest radiography, chest computed tomography, fluoroscopy, or echocardiography [42,43]. MAC generally has little or no hemodynamic impact on LV inflow or mitral valve (MV) function. However, extensive calcification may cause functional mitral stenosis (MS), mitral regurgitation (MR), or both (mixed disease) [44-46].
Mitral stenosis — In severe cases, MAC leads to calcific MS with hemodynamically significant obstruction of LV inflow at the mitral annular level, impairment of diastolic annular motion, and restriction of MV leaflet motion [45].
Mitral regurgitation — MAC may lead to MR by preventing normal systolic annular contraction [45] and restricting leaflet mobility. In a review of 24,380 echocardiograms, MAC was present in 11.7 percent of patients with MR and in 4.3 percent without MR [27].
ASSOCIATED CONDITIONS
Aortic valve disease — Given the similarities in pathologic appearance and clinical associations between MAC and aortic sclerosis, it is not surprising that patients with MAC often have concurrent calcification of the aortic valve annulus, aortic valve leaflets, and aortic root [47]. MAC is a risk factor for hemodynamic progression of calcific aortic valve disease [9]. In patient cohorts from transcatheter aortic valve implantation (TAVI) studies in which cardiac computed tomography (CT) is obtained during the pre-TAVI procedure evaluation, MAC is highly prevalent. In a single-center cohort of 346 patients referred for TAVI and screened with cardiac CT, 174 (50 percent) had MAC [48]. Of these, significant inflow obstruction (moderate or greater severity stenosis) was present in 34 percent of patients. In a cohort of 761 patients referred for TAVI, 49.3 percent had coexistent MAC [49]. Moderate MAC was present in 72 patients (9.5 percent), and severe MAC was present in 72 patients (9.5 percent).
Diastolic dysfunction — MAC is associated with reduced early- and late-diastolic annular velocities [50]. Reduction in mitral annular motion in patients with MAC may be due to diastolic dysfunction associated with LV hypertrophy, which is associated with MAC [27]. (See 'Interference with evaluation of concurrent conditions' below.)
Arrhythmias
Conduction system disease and bradyarrhythmias — MAC is associated with a high prevalence of conduction system disease (including AV block, bundle branch block, and intraventricular conduction delay) [44,51]. MAC is also associated with an increased rate of symptomatic bradyarrhythmias (due to sinus arrest or conduction system disease) requiring permanent pacemaker implantation [52]. In a single-center study of patients referred for TAVI, of 761 patients referred for TAVI, severe MAC was an independent predictor of need for new permanent pacer placement following TAVI procedure (odds ratio 2.83, 95% CI 1.08-7.47). There were 70 patients (11.6 percent) who required new pacemaker placement post-TAVI among the 606 patients that did not have a pacemaker prior to TAVI [49]. (See "Permanent cardiac pacing: Overview of devices and indications".)
The association between MAC and conduction disease may be due to direct extension of calcific deposits to the region of the AV node and His bundle. In a small study, conduction abnormalities (AV block), bundle branch block, or intraventricular conduction delay were more common in patients with MAC near the conduction system (53 percent) than in those with MAC further from the conduction system (26 percent) [53]. However, prevalence of conduction disturbances remote from MAC (eg, sinoatrial dysfunction) suggests that diffuse degenerative conduction system disease is also present [52].
Atrial fibrillation — There is an association between MAC and AF [33,54,55]. A report from the Framingham Heart Study with 16 years of follow-up of 1126 subjects found that MAC was an independent predictor of incident AF (adjusted hazard ratio 1.6, 95% CI 1.1-2.2) [55]. Among 6641 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), there was a strong association between MAC and AF, with higher risk for development of AF in patients who had progression of MAC severity across several evaluations [56,57].
Atherosclerotic cardiovascular disease — MAC is significantly associated with coronary artery disease as detected by radionuclide myocardial perfusion imaging [58], coronary CT [32,59], or invasive coronary angiography [60-62]. In a population of 2465 patients with mean age 69 years who underwent coronary angiography for suspected coronary artery disease, the presence of MAC was associated with increased prevalence of >70 percent coronary artery stenosis (80 percent in those with MAC versus 69 percent in those without MAC) [62]. In addition, significant three vessel disease was more common in patients with severe MAC (47 percent) and in those with mild to moderate MAC (35 percent) than in those with no MAC (30 percent).
