Mitral valve regurgitation: a disease with a wide spectrum of therapeutic options

Abstract

Over the past two decades interest in mitral valve regurgitation has increased as a result of the development of new technologies that have expanded the number of patients who can potentially benefit from mitral regurgitation treatments. To develop new devices for the treatment of mitral regurgitation, the focus has been placed on the functional anatomy and pathophysiology of the mitral valve, with the use of the most advanced methods of cardiac imaging that allow the best visualization of the mitral valve and a perfect understanding of the complexity of a specific disease. Mitral regurgitation is still underdiagnosed and undertreated in a substantial number of patients who have poor survival. Therefore, the priority should be to identify and treat these patients to increase their survival and quality of life. To achieve this goal, general physicians and cardiologists must be aware of all the treatment options that are currently available in dedicated centres of excellence. Patients referred to these centres can benefit from a tailored heart team-based approach. The aim of this Review is to analyse the basic principles of mitral regurgitation, discussing new concepts on the pathophysiology of the mitral valve that have been developed to facilitate the selection of patients for transcatheter procedures. We also describe the indications and timing of treatment, contemporary surgical and transcatheter techniques and the heart team approach, and highlight the need for centres of excellence.

Key points

  • Mitral regurgitation has generated growing interest over the past 20 years; nevertheless, mitral regurgitation is still underdiagnosed and undertreated in a large number of patients who have poor survival and quality of life.

  • Given the different aetiologies, lesions and pathophysiology underlying mitral regurgitation, a proper understanding of the characteristics of the disease is mandatory to plan the correct treatment.

  • The availability of novel and sophisticated multimodality imaging allows an accurate evaluation of the mitral valve complex, guiding the diagnosis, timing of intervention and treatment with surgical techniques or percutaneous technologies.

  • Surgical mitral valve repair is the gold-standard treatment in severe primary (mainly degenerative) mitral regurgitation, with excellent durability and restoration of normal life expectancy and good quality of life.

  • In secondary mitral regurgitation, the heart team should identify patients who are likely to benefit from treatment, given that a benefit has been demonstrated only in highly selected patients.

  • In the current era, given the wide range of imaging modalities and therapeutic options, offering each patient the most appropriate and tailored approach according to the individual aetiology, pathophysiology and risk profile is essential.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Secondary mitral regurgitation and chronic heart failure: a vicious cycle.
Fig. 2: Mitral valve morphologies and mitral regurgitation mechanisms.
Fig. 3: 3D echocardiography of the mitral valve.
Fig. 4: Advanced echocardiography approaches for mitral valve assessment.
Fig. 5: Echocardiography–fluoroscopy fusion imaging.
Fig. 6: Cardiac CT analysis of the mitral valve.
Fig. 7: Transcatheter mitral valve technologies.
Fig. 8: The challenge of choice in the management of mitral regurgitation.

References

  1. 1.

    Dziadzko, V. et al. Causes and mechanisms of isolated mitral regurgitation in the community: clinical context and outcome. Eur. Heart J. 40, 2194–2202 (2019).

    PubMed  Google Scholar 

  2. 2.

    Delling, F. N. et al. Evolution of mitral valve prolapse: insights from the Framingham Heart Study. Circulation 133, 1688–1695 (2016).

    PubMed  PubMed Central  Google Scholar 

  3. 3.

    Nkomo, V. T. et al. Burden of valvular heart diseases: a population-based study. Lancet 368, 1005–1011 (2006).

    PubMed  Google Scholar 

  4. 4.

    D’Arcy, J. L. et al. Large-scale community echocardiographic screening reveals a major burden of undiagnosed valvular heart disease in older people: the OxVALVE Population Cohort Study. Eur. Heart J. 37, 3515–3522 (2016).

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Mirabel, M. et al. What are the characteristics of patients with severe, symptomatic, mitral regurgitation who are denied surgery? Eur. Heart J. 28, 1358–1365 (2007).

    PubMed  Google Scholar 

  6. 6.

    Dal-Bianco, J. P. & Levine, R. A. Anatomy of the mitral valve apparatus: role of 2D and 3D echocardiography. Cardiol. Clin. 31, 151–164 (2013).

    PubMed  Google Scholar 

  7. 7.

    Maréchaux, S. et al. Functional anatomy and pathophysiologic principles in mitral regurgitation: non-invasive assessment. Prog. Cardiovasc. Dis. 60, 289–304 (2017).

    PubMed  Google Scholar 

  8. 8.

    Weir-McCall, J. R. et al. Mitral valve imaging with CT: relationship with transcatheter mitral valve interventions. Radiology 288, 638–655 (2018).

    PubMed  Google Scholar 

  9. 9.

    Prendergast, B. D. et al. Transcatheter heart valve interventions: where are we? Where are we going? Eur. Heart J. 40, 422–440 (2019).

    PubMed  Google Scholar 

  10. 10.

    Silbiger, J. J. & Bazaz, R. Contemporary insights into the functional anatomy of the mitral valve. Am. Heart J. 158, 887–895 (2009).

    PubMed  Google Scholar 

  11. 11.

    Carpentier, A. Cardiac valve surgery — the ‘French correction’. J. Thorac. Cardiovasc. Surg. 86, 323–337 (1983).

    CAS  PubMed  Google Scholar 

  12. 12.

    Anyanwu, A. C. & Adams, D. H. Etiologic classification of degenerative mitral valve disease: Barlow’s disease and fibroelastic deficiency. Semin. Thorac. Cardiovasc. Surg. 19, 90–96 (2007).

    PubMed  Google Scholar 

  13. 13.

    Enriquez-Sarano, M., Akins, C. W. & Vahanian, A. Mitral regurgitation. Lancet 373, 1382–1394 (2009).

    PubMed  Google Scholar 

  14. 14.

    Carpentier, A., Lacour-Gayet, F. & Camilleri, J. Fibroelastic dysplasia of the mitral valve: an anatomical and clinical entity. Circulation 3, 307 (1982).

    Google Scholar 

  15. 15.

    Barlow, J. B. & Pocock, W. A. The significance of late systolic murmurs and mid-late systolic clicks. Md. State Med. J. 12, 76–77 (1963).

    CAS  PubMed  Google Scholar 

  16. 16.

    Adams, D. H., Anyanwu, A. C., Sugeng, L. & Lang, R. M. Degenerative mitral valve regurgitation: surgical echocardiography. Curr. Cardiol. Rep. 10, 226–232 (2008).

    PubMed  Google Scholar 

  17. 17.

    Mills, W. R. et al. Biomechanical and echocardiographic characterization of flail mitral leaflet due to myxomatous disease: further evidence for early surgical intervention. Am. Heart J. 148, 144–150 (2004).

    PubMed  Google Scholar 

  18. 18.

    Abramowitz, Y., Jilaihawi, H., Chakravarty, T., Mack, M. J. & Makkar, R. R. Mitral annulus calcification. J. Am. Coll. Cardiol. 66, 1934–1941 (2015).

    PubMed  Google Scholar 

  19. 19.

    Remenyi, B., Carapetis, J., Wyber, R., Taubert, K. & Mayosi, B. M. Position statement of the World Heart Federation on the prevention and control of rheumatic heart disease. Nat. Rev. Cardiol. 10, 284–292 (2013).

