New understanding of the mechanism of mitral regurgitation: From a two-dimensional point to a four-dimensional space-time_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

PAN Wenzhi ^1,2 , LI Wei ^3,4 , PAN Cuizhen ^3,4 ,  ZHOU Daxin ^1,2 ,  GE Junbo ^1,2

1. Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, 200032, P. R. China;
2. National Clinical Research Center for Interventional Medicine, Shanghai, 200032, P. R. China;
3. Department of Echocardiography, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, 200032, P. R. China;
4. Shanghai Institute of Medical Imaging, Shanghai, 200032, P. R. China;

Corresponding?author：

ZHOU Daxin, Email: zhou.daxin@zs-hospital.sh.cn; GE Junbo, Email: ge.junbo2@zs-hospital.sh.cn

Keywords：

Mitral regurgitation; two-dimensional point; four-dimensional quadratic space

DOI：

10.7507/1007-4848.202109006

Video：

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Mitral regurgitation (MR) is a kind of valvular heart disease with a complicated pathogenesis. However, the current clinical understanding of MR mostly stays in a purely spatial perspective. We suggest that the evaluation of MR should break through the limited thinking of the area of a two-dimensional single frame, and transfer to a comprehensive evaluation of three-dimensional space-time integration (i.e. four-dimensional space-time). Secondly, it is of significance to pay attention to the time mechanism and time thinking of the occurrence of MR. The amount of MR may be different in different cardiac cycles or within the same cardiac cycle. Finally, changes in the time dimension of cardiac contraction can lead to the occurrence of MR and sometimes it is necessary to understand MR from time thinking rather than spatial thinking.

Citation： PAN Wenzhi, LI Wei, PAN Cuizhen, ZHOU Daxin, GE Junbo. New understanding of the mechanism of mitral regurgitation: From a two-dimensional point to a four-dimensional space-time. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2022, 29(7): 801-805. doi: 10.7507/1007-4848.202109006 Copy

