Background

Mitral annular calcification (MAC) is a chronic phenomenon affecting the mitral valve annulus and is associated with heightened cardiovascular mortality and morbidity. From its initial postmortem documentation, advancements in diagnostic methodologies have elevated cardiac CT scans to the status of the preferred standard for detecting and classifying MAC. The mere presence of MAC has been correlated with an elevated risk of cardiovascular mortality and morbidity.

It is characterized as a degenerative lesion, and the necessity for surgical correction, particularly in cases involving valve stenosis or insufficiency, is associated with elevated morbidity and mortality rates. Its significance lies in its connection to other diseases, necessitating a shift in both treatment and strategy as more intricate techniques become essential. Despite the long-standing recognition of the complexity of MAC, it remains a contemporary challenge in the domain of cardiovascular care. 

Epidemiology

Mitral annular calcification is more prevalent in older individuals, with the risk increasing with age. It is often seen in postmenopausal women, and studies suggest a higher prevalence in females compared to males. There may be variations in the prevalence of MAC among different ethnic and racial groups. Some studies have suggested a higher prevalence in certain populations. 

Anatomy

Pathophysiology

Mitral annular calcification is a degenerative process involving the fibrous ring surrounding the mitral valve in the heart. The pathophysiology of MAC is multifactorial and not fully elucidated, but it is thought to result from a complex interplay of metabolic, inflammatory, and hemodynamic factors. Chronic inflammation and endothelial dysfunction contribute to the initiation and progression of the calcification process.

Metabolic factors, such as abnormal calcium-phosphorus metabolism and dyslipidemia, may also play a role in the deposition of calcium within the mitral annulus. The accumulation of calcium deposits on the fibrous annular tissue leads to structural changes, causing thickening and rigidity of the mitral valve ring. These alterations can affect the normal functioning of the valve, potentially leading to impaired leaflet motion and changes in valve geometry. 

Additionally, MAC has been associated with other cardiovascular conditions, such as aortic valve sclerosis and coronary artery disease, suggesting systemic involvement. The clinical significance of MAC lies not only in its impact on mitral valve function but also in its potential association with adverse cardiovascular events, including stroke and myocardial infarction. Further research is needed to understand better the intricate pathophysiological mechanisms underlying MAC and to develop targeted interventions for this degenerative valvular condition. 

Etiology

The etiology of mitral annular calcification is complex and multifactorial, involving a combination of genetic, metabolic, inflammatory, and environmental factors. While the precise mechanisms are not fully understood, several key contributors have been identified: 

• Age  

 Aging is a significant risk factor for MAC. The degenerative changes associated with aging can lead to the accumulation of calcium deposits on the fibrous annular ring of the mitral valve. 

• Genetic Factors 

There is evidence to suggest a genetic predisposition to valvular calcification. Specific genetic variations may influence the susceptibility of individuals to develop MAC. 

• Metabolic Factors 

Disorders of mineral metabolism, including abnormal calcium and phosphorus homeostasis, may contribute to the development of MAC. Conditions such as hyperparathyroidism, chronic kidney disease, and disorders of calcium and phosphate metabolism can enhance the deposition of calcium in the mitral annulus. 

• Inflammation and Endothelial Dysfunction 

Chronic inflammation and endothelial dysfunction are implicated in the initiation and progression of MAC. Inflammatory processes in the valvular tissue may promote the deposition of calcium and contribute to the transformation of the mitral annulus. 

• Hemodynamic Factors 

Altered hemodynamics, such as turbulent blood flow or shear stress, may play a role in the development of MAC. Disturbed blood flow patterns can contribute to valvular calcification. 

• Lipid Metabolism 

 Dyslipidemia has been associated with MAC. Lipid accumulation and oxidative stress in the valvular tissue may contribute to the calcification process. 

• Hormonal Factors 

 Postmenopausal women have a higher prevalence of MAC, suggesting a potential hormonal influence. Changes in hormonal levels, particularly estrogen deficiency, may contribute to the development of valvular calcification. 

• Chronic Kidney Disease 

Impaired renal function is a known risk factor for MAC. Changes in mineral metabolism and increased calcium-phosphorus product in chronic kidney disease may contribute to valvular calcification. 

Genetics

Prognostic Factors

The prognosis of mitral annular calcification is generally considered to be relatively benign, and many individuals may remain asymptomatic throughout their lives. However, the prognosis can vary based on several factors, including the extent of calcification, the presence of associated complications, and the individual’s overall cardiovascular health. 

