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Treatment options for the management of atrial functional mitral regurgitation
  1. Chihiro Saito,
  2. Yuichiro Minami,
  3. Nobuhisa Hagiwara
  1. Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan
  1. Correspondence to Dr Yuichiro Minami, Department of Cardiology, Tokyo Women's Medical University, Tokyo 162-8666, Japan; yuichiro24{at}celery.ocn.ne.jp

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Functional mitral regurgitation (FMR) is a common problem, especially in patients with heart failure. Conventional FMR caused by left ventricular (LV) dilatation or LV dysfunction and mitral valve tethering (termed ventricular FMR (VFMR)) is widely recognised. However, with the ageing of the heart failure population, the concept of atrial FMR (AFMR) caused by left atrial (LA) enlargement but with normal LV size and function was recently proposed.1 Although AFMR generally occurs in patients with atrial fibrillation (AF) and/or heart failure with preserved ejection fraction (HFpEF), little is known about its pathophysiology, epidemiology, prognosis and treatment options.2

Sébastien Deferm and colleagues3 report the efficacy of mitral valve annuloplasty (MVA) for patients with AFMR (n=97) compared with those with VFMR (n=119). They defined AFMR as mitral regurgitation (MR) caused by isolated annular dilatation in the absence of intrinsic valvular and LV disease, with invariably normal LV volume and global/regional systolic function (ie, LV ejection fraction (LVEF) ≥50%). VFMR also included patients with subvalvular leaflet tethering, with reduced LVEF (<50%) and/or global or regional alterations in LV geometry. They showed that patients with AFMR were typically women, with a history of AF and with a larger LA size compared with patients with VFMR. During a follow-up of 3.3 years, prognosis after MVA for treatment of AFMR was better than that after MVA for treatment of VFMR, as reflected by lower all-cause mortality and recurrence of moderate or greater MR independent of baseline differences. This is the first study to show the long-term efficacy of MVA for AFMR.

Since first described by Gertz et al,1 AFMR has been widely discussed as a new concept. However, even the definition of AFMR remains ambiguous. According to this issue of Heart and several studies, the current mainstream definition of AFMR is that it is caused by isolated dilatation of the mitral annulus, but with a normal LV volume and systolic function (LVEF >50%).2 3 There are also various reports on the pathophysiology of AFMR (figure 1). Gertz et al and several other studies described isolated mitral annulus dilatation resulting from LA enlargement as the main cause of AFMR in patients with AF.1 HFpEF may also produce a similar situation of AFMR via LV diastolic dysfunction and mitral annular dilatation. Kim et al 4 reported that insufficient leaflet growth in response to annular stretch (termed the annulus annular–leaflet imbalance) is the next main cause of AFMR. Patients with AFMR showed significantly smaller mitral leaflets compared with mitral annulus, and the degree of leaflet remodelling was associated with the severity of AFMR. Another possible mechanism of AFMR, termed atriogenic leaflet tethering, was also reported.2 The posterior portion of the mitral annulus is attached to the junction of the LA and free wall of the LV, which is stretched outward when the LA and mitral annulus enlarge. Expansion of the LA wall leads to deviation of the posterior annulus towards the outside of the myocardium, causing tethering of the posterior leaflet. However, there are many unanswered questions about the pathophysiology of AFMR, such as which patients with AF and/or HFpEF have AFMR and which patients with AFMR have concomitant tricuspid regurgitation (TR). Many of these questions may eventually be answered by genomic studies in the future.

Figure 1

Pathophysiology of atrial functional mitral regurgitation.

