Prevalence of Calcification of the Mitral Valve Annulus in Patients Undergoing Surgical Repair of Mitral Valve Prolapse Laura Fusini, MSa,*, Sarah Ghulam Ali, MDa, Gloria Tamborini, MDa, Manuela Muratori, MDa, Paola Gripari, MDa, Francesco Maffessanti, PhDa, Fabrizio Celeste, MDa, Marco Guglielmo, MDa, Claudia Cefalù, MDa, Francesco Alamanni, MDa,b, Marco Zanobini, MDa, and Mauro Pepi, MDa Factors correlating to mitral annulus calcification (MAC) include risk factors predisposing to atherosclerosis. In patients with mitral valve (MV) prolapse (MVP), other anatomic or mechanical factors have been supposed to facilitate MAC. The aims of this study were, in patients with MVP undergoing MV repair, (1) to describe the prevalence and characteristics of MAC, (2) to correlate MAC with clinical risk factors, coronary involvement, and aortic valve disease, and (3) to describe prevalence, site, and extension of MAC in fibroelastic deficiency (FED) versus Barlow’s disease (BD) and correlate MAC to surgical outcomes (repair vs replacement). In 410 consecutive patients with MVP suitable for surgical MV repair, detailed clinical and echocardiographic data were collected to characterize MAC in BD and FED. MAC was found in 99 patients (24%). Age, female gender, coronary artery disease, and cardiovascular risk factors were correlated with MAC. MAC was equally distributed in FED and BD groups despite patients with FED being older with more cardiovascular risk factors. The most common localization of MAC was annular involvement adjacent to P2 (75%), P1 (31%), and P3 (35%). The presence of MAC affected surgical outcomes in both groups (8% patients with MAC underwent replacement after a first attempt of repair vs 3% without MAC). MAC is a common finding in patients undergoing MV repair, and several clinical characteristics correlate with MAC either in FED or BD. In conclusion, despite very high percentage of repairability, MAC influences surgical outcomes and very detailed echo evaluation is advocated. Ó 2014 Elsevier Inc. All rights reserved. (Am J Cardiol 2014;113:1867e1873) Mitral annulus calcification (MAC) is one of the more frequent abnormalities of the heart.1e3 Factors predisposing to MAC include age, hypertension, diabetes mellitus, hypercholesterolemia, chronic renal insufficiency, prolapsing mitral valve (MV), and other congenital and acquired diseases.4e8 The frequent occurrence of factors predisposing to atherosclerosis in patients with MAC supports a common etiologic basis for both MAC and atherosclerosis.9,10 In patients with MV prolapse (MVP), several anatomic or mechanical factors have been supposed to facilitate MAC. Specifically, an extensive calcification of the MV annulus is encountered either in elderly subjects with a fibroelastic deficiency (FED) of the MV or in younger adults with Barlow’s disease (BD).11 MV repair has become preferential to replacement in MVP.12 However, the operation in patients with MAC remains a challenge for the surgeon,13 because, both in patients with FED and patients with BD, an annuloplasty ring should be inserted to stabilize the annulus and the suture line with obvious technical implications in MAC cases. The aims of this study are threefold: (1) to a Centro Cardiologico Monzino IRCCS, Milan, Italy and bCardiovascular Section, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. Manuscript received January 15, 2014; revised manuscript received and accepted March 6, 2014. See page 1873 for disclosure information. *Corresponding author: Tel: (þ39) 02 58002011; fax: (þ39) 02 58002287. E-mail address: [email protected] (L. Fusini).
0002-9149/14/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2014.03.013
describe in detail the prevalence and anatomic characteristics (echocardiography) of MAC in a large consecutive series of patients undergoing MV repair for degenerative MVP, (2) to correlate MAC with clinical risk factors, coronary involvement, and coexisting aortic valve disease, and (3) to describe prevalence, site, and extension of MAC in patients with FED or BD and correlate echocardiographic findings to surgical outcomes (repair vs replacement). Methods This is a retrospective analysis including 410 consecutive patients with MVP who underwent MV surgery in our hospital from January 2008 to June 2012. All patients have an established diagnosis of severe mitral regurgitation (MR) due to degenerative MVP evaluated by 2-dimensional transthoracic echocardiography (TTE) and were suitable for surgical MV repair.14,15 Exclusion criteria were (1) association of MV stenosis, (2) previous or active endocarditis, and (3) history of coronary artery disease (CAD), previous myocardial ischemia or infarction, bypass graft surgery, or coronary stent implantation. The local ethics committee approved the study. Informed consent was obtained from all patients. Detailed baseline demographic and clinical data were collected. Current smoking was defined as self-report of 1 cigarettes in the past 30 days. Hyperglycemia requiring previous or ongoing pharmacologic therapy was considered as diabetes. High blood pressure was described as either www.ajconline.org
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The American Journal of Cardiology (www.ajconline.org)
Figure 1. Examples of patients with MVP without and with calcification in short-axis (A and C) and 4-chamber (B and D) views, respectively. LA ¼ left atrium; LV ¼ left ventricle.
