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. Author manuscript; available in PMC: 2009 Feb 17.
Published in final edited form as: JACC Cardiovasc Imaging. 2008 May;1(3):304–306. doi: 10.1016/j.jcmg.2008.04.003

MITRAL VALVE PROLAPSE: A DEEPER LOOK

Robert A Levine 1, Ronen Durst 1
PMCID: PMC2643371  NIHMSID: NIHMS82383  PMID: 19225572

Two myths have been prevalent regarding heart valve disease: that the valves are simply mechanical flaps, and that the importance to the patient of regurgitation in particular relates almost entirely to ventricular function only. The article in this issue of the Journal by Han et al. provides a more comprehensive picture that counterbalances these concepts.1

The authors set out to characterize mitral valve prolapse (MVP) by cardiovascular magnetic resonance (CMR) imaging, and found it could match the diagnostic sensitivity and specificity of transthoracic echocardiography. The three-dimensional CMR image can be sectioned in a parallel series of long-axis views to analyze segmental anatomy and provide a “road map” for repair.2 There are several messages from this study pertinent to cardiovascular imaging: 1) Understanding the basic principles of image acquisition affects interpretation of results. CMR provides a blunted measure of leaflet thickness and, to a lesser extent, leaflet length, likely caused by a partial volume effect from surrounding blood pool. 2) Three-dimensional acquisitions achieve their maximum value by providing not only 3D images but also spatially registered 2D views to explore segmental anatomy, as displayed admirably by O’Gara et al. for 3D transespophageal echocardiography in the March issue of the Journal.3 Three-dimensional acquisition has therefore contributed in many ways to our understanding of mitral valve disease, including improved diagnostic specificity, inspiration for annuloplasty ring design, and analysis of valve mechanics based on demonstrating the three-dimensional saddle-shape of the valve.4-10 A caveat is that the most useful segmental anatomy may be best derived from non-parallel views transecting the mitral coaptation line to intersect opposing central, medial, and lateral segments of both leaflets derived from a 3D scout view.3,11

The greatest novelty comes from the deeper and more profound look CMR provides into the biology of the valve and its linked myocardium, made possible in part by a technological advance, the improved spatial resolution provided by three-dimensional acquisition of images with delayed gadolinium (Gd) enhancement. Such enhancement occurs when the kinetics of Gd excretion is different in two adjacent compartments, so that over time, one compartment enhances more than the other. This has been a powerful tool to delineate infarcted and scarred myocardium, which excrete Gd slower than viable tissue.12-15 Han et al. report frequently delayed Gd enhancement in both the mitral leaflets themselves and the papillary muscle (PM) tips in patients with MVP and not in controls.1 This complementary and unique tissue characterization requires further exploration, but indicates biological differences in both the valve tissue and the myocardium directly linked to it.

Delayed Gd enhancement reinforces understanding of the myxomatous valve as one in which the processes of altered cell and extracellular matrix biology, normally quiescent in adult life, are reactivated.16,17 Noninvasive imaging may therefore be of value in confirming such intrinsic changes, with potential for strengthening phenotypic characterization in genetic studies of familial MVP18-21 and monitoring response to therapies targeting hyperactive growth factor stimulation.22,23 The altered PM tip appearance in patients with MVP may provide insight into the intriguing question of ventricular arrhythmias in MVP and the occurrence of sudden death with elongated leaflets alone, even in the absence of important MR or heart failiure.24-27 The pathology literature also includes evidence for localized ventricular changes in patients with MVP.28-30 We can speculate that the PM is altered by repetitive traction exerted by the prolapsing leaflets (Figure),31 which has been shown experimentally to lower the threshold for lethal arrhythmias.32 Mitral valve disease is therefore not a bystander but a primary actor in the entire clinical picture. We have recently recognized that mitral regurgitation (MR) plays an independent role in altering the biology of the remodeling ventricle following myocardial infarction,33,34 and strongly determines prognosis in the non-ischemic setting as well.35,36 This CMR study suggests a direct impact of the prolapsing valve on a ventricular structure. PM damage may in turn exacerbate prolapse in a vicious cycle, potentially explaining the frequently observed but as yet unexplained mid- to-late systolic onset of leaflet displacement, characteristic of the yield stress phenomenon in mechanical engineering in response to a critical threshold overcoming a counteracting force (Ajit P. Yoganathan, PhD, personal communication).

Figure 1.