The prevalence and prognostic implications of AFMR are also poorly understood. Although the prevalence varies widely between studies, this may relate to differences in the methods used for MR grading and the study population. AFMR was present in 4%–8% of patients with AF and the prevalence increased with duration of AF—up to 28% in patients with AF for >10 years.2 Moreover, the prevalence of AFMR increased up to 53% in patients with HFpEF.2 With respect to prognostic implications, we previously reported the prognosis of hospitalised patients with heart failure with AFMR.5 Patients with AFMR had a significantly higher prevalence of adverse events during the follow-up period, especially rehospitalisation for heart failure, compared with patients with no/mild MR.5 Furthermore, there were no differences in the composite endpoints of cardiac death and rehospitalisation for heart failure between patients with AFMR and patients with VFMR.5 Abe et al 6 reported the presence of AFMR and concomitant TR in patients with long-standing AF, with the combination of these regurgitations associated with a higher rate of the composite endpoint of cardiac death, rehospitalisation for heart failure, and mitral and/or tricuspid surgery. Mesi et al 7 recently reported that patients with severe AFMR had worse survival and a higher incidence of heart failure hospitalisation compared with patients with severe degenerative MR. Notably, patients with AFMR were less likely to undergo mitral valve intervention, although surgery was associated with improved survival. Therefore, patients with AFMR may require more intensive and careful treatment, and the treatment options should be thoroughly discussed.

There are limited studies on the therapeutic options for management of AFMR, while current guidelines do not discriminate between secondary MR and AFMR. Optimal heart failure medical therapy is the cornerstone treatment for secondary MR including AFMR, because MR adds volume overload to a decompensated LA and LV. However, at present, there are no drugs proven to reduce morbidity and/or mortality in patients with HFpEF. Good hypertension control (pharmacological and/or renal denervation) may reduce AFMR by improving LV diastolic dysfunction and the resulting HFpEF. Rhythm control strategies for AF include pharmacological therapies, cardioversion, and catheter or surgical ablation. Although pharmacological therapies are easy to initiate and are non-invasive, many antiarrhythmic drugs have negative inotropic and paradoxical arrhythmogenic effects and should be carefully used, especially in patients with heart failure. A previous study reported improvements in LA volume and less MR at 1 month after cardioversion.2 In addition, Gertz et al suggested that restoring sinus rhythm by AF catheter ablation had a therapeutic effect on AFMR by improving LA enlargement, suggesting a causal relationship between AF and MR, rather than AF being just a confounder or a consequence of significant MR.1 Thus, AFMR may benefit from sinus rhythm restoration strategies via reverse LA anatomical and mechanical remodelling. However, this strategy should only be adapted in the early stages of the disease because AF duration is inversely linked to the ability to maintain sinus rhythm. Further prospective trials that examine the effect of early-stage AF ablation on reversal of AFMR are required.

Surgical interventions may currently be the most reliable treatment option for MR in patients with AFMR. As shown in this issue of Heart, MVA can be a useful treatment option for AFMR, while concomitant tricuspid annuloplasty can be performed for surgical treatment. However, patients with AFMR with a predominantly elderly background may not be able to receive the relatively invasive procedure. Additionally, the criteria for intervention to concomitant TR in patients with AFMR remain unclear. As a less invasive option, catheter-based interventions may be an alternative for AFMR. Recently, Yoshida et al 8 reported the clinical outcomes of patients with AFMR who underwent the MitraClip procedure compared with those with conventional FMR and sinus rhythm. The authors found a reduction of MR in AFMR, which was likely due to the increase in the leaflet coaptation area. Although significant TR was more common after the MitraClip procedure in patients with AFMR than in those with sinus FMR, midterm outcomes were comparable between the two groups. In addition to MitraClip, several other devices with various unique mechanisms, including mimicking surgical annuloplasty, are being developed. These devices are expected to be effective in the annulus area to leaflet area imbalance. These catheter-based interventions may become useful alternatives for AFMR as these patients tend to be old, present with concomitant comorbidities and have high surgical risk.

The treatment options for patients with AFMR are summarised in figure 2. As reported by Deferm et al,3 MVA may be a useful treatment option for patients with advanced AFMR with low surgical risk. However, it is not entirely clear which of the variety of options should be chosen in each individual case with AFMR. Further research is needed to determine a proper definition, elucidate its pathophysiology, understand the prognostic significance and establish appropriate treatment strategies for AFMR.

Figure 2

Currently available treatment options for management of AFMR. AFMR, atrial functional mitral regurgitation; MVA, mitral valve annuloplasty.

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Acknowledgments

We thank Edanz (https://www.edanz.com/ac) for editing a draft of this manuscript.

References

Footnotes

  • Contributors This article was written by CS in collaboration with YM and NH.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Commissioned; externally peer reviewed.

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