Mitral Valve Prolapse: Current Views and Challenges (Review)
Mitral valve prolapse (MVP) is the most common valve abnormality. Many issues relating its diagnosis, epidemiology, prognosis, and genetics have lately been defined more precisely or revised.
The most principal changes in MVP diagnosis are connected with establishing a three-dimensional saddle-like shape of the mitral valve annulus, which made mandatory the assessment of the valve condition from the parasternal longitudinal position during ultrasound examination. Implementation of standard diagnostic criteria based on two-dimensional echocardiography, and making the results of the Framingham Heart Study public made it possible to overcome the contradictions relative to the prevalence of this pathology, which appeared to be lower than it had been considered earlier. Age, gender, and ethnic characteristics of MVP occurrence have been established. Notions not only about the incidence of mitral prolapse development but the severity of its sequelae were subjected to reassessment. If previously MVP was thought to be a disease with serious complications, findings of conducted epidemiological studies gave reasons to consider it as a benign pathology with a low probability of unfavorable consequences. Concurrently, factors of unfavorable prognosis were identified, and mitral regurgitation was recognized to be the main of them.
The results of molecular genetic investigations enriched essentially notion about MVP and improved its diagnosing. At present, this pathology is believed to be a result of multiple genetic disorders caused by identification of several genes linked with the onset of syndromic prolapse, and three loci for nonsyndromic one. Creation of large-scale registers of MVP patients and conduction of genome-wide studies will enable cardiologists to identify new genes related to the emergence of mitral prolapse and provide screening of asymptomatic patients. The leading role in various mechanisms of MVP pathogenesis is played by the impairment of regulation of transforming growth factor beta (TGF-β), understanding of pathogenetic role of which opens new perspectives of conservative treatment of this pathology with the application of antibodies neutralizing TGF-β, and angiotensin II receptor blockers. Such medical approaches may be rather promising at the early stage of undiagnosed MVP phenotypes, and also serve as an alternative to surgical treatment of clinical complications in patients with a verified diagnosis.
- Freed L.A., Levy D., Levine R.A., Larson M.G., Evans J.C., Fuller D.L., Lehman B., Benjamin E.J. Prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med 1999; 341(1): 1–7, http://dx.doi.org/10.1056/nejm199907013410101.
- Devereux R.B., Jones E.C., Roman M.J., Howard B.V., Fabsitz R.R., Liu J.E., Palmieri V., Welty T.K., Lee E.T. Prevalence and correlates of mitral valve prolapse in a population-based sample of American Indians: the Strong Heart Study. Am J Med 2001; 111(9): 679–685, https://doi.org/10.1016/s0002-9343(01)00981-0.
- Levine R.A., Slaugenhaupt S.A. Molecular genetics of mitral valve prolapse. Curr Opin Cardiol 2007; 22(3): 171–175, https://doi.org/10.1097/hco.0b013e3280f3bfcd.
- Grau J.B., Pirelli L., Yu P.J., Galloway A.C., Ostrer H. The genetics of mitral valve prolapse. Clin Genet 2007; 72(4): 288–295, https://doi.org/10.1111/j.1399-0004.2007.00865.x.
- Delling F.N., Vasan R.S. Epidemiology and pathophysiology of mitral valve prolapse: new insights into disease progression, genetics, and molecular basis. Circulation 2014; 129(21): 2158–2170, https://doi.org/10.1161/circulationaha.113.006702.
- Hayek E., Gring C.N., Griffin B.P. Mitral valve prolapse. Lancet 2005; 365(9458): 507–518, https://doi.org/10.1016/s0140-6736(05)70275-0.
- Schoen F.J. Evolving concepts of cardiac valve dynamics: the continuum of development, functional structure, pathobiology, and tissue engineering. Circulation 2008; 118(18): 1864–1880, https://doi.org/10.1161/circulationaha.108.805911.
- Levine R.A., Hagége A.A., Judge D.P., Padala M., Dal-Bianco J.P., Aikawa E., Beaudoin J., Bischoff J., Bouatia-Naji N., Bruneval P., Butcher J.T., Carpentier A., Chaput M., Chester A.H., Clusel C., Delling F.N., Dietz H.C., Dina C., Durst R., Fernandez-Friera L., Handschumacher M.D., Jensen M.O., Jeunemaitre X.P., Le Marec H., Le Tourneau T., Markwald R.R., Mérot J., Messas E., Milan D.P., Neri T., Norris R.A., Peal D., Perrocheau M., Probst V., Pucéat M., Rosenthal N., Solis J., Schott J.J., Schwammenthal E., Slaugenhaupt S.A., Song J.K., Yacoub M.H.; Leducq Mitral Transatlantic Network. Mitral valve disease — morphology and mechanisms Nat Rev Cardiol 2015; 12(12): 689–710, https://doi.org/10.1038/nrcardio.2015.161.
- Dolan A.L., Mishra M.B., Chambers J.B., Grahame R. Clinical and echocardiographic survey of the Ehlers–Danlos syndrome. Br J Rheumatol 1997; 36(4): 459–462, https://doi.org/10.1093/rheumatology/36.4.459.
- Loeys B.L., Schwarze U., Holm T., Callewaert B.L., Thomas G.H., Pannu H., De Backer J.F., Oswald G.L., Symoens S., Manouvrier S., Roberts A.E., Faravelli F., Greco M.A., Pyeritz R.E., Milewicz D.M., Coucke P.J., Cameron D.E., Braverman A.C., Byers P.H., De Paepe A.M., Dietz H.C. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med 2006; 355(8): 788–798, https://doi.org/10.1056/nejmoa055695.