Figure 1

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Long-axis schematic of the left ventricle (LV), indicating linked parallel motion of the prolapsing mitral leaflets and papillary muscle (PM) tip.

In summary, the study of Han et al.1 reinforces a new way to think of standardizing cardiovascular imaging based on exploring 3D images in registered 2D views. It provides a deeper and more profound look into valve biology and the impact of valvular heart disease on the myocardium to which it is inseparably linked, with the potential to monitor, understand, and ultimately treat underlying pathophysiologic mechanisms.

Acknowledgments

Supported in part by the Leducq Foundation Transatlantic Network of Excellence in Mitral Valve Disease, and by NIH grants K24 HL67434 and R01 HL38176. We thank Shirley Sims for her expert editorial assistance and Mark Handschumacher for the figure.

Footnotes

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References

  • 1.Han Y, Peters DC, Salton CJ, Bzymek D, Nezafat R, Goddu B, Kissinger KK, Zimetbaum PJ, Manning WJ, Yeon SB. Cardiovascular magnetic resonance characterization of mitral valve prolapse. J Am Coll Cardiol Imaging. 2008;1 doi: 10.1016/j.jcmg.2008.01.013. [DOI] [PubMed] [Google Scholar]
  • 2.Foster GP, Isselbacher EM, Rose GA, Torchiana DF, Akins CW, Picard MH. Accurate localization of mitral regurgitant defects using multiplane transesophageal echocardiography. Annals of Thoracic Surgery. 1998;65:1025. doi: 10.1016/s0003-4975(98)00084-8. [DOI] [PubMed] [Google Scholar]
  • 3.O’Gara P, Sugeng L, Lang R, Sarano M, Hung J, Raman S, Fischer G, Carabello B, Adams D, Vannan M. The role of imaging in chronic degenerative mitral regurgitation. J Am Coll Cardiol Imaging. 2008;1:221–37. doi: 10.1016/j.jcmg.2008.01.011. [DOI] [PubMed] [Google Scholar]
  • 4.Levine RA, Triulzi MO, Harrigan P, Weyman AE. The relationship of mitral annular shape to the diagnosis of mitral valve prolapse. Circulation. 1987;75:756–67. doi: 10.1161/01.cir.75.4.756. [DOI] [PubMed] [Google Scholar]
  • 5.Levine RA, Handschumacher MD, Sanfilippo AJ, Hagege AA, Harrigan P, Marshall JE, Weyman AE. Three-dimensional echocardiographic reconstruction of the mitral valve, with implications for the diagnosis of mitral valve prolapse. Circulation. 1989;80:589–98. doi: 10.1161/01.cir.80.3.589. [DOI] [PubMed] [Google Scholar]
  • 6.Tibayan FA, Rodriguez F, Langer F, Zasio MK, Bailey L, Liang D, Daughters GT, Ingels NB, Jr, Miller DC. Annular remodeling in chronic ischemic mitral regurgitation: Ring selection implications. Ann Thorac Surg. 2003;76:1549–54. doi: 10.1016/s0003-4975(03)00880-4. [DOI] [PubMed] [Google Scholar]
  • 7.Gorman JH, 3rd, Jackson BM, Enomoto Y, Gorman RC. The effect of regional ischemia on mitral valve annular saddle shape. Ann Thorac Surg. 2004;77:544–8. doi: 10.1016/S0003-4975(03)01354-7. [DOI] [PubMed] [Google Scholar]
  • 8.Watanabe N, Ogasawara Y, Yamaura Y, Wada N, Kawamoto T, Toyota E, Akasaka T, Yoshida K. Mitral annulus flattens in ischemic mitral regurgitation: geometric differences between inferior and anterior myocardial infarction: a real-time 3-dimensional echocardiographic study. Circulation. 2005;112(Suppl):I458–62. doi: 10.1161/CIRCULATIONAHA.104.524595. [DOI] [PubMed] [Google Scholar]
  • 9.Jimenez JH, Liou SW, Padala M, He Z, Sacks M, Gorman RC, Gorman JH, 3rd, Yoganathan AP. A saddle-shaped annulus reduces systolic strain on the central region of the mitral valve anterior leaflet. J Thorac Cardiovasc Surg. 2007;134:1562–68. doi: 10.1016/j.jtcvs.2007.08.037. [DOI] [PubMed] [Google Scholar]
