Abstract
We investigated predictors of left atrial volume reduction (LAVR) in patients with atrial fibrillation (AF) undergoing AF ablation.
Sixty patients with AF underwent pulmonary vein isolation (PVI) using a pulmonary vein ablation catheter (PVAC). All patients underwent cardiac imaging by computed tomography or magnetic resonance imaging to determine LAV 1 day before and 140 ± 9.5 days after PVI. Clinical follow-up and 72 h electrocardiogram Holter monitoring were performed 1, 3, and 6 months after ablation, and every 6 months thereafter. Significant LAVR (n = 60, 89.3 ± 3.9 vs. 79.5 ± 3.6 mL, P < 0.0001) was shown for the study group as a whole, caused particularly by the subgroup of patients with ablation success (n = 45, 85.2 ± 4.6 vs. 72.5 ± 3.7 mL, P < 0.0001). In addition, significant LAVR was shown for patients with lone AF (n = 25, 88.8 ± 6.8 vs. 72.7 ± 5.3 mL, P < 0.0001), but not for patients with AF and concomitant arterial hypertension (n = 32, 89 ± 4.8 vs. 86.7 ± 5 mL, P = 0.3), coronary artery disease (n = 12, 91.6 ± 7.8 vs. 89.1 ± 7.8 mL, P = 0.26), or left ventricular hypertrophy (n = 10, 86.3 ± 5.5 vs. 83.1 ± 5.3 mL, P = 0.27). Multivariate analysis revealed absence of arterial hypertension, lone AF, ablation success, and initial LA enlargement as independent predictors for significant LAVR following ablation (each P < 0.05).
Based on the subgroup of patients with lone AF, PVI leads to a significant LAVR 4 months after the procedure, especially in patients with clinical success in terms of AF freedom. Comorbidities such as arterial hypertension may prevent this reverse atrial remodelling, despite AF freedom. Clinical implications need to be further elucidated.
Pulmonary vein isolation for atrial fibrillation (AF) with pulmonary vein ablation catheter leads to a significant reduction in left atrial volume (LAV).
Only patients with lone AF showed this significant LAV reduction (LAVR) in contrast to patients with arterial hypertension or coronary artery disease.
Absence of arterial hypertension, lone AF, ablation success, and initial LA enlargement were independent predictors for significant LAVR following ablation.
Introduction
Frequent episodes of paroxysmal or even more persistent atrial fibrillation (AF) often result in left atrial (LA) enlargement. Besides increased atrial fibrosis and alterations of the ionic channel configuration, LA enlargement is known to be an important component of structural atrial remodelling, which again promotes AF (‘AF begets AF’).1 The left atrial volume (LAV) is a valid measure of LA size or enlargement and can be determined reliably by multidetector computed tomography (MDCT) or cardiac magnetic resonance imaging (CMRI).1–4 Pre-ablation enlargement of LAV measured by these non-invasive imaging techniques has been discussed as a predictor of success in studies treating AF using different ablation strategies.1,3,5–7 Conversely, successful ablation of AF and establishment of a stable sinus rhythm can result in a significant LAV reduction (LAVR), which may be characterized as reverse atrial remodelling, thus once again promoting sinus rhythm. Although some studies demonstrate LAVR following successful ablation of AF,8–11 there are only few data available on predictors for LAVR after pulmonary vein isolation (PVI). Identification of potential predictors such as structural heart disease, arterial hypertension, or others may play an important role, as concomitant treatment of those conditions could enhance ablation success.
Therefore, we investigated LAVR in patients with paroxysmal or persistent AF undergoing PVI by assessing LAV using pre- and post-procedural MDCT or CMRI and analysed predictors of outcome concerning the LAVR.
Methods
Patient characteristics
This retrospective non-randomized study was performed at the University Medical Center Regensburg, Germany. The study included patients with highly symptomatic AF (paroxysmal or persistent) presenting for PVI and available pre- and post-procedural cardiac imaging (CMRI or MDCT) allowing for LAV measurement. Exclusion criteria were poor image quality impeding tracing of LAV or clinically significant valvular disease or congenital heart defects (e.g. atrial septal defect). All patients had a history of recurrent arrhythmias for at least 12 months and were resistant to antiarrhythmic drug therapy. Atrial fibrillation burden before ablation was assessed by clinical data and categorized as follows: Frequency of AF category 1: 1 per year or less; 2: 1 per month, 3: 1 per week, 4: 3 per week, 5: 1 per day. Duration of a single AF episode category 1: <1 h, 2: 1–12h, 3: 12–48h, 4: 2–7 days, 5: 7–30 days, 6: >30 days. Informed written consent was obtained from all patients prior to the ablation procedure. The need for approval was waived by the institutional ethics commission.