- Rubegni P., Mondillo S., De Aloe G., Agricola E., Bardelli A.M., Fimiani M. Mitral valve prolapse in healthy relatives of patients with familial Pseudoxanthoma elasticum. Am J Cardiol 2000; 85(10): 1268–1271, https://doi.org/10.1016/s0002-9149(00)00745-1.
- van de Laar I.M., Oldenburg R.A., Pals G., Roos-Hesselink J.W., de Graaf B.M., Verhagen J.M., Hoedemaekers Y.M., Willemsen R., Severijnen L.A., Venselaar H., Vriend G., Pattynama P.M., Collée M., Majoor-Krakauer D., Poldermans D., Frohn-Mulder I.M., Micha D., Timmermans J., Hilhorst-Hofstee Y., Bierma-Zeinstra S.M., Willems P.J., Kros J.M., Oei E.H., Oostra B.A., Wessels M.W., Bertoli-Avella A.M. Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis. Nat Genet 2011; 43(2): 121–126, https://doi.org/10.1038/ng.744.
- Rabkin E., Aikawa M., Stone J.R., Fukumoto Y., Libby P., Schoen F.J. Activated interstitial myofibroblasts express catabolic enzymes and mediate matrix remodeling in myxomatous heart valves. Circulation 2001; 104(21): 2525–2532, https://doi.org/10.1161/hc4601.099489.
- Guy T.S., Hill A.C. Mitral valve prolapse. Annu Rev Med 2012; 63(1): 277–292, https://doi.org/10.1146/annurev-med-022811-091602.
- Avierinos J.F., Gersh B.J., Melton L.J., Bailey K.R., Shub C., Nishimura R.A., Tajik A.J., Enriquez-Sarano M. Natural history of asymptomatic mitral valve prolapse in the community. Circulation 2002; 106(11): 1355–1361, https://doi.org/10.1161/01.cir.0000028933.34260.09.
- Bayer-Topilsky T., Suri R.M., Topilsky Y., Marmor Y.N., Trenerry M.R., Antiel R.M., Mahoney D.W., Schaff H.V., Enriquez-Sarano M. Mitral valve prolapse, psychoemotional status, and quality of life: prospective investigation in the current era. Am J Med 2016; 129(10): 1100–1109, https://doi.org/10.1016/j.amjmed.2016.05.004.
- Bonow R.O., Carabello B.A., Chatterjee K., de Leon A.C. Jr., Faxon D.P., Freed M.D., Gaasch W.H., Lytle B.W., Nishimura R.A., O’Gara P.T., O’Rourke R.A., Otto C.M., Shah P.M., Shanewise J.S. 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2008; 118(15): e523–e661, https://doi.org/10.1161/circulationaha.108.190748.
- Dal-Bianco J.P., Levine R.A. Anatomy of the mitral valve apparatus: role of 2D and 3D echocardiography. Cardiol Clin 2013; 31(2): 151–164, https://doi.org/10.1016/j.ccl.2013.03.001.
- McGhie J.S., de Groot-de Laat L., Ren B., Vletter W., Frowijn R., Oei F., Geleijnse M.L. Transthoracic two-dimensional xPlane and three-dimensional echocardiographic analysis of the site of mitral valve prolapse. Int J Cardiovasc Imaging 2015; 31(8): 1553–1560, https://doi.org/10.1007/s10554-015-0734-7.
- Loardi C., Alamanni F., Trezzi M., Kassem S., Cavallotti L., Tremoli E., Pacini D., Parolari A. Biology of mitral valve prolapse: the harvest is big, but the workers are few. Int J Cardiol 2011; 151(2): 129–135, https://doi.org/10.1016/j.ijcard.2010.11.004.
- Padang R., Bagnall R.D., Semsarian C. Genetic basis of familial valvular heart disease. Circ Cardiovasc Genet 2012; 5(5): 569–580, https://doi.org/10.1161/circgenetics.112.962894.
- Yagoda A.V., Novikova M.V., Gladkikh N.N. Risk factors prognostic significance of cardiac arrhythmias in connective tissue dysplasia. Archive of internal medicine 2015; 1: 60–63.
- Turker Y., Ozaydin M., Acar G., Ozgul M., Hoscan Y., Varol E., Dogan A., Erdogan D., Yucel H. Predictors of ventricular arrhythmias in patients with mitral valve prolapse. Int J Cardiovasc Imaging 2010; 26(2): 139–145, https://doi.org/10.1007/s10554-009-9514-6.
- Semyonkin A.A., Tereshchenko Yu.V., Drokina O.V., Zhivilova L.A. Autonomic regulation features in youngs with connective tissue dysplasia. Sibirskiy meditsinskiy zhurnal 2011; 26(3–2): 56–59.
- Nedostup A.V. Some features of cardiac arrythmia treatment in outpatient practice. Ter Arkh 2006; 78(8): 5–13.
- Nechaeva G.I. Viktorova I.A., Druk I.V., Vershinina M.V. Connective tissue dysplasia: the pulmonary aspects. Pul’monologiya 2004; 2: 116–119.
- Torshin I.Yu., Gromova O.A., Kalacheva A.G., Oshchepkova E.V., Martynov A.I. Meta-analysis of clinical trials of cardiovascular effects of magnesium orotate. Ter Arkh 2015; 87(6): 88–97.
