There is not such a long time between late and too late: look at it earlier!

This editorial refers to ‘The unique mechanism of functional mitral regurgitation in acute myocardial infarction: a prospective dynamic 4D quantitative echocardiographic study’, by T. Kimura et al., pp. 396–406. Secondary mitral regurgitation (MR) embraces non-ischaemic and ischaemic and non-ischaemic aetiologies and, in its chronic phase, results from a functional imbalance between increased tethering forces and decreased closing forces. The imbalance between tethering and closing forces typically occurs in patients in all with prior myocardial infarction (MI) or when the left ventricle (LV) dilates, causing the papillary muscles (PM) to be displaced and/or to move dyssynchronously while also the closing force is generally impaired. As a result, increased tethering on the mitral valve leaflets occurs during systole resulting in incomplete leaflet coaptation and MR. It was believed for long that these pathophysiological mechanism occur in the presence of structurally normal valve which is now refuted since valvular tissue may adapt to tethering and modify its size and structure.1–3 Secondary MR has emerged as a leading cause of MR in Europe, representing up to 31% of patients in its isolated form, and being more frequent in men than in women.4 Dziadzko et al.5 recently reported that 65% of MR in Olmsted County were secondary MR, 36% related to ischaemic LV dysfunction. The prevalence of secondary MR represents 20–25% of patients after MI. In addition, due to the increase incidence of MI related to expansion of cardio-metabolic burden, combined with improvement of management and early care will probably results in higher prevalence of secondary MR in the next decades. Secondary MR is often symptomatic and is also associated with lower exercise capacity, increasing heart failure, and with excess mortality. Optimal therapeutic approach remains one of the most important unmet clinical needs in the field of structural heart disease. Nowadays, in the absence of evidence to support that surgery improves survival and clinical outcome, more than 50% of these patients are not undergoing surgery, most of them presenting with a non-ischaemic aetiology.3,5 Such undertreatment might reflect that these patients are referred to cardiology centres too late, with many of them presenting with advanced heart failure. Indeed, pathophysiologic mechanisms and therapeutical options were mainly studied in chronic clinical setting, but pathophysiology of secondary MR in the early phase of acute-MI remains poorly defined. Three-dimensional echocardiography may allow measuring annular and leaflet morphology in a more accurate and quantitative way and to follow these parameters throughout the cardiac cycle.6 It also permits the reorientation of regurgitant jets in a perpendicular planes for more accurate measurements.6 In the present bi-centric study, Kimura et al.7 sought to demonstrate that mitral apparatus dynamic alterations of the mitral apparatus differ between chronic and acute secondary MR of ischaemic aetiology using new 4D-imaging/software to quantify dynamically mitral and LV characteristics. They matched (1:1) two groups of patients with acute-MI with similar infarct size according to the presence or absence of MR. This results in highly similar groups regarding demographic, and clinical data, as well as risk factors. They showed that despite similar size of acute-MI and low regurgitant volumes, secondary MR was associated with marked haemodynamic alterations, larger LV volumes, and markedly reduced forward stroke-volume, worse with increasing MR severity. Contrasting with loss of dynamicity of annulus and PM of MR associated with chronic-MI, in acute-MI annulus and PM remained dynamic. The traditional secondary MR mechanisms, flattening/enlargement of mitral annulus and valvular tenting, while present in acute MR were modest, less severe than in chronic-MI, but were linked to MR severity. Moreover, the deformation typically associated with MR complicating acute-MI, consisted in a greater PM angulation resulting to excessive leaflets tension and regurgitation. PM excess angulation, while dynamic, remained widest throughout the cardiac cycle in secondary MR complicating acute-MI. Although animal studies have been performed in the early phases of acute-MI in order to evaluate the effects on MR,7,8,9 only few data are available in patients. In this particular study, the echocardiographic evaluation was performed early after the onset of acute-MI, using 3D echocardiography, the most up-to-date ultrasound approach to evaluate the mitral valve apparatus and the LV function and geometry. In parallel, patients with or without MR in more chronic phase of MI were also submitted to the same evaluation. The difference in mechanisms between acute and chronic-MI secondary MR are not that surprising. The physiopathology of secondary MR is mainly related to adaptative/maladaptative process occurring within the following months after the acute onset of MI. Several of them have been identified as change in LV sphericity, PM dyssynchrony, wall motion abnormalities, annular dilatation, and tenting. The effectiveness of revascularisation at the acute phase, the area at risk, the remaining significant epicardial arteries lesions, the presence of ischaemia … are many parameters that will condition the evolution of these processes over time. The comparison of the mechanisms in two separate cohorts is a first step to demonstrate these differences in acute vs. chronic-MI patients, but ideally the same patients should be followed with control echocardiography performed regularly to assess the dynamicity of the MR itself, as well as the driving parameters leading to a more chronic MR or evolving MR (progression or regression). A recent study performed in patients with secondary MR and severe LV dysfunction showed that an evolving severity of the MR was associated to worse prognosis, even compared with those presenting with a severe MR from the beginning of the follow-up.10 The chronic-MI group may be a group of survivors with the most diseased patients lost for inclusion. The OxVALVE study has shown that many patients have underdiagnosed valvular heart disease11 and some of the acute-MI group might present with a previous MR related to another aetiology. In a recent study,5 the cause of secondary MR was an isolated dilatation of the left atrium (LA) in 17% of the secondary MR population. It remains interesting to note that the acute-MI group presents with larger LA.12,13 More information regarding dyssynchrony of PM or the impact of scar/fibrosis post-revascularization on the evolution of the MR still needs to be assessed. Meanwhile, the present study offers a glimpse regarding new insights in the mechanisms of acute-MI secondary MR and the difference compared with chronic-MI secondary MR, using up-to-date echocardiographic modalities. More efforts are still needed to better understand which mechanisms will lead to rapid and/or long-term complications related to secondary MR and how to tackle them in due time. Conflict of interest: none declared.