Atrial functional mitral regurgitation: an electro-mechanical interplay

This editorial refers to ‘Incidence, risk factors, and outcomes of atrial functional mitral regurgitation in patients with atrial fibrillation or sinus rhythm’, by J.A. Naser et al., https://doi.org/10.1093/ehjci/jead199. Mitral regurgitation (MR) has long been classified as primary (or organic), when resulting from a structural abnormality of the leaflets or subvalvular apparatus, and secondary (or functional), when due to remodelling of the left ventricle (LV) leading to altered mechanics of the subvalvular apparatus with subsequent tenting of the leaflets and dilatation of the mitral annulus. Although atrial functional MR (AFMR), in which the causative mechanism underlying the development of MR is mainly atrial and annular dilatation typically due to atrial fibrillation (AF) and/or heart failure with preserved ejection fraction (HFpEF), was described by Gertz et al.,1 it is only in recent years that the role of AFMR has been increasingly recognized. In this issue of the Journal, Naser et al.2 present the results from a single-centre observational study assessing the incidence, prognosis, and risk factors of AFMR in 1747 adult patients with a new diagnosis of AF and 29,623 patients in sinus rhythm. Of note, no patient had evidence of left-sided valvular disease (including more than mild MR) or cardiomyopathy at baseline. AF was associated with a three-fold increase in the risk of developing more than mild AFMR (incidence rate 2.6 per 100-person years for patients with AF vs. 0.7 per 100-person years for those in sinus rhythm). AF remained associated with the development of AFMR in a propensity-score matched analysis based on age, sex, and comorbidities. In addition to rate (as opposed to rhythm) control, independent risk factors associated with incident AFMR were age ≥65 years, female sex, left atrial (LA) volume index, and diastolic dysfunction. Incident AFMR was the strongest predictor of all-cause death in both groups. Despite the inherent limitations due to the retrospective observational design of the study, including having potentially included sicker patients more prone to the development of AFMR, this study provides important information not only on the additional risk of AFMR occurrence in patients with AF but also on the time course. The proportion of patients developing incident AFMR started to increase as early as 1 year after a new diagnosis of AF compared to patients in sinus rhythm. Age ≥65 year was one of the identified risk factors for developing AFMR in patients with AF. However, because the median follow-up duration of this study was only 4.9 years, the development of new-onset AF in young patients should not be considered at low risk, since younger patients (<65 years) have most likely a higher cumulative lifetime risk of developing incident AFMR than do older patients. In this study by Naser et al., AFMR was defined as functional MR without LV dysfunction or enlargement, and LA enlargement, enabling a focus on pure AFMR. However, there may be some overlap between ventricular functional MR (VFMR) and AFMR.3 Indeed, longstanding significant VFMR results in dilatation of the left atrium and mitral annulus due to volume overload (‘VFMR begets AFMR’), whereas, on the other hand, longstanding significant AFMR may eventually result in LV dilatation/dysfunction (‘AFMR begets VFMR’) (Figure 1). These patients with mixed forms of functional MR were thus considered as having VFMR and not included, which may have led to an underestimation of AFMR incidence. Pathophysiology of AFMR. AFMR, defined as functional MR caused by LA and annular dilatation without significant LV enlargement or dysfunction, is typically caused by AF, and/or HFpEF. Longstanding significant AFMR may induce VFMR due to volume overload, resulting in ‘mixed’ functional MR, which in turn, may aggravate AFMR. See text for details. Abbreviation: MV, Mitral valve. Moreover, AFMR was reported as a dichotomous variable (> vs. ≤mild AFMR). Whether an estimate of AFMR severity would have improved prognostication or whether the cut-offs for MR severity proposed by the current ESC Guidelines4 should be similar in AFMR and VFMR, remains unknown. Because of the smaller size of the LV in AFMR than in VFMR, a given amount of regurgitant volume that would be consistent with moderate VFMR may turn out to be more severe in the typically normal-sized or relatively small ventricles of AFMR, thereby significantly reducing forward stroke volume. Of note, the study by Naser et al. focuses on the link between AF and AFMR, but the correlation is not necessarily causation: whether AF induces AFMR or whether AFMR promotes AF recurrence (Figure 1) cannot be ascertained, because of the study design. However, the independent protective value of successful rhythm control is consistent with the first hypothesis and in line with the EAST-AFNET 4 trial, in which early rhythm-control strategies were associated with a lower risk of adverse cardiovascular outcomes compared to usual care.5 Similar uncertainties apply to AFMR and HFpEF, namely, that in some patients with suspected HFpEF, heart failure may in fact result mainly from AFMR (Figure 1), rather than the other way around. Causation or not, it is likely that the deleterious effects of both AF and AFMR translate into a vicious circle that should be interrupted early. All efforts should thus be made to treat conditions prone to causing AF and diastolic dysfunction (including hypertension, obesity, diabetes, …). Once AF develops, reverse remodelling of the left atrium should be the goal. Prospective trials are needed to determine whether, in patients with established AFMR, this would best be achieved through strategies designed to restore and maintain sinus rhythm, or using structural procedures targeting MR, such as transcatheter or surgical MR correction (with or without concomitant rhythm-control strategies). The burden of AF is increasing in patients admitted for heart failure,6 reinforcing the need for better awareness of the incidence of AFMR and understanding of AF-/HFpEF-related pathophysiology, as well as consequent outcomes. At present, AFMR remains under-recognized and insufficiently understood.7 This study by Naser et al. makes a significant step forward in our knowledge about this condition, and its authors can be commended for it. None declared.