    CAS  PubMed  Google Scholar 

  20. 20.

    Andell, P. et al. Epidemiology of valvular heart disease in a Swedish nationwide hospital-based register study. Heart 103, 1696–1703 (2017).

    PubMed  PubMed Central  Google Scholar 

  21. 21.

    Carabello, B. A. Mitral regurgitation: basic pathophysiologic principles. Mod. Concepts Cardiovasc. Dis. 57, 53–58 (1988).

    Google Scholar 

  22. 22.

    West, J. B. & Mathieu-Costello, O. Vulnerability of pulmonary capillaries in heart disease. Circulation 92, 622–631 (1995).

    CAS  PubMed  Google Scholar 

  23. 23.

    Rich, S. & Rabinovitch, M. Diagnosis and treatment of secondary (non-category 1) pulmonary hypertension. Circulation 118, 2190–2199 (2008).

    PubMed  Google Scholar 

  24. 24.

    Champion, H. C., Michelakis, E. D. & Hassoun, P. M. Comprehensive invasive and noninvasive approach to the right ventricle-pulmonary circulation unit: state of the art and clinical and research implications. Circulation 120, 992–1007 (2009).

    PubMed  Google Scholar 

  25. 25.

    Gaasch, W. H. & Meyer, T. E. Left ventricular response to mitral regurgitation: implications for management. Circulation 118, 2298–2303 (2008).

    PubMed  Google Scholar 

  26. 26.

    Bennett, S. et al. Mitral annular disjunction: a systematic review of the literature. Echocardiography. 36, 1549–1558 (2019).

    PubMed  Google Scholar 

  27. 27.

    Perazzolo Marra, M. et al. Morphofunctional abnormalities of mitral annulus and arrhythmic mitral valve prolapse. Circ. Cardiovasc. Imaging. 9, e005030 (2016).

    PubMed  PubMed Central  Google Scholar 

  28. 28.

    Basso, C. et al. Arrhythmic mitral valve prolapse and sudden cardiac death. Circulation 132, 556–566 (2015). This paper provides specific data on patients with mitral valve prolapse and sudden cardiac death from a very large cardiology pathology registry.

    PubMed  Google Scholar 

  29. 29.

    Dejgaard, L. A. et al. The mitral annulus disjunction arrhythmic syndrome. J. Am. Coll. Cardiol. 72, 1600–1609 (2018).

    PubMed  Google Scholar 

  30. 30.

    Eriksson, M. J. et al. Mitral annular disjunction in advanced myxomatous mitral valve disease: echocardiographic detection and surgical correction. J. Am. Soc. Echocardiogr. 18, 1014–1022 (2005).

    PubMed  Google Scholar 

  31. 31.

    Essayagh, B. et al. Usefulness of 3-Tesla cardiac magnetic resonance to detect mitral annular disjunction in patients with mitral valve prolapse. Am. J. Cardiol. 124, 1725–1730 (2019).

    PubMed  Google Scholar 

  32. 32.

    Asgar, A. W., Mack, M. J. & Stone, G. W. Secondary mitral regurgitation in heart failure: pathophysiology, prognosis, and therapeutic considerations. J. Am. Coll. Cardiol. 65, 1231–1248 (2015).

    PubMed  Google Scholar 

  33. 33.

    Gertz, Z. M. et al. Evidence of atrial functional mitral regurgitation due to atrial fibrillation: reversal with arrhythmia control. J. Am. Coll. Cardiol. 58, 1474–1481 (2011).

    PubMed  Google Scholar 

  34. 34.

    Sherrid, M. V., Balaram, S., Kim, B., Axel, L. & Swistel, D. G. The mitral valve in obstructive hypertrophic cardiomyopathy: a test in context. J. Am. Coll. Cardiol. 67, 1846–1858 (2016). An in-depth review discussing the involvement of the mitral valve in the context of obstructive hypertrophic cardiomyopathy.

    PubMed  Google Scholar 

  35. 35.

    Rossi, A. et al. Independent prognostic value of functional mitral regurgitation in patients with heart failure. A quantitative analysis of 1256 patients with ischaemic and non-ischaemic dilated cardiomyopathy. Heart 97, 1675–1680 (2011).

    PubMed  Google Scholar 

  36. 36.

    Delgado, V. & Bax, J. J. Atrial functional mitral regurgitation: from mitral annulus dilatation to insufficient leaflet remodeling. Circ. Cardiovasc. Imaging. 10, e006239 (2017).

    PubMed  Google Scholar 

  37. 37.

    Hagège, A. A. et al. The mitral valve in hypertrophic cardiomyopathy: old versus new concepts. J. Cardiovasc. Transl Res. 4, 757–766 (2011).

    PubMed  Google Scholar 

  38. 38.

    Bhardwaj, B. et al. Outcomes and hospital utilization in patients with papillary muscle rupture associated with acute myocardial infarction. Am. J. Cardiol. 125, 1020–1025 (2020).

    PubMed  Google Scholar 

  39. 39.

    Grigioni, F., Enriquez-Sarano, M., Zehr, K. J., Bailey, K. R. & Tajik, A. J. Ischemic mitral regurgitation: long-term outcome and prognostic complications with quantitative Doppler assessment. Circulation 103, 1759–1764 (2001).

    CAS  PubMed  Google Scholar 

  40. 40.

    Piérard, L. A. & Carabello, B. A. Ischaemic mitral regurgitation: pathophysiology, outcomes and the conundrum of treatment. Eur. Heart J. 31, 2996–3005 (2010).

    PubMed  Google Scholar 

  41. 41.

    Lancellotti, P., Zamorano, J. L. & Vannan, M. A. Imaging challenges in secondary mitral regurgitation: unsolved issues and perspectives. Circ. Cardiovasc. Imaging 7, 735–746 (2014).

    PubMed  Google Scholar 

  42. 42.

    He, S., Fontaine, A. A., Schwammenthal, E., Yoganathan, A. P. & Levine, R. A. Integrated mechanism for functional mitral regurgitation: leaflet restriction versus coapting force: in vitro studies. Circulation 96, 1826–1834 (1997).

    CAS  PubMed  Google Scholar 

  43. 43.

    Beaudoin, J. et al. Mitral valve enlargement in chronic aortic regurgitation as a compensatory mechanism to prevent functional mitral regurgitation in the dilated left ventricle. J. Am. Coll. Cardiol. 61, 1809–1816 (2013).

    PubMed  PubMed Central  Google Scholar 

  44. 44.

    Tibayan, F. A. et al. Tenting volume: three-dimensional assessment of geometric perturbations in functional mitral regurgitation and implications for surgical repair. J. Heart Valve. Dis. 16, 1–7 (2007).

    PubMed  Google Scholar 

  45. 45.

    Spartera, M. et al. Role of cardiac dyssynchrony and resynchronization therapy in functional mitral regurgitation. Eur. Heart J. Cardiovasc. Imaging 17, 471–480 (2016). This paper discusses how cardiac resynchronization therapy can have therapeutic effects on secondary mitral regurgitation.

    PubMed  Google Scholar 

  46. 46.