1.	潘文志, 周達新, 葛均波. 二尖瓣反流機制的新認識及其應用. 中國醫學前沿雜志 (電子版), 2017, 9(10): 43-46.
2.	Van Mieghem NM, Piazza N, Anderson RH, et al. Anatomy of the mitral valvular complex and its implications for transcatheter interventions for mitral regurgitation. J Am Coll Cardiol, 2010, 56(8): 617-626.
3.	Levine RA, Hagége AA, Judge DP, et al. Mitral valve disease—Morphology and mechanisms. Nat Rev Cardiol, 2015, 12(12): 689-710.
4.	Cannata F, Regazzoli D, Barberis G, et al. Mitral valve stenosis after transcatheter aortic valve replacement: Case report and review of the literature. Cardiovasc Revasc Med, 2019, 20(12): 1196-1202.
5.	Ben-Shoshan J, Wang DD, Asgar AW. Left ventricular outflow tract obstruction: A potential obstacle for transcatheter mitral valve therapy. Interv Cardiol Clin, 2019, 8(3): 269-278.
6.	Perpetua EM, Levin DB, Reisman M. Anatomy and function of the normal and diseased mitral apparatus: Implications for transcatheter therapy. Interv Cardiol Clin, 2016, 5(1): 1-16.
7.	Fishbein GA, Fishbein MC. Mitral valve pathology. Curr Cardiol Rep, 2019, 21(7): 61.
8.	Duran Karaduman B, Ayhan H, Kele? T, et al. The playmaker of the mitral valve disease: Mitral annulus. Int J Cardiol, 2020, 316: 205-206.
9.	Topilsky Y, Vaturi O, Watanabe N, et al. Real-time 3-dimensional dynamics of functional mitral regurgitation: A prospective quantitative and mechanistic study. J Am Heart Assoc, 2013, 2(3): e000039.
10.	Goldberg SL, Hammerstingl C. Coronary sinus-based approach to mitral regurgitation. Interv Cardiol Clin, 2016, 5(1): 93-100.
11.	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, 17(12): 807-827.
12.	El Sabbagh A, Reddy YNV, Nishimura RA. Mitral valve regurgitation in the contemporary era: Insights into diagnosis, management, and future directions. JACC Cardiovasc Imaging, 2018, 11(4): 628-643.
13.	de Groot-de Laat LE, McGhie J, Ren B, et al. A modified echocardiographic classification of mitral valve regurgitation mechanism: The role of three-dimensional echocardiography. J Cardiovasc Imaging, 2019, 27(3): 187-199.
14.	潘翠珍, 潘文志, 李偉, 等. 二尖瓣解剖結構及反流的超聲心動圖心評價. 中華超聲影像學雜志, 2020, 29(12): 1095-1099.
15.	Ling LH, Enriquez-Sarano M, Seward JB, et al. Early surgery in patients with mitral regurgitation due to flail leaflets: A long-term outcome study. Circulation, 1997, 96(6): 1819-1825.
16.	Enriquez-Sarano M, Avierinos JF, Messika-Zeitoun D, et al. Quantitative determinants of the outcome of asymptomatic mitral regurgitation. N Engl J Med, 2005, 352(9): 875-883.
17.	Rossi A, Dini FL, Faggiano P, et al. Independent prognostic value of functional mitral regurgitation in patients with heart failure. A quantitative analysis of 1 256 patients with ischaemic and non-ischaemic dilated cardiomyopathy. Heart, 2011, 97(20): 1675-1680.
18.	Sannino A, Smith RL, Schiattarella GG, et al. Survival and cardiovascular outcomes of patients with secondary mitral regurgitation: A systematic review and meta-analysis. JAMA Cardiol, 2017, 2(10): 1130-1139.
19.	Goliasch G, Bartko PE, Pavo N, et al. Refining the prognostic impact of functional mitral regurgitation in chronic heart failure. Eur Heart J, 2018, 39(1): 39-46.
20.	Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS guidelines for the management of valvular heart disease. EuroIntervention, 2022, 17(14): e1126-e1196.
21.	Mirabel M, Iung B, Baron G, et al. What are the characteristics of patients with severe, symptomatic, mitral regurgitation who are denied surgery? Eur Heart J, 2007, 28(11): 1358-1365.
22.	Zhuge RQ, Hou XP, Qi XL, et al. Clinical features and treatment options for mitral regurgitation in elderly inpatients. J Geriatr Cardiol, 2018, 15(6): 428-433.
23.	潘文志, 周達新, 葛均波. 中國二尖瓣反流患者人群數量的估測. 中國胸心血管外科臨床雜志, 2021, 28(5): 495-498.
24.	Deferm S, Bertrand PB, Verbrugge FH, et al. Atrial functional mitral regurgitation: JACC review topic of the week. J Am Coll Cardiol, 2019, 73(19): 2465-2476.
25.	Delgado V, Bax JJ. Atrial functional mitral regurgitation: From mitral annulus dilatation to insufficient leaflet remodeling. Circ Cardiovasc Imaging, 2017, 10(3): e006239.