  • 10.Salgo IS, Gorman JH, 3rd, Gorman RC, Jackson BM, Bowen FW, Plappert T, St John Sutton MG, Edmunds LH., Jr Effect of annular shape on leaflet curvature in reducing mitral leaflet stress. Circulation. 2002;106:711–17. doi: 10.1161/01.cir.0000025426.39426.83. [DOI] [PubMed] [Google Scholar]
  • 11.Carpentier A. Cardiac valve surgery: the “French correction”. J Thorac Cardiovasc Surg. 1983;86:323–37. [PubMed] [Google Scholar]
  • 12.Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, Bundy J, Finn JP, Klocke FJ, Judd RM. Relationship of MRI Delayed Contrast Enhancement to Irreversible Injury, Infarct Age, and Contractile Function. Circulation. 1999;100:1992–2002. doi: 10.1161/01.cir.100.19.1992. [DOI] [PubMed] [Google Scholar]
  • 13.Kim RJ, Wu E, Rafael A, Chen EL, Parker MA, Simonetti O, Klocke FJ, Bonow RO, Judd RM. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med. 2000;343:1445–53. doi: 10.1056/NEJM200011163432003. [DOI] [PubMed] [Google Scholar]
  • 14.Lipton MJ, Bogaert J, Boxt LM, Reba RC. Imaging of ischemic heart disease. Eur Radiol. 2002;12:1061–80. doi: 10.1007/s003300101131. [DOI] [PubMed] [Google Scholar]
  • 15.Rozenshtein A, Boxt LM. Computed tomography and magnetic resonance imaging of patients with valvular heart disease. J Thorac Imaging. 2000;15:252–64. doi: 10.1097/00005382-200010000-00005. [DOI] [PubMed] [Google Scholar]
  • 16.Rabkin E, Aikawa M, Stone JR, Fukumoto Y, Libby P, Schoen FJ. Activated interstitial myofibroblasts express catabolic enzymes and mediate matrix remodeling in myxomatous heart valves. Circulation. 2001;104:2525–32. doi: 10.1161/hc4601.099489. [DOI] [PubMed] [Google Scholar]
  • 17.Rabkin-Aikawa E, Farber M, Aikawa M, Schoen FJ. Dynamic and reversible changes of interstitial cell phenotype during remodeling of cardiac valves. J Heart Valve Dis. 2004;13:841–47. [PubMed] [Google Scholar]
  • 18.Disse S, Abergel E, Berrebi A, Houot AM, Le Heuzey JY, 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;65:1242–51. doi: 10.1086/302624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Freed LA, Acierno JS, Jr, Dai D, Leyne M, Marshall JE, Nesta F, Levine RA, Slaugenhaupt SA. A locus for autosomal dominant mitral valve prolapse on chromosome 11p15.4. Am J Hum Genet. 2003;72:1551–59. doi: 10.1086/375452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Nesta F, Leyne M, Yosefy C, Simpson C, Dai D, Marshall JE, Hung J, Slaugenhaupt SA, Levine RA. New locus for autosomal dominant mitral valve prolapse on chromosome 13: Clinical insights from genetic studies. Circulation. 2005;112:2022–30. doi: 10.1161/CIRCULATIONAHA.104.516930. [DOI] [PubMed] [Google Scholar]
  • 21.Kyndt F, Gueffet JP, Probst V, Jaafar P, Legendre A, Le Bouffant F, Toquet C, Roy E, McGregor L, Lynch SA, Newbury-Ecob R, Tran V, Young I, Trochu JN, Le Marec H, Schott JJ. Mutations in the gene encoding filamin A as a cause for familial cardiac valvular dystrophy. Circulation. 2007;115:40–49. doi: 10.1161/CIRCULATIONAHA.106.622621. [DOI] [PubMed] [Google Scholar]
  • 22.Ng CM, Cheng A, Myers LA, Martinez-Murillo F, Jie C, Bedja D, Gabrielson KL, Hausladen JMW, Mecham RP, Judge DP, Dietz HC. TGF-ß-dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome. J Clin Invest. 2004;114:1586–92. doi: 10.1172/JCI22715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. 2006;312:117–21. doi: 10.1126/science.1124287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Kligfield P, Levy D, Devereux RB, Savage DD. Arrhythmias and sudden death in mitral valve prolapse. Am Heart J. 1987;113:1298–307. doi: 10.1016/0002-8703(87)90958-6. [DOI] [PubMed] [Google Scholar]