    Ling, L. H., Kistler, P. M., Kalman, J. M., Schilling, R. J. & Hunter, R. J. Comorbidity of atrial fibrillation and heart failure. Nat. Rev. Cardiol. 13, 131–147 (2016). A comprehensive review that highlights how the association between atrial fibrillation and heart failure presents unique diagnostic and management challenges.

    CAS  PubMed  Google Scholar 

  47. 47.

    Beeri, R. et al. Mitral regurgitation augments post-myocardial infarction remodeling failure of hypertrophic compensation. J. Am. Coll. Cardiol. 51, 476–486 (2008).

    PubMed  Google Scholar 

  48. 48.

    Daniels, L. B. et al. Influence of age, race, sex, and body mass index on interpretation of midregional pro atrial natriuretic peptide for the diagnosis of acute heart failure: results from the BACH multinational study. Eur. J. Heart Fail. 14, 22–31 (2012).

    CAS  PubMed  Google Scholar 

  49. 49.

    Adlbrecht, C. et al. Prognostic value of plasma midregional pro-adrenomedullin and C-terminal-pro-endothelin-1 in chronic heart failure outpatients. Eur. J. Heart Fail. 11, 361–366 (2009).

    CAS  PubMed  Google Scholar 

  50. 50.

    Volpe, M., Battistoni, A. & Rubattu, S. Natriuretic peptides in heart failure: current achievements and future perspectives. Int. J. Cardiol. 281, 186–189 (2019).

    PubMed  Google Scholar 

  51. 51.

    Bäcka, M., Pizarro, R. & Clavel, M. A. Biomarkers in mitral regurgitation. Prog. Cardiovasc. Dis. 60, 334–341 (2017). This review focuses on the usefulness of biomarkers in evaluating and managing patients with mitral regurgitation, particularly revealing subclinical and/or very early damage induced by LV volume overload.

    Google Scholar 

  52. 52.

    Dini, F. L. et al. Plasma N-terminal protype-B natriuretic peptide levels in risk assessment of patients with mitral regurgitation secondary to ischemic and nonischemic dilated cardiomyopathy. Am. Heart J. 155, 1121–1127 (2008).

    CAS  PubMed  Google Scholar 

  53. 53.

    Ciarka, A. et al. Predictors of mitral regurgitation recurrence in patients with heart failure undergoing mitral valve annuloplasty. Am. J. Cardiol. 106, 395–401 (2010).

    PubMed  Google Scholar 

  54. 54.

    Kron, I. L. et al. Predicting recurrent mitral regurgitation after mitral valve repair for severe ischemic mitral regurgitation. J. Thorac. Cardiovasc. Surg. 149, 752–761 (2015).

    PubMed  Google Scholar 

  55. 55.

    Agricola, E. et al. Echocardiographic classification of chronic ischemic mitral regurgitation caused by restricted motion according to tethering pattern. Eur. J. Echocardiogr. 5, 326–334 (2004).

    PubMed  Google Scholar 

  56. 56.

    Gaasch, W. H. & Meyer, T. E. Secondary mitral regurgitation (part 1): volumetric quantification and analysis. Heart 104, 634–638 (2018).

    PubMed  Google Scholar 

  57. 57.

    Benjamin, E. J. et al. Heart disease and stroke statistics — 2017 update: a report from the American Heart Association. Circulation 135, e146–e603 (2017).

    PubMed  PubMed Central  Google Scholar 

  58. 58.

    Krijthe, B. P. et al. Projections on the number of individuals with atrial fibrillation in the European Union, from 2000 to 2060. Eur. Heart J. 34, 2746–2751 (2013).

    PubMed  PubMed Central  Google Scholar 

  59. 59.

    Abe, Y. et al. Prevalence and prognostic significance of functional mitral and tricuspid regurgitation despite preserved left ventricular ejection fraction in atrial fibrillation patients. Circ. J. 82, 1451–1458 (2018).

    PubMed  Google Scholar 

  60. 60.

    Silbiger, J. J. Does left atrial enlargement contribute to mitral leaflet tethering in patients with functional mitral regurgitation? Proposed role of atriogenic leaflet tethering. Echocardiography 31, 1310–1311 (2014).

    PubMed  Google Scholar 

  61. 61.

    Reddy, S. T. et al. Mitral regurgitation recovery and atrial reverse remodeling following pulmonary vein isolation procedure in patients with atrial fibrillation: a clinical observation proof-of-concept cardiac MRI study. J. Interv. Card. Electrophysiol. 37, 3017–3025 (2013).

    Google Scholar 

  62. 62.

    Takahashi, Y. et al. Mitral valve repair for atrial functional mitral regurgitation in patients with chronic atrial fibrillation. Interact. Cardiovasc. Thorac. Surg. 21, 163–168 (2015).

    PubMed  Google Scholar 

  63. 63.

    Ro, R. et al. Vector flow mapping in obstructive hypertrophic cardiomyopathy to assess the relationship of early systolic left ventricular flow and the mitral valve. J. Am. Coll. Cardiol. 64, 1984–1995 (2014).

    PubMed  Google Scholar 

  64. 64.

    Klues, H. G., Maron, B. J., Dollar, A. L. & Roberts, W. C. Diversity of structural mitral valve alterations in hypertrophic cardiomyopathy. Circulation 85, 1651–1660 (1992).

    CAS  PubMed  Google Scholar 

  65. 65.

    Maron, M. S. et al. Mitral valve abnormalities identified by cardiovascular magnetic resonance represent a primary phenotypic expression of hypertrophic cardiomyopathy. Circulation 124, 40–47 (2011).

    CAS  PubMed  Google Scholar 

  66. 66.

    Vassileva, C. M. et al. Long-term survival of patients undergoing mitral valve repair and replacement: a longitudinal analysis of Medicare fee-for-service beneficiaries. Circulation 127, 1870–1876 (2013).

    PubMed  Google Scholar 

  67. 67.

    Vohra, H. A. et al. Outcome after redo-mitral valve replacement in adult patients: a 10-year single-centre experience. Interact. Cardiovasc. Thorac. Surg. 14, 575–579 (2012).

    PubMed  PubMed Central  Google Scholar 

  68. 68.

    Bourguignon, T. et al. Very late outcomes for mitral valve replacement with the Carpentier-Edwards pericardial bioprosthesis: 25-year follow-up of 450 implantations. J. Thorac. Cardiovasc. Surg. 148, 2004–2011 (2014).

    PubMed  Google Scholar 

  69. 69.

    Pibarot, P. & Dumesnil, J. G. Prosthetic heart valves: selection of the optimal prosthesis and long-term management. Circulation 119, 1034–1048 (2009).

    PubMed  Google Scholar 

  70. 70.

    Singhal, P., Luk, A. & Butany, J. Bioprosthetic heart valves: impact of implantation on biomaterials. ISRN Biomater. 2013, 728791 (2013).

    Google Scholar 

  71. 71.

    Hwang, H. Y. et al. Paravalvular leak after mitral valve replacement: 20-year follow-up. Ann. Thorac. Surg. 100, 1347–1352 (2015).

    PubMed  Google Scholar 

  72. 72.

    Ruiz, C. E. et al. Clinical trial principles and endpoint definitions for paravalvular leaks in surgical prosthesis: an expert statement. J. Am. Coll. Cardiol. 69, 2067–2087 (2017).

