Left Atrial Reservoir Strain and Recurrence of Atrial Fibrillation Following De-Novo Pulmonary Vein Isolation　― Results of the ASTRA-AF Pilot Study ―

Dorit Knappe; Julia Vogler; Jessica Weimann; Victor Banas; Julius Obergassel; Sevenai Yildirim; Felix Memenga; Juliana Senftinger; Laura Keil; Djemail Ismaili; Moritz Nies; Andreas Rillig; Stephan Willems; Stefan Blankenberg; Paulus Kirchhof; Andreas Metzner; Christoph Sinning

doi:10.1253/circj.CJ-24-0209

Abstract

Background: Achieving early rhythm control and maintaining sinus rhythm are associated with improved outcomes in patients with atrial fibrillation (AF). Pulmonary vein isolation (PVI) is a validated alternative to medical rhythm control. This study determined associations between left atrial strain reservoir (LAS_R) and AF recurrence after PVI.

Methods and Results: In all, 132 patients (88 with paroxysmal AF [PAF], 44 with persisting AF [PersAF]) who presented in sinus rhythm for de novo PVI of AF between December 2017 and January 2019 were included in the study. All patients underwent preprocedural echocardiography. After 12 months, all patients underwent 24-h Holter electrocardiogram monitoring to screen for AF recurrence. Kaplan-Meier curve analysis revealed an association between decreasing LAS_R and increased AF recurrence, with a cut-off at 31.4%. In univariable Cox regression analysis, LAS_R demonstrated an association with AF recurrence, with hazard ratios (HR) of 0.83 (95% confidence interval [CI] 073–0.93; P=0.001) per 5% increase in univariable models and 0.83 (95% CI 073–0.95; P=0.005) in multivariable analysis. When clinical variables with age, sex and type of AF (PAF/PersAF) were included in the multivariable analysis, LAS_R remained relevant in a model with age (HR 0.86; 95% CI 073–1.00; P=0.046).

Conclusions: In patients undergoing de novo PVI for AF, LAS_R could be of use in risk stratification regarding AF recurrence.

Pulmonary vein isolation (PVI) is an effective and safe treatment option for rhythm control in patients with atrial fibrillation (AF).¹^–³ In addition to improving AF-related symptoms, a rhythm control strategy reduces unfavorable outcomes in patients with AF.⁴^–⁶ In this context, rhythm control with catheter ablation is more effective than medication in preventing AF recurrence in patients with paroxysmal AF (PAF).⁷^,⁸ However, AF recurrence rates are reported to be 20–40%.⁷^,⁸ Therefore, screening patients with AF before the procedure may be advisable to identify those at increased risk of AF recurrence so that additional treatment may be considered, such as adding anti-arrhythmic drugs to AF ablation, and to reduce the risk of repeat procedures or additional healthcare utilization.¹^,⁹ Increased concentrations of cardiovascular biomolecules¹⁰ and intraprocedural cardioversion¹¹ have been associated with recurrent AF after a first ablation. Non-invasive imaging parameters could identify patients at risk of recurrent AF in current clinical routine, particularly because echocardiography is part of the recommended workup in every patient with AF to rule out structural alterations.¹^,²

Editorial p 162

Assessment of left atrial strain reservoir (LAS_R) has been suggested as suitable for the evaluation of left atrial (LA) function,¹² in addition to the measurement of left ventricular (LV) function as recommended by various guidelines.¹³^–¹⁵ LAS_R measurement has previously been shown to identify patients at high risk of AF in the setting of stroke¹⁶^–¹⁸ or heart failure.¹⁹ Even now, with the use of multimodal imaging being more common, 2-dimensional echocardiography remains the most common imaging modality and the central modality for evaluating LA function. LA strain derived from 2-dimensional echocardiography can help objectively assess LA function and demonstrates the 3 distinct phasic movements of the LA cycle with reservoir, conduit and contraction strain.²⁰ A previous study reported that following successful treatment of AF with catheter ablation there was reverse remodeling of the LA and that LA strain predicted the maintenance of sinus rhythm during follow-up.⁶^,²¹ Another study recently confirmed the association between LA strain and improved outcome.⁶ The most commonly variable recommended by guidelines to evaluate LA function is LA volume indexed to body surface area (LAVI).¹^,²²^,²³ The Atrial Strain in Atrial Fibrillation Ablation (ASTRA-AF) study assessed the timing of activation as an additional parameter of detecting tissue changes of the LA, such as atrial mechanical dispersion.²⁴^,²⁵ However, this parameter is more complicated to evaluate in clinical practice, and LAS_R is recommended in the current guidelines and can be measured more readily with current technology.¹²^,¹⁴^,²⁴