Similarly, in the MESA population of 6814 subjects undergoing coronary CT scans, coronary artery calcification was present in 3398 (50 percent of the study cohort). After taking into account demographics and other risk factors, the prevalence ratio of MAC in those with mild coronary artery calcification (1 to 99) was 2.13 (95% CI 1.69-2.69) but increased to 7.57 (95% CI 5.95-9.62) for coronary artery calcification >400. This association weakened but persisted after adjustment for age, sex, and other traditional cardiovascular risk factors, suggesting that MAC presence is an indicator of atherosclerotic burden [32].
MAC is also associated with atherosclerosis of the aorta, independent of cardiovascular risk factors, including carotid artery disease [14,63,64].
Endocarditis
MAC at or near nidus of infection — Case reports and published series have described infective endocarditis involving the mitral valve (MV) in patients with MAC. Endocarditis lesions have included MV leaflet vegetations, paravalvular abscess, and, less commonly, vegetations adherent to MAC [65]. These observational studies suggest that MAC endocarditis is associated with greater comorbidity (eg, diabetes mellitus and cancer) and poor clinical outcome with high in-hospital mortality [65]. A single-center retrospective review of echocardiographic studies in 56 patients with native MV endocarditis identified Staphylococcus aureus as the culprit in 28 patients and streptococcal species in 17 patients. When S. aureus was the infecting organism, the vegetation was adherent to MAC in 57 percent of cases. By contrast, streptococcal infections more predominantly affected the valve leaflets, suggesting that MAC may act as a nidus for infection, particularly for S. aureus infections [66]. The presence of MAC may obscure echocardiographic detection of adjacent abscess cavities due to acoustic shadowing of the ultrasound beam distal to the calcium. (See 'MAC may obscure an abscess' below.)
Limited data suggest a poor prognosis among patients with MAC undergoing surgery for MV infective endocarditis. In one series of 24 patients with MAC and endocarditis (18 with acute and 6 with healed endocarditis) undergoing mitral surgery, in-hospital mortality was 29 percent, with all early deaths occurring in patients operated on during the acute infection event [67]. Frequent comorbidities (eg, chronic kidney disease, cancer, coronary disease) contribute to poor outcomes.
MAC may obscure an abscess — The presence of MAC can interfere with echocardiographic identification of abscesses in the region of the calcified posterior mitral annulus. In a transesophageal echocardiography (TEE) study of 115 patients with definite infective endocarditis who underwent cardiac surgery, 38 percent had an abscess detected at surgery [68]. TEE detected an abscess in 48 percent of those with an abscess. The majority (61 percent) of missed abscesses were localized to the posterior mitral annulus, which was frequently calcified.
Tricuspid annular calcification — Tricuspid annular calcification (TAC) is much less common than MAC and does not typically progress to hemodynamically significant obstruction of right ventricular inflow. TAC has been reported in patients with chronic kidney disease [69] and in patients with pulmonic stenosis. Like MAC, a variant of TAC with caseous calcification has been reported (image 2) [6]. (See 'Caseous calcification' above.)
DIAGNOSTIC EVALUATION — The diagnostic evaluation includes identification and characterization of MAC and identification and characterization of mitral stenosis (MS) and mitral regurgitation (MR) and associated conditions.
Approach to diagnosis — Echocardiography is the primary imaging modality for identification and characterization of MAC and associated mitral valve (MV) disease. For patients with an indication for MV surgery, computed tomography (CT) is a complementary imaging modality for MAC [70]. If echocardiography and CT findings are indeterminate for caseous calcification, cardiac magnetic resonance (CMR) may be helpful. For symptomatic patients with severe MAC for whom the severity of MS is uncertain, cardiac catheterization with hemodynamic assessment can be helpful [46].
Echocardiography — Echocardiography enables identification of MAC, evaluation of MV anatomy and valve hemodynamics (including assessment for MR), evaluation of biventricular function, estimation of pulmonary pressures, and identification of concurrent valve and cardiac conditions. In a retrospective echocardiography study of 24,380 echocardiographic examinations, MAC was independently associated with the presence of LV hypertrophy, MR, tricuspid regurgitation, aortic stenosis, left atrial (LA) enlargement, and reversed early to late filling (E/A) ratio [27].
Identification of mitral annular calcification — MAC is visualized by echocardiography as an echodense, irregular shelf-like structure involving the MV annulus adjacent to the posterior AV groove with associated acoustic shadowing (image 1A-B). MAC is most commonly an incidental finding on echocardiographic imaging and is characteristically identified on parasternal and apical views of the left heart with acoustic shadowing of structures distal to the calcification. Although MV leaflets and chordae tendineae are generally not involved, in more advanced cases, calcification may progressively accumulate in the subvalvular region beneath the posterior leaflet with encroachment onto the leaflet and into the myocardial wall.