    PubMed  Google Scholar 

  73. 73.

    Ionescu, A., Fraser, A. G. & Butchart, E. G. Prevalence and clinical significance of incidental paraprosthetic valvar regurgitation: a prospective study using transoesophageal echocardiography. Heart 89, 1316–1321 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. 74.

    O’Rourke, D. J. et al. Outcome of mild periprosthetic regurgitation detected by intraoperative transesophageal echocardiography. J. Am. Coll. Cardiol. 38, 163–166 (2001).

    PubMed  Google Scholar 

  75. 75.

    Flameng, W., Meuris, B., Herijgers, P. & Herregods, M. C. Durability of mitral valve repair in Barlow disease versus fibroelastic deficiency. J. Thorac. Cardiovasc. Surg. 135, 274–282 (2008).

    PubMed  Google Scholar 

  76. 76.

    Suri, R. M. et al. Recurrent mitral regurgitation after repair: should the mitral valve be re-repaired? J. Thorac. Cardiovasc. Surg. 132, 1390–1397 (2006).

    PubMed  Google Scholar 

  77. 77.

    Anyanwu, A. C. & Adams, D. H. Why do mitral valve repairs fail? J. Am. Soc. Echocardiogr. 22, 1265–1268 (2009).

    PubMed  Google Scholar 

  78. 78.

    Zoghbi, W. A. et al. Recommendations for noninvasive evaluation of native valvular regurgitation: a report from the American Society of Echocardiography developed in collaboration with the Society for Cardiovascular Magnetic Resonance. J. Am. Soc. Echocardiogr. 30, 303–371 (2017). These are the latest recommendations from the American Society of Echocardiography in collaboration with the Society for Cardiovascular Magnetic Resonance addressing the non-invasive evaluation of native valvular regurgitation.

    PubMed  Google Scholar 

  79. 79.

    Nishimura, R. A. et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart diseases. Circulation 135, e1159–e1195 (2017). This article includes the latest US guidelines addressing the management of valvular heart diseases.

    PubMed  Google Scholar 

  80. 80.

    Baumgartner, H. et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eur. Heart J. 38, 2739–2791 (2017). This article includes the latest European guidelines addressing the management of valvular heart diseases.

    PubMed  Google Scholar 

  81. 81.

    Kim, H. M. et al. Myocardial strain in prediction of outcomes after surgery for severe mitral regurgitation. JACC Cardiovasc. Imaging 11, 1235–1244 (2018).

    PubMed  Google Scholar 

  82. 82.

    Faletra, F. F., Leo, L. A. & Paiocchi, V. L. Anatomy of mitral annulus: insight from non-invasive imaging techniques. Eur. Heart J. Cardiovasc. Imaging 20, 843–857 (2019). An extensive review that highlights the peculiar aspects of the mitral annulus as they appear with the use of different imaging techniques and discusses clinical implications related to this complex structure.

    PubMed  Google Scholar 

  83. 83.

    Lee, A. P. et al. Functional implication of mitral annular disjunction in mitral valve prolapse: a quantitative dynamic 3D echocardiographic study. JACC Cardiovasc. Imaging 10, 1424–1433 (2017).

    PubMed  Google Scholar 

  84. 84.

    Sugeng, L. et al. Accuracy of mitral valve area measurements using transthoracic rapid freehand 3-dimensional scanning: comparison with noninvasive and invasive methods. J. Am. Soc. Echocardiogr. 16, 1292–1300 (2003).

    PubMed  Google Scholar 

  85. 85.

    Blanke, P. et al. Multimodality imaging in the context of transcatheter mitral valve replacement: establishing consensus among modalities and disciplines. JACC Cardiovasc. Imaging 8, 1191–1208 (2015).

    PubMed  Google Scholar 

  86. 86.

    Heo, R. et al. Clinical implications of three-dimensional real-time color Doppler transthoracic echocardiography in quantifying mitral regurgitation: a comparison with conventional two-dimensional methods. J. Am. Soc. Echocardiogr. 30, 393–403 (2017).

    PubMed  Google Scholar 

  87. 87.

    Zeng, X. et al. Diagnostic value of vena contracta area in the quantification of mitral regurgitation severity by color Doppler 3D echocardiography. Circ. Cardiovasc. Imaging 4, 506–513 (2011).

    PubMed  PubMed Central  Google Scholar 

  88. 88.

    Nolan, M. T. & Thavendiranathan, P. Automated quantification in echocardiography. JACC Cardiovasc. Imaging 12, 1073–1092 (2019).

    PubMed  Google Scholar 

  89. 89.

    Faletra, F. F. et al. Echocardiographic-fluoroscopic fusion imaging for transcatheter mitral valve repair guidance. Eur. Heart J. Cardiovasc. Imaging 19, 715–726 (2018).

    PubMed  Google Scholar 

  90. 90.

    Myerson, S. G. et al. Determination of clinical outcome in mitral regurgitation with cardiovascular magnetic resonance quantification. Circulation 133, 2287–2296 (2016). This paper shows that CMR can be an adjunctive tool for the management of patients with mitral regurgitation, identifying those who develop symptoms or other indications for surgery.

    PubMed  Google Scholar 

  91. 91.

    Han, Y. et al. Cardiovascular magnetic resonance characterization of mitral valve prolapse. JACC Cardiovasc. Imaging 1, 294–303 (2008).

    PubMed  Google Scholar 

  92. 92.

    Van De Heyning, C. M. et al. Late gadolinium enhancement CMR in primary mitral regurgitation. Eur. J. Clin. Invest. 44, 840–847 (2014).

    Google Scholar 

  93. 93.

    Edwards, N. C. et al. Quantification of left ventricular interstitial fibrosis in asymptomatic chronic primary degenerative mitral regurgitation. Circ. Cardiovasc. Imaging 7, 946–953 (2014).

    PubMed  Google Scholar 

  94. 94.

    Miller, M. A. et al. Arrhythmic mitral valve prolapse. J. Am. Coll. Cardiol. 72, 2904–2914 (2018).

    PubMed  Google Scholar 

  95. 95.

    Cavalcante, J. L. et al. Prognostic impact of ischemic mitral regurgitation severity and myocardial infarct quantification by cardiovascular magnetic resonance. JACC Cardiovasc. Imaging https://doi.org/10.1016/j.jcmg.2019.11.008 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  96. 96.

    Liu, B., Edwards, N. C., Pennell, D. & Steeds, R. P. The evolving role of cardiac magnetic resonance in primary mitral regurgitation: ready for prime time? Eur. Heart J. Cardiovasc. Imaging 20, 123–130 (2019).

    PubMed  Google Scholar 

  97. 97.

    Blanke, P. et al. Mitral annular evaluation with CT in the context of transcatheter mitral valve replacement. JACC Cardiovasc. Imaging 8, 612–615 (2015).

    PubMed  Google Scholar 

  98. 98.

    Choure, A. J. et al. In vivo analysis of the anatomical relationship of coronary sinus to mitral annulus and left circumflex coronary artery using cardiac multidetector computed tomography: implications for percutaneous coronary sinus mitral annuloplasty. J. Am. Coll. Cardiol. 48, 1938–1945 (2006).