An increase in the LA volume is often associated with the presence of AF and recurrence of AF following PVI,²²^,²³^,²⁶ making this parameter frequently used in decision making. Recently, in addition to LV global longitudinal strain (LV-GLS), LAS_R was measured to evaluate the risk of AF onset in a cohort of patients at risk of developing heart failure.²⁷ In that study, along with conventional imaging parameters such as LV ejection fraction and LAVI, the measurement of LAS_R and LV-GLS provided additional information to identify subjects at risk of developing AF.²⁷ The aim of the present study was to assess the influence of newly described imaging parameters and available clinical markers in detecting patients at risk of developing AF recurrence following PVI.

Methods

The Ethics Review Board of the Federal County of Hamburg, Germany, did approved the protocol (PV5815) of the ASTRA-AF study. This single-center (Department of Cardiology, University Hospital Hamburg-Eppendorf) observational study included patients with paroxysmal AF (PAF) and persisting AF (PersAF) who underwent de novo PVI between December 2017 and January 2019 and were in sinus rhythm at the time of echocardiography before PVI. Patients underwent either radiofrequency ablation (RFA) or cryoballoon ablation at the discretion of the treating physician. The study was conducted in accordance with the Declaration of Helsinki and the ethical standards of the responsible ethics committee of the Hamburg Medical Council (Hamburg, Germany).

A flowchart of patient inclusion and exclusion is shown in Figure 1. Overall, the study cohort included 132 patients. Of the 88 patients with PAF, 40 underwent RFA and 48 underwent cryoablation; of the 44 patients with PersAF, 33 underwent RFA and 11 underwent cryoablation. Following earlier results from the CHASE-AF (Catheter Ablation of Persistent Atrial Fibrillation) study, the center’s preferred approach was to perform PVI only.²⁸ Two patients in the cohort experienced AF recurrence (1 with PAF, 1 with PersAF) within 1 year and were treated with additional linear lesions or complex fractionated atrial electrogram ablation.

Figure 1.

Flowchart showing study screening, patient inclusion, and the overall study cohort. ECG, electrocardiogram; LV, left ventricular; PVI, pulmonary vein isolation.

All patients underwent transthoracic and transesophageal echocardiography before ablation. Patients with reduced LV ejection fraction <50%, poor imaging quality, presenting with AF at time of echocardiography, more than moderate valvular heart disease, or less than 4 weeks following direct current cardioversion were excluded. Measurements of LV and LA strain were conducted using AutoStrain (IMAGE-COM, TOMTEC-ARENA; Tomtec Imaging System GmbH, Unterschleissheim, Germany). All measurements of LA and LV strain followed the imaging recommendations of the Strain Task Force standardization document.¹² LA volume and ejection fraction were measured as recommended,¹⁵ and the total emptying fraction was calculated using the following formula:

Total emptying fraction = (LAV_max − LAV_min) / LAV_max

where LAV_min is the minimum LA volume and LVA_max is the maximum LA volume. We also evaluated LAS_R because this parameter is most reported, although conduction and contraction strain were also measured.¹²^,¹⁴ Additional echocardiography included assessment of diastolic function, measurement of ventricular diameters and volumes, and, when available, 3-dimensional assessment of the LV.¹³ The CHA₂DS₂-VASc score was calculated according to current guidelines.¹^,²

After a period of 12 months, all patients were invited to undergo 24-h Holter electrocardiogram (ECG) monitoring to assess AF recurrence. Patients who could not attend the follow-up visit were interviewed using a questionnaire and asked to send a current 24-h Holter ECG to the study center. The study set up is shown in Figure 2.

Figure 2.