Cardiac imaging by cardiac magnetic resonance imaging, multidetector computed tomography, and echocardiography
Standard pre-procedural imaging with CMRI or MDCT was carried out at our clinic to define the PV anatomy. A recent study by Wen et al.12 showed that dual-source CT was comparable with CMRI in terms of detection of LAV. For safety reasons, additional post-procedural imaging was performed to rule out PV stenosis when using the pulmonary vein ablation catheter (PVAC) as a new technology. This allowed for retrospective assessment of the pre- and post-procedural LAV.
Imaging techniques using CMRI or MDCT have been described before in detail.5 Briefly, CMRI was performed with a 1.5-T MR system (Magnetom Avanto, Siemens Healthcare) employing a 32-channel cardiac coil. A T1-weighted 3D fast spoiled gradient echo sequence was used for contrast-enhanced MR angiography (ce-MRA) of LA and PV anatomy. Following a test bolus acquisition to evaluate transport time to the LA, 0.1 mmol/kg gadobutrol (Gadovist, Bayer Schering AG) was injected at a flow rate of 2 mL/s. The following parameters were used for the MRA sequence which was repeated twice during a single breath-hold: echo time 1.18 ms, repetition time 3.12 ms, flip angle 25°, field-of-view 350 mm, image matrix 269 × 384, slice thickness 1.2 mm (voxel size: 1.3 mm × 0.9 mm × 1.2 mm), acquisition time 12 s. Images of the LA and the PVs were reconstructed using maximum intensity projection and multiplanar reformations.
For MDCT cardiac imaging, we used a 16-slice MDCT scanner (Somatom Sensation 16, Siemens Healthcare) with acquisition parameters as follows: collimation 16 × 0.75 mm, rotation time 0.5 s, pitch 1.25, tube voltage 120 kV, tube current dose modulated 50–200 mAs. The injection protocol consisted of 100 mL of non-ionic iodinated contrast agent (Iohexol, Accupaque 300, Amersham Health) administered at a flow rate of 3 mL/s. The scan was started with a delay of 30s after contrast agent injection to achieve optimal contrast enhancement within the LA and the PVs. Multidetector computed tomography images were reconstructed at contiguous section widths of 2 mm in axial and coronal planes using a soft tissue reconstruction kernel.
Finally, left atrial diameter (LAD) in the long parasternal view and ejection fraction of the left ventricle (EF by Simpson's method) were assessed by echocardiography.
Measurement of left atrial volume
Performance of image analysis has been described in detail before.5 Briefly, analysis was carried out offline by an experienced single observer blinded to the results of the ablation procedure and the patient's clinical data and follow-up. The endocardial border of the LA was manually traced on each cross-sectional image incipient on the roof of the LA extending to the mitral annulus, which was excluded at the point of insertion of the mitral valve leaflets. Care was taken to exclude the PVs and the left atrial appendage (LAA) at the point of inflection between the LA wall and the PV or the LAA wall. Left atrial areas were automatically calculated and LAV was obtained by LA area summation.
Catheter ablation procedure
Pulmonary vein isolation was performed using a PVAC (PVAC™, Medtronic), which has been described in detail before.5,13–16 Briefly, systemic anticoagulation was achieved after transseptal puncture using intravenous heparin to maintain an activated clotting time of 300–350s. Three-dimensional rotational atriography (EP navigator, Philips Healthcare) was carried out to obtain 3D reconstruction of the LA. Subsequently, antral ablation was performed and radiofrequency (RF) energy was usually delivered at a target temperature of 60°C for 60s. Ablation was always started with an energy setting of 4 : 1 bipolar/unipolar. Only when no PVI could be achieved using this energy setting, was the energy ratio changed to 2 : 1 to increase lesion depth. Pulmonary vein ablation catheter ablation was continued until isolation of each PV was successful, confirmed by entrance block using differential pacing, and by evidence of exit block.
Follow-up
Patients were evaluated clinically 1, 3, and 6 months following the ablation procedure and every 6 months thereafter. Pre-procedural antiarrhythmic drug therapy was continued for 1 month in all patients. The majority of patients were prescribed beta-blockers following PVI. To assess for AF recurrence, all patients were asked to keep a log of their symptoms. In addition, at each follow-up visit 72 h electrocardiogram Holter monitoring was performed to reveal any clinically asymptomatic recurrences of AF. Recurrence of AF was defined as any documented AF episode lasting longer than 30s.
Statistical analysis
Statistical analysis was performed using GraphPad Prism 5.0 and IBM SPSS Statistics Analysis 20. Results are expressed as mean ± SEM. The LAVR in each group was evaluated by the paired t-test. Comparisons of LAVR between two groups were assessed by an unpaired t-test. The AF burden was evaluated by one-way analysis of variance with Bonferroni's multiple comparison test. The association of potential predictors of the change of LAV in millilitres was assessed in a univariate linear regression analysis. Variables selected for univariate analysis were: age, gender, body mass index (BMI), presence of hypercholesterolaemia, diabetes mellitus type II, coronary artery disease (CAD), arterial hypertension, AF burden (frequency of AF and duration of each AF episode), left ventricular hypertrophy (LVH), freedom from AF, smoker status, duration of AF, type of AF (persistent or paroxysmal), and LAV before ablation. Predictors with a P < 0.05 in the univariate analysis were entered in the multivariate regression analysis. Statistical significance was accepted at P < 0.05. Left atrial volume before ablation was also assessed by univariate analysis for relative change in LAV (as percentage change) to adjust extremely high and low LAV values.
