Morphological and functional characteristics of mitral annular calcification and their relationship to stroke

Autoři: Darae Kim aff001;  Chi Young Shim aff002;  Geu-Ru Hong aff002;  Hyeonju Jeong aff002;  Jong-Won Ha aff002
Působiště autorů: Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea aff001;  Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea aff002
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227753



Mitral annular calcification (MAC) is associated with risk of stroke. This study aimed to define the morphological and functional characteristics of MAC that are related to stroke.


A total of 460 subjects with MAC from transthoracic echocardiography in a single center from 2012 to 2016 was retrospectively reviewed. Subjects were classified into two groups according to history of stroke [Group 1 (n = 366): without stroke; Group 2 (n = 94): with stroke]. Morphological and functional features of MAC on echocardiogram were scored from 0 to 3 according to MAC mobility, presence of echodense mass with central echolucencies in the periannular region suggesting caseous necrosis, and functional stenosis.


Significantly more patients in group 2 were men and had history of diabetes mellitus, dyslipidemia, atrial fibrillation, or infective endocarditis. Although MAC thickness and extent did not differ between the two groups, group 2 showed a considerably higher MAC score than group 1 (0.50 ± 0.77 vs. 0.23 ±0.52 p<0.001) as a result of the higher prevalence of each component in group 2 [mobility (22 vs. 11%, p = 0.003), echodense mass with central areas of echolucencies suggesting caseous necrosis (23 vs. 7%, p<0.001), and functional mitral stenosis (12 vs. 7%, p = 0.042)]. On logistic regression analysis, MAC score was independently associated with stroke and showed significant incremental value to demographic factors and comorbidities in association with stroke in a consecutive manner.


In conclusion, morphological and functional characteristics of MAC had incremental value in association with stroke over traditional risk factors. MAC score consisting of MAC mobility, typical echodense mass with central echolucencies suggesting caseous necrosis, and functional mitral stenosis was independently associated with stroke. MAC with high-risk features may act as a source of stroke or more potent composite surrogate markers for stroke-related risk factors.

Klíčová slova:

Atrial fibrillation – Echocardiography – Endocarditis – Ischemic stroke – Medical risk factors – Necrosis – Stenosis – Stroke


1. Korn D, Desanctis RW, Sell S. Massive calcification of the mitral annulus. A clinicopathological study of fourteen cases. N Engl J Med. 1962; 267:900–9. doi: 10.1056/NEJM196211012671802 14034804

2. Pomerance A. Pathological and clinical study of calcification of the mitral valve ring. J Clin Pathol. 1970; 23:354–61. doi: 10.1136/jcp.23.4.354 5430424

3. Fertman MH, Wolff L. Calcification of the mitral valve. Am Heart J. 1946; 31:580–9. doi: 10.1016/0002-8703(46)90004-x 20981944

4. Fox CS, Vasan RS, Parise H, Levy D, O'Donnell CJ, D'Agostino RB, et al. Mitral annular calcification predicts cardiovascular morbidity and mortality—The Framingham Heart Study. Circulation. 2003; 107:1492–6. WOS:000181764600009 12654605

5. Gondrie MJA, van der Graaf Y, Jacobs PC, Oen AL, Mali WPTM, Grp PS. The association of incidentally detected heart valve calcification with future cardiovascular events. European Radiology. 2011; 21:963–73. WOS:000289291100009 21058039

6. Volzke H, Haring R, Lorbeer R, Wallaschofski H, Reffelmann T, Empen K, et al. Heart valve sclerosis predicts all-cause and cardiovascular mortality. Atherosclerosis. 2010; 209:606–10. WOS:000276158000048 19922935

7. Ramaraj R, Manrique C, Hashemzadeh M, Movahed MR. Mitral annulus calcification is independently associated with all-cause mortality. Experimental & Clinical Cardiology. 2013; 18:E5–E7. WOS:000319219000002

8. Atar S, Jeon DS, Luo H, Siegel RJ. Mitral annular calcification: a marker of severe coronary artery disease in patients under 65 years old. Heart. 2003; 89:161–4. WOS:000180611700016 12527666

9. Lu ML, Gupta S, Romero-Corral A, Matejkova M, De Venecia T, Obasare E, et al. Cardiac Calcifications on Echocardiography Are Associated with Mortality and Stroke. J Am Soc Echocardiogr. 2016; 29:1171–8. 27742243

10. Gardin JM, McCleland R, Kitzman D, Lima JAC, Bommer W, Klopfenstein HS, et al. M-mode echocardiographic predictors at six- to seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the Cardiovascular Health Study). American Journal of Cardiology. 2001; 87:1051–7. WOS:000168352700004 doi: 10.1016/s0002-9149(01)01460-6 11348601

11. Kizer JR, Wiebers DO, Whisnant JP, Galloway JM, Welty TK, Lee ET, et al. Mitral annular calcification, aortic valve sclerosis, and incident stroke in adults free of clinical cardiovascular disease: the Strong Heart Study. Stroke. 2005; 36:2533–7. doi: 10.1161/ 16254219

12. Benjamin EJ, Plehn JF, D'Agostino RB, Belanger AJ, Comai K, Fuller DL, et al. Mitral annular calcification and the risk of stroke in an elderly cohort. N Engl J Med. 1992; 327:374–9. doi: 10.1056/NEJM199208063270602 1625711

13. Allison MA, Cheung P, Criqui MH, Langer RD, Wright CM. Mitral and aortic annular calcification are highly associated with systemic calcified atherosclerosis. Circulation. 2006; 113:861–6. doi: 10.1161/CIRCULATIONAHA.105.552844 16461818