(A) Study work flow and (B,C) examples of reduced (B) and preserved (C) left atrial (LA) strain. AF, atrial fibrillation; Cryo, cryoablation; ECG, electrocardiogram; ECHO, echocardiography; LA, left atrium; LAS_R, left atrial strain reservoir; LAScd, left atrial strain conduit; LASct, left atrial strain contraction; LAVI, left atrial volume index; LV, left ventricular; PAF, paroxysmal atrial fibrillation; pts, patients; PVI, pulmonary vein isolation; RFA, radiofrequency ablation.

Statistical Analysis

Continuous variables are shown as the median with interquartile range (IQR) and were compared using the Mann-Whitney U test. Binary variables are shown as counts (frequencies) and were compared using the χ² test. Because this was an explorative study, no adjustments were made for multiple testing. P values are given for descriptive reasons only.²⁹ The median follow-up time was estimated by the reverse Kaplan-Meier estimator, and the event rate was estimated by the Kaplan-Meier method. The primary endpoint is censored at 1 year of follow-up.

Optimal cut-off values were determined using Cox regression and the function cutp from package survMisc to make the choice (version 0.5.5, URL: https://CRAN.R-project.org/package=survMisc). Bootstrap-corrected C indices were calculated with 1,000 repetitions.

Kaplan-Meier survival analysis was performed for different groups, and survival curves were compared between groups using the log-rank test.

Univariable Cox regression was performed to identify associations between patient characteristics and the recurrence of AF. All variables with P<0.25 in univariable regression were chosen for a multivariable model. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) are given. Forest plots were used to display the results. The vertical line at an HR of 1 is the line of no effect.

The two-tailed P value <0.05 was considered statistically significant in regression analysis. All analyses rely on complete cases and were performed using R Statistical Software Version 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria).

Results

In all, 132 patients were analyzed (40% women; median age 66 years [IQR 55–73 years], median CHA₂DS₂-VASc 2 [IQR: 1–3]), with 88 (66.7%) having PAF and 44 (33.3%) having PersAF (Supplementary Table 1). The cohort with AF recurrence (n=30; 22.7%) had a higher median age (75.0 years; IQR 57.9–78.0; P<0.001) and a higher CHA₂DS₂-VASc (3.0 (IQR 1.9–4.1; Table 1). Arterial hypertension was more common in patients with AF recurrence, with 24 (80%) individuals affected (P=0.02). Other cardiovascular risk factors and cardiovascular diseases, including prevalent coronary artery disease or ischemic stroke, did not differ significantly between patients with and without AF recurrence. Regarding medication, oral anticoagulants and anti-arrhythmic medication did not differ significantly at baseline, with 26 (86.7%) patients (P=0.29) and 9 (42.9%) patients (P=0.74) on oral anticoagulants and anti-arrhythmic medication, respectively, in the cohort with AF recurrence (Table 1).

Table 1.

Baseline Characteristics of Cohorts With and Without AF Recurrence

	Without AF recurrence (n=102)	With AF recurrence (n=30)	P value
Male sex (%)	62 (60.8)	17 (56.7)	0.85
Age (years)	62.0 [54.9~69.1]	75.0 [57.9~78.0]	<0.001
BMI (kg/m²)	26.3 [24.6~29.5]	26.2 [23.5~28.0]	0.26
BSA (m²)	2.0 [1.9~2.2]	2.0 [1.8~2.1]	0.11
CHA₂DS₂-VASc score	2.0 [1.0~3.0]	3.0 [1.9~4.1]	<0.001
Arterial hypertension	54 (52.9)	24 (80.0)	0.015
Smoking	26 (25.5)	7 (23.3)	1.00
Diabetes	5 (4.9)	2 (6.7)	1.00
Dyslipidemia	11 (10.9)	7 (23.3)	0.15
Stroke	9 (8.8)	4 (13.3)	0.70
Coronary artery disease	11 (10.8)	4 (13.3)	0.95
Cardioversion	40 (39.2)	17 (56.7)	0.14
Anti-arrhythmic medication	36 (50.0)	9 (42.9)	0.74
Oral anticoagulation	77 (75.5)	26 (86.7)	0.29
Radiofrequency ablation	58 (56.9)	15 (50.0)	0.65
Cryoballoon ablation	44 (43.1)	15 (50.0)	0.65
Persistent AF	34 (33.3)	10 (33.3)	1.00

Unless indicated otherwise, data are given as the median [interquartile range] or n (%). AF, atrial fibrillation; BMI, body mass index; BSA, body surface area.