Results
Patient characteristics and ablation procedure
Between November 2007 and May 2010, 65 patients with paroxysmal or persistent AF were eligible for the study. Five of these patients were subsequently excluded: four for technical reasons resulting in poor image quality, one because of a clinically relevant atrial septal defect. Finally, 60 patients were included in the statistical analysis. Baseline characteristics of these patients are summarized in Table 1. Concerning AF burden, the duration of each episode was categorized as 2.92 ± 0.42 for lone AF, 2.95 ± 0.3 for arterial hypertension, 2.56 ± 0.47 for CAD, and 3.17 ± 0.65 for LVH (P = 0.155). Frequency of AF episodes categories were 3.0 ± 0.25 for lone AF, 3.4 ± 0.26 for arterial hypertension, 3.6 ± 0.32 for CAD, and 4.25 ± 0.1 for LVH (P = 0.8). One day before the ablation procedure, CMRI was performed in 34 patients and MDCT in 26 patients. After a mean follow-up of 140 ± 9.5 days, cardiac imaging was carried out in 23 patients by CMRI and in 37 patients by MDCT.
Clinical outcome
The mean follow-up time was 19 ± 1.4 months. One patient was lost to follow-up after 3 months due to non-compliance. During the follow-up period, 45 out of 60 patients were free of AF (75%) based on symptoms and 3-day Holter monitoring. Of these 45 patients, 22 (48.9%) had lone AF (Tables 1 and 2). A repeat procedure was performed in 11 (18.3%) patients. There were no major complications.
Baseline characteristics data
| Patient characteristics | Mean ± SEM |
|---|---|
| Patients (n) | 60 |
| Age (years) | 62.1 ± 1.4 |
| Gender (male/female) | 32/28 |
| BMI (kg/m2) | 28.6 ± 0.6 |
| Lone AF | 25 |
| Arterial hypertension (patients) | 32 (53%) |
| CAD (patients) | 12 (20%) |
| Diabetes mellitus (patients) | 5 (8%) |
| Smoker | 13 (21.7%) |
| LVH (patients) | 10 (16.7%) |
| Type of AF (paroxysmal/persistent) | 44/16 (73.3/26.7%) |
| Duration of AF (years) | 5.4 ± 0.89 |
| Ineffective antiarrhythmic drugs (n = 0/1/2/3) | 4/34/21/1 (6.6/56.7/35/1.7%) |
| EF < 55% | 4 (6.7%) |
| Mean LAD (mm) | 45.5 ± 1.2 |
| Mean LA area (cm2) | 24.7 ± 1.8 |
| Mean LA volume (mL) in MDCT/CMRI | 89.3 ± 3.9 |
| Patient characteristics | Mean ± SEM |
|---|---|
| Patients (n) | 60 |
| Age (years) | 62.1 ± 1.4 |
| Gender (male/female) | 32/28 |
| BMI (kg/m2) | 28.6 ± 0.6 |
| Lone AF | 25 |
| Arterial hypertension (patients) | 32 (53%) |
| CAD (patients) | 12 (20%) |
| Diabetes mellitus (patients) | 5 (8%) |
| Smoker | 13 (21.7%) |
| LVH (patients) | 10 (16.7%) |
| Type of AF (paroxysmal/persistent) | 44/16 (73.3/26.7%) |
| Duration of AF (years) | 5.4 ± 0.89 |
| Ineffective antiarrhythmic drugs (n = 0/1/2/3) | 4/34/21/1 (6.6/56.7/35/1.7%) |
| EF < 55% | 4 (6.7%) |
| Mean LAD (mm) | 45.5 ± 1.2 |
| Mean LA area (cm2) | 24.7 ± 1.8 |
| Mean LA volume (mL) in MDCT/CMRI | 89.3 ± 3.9 |
Echocardiographic data presented in italics.