- Savage D.D., Garrison R.J., Devereux R.B., Castelli W.P., Anderson S.J., Levy D., McNamara P.M., Stokes J. 3rd, Kannel W.B., Feinleib M. Mitral valve prolapse in the general population. 1. Epidemiologic features: the Framingham Study. Am Heart J 1983; 106(3): 571–576, https://doi.org/10.1016/0002-8703(83)90704-4.
- Savage D.D., Devereux R.B., Garrison R.J., Castelli W.P., Anderson S.J., Levy D., Thomas H.E., Kannel W.B., Feinleib M. Mitral valve prolapse in the general population. 2. Clinical features: the Framingham Study. Am Heart J 1983; 106(3): 577–581, https://doi.org/10.1016/0002-8703(83)90705-6.
- Levine R.A., Stathogiannis E., Newell J.B., Harrigan P., Weyman A.E. Reconsideration of echocardiographic standards for mitral valve prolapse: lack of association between leaflet displacement isolated to the apical four chamber view and independent echocardiographic evidence of abnormality. J Am Coll Cardiol 1988; 11(5): 1010–1019, https://doi.org/10.1016/s0735-1097(98)90059-6.
- Apor A., Nagy A.I., Kovács A., Manouras A., Andrássy P., Merkely B. Three-dimensional dynamic morphology of the mitral valve in different forms of mitral valve prolapse — potential implications for annuloplasty ring selection. Cardiovasc Ultrasound 2016; 14(1): 32, https://doi.org/10.1186/s12947-016-0073-4.
- Russian Society of Cardiology. Hereditary disorders of connective tissue in cardiology. Diagnosis and treatment. Russian Guidelines (I revision). Rossiyskiy kardiologicheskiy zhurnal 2013; 1(Suppl 1): 1–32.
- Freed L.A., Benjamin E.J., Levy D., Larson M.G., Evans J.C., Fuller D.L., Lehman B., Levine R.A. Mitral valve prolapse in the general population: the benign nature of echocardiographic features in the Framingham Heart Study. J Am Coll Cardiol 2002; 40(7): 1298–1304, https://doi.org/10.1016/s1062-1458(02)01019-x.
- Maffessanti F., Mirea O., Tamborini G., Pepi M. Three-dimensional echocardiography of the mitral valve: lessons learned. Curr Cardiol Rep 2013; 15(7): 377, https://doi.org/10.1007/s11886-013-0377-z.
- Benenstein R., Saric M. Mitral valve prolapse: role of 3D echocardiography in diagnosis. Curr Opin Cardiol 2012; 27(5): 465–476, https://doi.org/10.1097/hco.0b013e328356afe9.
- Qamruddin S., Naqvi T.Z. Advances in 3D echocardiography for mitral valve. Expert Rev Cardiovasc Ther 2011; 9(11): 1431–1443, https://doi.org/10.1586/erc.11.137.
- Lang R.M., Tsang W., Weinert L., Mor-Avi V., Chandra S. Valvular heart disease. The value of 3-dimensional echocardiography. J Am Coll Cardiol 2011; 58(19): 1933–1944, https://doi.org/10.1016/j.jacc.2011.07.035.
- Jin C.N., Salgo I.S., Schneider R.J., Kam K.K., Chi W.K., So C.Y., Tang Z., Wan S., Wong R., Underwood M., Lee A.P. Using anatomic intelligence to localize mitral valve prolapse on three-dimensional echocardiography. J Am Soc Echocardiogr 2016; 29(10): 938–945, https://doi.org/10.1016/j.echo.2016.07.002.
- Dawber T.R., Meadors G.F., Moore F.E. Jr. Epidemiological approaches to heart disease: the Framingham Study. Am J Public Health Nations Health 1951; 41(3): 279–286, https://doi.org/10.2105/ajph.41.3.279.
- Kannel W.B., Feinleib M., McNamara P.M., Garrison R.J., Castelli W.P. An investigation of coronary heart disease in families. The Framingham offspring study. Am J Epidemiol 1979; 110(3): 281–290.
- Turker Y., Baltaci D., Basar C., Akkaya M., Ozhan H. The prevalence and clinical characteristics of mitral valve prolapse in a large population-based epidemiologic study: the MELEN study. Eur Rev Med Pharmacol Sci 2015; 19(12): 2208–2212.
- Strahan N.V., Murphy E.A., Fortuin N.J., Come P.C., Humphries J.O. Inheritance of the mitral valve prolapse syndrome. Discussion of a three-dimensional penetrance model. Am J Med 1983; 74(6): 967–972, https://doi.org/10.1016/0002-9343(83)90792-1.
- Zua M.S., Dziegielewski S.F. Epidemiology of symptomatic mitral valve prolapse in black patients. J Natl Med Assoc 1995; 87(4): 273–275.
- Gupta R., Jain B.K., Gupta H.P., Ranawat S.S., Sharma A.K., Gupta K.D. Mitral valve prolapse: two dimensional echocardiography reveals a high prevalence in three to twelve year old children. Indian Pediatr 1992; 29(4): 415–423.
- Oladapo O.O., Falase A.O. Prevalence of mitral valve prolapse in healthy adult Nigerians as diagnosed by echocardiography. Afr J Med Med Sci 2001; 30(1–2): 13–16.
- Nascimento R., Freitas A., Teixeira F., Pereira D., Cardoso A., Dinis M., Mendonça I. Is mitral valve prolapse a congenital or acquired disease? Am J Cardiol 1997; 79(2): 226–227, https://doi.org/10.1016/s0002-9149(96)00722-9.
