Abstract
Background
Pulmonary vein isolation (PVI) is a cornerstone of AF ablation. Posterior wall isolation (PWI) has become a frequently used adjunct to PVI. While there is data to suggest that PVI alone does not negatively impact left atrial function, the effect of PWI on left atrial mechanical function has not been definitively determined. Our aim was to determine if PVI plus PWI using a cryoballoon impacted left atrial mechanical function as measured by cardiac MRI.
Methods
We studied 28 patients who underwent ablation for AF. Fourteen patients had PVI alone and 14 patients had PVI plus PWI. All patients had cardiac magnetic resonance (CMR) before and after ablation. The primary outcome was change in LA ejection fraction (LAEF) as measured by CMR.
Results
There were no statistically significant differences in the average patient age, height, weight, type of AF, or frequency of concomitant diseases between groups. No statistically significant differences in LAEF, LA max volume, LA min volume, or LA stroke volume were identified between baseline and follow up CMRs for the PVI only group nor the PVI plus PWI group. When utilizing linear regression analysis to compare change in LAEF, LA max volume, LA min volume, and LA stroke volume before and after ablation between groups, no statistically significant differences were identified.
Conclusion
Cardiac MRI did not demonstrate a significant change in left atrial mechanical function as measured by left atrial ejection fraction after pulmonary vein isolation alone nor after PVI plus posterior wall isolation.
Graphical Abstract
Keywords: Atrial fibrillation, Atrial fibrillation ablation, Posterior wall isolation, Left atrial function, Cardiac MRI
Introduction
Pulmonary vein (PV) isolation (PVI) has been shown to be an effective strategy for treating paroxysmal atrial fibrillation (AF) [1]. However, PVI by itself is often an insufficient method for the treatment of patients with persistent AF [2] and the success associated with catheter ablation of persistent AF has remained low despite a wide range of ablation techniques [3]. On the other hand, observations from surgical posterior wall isolation (PWI) have implicated the region in-between the PVs as a potential major contributor to persistent AF. The original Cox Maze procedure and its modifications, which generally include complete exclusion of the posterior wall of the left atrium (LA), have demonstrated improved efficacy even in those with longstanding persistent AF [4, 5]. Recent catheter ablation studies in patients with persistent AF [6–12] have suggested benefit associated with PWI, particularly within the region lying between the PVs [13]. Anatomically, this region is defined by the LA roof superiorly, by the left and the right PVs laterally, and the plane extending from the lower borders of the left and the right inferior PVs inferiorly [13]. There is clinical, anatomic and electrophysiologic evidence that this region of the LA posterior wall may contribute to the genesis and maintenance of AF, particularly in those with persistent AF. Based on this data, PWI has become a routine part of invasive therapies for atrial fibrillation at our institution.
Previous studies have shown that pulmonary vein isolation alone does not negatively impact left atrial mechanical function [14–17]. However, results studying PWI’s effect on left atrial mechanical function have been conflicting. Echocardiographic measures to assess left atrial mechanical function after PWI did not demonstrate any adverse effects as measured by atrial Doppler velocity across the mitral valve [18]. However, left atrial pressure increases have been documented following pulmonary vein isolation alone with more pronounced increases in left atrial pressure if additional LA ablation was performed beyond pulmonary vein isolation [19]. A computational model created to simulate various left atrial ablation patterns demonstrated that active left atrial emptying volume decreased as extent of ablation increased [20].
Advanced cardiac imaging techniques utilizing cardiac MRI are now able to provide accurate and reproducible measures of left atrial structure and function. These advances now allow us to study how PVI and PWI impact left atrial mechanical function. Cardiac MRI has been utilized to assess left atrial mechanical function following pulmonary vein isolation, demonstrating preserved LA function post successful PVI [21]. To the best of our knowledge, no prior study has been performed to evaluate the effect of posterior wall isolation with a cryoballoon on left atrial mechanical function as measured by cardiac MRI.