Follow-up and Recurrence of AF in the Overall Cohort

The maximum follow-up duration was 1,115 days, with the median follow-up duration being 801 days (IQR 776–831 days). At the censored median follow-up time of 12 months, the AF recurrence rate was 22.8%.

Imaging Variables in Cohorts With and Without AF Recurrence

The imaging variables for the cohorts with and without AF recurrence, as well as the PAF and PersAF cohorts, are presented in Supplementary Table 2.

There were no significant differences between patients without and with AF recurrence in either mean LV ejection fraction determined using the 2-dimensional Simpson method (59.2% [IQR 54.0–64.3%] vs. 59.0% [IQR 52.2–64.1%], respectively; P=0.82) or LAVI (29.4 [IQR 22.8–35.8] vs 30.7 [IQR 22.7–35.2] mL/m², respectively; P=0.74). There were also no significant differences between the 2 groups in measures of diastolic dysfunction, namely E/A and E/e′ (Table 2), or in the imaging variable LV-GLS (−19.7% [IQR −22.9%, −18.0%] vs. −19.3% [IQR −20.9%, −17.6%] in the cohort without and with AF recurrence, respectively; P=0.15). There were significant differences between patients without and with AF recurrence in median LA ejection fraction (LAEF; 41.8% [IQR 33.9–50.5%] vs. 34.0% [IQR 29.1–43.7%], respectively; P=0.03) and LAS_R (30.1% [IQR 21.1–39.5%] vs. 19.8% [IQR 17.2–27.0%], respectively; P<0.001). The same difference were observed for LA conduit and contraction strain with less negative values for both variables in the cohort with AF recurrence (Table 2).

Table 2.

Imaging Variables of Cohorts With and Without AF Recurrence

	Without AF recurrence (n=102)	With AF recurrence (n=30)	P value
LA volume indexed to BSA (mL/m²)	29.4 (22.8~35.8)	30.7 (22.7~35.2)	0.74
LV ejection fraction (%)
3D	56.0 (53.3~60.0)	57.3 (52.0~62.1)	0.57
2D (Simpson)	59.2 (54.0~64.3)	59.0 (52.2~64.1)	0.82
LAEF 2D (Simpson) (%)	41.8 (33.9~50.5)	34.0 (29.1~43.7)	0.030
E/A	1.2 (1.0~1.5)	1.2 (1.0~1.8)	0.80
E/e′ *	8.3 (6.8~10.1)	9.0 (7.4~11.1)	0.24
LV global longitudinal strain (%)	−19.7 (−22.9~−18.0)	−19.3 (−20.9~−17.6)	0.15
LV strain 3D (%)	−18.0 (−20.3~−14.5)	−19.1 (−23.0~−15.7)	0.12
LAS_R (%)	30.1 (21.1~39.5)	19.8 (17.2~27.0)	<0.001
LA conduit strain (%)	−17.1 (−23.9~−12.0)	−12.9 (−15.9~−8.1)	<0.001
LA contraction strain (%)	−12.1 (−18.5~−6.3)	−8.4 (−14.9~−3.7)	0.020

Unless indicated otherwise, data are given as the median [interquartile range]. *Mean of septal and lateral tissue Doppler. 2D, 2-dimensional; 3D, 3-dimensional; AF, atrial fibrillation; BSA, body surface area; LA, left atrial; LAEF, left atrial ejection fraction; LAS_R, left atrial strain reservoir; LAVI, left atrial volume index; LV, left ventricular.

Imaging Variables in the Cohort With PAF and PersAF

There was a significant difference in LAVI between patients with PAF and PersAF (28.9 [IQR 21.2–35.0] vs. 30.5 [IQR 25.9–44.2] mL/m², respectively; P=0.03), but no significant differences in LAEF and LV-GLS between the 2 groups (Supplementary Table 2). LAS_R differed significantly between the PAF and PersAF cohorts (29.8% [IQR 19.5–41.0%] vs. 24.3% [IQR 16.4–32.7%], respectively; P=0.01), as did conduit and contraction strain (Supplementary Table 2).