26.	Tabata N, Weber M, Sugiura A, et al. Impact of the leaflet-to-annulus index on residual mitral regurgitation in patients undergoing edge-to-edge mitral repair. JACC Cardiovasc Interv, 2019, 12(24): 2462-2472.
27.	Colli A, Besola L, Montagner M, et al. Prognostic impact of leaflet-to-annulus index in patients treated with transapical off-pump echo-guided mitral valve repair with NeoChord implantation. Int J Cardiol, 2018, 257: 235-237.
28.	Topilsky Y. Mitral regurgitation: Anatomy, physiology, and pathophysiology-lessons learned from surgery and cardiac imaging. Front Cardiovasc Med, 2020, 7: 84.
29.	Matsumoto K, Tanaka H, Okajima K, et al. Relation between left ventricular morphology and reduction in functional mitral regurgitation by cardiac resynchronization therapy in patients with idiopathic dilated cardiomyopathy. Am J Cardiol, 2011, 108(9): 1327-1334.
30.	Hang D, Schaff HV, Nishimura RA, et al. Accuracy of jet direction on doppler echocardiography in identifying the etiology of mitral regurgitation in obstructive hypertrophic cardiomyopathy. J Am Soc Echocardiogr, 2019, 32(3): 333-340.
31.	Gertz ZM, Raina A, Saghy L, et al. Evidence of atrial functional mitral regurgitation due to atrial fibrillation: Reversal with arrhythmia control. J Am Coll Cardiol, 2011, 58(14): 1474-1481.
32.	Palmiero G, Melillo E, Ferro A, et al. Significant functional mitral regurgitation affects left atrial function in heart failure patients: Haemodynamic correlations and prognostic implications. Eur Heart J Cardiovasc Imaging, 2019, 20(9): 1012-1019.
33.	Mesi O, Gad MM, Crane AD, et al. Severe atrial functional mitral regurgitation: Clinical and echocardiographic characteristics, management and outcomes. JACC Cardiovasc Imaging, 2021, 14(4): 797-808.
34.	Hu X, Jiang W, Li H, et al. Timing of valve repair for asymptomatic mitral regurgitation and preserved left ventricular function. Ann Thorac Surg, 2021, 111(3): 862-870.
35.	Zhou T, Li J, Lai H, et al. Benefits of early surgery on clinical outcomes after degenerative mitral valve repair. Ann Thorac Surg, 2018, 106(4): 1063-1070.
36.	Bergstra A, Simsek C, van den Heuvel AFM. Mitral regurgitation: When to intervene?: A historical perspective. Neth Heart J, 2020, 28(5): 266-271.
37.	Writing Committee Members, Otto CM, Nishimura RA, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol, 2021, 77(4): e25-e197.
38.	王斌, 楊杰, 王焱. 《2020 ACC/AHA 心臟瓣膜病管理指南》解讀. 華西醫學, 2021, 36(9): 1184-1190.
39.	Cimino S, Guarracino F, Valenti V, et al. Echocardiography and correction of mitral regurgitation: An unbreakable link. Cardiology, 2020, 145(2): 110-120.
40.	Donal E, Coisne A, Agricola E. Dynamic secondary mitral regurgitation: Squaring the circle. Eur Heart J Cardiovasc Imaging, 2021, 22(5): 539-540.
41.	Hamada S, Altiok E, Frick M, et al. Comparison of accuracy of mitral valve regurgitation volume determined by three-dimensional transesophageal echocardiography versus cardiac magnetic resonance imaging. Am J Cardiol, 2012, 110(7): 1015-1020.
42.	Ailawadi G, Lim DS, Mack MJ, et al. One-year outcomes after mitraclip for functional mitral regurgitation. Circulation, 2019, 139(1): 37-47.
43.	Wolff R, Uretsky S. Defining the left ventricular base in mitral valve prolapse: Impact on systolic function and regurgitation. Int J Cardiovasc Imaging, 2020, 36(11): 2221-2227.
44.	van der Land V, Germans T, van Dijk J, et al. The effect of left bundle branch block on left ventricular remodeling, dyssynchrony and deformation of the mitral valve apparatus: An observational cardiovascular magnetic resonance imaging study. Int J Cardiovasc Imaging, 2007, 23(4): 529-536.
45.	Rosa I, Marini C, Stella S, et al. Mechanical dyssynchrony and deformation imaging in patients with functional mitral regurgitation. World J Cardiol, 2016, 8(2): 146-162.
46.	Li Q, Liu Y, Zuo W, et al. Mechanisms, features, and significance of diastolic mitral regurgitation: A case series. Eur Heart J Case Rep, 2020, 4(5): 1-8.