Methods
Patient population
Consecutive patients from a single institution that underwent PVI + PWI utilizing a cryoballoon for paroxysmal or persistent AF over a 5-year period (6/2018 to 6/2023) were considered for study inclusion. Patients without a baseline pre-procedure cardiac MRI (CMR) were excluded. Patients in permanent AF were excluded to ensure that CMRs could be performed in sinus rhythm. The most common reason for exclusion was lack of pre-procedure CMR. There were 14 patients identified that received PWI and had a baseline CMR performed in sinus rhythm. An additional 14 patients, matched by age, gender, and AF class (paroxysmal versus persistent) were then identified that received PVI alone utilizing a cryoballoon and had a pre-procedure CMR performed in sinus rhythm. All 28 patients then underwent repeat CMR post ablation. Left atrial ejection fraction (LAEF), LA minimum volume, LA maximum volume, and LA stroke volume were then compared between pre and post procedure CMRs using a paired samples t test. Left ventricular ejection fraction (LVEF) was compared as a secondary outcome. Additional patient descriptive data were evaluated for each group. Multivariate analyses were used to correct for potential confounding variables including time between cardiac MRIs and time from ablation to cardiac MRI.
Pulmonary vein isolation procedure
Our techniques for cryoballoon PVI have been previously reported as a standard approach to cryoballoon PVI [22]. Briefly, all patients underwent PVI using a 28-mm cryoballoon (Arctic Front Advance; Medtronic, Inc, Minneapolis, MN), inserted via a 15-Fr steerable sheath (FlexCath; Medtronic, Inc) over a circular inner lumen mapping catheter/guidewire (Achieve; Medtronic, Inc). Based on available data [21], between one and two 120–180 s cryoapplications were delivered to each PV guided by time-to-PVI. A detailed post-ablation 3D electroanatomic map was created in each patient to validate the endpoint. Pre-ablation voltage mapping was also performed. Baseline posterior wall fibrosis was defined as any region of posterior wall voltage < 0.5 mV measured during sinus rhythm. Additionally, PVI was confirmed by testing for entrance/exit block and high-output pacing. Luminal esophageal temperature (LET) was monitored throughout ablation. LET < 25 °C resulted in immediate termination of an application. During cryoablation of the right PVs, high-output right phrenic nerve stimulation was performed using a diagnostic electrophysiology catheter from the superior vena cava. Whenever diminished/loss of pacing capture was observed, cryoablation was terminated.
Pulmonary vein isolation + posterior wall isolation
Our techniques for cryoballoon PVI + PWI have also been previously reported [23]. PVI + PWI was performed using a 28-mm cryoballoon (Arctic Front Advance; Medtronic). Briefly, by anchoring the inner lumen catheter/guidewire in one of the PVs, the LA posterior wall was ablated in a segmental fashion. For ablation of the superior posterior wall segments the inner lumen catheter/guidewire was typically anchored inside the superior PVs, whereas the right inferior PV was more commonly utilized for ablation of inferior segments of the posterior wall due to its more posterior takeoff. Advancing/retracting the inner lumen catheter distally/proximally within the PV, facilitated positioning of the cryoballoon along the different segments of the posterior wall. Additionally, CARTOSound image integration (Biosense Webster, Inc) was often used to record the precise locations of the balloon on the posterior wall. A series of single 120-s cryoapplications were delivered at each site. Once again, LET was monitored throughout ablation and temperatures < 25 °C were avoided. Once completed, PWI was confirmed by testing for entrance/exit block and PVI + PWI was validated using a detailed post-ablation 3D map created in each patient using a high-density mapping catheter. As with the PVI-only group, pre-ablation voltage mapping was also performed. Baseline posterior wall fibrosis was defined as any region of posterior wall voltage < 0.5 mV measured during sinus rhythm.