- Hickey A.J., Wilcken D.E. Age and the clinical profile of idiopathic mitral valve prolapse. Br Heart J 1986; 55(6): 582–586, https://doi.org/10.1136/hrt.55.6.582.
- Flack J.M., Kvasnicka J.H., Gardin J.M., Gidding S.S., Manolio T.A., Jacobs D.R. Jr. Anthropometric and physiologic correlates of mitral valve prolapse in a biethnic cohort of young adults: the CARDIA study. Am Heart J 1999; 138(3 Pt 1): 486–492, https://doi.org/10.1016/s0002-8703(99)70151-1.
- Theal M., Sleik K., Anand S., Yi Q., Yusuf S., Lonn E. Prevalence of mitral valve prolapse in ethnic groups. Can J Cardiol 2004; 20(5): 511–515.
- Zemtsovskiy E.V., Malev E.G. Mitral valve prolapse: a modern view of the problem. Byulleten’ Federal’nogo tsentra serdtsa, krovi i endokrinologii im. V.A. Almazova 2011; 3: 25–30.
- Taub C.C., Stoler J.M., Perez-Sanz T., Chu J., Isselbacher E.M., Picard M.H., Weyman A.E. Mitral valve prolapse in Marfan syndrome: an old topic revisited. Echocardiography 2009; 26(4): 357–364, https://doi.org/10.1111/j.1540-8175.2008.00825.x.
- Gu X., He Y., Li Z., Han J., Chen J., Nixon J.V. Echocardiographic versus histologic findings in Marfan syndrome. Tex Heart Inst J 2015; 42(1): 30–34, https://doi.org/10.14503/thij-13-3848.
- Attias D., Stheneur C., Roy C., Collod-Béroud G., Detaint D., Faivre L., Delrue M.A., Cohen L., Francannet C., Béroud C., Claustres M., Iserin F., Khau Van Kien P., Lacombe D., Le Merrer M., Lyonnet S., Odent S., Plauchu H., Rio M., Rossi A., Sidi D., Steg P.G., Ravaud P., Boileau C., Jondeau G. Comparison of clinical presentations and outcomes between patients with TGFBR2 and FBN1 mutations in Marfan syndrome and related disorders. Circulation 2009; 120(25): 2541–2549, https://doi.org/10.1161/circulationaha.109.887042.
- Devereux R.B., Kramer-Fox R., Shear M.K., Kligfield P., Pini R., Savage D.D. Diagnosis and classification of severity of mitral valve prolapse: methodologic, biologic, and prognostic considerations. Am Heart J 1987; 113(5): 1265–1280, https://doi.org/10.1016/0002-8703(87)90955-0.
- Zuppiroli A., Rinaldi M., Kramer-Fox R., Favilli S., Roman M.J., Devereux R.B. Natural history of mitral valve prolapse. Am J Cardiol 1995; 75(15): 1028–1032, https://doi.org/10.1016/s0002-9149(99)80718-8.
- Mulumudi M.S., Vivekananthan K. Mysteries of mitral valve prolapse. Proper treatment requires consideration of all clues. Postgrad Med 2001; 110(2): 43–44, https://doi.org/10.3810/pgm.2001.08.994.
- Playford D., Weyman A.E. Mitral valve prolapse: time for a fresh look. Rev Cardiovasc Med 2001; 2(2): 73–81.
- Hayek E., Griffin B. Mitral valve prolapse: old beliefs yield to new knowledge. Cleve Clin J Med 2002; 69(11): 889–896, https://doi.org/10.3949/ccjm.69.11.889.
- Stefanadis C., Toutouzas P. Mitral valve prolapse: the merchant of Venice or much ado about nothing? Eur Heart J 2000; 21(4): 255–258, https://doi.org/10.1053/euhj.1999.1926.
- Bensaid J. When should mitral valve prolapse be considered a real disease? Ann Cardiol Angeiol 2000; 49(7): 411–413.
- Gilon D., Buonanno F.S., Joffe M.M., Leavitt M., Marshall J.E., Kistler J.P., Levine R.A. Lack of evidence of an association between mitral-valve prolapse and stroke in young patients. N Engl J Med 1999; 41(1): 8–13, https://doi.org/10.1056/nejm199907013410102.
- Mas J.L. Cardiopathies associated with a low embolic risk. Rev Neurol 1999; 155(9): 677–683.
- Koegelenberg C.F., Doubell A., Orth H., Reuter H. Infective endocarditis in the Western Cape Province of South Africa: a three-year prospective study. QJM 2003; 96(3): 217–225, https://doi.org/10.1093/qjmed/hcg028.
- Rosenhek R., Rader F., Klaar U., Gabriel H., Krejc M., Kalbeck D., Schemper M., Maurer G., Baumgartner H. Outcome of watchful waiting in asymptomatic severe mitral regurgitation. Circulation 2006; 113(18): 2238–2244, https://doi.org/10.1161/circulationaha.105.599175.
- Ling L.H., Enriquez-Sarano M., Seward J.B., Orszulak T.A., Schaff H.V., Bailey K.R., Tajik A.J., Frye R.L. Early surgery in patients with mitral regurgitation due to flail leaflets: a long-term outcome study. Circulation 1997; 96(6): 1819–1825, https://doi.org/10.1161/01.cir.96.6.1819.