  • 25.Duren DR, Becker AE, Dunning AJ. Long-term follow-up of idiopathic mitral valve prolapse in 300 patients: A prospective study. J Am Coll Cardiol. 1988;11:42–47. doi: 10.1016/0735-1097(88)90164-7. [DOI] [PubMed] [Google Scholar]
  • 26.Grigioni F, Enriquez-Sarano M, Ling LH, Bailey KR, Seward JB, Tajik AJ, Frye RL. Sudden death in mitral regurgitation due to flail leaflet. J Am Coll Cardiol. 1999;34:2078–85. doi: 10.1016/s0735-1097(99)00474-x. [DOI] [PubMed] [Google Scholar]
  • 27.Farb A, Tang AL, Atkinson JB, McCarthy WF, Virmani R. Comparison of cardiac findings in patients with mitral valve prolapse who die suddenly to those who have congestive heart failure from mitral regurgitation and to those with fatal noncardiac conditions. Am J Cardiol. 1992;70:234–39. doi: 10.1016/0002-9149(92)91281-8. [DOI] [PubMed] [Google Scholar]
  • 28.Morales AR, Romanelli R, Boucek RJ, Tate LG, Alvarez RT, Davis JT. Myxoid heart disease: An assessment of extravalvular cardiac pathology in severe mitral valve prolapse. Hum Pathol. 1992;23:129–37. doi: 10.1016/0046-8177(92)90233-s. [DOI] [PubMed] [Google Scholar]
  • 29.Dollar AL, Roberts WC. Morphologic comparison of patients with mitral valve prolapse who died suddenly with patients who died from severe valvular dysfunction or other conditions. J Am Coll Cardiol. 1991;17:921–31. doi: 10.1016/0735-1097(91)90875-a. [DOI] [PubMed] [Google Scholar]
  • 30.La Vecchia L, Ometto R, Centofante P, et al. Arrhythmic profile, ventricular function, and histomorphometric findings in patients with idiopathic ventricular tachycardia and mitral valve prolapse: Clinical and prognostic evaluation. Clin Cardiol. 1998;21:731–35. doi: 10.1002/clc.4960211007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Sanfilippo AJ, Harrigan P, Popovic AD, Weyman AE, Levine RA. Papillary muscle traction in mitral valve prolapse: Quantitation by two-dimensional echocardiography. J Am Coll Cardiol. 1992;19:564–71. doi: 10.1016/s0735-1097(10)80274-8. [DOI] [PubMed] [Google Scholar]
  • 32.Gornick CC, Tobler HG, Pritzker MC, Tuna IC, Almquist A, Benditt DG. Electro-physiologic effects of papillary muscle traction in the intact heart. Circulation. 1986;73:1013–21. doi: 10.1161/01.cir.73.5.1013. [DOI] [PubMed] [Google Scholar]
  • 33.Beeri R, Yosefy C, Guerrero JL, Nesta F, Abedat S, del Monte F, Handschumacher MD, Stroud R, Sullivan S, Pugatsch T, Gilon D, Vlahakes GJ, Spinale FG, Hajjar RJ, Levine RA. Mitral regurgitation augments post-myocardial infarction remodeling: Failure of hypertrophic compensation. J Am Coll Cardiol. 2008;51:476–86. doi: 10.1016/j.jacc.2007.07.093. [DOI] [PubMed] [Google Scholar]
  • 34.Beeri R, Yosefy C, Guerrero JL, Abedat S, Handschumacher M, Stroud R, Sullivan S, Chaput M, Gilon D, Vlahakes G, Spinale F, Hajjar RJ, Levine RA. Early repair of moderate ischemic mitral regurgitation reverses left ventricular remodeling: A functional and molecular study. Circulation. 2007;116:I–288. doi: 10.1161/CIRCULATIONAHA.106.681114. [DOI] [PubMed] [Google Scholar]
  • 35.Ling LH, Enriquez-Sarano M, Seward JB, Tajik AJ, Schaff HV, Bailey KR, Frye RL. Clinical outcome of mitral regurgitation due to flail leaflet. N Engl J Med. 1996;335:1417–23. doi: 10.1056/NEJM199611073351902. [DOI] [PubMed] [Google Scholar]
  • 36.Enriquez-Sarano M, Avierinos JF, Messika-Zeitoun D, Detaint D, Capps M, Nkomo V, Scott C, Schaff HV, Tajik AJ. Quantitative determinants of the outcome of asymptomatic mitral regurgitation. N Engl J Med. 2005;352:875–83. doi: 10.1056/NEJMoa041451. [DOI] [PubMed] [Google Scholar]

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