Cardiac magnetic resonance
CMR studies were performed on a 1.5 Tesla Scanner (Aera or Sola, Siemens Healthineers, Erlangen, Germany). All CMR studies included scout imaging followed by balanced steady-state free precision cine sequences. A short-axis stack of 8 mm thick short axis images with 2 mm gap covered the entire left ventricle and right ventricle. Long-axis images were obtained to include a 2- and 4-chamber view. Images were analyzed by experienced CMR readers using commercially post-processing software (CVI42, Circle Cardiovascular Imaging, Calgary, Canada) to obtain left atrial maximum and minimum volumes and left atrial EF using the biplane area-length method as previously described [24]. Short-axis cine images were contoured for each short-axis slice, with total LV mass, end-diastolic volume, end-systolic volume, stroke volume and EF measured.
Monitoring for recurrent arrhythmia
In addition to routine electrocardiograms obtained at each follow-up visit, patients underwent 14-day continuous ambulatory monitoring at 3, 6, and 12 months post ablation, unless a cardiac implantable electronic device already existed. Timing of first atrial arrhythmia recurrence was documented after a 3-month blanking period. Recurrence of AF and other atrial arrhythmias (i.e., atrial flutters/tachycardias) was defined as > 30 s on any cardiac rhythm recording following a 90-day blanking period.
Statistical analysis
Normality of continuous data was assessed using the Shapiro–Wilk test and verified visually with box plots and quantile–quantile plots (theoretical vs. sample quantiles). Descriptive statistics between PWI and PVI only were compared using parametric t tests and verified with linear regression. Binary descriptive statistics were assessed using Chi-Square tests to determine if the distribution of disease prevalence prior to surgery and incidence of surgical parameters differed between PVI + PWI and PVI only groups. Paired t tests were performed to compare pre- and post-surgical measures of left ventricle ejection fraction and left atrium measures of ejection fraction, maximum volume, minimum volume, and stroke volume for each group. The sample mean of the pre- and post-surgical paired differences were verified and reported using a bootstrapping procedure to construct an empirical distribution of the mean between the paired differences (2,000 iterations), thereby making no assumptions about the distribution of these parameters. Linear regression analyses were used to assess the pre- and post-surgical paired differences between groups for left ventricle and left atrial measures; linear regression coefficients were bootstrapped by case-wise resampling across 2,000 iterations to provide the bias-corrected and accelerated (BCa) 95% confidence intervals for each measure. All statistical procedures were performed using R (version 4.3.1) with α set at 0.05.
Results
Baseline characteristics
Baseline characteristics of the patients are detailed in Table 1. AF was paroxysmal in 28% of patients and persistent in 72% of patients in both groups. There were no statistically significant differences in the average patient age, height, or weight between groups. Thirty-five percent of patients in both groups were female and 65% of patients were male. Concomitant diseases included hypertension (35%), coronary artery disease (14%), and Diabetes Mellitus (14%). There was no significant difference in the frequency of concomitant diseases between groups. There was no statistically significant difference in the presence of baseline posterior wall fibrosis between groups. Radiofrequency ablation touch up was seen more commonly in the PVI + PWI patients (57%) than the PVI only group (28%) but this difference did not meet statistical significance. Patients in the PVI + PWI group had fewer AF recurrences during follow up compared to the PVI only group (7.1% versus 21.4%). This result also did not reach statistical significance (p = 0.58). The PVI only group had a significantly longer average time between baseline and follow up CMR (90.9 ± 44.8 weeks) compared to the PVI + PWI group (59.6 ± 34.9 weeks) (P = 0.04). Additionally, the PVI only group had a significantly longer average time interval between ablation and follow up CMR (75.6 ± 26.2 weeks) compared to the PVI + PWI group (46.4 ± 31.9 weeks) (p = 0.01).
Table 1.