systolic or diastolic elevation of blood pressure (>140/ 90 mm Hg) or ongoing antihypertensive treatment. Hypercholesterolemia was defined as total cholesterol level of >200 mg/dl or a value 6 mm Hg), and/or systolic anterior motion of the anterior leaflet evaluated by intraoperative transesophageal echocardiography. MV replacement was performed only in case of unsuccessful repair. A complete presurgical TTE was performed in all patients using a Philips iE33 or a GE Vivid 7 ultrasound system equipped with S5 or M4S probes, respectively (Philips Medical Systems, Andover, Massachusetts, or GE Healthcare, Horten, Norway). All images were digitally acquired and stored for off-line analysis and included standard 2-dimensional, color, and pulse- and continuous-wave Doppler acquisitions.15e17 MR was defined as severe when the effective regurgitant orifice area was 0.4 cm2 estimated by proximal isovelocity surface area and/or in presence of vena contracta width >7 mm or of chordal rupture associated with flail leaflets.18 MVP diagnosis was based on 2and 3-dimensional TTE.19,20 To assess MV anatomy, we
used Carpentier’s widely recognized nomenclature that divides the posterior leaflet into 3 scallops: lateral (P1), middle (P2), and medial (P3), and the anterior leaflet into 3 segments: lateral (A1), middle (A2), and medial (A3).21 The anterolateral and posteromedial commissures were also evaluated. All segments were classified as normal, prolapsing (3 mm beyond the annulus plane), or flail. The presence of ruptured chordae was annotated. MAC was defined as an intense echo-producing structure with stone shadow, usually localized at the posterior mitral annulus, sometimes involving the whole annulus, the base of 1 MV scallops, chordae, and ventricular endocardium (Figure 1). To assign the localization of each calcification involving the annulus, the leaflets, or the commissures, we used the conventional Carpentier’s nomenclature as described previously. Patients were divided into 2 subgroups based on the 2 main phenotypes of degenerative MVP, which are BD and FED. BD is characterized by severe myxomatous degeneration of the leaflets with excess thickened tissue, billowing and/or prolapse of multiple segments of the valve, elongated and thickened, fused, or calcified chordae, and highly dilated annulus. Conversely, the diagnosis of FED is established in case of normal or even thinner leaflets because of impaired production of connective tissue that affects also the chordae tendineae, no billowing, a single prolapsing segment (usually P2) frequently associated with chordal rupture, and slight annular dilation. In the intermediate forms in which the sole prolapsed area presented some
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Table 1 Baseline clinical and transthoracic echocardiographic characteristics of the study population and comparison between patients with and without mitral annulus calcification Variable
Age (yrs) Men Body surface area (m2) Hypertension Diabetes mellitus Dyslipidemia Smoker Coronary artery disease No. of coronary arteries involved 0 1 2 3 End-diastolic volume index (ml/m2) End-systolic volume index (ml/m2) Ejection fraction (%) Aortic valve calcification Pulmonary artery systolic pressure (mm Hg) Annulus anteroposterior diameter (mm) Annulus mediolateral diameter (mm) Eccentricity
Overall (n ¼ 410)
Mitral Annular Calcium Yes (n ¼ 99)
No (n ¼ 311)
62 13 274 (67) 1.81 0.19 224 (55) 22 (5) 265 (65) 43 (11) 87 (21)
68 10 51 (51) 1.75 0.18 67 (68) 8 (8) 75 (76) 16 (16) 32 (32)
60 13 223 (72) 1.82 0.18 157 (51) 14 (4) 190 (61) 27 (9) 55 (18)
323 (79) 50 (12) 20 (5) 17 (4) 76 19 27 9 65 7 18 (4) 38 12 36 5 40 5 0.10 0.07
67 (68) 18 (18) 6 (6) 8 (8) 73 16 27 9 64 8 13 (13) 40 12 35 5 39 5 0.11 0.07
256 (82) 32 (10) 14 (5) 9 (3) 77 20 27 10 65 7 5 (2) 37 12 36 5 41 5 0.10 0.07
p Value
0002-9149/14/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2014.03.013
describe in detail the prevalence and anatomic characteristics (echocardiography) of MAC in a large consecutive series of patients undergoing MV repair for degenerative MVP, (2) to correlate MAC with clinical risk factors, coronary involvement, and coexisting aortic valve disease, and (3) to describe prevalence, site, and extension of MAC in patients with FED or BD and correlate echocardiographic findings to surgical outcomes (repair vs replacement). Methods This is a retrospective analysis including 410 consecutive patients with MVP who underwent MV surgery in our hospital from January 2008 to June 2012. All patients have an established diagnosis of severe mitral regurgitation (MR) due to degenerative MVP evaluated by 2-dimensional transthoracic echocardiography (TTE) and were suitable for surgical MV repair.14,15 Exclusion criteria were (1) association of MV stenosis, (2) previous or active endocarditis, and (3) history of coronary artery disease (CAD), previous myocardial ischemia or infarction, bypass graft surgery, or coronary stent implantation. The local ethics committee approved the study. Informed consent was obtained from all patients. Detailed baseline demographic and clinical data were collected. Current smoking was defined as self-report of 1 cigarettes in the past 30 days. Hyperglycemia requiring previous or ongoing pharmacologic therapy was considered as diabetes. High blood pressure was described as either www.ajconline.org
1868
The American Journal of Cardiology (www.ajconline.org)
Figure 1. Examples of patients with MVP without and with calcification in short-axis (A and C) and 4-chamber (B and D) views, respectively. LA ¼ left atrium; LV ¼ left ventricle.
