Mitral Valve Insufficiency in the Context of Barlow's Disease: A Contemporary Review of Etiopathogenesis, Multimodal Assessment, and Evolving Management Paradigms
Main Article Content
Abstract
Barlow's disease represents a distinct and complex morphological variant of degenerative mitral valve disease, characterized by a unique pathophysiological substrate leading to severe mitral insufficiency. This extensive review provides a comprehensive synthesis of contemporary understanding, emphasizing the transition from a purely anatomical curiosity to a clinically nuanced entity with significant implications for management. The etiopathogenesis is explored through the lens of advanced histopathological and molecular studies, highlighting the interplay between myxomatous degeneration, abnormal collagen metabolism, and genetic predispositions beyond the classic FBN1 and FLNA associations. A critical appraisal of current multimodal imaging is undertaken, detailing the pivotal role of high-resolution three-dimensional echocardiography in delineating the hallmark bileaflet prolapse with multisegment involvement, excessive leaflet tissue, and annular disjunction. Cardiac magnetic resonance and computed tomography are discussed for their growing utility in quantifying regurgitation volume, assessing ventricular remodeling, and informing surgical planning. The core of this review contrasts traditional surgical approaches, predominantly involving complex valve repair with extensive leaflet resection and annuloplasty, against emerging reparative techniques and the evolving, albeit controversial, potential of transcatheter edge-to-edge repair in select, high-risk cohorts with suitable anatomy. Long-term outcome data and persistent challenges, including repair durability, arrhythmic risk, and the management of asymptomatic severe regurgitation, are examined. This synthesis concludes by identifying critical knowledge gaps and future directions, particularly the need for refined risk stratification models integrating quantitative imaging biomarkers and genetics, and the call for dedicated randomized trials to guide therapeutic escalation in this heterogeneous patient population.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
I. Silbiger, J.J. Mechanistic Insights into Ischemic Mitral Regurgitation: Echocardiographic and Surgical Implications. J. Am. Soc. Echocardiogr. 2011, 24, 707–719.
II. Zoghbi, W.A.; Levine, R.A.; Flachskampf, F.; Grayburn, P.; Gillam, L.; Leipsic, J.; Thomas, J.D.; Kwong, R.Y.; Vandervoort, P.; Chandrashekhar, Y. Atrial Functional Mitral Regurgitation. JACC Cardiovasc. Imaging 2022, 15, 1870–1882.
III. Farhan, S.; Silbiger, J.J.; Halperin, J.L.; Zhang, L.; Dukkipati, S.R.; Vogel, B.; Kini, A.; Sharma, S.; Lerakis, S. Pathophysiology, Echocardiographic Diagnosis, and Treatment of Atrial Functional Mitral Regurgitation. J. Am. Coll. Cardiol. 2022, 80, 2314–2330.
IV. Okamoto, C.; Okada, A.; Nishimura, K.; Moriuchi, K.; Amano, M.; Takahama, H.; Amaki, M.; Hasegawa, T.; Kanzaki, H.; Fujita, T.; et al. Prognostic comparison of atrial and ventricular functional mitral regurgitation. Open Heart 2021, 8, e001574.
V. Coffey, S.; Roberts-Thomson, R.; Brown, A.; Carapetis, J.; Chen, M.; Enriquez-Sarano, M.; Zühlke, L.; Prendergast, B.D. Global epidemiology of valvular heart disease. Nat. Rev. Cardiol. 2021, 18, 853–864.
VI. So, K.C.-Y.; Yap, J.; Song, G.-Y.; Poon, K.; Sung, S.H.; Chandavimol, M.; Hayashida, K.; Park, D.-W.; Ewe, S.-H.; Chen, M.; et al. Epidemiology of Valvular Heart Disease in Asia Pacific Region. JACC Asia 2025, 5, 718–743.
VII. Lazam, S.; Vanoverschelde, J.L.; Tribouilloy, C.; Grigioni, F.; Suri, R.M.; Avierinos, J.F.; de Meester, C.; Barbieri, A.; Rusinaru, D.; Russo, A.; et al. Twenty-Year Outcome After Mitral Repair Versus Replacement for Severe Degenerative Mitral Regurgitation. Circulation 2017, 135, 410–422.
VIII. Acker, M.A.; Parides, M.K.; Perrault, L.P.; Moskowitz, A.J.; Gelijns, A.C.; Voisine, P.; Smith, P.K.; Hung, J.W.; Blackstone, E.H.; Puskas, J.D.; et al. Mitral-Valve Repair versus Replacement for Severe Ischemic Mitral Regurgitation. N. Engl. J. Med.2014, 370, 23–32.
IX. Davierwala, P.M.; Seeburger, J.; Pfannmueller, B.; Garbade, J.; Misfeld, M.; Borger, M.A.; Mohr, F.W. Minimally invasive mitral valve surgery: “The Leipzig experience”. Ann. Cardiothorac. Surg. 2013, 2, 744–750.
X. Feldman, T.; Wasserman, H.S.; Herrmann, H.C.; Gray, W.; Block, P.C.; Whitlow, P.; St Goar, F.; Rodriguez, L.; Silvestry, F.; Schwartz, A.; et al. Percutaneous Mitral Valve Repair Using the Edge-to-Edge Technique. J. Am. Coll. Cardiol. 2005, 46, 2134–2140.