Baseline Patient Characteristics
| PVI + PWI | PVI only | P value | |
|---|---|---|---|
| Age (yrs) |
69 ± 5 [66, 72] |
70 ± 10 [64, 75] |
0.81 |
| Height (m) |
1.75 ± 0.11 [1.67, 1.81] |
1.71 ± 0.12 [1.64, 1.78] |
0.4 |
| Weight (kg) |
91.1 ± 21.1 [79.0, 103.3] |
88.7 ± 25.3 [74.1, 103.3] |
0.78 |
| Female gender (%) | 35.7 (5/14) | 35.7 (5/14) | 1 |
| Male gender (%) | 64.3 (9/14) | 64.3 (9/14) | 1 |
| Paroxysmal AF (%) | 28.5 (4/14) | 28.5 (4/14) | 1 |
| Persistent AF (%) | 71.4 (10/14) | 71.4 (10/14) | 1 |
| CAD (%) | 7.1 (1/14) | 21.4 (3/14) | 0.58 |
| Hypertension (%) | 35.7 (5/14) | 35.7 (5/14) | 1 |
| Diabetes (%) | 7.1 (1/14) | 21.4 (3/14) | 0.58 |
| RF touch up (%) | 57.1 (8/14) | 28.5 (4/14) | 0.25 |
| Time between CMRs (wks) |
59.6 ± 34.9 [39.4, 79.7] |
90.9 ± 44.8 [65.1, 116.8] |
0.04 |
| Ablation to CMR (wks) |
46.4 ± 31.9 [28.0, 64.9] |
75.6 ± 26.2 [60.5, 90.7] |
0.01 |
| Recurrent AF (%) | 7.1 (1/14) | 21.4 (3/14) | 0.58 |
| Baseline posterior wall fibrosis (%) | 21.4 (3/14) | 7.1 (1/14) | 0.58 |
Table 2 shows cardiac MRI variables pre- and post-ablation in the PVI only group. No statistically significant differences in LA ejection fraction (48.3% ± 15.8%, 48.6% ± 12.2%, P = 0.93), LA max volume (87.5 cc ± 26.4 cc, 80.5 cc ± 21.0 cc, P = 0.16), LA min volume (47.3 cc ± 23.3 cc, 43.2 cc ± 18.2 cc, P = 0.34), or LA stroke volume (39.4 cc ± 10.3 cc, 37.2 cc ± 6.4 cc, P = 0.4) were identified. Cardiac MRI variables pre- and post-ablation in the PVI + PWI group are shown in Table 3. There was also no statistically significant difference in LA ejection fraction (37.1% ± 16.2%, 37.2% ± 14.1%, P = 0.98), LA max volume (102.6 cc ± 47.4 cc, 105.1 cc ± 53.9 cc, P = 0.68), LA min volume (71.5 cc ± 44.0 cc, 71.6 cc ± 48.4 cc, P = 0.98), or LA stroke volume (34.1 cc ± 15.6 cc, 33.5 cc ± 10.5 cc, P = 0.9) in the PVI + PWI group. While not statistically significant, the average LA maximum and minimum volumes decreased post ablation in the PVI only group. For the PVI + PWI group, maximum LA volume had a nonsignificant increase post ablation. When utilizing linear regression analysis to compare change in LAEF, LA max volume, LA min volume, and LA stroke volume before and after ablation between groups, no statistically significant differences were identified.
Table 2.
PVI only patients Cardiac Magnetic Resonance Variables of LA and LV function Pre- and Post-ablation
| Baseline | Follow Up | Difference | P Value | |
|---|---|---|---|---|
| Left Ventricle | ||||
| Ejection Fraction (%) | 60.7 ± 7.6 | 62.3 ± 11.8 | −1.6 | 0.59 |
| [56.3, 65.1] | [55.5, 69.1] | [−7.9, 4.7] | ||
| Left Atrium | ||||
| Ejection Fraction (%) | 48.3 ± 15.8 | 48.6 ± 12.2 | −0.3 | 0.93 |
| [39.3, 57.5] | [41.6, 55.7] | [−7.5, 7.0] | ||
| Max Volume (cc) | 87.5 ± 26.4 | 80.5 ± 21.0 | 7.0 | 0.16 |
| [72.2, 102.8] | [68.4, 92.6] | [−3.3, 17.3] | ||
| Min Volume (cc) | 47.3 ± 23.3 | 43.2 ± 18.2 | 4.1 | 0.34 |
| [33.8, 60.7] | [32.7, 53.7] | [−4.8, 13.0] | ||
| Stroke Volume (cc) | 39.4 ± 10.3 | 37.2 ± 6.4 | 2.1 | 0.4 |
| [33.4, 45.3] | [33.5, 40.9] | [−3.2, 7.5] |
Mean ± standard deviation (SD) [95% Confidence Interval] of the paired difference between baseline and follow-up measures
Table 3.