    PubMed  Google Scholar 

  99. 99.

    Van Mieghem, N. M. et al. Computed tomography optimised fluoroscopy guidance for transcatheter mitral therapies. EuroIntervention 11, 1428–1431 (2016).

    PubMed  Google Scholar 

  100. 100.

    Blanke, P. et al. Predicting LVOT obstruction in transcatheter mitral valve implantation: concept of the neo-LVOT. JACC Cardiovasc. Imaging 10, 482–485 (2017).

    PubMed  Google Scholar 

  101. 101.

    Van Rosendael, P. J. et al. Integrated imaging of echocardiography and computed tomography to grade mitral regurgitation severity in patients undergoing transcatheter aortic valve implantation. Eur. Heart J. 38, 2221–2226 (2017).

    PubMed  Google Scholar 

  102. 102.

    Biner, S. et al. Reproducibility of proximal isovelocity surface area, vena contracta, and regurgitant jet area for assessment of mitral regurgitation severity. JACC Cardiovasc. Imaging 3, 235–243 (2010).

    PubMed  Google Scholar 

  103. 103.

    Grayburn, P. A. et al. Defining “severe” secondary mitral regurgitation: emphasizing an integrated approach. J. Am. Coll. Cardiol. 64, 2792–2801 (2014).

    PubMed  Google Scholar 

  104. 104.

    Di Tullio, M. R. & Homma, S. Direct measurement of multiple vena contracta areas for assessing the severity of mitral regurgitation using 3D TEE. JACC Cardiovasc. Imaging 5, 669–676 (2012).

    PubMed  Google Scholar 

  105. 105.

    Shanks, M. et al. Quantitative assessment of mitral regurgitation comparison between three-dimensional transesophageal echocardiography and magnetic resonance imaging. Circ. Cardiovasc. Imaging 3, 694–700 (2010).

    PubMed  Google Scholar 

  106. 106.

    Lancellotti, P. et al. Recommendations for the echocardiographic assessment of native valvular regurgitation: an executive summary from the European Association of Cardiovascular Imaging. Eur. Heart J. Cardiovasc. Imaging 14, 611–614 (2013). This article includes the latest recommendations from the European Association of Cardiovascular Imaging for the echocardiographic assessment of native valvular regurgitation.

    PubMed  Google Scholar 

  107. 107.

    Dujardin, K. S. et al. Grading of mitral regurgitation by quantitative Doppler echocardiography: calibration by left ventricular angiography in routine clinical practice. Circulation 96, 3409–3415 (1997).

    CAS  PubMed  Google Scholar 

  108. 108.

    Uretsky, S. et al. Quantification of left ventricular remodeling in response to isolated aortic or mitral regurgitation. J. Cardiovasc. Magn. Reson. 12, 32 (2010).

    PubMed  PubMed Central  Google Scholar 

  109. 109.

    Penicka, M. et al. Prognostic implications of magnetic resonance-derived quantification in asymptomatic patients with organic mitral regurgitation: comparison with Doppler echocardiography-derived integrative approach. Circulation 137, 1349–1360 (2018).

    PubMed  Google Scholar 

  110. 110.

    Harris, A. W. et al. Cardiac magnetic resonance imaging versus transthoracic echocardiography for prediction of outcomes in chronic aortic or mitral regurgitation. Am. J. Cardiol. 119, 1074–1081 (2017).

    PubMed  Google Scholar 

  111. 111.

    Khattar, R. S. & Senior, R. Stress echocardiography in the assessment of native valve disease. Heart 105, 1034–1043 (2019).

    PubMed  Google Scholar 

  112. 112.

    Lancellotti, P. et al. The clinical use of stress echocardiography in non-ischaemic heart disease: recommendations from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. J. Am. Soc. Echocardiogr. 30, 101–138 (2017).

    PubMed  Google Scholar 

  113. 113.

    Magne, J. et al. Impact of exercise pulmonary hypertension on postoperative outcome in primary mitral regurgitation. Heart 101, 391–396 (2015).

    PubMed  Google Scholar 

  114. 114.

    Lee, R. et al. Functional and prognostic implications of left ventricular contractile reserve in patients with asymptomatic severe mitral regurgitation. Heart 91, 1407–1412 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. 115.

    Kusunose, K., Popovic´, Z. B., Motoki, H. & Marwick, T. H. Prognostic significance of exercise-induced right ventricular dysfunction in asymptomatic degenerative mitral regurgitation. Circ. Cardiovasc. Imaging 6, 167–176 (2013).

    PubMed  Google Scholar 

  116. 116.

    Utsunomiya, H. et al. Exercise-stress echocardiography and effort intolerance in asymptomatic/minimally symptomatic patients with degenerative mitral regurgitation combined invasive–noninvasive hemodynamic monitoring. Circ. Cardiovasc. Imaging 11, e007282 (2018).

    PubMed  Google Scholar 

  117. 117.

    Dulgheru, R. et al. Exercise testing in mitral regurgitation. Prog. Cardiovasc. Dis. 60, 342–350 (2017).

    PubMed  Google Scholar 

  118. 118.

    Lancellotti, P., Troisfontaines, P., Toussaint, A. & Pierard, L. A. Prognostic importance of exercise-induced changes in mitral regurgitation in patients with chronic ischemic left ventricular dysfunction. Circulation 108, 1713–1717 (2003).

    PubMed  Google Scholar 

  119. 119.

    Lancellotti, P., Gérard, P. L. & Piérard, L. A. Long-term outcome of patients with heart failure and dynamic functional mitral regurgitation. Eur. Heart J. 26, 1528–1532 (2005).

    PubMed  Google Scholar 

  120. 120.

    Tribouilloy, C. M. et al. Impact of preoperative symptoms on survival after surgical correction of organic mitral regurgitation: rationale for optimizing surgical indications. Circulation 99, 400–405 (1999).

    CAS  PubMed  Google Scholar 

  121. 121.

    Nashef, S. A. et al. European system for cardiac operative risk evaluation (EuroSCORE). Eur. J. Cardiothorac. Surg. 16, 9–13 (1999).

    CAS  PubMed  Google Scholar 

  122. 122.

    Shahian, D. M. & Edwards, F. H. The Society of Thoracic Surgeons 2008 cardiac surgery risk models: introduction. Ann. Thorac. Surg. 88 (Suppl. 1), 1 (2009).

    Google Scholar 

  123. 123.

    Mack, M. J. Risk scores for predicting outcomes in valvular heart disease: how useful? Curr. Cardiol. Rep. 13, 107–112 (2011).

    PubMed  Google Scholar 

  124. 124.

    Nashef, S. A. et al. EuroSCORE II. Eur. J. Cardiothorac. Surg. 41, 734–744 (2012).

    PubMed  Google Scholar 

  125. 125.

    Barili, F. et al. Reliability of new scores in predicting perioperative mortality after mitral valve surgery. J. Thorac. Cardiovasc. Surg. 147, 1008–1012 (2014).

    PubMed  Google Scholar 

  126. 126.

    Carabello, B. A. The current therapy for mitral regurgitation. J. Am. Coll. Cardiol. 52, 319–326 (2008).

    PubMed  Google Scholar 

  127. 127.

