Discussion
In this study, we established a joint model based on MR degree and left
atrial appendage function assessed by preoperative echocardiogram in PAF
patients, in order to predict the risk of recurrence after CPVA. The
diagnostic efficiency of the model was validated. Atrial fibrillation
has caused increasing burden on patients and the medical system.
Catheter ablation has more advantages over drug therapy in the treatment
of AF patients to maintain sinus rhythm[15], and
has become the first-line treatment for patients with
PAF[16]. The maintenance of sinus rhythm after
ablation is related to reverse remodeling, which can reduce LA size and
improve left ventricular (LV) function. However, because atrial
fibrillation is more likely to recur after CPVA, early and late
recurrences require multiple operations and drug adjustments, and the
scar after ablation can aggravate the structural remodeling of the left
atrium. Therefore, we need to find some preoperative non-invasive
indicators to identify patients at high-risk of recurrence after
ablation, which will facilitate the adjustment of individualized
treatment plans and precision medicine.
Many diagnostic techniques have been proven to help predict the
recurrence of atrial fibrillation, including blood tests,
echocardiography, computed tomography, and electrophysiological
examinations. In addition, researchers have established multiple
prediction models through the multiple indicators, including APPLE,
ATLAS, CAAP-AF scores, etc[17-19]. The detection
echocardiography is cost effective, convenient, and widely accepted in
daily workup[20]. Previous studies have shown that
the recurrence after catheter ablation (CA) in AF patients is largely
dependent on the changes in the structure and function of the left
atrium[21, 22]. The PAF patients selected in this
study were mostly in the early stages of AF, with normal or slightly
enlarged left atrium inner diameter. Their changes in left atrial
structure were not significant. Since the PAF patients selected in this
study were mostly in the early stages of AF, it is necessary to further
search for indicators that can reflect atrial function and remodeling.
These indicators are easy to detect and can provide valuable
information.
The left atrium plays a vital role in the normal operation of the mitral
valve, and timely atrial contraction is very important for mitral valve
closure[23]. The MR of patients with AF is mostly
functional type I MR, which may be caused by dilation of the mitral
valve annulus due to atrial remodeling. In addition, MR is also related
to the patient’s age and the type of atrial
fibrillation[24]. MR is easy to detect. The
advances in equipment and clinical research have promoted more accurate
methods for quantifying the degree of MR. Echocardiogram is particularly
important in the evaluation of MR regurgitation. Other than the primary
valvular disease and left ventricular insufficiency, 7.4% to 29% of AF
patients have significant FMR[25-27], and 7.4% of
the patients qualified for atrial fibrillation ablation have moderate or
higher FMR. Recovering sinus rhythm can improve atrial
function[24]. About 10.9% of PAF patients in this
study had moderate or above FMR. Previous studies have shown that AF
patients with MR are more likely to have recurrent AF after ablation. LZ
et al. showed that the severity of MR in PAF patients was positively
correlated with the incidence of recurrence after radiofrequency
ablation[28]. Qiao et al. found that FMR was
closely related to the matrix remodeling of the left atrium in PAF
patients, and FMR was an independent risk factor for recurrence after
radiofrequency ablation[29]. In this study, the
risk of recurrence after radiofrequency in PAF patients gradually
increased with the aggravation of mitral valve regurgitation. Previous
research showed that the left atrial matrix remodeling , corresponding
mitral valve annulus (MVA) expansion , mitral valve compensatory growth
restriction, and decreased dynamic changes of the valve leaflets were
important factors causing mitral valve
regurgitation[26, 30]. After remodeling, the left
atrium enlarges, the posterior leaflet annulus of the mitral valve
shifts outward, and the anterior leaflet annulus shifts upwards by
passive counterclockwise twisting; these changes lead to increased
distance between the annulus papillary muscles, which limits the
movement of mitral valve leaflet. In addition, the expansion of the
mitral valve annulus is particularly obvious in the expansion of the
posterior leaflet annulus[31]. The posterior
leaflet of the mitral valve continues with the posterior wall of left
atrium. The enlargement of left atrium causes the posterior leaflet of
mitral valve to shift backward and downward. In addition, factors from
left atrium, left ventricle, and annulus cause or aggravate the
functional mitral valve regurgitation, which further promotes the
enlargement of left atrium, leading to the occurrence and maintenance of
atrial fibrillation[32]. Therefore, for PAF
patients with insignificant left atrium enlargement, MR can be used as a
predictor for LA matrix remodeling[29]. These
studies all provide evidence for using MR as a potential marker of left
atrial matrix remodeling in AF patients.
The left atrial appendage is an extremely important accessory structure
of the left atrium. Its morphology and structure are more
complex[33]. The loss of coordination between
contraction and diastole of the left atrial appendage in AF patients
results in slow internal blood flow. The transesophageal
echocardiography before AF radiofrequency ablation allows the
observation of patient’s left atrial appendage (LAA) hemodynamic changes
from multiple angles, and yields the maximum emptying velocity of left
atrial appendage. In addition, this study also used LAAV to rule out the
effect of left atrial stunning on atrial function during the conversion
of atrial fibrillation[34]. Therefore, LAAV plays
an important role in clinical evaluation of left atrial appendage
function. Melduni et al. found that, in patients with persistent AF
after successful electrical cardioversion, the ones with reduced LAAV
had increased risk of AF recurrence, stroke and
death[35]. LAAV >40 cm/s could
independently predict sinus rhythm persistence at 1
year[36]. In this study, the AUC of predicting AF
recurrence based on LAAV alone was only 0.731, which may be related to
the effects from heart function, heart rate, acquisition time and other
factors on left atrial appendage function.
In this study, the degree of MR and LAAV were both independent
predictors of atrial fibrillation recurrence after CPVA, but the
diagnostic power of univariate indicator was still insufficient. Thus,
we performed multivariate logistic regression on the observed indicators
to establish a predictive model, which integrated clinical and
echocardiographic parameters, and had more advantages over single-factor
prediction. The calibration curve showed that the model had good
prediction accuracy in both the modeling group and verification group.
Many predicting models for recurrence after radiofrequency also showed
similar results. He et al. found that a model constructed with LAAV
could predict the risk of recurrence in PAF patients at 12 months after
radiofrequency[37]. Yang et al. found that: the
combined model integrating LA function and blood BNP level had good
predictive value for the recurrence of early persistent AF after
CPVA[38]. For the treatment of secondary MR, the
management of primary disease is the most important; For severe cases,
the MR guidelines recommend mitral valvuloplasty, mitral replacement,
and percutaneous mitral valve repair. In this study, although the AF
patients had moderate or higher MR before operation, their valve
function was significantly improved after the recovery of sinus rhythm,
and the degree of MR regurgitation was less than before. There was no
patient with severe MR after radiofrequency.
This study still has limitations: (1) Although this study is a
multi-center retrospective study, the number of cases included is small,
and the small sample size may lead to selection bias; (2) All patients
received 24-hour Holter monitoring during the follow-up, but they were
not implanted with ring recorder, which may underestimate the recurrence
rate of AF.
In summary, this study constructed and verified a model for predicting
the recurrence of atrial fibrillation after CPVA in patients with PAF.
The model took into account clinical and echocardiographic parameters
and had good predictive performance. The model can identify high-risk
patients with atrial fibrillation recurrence, and help doctors to
optimize patient selection, inform patients of the recurrence risk, and
design personalized treatment plans.