Atrial Fibrillation in Mitral Regurgitation Patients: A Harbinger for Poorer Outcomes

Atrial fibrillation (AF) is one of the most common arrhythmias in the general population and is associated with increased mortality. Among a community cohort of over 9,700 individuals with AF, 27.5% had significant valvular heart disease, the majority of which had mitral regurgitation (MR). The combination of MR and AF in this cohort was associated with 8.6 deaths per 100 patient-years. In this issue of Structural Heart, Megaly et al. present the results of a meta-analysis to evaluate the impact of atrial fibrillation on outcomes following transcatheter mitral valve repair for MR using the MitraClip device. The meta-analysis combined results from four observational studies with a total of 1510 patients and a mean follow-up of 10.2 months. Patients were older (mean age > 75 years), and secondary MR was the predominant etiology. At follow-up, the presence of AF was associated with an increased risk of mortality, OR 1.54 (95% CI 1.16, 2.04, p = 0.003) and major adverse cardiac events OR 1.46 (95% CI 1.03, 2.07 p = 0.03). There was no effect of AF on procedural success or stroke at 14-month follow-up. The data are interesting and certainly raise questions as to the impact of AF on outcomes of transcatheter treatment of MR. There are however important limitations. The analysis did not present any information related to previous history of heart failure or left ventricular function, which is a powerful predictor of mortality in patients treated with MitraClip. In addition, procedural success was only 88%, low by contemporary standards, and there were no data on residual MR post-intervention, also a predictor of long-term outcomes following MitraClip. Despite the limitations of this work, this observational meta-analysis demands the review of the relationship between AF and MR as well as their interaction with heart failure (Figure 1) and begs the question as to whether we need to adjust the timing of transcatheter treatment for MR. MR results in a volume overload of the left ventricle (LV) that causes increased LV wall stress. As a result, the LV dilates and there is increased fractional shortening to maintain normal diastolic pressures in the chronic compensated state. Over time as the disease progresses and MR severity increases, irreversible dilatation of the LV may occur, and filling pressures become elevated in both the left atrium and left ventricle leading to heart failure and atrial fibrillation, both of which are associated with reduced survival. AF may also cause MR. Persistent AF may lead to atrial remodeling, resulting in mitral annular dilation and secondary MR also described as atrial functional MR. Patients with atrial MR tend to be older, with dilated left atria and persistent AF. Atrial MR has been shown to improve with restoration of sinus rhythm and has been treated successfully with surgical mitral valve repair. For those patients with primary MR in sinus rhythm, a long-term study on medical therapy demonstrated that the risk of developing AF was high, 18 ± 3% at 5 years and 48 ± 6% at 10 years. Development of AF was associated with a high risk of cardiac death or heart failure (adjusted risk ratio 2.23, p = 0.025). As a result, new onset of AF is included as a IIa indication for surgical intervention of asymptomatic primary MR. Surgical studies of mainly primary MR have documented a prevalence of pre-operative AF in 50% of patients. Patients with AF and MR were older with more left atrial dilatation than those in sinus rhythm. Although there were no early differences in mortality, the presence of AF was associated with higher mortality at 3 and 5 years with a strong interaction between poor left ventricular function and mortality. AF frequently coexists in patients with heart failure, with an estimated prevalence of 13–27%. The prevalence of AF in patients with secondary MR is less well documented. In a registry of Japanese patients with heart failure and secondary MR, 40% had documented AF. For those patients with secondary MR and an indication for resynchronization therapy for heart failure, AF has been implicated as a cause of non-response to therapy. Is atrial fibrillation a risk factor for increased mortality in the setting of MR or just a marker for a worse prognosis? To date there have been no randomized trials of restoring sinus rhythm in patients with MR however the surgical literature does provide insight with the results of surgical maze at the time of mitral valve surgery. For those patients with mechanical mitral valve replacement requiring systemic anticoagulation, concomitant maze was compared to valve replacement alone in a retrospective study of over 500 patients. Freedom from AF was higher in those treated with the maze procedure, 80% versus 20% (p < 0.001) compared to valve replacement only. At 5-year follow-up however, there was no difference in adjusted all-cause mortality or readmission for heart failure in those with maze procedure compared to those without.