PVI + PWI patients Cardiac Magnetic Resonance Variables of LA and LV function Pre- and Post-ablation
| Baseline | Follow Up | Difference | P Value | |
|---|---|---|---|---|
| Left Ventricle | ||||
| Ejection Fraction (%) | 54.3 ± 10.1 | 59.4 ± 9.3 | −5.1 | 0.03 |
| [48.5, 60.2] | [56.0, 62.9] | [−9.6, −0.6] | ||
| Left Atrium | ||||
| Ejection Fraction (%) | 37.1 ± 16.2 | 37.2 ± 14.1 | −0.1 | 0.98 |
| [27.7, 46.4] | [29.0, 45.3] | [−10.2, 10.1] | ||
| Max Volume (cc) | 102.6 ± 47.4 | 105.1 ± 53.9 | −2.6 | 0.68 |
| [75.2, 129.9] | [74.0, 136.3] | [−16.1, 11.0] | ||
| Min Volume (cc) | 71.5 ± 44.0 | 71.6 ± 48.4 | −0.1 | 0.98 |
| [46.1, 96.9] | [43.7, 99.6] | [−15.9, 15.6] | ||
| Stroke Volume (cc) | 34.1 ± 15.6 | 33.5 ± 10.5 | 0.6 | 0.90 |
| [25.1, 43.1] | [27.4, 39.6] | [−9.7, 10.9] |
Mean ± standard deviation (SD) [95% Confidence Interval] of the paired difference between baseline and follow-up measures
Left ventricular ejection fraction was not significantly changed pre- and post-ablation in the PVI only group (60.7% ± 7.6%, 62.3% ± 11.8%, P = 0.59). In the PVI + PWI group, a significant improvement in average LVEF was noted post-ablation with a baseline average LVEF of 54.3% and a post-ablation LVEF of 59% (P = 0.03). No patients in either group had evidence of late gadolinium enhancement on CMR. No late gadolinium enhancement was seen in the left atrial posterior wall or pulmonary vein antra but CMRs in the study were not protocoled to assess for left atrial fibrosis.
Discussion
Cardiac MRI did not demonstrate a significant change in left atrial mechanical function as measured by left atrial ejection fraction after pulmonary vein isolation alone nor after PVI plus posterior wall isolation. While this evidence supports the results of previous trials demonstrating that pulmonary vein isolation alone does not negatively impact left atrial mechanical function [15–17], to our knowledge, this is the first study to show that performing PWI in addition to PVI utilizing a cryoballoon does not adversely impact left atrial mechanical function as measured by cardiac MRI.
Average maximum left atrial volume following PVI alone decreased on post-ablation CMR. Although this decrease did not reach statistical significance, the same finding has been previously demonstrated [20]. Left atrial volumes were minimally increased on post-ablation CMR for patients that received PWI in addition to PVI, but this change was also not statistically significant. It is important to note that, while the two groups were matched for baseline clinical parameters, the two groups were not matched for baseline LA characteristics on CMR. Patients in the PVI only group had smaller LA volumes and higher LA stroke volumes compared to patients in the PVI + PWI group. This difference may have impacted the above result and limits our ability to interpret any differential effect of the two ablation strategies on LA function between groups. Further study is needed to determine whether PWI impacts left atrial volumes differently than PVI alone post ablation.