- Antiochos P., Muller O., Kirsch M., Agostini M., Qanadli S., Eeckhout E., Vogt P., Prêtre R., Delabays A., Jeanrenaud X., Monney P. Approach to chronic mitral regurgitation in 2016. Rev Med Suisse 2016; 12(520): 1042–1048.
- Taramasso M., Gaemperli O., Maisano F. Treatment of degenerative mitral regurgitation in elderly patients. Nat Rev Cardiol 2015; 12(3): 177–183, https://doi.org/10.1038/nrcardio.2014.210.
- Avierinos J.F., Detaint D., Messika-Zeitoun D., Mohty D., Enriquez-Sarano M. Risk, determinants, and outcome implications of progression of mitral regurgitation after diagnosis of mitral valve prolapse in a single community. Am J Cardiol 2008; 101(5): 662–667, https://doi.org/10.1016/j.amjcard.2007.10.029.
- Enriquez-Sarano M., Avierinos J.F., Messika-Zeitoun D., Detaint D., Capps M., Nkomo V., Scott C., Schaff H.V., Tajik A.J. Quantitative determinants of the outcome of asymptomatic mitral regurgitation. N Engl J Med 2005; 352(9): 875–883, https://doi.org/10.1056/nejmoa041451.
- Enriquez-Sarano M., Basmadjian A.J., Rossi A., Bailey K.R., Seward J.B., Tajik A.J. Progression of mitral regurgitation: a prospective Doppler echocardiographic study. J Am Coll Cardiol 1999; 34(4): 1137–1144, https://doi.org/10.1016/s0735-1097(99)00313-7.
- Delling F.N., Rong J., Larson M.G., Lehman B., Fuller D., Osypiuk E., Stantchev P., Hackman B., Manning W.J., Benjamin E.J., Levine R.A., Vasan R.S. Evolution of mitral valve prolapse: insights from the Framingham Heart Study. Circulation 2016; 133(17): 1688–1695, https://doi.org/10.1161/circulationaha.115.020621.
- Boudoulas K.D., Boudoulas H. Floppy mitral valve (FMV)/mitral valve prolapse (MVP) and the FMV/MVP syndrome: pathophysiologic mechanisms and pathogenesis of symptoms. Cardiology 2013; 126(2): 69–80, https://doi.org/10.1159/000351094.
- Otani K., Takeuchi M., Kaku K., Haruki N., Yoshitani H., Eto M., Tamura M., Okazaki M., Abe H., Fujino Y., Nishimura Y., Levine R.A., Otsuji Y. Evidence of a vicious cycle in mitral regurgitation with prolapse. Circulation 2012; 126(11 Suppl 1): S214–S221, https://doi.org/10.1161/circulationaha.111.084178.
- Gertz Z.M., Raina A., Saghy L., Zado E.S., Callans D.J., Marchlinski F.E., Keane M.G., Silvestry F.E. Evidence of atrial functional mitral regurgitation due to atrial fibrillation. J Am Coll Cardiol 2011; 58(14): 1474–1481, https://doi.org/10.1016/j.jacc.2011.06.032.
- Grigioni F., Tribouilloy C., Avierinos J.F., Barbieri A., Ferlito M., Trojette F., Tafanelli L., Branzi A., Szymanski C., Habib G., Modena M.G., Enriquez-Sarano M. Outcomes in mitral regurgitation due to flail leaflets a multicenter European study. JACC Cardiovasc Imaging 2008; 1(2): 133–141, https://doi.org/10.1016/j.jcmg.2007.12.005.
- Ling L.H., Enriquez-Sarano M., Seward J.B., Tajik A.J., Schaff H.V., Bailey K.R., Frye R.L. Clinical outcome of mitral regurgitation due to flail leaflet. N Engl J Med 1996; 335(19): 1417–1423, https://doi.org/10.1056/nejm199611073351902.
- Avierinos J.F., Inamo J., Grigioni F., Gersh B., Shub C., Enriquez-Sarano M. Sex differences in morphology and outcomes of mitral valve prolapse. Ann Intern Med 2008; 149(11): 787–795, https://doi.org/10.7326/0003-4819-149-11-200812020-00003.
- De Backer J. Cardiovascular characteristics in Marfan syndrome and their relation to the genotype. Verh K Acad Geneeskd Belg 2009; 71(6): 335–371.
- Khan R., Sheppard R. Fibrosis in heart disease: understanding the role of transforming growth factor-beta in cardiomyopathy, valvular disease and arrhythmia. Immunology 2006; 118(1): 10–24, https://doi.org/10.1111/j.1365-2567.2006.02336.x.
- Malev E.G., Pshepyi A.P., Vasina L.V., Reeva S.V., Timofeev E.V., Korshunova A.L. Left ventricular remodelling and diastolic dysfunction in mitral valve prolapse. Rossiyskiy kardiologicheskiy zhurnal 2013; 100(2): 12–19.
- Bui A.H., Roujol S., Foppa M., Kissinger K.V., Goddu B., Hauser T.H., Zimetbaum P.J., Ngo L.H., Manning W.J., Nezafat R., Delling F.N. Diffuse myocardial fibrosis in patients with mitral valve prolapse and ventricular arrhythmia. Heart 2017; 103(3): 204–209, https://doi.org/10.1136/heartjnl-2016-309303.
- de la Pompa J.L., Timmerman L.A., Takimoto H., Yoshida H., Elia A.J., Samper E., Potter J., Wakeham A., Marengere L., Langille B.L., Crabtree G.R., Mak T.W. Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum. Nature 1998; 392(6672): 182–186, https://doi.org/10.1038/32419.