XI. Feldman, T.; Foster, E.; Glower, D.D.; Kar, S.; Rinaldi, M.J.; Fail, P.S.; Smalling, R.W.; Siegel, R.; Rose, G.A.; Engeron, E.; et al. Percutaneous Repair or Surgery for Mitral Regurgitation. N. Engl. J. Med. 2011, 364, 1395–1406.
XII. Stone, G.W.; Abraham, W.T.; Lindenfeld, J.; Kar, S.; Grayburn, P.A.; Lim, D.S.; Mishell, J.M.; Whisenant, B.; Rinaldi, M.; Kapadia, S.R.; et al. Five-Year Follow-up after Transcatheter Repair of Secondary Mitral Regurgitation. N. Engl. J. Med.2023, 388, 2037–2048
XIII. Praz, F.; Borger, M.A.; Lanz, J.; Marin-Cuartas, M.; Abreu, A.; Adamo, M.; Ajmone Marsan, N.; Barili, F.; Bonaros, N.; Cosyns, B.; et al. 2025 ESC/EACTS Guidelines for the management of valvular heart disease. Eur. J. Cardio-Thorac. Surg. 2025, 67, ezaf276.
XIV. Yousef, S.; Arnaoutakis, G.J.; Gada, H.; Smith, A.J.C.; Sanon, S.; Sultan, I. Transcatheter mitral valve therapies: State of the art. J. Card. Surg. 2022, 37, 225–233.
XV. Lancellotti, P.; Pibarot, P.; Chambers, J.; La Canna, G.; Pepi, M.; Dulgheru, R.; Dweck, M.; Delgado, V.; Garbi, M.; Vannan, M.A.; et al. Multi-modality imaging assessment of native valvular regurgitation: An EACVI and ESC council of valvular heart disease position paper. Eur. Heart J. Cardiovasc. Imaging 2022, 23, E171–232.
XVI. Agricola, E.; Ancona, F.; Bartel, T.; Brochet, E.; Dweck, M.; Faletra, F.; Lancellotti, P.; Mahmoud-Elsayed, H.; Marsan, N.A.; Maurovich-Hovart, P.; et al. Multimodality imaging for patient selection, procedural guidance, and follow-up of transcatheter interventions for structural heart disease: A consensus document of the EACVI Task Force on Interventional Cardiovascular Imaging: Part 1: Access routes, transcatheter aortic valve implantation, and transcatheter mitral valve interventions. Eur. Heart J. Cardiovasc. Imaging 2023, 24, e209–e268.
XVII. Antonides, C.F.J.; Mack, M.J.; Kappetein, A.P. Approaches to the Role of The Heart Team in Therapeutic Decision Making for Heart Valve Disease. Struct. Heart 2017, 1, 249–255.
XVIII. Lio, A.; Loreni, F.; Miceli, A.; Wiedemann, D. Editorial: Evolution of mitral valve disease treatment: From surgery to transcatheter therapy. Front. Cardiovasc. Med. 2024, 11, 1369596.
XIX. Little, S.H. Interventional Echocardiography: The Emergence of a New Imaging Specialty. J. Am. Soc. Echocardiogr.2023, 36, A13–A14.
XX. Carpentier, A. Cardiac valve surgery-the “French correction”. J. Thorac. Cardiovasc. Surg. 1983, 86, 323–337.
XXI. Dreyfus, G.D.; Dulguerov, F.; Marcacci, C.; Haley, S.R.; Gkouma, A.; Dommerc, C.; Albert, A. “Respect when you can, resect when you should”: A realistic approach to posterior leaflet mitral valve repair. J. Thorac. Cardiovasc. Surg. 2018, 156, 1856–1866.e3.
XXII. van Wijngaarden, A.L.; Tomšič, A.; Mertens, B.J.A.; Fortuni, F.; Delgado, V.; Bax, J.J.; Klautz, R.J.M.; Marsan, N.A.; Palmen, M. Mitral valve repair for isolated posterior mitral valve leaflet prolapse: The effect of respect and resect techniques on left ventricular function. J. Thorac. Cardiovasc. Surg. 2022, 164, 1488–1497.e3.
XXIII. Wagner, C.M.; Brescia, A.A.; Watt, T.M.F.; Bergquist, C.; Rosenbloom, L.M.; Ceniza, N.N.; Markey, G.E.; Ailawadi, G.; Romano, M.A.; Bolling, S.F. Surgical strategy and outcomes for atrial functional mitral regurgitation: All functional mitral regurgitation is not the same! J. Thorac. Cardiovasc. Surg. 2024, 167, 647–655.
XXIV. Moore, R.A.; Wierup, P.; Tappuni, S.; Houghtaling, P.L.; Burns, D.J.P.; Chemtob, R.; Blackstone, E.H.; Svensson, L.G.; Gillinov, A.M. Reoperation after early and late failure of mitral valve repair for degenerative disease. J. Thorac. Cardiovasc. Surg. 2024, 167, 1251–1262.e8.