Clinical History

MAC is more commonly observed in older individuals, with an increased prevalence in those over the age of 60. Postmenopausal women have a higher likelihood of developing MAC. Individuals often have associated cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, and chronic kidney disease. MAC itself is often asymptomatic, and individuals may not experience any noticeable signs related to the condition.

However, in some cases, symptoms may be associated with complications or changes in mitral valve function. MAC can lead to changes in the structure of the mitral valve, potentially causing leakage of blood backward into the left atrium. Symptoms of mitral regurgitation may include fatigue, shortness of breath, and palpitations.

The onset of MAC is gradual, and the duration may span many years. The calcification process tends to progress slowly over time, and individuals may remain asymptomatic for extended periods. The duration of MAC is often associated with the aging process, with a higher prevalence observed in older individuals. The condition is generally chronic, and the rate of progression can vary among individuals. 

Physical Examination

Physical examination findings related to mitral annular calcification may vary, and in many cases, individuals may not exhibit specific signs on routine examination. MAC itself is often asymptomatic, and its detection is frequently incidental during imaging studies. However, specific findings may be observed in individuals with significant mitral valve involvement or associated complications.

In some cases, extra-cardiac sounds related to complications, such as embolic events, may be detected during physical examination. For instance, a neurological examination may reveal signs of a stroke if emboli have traveled to the brain. Palpation of the chest may reveal the point of maximal impulse, which can be displaced in the presence of significant mitral valve dysfunction. In advanced cases, there may be a palpable pulsation of the calcified mitral annulus during the cardiac cycle. 

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Mitral Valve Stenosis 

Mitral Valve Prolapse 

Rheumatic Heart Disease 

Degenerative Aortic Stenosis 

Fibroelastoma 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Focus on controlling cardiovascular risk factors such as hypertension, diabetes, and dyslipidemia. Anticoagulation therapy may be considered based on individual risk factors for embolic events. Address symptoms associated with mitral valve dysfunction, such as heart failure or arrhythmias. Use medications like beta-blockers, calcium channel blockers, or antiarrhythmics as needed.

Consider surgical mitral valve repair or replacement if MAC leads to significant valvular dysfunction. Surgical approaches include extensive annular decalcification and reconstruction or more conservative strategies to minimize risks associated with calcium removal. Explore transcatheter interventions for high-risk or inoperable patients involving the placement of a balloon-expandable transcatheter valve within the calcified annulus. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Severe cases of mitral valve dysfunction due to MAC may require surgical intervention. This can include mitral valve repair or replacement. The decision for surgery depends on the severity of symptoms, the degree of valvular dysfunction, and the overall health of the patient. 

Historically, two distinct approaches have been described: the first involves extensive annular decalcification and reconstruction, referred to as the “resect” strategy. In contrast, the second adopts a more conservative approach to minimize the risks associated with calcium removal.

Conservative approaches include partial decalcification or MAC avoidance, where sutures are placed around the calcium bar, either behind it or on the mitral leaflets. Recent findings regarding mitral valve surgery in patients with MAC indicate an operative mortality ranging from 1% to 5.8% and a 5-year survival rate ranging from 38.8% to 78.8%. 

Transatrial Hybrid Procedure 

In the search for alternatives to traditional mitral valve surgery, one of the initial options under consideration involved the direct placement of a balloon-expandable transcatheter valve within the calcified annulus. This approach utilizes a hybrid strategy that incorporates cardiopulmonary bypass, cardioplegic arrest, and a surgical left atriotomy. 

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

lifestyle-modifications

Control of cardiovascular risk factors such as hypertension, diabetes, and dyslipidemia are essential. Lifestyle modifications, including a heart-healthy diet, regular exercise, and smoking cessation, are emphasized to reduce the overall risk of cardiovascular events. 

Administration of a pharmaceutical agent

Anticoagulation therapy may be considered in individuals with MAC, particularly when there is an increased risk of embolic events such as strokes.

The decision to use anticoagulants depends on individual risk factors, including the presence of atrial fibrillation, history of embolic events, and overall cardiovascular health.

Individuals may be at an increased risk of arrhythmias. Management may include antiarrhythmic medications or, in some cases, procedures such as catheter ablation. 

Medication

Future Trends

Media Gallary

References

• Mitral annular calcification: challenges and future perspectives – PMC (nih.gov) 
• Mitral Annular Calcification: Diagnosis, Treatment, & Risks (myheart) 
• Mitral annular calcification | Radiology Reference Article | Radiopaedia.org