    Ahmed, M. I., Aban, I. & Lloyd, S. G. A randomized controlled phase IIb trial of beta(1)-receptor blockade for chronic degenerative mitral regurgitation. J. Am. Coll. Cardiol. 9, 833–838 (2012).

    Google Scholar 

  128. 128.

    He, Z. et al. Efficacy and safety of supramaximal titrated inhibition of renin-angiotensin-aldosterone system in idiopathic dilated cardiomyopathy. ESC. Heart Fail. 2, 129–138 (2015).

    PubMed  PubMed Central  Google Scholar 

  129. 129.

    Packer, M. & Grayburn, P. A. Neurohormonal and transcatheter repair strategies for proportionate and disproportionate functional mitral regurgitation in heart failure. JACC Heart. Fail. 7, 518–522 (2019).

    PubMed  Google Scholar 

  130. 130.

    Nasser, R. et al. Evolution of functional mitral regurgitation and prognosis in medically managed heart failure patients with reduced ejection fraction. JACC Heart. Fail. 5, 652–659 (2017).

    PubMed  Google Scholar 

  131. 131.

    Kang, D. H. et al. Angiotensin receptor neprilysin inhibitor for functional mitral regurgitation. Circulation 139, 1354–1365 (2019).

    CAS  PubMed  Google Scholar 

  132. 132.

    Cipriani, M. et al. Prognostic implications of mitral regurgitation in patients after cardiac resynchronization therapy. Eur. J. Heart Fail. 18, 1060–1068 (2016).

    PubMed  Google Scholar 

  133. 133.

    Onishi, T. et al. Mechanistic features associated with improvement in mitral regurgitation after cardiac resynchronization therapy and their relation to long-term patient outcome. Circ. Heart. Fail. 6, 685–693 (2013).

    PubMed  Google Scholar 

  134. 134.

    Van Bommel, R. J. et al. Cardiac resynchronization therapy as a therapeutic option in patients with moderate-severe functional mitral regurgitation and high operative risk. Circulation 124, 912–919 (2011).

    PubMed  Google Scholar 

  135. 135.

    Castillo, J. G., Anyanwu, A. C., El-Eshmawi, A. & Adams, D. H. All anterior and bileaflet mitral valve prolapses are repairable in the modern era of reconstructive surgery. Eur. J. Cardiothorac. Surg. 45, 139–145 (2014).

    PubMed  Google Scholar 

  136. 136.

    Castillo, J. G., Anyanwu, A. C., Fuster, V. & Adams, D. H. A near 100% repair rate for mitral valve prolapse is achievable in a reference center: implications for future guidelines. J. Thorac. Cardiovasc. Surg. 144, 308–312 (2012).

    PubMed  Google Scholar 

  137. 137.

    Watt, T. M. F. et al. Degenerative mitral valve repair restores life expectancy. Ann. Thorac. Surg. 109, 794–801 (2020).

    PubMed  Google Scholar 

  138. 138.

    Coutinho, G. F., Correia, P. M., Branco, C. & Antunes, M. J. Long-term results of mitral valve surgery for degenerative anterior leaflet or bileaflet prolapse: analysis of negative factors for repair, early and late failures, and survival. Eur. J. Cardiothorac. Surg. 50, 66–74 (2016).

    PubMed  Google Scholar 

  139. 139.

    Dillon, J. et al. Comparative long-term results of mitral valve repair in adults with chronic rheumatic disease and degenerative disease: is repair for “burnt-out” rheumatic disease still inferior to repair for degenerative disease in the current era? J. Thorac. Cardiovasc. Surg. 149, 771–777 (2015).

    PubMed  Google Scholar 

  140. 140.

    Kanemitsu, H., Nakamura, K., Fukunaga, N. & Koyama, T. Long-term outcomes of mitral valve repair for active endocarditis. Circ. J. 80, 1148–1152 (2016).

    PubMed  Google Scholar 

  141. 141.

    Schnittman, S. R. et al. Survival and long-term outcomes after mitral valve replacement in patients aged 18 to 50 years. J. Thorac. Cardiovasc. Surg. 155, 96–102 (2018).

    PubMed  Google Scholar 

  142. 142.

    Wu, A. H. et al. Impact of mitral valve annuloplasty on mortality risk in patients with mitral regurgitation and left ventricular systolic dysfunction. J. Am. Coll. Cardiol. 45, 381–387 (2005).

    PubMed  Google Scholar 

  143. 143.

    De Bonis, M. et al. Long-term results of mitral repair in patients with severe left ventricular dysfunction and secondary mitral regurgitation: does the technique matter? Eur. J. Cardiothorac. Surg. 50, 882–889 (2016).

    PubMed  Google Scholar 

  144. 144.

    Stone, G. W. et al. Transcatheter mitral-valve repair in patients with heart failure. N. Engl. J. Med. 379, 2307–2318 (2018). This paper reports the results of the COAPT trial in patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy, randomly assigned to be treated or not by transcatheter mitral valve repair.

    PubMed  Google Scholar 

  145. 145.

    Rosenhek, R. et al. Outcome of watchful waiting in asymptomatic severe mitral regurgitation. Circulation 113, 2238–2244 (2006).

    PubMed  Google Scholar 

  146. 146.

    Uretsky, S. et al. Discordance between echocardiography and MRI in the assessment of mitral regurgitation severity: a prospective multicenter trial. J. Am. Coll. Cardiol. 65, 1078–1088 (2015).

    PubMed  Google Scholar 

  147. 147.

    Adams, D. H., Rosenhek, R. & Falk, V. Degenerative mitral valve regurgitation: best practice revolution. Eur. Heart J. 31, 1958–1966 (2010).

    PubMed  PubMed Central  Google Scholar 

  148. 148.

    Bortolotti, U., Milano, A. D. & Frater, R. W. Mitral valve repair with artificial chordae: a review of its history, technical details, long-term results, and pathology. Ann. Thorac. Surg. 93, 684–691 (2012).

    PubMed  Google Scholar 

  149. 149.

    Falk, V. et al. How does the use of polytetrafluoroethylene neochordae for posterior mitral valve prolapse (loop technique) compare with leaflet resection? A prospective randomized trial. J. Thorac. Cardiovasc. Surg. 136, 1205 (2008).

    PubMed  Google Scholar 

  150. 150.

    Suri, R. M. et al. Effect of recurrent mitral regurgitation following degenerative mitral valve repair: long-term analysis of competing outcomes. J. Am. Coll. Cardiol. 67, 488–498 (2016). This paper demonstrates how recurrent mitral regurgitation following degenerative mitral valve repair is associated with adverse LV remodelling and late death, highlighting the need to refer complex mitral valve prolapse to centres of excellence.

    PubMed  Google Scholar 

  151. 151.

    Lazam, S. et al. Twenty-year outcome after mitral repair versus replacement for severe degenerative mitral regurgitation: analysis of a large, prospective, multicenter, international registry. Circulation 135, 410–422 (2017).

    PubMed  Google Scholar 

  152. 152.

    Gammie, J. S., O’Brien, S. M., Griffith, B. P., Ferguson, T. B. & Peterson, E. D. Influence of hospital procedural volume on care process and mortality for patients undergoing elective surgery for mitral regurgitation. Circulation 115, 881–887 (2007).