Severity of MAC is typically reported qualitatively, with calcification of less than one-third of the annulus graded as "mild" and greater than two-thirds graded as "severe." The thickness of the calcific band may also be measured via M-mode imaging from the parasternal long-axis view. (See "Management and prognosis of mitral annular calcification", section on 'Prognosis'.)
Caseous calcification — As noted above, caseous calcification is a rare variant of MAC. On echocardiography, caseous calcification is less echodense than typical MAC, a central echolucent zone is present, and acoustic shadowing is absent. The caseous contents of the mass have a putty-like consistency with microscopic features consistent with liquefaction necrosis with amorphous eosinophilic acellular material surrounded by macrophages and lymphocytes and multiple small calcifications [6].
Limited longitudinal observations indicate that caseous calcification may be a dynamic condition. Caseous calcification may spontaneously resolve [71] or convert to typical MAC, and typical MAC may rarely convert to caseous calcification [7]. Caseous calcification should not be misdiagnosed as a myocardial abscess, tumor, or thrombus.
Evaluation of mitral stenosis — MAC rarely progresses to significant obstruction to LV inflow and calcific MS. When calcific MS is suspected, the MV gradient and the MV area (MVA) should be assessed. In early-stage MS due to rheumatic valve disease, leaflet pliability is relatively preserved with inflow obstruction at the leaflet tips due to commissural fusion, resulting in a funnel shaped valve. In contrast, obstruction of mitral inflow with calcific MS due to MAC is at the level of the mitral annulus, with relative sparing of the leaflet tips, resulting in more of a tunnel-shaped orifice. As a consequence, there is relatively more rapid equalization of the LA to LV pressure gradient for calcific MS relative to that seen in rheumatic MS.
Hemodynamic assessment for mitral stenosis — Spectral Doppler interrogation of the MV from the apical views of the heart provides hemodynamic data on functional restriction of LV inflow (image 3). The LA to LV diastolic mean pressure gradient is calculated from the transmitral continuous wave Doppler signal, utilizing the simplified Bernoulli equation [72]. Stenosis of the MV with inflow obstruction increases transvalvular flow. Other conditions that increase transvalvular flow, such as increased heart rate or significant MR, will also increase transmitral gradient. Therefore, in addition to severity of inflow obstruction, transmitral gradients depend on length of the diastolic filling period, cardiac output, severity of associated MR (transvalvular flow), and factors which affect hemodynamic load, such as LV diastolic filling pressure and chamber compliance. Severity of anatomic valve obstruction from MAC, as assessed by the transmitral gradient, should account for LV diastolic dysfunction with high LV filling pressures, decreased LA compliance, and MR (increasing the early diastolic gradient, the mitral "E" wave). Without accounting for hemodynamic loading conditions, the transmitral gradient alone would overestimate anatomic severity of stenosis attributed to MAC. While higher diastolic mean gradients (over 5 mmHg) may be seen in severe cases of inflow obstruction, diastolic mean gradient is highly variable, dependent on heart rate and transmitral flow. As such, the transmitral gradient is not primarily recommended as a formal diagnostic criterion for MS severity in the clinical practice guidelines for valvular heart disease, which instead rely on Doppler-derived measurements of pressure half-time (PHT) and measurement of MVA [73].
A single-center retrospective study of patients with calcific MV disease correlated a "projected" transmitral mean gradient to the MVA. This study utilized data from 3315 patients to derive a formula for the projected mean gradient, accounting for heart rate, sex, and stroke volume, and validated their formula on an additional 1658 patients. A projected mean gradient >6 mmHg was highly specific for identifying severe stenosis [74].
Estimation of MVA in patients with MAC is challenging, and none of the methods validated for rheumatic MS have been validated for calcific MS patients. Planimetry by two- or three-dimensional imaging rarely is possible because the flow-limiting area is the irregularly shaped, nonplanar calcified annulus, rather than a simple elliptical diastolic orifice seen with rheumatic disease. Also, relatively poor image quality from heavy calcium in MAC hinders direct planimetry of the tunnel-like orifice. If there is no significant aortic or MV regurgitation or AF, MVA calculation by continuity equation (using the mitral and LV outflow velocity time integrals to calculate volume of flow across the MV relative to forward stroke volume) is an alternative to planimetry (particularly if image quality is suboptimal) [46,75]. However, this method is less accurate in the setting of concurrent aortic valve disease. The proximal isovelocity surface area (PISA) method is another option to calculate MVA but is technically challenging to apply in the setting of calcific MS, given difficulty in measuring leaflet angles due to the bulky annular calcification.