1. 潘文志, 周達新, 葛均波. 二尖瓣反流機制的新認識及其應用. 中國醫學前沿雜志 (電子版), 2017, 9(10): 43-46.
2. Van Mieghem NM, Piazza N, Anderson RH, et al. Anatomy of the mitral valvular complex and its implications for transcatheter interventions for mitral regurgitation. J Am Coll Cardiol, 2010, 56(8): 617-626.
3. Levine RA, Hagége AA, Judge DP, et al. Mitral valve disease—Morphology and mechanisms. Nat Rev Cardiol, 2015, 12(12): 689-710.
4. Cannata F, Regazzoli D, Barberis G, et al. Mitral valve stenosis after transcatheter aortic valve replacement: Case report and review of the literature. Cardiovasc Revasc Med, 2019, 20(12): 1196-1202.
5. Ben-Shoshan J, Wang DD, Asgar AW. Left ventricular outflow tract obstruction: A potential obstacle for transcatheter mitral valve therapy. Interv Cardiol Clin, 2019, 8(3): 269-278.
6. Perpetua EM, Levin DB, Reisman M. Anatomy and function of the normal and diseased mitral apparatus: Implications for transcatheter therapy. Interv Cardiol Clin, 2016, 5(1): 1-16.
7. Fishbein GA, Fishbein MC. Mitral valve pathology. Curr Cardiol Rep, 2019, 21(7): 61.
8. Duran Karaduman B, Ayhan H, Kele? T, et al. The playmaker of the mitral valve disease: Mitral annulus. Int J Cardiol, 2020, 316: 205-206.
9. Topilsky Y, Vaturi O, Watanabe N, et al. Real-time 3-dimensional dynamics of functional mitral regurgitation: A prospective quantitative and mechanistic study. J Am Heart Assoc, 2013, 2(3): e000039.
10. Goldberg SL, Hammerstingl C. Coronary sinus-based approach to mitral regurgitation. Interv Cardiol Clin, 2016, 5(1): 93-100.
11. 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, 17(12): 807-827.
12. El Sabbagh A, Reddy YNV, Nishimura RA. Mitral valve regurgitation in the contemporary era: Insights into diagnosis, management, and future directions. JACC Cardiovasc Imaging, 2018, 11(4): 628-643.
13. de Groot-de Laat LE, McGhie J, Ren B, et al. A modified echocardiographic classification of mitral valve regurgitation mechanism: The role of three-dimensional echocardiography. J Cardiovasc Imaging, 2019, 27(3): 187-199.
14. 潘翠珍, 潘文志, 李偉, 等. 二尖瓣解剖結構及反流的超聲心動圖心評價. 中華超聲影像學雜志, 2020, 29(12): 1095-1099.
15. Ling LH, Enriquez-Sarano M, Seward JB, et al. Early surgery in patients with mitral regurgitation due to flail leaflets: A long-term outcome study. Circulation, 1997, 96(6): 1819-1825.
16. Enriquez-Sarano M, Avierinos JF, Messika-Zeitoun D, et al. Quantitative determinants of the outcome of asymptomatic mitral regurgitation. N Engl J Med, 2005, 352(9): 875-883.
17. Rossi A, Dini FL, Faggiano P, et al. Independent prognostic value of functional mitral regurgitation in patients with heart failure. A quantitative analysis of 1 256 patients with ischaemic and non-ischaemic dilated cardiomyopathy. Heart, 2011, 97(20): 1675-1680.
18. Sannino A, Smith RL, Schiattarella GG, et al. Survival and cardiovascular outcomes of patients with secondary mitral regurgitation: A systematic review and meta-analysis. JAMA Cardiol, 2017, 2(10): 1130-1139.
19. Goliasch G, Bartko PE, Pavo N, et al. Refining the prognostic impact of functional mitral regurgitation in chronic heart failure. Eur Heart J, 2018, 39(1): 39-46.
20. Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS guidelines for the management of valvular heart disease. EuroIntervention, 2022, 17(14): e1126-e1196.
21. Mirabel M, Iung B, Baron G, et al. What are the characteristics of patients with severe, symptomatic, mitral regurgitation who are denied surgery? Eur Heart J, 2007, 28(11): 1358-1365.
22. Zhuge RQ, Hou XP, Qi XL, et al. Clinical features and treatment options for mitral regurgitation in elderly inpatients. J Geriatr Cardiol, 2018, 15(6): 428-433.
23. 潘文志, 周達新, 葛均波. 中國二尖瓣反流患者人群數量的估測. 中國胸心血管外科臨床雜志, 2021, 28(5): 495-498.
24. Deferm S, Bertrand PB, Verbrugge FH, et al. Atrial functional mitral regurgitation: JACC review topic of the week. J Am Coll Cardiol, 2019, 73(19): 2465-2476.
25. Delgado V, Bax JJ. Atrial functional mitral regurgitation: From mitral annulus dilatation to insufficient leaflet remodeling. Circ Cardiovasc Imaging, 2017, 10(3): e006239.