Baseline characteristics data
| Patient characteristics | Mean ± SEM |
|---|---|
| Patients (n) | 60 |
| Age (years) | 62.1 ± 1.4 |
| Gender (male/female) | 32/28 |
| BMI (kg/m2) | 28.6 ± 0.6 |
| Lone AF | 25 |
| Arterial hypertension (patients) | 32 (53%) |
| CAD (patients) | 12 (20%) |
| Diabetes mellitus (patients) | 5 (8%) |
| Smoker | 13 (21.7%) |
| LVH (patients) | 10 (16.7%) |
| Type of AF (paroxysmal/persistent) | 44/16 (73.3/26.7%) |
| Duration of AF (years) | 5.4 ± 0.89 |
| Ineffective antiarrhythmic drugs (n = 0/1/2/3) | 4/34/21/1 (6.6/56.7/35/1.7%) |
| EF < 55% | 4 (6.7%) |
| Mean LAD (mm) | 45.5 ± 1.2 |
| Mean LA area (cm2) | 24.7 ± 1.8 |
| Mean LA volume (mL) in MDCT/CMRI | 89.3 ± 3.9 |
| Patient characteristics | Mean ± SEM |
|---|---|
| Patients (n) | 60 |
| Age (years) | 62.1 ± 1.4 |
| Gender (male/female) | 32/28 |
| BMI (kg/m2) | 28.6 ± 0.6 |
| Lone AF | 25 |
| Arterial hypertension (patients) | 32 (53%) |
| CAD (patients) | 12 (20%) |
| Diabetes mellitus (patients) | 5 (8%) |
| Smoker | 13 (21.7%) |
| LVH (patients) | 10 (16.7%) |
| Type of AF (paroxysmal/persistent) | 44/16 (73.3/26.7%) |
| Duration of AF (years) | 5.4 ± 0.89 |
| Ineffective antiarrhythmic drugs (n = 0/1/2/3) | 4/34/21/1 (6.6/56.7/35/1.7%) |
| EF < 55% | 4 (6.7%) |
| Mean LAD (mm) | 45.5 ± 1.2 |
| Mean LA area (cm2) | 24.7 ± 1.8 |
| Mean LA volume (mL) in MDCT/CMRI | 89.3 ± 3.9 |
Echocardiographic data presented in italics.
Left atrial volume (in mL) in AF-free patients before and after ablation
| Variable | AF freedom | ||
|---|---|---|---|
| LAV(mL) before/after PVI | (n) | P value | |
| All patients | 85.2 ± 4.6 to 72.5 ± 3.7 | (45) | 0.0001 |
| Lone AF | 84.5 ± 6.9 to 67.4 ± 4.7 | (22) | 0.0002 |
| CAD | 87.4 ± 10.7 to 77.2 ± 11.1 | (7) | 0.34 |
| Arterial hypertension | 83.5 ± 6.1 to 79.7 ± 5.6 | (21) | 0.2 |
| LVH | 84.5 ± 7.0 to 81.8 ± 6.3 | (6) | 0.46 |
| Paroxysmal AF | 80.7 ± 4.2 to 69.8 ± 3.8 | (36) | 0.0001 |
| Persistent AF | 103.4 ± 13.6 to 83.0 ± 9.6 | (9) | 0.09 |
| AF duration <24 months | 90.8 ± 15.5 to 62.1 ± 10.6 | (8) | 0.028 |
| AF duration ≥24 months | 84.7 ± 4.7 to 78.0 ± 4.5 | (30) | 0.005 |
| Variable | AF freedom | ||
|---|---|---|---|
| LAV(mL) before/after PVI | (n) | P value | |
| All patients | 85.2 ± 4.6 to 72.5 ± 3.7 | (45) | 0.0001 |
| Lone AF | 84.5 ± 6.9 to 67.4 ± 4.7 | (22) | 0.0002 |
| CAD | 87.4 ± 10.7 to 77.2 ± 11.1 | (7) | 0.34 |
| Arterial hypertension | 83.5 ± 6.1 to 79.7 ± 5.6 | (21) | 0.2 |
| LVH | 84.5 ± 7.0 to 81.8 ± 6.3 | (6) | 0.46 |
| Paroxysmal AF | 80.7 ± 4.2 to 69.8 ± 3.8 | (36) | 0.0001 |
| Persistent AF | 103.4 ± 13.6 to 83.0 ± 9.6 | (9) | 0.09 |
| AF duration <24 months | 90.8 ± 15.5 to 62.1 ± 10.6 | (8) | 0.028 |
| AF duration ≥24 months | 84.7 ± 4.7 to 78.0 ± 4.5 | (30) | 0.005 |
P values are calculated using the paired t-test.
