Deep Dive into Atrial Functional Mitral Regurgitation

Abstract

Atrial functional mitral regurgitation (AFMR) has been recently recognized as a subcategory of functional mitral regurgitation characterized by severe left atrial (LA) dilation and normal left ventricular (LV) dimensions and function. AFMR typically occurs in patients with atrial fibrillation (AF) and/or heart failure with preserved ejection fraction.1Kagiyama N Mondillo S Yoshida K Mandoli GE Cameli M Subtypes of atrial functional mitral regurgitation: imaging insights into their mechanisms and therapeutic implications.JACC Cardiovasc Imaging. 2020; 13 (doi:10.1016/j.jcmg.2019.01.040.): 820-835Google Scholar Mitral annular dilation caused by severe LA remodeling has been traditionally considered the key mechanism of AFMR.1Kagiyama N Mondillo S Yoshida K Mandoli GE Cameli M Subtypes of atrial functional mitral regurgitation: imaging insights into their mechanisms and therapeutic implications.JACC Cardiovasc Imaging. 2020; 13 (doi:10.1016/j.jcmg.2019.01.040.): 820-835Google Scholar However, the use of 3-dimensional imaging techniques and the study of LA mechanics have shown that other factors such as insufficient leaflet remodeling, atriogenic leaflet tethering, impaired annular dynamics and altered atrial mechanics may contribute to AFMR pathogenesis. The mitral leaflets are not static structures and they remodel in response to annular dilatation and increased tethering. However, when the leaflet remodeling is insufficient to compensate the mitral annulus dilation or the excessive tethering, significant mitral regurgitation will occur. Recent studies with 3-dimensional echocardiography (3DE) showed that in patients with AFMR the ratio of mitral leaflet area to the mitral annular area was significantly reduced in comparison to patients with AF but without AFMR.2Kagiyama N Hayashida A Toki M et al.Insufficient leaflet remodeling in patients with atrial fibrillation: association with the severity of mitral regurgitation.Circ Cardiovasc Imaging. 2017; 10 (doi:10.1161/CIRCIMAGING.116.005451.): e005451Google Scholar,3Kim DH Heo R Handschumacher MD et al.Mitral valve adaptation to isolated annular dilation: insights into the mechanism of atrial functional mitral regurgitation.JACC Cardiovasc Imaging. 2019; 12 (doi:10.1016/j.jcmg.2017.09.013.): 655-677Google Scholar In addition, Dr Silbiger has proposed specific “atriogenic leaflet tethering” of the mitral valve that can lead to mitral regurgitation.4Silbiger JJ Does left atrial enlargement contribute to mitral leaflet tethering in patients with functional mitral regurgitation? Proposed role of atriogenic leaflet tethering.Echocardiography. 2014; 31 (doi:10.1111/echo.12629.): 1310-1311Google Scholar The LA dilation displaces the posterior mitral annulus toward the outside of the LV myocardium causing 1) reduction of the posterior leaflet area available for the coaptation 2) tethering of the posterior mitral leaflet by increasing the annulo-papillary muscle distance and 3) counterclockwise-directed torque of the anterior annulus with a subsequent tethering of the anterior mitral leaflet.4Silbiger JJ Does left atrial enlargement contribute to mitral leaflet tethering in patients with functional mitral regurgitation? Proposed role of atriogenic leaflet tethering.Echocardiography. 2014; 31 (doi:10.1111/echo.12629.): 1310-1311Google Scholar This pathophysiological mechanism of AFMR has been demonstrated in several 3DE studies that showed increased annular-posterior leaflet tip angle, as result of the posterior leaflet bending toward the LV cavity.5Ito K Abe Y Takahashi Y et al.Mechanism of atrial functional mitral regurgitation in patients with atrial fibrillation: a study using three dimensional transesophageal echocardiography.J Cardiol. 2017; 70 (doi:10.1016/j.jjcc.2017.03.013.): 584-590Google Scholar,6Takahashi Y Abe Y Sasaki Y et al.Mitral valve repair for atrial functional mitral regurgitation in patients with chronic atrial fibrillation.Interact Cardiovasc Thorac Surg. 2015; 21 (doi:10.1093/icvts/ivv119.): 163-168Google Scholar Additionally, a larger reduction of fractional mitral annular area change, together with a flattened annulus has been described in patient with AF and AFMR, as compared to patients with AF but without AFMR and individuals without AF and mitral regurgitation.7Machino-Ohtsuka T Seo Y Ishizu T et al.Novel mechanistic insights into atrial functional mitral regurgitation-3-dimensional echocardiographic study.Circ J. 2016; 80 (doi:10.1253/circj.CJ-16-0435.): 2240-2248Google Scholar,8Tang Z Fan YT Wang Y Jin CN Kwok KW Lee AP Mitral annular and left ventricular dynamics in atrial functional mitral regurgitation: a three-dimensional and speckle-tracking echocardiographic study.J Am Soc Echocardiogr. 2019; 32 (doi:10.1016/j.echo.2018.11.009.): 503-513Google Scholar Impaired LV longitudinal strain and LA strain were significantly associated with reduced mitral annulus dynamics but only the impairment of LV longitudinal strain was associated with the presence of significant mitral regurgitation.8Tang Z Fan YT Wang Y Jin CN Kwok KW Lee AP Mitral annular and left ventricular dynamics in atrial functional mitral regurgitation: a three-dimensional and speckle-tracking echocardiographic study.J Am Soc Echocardiogr. 