Mitral plasticity: possible target for intervention in patients with ischaemic mitral regurgitation?

This editorial refers to ‘Clinical and echocardiographic factors associated with mitral plasticity in patients with chronic inferior myocardial infarction’ by N. Ávila-Vanzzinie et al., pp. 508–515. Ischaemic mitral regurgitation (IMR) occurs despite structurally normal mitral leaflets as a consequence of left ventricular (LV) dysfunction.1 Severe IMR is associated with poor haemodynamics and prognosis2 underscoring the importance of comprehending its determinants. IMR is indisputably associated with LV remodelling and enlargement, but has been variably attributed also to mitral annulus enlargement, and displacement of papillary muscles leading to excess valvular tenting.3 In patients with inferior myocardial infarction (MI), 3D echo analysis showed that patients with MR have similar annular area, but a lower saddle-shape depth, larger distances between the posterior papillary muscle and the anterior annulus, and asymmetric papillary muscle position compared to patients with inferior MI and no MR.4 Recent studies have shown that the mitral valve is able to adjust, or mal-adapt to stress imposed by the failing left ventricle. It may enlarge to compensate for LV remodelling and tenting, or to the stress generated by turbulent MR jets on the atrial face of the valve,5 improving its coaptation surface, and decreasing the severity of MR.6,7 This process was termed ‘mitral plasticity’. However, not all patients with inferior MI exhibit plasticity, and in some that do, it may be insufficient to prevent significant MR. Furthermore, in some patients with IMR, leaflets may become thick and fibrotic, worsening MR.8,9 Studies have shown that mechanical tethering is a trigger for mitral plasticity, and it is suggested that this increase in leaflet length represents an adaptation mechanism. In this issue of the European Heart Journal – Cardiovascular Imaging, Avila-Vanzzinie et al.10 conducted an observational, retrospective multicentre study that tried to identify the clinical factors associated with mitral valve plasticity in patients with chronic inferior MI. They also tried to determine if mitral plasticity correlates with the severity of IMR and identify structural LV parameters beyond the mitral valve that could be associated to plasticity. The authors evaluated 91 patients with chronic inferior MI and 46 consecutive controls. Out of the 91 inferior MI patients, 60 had mitral plasticity [defined as at least two of three: long anterior leaflet, long posterior leaflet, or longer posterior chords (compared to accepted normal values)], and 31 patients had no plasticity. Multivariate analysis demonstrated less plasticity in smokers but more plasticity in patients with long duration of type-2 diabetes and high haemoglobin. Surprisingly, patients with mitral plasticity did not exhibit significantly larger LV volumes, tenting area or height, compared to patients with no plasticity. The only structural difference between patients with, or without plasticity was increased anterior papillary muscle to annulus length in the plasticity patients, far away from the scarred segments. As expected, they found that patients with plasticity had less IMR compared to non-plasticity inferior MI patients. The authors speculated that smoking may be associated with absence of plasticity because of the toxic effect of nicotine on both the ventricular and atrial myocardium, leading to interstitial fibrosis of the leaflets.11 They suggested that the independent positive association between type-2 diabetes and plasticity may be due to the mitotic effect of excess insulin, present in many patients with insulin resistance. As to the strong association between anaemia and lack of plasticity, they speculated that lack of plasticity resulted in IMR, creating turbulent viscous shear stress forces, resulting in low-grade haemolysis.12 The haemolysis would result in lower haemoglobin levels in inferior MI patients with no plasticity who exhibit significantly worse Ischemic Mitral Regurgitation severity. Still, it is important to remember that although the present work seems to be a first important step in the right direction for searching for ways to induce accelerated plasticity, the article has several limitations. The researchers used 2D Trans Thoracic Echo which is not the ideal method to evaluate the complex interplay of the 3D mitral valve apparatus. Quantification of MR was not performed for all patients. The study included only patients with re-vascularized inferior MI, thus may not relate to other types of patients with IMR. Due to its retrospective nature the study is subject to selection bias and its results imply association and not cause and effect. The lack of interaction between LV volumes, tenting area or height, and plasticity should be interpreted cautiously due to the relatively small number of patients. Yet, despite these limitations, the observations presented in the study have important clinical implications. The current medical, surgical, or percutaneous treatment for patients suffering from MI and IMR has not yielded the expected beneficial results.13 As we search for better therapies for IMR, that could promote plasticity and reduce or prevent the detrimental effects of regurgitation, the first reasonable step is to see why some patients have plasticity and others do not, focusing for clinical modifiable factors. We believe it is essential to perform larger trials in patients with all types of IMR to conclude what are the factors associated with plasticity, to analyse the patho-physiological mechanisms linking between these factor and plasticity before moving to the last step, possible targets for intervention in IMR. Conflict of interest: None declared.