Left atrial volume (in mL) in AF-free patients before and after ablation
| Variable | AF freedom | ||
|---|---|---|---|
| LAV(mL) before/after PVI | (n) | P value | |
| All patients | 85.2 ± 4.6 to 72.5 ± 3.7 | (45) | 0.0001 |
| Lone AF | 84.5 ± 6.9 to 67.4 ± 4.7 | (22) | 0.0002 |
| CAD | 87.4 ± 10.7 to 77.2 ± 11.1 | (7) | 0.34 |
| Arterial hypertension | 83.5 ± 6.1 to 79.7 ± 5.6 | (21) | 0.2 |
| LVH | 84.5 ± 7.0 to 81.8 ± 6.3 | (6) | 0.46 |
| Paroxysmal AF | 80.7 ± 4.2 to 69.8 ± 3.8 | (36) | 0.0001 |
| Persistent AF | 103.4 ± 13.6 to 83.0 ± 9.6 | (9) | 0.09 |
| AF duration <24 months | 90.8 ± 15.5 to 62.1 ± 10.6 | (8) | 0.028 |
| AF duration ≥24 months | 84.7 ± 4.7 to 78.0 ± 4.5 | (30) | 0.005 |
| Variable | AF freedom | ||
|---|---|---|---|
| LAV(mL) before/after PVI | (n) | P value | |
| All patients | 85.2 ± 4.6 to 72.5 ± 3.7 | (45) | 0.0001 |
| Lone AF | 84.5 ± 6.9 to 67.4 ± 4.7 | (22) | 0.0002 |
| CAD | 87.4 ± 10.7 to 77.2 ± 11.1 | (7) | 0.34 |
| Arterial hypertension | 83.5 ± 6.1 to 79.7 ± 5.6 | (21) | 0.2 |
| LVH | 84.5 ± 7.0 to 81.8 ± 6.3 | (6) | 0.46 |
| Paroxysmal AF | 80.7 ± 4.2 to 69.8 ± 3.8 | (36) | 0.0001 |
| Persistent AF | 103.4 ± 13.6 to 83.0 ± 9.6 | (9) | 0.09 |
| AF duration <24 months | 90.8 ± 15.5 to 62.1 ± 10.6 | (8) | 0.028 |
| AF duration ≥24 months | 84.7 ± 4.7 to 78.0 ± 4.5 | (30) | 0.005 |
P values are calculated using the paired t-test.
Left atrial volume reduction in patients with and without ablation success
A significant reduction in LAV following AF ablation (89.3 ± 3.9 vs. 79.5 ± 3.6 mL, P < 0.0001) was found for the study group as a whole (n = 60 patients), caused particularly by the subgroup of patients with ablation success (n = 45 patients; 85.2 ± 4.6 vs. 72.5 ± 3.7 mL, P < 0.0001). As validation of concept, all patients without ablation success (n = 14 patients) had no LAVR (102.8 ± 6.8 vs. 101.6 ± 7.5 mL, P = 0.72), irrespective of lone AF, CAD, or arterial hypertension (Figure 1). Interestingly, patients with paroxysmal AF showed a significant LAVR (paroxysmal AF: 82.4 ± 3.6 to 73.7 ± 3.7 mL, P = 0.0005, n = 44; persistent AF: 108.4 ± 9.1 to 95.3 ± 8.3, P = 0.058, n = 16).
Left atrial volume (LAV) before and after ablation in (A) all patients (n = 60), (B) AF-free patients (n = 45), and (C) patients with AF recurrences (n = 14).
Echocardiography also demonstrated a significant reduction of LAD (45.5 ± 1.2 vs. 43.1 ± 1.3 mm, P = 0.027).
Left atrial volume reduction in relation to comorbidity in patients with ablation success
Significant LAVR was present in patients with lone AF, but not in patients with concomitant arterial hypertension, CAD, or LVH (Figure 2). To demonstrate that significant LAVR in patients with lone AF was not related to a better clinical outcome with more AF freedom, we re-evaluated the effect of different comorbidities in a subgroup of patients with ablation success (n = 45). Similarly, in this subgroup analysis AF-free patients with lone AF (n = 22) showed a significant reduction in LAV, whereas AF-free patients with arterial hypertension (n = 21) or CAD (n = 7) showed no significant LAVR (Table 2 and Figure 3). Patients with paroxysmal AF showed a significant reduction in LAV (see Table 2).
Left atrial volume (LAV) before and after ablation in (A) lone AF (n = 25), (B) arterial hypertension (n = 32), (C) CAD (n = 12), and (D) LVH (n = 10). n.s., not significant.
Atrial fibrillation (AF)-free patients: LAV before and after ablation in the two subgroups lone AF (n = 22) and non-lone AF (LVH + CAD + arterial hypertension, n = 22): (A) the LAVs before and after PVI ablation comparing lone AF with non-lone AF, (B) change in LAV (in mL) by PVI ablation comparing lone AF with non-lone AF.
Comparison of changes in left atrial volume between different subgroups of patients with ablation success
The difference in change of LAV was significant in AF-free patients in comparison to patients with AF recurrences (P = 0.006). Looking at the AF-free group, the change in LAV between lone AF and patients with arterial hypertension was significant (P = 0.0014) as well as between lone AF and LVH (P = 0.02) and between lone AF and CAD (P = 0.0004). Taken together, the difference in change of LAV between non-lone AF and lone AF was also significant (Figure 3B). Atrial fibrillation duration <24 months showed no significant change in LAV in comparison with AF duration ≥24 months (P = 0.06). Paroxysmal AF showed no significant LAVR in comparison with persistent AF (P = 0.75).
