JACC: CARDIOVASCULAR IMAGING VOL. 9, NO. 11, 2016 ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION ISSN 1936-878X/$36.00 PUBLISHED BY ELSEVIER http://dx.doi.org/10.1016/j.jcmg.2016.09.001 STATE-OF-THE-ART PAPERS Severe Mitral Annular Calcification Multimodality Imaging for Therapeutic Strategies and Interventions Mackram F. Eleid, MD, Thomas A. Foley, MD, Sameh M. Said, MD, Sorin V. Pislaru, MD, PHD, Charanjit S. Rihal, MD, MBA ABSTRACT Mitral annular calcification (MAC) is a chronic degenerative process associated with advanced age and conditions predisposing to left ventricular hypertrophy. Assessment of mitral valve disease in patients with severe MAC can be a challenge. When severe MAC results in mitral stenosis or regurgitation, multimodality imaging with 2-dimensional, 3-dimensional, and Doppler echocardiography and cardiac computed tomography angiography can delineate the severity and pathoanatomic features to help guide therapeutic strategies. New approaches using computer-assisted simulation of transcatheter valves and novel percutaneous and surgical techniques are being used to devise effective alternative strategies to conventional mitral valve replacement in this high-risk group of patients. (J Am Coll Cardiol Img 2016;9:1318–37) © 2016 by the American College of Cardiology Foundation. itral annular calcification (MAC) is a being investigated, offering hope for this challenging M chronic degenerative process that, when group of patients. severe, can result in mitral stenosis (MS) and/or mitral regurgitation (MR). The prevalence of PATHOPHYSIOLOGY OF MAC significant MS due to severe MAC is increasing in the developed world due to the growing population MAC is a result of slowly progressive calcification of ofelderlypatientsandriskfactorssuchashyperten- the fibrous mitral annulus (Figure 1) (1). The estimated sive and radiation heart disease. Treatment options prevalence of MAC is 10%, with the posterior annulus for severe MAC are limited. With no specificmedical being more commonly affected than the anterior therapy for MAC, treatment is symptomatic. Balloon annulus (1).MACthatresultsinanelevationinthe valvuloplasty is not suitable for MS due to MAC and mean transmitral gradient is relatively rare, occurring mitral valve surgery is associated with excessive in 0.2% of patients undergoing transthoracic echo- morbidity and mortality in patients with extensive cardiography, with prevalence increasing to 2.5% in annular calcification. Additionally, the complex anat- patients >90 years of age (2,3). omy of the mitral apparatus and challenging left ven- Risk factors for MAC include advanced age, female tricular (LV) geometry in patients with severe MAC sex, chronic kidney disease, and conditions predis- pose unique challenges to minimally invasive mitral posing to LV hypertrophy including hypertension and valve implantation using transcatheter devices. aortic stenosis (4). Prior chest irradiation, most Recent advances in multimodality cardiac imaging commonly as a treatment for Hodgkin’s lymphoma, is and novel percutaneous and surgical techniques are another cause of MAC, often in combination with From the Department of Cardiovascular Diseases and Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received June 27, 2016; revised manuscript received August 29, 2016, accepted September 1, 2016. JACC: CARDIOVASCULAR IMAGING, VOL. 9, NO. 11, 2016 Eleid et al. 1319 NOVEMBER 2016:1318– 37 Imaging and Therapy for Severe MAC aortic valve disease and restrictive cardiomyopathy. can be gathered by 2-dimensional (2D) imag- ABBREVIATIONS MAC appears to be a multifactorial condition result- ing, the en face atrial and ventricular views AND ACRONYMS ing from a varying combination of abnormal calcium of the mitral valve at 3-dimensional (3D) CTA = computed tomography and phosphorus metabolism (5), increased mitral imaging provides the best information for angiography valve hemodynamic stress (6), and atherosclerotic topographical description of the mitral valve, LV = left ventricular processes (7–10). Although MAC is typically confined and was a key development for the growing LVOT = left ventricular fl to the mitral annulus and the base of the lea ets, in number of percutaneous interventions. outflow tract fi some cases MS can occur when calci cation extends Direct visualization of the extent and MAC = mitral annular further into the leaflets, particularly the anterior magnitude of MAC with 3D imaging is a use- calcification leaflet, resulting in restricted mobility (9). An impor- ful adjunct to understand the severity of MS MR = mitral regurgitation tant distinction compared to rheumatic MS is that in and for determination of therapeutic options. MS = mitral stenosis fl