- Hurlstone A.F., Haramis A.P., Wienholds E., Begthel H., Korving J., Van Eeden F., Cuppen E., Zivkovic D., Plasterk R.H., Clevers H. The Wnt/beta-catenin pathway regulates cardiac valve formation. Nature 2003; 425(6958): 633–637, https://doi.org/10.1038/nature02028.
- Salhiyyah K., Yacoub M.H., Chester A.H. Cellular mechanisms in mitral valve disease. J Cardiovasc Transl Res 2011; 4(6): 702–709, https://doi.org/10.1007/s12265-011-9318-7.
- Wheeler J.B., Ikonomidis J.S., Jones J.A. Connective tissue disorders and cardiovascular complications: the indomitable role of transforming growth factor-beta signaling. Adv Exp Med Biol 2014; 802: 107–127, https://doi.org/10.1007/978-94-007-7893-1_8.
- Bischoff J., Aikawa E. Progenitor cells confer plasticity to cardiac valve endothelium. J Cardiovasc Transl Res 2011; 4(6): 710–719, https://doi.org/10.1007/s12265-011-9312-0.
- Greenhouse D.G., Murphy A., Mignatti P., Zavadil J., Galloway A.C., Balsam L.B. Mitral valve prolapse is associated with altered extracellular matrix gene expression patterns. Gene 2016; 586(1): 56–61, https://doi.org/10.1016/j.gene.2016.04.004.
- Rizzo S., Basso C., Lazzarini E., Celeghin R., Paolin A., Gerosa G., Valente M., Thiene G., Pilichou K. TGF-beta1 pathway activation and adherens junction molecular pattern in nonsyndromic mitral valve prolapse. Cardiovasc Pathol 2015; 24(6): 359–367, https://doi.org/10.1016/j.carpath.2015.07.009.
- Bertolino P., Deckers M., Lebrin F., ten Dijke P. Transforming growth factor-beta signal transduction in angiogenesis and vascular disorders. Chest 2005; 128(6 Suppl): 585S–590S, https://doi.org/10.1378/chest.128.6_suppl.585s.
- LaHaye S., Lincoln J., Garg V. Genetics of valvular heart disease. Curr Cardiol Rep 2014; 16(6): 487, https://doi.org/10.1007/s11886-014-0487-2.
- Ignotz R.A., Massague J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem 1986; 261(9): 4337–4345.
- Yan C., Boyd D.D. Regulation of matrix metalloproteinase gene expression. J Cell Physiol 2007; 211(1): 19–26, https://doi.org/10.1002/jcp.20948.
- Kwak H.J., Park M.J., Cho H., Park C.M., Moon S.I., Lee H.C., Park I.C., Kim M.S., Rhee C.H., Hong S.I. Transforming growth factor-beta1 induces tissue inhibitor of metalloproteinase-1 expression via activation of extracellular signal-regulated kinase and Sp1 in human fibrosarcoma cells. Mol Cancer Res 2006; 4(3): 209–220, https://doi.org/10.1158/1541-7786.mcr-05-0140.
- Jones J.A., Spinale F.G., Ikonomidis J.S. Transforming growth factor-beta signaling in thoracic aortic aneurysm development: a paradox in pathogenesis. J Vasc Res 2009; 46(2): 119–137, https://doi.org/10.1159/000151766.
- Kim E.S., Kim M.S., Moon A. TGF-beta-induced upregulation of MMP-2 and MMP-9 depends on p38 MAPK, but not ERK signaling in MCF10A human breast epithelial cells. Int J Oncol 2004; 25(5): 1375–1382, https://doi.org/10.3892/ijo.25.5.1375.
- Laiho M., Saksela O., Keski-Oja J. Transforming growth factor beta alters plasminogen activator activity in human skin fibroblasts. Exp Cell Res 1986; 164(2): 399–407, https://doi.org/10.1016/0014-4827(86)90038-8.
- Disatian S., Ehrhart E.J. 3rd, Zimmerman S., Orton E.C. Interstitial cells from dogs with naturally occurring myxomatous mitral valve disease undergo phenotype transformation. J Heart Valve Dis 2008; 17(4): 402–411.
- Geirsson A., Singh M., Ali R., Abbas H., Li W., Sanchez J.A., Hashim S., Tellides G. Modulation of transforming growth factor-beta signaling and extracellular matrix production in myxomatous mitral valves by angiotensin II receptor blockers. Circulation 2012; 126(11 Suppl 1): 189–197, https://doi.org/10.1161/circulationaha.111.082610.
- Hulin A., Deroanne C., Lambert C., Defraigne J.O., Nusgens B., Radermecker M., Colige A. Emerging pathogenic mechanisms in human myxomatous mitral valve: lessons from past and novel data. Cardiovasc Pathol 2013; 22(4): 245–250, https://doi.org/10.1016/j.carpath.2012.11.001.
- Kimura N., Shukunami C., Hakuno D., Yoshioka M., Miura S., Docheva D., Kimura T., Okada Y., Matsumura G., Shin’oka T., Yozu R., Kobayashi J., Ishibashi-Ueda H., Hiraki Y., Fukuda K. Local tenomodulin absence, angiogenesis, and matrix metalloproteinase activation are associated with the rupture of the chordae tendineae cordis. Circulation 2008; 118(17): 1737–1747, https://doi.org/10.1161/circulationaha.108.780031.