systolic or diastolic elevation of blood pressure (>140/ 90 mm Hg) or ongoing antihypertensive treatment. Hypercholesterolemia was defined as total cholesterol level of >200 mg/dl or a value 6 mm Hg), and/or systolic anterior motion of the anterior leaflet evaluated by intraoperative transesophageal echocardiography. MV replacement was performed only in case of unsuccessful repair. A complete presurgical TTE was performed in all patients using a Philips iE33 or a GE Vivid 7 ultrasound system equipped with S5 or M4S probes, respectively (Philips Medical Systems, Andover, Massachusetts, or GE Healthcare, Horten, Norway). All images were digitally acquired and stored for off-line analysis and included standard 2-dimensional, color, and pulse- and continuous-wave Doppler acquisitions.15e17 MR was defined as severe when the effective regurgitant orifice area was 0.4 cm2 estimated by proximal isovelocity surface area and/or in presence of vena contracta width >7 mm or of chordal rupture associated with flail leaflets.18 MVP diagnosis was based on 2and 3-dimensional TTE.19,20 To assess MV anatomy, we
used Carpentier’s widely recognized nomenclature that divides the posterior leaflet into 3 scallops: lateral (P1), middle (P2), and medial (P3), and the anterior leaflet into 3 segments: lateral (A1), middle (A2), and medial (A3).21 The anterolateral and posteromedial commissures were also evaluated. All segments were classified as normal, prolapsing (3 mm beyond the annulus plane), or flail. The presence of ruptured chordae was annotated. MAC was defined as an intense echo-producing structure with stone shadow, usually localized at the posterior mitral annulus, sometimes involving the whole annulus, the base of 1 MV scallops, chordae, and ventricular endocardium (Figure 1). To assign the localization of each calcification involving the annulus, the leaflets, or the commissures, we used the conventional Carpentier’s nomenclature as described previously. Patients were divided into 2 subgroups based on the 2 main phenotypes of degenerative MVP, which are BD and FED. BD is characterized by severe myxomatous degeneration of the leaflets with excess thickened tissue, billowing and/or prolapse of multiple segments of the valve, elongated and thickened, fused, or calcified chordae, and highly dilated annulus. Conversely, the diagnosis of FED is established in case of normal or even thinner leaflets because of impaired production of connective tissue that affects also the chordae tendineae, no billowing, a single prolapsing segment (usually P2) frequently associated with chordal rupture, and slight annular dilation. In the intermediate forms in which the sole prolapsed area presented some
Valvular Heart Disease/MAC in Mitral Valve Prolapse Patients
1869
Table 1 Baseline clinical and transthoracic echocardiographic characteristics of the study population and comparison between patients with and without mitral annulus calcification Variable
Age (yrs) Men Body surface area (m2) Hypertension Diabetes mellitus Dyslipidemia Smoker Coronary artery disease No. of coronary arteries involved 0 1 2 3 End-diastolic volume index (ml/m2) End-systolic volume index (ml/m2) Ejection fraction (%) Aortic valve calcification Pulmonary artery systolic pressure (mm Hg) Annulus anteroposterior diameter (mm) Annulus mediolateral diameter (mm) Eccentricity
Overall (n ¼ 410)
Mitral Annular Calcium Yes (n ¼ 99)
No (n ¼ 311)
62 13 274 (67) 1.81 0.19 224 (55) 22 (5) 265 (65) 43 (11) 87 (21)
68 10 51 (51) 1.75 0.18 67 (68) 8 (8) 75 (76) 16 (16) 32 (32)
60 13 223 (72) 1.82 0.18 157 (51) 14 (4) 190 (61) 27 (9) 55 (18)
323 (79) 50 (12) 20 (5) 17 (4) 76 19 27 9 65 7 18 (4) 38 12 36 5 40 5 0.10 0.07
67 (68) 18 (18) 6 (6) 8 (8) 73 16 27 9 64 8 13 (13) 40 12 35 5 39 5 0.11 0.07
256 (82) 32 (10) 14 (5) 9 (3) 77 20 27 10 65 7 5 (2) 37 12 36 5 41 5 0.10 0.07
p Value