PHT is the duration of time for the peak diastolic pressure gradient to decrease by half, derived from the continuous wave Doppler transmitral signal. From this, MVA may be calculated from the empirically derived equation (MVA = 220/PHT). However, this method for estimating MVA is relatively limited in patients with tachycardia, increased LV filling pressure, or abnormal LA compliance, conditions which are frequently concomitantly present in patients with advanced MAC [76]. With calcific MS, the initial transmitral gradient is higher with a shorter duration for PHT; therefore, MVA calculation using PHT tends to overestimate MVA [77,78]. In a study comparing methods for estimating MVA in patients with calcific MS, the PHT method overestimated MVA compared with MVA calculated by the continuity equation, while MVA determined by three-dimensional echocardiography was comparable with the continuity equation calculation [77].
From a practical standpoint, because of the challenges in evaluating MS severity in calcific MS, many clinicians utilize the PHT approach coupled with Doppler measures of the mean transmitral gradient, taking into account the effect of hemodynamic loading conditions, heart rate, and transmitral flow on diastolic gradients. Additional clinical indicators of disease severity include secondary changes due to MV obstruction, such as pulmonary hypertension, LA enlargement, and bowing the atrial septum.
Evaluation of mitral regurgitation — Color Doppler imaging can aid in evaluating the mechanism and severity of concurrent MR, although transthoracic images of MR jets in the LA are frequently suboptimal due to acoustic shadowing (image 4). The impact of such shadowing may be reduced by acquiring multiple views of the valve on transthoracic echocardiography, although in some cases TEE (in which the LA is closer to the transducer and therefore not obscured by MAC) may be helpful to better visualize the extent of regurgitation. (See "Echocardiographic evaluation of the mitral valve" and "Transesophageal echocardiography in the evaluation of mitral valve disease".)
Interference with evaluation of concurrent conditions — MAC can interfere with echocardiographic evaluation of MR (see 'Evaluation of mitral regurgitation' above), detection of MV abscess (see 'MAC may obscure an abscess' above), interpretation of tissue Doppler velocities, and evaluation of other adjacent structures. (See 'Evaluation of mitral regurgitation' above and 'MAC may obscure an abscess' above.)
The presence of MAC impairs the accuracy of the early mitral inflow velocity to mitral annular early diastolic velocity (E/e') ratio estimation of pulmonary capillary wedge pressure. The mitral annular early diastolic velocity (e') is usually reduced in patients with significant MAC [50]. In addition, the early mitral inflow velocity (E) may be increased in the setting of significant MR, increased mitral inflow gradient, and decreased ventricular compliance. Therefore, the E/e' ratio is not accurate as an index of filling pressures in patients with heavy MAC [79]. (See "Echocardiographic evaluation of left ventricular diastolic function in adults".)
In a study of 50 patients with MAC in which 26 patients had mild MAC and 24 patients had moderate or severe MAC, there was weak correlation (r = 0.42) between the E/e' ratio and LV filling pressure [80]. This study proposed a clinical algorithm utilizing mitral early to late filling (E/A) ratio and isovolumic relaxation time for prediction of higher LV filling pressure. A validation of the algorithm in a separate cohort yielded diagnostic accuracy of 94 percent. (See "Echocardiographic evaluation of left ventricular diastolic function in adults".)
Cardiac catheterization — For symptomatic patients with severe MAC for whom the severity of MS is uncertain, cardiac catheterization with hemodynamic assessment can be helpful [46]. The study should include simultaneous direct measurement of LA and LV pressures to measure the mean transmitral gradient as well as concomitant measurement of cardiac output with right heart catheterization to measure the MVA using the Gorlin formula, as discussed separately. (See "Hemodynamics of valvular disorders as measured by cardiac catheterization", section on 'Mitral stenosis' and "Rheumatic mitral stenosis: Clinical manifestations and diagnosis", section on 'Cardiac catheterization'.)