    PubMed  Google Scholar 

  153. 153.

    De Bonis, M. et al. Very long-term durability of the edge-to-edge repair for isolated anterior mitral leaflet prolapse: up to 21 years of clinical and echocardiographic results. J. Thorac. Cardiovasc. Surg. 148, 2027–2032 (2014). This paper shows how mitral valve repair can ensure excellent long-term results when performed in high-volume centres of excellence.

    PubMed  Google Scholar 

  154. 154.

    David, T. E., Armstrong, S. & Ivanov, J. Chordal replacement with polytetrafluoroethylene sutures for mitral valve repair: a 25-year experience. J. Thorac. Cardiovasc. Surg. 145, 1563–1569 (2013).

    PubMed  Google Scholar 

  155. 155.

    Di Bardino, D. J. et al. Four decades of experience with mitral valve repair: analysis of differential indications, technical evolution, and long-term outcome. J. Thorac. Cardiovasc. Surg. 139, 76–83 (2010).

    Google Scholar 

  156. 156.

    Bonow, R. O. & Adams, D. H. The time has come to define centers of excellence in mitral valve repair. J. Am. Coll. Cardiol. 67, 499–501 (2016).

    PubMed  Google Scholar 

  157. 157.

    Obadia, J. F. et al. Percutaneous repair or medical treatment for secondary mitral regurgitation. N. Engl. J. Med. 379, 2297–2306 (2018). This paper reports the results of the MITRA-FR trial in patients with severe secondary mitral regurgitation and chronic heart failure who were randomly assigned to be treated with percutaneous mitral valve repair in addition to medical therapy or with medical therapy alone.

    PubMed  Google Scholar 

  158. 158.

    Grossi, E. A. et al. Outcomes of coronary artery bypass grafting and reduction annuloplasty for functional ischemic mitral regurgitation: a prospective multicenter study (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve). J. Thorac. Cardiov. Sur. 141, 91–97 (2011).

    Google Scholar 

  159. 159.

    Fattouch, K. et al. POINT: efficacy of adding mitral valve restrictive annuloplasty to coronary artery bypass grafting in patients with moderate ischemic mitral valve regurgitation: a randomized trial. J. Thorac. Cardiov. Sur. 138, 278–285 (2009).

    Google Scholar 

  160. 160.

    Smith, P. K. et al. Surgical treatment of moderate ischemic mitral regurgitation. N. Engl. J. Med. 371, 2178–2188 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  161. 161.

    Michler, R. E. et al. Two-year outcomes of surgical treatment of moderate ischemic mitral regurgitation. N. Engl. J. Med. 374, 1932–1941 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  162. 162.

    Onorati, F. et al. Midterm clinical and echocardiographic results and predictors of mitral regurgitation recurrence following restrictive annuloplasty for ischemic cardiomyopathy. J. Thorac. Cardiov. Surg. 138, 654–662 (2009).

    PubMed  Google Scholar 

  163. 163.

    Goldstein, D. et al. Two-year outcomes of surgical treatment of severe ischemic mitral regurgitation. N. Engl. J. Med. 374, 344–353 (2016).

    CAS  PubMed  Google Scholar 

  164. 164.

    Abbott. Breakthrough TMVr therapy for select patients with mitral regurgitation (MR). Structural Heart Solutions https://www.structuralheartsolutions.com/structural-heart-products-solutions/mitral-valve-mitraclip/overview/ (2019).

  165. 165.

    Feldman, T. et al. Percutaneous mitral repair with the MitraClip system: safety and midterm durability in the initial EVEREST (Endovascular Valve Edge-to-Edge REpair Study) cohort. J. Am. Coll. Cardiol. 54, 686–694 (2009).

    PubMed  Google Scholar 

  166. 166.

    Mauri, L. et al. Four-year results of a randomized controlled trial of percutaneous repair versus surgery for mitral regurgitation. J. Am. Coll. Cardiol. 62, 317–328 (2013).

    PubMed  Google Scholar 

  167. 167.

    Sorajja, P. et al. Outcomes with transcatheter mitral valve repair in the United States: an STS/ACC TVT registry report. J. Am. Coll. Cardiol. 70, 2315–2327 (2017).

    PubMed  Google Scholar 

  168. 168.

    Puls, M. et al. One-year outcomes and predictors of mortality after MitraClip therapy in contemporary clinical practice: results from the German transcatheter mitral valve interventions registry. Eur. Heart J. 37, 703–712 (2016).

    PubMed  Google Scholar 

  169. 169.

    Feldman, T. et al. Percutaneous repair or surgery for mitral regurgitation. N. Engl. J. Med. 364, 1395–1406 (2011).

    CAS  PubMed  Google Scholar 

  170. 170.

    Glower, D. D. et al. Percutaneous mitral valve repair for mitral regurgitation in high-risk patients: results of the EVEREST II study. J. Am. Coll. Cardiol. 64, 172–181 (2014).

    PubMed  Google Scholar 

  171. 171.

    Praz, F. et al. Mitral regurgitation in heart failure: time for a rethink. Eur. Heart J. 40, 2189–2193 (2019).

    PubMed  Google Scholar 

  172. 172.

    Senni, M., Adamo, M., Metra, M., Alfieri, O. & Vahanian, A. Treatment of functional mitral regurgitation in chronic heart failure: can we get a ‘proof of concept’ from the MITRA-FR and COAPT trials? Eur. J. Heart Fail. 21, 852–861 (2019).

    PubMed  Google Scholar 

  173. 173.

    Stone, G. W. & Alfieri, O. The five Ws of transcatheter mitral valve repair: who, what, when, where, and why. EuroIntervention. 15, 837–840 (2019).

    PubMed  Google Scholar 

  174. 174.

    Packer, M. & Grayburn, P. A. Contrasting effects of pharmacological, procedural, and surgical interventions on proportionate and disproportionate functional mitral regurgitation in chronic heart failure. Circulation 140, 779–789 (2019).

    PubMed  Google Scholar 

  175. 175.

    Buzzatti, N. et al. Mid-term outcomes (up to 5 years) of percutaneous edge-to-edge mitral repair in the real-world according to regurgitation mechanism: a single-center experience. Catheter. Cardiovasc. Interv. 94, 427–435 (2019).

    PubMed  Google Scholar 

  176. 176.

    Lim, D. S. et al. Transcatheter valve repair for patients with mitral regurgitation: 30-day results of the CLASP study. JACC Cardiovasc. Interv. 12, 1369–1378 (2019).

    PubMed  Google Scholar 

  177. 177.

    Gammie, J. S. et al. Beating-heart mitral valve repair using a novel ePTFE cordal implantation device: a prospective trial. J. Am. Coll. Cardiol. 71, 25–36 (2018).

    PubMed  Google Scholar 

  178. 178.

    Seeburger, J. et al. Off-pump transapical implantation of artificial neo-chordae to correct mitral regurgitation: the TACT trial (Transapical Artificial Chordae Tendinae) proof of concept. J. Am. Coll. Cardiol. 63, 914–919 (2014).

    PubMed  Google Scholar 

  179. 179.

    Colli, A. et al. Transapical off-pump mitral valve repair with NeoChord implantation: early clinical results. Int. J. Cardiol. 204, 23–28 (2016).