Predictors of left atrial volume reduction
Univariate and multivariate analyses were performed to identify predictors of LAVR after PVI for AF. The univariate linear regression analysis showed the following parameters to be significantly associated with the LAVR: presence of arterial hypertension, lone AF, AF freedom, and LAV before ablation (each P< 0.05). Similarly, the multivariate analysis detected absence of arterial hypertension, lone AF, clinical success, and an enlarged pre-procedural LAV as independent predictors of significant reduction of LAV following ablation (each P < 0.05) with regard to the entire study group (Table 3). To adjust extremely high and low LAV values, LAV before ablation was also assessed by the univariate analysis for relative change in LAV (as percentage change). Here, LAV at baseline also showed significant association with relative change in LAV (P = 0.04; slope −0.15; 95% CI: −0.3 to −0.008).
Univariate and multivariate linear regression analysis for different predictors of LAVR in the subgroup of AF-free patients
| Variable | Univariate regression analysis | Multivariate regression analysis | ||
|---|---|---|---|---|
| Slope (95% CI) | P value | Slope (95% CI) | P value | |
| Arterial hypertension | 16.11 (7.45 to 24.76) | <0.0001 | 33.53 (16.99 to 50.07) | <0.0001 |
| Lone AF | −10.73 (−20.07 to −1.4) | 0.025 | 22.61 (5.81 to 39.41) | 0.009 |
| Clinical success | −11.61 (−22.68 to −0.55) | 0.04 | −14.55 (−23.44 to −5.65) | 0.002 |
| LAV before ablation | −0.25 (−0.38 to −0.1) | 0.002 | −0.29 (−0.41 to −0.16) | <0.0001 |
| Age | −0.13 (−0.57 to 0.32) | 0.57 | – | |
| Gender | 6.87 (−2.59 to 16.34) | 0.15 | – | |
| BMI | 0.58 (−0.53 to 1.69) | 0.30 | – | |
| Hypercholesterolaemia | 2.01 (−8.64 to 12.7) | 0.71 | – | |
| Diabetes mellitus | −8.55 (25.80 to 8.69) | 0.33 | – | |
| Smoker | −4.81 (−16.41 to −6.79) | 0.41 | – | |
| Type of AF | −3.47 (−13.32 to 6.37) | 0.48 | – | |
| Duration of AF | 5.33 (−0.74 to 11.39) | 0.08 | – | |
| CAD | 3.16 (−8.83 to 15.15) | 0.60 | – | |
| LVH | 7.93 (−4.94 to 20.79) | 0.22 | – | |
| Frequency of AF | −1.37 (−8.21 to 5.47) | 0.69 | ||
| Duration of episodes | 1.04 (−2.89 to 4.98) | 0.59 | ||
| Variable | Univariate regression analysis | Multivariate regression analysis | ||
|---|---|---|---|---|
| Slope (95% CI) | P value | Slope (95% CI) | P value | |
| Arterial hypertension | 16.11 (7.45 to 24.76) | <0.0001 | 33.53 (16.99 to 50.07) | <0.0001 |
| Lone AF | −10.73 (−20.07 to −1.4) | 0.025 | 22.61 (5.81 to 39.41) | 0.009 |
| Clinical success | −11.61 (−22.68 to −0.55) | 0.04 | −14.55 (−23.44 to −5.65) | 0.002 |
| LAV before ablation | −0.25 (−0.38 to −0.1) | 0.002 | −0.29 (−0.41 to −0.16) | <0.0001 |
| Age | −0.13 (−0.57 to 0.32) | 0.57 | – | |
| Gender | 6.87 (−2.59 to 16.34) | 0.15 | – | |
| BMI | 0.58 (−0.53 to 1.69) | 0.30 | – | |
| Hypercholesterolaemia | 2.01 (−8.64 to 12.7) | 0.71 | – | |
| Diabetes mellitus | −8.55 (25.80 to 8.69) | 0.33 | – | |
| Smoker | −4.81 (−16.41 to −6.79) | 0.41 | – | |
| Type of AF | −3.47 (−13.32 to 6.37) | 0.48 | – | |
| Duration of AF | 5.33 (−0.74 to 11.39) | 0.08 | – | |
| CAD | 3.16 (−8.83 to 15.15) | 0.60 | – | |
| LVH | 7.93 (−4.94 to 20.79) | 0.22 | – | |
| Frequency of AF | −1.37 (−8.21 to 5.47) | 0.69 | ||
| Duration of episodes | 1.04 (−2.89 to 4.98) | 0.59 | ||
Slope stands for the regression coefficient β.