- Dietz H.C., Cutting G.R., Pyeritz R.E., Maslen C.L., Sakai L.Y., Corson G.M., Puffenberger E.G., Hamosh A., Nanthakumar E.J., Curristin S.M., Stetten G., Meyers D.A., Francomano C.A. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 1991; 352(6333): 337–339, https://doi.org/10.1038/352337a0.
- Kumar A., Agarwal S. Marfan syndrome: an eyesight of syndrome. Meta Gene 2014; 2: 96–105, https://doi.org/10.1016/j.mgene.2013.10.008.
- Mizuguchi T., Collod-Beroud G., Akiyama T., Abifadel M., Harada N., Morisaki T., Allard D., Varret M., Claustres M., Morisaki H., Ihara M., Kinoshita A., Yoshiura K., Junien C., Kajii T., Jondeau G., Ohta T., Kishino T., Furukawa Y., Nakamura Y., Niikawa N., Boileau C., Matsumoto N. Heterozygous TGFBR2 mutations in Marfan syndrome. Nat Genet 2004; 36(8): 855–860, https://doi.org/10.1038/ng1392.
- Ng C.M., Cheng A., Myers L.A., Martinez-Murillo F., Jie C., Bedja D., Gabrielson K.L., Hausladen J.M., Mecham R.P., Judge D.P., Dietz H.C. TGF-beta-dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome. J Clin Invest 2004; 114(11): 1586–1592, https://doi.org/10.1172/jci22715.
- Habashi J.P., Doyle J.J., Holm T.M., Aziz H., Schoenhoff F., Bedja D., Chen Y., Modiri A.N., Judge D.P., Dietz H.C. Angiotensin II type 2 receptor signaling attenuates aortic aneurysm in mice through ERK antagonism. Science 2011; 332(6027): 361–365, https://doi.org/10.1126/science.1192152.
- Groenink M., den Hartog A.W., Franken R., Radonic T., de Waard V., Timmermans J., Scholte A.J., van den Berg M.P., Spijkerboer A.M., Marquering H.A., Zwinderman A.H., Mulder B.J. Losartan reduces aortic dilatation rate in adults with Marfan syndrome: a randomized controlled trial. Eur Heart J 2013; 34(45): 3491–500, https://doi.org/10.1093/eurheartj/eht334.
- Lacro R.V., Guey L.T., Dietz H.C., Pearson G.D., Yetman A.T., Gelb B.D., Loeys B.L., Benson D.W., Bradley T.J., De Backer J., Forbus G.A., Klein G.L., Lai W.W., Levine J.C., Lewin M.B., Markham L.W., Paridon S.M., Pierpont M.E., Radojewski E., Selamet Tierney E.S., Sharkey A.M., Wechsler S.B., Mahony L.; Pediatric Heart Network Investigators. Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy. Am Heart J 2013; 165(5): 828–835.e3, https://doi.org/10.1016/j.ahj.2013.02.019.
- Lacro R.V., Dietz H.C., Sleeper L.A., Yetman A.T., Bradley T.J., Colan S.D., Pearson G.D., Selamet Tierney E.S., Levine J.C., Atz A.M., Benson D.W., Braverman A.C., Chen S., De Backer J., Gelb B.D., Grossfeld P.D., Klein G.L., Lai W.W., Liou A., Loeys B.L. Atenolol versus losartan in children and young adults with Marfan’s syndrome. N Engl J Med 2014; 371(22): 2061–2071, https://doi.org/10.1056/nejmoa1404731.
- Judge D.P., Rouf R., Habashi J., Dietz H.C. Mitral valve disease in Marfan syndrome and related disorders. J Cardiovasc Transl Res 2011; 4(6): 741–747, https://doi.org/10.1007/s12265-011-9314-y.
- Disse S., Abergel E., Berrebi A., Houot A.M., Le Heuzey J.Y., Diebold B., Guize L., Carpentier A., Corvol P., Jeunemaitre X. Mapping of a first locus for autosomal dominant myxomatous mitral-valve prolapse to chromosome 16p11.2-p12.1. Am J Hum Genet 1999; 65(5): 1242–1251, https://doi.org/10.1086/302624.
- Freed L.A., Acierno J.S., Dai D., Leyne M., Marshall J.E., Nesta F., Levine R.A., Slaugenhaupt S.A. A locus for autosomal dominant mitral valve prolapse on chromosome 11p15.4. Am J Hum Genet 2003; 72(6): 1551–1559, https://doi.org/10.1086/375452.
- Nesta F., Leyne M., Yosefy C., Simpson C., Dai D., Marshall J.E., Hung J., Slaugenhaupt S.A., Levine R.A. New locus for autosomal dominant mitral valve prolapse on chromosome 13: clinical insights from genetic studies. Circulation 2005; 112(13): 2022–2030, https://doi.org/10.1161/circulationaha.104.516930.
- Klemenov A.V. Idiopathic mitral valve prolapse in adulthood and old age. Klinicheskaya gerontologiya 2001; 7(5–6): 57–59.
- Tourneau T., Lardeux A., Kyndt F., Mérot J., Hagege A., Levine R., Marec H., Schott J.-J., Probst V. New findings in mitral valve prolapse related to filamin-A mutations. Archives of Cardiovascular Diseases Supplements 2012; 4(1): 59, https://doi.org/10.1016/s1878-6480(12)70583-9.