    PubMed  Google Scholar 

  180. 180.

    Colli, A. et al. An early European experience with transapical off-pump mitral valve repair with NeoChord implantation. Eur. J. Cardiothorac. Surg. 54, 460–466 (2018).

    PubMed  Google Scholar 

  181. 181.

    Nickenig, G. et al. Treatment of chronic functional mitral valve regurgitation with a percutaneous annuloplasty system. J. Am. Coll. Cardiol. 67, 2927–2936 (2016).

    PubMed  Google Scholar 

  182. 182.

    Nickenig, G. et al. Transcatheter mitral annuloplasty in chronic functional mitral regurgitation: 6-month results with the Cardioband percutaneous mitral repair system. JACC Cardiovasc. Interv. 9, 2039–2047 (2016).

    PubMed  Google Scholar 

  183. 183.

    Bail, D. H. Treatment of functional mitral regurgitation by percutaneous annuloplasty using the Carillon mitral contour system — currently available data state. J. Interv. Cardiol. 30, 156–162 (2017).

    PubMed  Google Scholar 

  184. 184.

    Sorajja, P., Cavalcante, J. L. & Gössl, M. The need for transcatheter mitral valve replacement. J. Am. Coll. Cardiol. 73, 1247–1249 (2019).

    PubMed  Google Scholar 

  185. 185.

    Taramasso, M., Gavazzoni, M., Nickenig, G. & Maisano, F. Transcatheter mitral repair and replacement: which procedure for which patient? EuroIntervention 15, 867–874 (2019).

    PubMed  Google Scholar 

  186. 186.

    Sorajja, P. et al. Novel transcatheter mitral valve prosthesis for patients with severe mitral annular calcification. J. Am. Coll. Cardiol. 74, 1431–1440 (2019).

    PubMed  Google Scholar 

  187. 187.

    Regueiro, A., Granada, J. F., Dagenais, F. & Rodés-Cabau, J. Transcatheter mitral valve replacement: insights from early clinical experience and future challenges. J. Am. Coll. Cardiol. 69, 2175–2192 (2017).

    PubMed  Google Scholar 

  188. 188.

    Del Val, D. et al. Early experience with transcatheter mitral valve replacement: a systematic review. J. Am. Heart. Assoc. 8, e013332 (2019).

    PubMed  PubMed Central  Google Scholar 

  189. 189.

    Stoler, R. C. et al. Transcatheter mitral valve replacement for patients with symptomatic mitral regurgitation: a global feasibility trial. J. Am. Coll. Cardiol. 69, 381–391 (2017).

    PubMed  Google Scholar 

  190. 190.

    Mehaffey, H. J. et al. Contemporary outcomes in reoperative mitral valve surgery. Heart 104, 652–656 (2018).

    PubMed  Google Scholar 

  191. 191.

    Eleid, M. F. et al. Percutaneous transvenous transseptal transcatheter valve implantation in failed bioprosthetic mitral valves, ring annuloplasty, and severe mitral annular calcification. JACC Cardiovasc. Interv. 9, 1161–1174 (2016).

    PubMed  Google Scholar 

  192. 192.

    Ye, J. et al. Transcatheter aortic and mitral valve-in-valve implantation for failed surgical bioprosthetic valves: an eight-year single-center experience. JACC Cardiovasc. Interv. 8, 1735–1744 (2015).

    PubMed  Google Scholar 

  193. 193.

    Alkhouli, M. et al. Transcatheter and surgical management of mitral paravalvular leak: long-term outcomes. JACC Cardiovasc. Interv. 10, 1946–1956 (2017).

    PubMed  Google Scholar 

  194. 194.

    Chikwe, J. et al. Relation of mitral valve surgery volume to repair rate, durability, and survival. J. Am. Coll. Cardiol. 69, 2397–2406 (2017).

    Google Scholar 

  195. 195.

    Chiarito, M. et al. Outcome after percutaneous edge-to-edge mitral repair for functional and degenerative mitral regurgitation: a systematic review and meta-analysis. Heart. 104, 306–312 (2018).

    PubMed  Google Scholar 

  196. 196.

    Buzzatti, N. et al. Comparison of outcomes of percutaneous MitraClip versus surgical repair or replacement for degenerative mitral regurgitation in octogenarians. Am. J. Cardiol. 115, 487–492 (2015).

    PubMed  Google Scholar 

  197. 197.

    Goliasch, G. et al. Refining the prognostic impact of functional mitral regurgitation in chronic heart failure. Eur. Heart J. 39, 39–46 (2018). This paper shows that in patients receiving optimal medical therapy, the adverse prognostic effect of secondary mitral regurgitation occurs predominantly in a subgroup of patients with a specific intermediate heart failure phenotype.

    CAS  PubMed  Google Scholar 

  198. 198.

    Braun, D., Näbauer, M., Massberg, S. & Hausleiter, J. One-stop shop: simultaneous direct mitral annuloplasty and percutaneous mitral edge-to-edge repair in a patient with severe mitral regurgitation. Catheter. Cardiovasc. Interv. 93, E318–E319 (2019).

    PubMed  Google Scholar 

  199. 199.

    Ferrazzi, P. et al. Transaortic chordal cutting: mitral valve repair for obstructive hypertrophic cardiomyopathy with mild septal hypertrophy. J. Am. Coll. Cardiol. 66, 1687–1696 (2015).

    PubMed  Google Scholar 

  200. 200.

    Sado, D. M. et al. Myectomy plus Alfieri technique for outflow tract obstruction in hypertrophic cardiomyopathy. Circulation 122, 938–939 (2010).

    PubMed  Google Scholar 

  201. 201.

    Aphram, G. et al. Re-repair of the failed mitral valve: insights into aetiology and surgical management. Eur. J. Cardiothorac. Surg. 54, 774–780 (2018).

    PubMed  Google Scholar 

  202. 202.

    Allende, R. et al. Transcatheter mitral “valve-in-ring” implantation: a word of caution. Ann. Thorac. Surg. 99, 1439–1442 (2015).

    PubMed  Google Scholar 

  203. 203.

    Grayburn, P. A., Sannino, A. & Packer, M. Proportionate and disproportionate functional mitral regurgitation: a new conceptual framework that reconciles the results of the MITRA-FR and COAPT trials. JACC Cardiovasc. Imaging 12, 353–362 (2019). This paper addresses the novel concept of proportionate and disproportionate functional mitral regurgitation in chronic heart failure.

    PubMed  Google Scholar 

Download references

Acknowledgements

O.A. is President of the Alfieri Heart Foundation, which aims to encourage training, innovation and research in structural heart disease.

Author information

Affiliations

Authors

Contributions

B.D.F., M.D.B., E.A., F.M., D.S. and O.A. researched the data for the article, provided substantial contributions to discussions of its content, wrote the article and reviewed and/or edited the manuscript before submission. A.C. and M.M. provided substantial contributions to revision of the manuscript.

Corresponding author

Correspondence to Ottavio Alfieri.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Del Forno, B., De Bonis, M., Agricola, E. et al. Mitral valve regurgitation: a disease with a wide spectrum of therapeutic options. Nat Rev Cardiol (2020). https://doi.org/10.1038/s41569-020-0395-7

Download citation