Univariate and multivariate linear regression analysis for different predictors of LAVR in the subgroup of AF-free patients
| Variable | Univariate regression analysis | Multivariate regression analysis | ||
|---|---|---|---|---|
| Slope (95% CI) | P value | Slope (95% CI) | P value | |
| Arterial hypertension | 16.11 (7.45 to 24.76) | <0.0001 | 33.53 (16.99 to 50.07) | <0.0001 |
| Lone AF | −10.73 (−20.07 to −1.4) | 0.025 | 22.61 (5.81 to 39.41) | 0.009 |
| Clinical success | −11.61 (−22.68 to −0.55) | 0.04 | −14.55 (−23.44 to −5.65) | 0.002 |
| LAV before ablation | −0.25 (−0.38 to −0.1) | 0.002 | −0.29 (−0.41 to −0.16) | <0.0001 |
| Age | −0.13 (−0.57 to 0.32) | 0.57 | – | |
| Gender | 6.87 (−2.59 to 16.34) | 0.15 | – | |
| BMI | 0.58 (−0.53 to 1.69) | 0.30 | – | |
| Hypercholesterolaemia | 2.01 (−8.64 to 12.7) | 0.71 | – | |
| Diabetes mellitus | −8.55 (25.80 to 8.69) | 0.33 | – | |
| Smoker | −4.81 (−16.41 to −6.79) | 0.41 | – | |
| Type of AF | −3.47 (−13.32 to 6.37) | 0.48 | – | |
| Duration of AF | 5.33 (−0.74 to 11.39) | 0.08 | – | |
| CAD | 3.16 (−8.83 to 15.15) | 0.60 | – | |
| LVH | 7.93 (−4.94 to 20.79) | 0.22 | – | |
| Frequency of AF | −1.37 (−8.21 to 5.47) | 0.69 | ||
| Duration of episodes | 1.04 (−2.89 to 4.98) | 0.59 | ||
| Variable | Univariate regression analysis | Multivariate regression analysis | ||
|---|---|---|---|---|
| Slope (95% CI) | P value | Slope (95% CI) | P value | |
| Arterial hypertension | 16.11 (7.45 to 24.76) | <0.0001 | 33.53 (16.99 to 50.07) | <0.0001 |
| Lone AF | −10.73 (−20.07 to −1.4) | 0.025 | 22.61 (5.81 to 39.41) | 0.009 |
| Clinical success | −11.61 (−22.68 to −0.55) | 0.04 | −14.55 (−23.44 to −5.65) | 0.002 |
| LAV before ablation | −0.25 (−0.38 to −0.1) | 0.002 | −0.29 (−0.41 to −0.16) | <0.0001 |
| Age | −0.13 (−0.57 to 0.32) | 0.57 | – | |
| Gender | 6.87 (−2.59 to 16.34) | 0.15 | – | |
| BMI | 0.58 (−0.53 to 1.69) | 0.30 | – | |
| Hypercholesterolaemia | 2.01 (−8.64 to 12.7) | 0.71 | – | |
| Diabetes mellitus | −8.55 (25.80 to 8.69) | 0.33 | – | |
| Smoker | −4.81 (−16.41 to −6.79) | 0.41 | – | |
| Type of AF | −3.47 (−13.32 to 6.37) | 0.48 | – | |
| Duration of AF | 5.33 (−0.74 to 11.39) | 0.08 | – | |
| CAD | 3.16 (−8.83 to 15.15) | 0.60 | – | |
| LVH | 7.93 (−4.94 to 20.79) | 0.22 | – | |
| Frequency of AF | −1.37 (−8.21 to 5.47) | 0.69 | ||
| Duration of episodes | 1.04 (−2.89 to 4.98) | 0.59 | ||
Slope stands for the regression coefficient β.
Discussion
Here, we present the first data systematically demonstrating predictors of LAVR following PVI for AF. First, we were able to confirm that PVI leads to a significant reduction in LAV, especially in patients with ablation success. Secondly, significant LAVR was observed in the subgroup of patients with lone AF. The presence of comorbidities such as arterial hypertension, CAD, and LVH precluded a significant LAVR, as did recurrence of AF following PVI. This was also revealed in a subgroup analysis of patients with ablation success, which was performed to demonstrate that significant LAVR in patients with lone AF was not related to a better clinical outcome with higher freedom from AF. Finally, multivariate analysis detected clinical success, lone AF, absence of arterial hypertension, and pre-ablation LA enlargement as independent predictors of significant LAVR.
Significant reduction of left atrial volume after pulmonary vein isolation in relation to clinical success
First of all, our data on LAVR following PVI are in line with other studies investigating this phenomenon: PVI leads to a significant decrease in LAV. One study based on echocardiography showed that PVI leads to a significant decrease in LA area in serial echocardiographic measurements after up to 12 months in 48 patients with lone AF. Patients with comorbidities were not included.8 A different study demonstrated a more distinct LAVR in patients with chronic AF than in patients with paroxysmal AF9 using 3D echocardiography, which was performed at baseline and after 6 months of follow-up. This is in contrast to our study, where we found a more pronounced LAVR in patients with paroxysmal AF. Although patients with persistent AF showed a LAVR too, this did not reach statistical significance in our study (P = 0.058), which may be due to the small sample size. Müller et al. found that patients with AF recurrences (23%) had a similar LAVR compared with those who were free from AF. This interesting finding is also in clear contrast to our data which did not demonstrate LAVR in patients with AF recurrences. One possible explanation could be a reduction of AF episodes in the group of patients with AF recurrences in the echocardiographic study (occurrence of fewer and shorter AF episodes). The differences concerning LAVR in paroxysmal/persistent AF and concerning LAVR in AF recurrences may also be due to different non-correlating imaging techniques (MDCT/CMRI vs. echocardiography) or to different ablation techniques (segmental single-tip RF approach vs. multielectrode duty-cycled RF ablation catheter approach). One of the PVI methods may lead to more LA scarring17 leading to different LA remodelling processes. So far, there are no data comparing the extent of scarring after PVI for different ablation techniques.
