- Academic Editor
Atrial fibrosis is an independent predictor of the recurrence of atrial fibrillation (AF) after catheter ablation. Low-voltage areas (LVA) measured during catheter ablation for AF are a commonly used surrogate for the presence of atrial fibrosis. LVA are associated with clinical outcomes and comorbidities and have links to triggering sites for AF. Several trials have shown promising data of targeting ablation in LVA, however the results have been mixed. This article will review the role of LVA in the prediction of adverse events in AF patients, including stroke, how to predict the presence of LVA, and the impact of LVA ablation on the recurrence of AF.
Atrial fibrillation (AF) is a common cardiac arrhythmia that is closely associated with adverse events such as ischemic stroke, heart failure, death, and decreased quality of life [1]. Heart rate control and rhythm control are two strategies for the treatment of AF. Rhythm control has been shown to reduce the recurrence of atrial arrhythmias and composite cardiovascular endpoint events compared to rate control [2]. Clinical studies and meta-analyses have shown that catheter ablation is superior to antiarrhythmic drugs in maintaining sinus rhythm, avoiding side effects of bradycardia and arrhythmias caused by antiarrhythmic drugs, and improving clinical outcomes [3, 4, 5]. However, the recurrence of AF after ablation remains high. Many patients require several procedures of catheter ablation [6, 7, 8] with the development of new ways of catheter ablation being needed.
The presence of atrial fibrosis is a predictor of AF recurrence after
radiofrequency ablation [9]. Such atrial fibrotic areas usually have low voltage
by intracardial voltage mapping. A low-voltage area (LVA) is defined as an area
with bipolar voltage
AF has a five-fold increased risk of thromboembolic events. A silent cerebral
ischemia can be found in up to 90% of AF patients on cerebral
delayed-enhancement magnetic resonance imaging (MRI). A powerful risk
stratification is therefore crucial for patients with AF. The current
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In addition, the presence of LVA, especially
Moreover, extensive LVA seems to be associated with sinus node dysfunction. A large retrospective study that included more than 1200 patients who underwent catheter ablation for persistent AF found that 3.2% of those patients needed pacemaker implantation because of sinus node dysfunction [15]. LVA are identified in the same study as strong predictors for acute cardiac pacing.
Presently, intracardiac voltage mapping has emerged as a reliable modality to
detect abnormal atrial substrates. However, the standardization of voltage
mapping in the detection of LVA is still lacking. The number of voltage points
during mapping can vary from 90 to 2566 points per left atrium [16], leading to
different mapping resolution and therefore variable capacity in the detection of
LVA. Most studies utilize high-density bipolar mapping catheters, which generally
collect larger volume of mapping points than the catheters used in earlier
studies. However, it is essential to verify those collected points by excluding
incorrectly annotated signals in the presence of atrial ectopy, uncaptured
pacing, noise, and ventricular and atrial far-field sensing. Radoslaw M
et al. [17] excluded the tubular and antral portions of pulmonary veins (PVs) inside the
ablation encirclement and left atrial appendage from the total atrial area, which
could be one of the reasons explaining their different LVA percentage from the
other studies. Moreover, different electrodes and catheters used in high-density
voltage mapping can generate various degrees of LVA. Masaharu et al.
[18] have compared a direction-independent grid catheter with a conventional
circular mapping catheter in the measurement of LVA area. They found that the
grid catheter took less time in collecting mapping points and had better tissue
contact during voltage contact, which leads to higher voltages collected during
mapping and therefore less area of LVA compared to the circular catheter. This
could explain why the LVA identified in specific studies could be reclassified as
normal tissue in other studies. Furthermore, the voltage cut-off during mapping
is a key to defining how much LVA is detected. Diverse cut-off values, e.g.,
0.1–1.5 mV used in previous studies, lead to different calculated LVA area
percentages [13, 18, 19]. However, no cut-off value has been validated due to the
lack of histological examination for verification of fibrosis. At present, a
cut-off value
Rhythm during voltage mapping is another factor that affects LVA detection.
