© 2014, Wiley Periodicals, Inc. DOI: 10.1111/echo.12861


Association of Mitral Annular Calcification with Left Ventricular Mechanics: A Speckle Tracking Study € kdeniz, M.D.,* Faruk Boyaci, M.D.,† Engin Hatem, M.D.,† Hu € seyin Bektasß, M.D.,† Tayyar Go  lu, M.D.,† Mustafa Ozan Gu  rı Aykan, M.D.,† Banu Sßahin Yıldız, M.D.,§ € rsoy, M.D.,‡ Ahmet C Ezgi Kalaycıog ß ag and Bernas Altıntasß, M.D.¶ *Department of Cardiology, Medical School, Kafkas University, Kars, Turkey; †Department of Cardiology, Ahi Evren Chest and Cardiovascular Surgery Education and Research Hospital, Trabzon, Turkey; ‡Department of € ren State Hospital, _Izmir, Turkey; §Department of Internal Medicine, Cardiology, Gaziemir Salih Nevvar _Isßgo Dr Lutfu Kırdar Kartal Educational and Research Hospital, _Istanbul, Turkey; and ¶Department of Cardiology, Diyarbakır Education and Research Hospital, Diyarbakır, Turkey

Background: Mitral annular calcification (MAC) is a common echocardiographic finding in clinical practice and is associated with cardiovascular risk factors and atherosclerosis. However, data regarding left ventricular (LV) functions are lacking. We aimed to evaluate the relationship between MAC and LV mechanical functions with the utility of two-dimensional speckle tracking echocardiography (2DSTE). Methods: The study involved 91 patients with MAC and 48 control subjects. Mitral annular thickness of 1–2 mm was reported as mild, 2–5 mm as moderate, and >5 mm as severe MAC. All patients underwent 2D echocardiography. Results: MAC was observed in 91 (65.5%) patients. Of LV diastolic parameters, E/Em ratio, LAVI, LV mass index, and t-LV UR were increased. Of LV systolic parameters, GLS and Sm were decreased, whereas Ar, Ar-rate systole, peak LV twist, peak LV twist rate, LV-tor, and MPI were increased, which were all correlated with presence and severity of MAC. Multivariate linear regression analysis showed that LV mass index (b = 0.225, P = 0.012), t-LV UR (b = 0.370, P < 0.001), LV mass index (b = 0.183, P = 0.025), MPI (b = 0.288, P < 0.001), and GLS (b = 0.385, P < 0.001) were significantly associated with MAC severity. Conclusion: The presence and severity of MAC is associated with impaired LV systolic and diastolic functions. Therefore, preventive strategies might be taken in patients with MAC to avoid LV systolic and diastolic dysfunction. (Echocardiography 2015;32:1374– 1383) Key words: mitral annular calcification, left ventricular mechanical functions, two-dimensional speckle tracking echocardiography, subclinical left ventricle systolic dysfunction Mitral annular calcification (MAC) is a chronic, degenerative process characterized by calcification of the surrounding fibrous support of the mitral valve.1,2 Although the exact mechanism is not well understood, MAC appears to be associated with cardiovascular risk factors and clinical atherosclerosis.1 However, it has been well established that the presence of MAC is not merely a marker of systemic atherosclerosis. It is also an independent predictor of cardiovascular disease (CVD) (including myocardial infarction, coronary insufficiency, heart failure, and nonhemorrhagic stroke) and associated with increased risks of death from all causes and CVD.3,4 The mechanisms of increased risk are undoubtedly multifactorial and include mechanical characteristics of MAC, shared risk factors between MAC and CV Address for correspondence and reprint requests: Tayyar € kdeniz, M.D., Department of Cardiology, Medical School, Go Kafkas University, 36000 Kars, Turkey. Fax: +90 474 225 14 30; E-mail: [email protected]


outcomes and valvular calcification as an overall marker of atherosclerotic burden.3 The mitral annulus is an essential, dynamic, and tightly coupled component of the mitral valve/left atrial/left ventricular (LV) complex that aids in effective and efficient valve closure and unimpeded LV filling. The mitral annulus has a complex shape and motion, and its excursion has been correlated with LV function.5 Also, although mitral leaflets and chordae tendinea are generally not involved, calcification may progressively accumulate in the subvalvular region beneath the posterior leaflet with encroachment on the leaflet,6,7 and can impair LV systolic functions. In current literature, there are limited data regarding the relationship between MAC and LV systolic functions. Two-dimensional speckle tracking echocardiography (2DSTE) is a new automated and quantitative technique for the measurement of cardiac mechanics. 2DSTE is based on speckles which are

MAC and LV Functions

created by constructive and destructive interference of ultrasound beams within tissue. Speckles are tracked on a frame-by-frame basis throughout the cardiac cycle.8,9 This technique has some advantages over conventional echocardiography including angle independency, free of tethering and translation effects, low signal-tonoise ratio, and low measurement variability.10,11 In this study, we aimed to analyze the relationship between MAC and LV mechanical functions with the utility of 2DSTE. Methods: Study Sample: This was a single center, cross-sectional prospective study, conducted between August 2012 and March 2013. A total of 98 consecutive patients with diagnosis of MAC and 49 age- and sexmatched control subjects (matching was carried out 1 on 2) who were found to have a normal cardiac exam were enrolled in the study. Patients with poor echocardiographic window, coronary artery disease (CAD), symptoms or clinical signs of cardiac disease, positive treadmill test or nuclear perfusion stress test, ischemic electrocardiographic findings, aortic stenosis, moderatesevere aortic or mitral regurgitation, rheumatic valvular disease, heart failure, hypertrophicdilated cardiomyopathy, arrhythmias, renal dysfunction, asthma, or malignancy were excluded. The remaining 139 patients (91 MAC and 48 controls) constituted the study population. Informed consent was obtained from the patients and the study was approved by the local ethics board. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease (MDRD) Study equation.12 Body mass index (BMI) was calculated as weight (kg)/ height (m2). The body surface area was calculated according to the following formula in square meters: 0.007184 9 weight (kg)0.425 9 height (cm)0.725. Conventional Echocardiography: The echocardiographic studies were performed with the use of a commercially available echocardiography machine (VIVID S-5 General Electric Medical System Vingmed Ultrasound AS, Horten, Norway) equipped with 3,6-MHz transducer. Measurements were performed according to the American Society of Echocardiography guidelines.13 MAC was considered to be present from parasternal long-axis view, if an echo dense band was visualized throughout systole and diastole, was distinguishable from the posterior mitral valve leaflet, and was located anterior and parallel to the posterior LV wall.3 The severity of MAC,