26. Tabata N, Weber M, Sugiura A, et al. Impact of the leaflet-to-annulus index on residual mitral regurgitation in patients undergoing edge-to-edge mitral repair. JACC Cardiovasc Interv, 2019, 12(24): 2462-2472.
27. Colli A, Besola L, Montagner M, et al. Prognostic impact of leaflet-to-annulus index in patients treated with transapical off-pump echo-guided mitral valve repair with NeoChord implantation. Int J Cardiol, 2018, 257: 235-237.
28. Topilsky Y. Mitral regurgitation: Anatomy, physiology, and pathophysiology-lessons learned from surgery and cardiac imaging. Front Cardiovasc Med, 2020, 7: 84.
29. Matsumoto K, Tanaka H, Okajima K, et al. Relation between left ventricular morphology and reduction in functional mitral regurgitation by cardiac resynchronization therapy in patients with idiopathic dilated cardiomyopathy. Am J Cardiol, 2011, 108(9): 1327-1334.
30. Hang D, Schaff HV, Nishimura RA, et al. Accuracy of jet direction on doppler echocardiography in identifying the etiology of mitral regurgitation in obstructive hypertrophic cardiomyopathy. J Am Soc Echocardiogr, 2019, 32(3): 333-340.
31. Gertz ZM, Raina A, Saghy L, et al. Evidence of atrial functional mitral regurgitation due to atrial fibrillation: Reversal with arrhythmia control. J Am Coll Cardiol, 2011, 58(14): 1474-1481.
32. Palmiero G, Melillo E, Ferro A, et al. Significant functional mitral regurgitation affects left atrial function in heart failure patients: Haemodynamic correlations and prognostic implications. Eur Heart J Cardiovasc Imaging, 2019, 20(9): 1012-1019.
33. Mesi O, Gad MM, Crane AD, et al. Severe atrial functional mitral regurgitation: Clinical and echocardiographic characteristics, management and outcomes. JACC Cardiovasc Imaging, 2021, 14(4): 797-808.
34. Hu X, Jiang W, Li H, et al. Timing of valve repair for asymptomatic mitral regurgitation and preserved left ventricular function. Ann Thorac Surg, 2021, 111(3): 862-870.
35. Zhou T, Li J, Lai H, et al. Benefits of early surgery on clinical outcomes after degenerative mitral valve repair. Ann Thorac Surg, 2018, 106(4): 1063-1070.
36. Bergstra A, Simsek C, van den Heuvel AFM. Mitral regurgitation: When to intervene?: A historical perspective. Neth Heart J, 2020, 28(5): 266-271.
37. Writing Committee Members, Otto CM, Nishimura RA, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol, 2021, 77(4): e25-e197.
38. 王斌, 楊杰, 王焱. 《2020 ACC/AHA 心臟瓣膜病管理指南》解讀. 華西醫學, 2021, 36(9): 1184-1190.
39. Cimino S, Guarracino F, Valenti V, et al. Echocardiography and correction of mitral regurgitation: An unbreakable link. Cardiology, 2020, 145(2): 110-120.
40. Donal E, Coisne A, Agricola E. Dynamic secondary mitral regurgitation: Squaring the circle. Eur Heart J Cardiovasc Imaging, 2021, 22(5): 539-540.
41. Hamada S, Altiok E, Frick M, et al. Comparison of accuracy of mitral valve regurgitation volume determined by three-dimensional transesophageal echocardiography versus cardiac magnetic resonance imaging. Am J Cardiol, 2012, 110(7): 1015-1020.
42. Ailawadi G, Lim DS, Mack MJ, et al. One-year outcomes after mitraclip for functional mitral regurgitation. Circulation, 2019, 139(1): 37-47.
43. Wolff R, Uretsky S. Defining the left ventricular base in mitral valve prolapse: Impact on systolic function and regurgitation. Int J Cardiovasc Imaging, 2020, 36(11): 2221-2227.
44. van der Land V, Germans T, van Dijk J, et al. The effect of left bundle branch block on left ventricular remodeling, dyssynchrony and deformation of the mitral valve apparatus: An observational cardiovascular magnetic resonance imaging study. Int J Cardiovasc Imaging, 2007, 23(4): 529-536.
45. Rosa I, Marini C, Stella S, et al. Mechanical dyssynchrony and deformation imaging in patients with functional mitral regurgitation. World J Cardiol, 2016, 8(2): 146-162.
46. Li Q, Liu Y, Zuo W, et al. Mechanisms, features, and significance of diastolic mitral regurgitation: A case series. Eur Heart J Case Rep, 2020, 4(5): 1-8.

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