Voltage mapping can be done before cardioversion of AF (AF rhythm) or after
cardioversion of AF (sinus rhythm). Ndrepepa et al. [20] found that
voltages in the atria were lower during AF than during sinus rhythm. Coronary
sinus pacing may normalize the low voltage levels in LVA. The cut-off value
Voltage mapping before and after pulmonary vein isolation (PVI) is another way to affect LVA detection. Post-PVI can reduce the overall atrial scar burden and therefore voltage mapping may miss the atrial LVA in the pulmonary vein antrum, giving lower detection of LVA and therefore a smaller extent of LVA [17, 18]. Moreover, factors that affect the collection of bipolar electrograms can influence the measurement of LVA extent. Bipolar electrograms demonstrate voltage difference recorded by two closed placed electrodes. Therefore, the affecting variables can be interelectrode spacing, tissue contact, filtering, mapping density and resolution, and activation vector.
Non-invasive methods have been studied in the detection of LVA. A systemic
review of MRI has shown a correlation between late gadolinium enhancement (LGE)
in MRI and voltage mapping in the detection of LVA [16]. Measurement of the
plasma level of suppression of tumorigenicity 2 (ST2) could be a potential way to
predict LVA. Patients with LVA area
As a simple, fast and economical examination method, electrocardiogram (ECG) is
also valuable in predicting LVA. The amplitude of P wave in lead I has been shown
to negatively correlate with the presence of LVA, while the duration of P wave in
some leads may be positively correlated with the presence of LVA [27]. When 0.062
mV was used as a cut-off, its sensitivity and specificity in predicting LVA
Several scoring systems have been developed to predict LVA, such as the DR-FLASH
score (diabetes, renal dysfunction, persistent AF, left atrial diameter
Rolf et al. [34] were the first group to perform LVA ablation in
patients with AF. They demonstrated that PVI combined with LVA ablation reduced
the recurrence of AF/atrial tachycardia. The study by Jadidi et al. [35]
revealed that PVI together with LVA ablation had a higher successful rate of
ablation, defined as no arrhythmia within one year, 69% vs 47%, p
In the study of Kircher et al. [38], PVI plus LVA ablation were
administered to patients with AF regardless of whether the AF was paroxysmal or
persistent. After 1-year follow-up, the proportion of no arrhythmia in the
PVI+LVA ablation group was found to be significantly higher than that in the
control group (68% vs 42%, p = 0.003). The suggestion is that
individualized ablation under the guidance of LVA may be superior to conventional
ablation strategy. It can be done by adding LVA ablation if traditional PVI is
not able to terminate AF. This would result in 40% of patients with AF
converting to sinus rhythm with a decreased recurrence [39]. This suggests that
additional LVA ablation can increase the success rate of AF ablation. However,
the STABLE-SR study and its follow-up STABLE-SR-II study have shown diverse
results [40, 41]. The investigators were not able to reduce the recurrence of
arrhythmia by adding LVA ablation to the traditional PVI. The different result
could be due to the severity of fibrosis or the extent of LVA. The prevalence of
LVA has been shown to be 10–63% in paroxysmal AF and 35–100% in persistent AF
[42]. Takanori et al. [43] have classified LVA into four stages based on
extension of LVA. PVI plus LVA ablation did not reduce AF recurrence or improve
clinical outcomes in patients with extensive LVA (LVAs
Atrial remodeling is a genesis of AF recurrence after ablation. LVAs in the
atria, a surrogate of atrial remodeling, are highly associated with
thromboembolic events. This can be a potential factor added to the traditional
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YG contributed to the conception, design and writing of this review; YS contributed to the conception, design and revision; SL participated in the design and conception; TL contributed to the conception, final review and provided essential intellectual contribution to this article. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.
Not applicable.
Not applicable.
Henan Province Key R&D and Promotion Project (No. 222102310076). Henan Provincial Science and Technology Research Project (No. LHGJ20220933).
The authors declare no conflict of interest. Tong Liu is serving as Guest Editor of this journal. We declare that Tong Liu had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Konstantinos P. Letsas.
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