The main findings in this study were as follows: (1) in patients with AF and significant functional MR, catheter ablation is associated with a significantly lower risk of target clinical events (heart failure-related hospitalization, stroke, and TIA) than is conventional drug therapy. (2) In these patients, catheter ablation reduces the severity of MR and improves cardiac remodeling.
A previous study evaluating the prognostic significance of residual functional MR in hospitalized patients with chronic AF and heart failure but a preserved LVEF showed that after optimized drug therapies, the mean MR grade at discharge was significantly lower than that during hospitalization [13]. These findings suggest that conventional drug therapy alone may significantly reduce the severity of MR in patients with AF and functional MR, which is supported by our finding that patients in the Non-ablation group showed a significant decrease in the severity of MR during the follow-up period compared with baseline. In addition, several studies have examined the efficacy of catheter ablation of AF in patients with MR. A study retrospectively compared 53 patients with significant functional MR and normal LV systolic function (LVEF ≥ 50%) with a matched AF cohort with trivial and/or mild MR during first AF ablation [2]. This previous study showed that successful ablations were associated with a significant reduction in severity of MR and LA size. In a recent study investigating the outcomes of catheter ablation of AF in a subgroup of patients presenting with functional MR and LV systolic dysfunction, we also found associations between freedom from recurrent atrial tachyarrhythmia after ablation and a reduction in severity of MR and with positive LA and LV remodeling [7]. Our findings suggest that, similarly to patients with AF with functional MR and normal LV function, patients with AF with functional MR and LVSD also benefit from restoration of sinus rhythm by catheter ablation of AF. However, whether catheter ablation is more beneficial than conventional drug therapy in improving clinical outcomes in patients with AF and functional MR is unclear.
In this comparative study of catheter ablation versus medical therapy in patients with AF and functional MR, we found lower annual overall rates of target clinical events in the Ablation than in the Non-ablation group. According to univariate and multivariate analyses, catheter ablation therapy is significantly associated with fewer subsequent target clinical events, namely heart failure-related hospitalization and strokes/TIA. Our findings suggest that the rates of clinical outcomes may be more effectively reduced by catheter ablation than by conventional drug therapy in patients with AF and functional MR. This may be explained by our finding that besides a significant reduction in the severity of MR in the two groups, patients in the Ablation group also showed a significant decrease in the LA diameter and improvement in the LVEF whereas patients in the Non-ablation group did not.
In our previous study, we showed that freedom from recurrent AF is associated with a reduction in the severity of MR and positive cardiac reverse remodeling, whereas patients with AF recurrence after AF ablation do not experience these benefits [7]. These findings suggest that maintenance of sinus rhythm after ablation is important in achieving reduction in the severity of MR and positive cardiac reverse remodeling, and may be associated with subsequent better clinical outcomes. However, AF patients with functional MR have high recurrence rates after AF ablation [14]. A previous study of 216 patients with long-standing persistent AF who underwent catheter ablation identified both MR and LA size as independent predictors of recurrence of AF [15]. In the current study, we found a 46.5% rate of recurrence of AF during a mean follow-up period of 16.7 ± 10.2 months after a single ablation procedure. Because the rates of recurrence of AF after ablation are higher with longer term follow-up, whether catheter ablation is still associated with a lower risk of clinical events than conventional drug therapy during longer term follow-up is unknown. Therefore, further studies incorporating long-term follow-up are required for these patients.
Among patients with AF and functional MR, some have normal LV systolic function, in which functional MR develops as a result of LA dilatation. This MR is known as atrial functional MR[16]. However, in present study, we did not stratify patients with atrial functional MR or functional MR secondary to LV dilatation for two reasons. First, atrial functional MR is not well understood and is still under evaluation. The definition of “atrial functional MR” is yet not widely adopted. Second, because AF can also result in LV systolic dysfunction due to loss of atrioventricular synchrony or can be a direct cause of tachycardia-induced ventricular cardiomyopathy, patients with AF and functional MR usually have LV dilatation. Additionally, LV dilatation can precede functional MR and AF because pre-existing ventricular cardiomyopathy can result in subsequent functional MR and atrial dilatation, which increase the likelihood of AF development [17, 18]. Thus, for the majority of patients with AF co-existent with LV dilatation and functional MR, the mechanism of MR usually includes both LV and LA dilatation, and it is difficult to differentiate the mechanism of MR from LV dilatation or LA dilatation.
Several limitations of our study should be considered. First, the small sample size is a major limitation of this study and may have introduced statistical bias. Further studies with larger sample sizes are needed. Second, because there were multiple differences at baseline between the Ablation and Non-ablation groups, propensity-matching techniques were used in this study. Because the sample size was small, we did not match all of the differences between the two groups. The patients’ age [19], CHA2DS2-VASc scores [20], and LVEF [21, 22] were significantly associated with the target clinical events (heart failure-related hospitalization or strokes/TIA); therefore, the patients were propensity score-matched on the basis of these three parameters. Fortunately, the patient characteristics appeared well balanced between the two groups after matching; the only statistically significant difference between them was the LA diameter. However, multivariable Cox analysis showed that the LA diameter was not an independent predictor of the target clinical events, suggesting that this bias would not have affected our conclusions. Third, for patients with persistent AF, we performed ipsilateral PVI and atrial substrate modification. However, different patients may have been treated by different techniques of atrial substrate modification according to the operator’s discretion and patients’ clinical features, and this may have introduced bias. Notably, the current guidelines contain no consensus regarding the techniques of atrial substrate modification for persistent AF [4]. Further prospective studies in which the same atrial substrate modification techniques are used may be required. Fourth, follow-up echocardiograms were available in only 53 of the 86 patients, including 81.4% (35/43) patients in the Ablation group and 41.9% (18/43) patients in the Non-ablation group. Although this may not have affected our findings in the Ablation group, the findings regarding the severity of MR and cardiac remodeling in the Non-ablation group are not convincing because follow-up echocardiograms were available only in 41.9% (18/43) of patients. However, a previous study showed that conventional drug therapy alone may significantly reduce the severity of MR in patients with AF and functional MR [13], which supports our findings in the Non-ablation group. Further studies are required to clarify our findings. Fifth, we did not assess differences in quality of life associated with long-term drug therapy or ablation between the two study groups because these measures are not routinely captured in medical records. Finally, the generalizability of our findings may be limited by the single-center, retrospective, observational approach.