Jayam et al.10 performed MRA in 51 patients before and 6–8 weeks after PVI with a segmental approach. They also found a significant LAVR regardless of the clinical outcome. However, no data were evaluated regarding comorbidities including their potential role as predictors in LAVR. Jahnke et al.11 demonstrated a significant and progressive LAVR after PVI with serial MRIs after several months post-ablation. In their study, patients with clinical success showed a significant LAVR at the 3-month follow-up according to our data. Their study adds the interesting finding that this atrial reverse volume reduction after PVI is a progressive process, where the timing of LAV measurement is crucial. However, once again, in contrast to our study, no data regarding predictors were evaluated.
Lone atrial fibrillation as a positive predictor of left atrial volume reduction after pulmonary vein isolation
In the present study, the absence of arterial hypertension is shown to be a positive predictor of LAVR following PVI. No data regarding clinical predictors have been published so far. Concerning ventricular reverse remodelling, one study has been published: following mitral valve surgery for severe chronic mitral regurgitation, arterial hypertension predisposed to less left ventricular reverse remodelling than patients free of arterial hypertension.18 Our data, however, refer for the first time to reverse LA remodelling. Heist et al.19 demonstrated that the presence of arterial hypertension is a positive predictor of clinical success of catheter ablation of persistent AF (odds ratio 2.83). Although a direct comparison to our study is not possible due to the lack of LAV measurement, the data presented by Heist et al. suggest that, besides precluding LAVR, arterial hypertension may also have a favourable effect on LA remodelling. The authors did not comment this phenomenon.
Why does arterial hypertension preclude reverse atrial remodelling after PVI in our study group? One explanation could be the influence of the activated renin–angiotensin system and of the elevated afterload on the atrial remodelling process in arterial hypertension.20 Another explanation could be more silent AF recurrences caused by arterial hypertension in the ‘AF-free’ group, which precludes LAVR. More studies are needed to further elucidate these processes.
Baseline left atrial enlargement as a positive predictor of left atrial volume reduction after pulmonary vein isolation
We were able to show that a baseline LA enlargement is a positive predictor of LAVR after PVI. These data are consistent with previously published data,10 where pre-ablation LAV was determined as an independent predictor of percentage LAVR. An echocardiographic study revealed that patients free from AF after PVI with an LAVR >22% (defined as responders) had a higher baseline LAV.21
A high baseline LAV was associated with a high degree of LAVR after PVI. This finding is surprising against the background that long-standing AF leads to enlarged LAs with severe structural and electrical remodelling. Even the highly enlarged LA reduces in size after successful PVI, despite its structural and electrical remodelling.
Clinical implications
As we have shown, clinical success after PVI for AF is an independent predictor of LAVR. Conversely, persistence of LA enlargement after PVI may be an additional risk factor for AF recurrences. In this context, concomitant treatment of the comorbidities of AF patients is important: arterial hypertension, in particular, must be treated according to the guidelines. However, in a multivariate analysis, Khaykin etal.22 were able to show that the presence of arterial hypertension is associated with an increased risk of AF recurrence after PVI. Optimizing the treatment of arterial hypertension could therefore be an important step towards improving clinical success after PVI by simple measures. Thus, concomitant and consistent treatment of structural heart diseases and arterial hypertension should be kept in mind to favour freedom from AF after PVI.
Limitations
The study has several limitations. First, this was a non-randomized retrospective study. Randomized multicenter trials are now warranted to evaluate the clinical impact of these findings. Secondly, the number of patients included in the study is limited, especially in the subgroup analysis. Nevertheless, the statistical differences are convincing despite the low number of patients and the results are for the most part consistent with the literature. Thirdly, MDCT and CMRT were used randomly to evaluate the LAV. A recent study by Wen et al.12 showed that dual-source CT was comparable to CMRI in terms of detection of LAV. Nevertheless, despite the similarity of the image methodologies in establishing the LAV, small differences in LAV measurements cannot be excluded.
Conclusion
Pulmonary vein isolation leads to a significant reduction of LAV 4 months after ablation in patients with AF. Pre-procedural LA dilatation and notably lone AF as well as the absence of arterial hypertension were independent predictors of this LAVR. The clinical implications of these findings need to be further evaluated.
Conflict of interest: none declared.