MS due to MAC, there is lack of mitral lea et Whenever MS is suspected on the 2D/3D PISA = proximal isovelocity commissural fusion (Figure 2). images, careful quantitation of disease surface area In isolated MAC, valve leaflet motion is preserved, severity must be performed by measuring TEE = transesophageal and ventricular filling occurs unimpeded. However, mitral valve gradient and mitral valve area. echocardiography over time calcific degeneration tends to further This information is critical for further clinical TTE = transthoracic expand into the leaflets resulting in impaired mobility decisions in patient management. echocardiography and geometric distortion. These anatomic changes Mitral valve gradients are estimated from the typically lead to development of both MS and MR. continuous wave (CW) Doppler spectrum obtained Either lesion may be dominant in a given patient, but from apical (TTE) or mid-esophageal (TEE) windows. more commonly there is mixed disease. When MS or We recommend that color Doppler imaging is first MR become severe, heart failure symptoms including performed to assess which imaging view allows for dyspnea and exercise intolerance may ensue. the best alignment of the CW Doppler line of inter- rogation with the direction of mitral inflow. The mean ASSESSMENT OF MS IN SEVERE MAC gradient is derived by integrating the CW velocity spectral envelope, and closely correlates with the Echocardiography is particularly well suited for gradient directly measured at catheterization (11). anatomic and physiological assessment of valvular The mitral gradient cannot be used in isolation for function, and is the cornerstone in assessment of quantitating MS severity because it is highly depen- calcific mitral valve disease. We recommend a sys- dent on factors other than stenotic area, most notably tematic approach to diagnosis, which should include on heart rate, cardiac output, and associated MR (12). assessment of qualitative (visual appearance, calcifi- Mitral valve area by continuity equation is the cation, thickening, leaflet mobility, adequacy of recommended method in the case of calcificMS(12), coaptation) and quantitative parameters (mitral valve but its value is limited in the presence of concomitant area, gradients, indices of regurgitation severity). At aortic and mitral valve regurgitation. Direct planim- the completion of the imaging study, internal con- etry may be challenging in calcific degeneration of the sistency between visual cues, measured parameters, valve (12); 3D technology seems to improve accuracy and clinical findings must be verified. and reproducibility of planimetric measurements. Visual inspection of the entire mitral apparatus Whenever TTE evaluation is inconclusive, we should be systematic. We begin with assessment of recommend additional TEE imaging; 3D-TEE extent of annular calcification (focal vs. circumfer- planimetry of valve area is feasible in the majority of ential), best achieved on short-axis views of the mitral patients (Figure 3). Pressure half-time is influenced by valve (parasternal short-axis at the base on trans- numerous factors beyond MS severity (left atrial and thoracic echocardiography [TTE], or short-axis from ventricular compliance, delayed ventricular relaxa- the gastro-esophageal junction on transesophageal tion, concomitant aortic regurgitation), and has echocardiography [TEE]). If short-axis images are limited utility in estimating mitral valve area in unavailable, inspection of the mitral annulus by elderly patients with calcificMS.Theinflow proximal rotating the imaging plane from the apical (TTE) or isovelocity surface area (PISA) method can also be mid-esophageal windows (TEE) allows systematic used for estimating mitral valve area, but is highly evaluation of circumferential extent. Visual inspec- dependent on operator experience, image quality, tion of the mitral leaflets should describe presence and correct measurement of the PISA radius and and location of degenerative changes, their location angle of leaflet correction. For patients with symp- according to the Carpentier nomenclature, and extent toms that are disproportionate to the resting mitral from base to coaptation line. While all information valve gradient and/or valve area, an exercise or 1320 Eleid et al. JACC: CARDIOVASCULAR IMAGING, VOL. 9, NO. 11, 2016 Imaging and Therapy for Severe MAC NOVEMBER 2016:1318– 37 for accurate assessment of the mean transmitral FIGURE 1 Mitral Annular Calcification gradient and also provides valuable insight into the compliance properties of the left atrium and the LV diastolic function. Concomitant measurement of cardiac output with simultaneous right heart cathe- terization will allow for measurement