Discussion
Our analysis, using the world’s largest echocardiographic database, demonstrates that AFMR is a relatively common underlying cause of moderate or severe FMR, comprising 40% of this group. AFMR subjects were more likely to be female, older aged and have AF at the time of their echo, when compared with VFMR subjects.
Consistent with our findings, recent studies of FMR subtypes report a ratio of VFMR to AFMR of 1.5-2:1. Kim et al report on a Japanese cohort of 898 patients with ≥3+ MR; of the 579 individuals (64%) with FMR, AFMR was found in 32% and VFMR in 68%.19 Dziadzko et al reported on 727 patients with moderate or severe MR from Olmstead County; of the 475 (65%) patients with FMR, 59% were classified as VFMR and 41% as AFMR.10
Significant AFMR has been observed in 8% of patients with AF and no underlying structural heart disease,20 in 28% of patients with longstanding AF,10 and in 20% of patients with heart failure with preserved left ventricular ejection fraction (HFpEF).21 The presence of significant AFMR in HFpEF (‘disproportionate’ FMR) has been associated with greater haemodynamic severity of disease and poorer functional capacity,22 as well as high morbidity and mortality.18 19 23
Our data demonstrate poor long-term survival in AFMR, although relatively better all-cause and cardiovascular survival compared with VFMR. The relatively poorer prognosis in VFMR compared with AFMR was closely associated with reduced LVEF, as adjusting for LVEF in multivariate modelling neutralised the survival difference between AFMR and VFMR. This finding suggests that left ventricular systolic impairment accounts for the poorer survival in VFMR vs AFMR. In the overall FMR cohort, left ventricular impairment, age and pulmonary hypertension, but not MR severity, AF, presence of significant TR, or RV dysfunction, conferred the most important prognostic impact on survival in FMR.16 24 25
Okamoto et al recently reported prognostic comparisons between AFMR and VFMR in a single-centre Japanese cohort of 378 consecutive FMR patients (288 VFMR and 90 AFMR), demonstrating higher event rates for all-cause mortality, cardiovascular mortality and HF hospitalisation in VFMR, as well as identifying distinct prognostic predictors of the composite endpoint that highlighted the importance of clinically discriminating these unique FMR aetiologies.26 Our comparative prognostic data support the findings of this small cohort, enhancing the generalisability and validity of these observations to broader clinical contexts.
Despite the significant prevalence in the general population, particularly among older individuals, the relative under-reporting of AFMR compared with VFMR indicates that AFMR is an underappreciated and therefore likely undiagnosed subgroup of MR.9 27 In highlighting the demographic and survival differences between AFMR and VFMR, our study seeks to increase awareness of AFMR as a distinct and important entity, in order to enhance recognition and diagnosis, inform clinical discussions regarding prognosis, and encourage further studies into medical management and intervention.
Defining AFMR
There have been no published echocardiographic guidelines to define the parameters and features that identify AFMR as a subgroup of FMR, with varied definitions used in prior studies.5 19 20 28 In individuals with moderate or worse FMR, we defined VFMR by LVEF <50% and/or moderate or worse LV dilatation, and AFMR as severe LA dilatation in the absence of these LV changes (as illustrated in figure 1). These simple and readily applied definitions can be applied prior to more detailed anatomical assessment to facilitate FMR subgroup categorisation (ie, into ‘atrial’, ‘ventricular’ or ‘mixed’ FMR) in a primary care setting. Due to the evolution of recommendations over the inclusion period of this study, we accepted both two-dimensional and three-dimensional chamber quantification measurements, however, we strongly recommend the use of indexed volumes for chamber quantification in all future AFMR studies as per current echocardiography guidelines.14 16
Clinical implications
Understanding the underlying aetiology of MR is critical in guiding optimal clinical management, and relies on careful transthoracic and/or transoesophageal echocardiographic assessment. Significant MR in the setting of preserved LV function, normal mitral valve leaflet appearance and a dilated mitral annulus likely represents AFMR, particularly in elderly female patients with a history of AF. Clinicians making this diagnosis should be aware of mechanisms and relative prognosis compared with VFMR, use medical management including addressing lifestyle factors, diuretics and blood pressure control,5 29 and evaluate suitability for potentially effective interventions in symptomatic AFMR, such as AF ablation, surgical repair (mitral annuloplasty),23 30 and transcatheter edge-to-edge repair.23 31 32 Mitral edge-to-edge repair has been demonstrated to be safe and effective in AFMR cohorts, demonstrating durable reduction in MR severity, positive mitral annular remodelling and rates of a composite outcome of all-cause death or HF hospitalisations ranged between 55% and 78%.23 33 34 Reduction of AFMR through targeted intervention may represent a potential therapeutic avenue for patients with HFpEF and AF; future studies are needed to explore this hypothesis further.