Selection of Optimal Cut-Off Values and Associations of Imaging Variables With AF Recurrence

For the imaging variables, optimal cut-off values were calculated for the classification of AF recurrence not including the blanking period of the first 3 months. The calculated cut-off values were 27.7 mL/m² for LAVI, 31.4% for LAS_R, −22.2% for LV-GLS, and 35.7% for LAEF. The cut-off values for LAS_R (P<0.01) and LAEF (P<0.01) were significantly associated with AF recurrence, but no significant association could be demonstrated between LAVI or LV-GLS and AF recurrence (Figure 3). The calculated C-indices for LAS_R and LAEF were 0.66 and 0.62, respectively. C-Index values are presented in Supplementary Table 3.

Figure 3.

Kaplan-Meier curves excluding the first 3 months of follow-up, representing the blanking time, showing the association of imaging variables with the risk of atrial fibrillation (AF) recurrence. 2D, 2-dimensional; LA, left atrial; LAVI, left atrial volume index; LV, left ventricular.

Uni- and Multivariable Cox Regression Analysis of Associations With Risk of AF Recurrence

In univariable Cox regression analysis of associations between imaging variables and AF recurrence, LAS_R was found to be significantly associated with AF recurrence (HR 0.83; 95% CI 0.73–0.93; P=0.0014; Figure 4). None of the other imaging variables was associated with the risk of AF recurrence. For clinical variables, only age was associated with the risk of AF recurrence. In the multivariable analysis model including the imaging variables (LAS_R and LAEF), only LAS_R was found to be associated with the risk of AF recurrence (HR 0.83 [95% CI 0.73–0.95; P=0.005] for every 5% increase in LAS_R). In the multivariable analysis model including all clinical and imaging variables, age (HR 1.06; 95% CI 1.01–1.10; P=0.009) and LAS_R (HR 0.86; 95% CI 0.73–1.00; P=0.046) were associated with the risk of AF recurrence (Figure 4).

Figure 4.

Forest plots showing the results of univariable and multivariable Cox regression analysis of the association of imaging and clinical variables with atrial fibrillation (AF) recurrence. Clipped confidence intervals (CIs) are indicated by arrows. (A,B) Univariable analysis for imaging (A) and clinical (B) variables. (C,D) Multivariable analysis for imaging (C) and clinical (D) variables. 2D, 2-dimensional; HR, hazard ratio; LA, left atrial; LAVI, left atrial volume index; LV, left ventricular.

Discussion

This analysis of the ASTRA-AF study found that: (1) LAS_R was associated with the risk of AF recurrence in a model including all the imaging variables investigated; (2) LAS_R was also associated with the risk of AF recurrence in a multivariable model including age, sex, and type of AF; (3) there was no significant difference in LAVI between patients with and without AF recurrence when compated to established risk indicators for AF like arterial hypertension, diabetes mellitus or heart failure;³⁰ and (4) LAS_R differed between patients with PAF and PersAF. In a cohort including PAF and PersAF patients undergoing either RFA or cryoballoon ablation, the AF recurrence rate was 22.8%.

LAS_R and AF Recurrence

The presence of AF can lead to structural changes in the LA, resulting in impaired LA function¹⁷ and a reduction in LAS_R. This impairment in LA function may indicate an increased risk of stroke or new onset of AF in heart failure patients.¹⁶^,¹⁹ A suggested cut-off value of 30% for LAS_R has been proposed as an indicator of relevant structural remodeling of the LA.¹⁴ In our study cohort, we found that lower LAS_R values, as well as LA conduction and LA contraction strain, were associated with AF recurrence. The calculated LAS_R cut-off value in our cohort for AF recurrence was 31.4%, which is similar to the suggested cut-off of 30%. However, it is important to note that cut-off value derived from our cohort should be evaluated in larger studies as it was calculated in a specific cohort.