14. Adler Y, Vaturi M, Fink N, Tanne D, Shapira Y, Weisenberg D, et al. Association between mitral annulus calcification and aortic atheroma: a prospective transesophageal echocardiographic study. Atherosclerosis. 2000; 152:451–6. ISI:000089651000020 doi: 10.1016/s0021-9150(99)00497-9 10998474

15. O'Neal WT, Efird JT, Nazarian S, Alonso A, Heckbert SR, Soliman EZ. Mitral annular calcification and incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis. Europace. 2015; 17:358–63. ISI:000351605000005 doi: 10.1093/europace/euu265 25341740

16. O'Neal WT, Efird JT, Nazarian S, Alonso A, Michos ED, Szklo M, et al. Mitral annular calcification progression and the risk of atrial fibrillation: results from MESA. European Heart Journal-Cardiovascular Imaging. 2018; 19:279–84. ISI:000427282100008 doi: 10.1093/ehjci/jex093 28460029

17. Pressman GS, Rodriguez-Ziccardi M, Gartman CH, Obasare E, Melendres E, Arguello V, et al. Mitral Annular Calcification as a Possible Nidus for Endocarditis: A Descriptive Series with Bacteriological Differences Noted. Journal of the American Society of Echocardiography. 2017; 30:572–8. ISI:000405452500009 doi: 10.1016/j.echo.2017.01.016 28366636

18. Kohsaka S, Jin Z, Rundek T, Boden-Albala B, Homma S, Sacco RL, et al. Impact of mitral annular calcification on cardiovascular events in a multiethnic community: the Northern Manhattan Study. JACC Cardiovasc Imaging. 2008; 1:617–23. doi: 10.1016/j.jcmg.2008.07.006 19356491

19. Vaziri S, Bikkina M, Levy D. Predictors of thromboembolism in atrial fibrillation. Ann Intern Med. 1992; 117:89–90. doi: 10.7326/0003-4819-117-1-89 1596053

20. Aho K, Harmsen P, Hatano S, Marquardsen J, Smirnov VE, Strasser T. Cerebrovascular disease in the community: results of a WHO collaborative study. Bull World Health Organ. 1980; 58:113–30. 6966542

21. Eknoyan G, Levin NW. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification—Foreword. American Journal of Kidney Diseases. 2002; 39:S14–S266. WOS:000174176800001

22. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015; 28:1–39 e14. doi: 10.1016/j.echo.2014.10.003 25559473

23. Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, et al. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016; 29:277–314. doi: 10.1016/j.echo.2016.01.011 27037982

24. Deluca G, Correale M, Ieva R, Del Salvatore B, Gramenzi S, Di Biase M. The incidence and clinical course of caseous calcification of the mitral annulus: A prospective echocardiographic study. Journal of the American Society of Echocardiography. 2008; 21:828–33. WOS:000257205300011 doi: 10.1016/j.echo.2007.12.004 18222637

25. Harpaz D, Auerbach I, Vered Z, Motro M, Tobar A, Rosenblatt S. Caseous calcification of the mitral annulus: a neglected, unrecognized diagnosis. J Am Soc Echocardiogr. 2001; 14:825–31. doi: 10.1067/mje.2001.111877 11490332

26. Akram MR, Chan T, McAuliffe S, Chenzbraun A. Non-rheumatic annular mitral stenosis: prevalence and characteristics. Eur J Echocardiogr. 2009; 10:103–5. doi: 10.1093/ejechocard/jen179 18579487

27. Furlan AJ, Craciun AR, Salcedo EE, Mellino M. Risk of stroke in patients with mitral annulus calcification. Stroke. 1984; 15:801–3. doi: 10.1161/01.str.15.5.801 6474529

28. Fox CS, Parise H, Vasan RS, Levy D, O'Donnell CJ, D'Agostino RB, et al. Mitral annular calcification is a predictor for incident atrial fibrillation. Atherosclerosis. 2004; 173:291–4. ISI:000221755700016 doi: 10.1016/j.atherosclerosis.2003.12.018 15064104

29. Pujadas R, Arboix A, Anguera N, Rafel J, Sagues F, Casanas R. Mitral annular calcification as a marker of complex aortic atheroma in patients with stroke of uncertain etiology. Echocardiography. 2008; 25:124–32. doi: 10.1111/j.1540-8175.2007.00570.x 18269556

30. Adler Y, Koren A, Fink N, Tanne D, Fusman R, Assali A, et al. Association between mitral annulus calcification and carotid atherosclerotic disease. Stroke. 1998; 29:1833–7. doi: 10.1161/01.str.29.9.1833 9731604

31. Eicher JC, Soto FX, DeNadai L, Ressencourt O, Falcon-Eicher S, Giroud M, et al. Possible association of thrombotic, nonbacterial vegetations of the mitral ring-mitral annular calcium and stroke. Am J Cardiol. 1997; 79:1712–5. doi: 10.1016/s0002-9149(97)00233-6 9202375

32. Lin CS, Schwartz IS, Chapman I. Calcification of the mitral annulus fibrosus with systemic embolization. A clinicopathologic study of 16 cases. Arch Pathol Lab Med. 1987; 111:411–4. 3566471

33. Chevalier B, Reant P, Laffite S, Barandon L. Spontaneous fistulization of a caseous calcification of the mitral annulus: an exceptional cause of stroke. Eur J Cardiothorac Surg. 2011; 39:e184–5. doi: 10.1016/j.ejcts.2011.01.038 21376613

34. Marci M, Lo Jacono F. Mitral regurgitation due to caseous calcification of the mitral annulus: two case reports. Cases J. 2009; 2:95. doi: 10.1186/1757-1626-2-95 19178692

Článek vyšel v časopise


2020 Číslo 1