- Kyndt F., Schott J.J., Trochu J.N., Baranger F., Herbert O., Scott V., Fressinaud E., David A., Moisan J.P., Bouhour J.B., Le Marec H., Benichou B. Mapping of X-linked myxomatous valvular dystrophy to chromosome Xq28. Am J Hum Genet 1998; 62(3): 627–632, https://doi.org/10.1086/301747.
- Lardeux A., Kyndt F., Lecointe S., Marec H., Mérot J., Schott J.J., Tourneau T., Probst V. Filamin-A-related myxomatous mitral valve dystrophy: genetic, echocardiographic and functional aspects. J Cardiovasc Transl Res 2011; 4(6): 748–756, https://doi.org/10.1007/s12265-011-9308-9.
- Duval D., Labbé P., Bureau L., Le Tourneau T., Norris R.A., Markwald R.R., Levine R., Schott J.J., Mérot J. MVP-associated filamin A mutations affect FlnA-PTPN12(PTP-PEST) interactions. J Cardiovasc Dev Dis 2015; 2(3): 233–247, https://doi.org/10.3390/jcdd2030233.
- Nakamura F., Stossel T.P., Hartwig J.H. The filamins: organizers of cell structure and function. Cell Adh Migr 2011; 5(2): 160–169, https://doi.org/10.4161/cam.5.2.14401.
- Ciobanasu C., Faivre B., Le Clainche C. Integrating actin dynamics, mechanotransduction and integrin activation: the multiple functions of actin binding proteins in focal adhesions. Eur J Cell Biol 2013; 92(10–11): 339–348, https://doi.org/10.1016/j.ejcb.2013.10.009.
- Razinia Z., Mäkelä T., Ylänne J., Calderwood D.A. Filamins in mechanosensing and signaling. Annu Rev Biophys 2012; 41: 227–246, https://doi.org/10.1146/annurev-biophys-050511-102252.
- Jahed Z., Shams H., Mehrbod M., Mofrad M.R. Mechanotransduction pathways linking the extracellular matrix to the nucleus. Int Rev Cell Mol Biol 2014; 310: 171–220, https://doi.org/10.1016/b978-0-12-800180-6.00005-0.
- Norris R.A., Moreno-Rodriguez R., Wessels A., Merot J., Bruneval P., Chester A.H., Yacoub M.H., Hagège A., Slaugenhaupt S.A., Aikawa E., Schott J.J., Lardeux A., Harris B.S., Williams L.K., Richards A., Levine R.A., Markwald R.R. Expression of the familial cardiac valvular dystrophy gene, filamin-A, during heart morphogenesis. Dev Dyn 2010; 239(7): 2118–2127, https://doi.org/10.1002/dvdy.22346.
- Sauls K., Toomer K., Williams K., Johnson A.J., Markwald R.R., Hajdu Z., Norris R.A. Increased infiltration of extra-cardiac cells in myxomatous valve disease. J Cardiovasc Dev Dis 2015; 2(3): 200–213, https://doi.org/10.3390/jcdd2030200.
- Dalkilic I., Schienda J., Thompson T.G., Kunkel L.M. Loss of filamin C (FLNc) results in severe defects in myogenesis and myotube structure. Mol Cell Biol 2006; 26(17): 6522–6534, https://doi.org/10.1128/mcb.00243-06.
- Zhou X., Tian F., Sandzén J., Cao R., Flaberg E., Szekely L., Cao Y., Ohlsson C., Bergo M.O., Borén J., Akyürek L.M. Filamin B deficiency in mice results in skeletal malformations and impaired microvascular development. Proc Natl Acad Sci USA 2007; 104(10): 3919–3924, https://doi.org/10.1073/pnas.0608360104.
- Sasaki A., Masuda Y., Ohta Y., Ikeda K., Watanabe K. Filamin associates with Smads and regulates transforming growth factor-beta signaling. J Biol Chem 2001; 276(21): 17871–17877, https://doi.org/10.1074/jbc.m008422200.
- Cushing M.C., Liao J.T., Anseth K.S. Activation of valvular interstitial cells is mediated by transforming growth factor-beta1 interactions with matrix molecules. Matrix Biol 2005; 24(6): 428–437, https://doi.org/10.1016/j.matbio.2005.06.007.
- Charitakis K., Basson C.T. Degenerating heart valves: fill them up with filamin? Circulation 2006; 115(1): 2–4, https://doi.org/10.1161/circulationaha.106.663237.
- Dina C., Bouatia-Naji N., Tucker N., Delling F.N., Toomer K., Durst R., Perrocheau M., Fernandez-Friera L., Solis J., Le Tourneau T., Chen M.H., Probst V., Bosse Y., Pibarot P., Zelenika D., Lathrop M., Hercberg S., Roussel R., Benjamin E.J., Bonnet F., Lo S.H., Dolmatova E., Simonet F., Lecointe S., Kyndt F., Redon R., Le Marec H., Froguel P., Ellinor P.T., Vasan R.S., Bruneval P., Markwald R.R., Norris R.A., Milan D.J., Slaugenhaupt S.A., Levine R.A., Schott J.J., Hagege A.A., Jeunemaitre X. Genetic association analyses highlight biological pathways underlying mitral valve prolapse. Nat Genet 2015; 47(10): 1206–1211, https://doi.org/10.1038/ng.3383.
- Siordia J.A. Current discoveries and interventions for barlow’s disease. Curr Cardiol Rep 2016; 18(8): 73, https://doi.org/10.1007/s11886-016-0754-5.