2019; 32 (doi:10.1016/j.echo.2018.11.009.): 503-513Google Scholar In the current issue of Structural Heart: The Journal of the Heart Team, Matta et al.9Matta M, Ayoub C, Ossama K, et al. Anatomic and functional determinants of atrial functional mitral regurgitation. Struct Heart. 2021;this issue. doi:10.1080/24748706.2021.1943765.Google Scholar provide additional insights into the anatomic and functional determinants of AFMR. Among patients with AF referred to cardiac CT for pulmonary vein isolation or appendage occlusion, 50 patients with at least moderate AFMR were selected and matched by sex and age with 50 patients with AF and no AFMR. The authors performed a comprehensive multimodality imaging assessment of mitral valve apparatus, LV and LA volumes and mechanics. On cardiac CT, patients with AFMR showed larger LA area and mitral annular dimensions, as compared to controls, but smaller leaflet length to annular area ratio, indicating an insufficient leaflet remodeling. Additionally, the AFMR group presented more acute posterior closing angle (measured between the annular plane and the posterior leaflet), reflecting the outward displacement of the posterior annulus and the subsequent atriogenic tethering of the posterior leaflet. Interestingly, tenting height and area of the mitral valve, were not significantly different between the two groups, a distinct characteristic that makes AFMR different from functional mitral regurgitation caused by LV dilation and dysfunction. Signs of a more advanced LV diastolic dysfunction (shorter deceleration time and isovolumetric relaxation time) and higher estimated pulmonary systolic pressure were also observed in patients with AFMR, in comparison to controls. Additionally, the AFMR group showed a larger impairment of both LA and LV longitudinal strain. In terms of 3D quantitative analysis of mitral geometry using cardiac CT, the authors confirmed the findings of previous 3DE studies regarding the role of insufficient leaflet remodeling2Kagiyama N Hayashida A Toki M et al.Insufficient leaflet remodeling in patients with atrial fibrillation: association with the severity of mitral regurgitation.Circ Cardiovasc Imaging. 2017; 10 (doi:10.1161/CIRCIMAGING.116.005451.): e005451Google Scholar,3Kim DH Heo R Handschumacher MD et al.Mitral valve adaptation to isolated annular dilation: insights into the mechanism of atrial functional mitral regurgitation.JACC Cardiovasc Imaging. 2019; 12 (doi:10.1016/j.jcmg.2017.09.013.): 655-677Google Scholar and atriogenic leaflet tethering5Ito K Abe Y Takahashi Y et al.Mechanism of atrial functional mitral regurgitation in patients with atrial fibrillation: a study using three dimensional transesophageal echocardiography.J Cardiol. 2017; 70 (doi:10.1016/j.jjcc.2017.03.013.): 584-590Google Scholar,6Takahashi Y Abe Y Sasaki Y et al.Mitral valve repair for atrial functional mitral regurgitation in patients with chronic atrial fibrillation.Interact Cardiovasc Thorac Surg. 2015; 21 (doi:10.1093/icvts/ivv119.): 163-168Google Scholar in the development of significant mitral regurgitation, adding evidence on the multifactorial nature of AFMR pathogenesis. It is important to note, that the present study included patients with mostly moderate AFMR for whom current guidelines do not have specific recommendation to intervene. However, the inclusion of patients with severe AFMR could have led perhaps to inconclusive results since, in patients with more severe mitral regurgitation, the alterations in the mitral valve geometry may be more advanced and indistinguishable from functional mitral regurgitation caused by LV dysfunction. Alternatively, proving that successful pulmonary vein isolation leads to restoration of mitral valve geometry, improvement in mitral annulus dynamics and LV and LA mechanics and disappearance of AFMR, is important to emphasize the need of rhythm control. The benefit of early rhythm control on cardiovascular outcomes has been recently demonstrated by the Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST-AFNET 4),10Kirchhof P Camm AJ Goette A et al.Early rhythm-control therapy in patients with atrial fibrillation.N Engl J Med. 2020; 383 (doi:10.1056/NEJMoa2019422.): 1305-1316Google Scholar but randomized studies demonstrating the efficacy of this strategy on reversing AFMR are awaited. Matta et al.9Matta M, Ayoub C, Ossama K, et al. Anatomic and functional determinants of atrial functional mitral regurgitation. Struct Heart. 2021;this issue. doi:10.1080/24748706.2021.1943765.Google Scholar showed that in a subgroup of 7 patients with successful pulmonary vein isolation and AFMR who had echocardiographic data at follow-up, 5 had reduction of AFMR to mild grade. However, no data on mitral valve geometry and dynamics and LV and LA dimensions and strain were reported. Improving our understanding in the pathophysiology of AFMR will help to develop effective strategies to treat the patients and improve outcomes.