Left ventricular ejection fraction significantly improved in patients that received posterior wall isolation in addition PVI but not in those patients that received PVI alone. The significance of this finding is not clear. Patients in the two groups were not matched for baseline LV function, limiting the applicability of comparison of changes in LV function between groups. Furthermore, as patients were not randomized to receive PWI in this series, selection bias may have played a role in this result as patients with worse LV function at baseline may have been more likely to receive PWI. Average pre-ablation LVEF was higher in the PVI only group as compared to the PVI plus PWI group. PVI + PWI patients may have had a higher prevalence of tachycardia-mediated cardiomyopathy which improved post ablation.
Frequency of AF recurrence was lower in the PVI + PWI group compared to the PVI only group but this result was not statistically significant. This finding should be interpreted with caution given the small number of patients included in this study, particularly as this study was not designed to study this outcome.
There are several important limitations to recognize in the current study. The first limitation is the retrospective nature of this study. Selection bias may have impacted the results of this study as patient inclusion was based on whether or not a patient had a pre-ablation CMR and patients were not randomized to PVI alone versus PVI plus PWI. Prevalence of patient comorbidities known to effect left atrial size and function such as hypertension, obesity, and baseline left atrial fibrosis were not significantly different between groups. However, these comorbidities were not controlled for in the current study which may have impacted results. Ideally, LA fibrosis would have been assessed with LGE on CMR to confirm findings from baseline 3D voltage mapping. Unfortunately, this data was not available for analysis due to CMR protocols utilized.
Only a single modality (CMR) was utilized to assess left atrial mechanical function. Alternative modalities such as LA strain as measured by echocardiography could have provided additional information regarding the effect of posterior wall isolation on left atrial mechanical function. The time between initial and follow up CMR was significantly longer in the PVI only group compared to the PVI + PWI group. The PVI only group also had a significantly longer time interval between ablation and follow up CMR. LA size and function can vary over time based on many patient-specific variables beyond left atrial ablation. As such, the further out from ablation LA structure and function is assessed, the more potential there is for variance based on non-ablation variables.
Additionally, the sample size of this study is small which may have prevented some differences from reaching statistical significance. As our study population was limited, an a priori power calculation was not performed to determine study sample size. Despite this, a Cohen’s D test to assess the effect of sample size on the primary measure of change in LAEF before and after PVI alone and PVI plus PWI estimated a sample of 16,839 and 339,631 patients respectively would need to be studied to power differences of the magnitude seen in the current study. This result would suggest that even a study with a much larger sample size would be unlikely to demonstrate a statistically significant change in LA function after ablation. Finally, it is important to recognize that the cryoballoon is not the only tool at our disposal for isolation of the left atrial posterior wall. Radiofrequency ablation and pulsed field ablation are both widely used to isolate the posterior wall in current practice and this data may not be applicable to non-cryoballoon ablation strategies.
Despite the above limitations, the results of this study suggest that posterior wall isolation in addition to pulmonary vein isolation with a cryoballoon does not negatively impact left atrial mechanical function. As posterior wall isolation becomes a more frequent intervention for atrial fibrillation, additional study will be required to further understand its impact on left atrial function over time.
Conclusions
Cardiac MRI did not demonstrate a significant change in left atrial mechanical function as measured by left atrial ejection fraction after pulmonary vein isolation alone nor after PVI plus posterior wall isolation.
Funding
This study was funded by the UCHealth Northern Colorado Foundation.
Data availability
The data that support the findings of this study are available from the corresponding author, ERE, upon reasonable request.
Declarations
Ethics approval
This study was granted exemption by the appropriate institutional review board and ethics committee. Written informed consent was obtained for all patients prior to enrollment.
Competing interests
The authors have no relevant financial or non-financial interests to disclose. The authors have no competing interests to declare that are relevant to the content of this article.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author, ERE, upon reasonable request.