Mitral Annular Calcification Clinical Presentation

Updated: Mar 06, 2017
  • Author: Saurabh Sharma, MD, FACC, FACP; Chief Editor: David J Maron, MD, FACC, FAHA  more...
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Patients with mitral annular calcification (MAC) may have multiple associated comorbidities. The comorbidities with the strongest association with MAC are described below. Patients with MAC may present with physical signs of any of these comorbid conditions.


The association of MAC and stroke was initially proposed by Rytand and Lipsitch in 1946. [36] One of the first observational studies on the subject was a prospective study in 1989 by Nair et al, in which patients with MAC were found to be at increased risk for stroke. [37] In 1992, Benjamin et al presented a prospective study from the Framingham group; 1159 subjects were studied and followed for an average of 8 years. After adjusting for known risk factors for cerebrovascular events, subjects with MAC still had a higher risk of stroke. Moreover, the multivariate analysis showed that for every additional millimeter of MAC width, the relative risk of stroke increased by approximately 25%. [38]

However, it remains uncertain whether the increased risk for stroke is caused by MAC itself or merely through its relationship with risk factors for cerebrovascular disease. [38, 39] MAC has been associated with carotid stenosis, aortic atheroma, markers of inflammation, and other biomarkers. Although embolic events in MAC patients might be due to calcific material that dislodges from the annulus, the more common scenario is that of associated conditions that are the direct cause of stroke. Further, the association between MAC and stroke is not present in all studies. The Strong Heart Study found that MAC was associated with an increased stroke risk, [40] whereas the Boston Area Anticoagulation Trial for Atrial Fibrillation [41] and the Cardiovascular Health Study [42] did not.


Atherosclerotic disease has a tendency to initiate in areas with decreased shear stress or increased turbulence of blood flow, both of which are present at the attachment points of the aortic and mitral leaflets to their annuli. In animal studies, induced atherosclerosis produces plaque formation in the posterior leaflet of the mitral valve. [43] Clinical studies have observed an association between MAC and risk factors for atherosclerosis. [44] The association between MAC and atherosclerosis has been found in different vascular beds: the coronary tree, [45] the aorta, [46] and the carotid arteries. [47] Thus, it seems feasible that MAC and atherosclerosis represent two facets of the same disease. [48, 49]

MAC is a predictor of coronary artery disease. [50] Moreover, its presence has been related to vulnerable plaque [51] and a greater burden of coronary disease (more than 1 vessel involved). [52]

MAC is also associated with coronary artery calcium (CAC), a marker of coronary atherosclerosis. In one study, the presence of any MAC had a sensitivity and specificity of 71% and 56%, respectively, for detecting CAC above 400; positive (PPV) and negative predictive values (NPV) were 45% and 79%, respectively. [53]  When using the parameter of CAC over 100, the sensitivity was 65% and specificity was 57%, with a PPV of 59% and an NPV of 63%.

Chronic kidney disease

In a community-based sample from the Framingham Heart Study, MAC was more common in patients with chronic kidney disease (CKD) versus patients with normal kidney function. [54] Furthermore, participants with CKD were 50% more likely to have at least one calcified valve. This relationship was attenuated by adjustment for cardiovascular risk factors, suggesting that shared risk factors partially mediate the increased prevalence. In another study of patients with severe MAC, nearly 60% had clinically significant CKD. The authors suggested that severe MAC on echocardiography should alert the physician to the likely presence not only of atherosclerosis but also CKD. [54]

Among dialysis patients, prevalence rates for MAC are 4-5 times higher than in the general population. [55] Moreover, calcium-phosphorus product and parathyroid hormone levels are higher in patients with MAC. [56, 57, 58] For CKD and dialysis patients, some [59, 60] but not all studies [61, 62] have found that MAC correlates with higher total and cardiovascular mortality. In addition, MAC serves as a marker for left ventricular systolic dysfunction in these patients, with or without end-stage renal disease. [63, 64]

Mitral regurgitation

Mitral regurgitation is a hemodynamic abnormality commonly associated with MAC, with a prevalence of up to 63%. [65] Calcium infiltration of the base of the posterior leaflet reduces leaflet mobility, increases traction on the chordae, and elevates the leaflets, which facilitates chordal elongation or rupture, causing secondary mitral regurgitation. [66] Another proposed mechanism is failure of the calcified annulus to contract at the end of diastole. [67] MAC has been reported to lead to regurgitation severe enough to require surgery in some cases. [66]

Mitral stenosis

Mitral stenosis is a rare complication of MAC. [68, 69] However, MAC can occasionally cause mitral stenosis severe enough to warrant valve replacement. [6] The pathophysiology is thought to be an absence of normal annular dilatation during diastole, resulting in functional mitral stenosis. [70] Alternatively, decreased mobility of the valve when annular calcium limits leaflet excursion, particularly of the anterior leaflet, may be responsible. [71]


MAC is associated with a high frequency of conduction defects, including atrioventricular block, bundle branch block, and intraventricular conduction delay, especially in more severe cases. [3, 72] MAC is also associated with symptomatic bradyarrhythmias requiring pacemaker implantation. [73, 74] This is likely secondary to infiltration of calcium into the conduction system.

Atrial fibrillation

Data from the Framingham cohort show that MAC is associated with an increased risk of incident atrial fibrillation, even when adjusted for atrial size. [75] Nair et al found a similar association. [76] This is not surprising given that MAC is more prevalent in elderly people and that MAC, atherosclerosis, and atrial fibrillation all share common risk factors. The mechanisms by which MAC is predisposed to incident atrial fibrillation are likely multifactorial, but they appear to be partially mediated through left atrial enlargement. [77]  MAC may also interrupt the interatrial and intra-atrial conduction processes, leading to conduction system and atrial conduction defects, thus resulting in atrial fibrillation. [78]


Infective endocarditis is a possible complication of MAC. [79] One prospective study of 976 elderly patients demonstrated a higher incidence of infective endocarditis in patients with MAC (3% vs 1%). [80]  In a study by Pressman et al, MAC has also been shown as a nidus for infection, especially with Staphylococcus aureus. [81]

Aortic valve disease

In a retrospective study among 24,380 patients, Movahed et al found that MAC was present in 15% of patients with aortic stenosis, compared with only 6% of patients without aortic stenosis. [82] In another study that included 219 patients with a mean age of 57 years, MAC was strongly associated with aortic valve calcification. [83] MAC has also been found to be associated with more severe aortic stenosis in a study by Michel et al. [84]