In previous studies,¹⁶^,³¹ LAS_R was reported to be associated with cardiovascular events like stroke and was proposed, together with the already established CHA₂DS₂-VASc score, as a method to assess stroke risk.¹⁶ Further, LAS_R was reported to be impaired in patients with AF compared with controls, suggesting an increasing burden of fibrosis and LA structural remodeling with the progression of AF.¹⁷

In our univariable analysis, LAS_R was the variable with a relevant association to recurrence of AF and increasing values of LAS_R were related to a lower recurrence risk, with higher values being associated with a better outcome, indicating that patients with higher LAS_R are less likely to develop AF recurrence during follow-up. Even in adjusted models that included commonly included variables such as sex, age, and type of AF,³⁰ LAS_R and age were associated with AF recurrence. Although age is a non-modifiable variable, previous studies have shown evidence of improving LAS_R during follow-up following successful catheter ablation of AF.²¹^,³² Therefore, there may be potential for improvement in LAS_R over time. However, in the context of the present study, LAS_R appears useful for assessing the risk of AF recurrence, although additional variables, Particularly clinical variables (e.g., sex, age, and type of AF), should also be assessed.³⁰

Clinical Variables Predicting AF Recurrence After PVI

The most common described risk factor associated with AF recurrence in the literature is LA volume.¹^,²^,¹⁵ In the present study, LAVI did not differ between those with and without AF recurrence. This can be explained by the fact that most of the patients in the study had PAF, which typically does not exhibit the same degree of structural alterations as seen in PersAF.¹⁷ In our ASTRA-AF cohort, patients with PersAF had a larger overall LA volume, as reflected by LAVI. However, it is important to note that LAVI was below the threshold of 34 mL/m² in all groups in this study, regardless of the recurrence or type of AF.

Of the clinical variables, age has been reported to have the strongest association with the risk of AF recurrence.¹^,³⁰ In our cohort, patients with AF recurrence were older than those without AF recurrence, highlighting the importance of age in AF risk prediction. As a specific risk factor, age cannot be modified.¹^,³⁰ The type of AF as a risk factor is not as important as age, because approximately the same percentage of patients with PAF and PersAF develop AF recurrence (33%).³⁰ Indeed procedure-related variables, such as low-voltage areas, have been shown to be associated with AF recurrence,³³ and low-voltage zones may be targets for additional ablation in patients with PersAF.³⁴ However, these variables were not assessed in our cohort.

LAEF, LV-GLS, Atrial Mechanical Dispersion, and AF Recurrence After PVI

In addition to LAVI, LAEF was measured to reflect the phasic volume changes of the LA with the total emptying fraction. Despite differences in LAEF between patients with and without AF recurrence, LAEF was not selected in uni- and multivariable analyses. Although an association between the type of AF and structural remodeling reflected by low-voltage areas has been reported,³²^,³⁵ our study confirmed reduced LAEF in patients with AF recurrence during follow-up, but did not find the previously reported association between PAF and PersAF and its association with recurrence of AF.³⁰ Previous data have also shown that LAEF is a predictor of cardiovascular events and heart failure hospitalisations.³⁶ Furthermore, LV-GLS has been reported to be associated with the risk of developing AF in a high-risk cohort following cryptogenic stroke.²⁷ In that study²⁷ the combination of LV-GLS and LA strain was superior in identifying patients with cryptogenic stroke developing AF than other imaging variables like LA volume. However, in our ASTRA-AF cohort, LV-GLS was not associated with the risk of AF recurrence. This apparent discrepancy may be related to the fact that LA volume was not increased as reported in the previous study,²⁷ in which LV-GLS was most useful in patients with a dilated LA.