Computed tomography — CT is an effective, noninvasive diagnostic test for cardiac calcification (atherosclerotic disease, valve calcification, aortic atherosclerosis). High spatial resolution of cardiac CT allows for accurate identification of the severity and extent of calcification. Gating of the CT scan to the electrocardiogram decreases artifact due to cardiac motion, improving image quality. Although both contrast and noncontrast CT studies can assess the extent of mitral calcification, contrast is needed to evaluate cardiac structures, such as MV leaflet calcification, involvement of the subvalvular apparatus, or extension of calcification to the myocardium. Cardiac CT imaging also allows for anatomic assessment of other cardiac structures, including coronary arteries and the aorta, but does not allow for hemodynamic assessment of valve function [46].
CT is helpful for distinguishing caseous calcification from other types of cardiac mass. On CT, caseous calcification is identified as a non-contrast-enhancing, well-defined oval or crescent-shaped, hyperdense mass surrounded by dense calcification, usually located along the posterior mitral annulus [8,46].
Cardiac CT is increasingly utilized in preprocedure planning to evaluate mitral annular calcium burden and anatomy. For patients under evaluation for percutaneous transcatheter valve interventions, preprocedure CT may aid in assessment for potential LV outflow tract (LVOT) obstruction created by protrusion of the valve and displaced anterior MV leaflet into the LVOT. Risk of LVOT obstruction is higher in patients with a small LV, longer or redundant anterior MV leaflet, and small aortomitral angle.
Cardiac magnetic resonance — CMR is not generally used to detect MAC, as calcium is hypointense relative to myocardium [43], but CMR may be helpful in evaluating caseous calcification [8,46]. On CMR, caseous calcification appears as a well-defined mass with a hyperintense center and hypointense rim on T1-weighted fast spin-echo imaging or T1-weighted spoiled gradient-echo imaging [8]. On T2-weighted imaging, caseous calcification appears as a mass without central signal and with a high intensity ring [8].
Differential diagnosis — While MAC is generally recognized by its characteristic density, location, and shape on echocardiography and CT, unusual variants are sometimes confused with other lesions. Characteristic features of MAC (including caseous calcification) on echocardiography, CT, and CMR as described above distinguish MAC from myocardial abscess, tumor, or thrombus or lipomatosis of the AV groove. (See 'Caseous calcification' above and "Cardiac tumors".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease".)
SUMMARY AND RECOMMENDATIONS
●Mitral annular calcification (MAC) may be caused by a process similar to atherosclerosis and calcific aortic valve disease. There is a strong association between MAC and atherosclerotic risk factors and valve calcification. (See 'Pathophysiology' above.)
●The prevalence and severity of MAC increase with age. MAC is particularly common in patients with end-stage kidney disease. (See 'Prevalence' above.)
●MAC is generally an incidental finding associated with aging, although it is occasionally prominent enough to cause mitral stenosis (MS), mitral regurgitation (MR), or both (mixed disease). (See 'Clinical manifestations' above.)
●MAC is associated with a number of conditions including calcific aortic valve disease, diastolic dysfunction, conduction system disease, atrial fibrillation (AF), and atherosclerotic cardiovascular disease. (See 'Associated conditions' above.)
●Endocarditis lesions identified in patients with MAC have vegetations on the mitral valve (MV) leaflets and, less commonly, vegetations adherent to MAC, as well as paravalvular abscesses in the region of MAC. The presence of MAC can interfere with identification of an abscess near the posterior mitral annulus. (See 'Endocarditis' above.)
●Echocardiography is the primary imaging modality for identification and characterization of MAC and associated MV disease. For patients undergoing evaluation for MV replacement, computed tomography is a complementary imaging modality that allows for assessment of the extent and location of annular calcium. (See 'Diagnostic evaluation' above.)
●In patients with MAC, the initial transmitral gradient may be increased due to other comorbid conditions, such as high LV filling pressures, decreased left atrial compliance, or high transvalvular flow from concomitant MR (rather than valve obstruction), potentially leading to overestimation of stenosis severity.
●MV area (MVA) estimation in patients with MAC is challenging; pressure half-time calculation of MVA in patients with MAC tends to overestimate valve area and planimetry of orifice area is rarely possible. From a practical standpoint, because of the challenges in evaluating MS severity in calcific MS, many clinicians utilize the pressure half-time (PHT) approach coupled with Doppler measures of the mean transmitral gradient, taking into account the effect of hemodynamic loading conditions, heart rate, and transmitral flow on diastolic gradients. (See 'Evaluation of mitral stenosis' above.)
●The presence of MAC can obscure echocardiographic quantification of MR, identification of MV abscess, and estimation of pulmonary capillary wedge pressure. (See 'Interference with evaluation of concurrent conditions' above.)
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