expressed as maximal thickness in millimeters, was measured from the leading anterior to the trailing posterior edge at its greatest width.3 Calcification thickness of 1–2 mm was reported as mild, >2 to 5 mm as severe MAC.14 LV volumes and left ventricle ejection fraction (LVEF) were measured using the modified Simpson method. LV mass was calculated according to Devereux formula and was indexed to the body surface area. Diastolic peak early (E) and peak late transmitral flow velocity (A) were evaluated by pulsewave Doppler and measured by using the average of 3 beats. Doppler time intervals were also measured from the mitral inflow and LV outflow velocities and LV myocardial performance index (MPI) was measured as described previously.15 Systolic and early diastolic annular tissue velocity (Sm) and (Em), respectively, were measured at the lateral corner of the annulus by TDI using the pulse-wave Doppler. To evaluate LV filling pressures, E/Em ratio was calculated. Left atrial volume was measured by using area-length (L) method using apical four-chamber view (A1) and apical two-chamber view (A2) at ventricular end-systole. The information is put in the formula 0.85 (A1 9 A2) divided by L for the atrial volume and indexed to body surface area (BSA) giving us the left atrial volume index (LAVI).16 Two-Dimensional Speckle Tracking Analysis: 2DSTE images of the LV were acquired in apical four-chamber (A4C), apical three-chamber (A3C), and apical two-chamber (A2C), and shortaxis (SAX) views of basal and apical planes. Basal and apical SAX views were obtained at the mitral valve level and just proximal to the level with end-systolic LV luminal obliteration, respectively. Special attention was paid to acquire circularshaped SAX views. Using commercially available 2D strain software (EchoPAC 108.1.12; General Electric Medical Systems, Horten, Norway), the endocardial border in the end-systolic frame was manually traced from the 3 apical and the SAX views and a region of interest was adjusted to include the entire myocardium. Apical and SAX views of LV were divided into 6 equidistant segments by the software. Segments were tracked on a frame-by-frame basis using the sum of absolute difference algorithm. Global longitudinal strain (GLS) as the average of all 17 segments was calculated by software. From both basal and apical SAX views, circumferential and radial strain (CircSbase, RadSbase, CircSapex, and RadSapex, respectively) and systolic circumferential (CircSRSbase and CircSR-Sapex) and radial (RadSR-Sbase and RadSR-Sapex) strain rates were calculated. 1375

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TABLE I Comparison Baseline Characteristics between Control and MAC Groups Variables

Normal Controls (n = 48)

Patients With MAC (n = 91)

P Value

Age (years) Male (n, %) HT (n, %) DM (n, %) BSA (m2) BMI (kg/m2) eGFR≥60 (mL/min per 1.73 m2) (n, %) LDL-cholesterol (mg/dL) HDL-cholesterol (mg/dL) Triglycerides (mg/dL) Total cholesterol (mg/dL) Fast plasma glucose (mg/dL) Calcium channel blockers (%) b-blockers (%) ACE inhibitors or ARB (%) Statins (%) LV end-diastolic volume (mL/m2) LV end-systolic volume (mL/m2) LV ejection fraction (%) E/A ratio Sm (systolic tissue velocity, cm/sec) E/Em ratio MPI LV mass index (g/m2) LAVI (mL/m2)

71.5  5.6 10 (20.8%) 28 (58.3%) 9 (18.8%) 1.6  0.4 27.8  2.2 39 (81.3%) 126.0  15.0 40.3  6.2 149.9  15.6 185.0  18.2 97.6  23.0 9 (18.8%) 12 (25%) 8 (16.7%) 13 (27.1%) 84.1  13.8 33.5  6.8 61.1  4.7 1.1  0.4 12.9  1.9 7.9  2.6 0.33  0.04 105.5  6.5 25.5  7.9

73.3  8.5 16 (17.6%) 69 (75.8%) 33 (36.3%) 1.7  0.5 28.5  2.4 73 (80.2%) 134.2  18.9 39.0  6.3 158.1  21.1 195.2  16.7 105.2  25.3 34 (37.4%) 30 (33%) 32 (35.2%) 36 (39.6%) 85.7  18.2 35.3  8.3 60.0  4.8 0.9  0.2 11.4  1.9 8.7  1.9 0.37  0.04 111.9  11.3 30.8  6.5

0.132 0.640 0.033 0.028 0.474 0.092 0.884 0.010 0.255 0.019 0.002 0.075 0.024 0.331 0.022 0.143 0.560 0.173 0.188 0.004

Association of Mitral Annular Calcification with Left Ventricular Mechanics: A Speckle Tracking Study.

Mitral annular calcification (MAC) is a common echocardiographic finding in clinical practice and is associated with cardiovascular risk factors and a...
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