We also investigated atrial mechanical dispersion in the ASTRA-AF study cohort; however, despite the fact that with an prolonged time to peak strain measured as standard deviation of that time reflecting potential tissue alterations, atrial mechanical dispersion is variable and not easy to measure.²⁴^,²⁵^,³⁷ Atrial mechanical dispersion investigates the timing of LA activation, and thus may reflect changes of the tissue, such as fibrosis. The LAS is more a parameter of LA function because it is already recommended in the guidelines. Although atrial mechanical dispersion can detect patients at increased risk of AF recurrence, LAS_R estimates are often more standardized and easier to obtain in clinical practice.¹⁴^,³⁸

LAS_R in Patients With PAF and PersAF

As of now, PAF and PersAF are typically described based on the duration of AF.¹^,² However, there is a growing interest in identifying functional parameters that can provide a more detailed characterization of the different types of AF. In our study, we found that LAS_R and LAVI differed between these 2 types of AF. Although LAVI is a well-characterized variable and patients with PersAF often have an enlarged LA, reduced LAS_R may be a feature to better characterize patients as having PersAF or PAF. It is important to note that due to the small number of patients in the present study, this finding is currently descriptive and would benefit from further investigation in larger studies.

Implications of Measuring LAS_R Before PVI

Imaging with echocardiography is recommended upon diagnosis of AF in patients² to rule out structural changes of the heart, such as valvular heart disease, which can be related to the onset of AF. However, there is currently evidence that early rhythm control and sustained sinus rhythm are important for the management of AF patients.²^,⁴^,⁶ LAS_R has been reported to be associated with the risk of AF recurrence following ablation therapy.²^,¹⁴^,³⁹ During follow-up, patients with impaired LAS_R may be candidates for more strict rhythm monitoring, potentially using wearables.²

In conclusion, in the ASTRA-AF study, LAS_R was the only imaging variable in addition to the clinical variable of age that was associated with the risk of AF recurrence in both univariate and multivariate analyses. Other variables, such as sex and type of AF were not associated with the risk of AF recurrence.

Strengths and Limitations

The strength of the study lies in its representation of a contemporary cohort of patients presenting with PAF and PersAF for de novo PVI. The investigators responsible for the measurements were experienced with the software and routinely used this measurement in the echocardiography laboratory.

However, there are several limitations to consider. All patients were recruited at a single institution, which means that no comparison with data from other institutions is possible. In addition, the sample size was small, and the data must be considered as descriptive. Furthermore, follow-up echocardiography to assess LA reverse remodeling was not available for additional analysis. These limitations should be considered when interpreting the findings of the study.

Conclusions

The data from the ASTRA-AF study indicate that LAS_R can be used to assess the risk of recurrence of AF following de novo PVI. Further research is necessary to validate these findings and their potential clinical implications.

Acknowledgments

The authors thank the study staff and study participants for their support and participation.

Sources of Funding

This study did not receive any specific funding.

Disclosures

S.B. has received grants and personal fees from Abbott Diagnostics, Bayer, Siemens, Thermo Fisher; grants from Singulex; personal fees from Abbott, AstraZeneca, Amgen, Medtronic, Pfizer, Roche, Siemens Diagnostics, and Novartis outside of the submitted work. P.K. was supported, in part, by European Union AFFECT-AF (Grant agreement 847770), MAESTRIA (Grant agreement 965286), the British Heart Foundation (PG/17/30/32961; PG/20/22/35093; AA/18/2/34218), the German Centre for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK), Deutsche Forschungsgemeinschaft (Ki 509167694), and Leducq Foundation. P.K. also reports research support for basic, translational, and clinical research projects from the European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK), and German Centre for Cardiovascular Research, and from several drug and device companies active in atrial fibrillation; and has received honoraria from several such companies in the past, but not in the past 3 years. P.K. is also listed as inventor on 2 issued patents held by the University of Hamburg (Atrial Fibrillation Therapy WO 2015140571; Markers for Atrial Fibrillation WO 201612783). C.S. has received honoraria for lectures from Böhringer Ingelheim. The remaining authors have no conflicts of interest to declare.

IRB Information

This study was approved by the Ethics Review Board of the Hamburg Medical Council, Federal County of Hamburg, Germany (Study protocol no. PV5815).

Data Availability

The deidentified participant data will be shared on a request basis. Please contact the corresponding author directly to request data sharing. All datasets used will be available, including the study protocol. Data will be shared as soon as the IRB at University Hospital Hamburg-Eppendorf approves the request, and will be available thereafter. Once consent has been given to share the data, any analysis of the data will be shared as an output file via a password-protected email, subject to approval.

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circj.CJ-24-0209

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