Rhythm Control as a Strategy to Mitigate Atrial Functional Mitral Regurgitation and Tricuspid Regurgitation

Atrial fibrillation (AF) and valvular regurgitation frequently coexist, often exacerbating each other's severity. Atrial functional mitral regurgitation (AFMR) has emerged as a distinct subtype of secondary MR, wherein AF-driven left atrial (LA) enlargement and mitral annular dilation lead to significant MR despite normal mitral leaflets.¹⁾ Unlike classic functional MR caused by left ventricular (LV) dysfunction, AFMR arises from LA remodeling—annular enlargement, loss of atrial contraction, and "atriogenic" leaflet tethering. Importantly, AF itself can precipitate or worsen MR, and conversely MR-induced volume overload can promote AF, creating a bidirectional pathological loop. Only 3% of patients with AF duration ≤1 year had significant MR, versus 28% of those with AF >10 years.¹⁾ These findings underscore that the longer AF is left untreated, the greater the chance of developing significant MR, and vice versa, each condition exacerbates the other.

Recent evidence supports rhythm control as a therapeutic strategy for AFMR. A post hoc sub-analysis of the CABANA trial involving 1,423 patients (65% of the total cohort) showed that 52% had coexisting MR. While the main CABANA trial showed no significant difference in primary clinical outcomes between ablation and drug therapy, this subgroup analysis revealed greater reduction in MR severity in the ablation group compared to drug therapy (odds ratio, 0.69; 95% confidence interval, 0.47–0.98; p for interaction=0.040).²⁾ Importantly, patients with both AF and MR derived greater symptomatic improvement from rhythm control than those without MR—suggesting that treating AF in these patients yields a "double dividend": suppressing arrhythmia and improving valve function. Key mechanistic studies have demonstrated that restoring atrial contractile function and normalizing LA size allow the mitral leaflets to coapt more effectively. Deferm et al.³⁾ showed significant improvement in mitral annular dynamics following cardioversion, with significant reductions in effective regurgitant orifice area. Masuda et al.⁴⁾ demonstrated substantial improvement rates in MR grade following catheter ablation. The seminal study by Gertz et al.⁵⁾ showed that among AF patients with significant MR, those maintaining sinus rhythm after ablation had dramatically lower recurrent significant AFMR (~24%) compared to those who fell back into AF (~82%).

In this issue of the Korean Circulation Journal, researchers present compelling evidence from a large-scale propensity-matched cohort study examining rhythm control's influence on AFMR and atrial functional tricuspid regurgitation (AFTR).⁶⁾ This study of 817 matched pairs provides robust real-world evidence supporting rhythm control as a therapeutic strategy. The study demonstrates clinically meaningful results. Rhythm control was associated with significant reduction in moderate or greater MR (7.3% to 4.9%, p=0.008) and attenuated TR progression (9.1% to 9.3%, p=0.796), in contrast to worsening trends in the control group. Sinus rhythm restoration was more frequent in the rhythm control group (60.2% vs. 48.1%, p<0.001), and patients maintaining sinus rhythm showed the greatest MR improvement (7.3% to 3.5%, p=0.002).

Beyond valve function, rhythm control was associated with reverse cardiac remodeling, including significant reductions in LA volume index and improved LV ejection fraction. Notably, these benefits were observed even in patients with progressed disease status, such as LA enlargement and persistent AF—traditionally considered high-risk for AF recurrence. The study's mediation analysis revealed that rhythm control improves outcomes through both direct and indirect pathways. Patients achieving sinus rhythm or valve improvement had the lowest risk of adverse outcomes, while those with neither rhythm control nor regurgitation improvement had the highest risk.

The Korean study also provides important insights into AFTR. Recent case reports have demonstrated dramatic TR improvement (from severe to mild by 4 months) after rhythm control, with heart failure symptoms resolving without tricuspid intervention.⁷⁾ Given the poor prognosis of severe TR and complexity of late interventions, these findings advocate for early rhythm control in patients with AF and significant TR.

These findings reshape how we approach AF patients with valvular regurgitation. AFMR or TR in these patients should be viewed as potentially reversible conditions—therapeutic targets, not just bystanders.⁸⁾ Rather than reflexively proceeding to valve intervention, clinicians should first ensure that sinus rhythm restoration has been optimally attempted.

An integrated approach is warranted: aggressively treat AF and optimize medical therapy, then re-evaluate the valve. As the authors note, echocardiography can provide valuable information for identifying optimal timing of rhythm control intervention and assessing treatment response. While current evidence is compelling, the next critical step is prospective randomized trials comparing early AF ablation versus early mitral repair in patients with AFMR. Such trials could definitively clarify long-term outcomes and establish evidence-based treatment algorithms. Furthermore, future research should explore optimal patient selection criteria for rhythm-first strategies, timing of intervention, and the role of combined approaches (rhythm control plus valve intervention) in advanced cases. The development of predictive models incorporating echocardiographic parameters, AF burden, and atrial remodeling markers could help identify patients most likely to benefit from rhythm control.